table of contents table of contents the use of virtual reality to treat anxiety-related disorders......................1 progression in understanding combat induced mental disorders......................6 symptoms and possible causes cures for parkinsons disease.......................8 loneliness in the mind.......................................................................................11 alcoholic disruption of function in neurophysiological pathways and retrogressive development in size and capability of cognitive neurobiological structures throughcontinual exposure................................14 rajvi javeri dominick ramirez michael mchenry hari balachandran juan bautista copy of brain matters template final about brain matters brain matters discusses all things neuroscience, psychology, and biology written by uiuc’s very own. authors come from diverse backgrounds, such as computer science and engineering majors. not to mention, the journal welcomes all authors no matter their area of study or year. this diversity allows volumes to have a wide range of articles. the journal is mainly written for the college community yet is accessible to anyone as brain matters is uploaded as an open access journal format by the university library. sponsors the undergraduate neuroscience society (uns) sponsors the brain matters journal. uns is a uiuc registered student organization that is dedicated to establishing and growing the neuroscience community on campus. table of contents outline on exercise and brain function andrew zhang...............................................................................1 brain matters・volume v issue ii i the academic advantages of a bilingual brain emma ibanez.................................................................................8 ependymoma tumor diagnosis: pathophysiology and prognosis of pediatric and adult patients christopher jones...........................................................................5 the duality of languages: bilingualism and its effects on the brain estefania baez................................................................................10 articles...................................................................................1 about the writers........................................................................28 meet the board...........................................................................24 the future of neuroregeneration hanifa mohammed..........................................................................16 olfactory responses by memory laura kilikevicius...........................................................................20 the thalamic bridge to cognition and consciousness lina issa........................................................................................13 15 writer’s bio do yeon (jason) kim, writer jason is a senior majoring in agricultural & biological engineering, in nanoscale engineering concentration. he will attend graduate school in the fall of 2019 for biomedical engineering. jason is also involved in other rso’s such as illini biohackers, illini algae and the american society of agricultural and biological engineering. he is always willing to learn new topics and challenge himself. luke lalonde, writer luke is a freshman majoring in molecular and cellular biology. along with writing for the journal, he works as a research assistant in the saif lab of cell mechanics and nanoscale materials on campus. he is excited to see “brain matters” continue to grow throughout his time at uiuc. victoria wu, writer victoria is a sophomore completing and independent plan of study in neurotheology and a minor in chemistry. she is the founder and president of juvenile detention center tutoring at uiuc. outside of academics, she enjoys travelling, reading, long runs, and yoga. she is looking forward working and learning with the collaborators and readers of njcomm at uiuc. bailey zinger, writer bailey is a sophomore in bioengineering and has interests in neuroscience, computational biology, and imaging. apart from writing for brain matters, bailey is currently working as a research assistant in machine learning applications to problems in medicine. she is excited to help facilitate general knowledge and interest in neuroscience topics through brain matters. neil doherty, writer *see editor’s note copy of brain matters template final my name is karishma patel and i am an incoming senior studying psychology with a concentration in cognitive neuroscience. my article investigates the impact early life stress can have on child development. this paper highlights the neurodevelopmental/neurobiological changes that occur in the brain due to stressful events and circumstances early in development. furthermore, this essay assesses how the relationship between children and their caregivers can modulate the activity of stress hormones in early life. apurva is a senior majoring in molecular and cellular biology with minors in sociology and chemistry on the pre-med track. she currently works on campus as a research assistant in the physical activity and neurocognitive health lab and is a student worker at mckinley. she is excited to be a part of this volume of brain matters to increase discussion. andrew zhang is a sophomore majoring in molecular and cellular biology. currently, he is a research assistant in dr. huimin zhao’s lab and also part of uiuc’s american chemistry society and react. he believes that neuroscience is a great field to learn about. there are so many things to learn about the brain especially ideas that can improve our lives. he is excited to be a part of brain matters in sharing neuroscience! apil is a sophomore majoring in molecular and cellular biology with interests in neuroscience research. outside of studying biology, he volunteers at both riverside hospital and riverside senior life center where he works with alzheimer patients. his other hobbies include playing basketball and soccer. brain matters writers 5 br ai n m at te rs w ri te rs nabiha javed is a student at the university of illinois, urbana-champaign, who is double-majoring in political science and history. she is the author of the article, 'the life cycle of neurons’. brain matters・volume v 6 brain matters board julia gainski is a junior majoring in integrative biology with a minor in german. she is the public relations chair and a writer for brain matters. she is a research assistant at the control & network connectivity team (connectlab) at the beckman institute of advanced science and technology, where she assists with an eeg procedure in a concurrent eeg-fmri study. additionally, she is a personal assistant for students with physical disabilities at beckwith residential support services at nugent hall on campus, the secretary and a mentor of the pre-physician assistant club, and a member of the illini club tennis team. chief-editor public relations chair editors fiza is a junior majoring in molecular and cellular biology on the pre-med track. in addition to her involvement in the neuroscience journal committee, she has communicated her illinois experience by being a former uiuc admissions blogger and enjoys science through volunteering at a local free clinic and doing research at vet med. she is thrilled to promote a neuroscience dialogue on campus! laura is a junior majoring in molecular and cellular biology and is pursuing a minor in food science. she is very excited to showcase the new volume and hopes to expand the journal to new horizons. aside from working on the journal, she is an assistant researcher in the robinson lab, is an mcb leader, an orientation leader, a member of bioscience journal club, and an executive board member of the undergraduate neuroscience society. assistant chief-editor rajvi javeri is a sophomore pursuing a major in psychology with a concentration in behavioral neuroscience and a minor in music. apart from being a part of the undergraduate neuroscience society, she helps out as a research assistant at the cognitive neuroimaging laboratory at the beckman institute. in her free time. she likes to practice guitar and sing. she also loves drinking infused teas and reading books whenever she can. she loves going on treks and any outdoor activities in general and is also a part of the uiuc archery club! brain matters board carolyn is a junior majoring in molecular and cellular biology and is currently conducting research in neurochemistry in dr. jonathan v. sweedler’s lab. outside of academics, she is passionate about illinithon, the university of illinois’ dance marathon program that fundraises for st. john’s children’s hospital in springfield, il. she is excited to collaborate with the other students behind “brain matters” and promote brain awareness on campus. sarah is a junior majoring in biochemistry and intradisciplinary psychology. in addition to editing for brain matters, sarah works in dr. auinash kalsotra’s biochemistry lab as a research assistant and in dr. kara federmeier’s cognitive neuroscience lab. in the future, sarah hopes to pursue an md-phd in biochemistry to study the mechanisms of neurodegenerative disorders. in her free time, sarah loves to play soccer, go hiking, watch television, and spend time with friends. samantha is a junior majoring in journalism with a minor in astronomy. outside of academics, samantha photographs and models for the fashion network. she is excited about mixing her skills of writing and photography to promote brain awareness and neuroscience knowledge on campus. eva is a junior majoring in molecular and cellular biology and minoring in creative writing. aside from her passion for mental health and neuroscience awareness, she enjoys writing and dancing, and is a proud member of uiuc’s legend dance company. she is so excited to work with her fellow students to expand our campus’s appreciation for neuroscience through brain matters! eva is a junior majoring in molecular and cellular biology and minoring in creative writing. aside from her passion for mental health and neuroscience awareness, she enjoys writing and dancing, and is a proud member of uiuc’s legend dance company. she is so excited to work with her fellow students to expand our campus’s appreciation for neuroscience through brain matters! brain matters board jade is a third year undergraduate in cognitive science with a concentration in linguistics. she is passionate about voice technology and its effects on human behavior. in her free time she sings, plays guitar and piano, and loves trying new foods. she also enjoys traveling and immersing herself in other cultures. her love of writing and editing is shown through her work for the illinimedia company and article written for soundhound inc’s speech-to-meaning blog. she is happy to be editing and designing for the “brain matters” journal. jade is a third year undergraduate in cognitive science with a concentration in linguistics. she is passionate about voice technology and its effects on human behavior. in her free time she sings, plays guitar and piano, and loves trying new foods. she also enjoys traveling and immersing herself in other cultures. her love of writing and editing is shown through her work for the illinimedia company and article written for soundhound inc’s speech-to-meaning blog. she is happy to be editing and designing for the “brain matters” journal. apil is a sophomore majoring in molecular and cellular biology with interests in neuroscience research. outside of studying biology, he volunteers at both riverside hospital and riverside senior life center where he works with alzheimer patients. his other hobbies include playing basketball and soccer. design board loneliness in the mind loneliness in the mind hari balachandran in times of unprecedented levels of social isolation, loneliness has affected more people than normal. loneliness is defined as a complex set of feelings encompassing reactions to the absence of intimate and social needs (ernst, 1999). typically, the terms lonely and alone are used interchangeably, but they are not the same. being alone simply means being by oneself. a person being alone does not necessarily mean they suffer from the feelings of social isolation. likewise, a lonely person may be in a room full of people, and still lack the sufficient personal connections to satisfy their social needs. loneliness, like other feelings, can be caused by a lack of positive emotional states and an excess of negative emotional states (matthews, 2016). examples of positive states include interactions with others, which leads to security and reduces the total energy needed to survive. an absence of these interactions can lead to loneliness, which is, in other words, a negative emotional state (eisenberger, 2012). the negative state prompts a neurological change which pushes the organism to seek social interaction. the carrot of interaction and the stick of isolation constitute the feelings of loneliness, and push humans to a much more interconnected existence. to study the neurological effects of loneliness, testing must often be done; however, given the ethical issues of isolating humans, rodents are used instead of humans. rodents, like humans, are social animals, and have been shown to prefer interaction over isolation (loo et al., 2001). while rodent models are not perfect substitutes for human testing, especially in the field of neuroscience, rodents have been used in the development of new drugs and are primarily used for their accuracy in modeling parts of human physiology and function. the physical effects of loneliness are not centralized to one specific region of the brain. however, one particular region of note is the dorsal raphe nucleus (drn), a region in the brain stem found in the midbrain and pons. to test methods that the brain uses to reward interaction and punish isolation, an in vivo calcium image was taken of rodents. in vivo calcium imaging works by using calcium indicators, special chemicals that light up when they bond to calcium (ii) ions. these ions are released within a cell when an extracellular messenger, such as dopamine, interacts with the cell. the entire process works like a series of dominos, as the dopamine movement triggers a release of calcium ions, which interact with the luminescent indicators that are then observed by researchers. following a period of isolation, an increase in dopamine receptor activity in the dorsal raphe nucleus was found once the rodents were able to interact with other rodents (matthews, 2016). the increased activity of dopamine, the “happiness hormone” brought about a pleasurable feeling to the rat. similar to the rush a person might feel after exercise, this new rush incentivized the rat to pursue similar social activities, thus increasing their dopamine levels. another region important to understanding the effects of loneliness is the prefrontal cortex. the prefrontal cortex is a region of the brain that governs decision making, personality, complex thought, and moderation of social behavior. within the prefrontal cortex, small-conductance calcium-activated potassium channels, or sk channels, were found to be responsible for the changes in the serotonergic neurons, neurons in charge of serotonin synthesis. serotonin, the “feel-good hormone,” is a mood stabilizer and is frequently produced when participating in group activities or exercise. the sk channels changed the serotonergic neurons by reducing the rate they fire following a period of social isolation, which resulted in mice having elevated levels of aggression, anxiety, depression, and antisocial behavior. however, a treatment of an excitation of serotonergic neurons was able to curb those behaviors. this treatment differed from previous trials, which used traditional pharmacological means to control serotonin levels within the mice. the new treatment was done using optogenetic and chemogenetic control. researchers were able to excite the serotonergic neurons by changing the dna in the mice themselves. the new dna attaches either light-sensitive or chemical-sensitive receptors to the serotonergic neurons, which the researchers were then able to manipulate. these manipulations resulted in a decrease in aggression and an increase in social behavior in the mice (sargin, 2009). isolation deprived the mice of contact with others, which starved them of serotonin, and led to a variety of psychological issues. for this reason, treatments for loneliness may be found vol. 3 11 by addressing the serotonin deficiency. addressing the symptoms of serotonin deficiency, such as the aforementioned anxiety and depression, via anti-anxiety/ depressant medication is likely the best place to start when attempting to curb the effects of loneliness. there is another method in which social isolation can be observed within the brain. this is visible with the presence of the neuropeptide tachykinin 2 (tac2)/neurokinin b (nkb), two different chemicals used to transmit messages between neurons in the brain. when mice were isolated for two weeks, tac2 concentrations spiked across the entire brain. like the previous study, aggressive behavior was noted in the animals, yet interestingly there were also defensive behaviors present in the mice. the presence of tac2 triggered the “freeze” response in many mice. prolonged loneliness, it was found, triggered fear responses in mice, in addition to anxiety and aggression. (zelikowsky, 2018). the heightened fear response likely suggests that social isolation may have been causing harm to the mice. fear is typically associated with the perception of danger, and being alone for nearly two weeks was enough for the mice to feel threatened by their environment. when scientists in the zelikowsky study increased the expression for the tac2 gene in mice that had not faced social isolation, the mice began to exhibit aggressive and anxious behaviors, similar to those that had undergone isolation. thus, it was shown that tac2 was likely the primary culprit for the feelings of loneliness in mice, and that more importantly, finding a way to inhibit that may cure the mice. as stated earlier, mice that were isolated displayed various hostile behaviors, such as chronic fear, increased aggression and an increased sensitivity to threatening stimuli. these mice were all found to have elevated levels of tac2 in both the amygdala and the hypothalamus. providing doses of osanetant, a former schizophrenia medicine that also acts as a way to block the processing of nkb chemicals, showed a reduction in these traits, resulting in a mitigation of the effects of social isolation. interestingly, the researchers discovered different effects when blocking the expression of the tac2 gene in different regions of the mices’ brains. when blocking the expression in the amygdala, the mice lost many behaviors related to the increased fear, such as hypersensitivity and chronic fear. when blocking the tac2 expression in the hypothalamus, the mice retained the increase in fear, yet saw a decrease in the increased aggression brought about from social isolation (zelikowsky, 2018). not only are there different chemical reactions that occur in the brain when a person experiences loneliness, but the shape of the brain is also subject to change. using voxel-based morphology, individuals suffering from chronic loneliness were found to have less gray matter in the left posterior superior temporal sulcus (psts). this region of the brain is associated primarily with social perception. accounting for other factors, such as empathy, other disorders individuals face, and the size of their social circles, there was a direct correlation found between loneliness and basic social perception. in other words, loneliness directly hindered an individual’s ability to process social cues. it is unknown whether loneliness contributes to a loss in gray matter in the psts or if a person born with less gray matter in the psts is more likely to be lonely. given the harmful, stress-inducing effects of an increase in tac2 expression, and the fact that stress has already shown to cause neuron death in other parts of the brain, such as the hippocampus (lee, 2002), it is not outside of the realm of possibility for tac2 expression to result in a loss of gray matter. however, until further research is done, this question remains unsolved. loneliness is a rather insidious chemical process in the brain. although mice were primarily used in testing, many of the processes observed are homologous in humans. it can be difficult to define loneliness, as the needs for every person changes. the difference between an individual’s needs and the amount of interaction an individual feels is one way to determine how lonely a person feels. the important factor is not actual social interaction, but perceived social interaction. a poor perceived social interaction leads to a worse cognitive function, higher negativity, and greater chance of death (cacioppo, 2009). as shown in the 2018 study by zelikowsky, a fear response in rodents was triggered after prolonged isolation. in humans, this likely manifests itself in a cognitive bias to social context (spithoven, 2017, kanai 2012). loneliness was shown to lead to people having a much more negative outlook in all stages of a social interaction processing model. an unfortunate circumstance of this behavior is that it becomes increasingly difficult for those with a negative outlook to gain the interaction they need, which leads to increasing levels of loneliness. in essence, a dangerous feedback loop is created. however, as more experimentation is done, more is being found to combat this issue. serotonin treatments have already shown promise, and future vol. 3 12 treatments to limit tac2 production may yield fruitful results. while these results are promising, no trials have been conducted on humans. for now, it has yet to be seen if one day a viable cure to loneliness can be found. aside from pharmacological means, other forms of treatment are being explored. technology has shortened the distance between people, and for individuals that are unable to meet face-to-face, it can serve as a way for them to connect. more research is needed to determine the effectiveness of technology in bolstering connections between humans, but as our world revolves around technology more, it will be interesting to see the effects of these changes. given the recommended social-distancing policies due to covid-19 in place at the time of writing, it will be interesting to see the short and long term effects of isolation. no doubt cases of loneliness amongst the population in the world have increased, but the extent to which social isolation has contributed to loneliness, and the societal outcomes of these cases have yet to be seen and studied. future studies may combine the two ideas and attempt to discern a connection between a society’s level of technology use and the effects of loneliness on the populace. loneliness has become more prevalent in recent months. it is worth our effort to study and understand this debilitating disease. references dorsal raphe dopamine neurons represent the experience of social isolation. https://www.ncbi.nlm.nih.gov/pubmed/26871628 serotonin regulation of the prefrontal cortex: cognitive relevance and the impact of developmental perturbation. social isolation co-opts fear and aggression circuits https://www.cell.com/cell/fulltext/s0092-8674(18)30524-5 “chronic social isolation stress triggers an increase in neuronal tachykinin signaling across distinct brain regions that mediate fear and aggression, elucidating the neural basis of these maladaptive responses.” the neuropeptide tac2 controls a distributed brain state induced by chronic social isolation stress https://www.cell.com/cell/fulltext/s0092-8674(18)30361-1#secsectitle0010 perceived social isolation and cognition https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2752489/ social relationships and health: a flashpoint for health policy https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3150158/ vol. 3 13 introduction it is estimated that over half of the worlds’ population is fluent in more than one language. when you think about children in north america who speak english at school and another language at home, there was not necessarily a choice of becoming bilingualit was a matter of housing, family, place of birth, immigration history, etc. (bialystok, 2012) that cultivated an environment for it. it was commonly thought that learning two languages at once would be confusing and detrimental to childrenbut researchers argue that it actually provides cognitive and neurological benefits. ever growing inquiries about the plasticity of the brain creates a pathway for us to discover why younger people are more likely than older adults to acquire fluency in more than one language. the physiological differences between bilingual and monolingual brains continue to intrigue researchers, and discussions about cognitive benefits of speaking more than one language should be continued and further held. plasticity and brain differences from the ages of 0-3, an infant's brain reaches peak lifetime plasticity. neuroplasticity can be referred to as the brain’s ability to adapt, modify, or alter in response to lifelong growth, learning, or changes. for children that grow up in households where more than one language is spoken, it comes easy for them to learn both at the same time. learning a new language uses plasticity because it includes repeated auditory exposure, semantic processing, retrieval, and speaking. the repetition of these processes over time results in gaining fluency of a language. there is a critical period that every human experiences, which is a timeframe that an individual has for optimal language acquisition. after the critical period, which is around the first 5 years of a person’s life, it becomes increasingly difficult for primary language acquisition to occur. in a study hosted by paul thompson, it was discovered through continuous brain scans of children aged 3-15 that peak growth rates were attenuated after puberty. abstract research over the past two decades has shown the vital role of brain plasticity in language acquisition, specifically in children. when compared with older adolescents, kids in early childhood are more efficient at learning a second language. researchers still seek to know the physiological differences in brain structure and function between bilinguals and monolinguals. promising studies show disparities between white and grey matter structures. in addition, bilingual individuals experience a specific pattern of brain activity when switching from one language to anotherdubbed ‘codeswitching’. such a pattern is found in two regions: the anterior cingulate cortex, which helps us pay attention, and the prefrontal cortex, which is the 'thinking' part of the brain (mcrae, 2018). the culmination of elevated neurocognitive processes experienced by bilingual individuals leads to their variations in protection against neurodegenerative diseases and heightened performances in cognitive tasks. the duality of languages: bilingualism and its effects on the brain estefania baez the discovery arose through studying the fibers that innervate association and language cortices, for example the temporal lobe or visual cortex. these contrasted sharply with a severe, spatially localized loss of subcortical grey matter (thompson et. al, 2000). during these critical periods, children are perceiving language for the first time, which leaves a large impression and allows for the greatest amount of growth in the brain and plasticity. while they are learning words and forming associations every day, the process of synaptic pruning contributes to the loss of subcortical grey matter. grey matter is made up of dendrites and cell bodies of neurons, while white matter is made up of myelinated axons. dendrites are branches in neurons that extend to synapses and receive information from other cells, and axons are the lengthy tubes of the neurons that transmit information to the synapse, where another nearby neuron can receive it. this pruning is a process that is important for learning and memory because it removes unused synapses so that the brain can work as coherently as it can. these processes occur faster at younger ages and allow adults with more developed brains to transmit information more efficiently. 10brain matters・volume v issue ii 11 in a general view, bilinguals of all ages demonstrate better executive control than monolinguals who are matched in age and other background factors. bilingual children have outperformed monolingual children in non-verbal conflict tasks, and bilingual adults performed better than their monolingual counterparts in tests like the stroop effect and simon tasks (bialystok et. al, 2012). these neurocognitive tasks are commonly used to test monitoring of interference, focus, and ability to focus on stimuli. successful performance on cognitive tasks can translate into real-world problem-solving skills, like recalling details, inhibitory control, and quick decision making; these are universal abilities that aid in workplaces, education, and everyday incompetencies. studies show evidential parallels of bilingual individuals experiencing neural processes where increased activity is detected. highly proficient bilinguals show increased subcortical representation of linguistic sounds, as revealed by a larger electrical brain response in the range of the sounds' fundamental frequencies. this suggests that bilinguals have more efficient and flexible auditory processing than monolinguals (costa et. al, 2014). when neurons are consistently firing at higher rates and increasing action potentials, long-term potentiation (ltp) occurs. ltp is the process of strengthening synaptic connections between neurons that has long lasting effects. the increasing processing demands that come with bilingualism can be associated with higher performances on cognitive tasks, as well as the refined synaptic connections that allow for speedy neural transmission. in bilingual individuals, previous studies have shown our anterior cingulate and prefrontal cortices activate when we jump from one language to another (mcrae, 2018). it was shown that it isn’t starting to speak one language that is costly in brain effort, but the stopping of one language to start speaking in a second one that activates the most brain activity. individuals who are fluent in both english and american sign language (asl) have been studied for this phenomenon and have provided evidence to support the idea. while repeating prompted words in both languages, ‘switching off’ the asl and continuing to produce words in english proved to be more effortful than ‘switching on’ the asl (blanco-elorrieta et. al, 2018). turning a language off required increased engagement of the prefrontal cortex and anterior cingulate cortex, both part of the frontal lobe, which is the area of the brain largely responsible for decision making and impulse control. these series of specific neural activations are processes that monolinguals don’t especially use, and could be explanations as to why they underperform in cognitive tasks and show less neural activity compared to their bilingual counterparts. as for long-term structural changes, a study of older, highly proficient, successive bilingual adults (70-year-olds) reported greater white matter integrity in the corpus callosum in comparison to monolinguals (costa et. al, 2014). white matter in the brain consists of axons wrapped in myelin sheaths, which aid in the acceleration of action potentials and insulation of the axon. the more protected and the more that a neuron fires, the more the likelihood that the onset of neuro-degenerative disease would be delayed. findings indicate that lifelong bilingualism acts as a powerful cognitive reserve proxy in dementia and exerts neuroprotective effects against neurodegeneration. for example, bilingual elders have displayed an average of a 4.5-year delay in the onset of alzheimer’s’ dementia compared with monolinguals of similar age (perani et.al, 2017). predicted causes for this delay include neural reserve and neural compensation for hypometabolism, which is the decreased metabolic rate of neurotransmitters. hypometabolism is also often associated with neurodegenerative diseases such as alzheimer’s. along with symptom delay, bilingual individuals with alzheimer's dementia also showed increased activity in frontal brain regions when the posterior regions had lower metabolic activity. the likely cause for this effect would be the consistent neural transmission over time that comes with the executive function of controlling two languages. this results in a neural reserve that eventually renders the bilingual brain more resistant against brain aging effects (perani et. al, 2017). conclusion study after study, we find increasing evidence that the benefits of acquiring a second language at an early childhood age would translate to increased cognitive processes. in comparison with monolinguals, people who are fluent in more than one language have shown better performance on cognitive tasks, as well as physiological differences in white and grey matter density. the implications of being bilingual from an early age are consistent with having increased attention, focusing ability, and interference control. there is especially evidence of frontal lobe neural reserve that is hypothesized to be behind protection against early onset dementia. there are still many unknown neurological mechanisms that we seek to understand, such as the compartmentalization of various languages, as well as the precise neuro-preventative effects of bilingualism. even so, educators and leaders around the world should emphasize the benefits of becoming fluent in another language and perhaps encourage further exploration into the world of multilingualism. references 1. bialystok, e., craik, f. i. m., & luk, g. (2012, april). bilingualism: consequences for mind and brain. trends in cognitive sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3322418/. 2. blanco-elorrieta, e., emmorey, k., & pylkkänen, l. (2018, september 25). language switching decomposed through meg and evidence from bimodal bilinguals. pnas. https://doi.org/10.1073/pnas.1809779115. 3. costa, a., sebastián-gallés, n. how does the bilingual experience sculpt the brain?. nat rev neurosci 15, 336–345 (2014). https://doi.org/10.1038/nrn3709 4. mcrae, m. (n.d.). neuroscientists have finally tracked down the bilingual language switch in the brain. september 13, 2018. code switch in languages 5. j;, m. v. s. m. h. (n.d.). shared and separate systems in bilingual language processing: converging evidence from eyetracking and brain imaging. brain and language. https://pubmed.ncbi.nlm.nih.gov/12821416/. 6. thompson pm;giedd jn;woods rp;macdonald d;evans ac;toga aw; (n.d.). growth patterns in the developing brain detected by using continuum mechanical tensor maps. nature. https://pubmed.ncbi.nlm.nih.gov/10724172/. https://www.pnas.org/content/114/7/1690 12brain matters・volume v issue ii http://www.pnas.org/content/114/7/1690 http://www.pnas.org/content/114/7/1690 copy of brain matters template final neurons are one of the most important cells in the human body; they are used to signal other parts of our body to start or stop processes vital for sustaining life. despite all of our somatic cells being bound to the process that is the cell cycle, the life cycle of neurons is something that is quite different from other cells in the human body. our somatic cells go through the life cycle of becoming differentiated, carrying out their respective jobs, and then undergoing apoptosis once they are worn out or damaged. the majority of neurons we have in our brains are present by the time of birth, however there is evidence that neurogenesis is a lifelong process, which is a belief contrasting starkly to the previous thought that humans are born with all the neurons they were going to ever have. once cells in our body die, they are destroyed and are consequently replaced by new cells. neurogenesis replaces neurons that have died, however, are not replaced by new cells in the way that other specialized cells in our body are. neurons are limited in their capacity to proliferate. when neurons die unnaturally, the brain suffers ramifications, making way for neurological and neurodegenerative diseases such as types of dementias. in order to better understand the causes and effects of such neurological and neurodegenerative disorders, we must examine the life cycle of a neuron, from neurogenesis to death. we must also understand what the structure and function of a neuron is, and why neurons are so important to the human brain and the human body at large. the majority of cells undergo these cycles, on average, 40 to 60 times in their lifetime; this is quite different from neurons, who often remain in a phase known as g0. g0 is a nondividing and nonrein order to understand what the life cycle of a neuron is, it is fundamental to first acknowledge the cell cycle and its implications on the neuron’s development and eventual death. the cell cycle has four main phases: g1, s, g2, and m (1). in eukaryotes, somatic cells undergo mitosis, which is where the parent cell duplicates its genetic material and splits into two subsequent daughter cells identical to its initial composition. this creates two new cells that are genetically identical to the mothering cell. mitosis consists of 4 phases: prophase, metaphase, anaphase, and cytokinesis. after all four steps of mitosis are complete, the two resulting daughter cells are functional and complete. plicating phase of the cell cycle. progression through the cell cycle is closely monitored by checkpoints resulting from the activation of different signalling pathways, leading to inhibition of cdk (2) and cyclin complexes. each cell must complete the phases in order before progressing to the next one. if any defect is detected by proteins involved in regulating the cell cycle, the proteins halt the progression of the cycle until this defect is addressed. this makes it nearly impossible for a defective cell to make it past the cell cycle without being corrected, if possible, or sent into programmed cell death if the defect is too extensive to be fixed. the central nervous system, composed of the brain and spinal-cord, is made up of 2 basic cell types, one of these types being neurons. in order to understand the functions of a neuron, it is necessary to understand the structure of a neuron. neurons vary in their morphology depending on what variety of neuron they are, however, they all have basic structure similarities with one another. all neurons contain four distinct regions: the cell body, dendrites, axon, and axon terminals. all four of these regions serve distinct and different purposes that are vital to the function of a neuron in terms of it being a messenger cell. the cell body of a neuron, also known as the soma, contains the nucleus, which is the control center and the ‘brain’ of the neuron. essentially all neuronal proteins and membranes are synthesized in the nuclei of neurons. from this cell body, the dendrites and axon branch out from the left and right, respectively. in order to communicate with each other, neurons send messages across the synapse, a gap between one neuron’s dendrites and the other’s axon. most neurons have multiple dendrites, which serve to receive chemical signals originating from the axon terminals of other nearby neurons. neurons’ axons do not contain any ribosomes, and thus do not synthesize proteins. axons are the channel by which action potential travels over a neuron, from the dendrites all the way to the end of the axon terminals of a neuron. neurons are the cells that help our central nervous system relay messages all over our body. this makes our organ systems do what they do, and helps us respond to our environment in the ways we react. despite there being the previous belief of neurons dying off and not being replaced by subsequent neurons after the fact, there is now evidence neurogenesis does happen over the span of a person’s lifetime. neurogenesis, or the birth of neurons, is the process by which new neurons are created and introduced into the human body for use. neurons are born in areas in the brain rich with neural stem cells; neural stem cells have the ability to create most, if not all, of the varieties of neurons and glial cells found in the brain and spinal cord. after the birth of a neuron, migration occurs. migration is the process by which neurons go to parts of the braion or spinal cord that need their services. migration is the part of a neuron’s life cycle where a lot of neurons do end up dying off, despite neurons being the longest living cells in the human body. scientists speculate that only a third of neurons make it to their destination. life cycle of neurons nabiha javed 7 once a neuron reaches its destination, it will differentiate in order to become a specialized neuron specific to the job it will be carrying out. neurons are responsible for the uptake of neurotransmitters, chemicals that relay messages to the brain, and thus differentiation is an important component of a neuron’s function. unlike most other cells, neurons are believed to lose their ability to proliferate once. this means that neurons cannot divide and make more of themselves after they have undergone the process of differentiation. differentiation is the process by which neurons become specialized to do specific jobs around the brain and nervous system. the ramifications of adult neurons dying leads to many neurological and neurodegenerative diseases we see, such as varieties of dementias or parkinson’s disease. although neurogenesis is indeed a lifelong process, adult neurons have challenges in proliferating and being replaced after dying in development and migration. neurons can die in a variety of ways, but the unnatural neuronal death that occurs occasionally in a human brain can lead to diseases and disorders. the progressive death of specific neuron populations is what is characteristic of neurodegenerative disorders. for example, alzheimer’s disease, the most common cause of dementia, is characterized by neurons reentering the cell cycle. research has further suggested that alzheimers involves a dysfunction in this cell cycle reentry, leading to what is known as the two-hit hypothesis of alzheimer's disease. the first hit in this hypothesis is abnormal cell cycle reentry, typically resulting in neuronal apoptosis and thus a prevention of alzheimer's disease in the brain. the second hit, however, involves chronic oxidative damage that prevents apoptosis of the neurons, leading to the plaques and tangles characteristic of an alzheimer's brain. neurons are quite apt to oxidative stress as a result of the high oxidative metabolism rate in the brain, which explains this chronic damage. oxidative stress is also seen as a major damage to genetic material. cells with extensively damaged dna often will be destroyed via apoptosis to prevent complications from arising, as seen by neuronal apoptosis in the first hit in the two hit hypothesis. other unnatural causes of neuronal death are stress, head trauma, strokes, or physical illnesses. glucocorticoids are hormones that are released when we are stressed, and extended exposure to these substances can damage the brain, making our neurons more exposed to neurological injuries. preventing stress in day to day life may make our brains more resistant to strokes, forms of dementias, and other types of neurological disorders. the brain is made up of tissues, composed of various kinds of cells. of these cells are neurons, which are the messengers and signal relayers of our brain. from birth, migration, differentiation, to death, a neuron carries out several important tasks for our wellbeing, such as taking up neurotransmitters and signaling other parts of the body on when to start and stop processes vital to the processes of living. references 1. barrio-alonso,8 e et al. “cell cycle reentry triggers hyperploidization and synaptic dysfunction followed by delayed cell death in differentiated cortical neurons.” scientific reports vol. 8,1 14316. 25 sep. 2018, doi:10.1038/s41598-018-3270-4 2. brain basics: the life and death of a neuron. www.ninds.nih.gov/disorders/patient-caregivereducation/life-and-death-neuron. 3.6. frade, j., 2015. neuronal cell cycle: the neuron itself and its circumstances. [online] taylor & francis. available at: https://www.tandfonline.com/doi/full/10.1080/15384101.2015 .1004937> [accessed 18 september 2020]. 4. fricker, michael et al. “neuronal cell death.” physiological reviews vol. 98,2 (2018): 813-880. doi:10.1152/physrev.00011.2017 5. jellinger, kurt a., and christine stadelmann. “problems of cell death in neurodegeneration and alzheimer's disease.” journal of alzheimer's disease : jad vol. 3,1 (2001): 31-40. doi:10.3233/jad-2001-3106 6. 10. krantic, s., mechawar, n., reix, s. and quirion, r., 2020. apoptosis-inducing factor: a matter of neuron life and death. 7. kruman, inna i. why do neurons enter the cell cycle? 5 apr. 2004, www.tandfonline.com/doi/abs/10.4161/cc.3.6.901? src=recsys. 8. lodish h, berk a, zipursky sl, et al. molecular cell biology. 4th edition. new york: w. h. freeman; 2000. section 21.1, overview of neuron structure and function. https://www.ncbi.nlm.nih.gov/books/nbk21535/ 9. moh c., kubiak j.z., bajic v.p., zhu x., smith m.a., lee h. (2011) cell cycle deregulation in the neurons of alzheimer’s disease. in: kubiak j. (eds) cell cycle in development. results and problems in cell differentiation. springer, berlin, heidelberg. https://doi.org/10.1007/978-3642-19065-0_23 10. neary, d., snowden, j., mann, d., northen, b., goulding, p. and macdermott, n., 1990. frontal lobe dementia and motor neuron disease. journal of neurology, neurosurgery & psychiatry, 53(1), pp.23-32. 11. sapolsky, r. m. (1992). stress, the aging brain, and the mechanisms of neuron death. the mit press. brain matters・volume v 8 copy of volume 6 publication can gene editing be the key to treating alzheimers? saani kulkarni commonly known as the most complex part of the human body, the brain contains millions of neurons, each with the ability to send and receive unique messages utilizing electrochemical signals. however, in individuals with alzheimers and other neurodegenerative diseases, the typical function of neurons is impaired greatly. the lifespan of a neuron is dependent upon 3 primary factors: communication, metabolism, and its ability to repair itself. without proper signaling, neurons are unable to access their target cells and gain access to necessary trophic factors. moreover, neurons require adequate nutrients and chemicals to operate, gaining their energy through oxygen and glucose from the blood; the lack of these necessities will result in the death of the neuron. they must also be able to maintain a healthy state throughout their lifespan; while other human body cells may die quickly, neurons are observed to be able to live beyond 100 years of age in the human body. while in a healthy human brain neurons may possess all these qualities, the opposite can be said for the brain in regards to alzheimers; eventually, many neurons stop functioning and die out. due to this, essential connections at the synapse may be broken down, impairing an individual from receiving necessary signals to carry out tasks. while researchers continue to investigate all causes behind alzheimers, the beta-amyloid protein is commonly known as a major factor in the development of the disease. the cause of the cleavage of the amyloid precursor protein (app), the presence of the beta-amyloid protein is originally beneficial, as it plays a significant part in neural growth and neural repair. however, a form of beta-amyloid known as betaamyloid peptide 42 has been proven to be significantly toxic to the human body. almost plaque-like, beta-amyloid 42 begins to gather in large quantities between neurons, damaging their functioning and breaking down their connections. alongside b-amyloid 42, a protein known by tau that functions as a stabilizer for microtubules by attaching to them is often found in the human body as well. however, tau can separate and connects to other tau molecules instead, creating numerous knots and disruptions inside the neuron and ultimately affecting their ability to communicate. researchers have found a positive correlation between an increased presence of tau and that of beta-amyloid, hinting at the fact that there are multiple mechanisms intertwined in the progression of alzheimers. once neuronal networks begin to disappear, the memory of the individual, with parts of the brain such as the hippocampus and entorhinal cortex, is the first to be affected. as the disease spreads, the cerebral cortex of the brain is next, and ultimately individuals may be unable to carry out many basic behaviors independently. with such an extreme increase in severity, researchers have attempted to devise methods that will be able to treat alzheimers and be able to reduce the symptoms gained as a result of it. while originally researchers believed that a type of anti-beta amyloid drug would be a viable solution, it was soon understood that the state of the disease was already at a level of severity where simply treating it by affecting the amount of beta-amyloid protein in the brain would not necessarily result in a major change of quality of life nor health. in order to target the protein, the protein accumulation is removed as efficiently and quickly as possible in order to preserve the remaining parts of the brain. due to the precision of gene editing and the nature of the disease, teams worldwide have been examining the potential to treat alzheimers using a variety of gene editing techniques. a significant positive towards gene editing would be the failure of other treatments to surpass the blood-brain barrier; however, gene therapy has the ability to surpass such obstructions. despite this, many experiments regarding gene editing have not yet resulted in effects that would be considered noteworthy to the point of a fixed treatment. researchers wish to continue experimentation by altering the type of viral vector, target for the therapeutic gene, and the route through which the vector should take. viral vectors are considered one of the most effective ways for gene delivery to any target cells. when done ex-vivo, the target cells are drawn out from the organism’s body, then introduced to the therapeutic gene, and planted back into the organism; in-vivo requires the process to be done within the organism itself. this can result in either gene silencing or overexpression, all of which is dependent on the target cell itself. considering the wide range in virus shapes and structures, many types of viral vectors are utilized in order to attain precision and efficacy. in treatments for alzheimers, researchers have traditionally experimented with adeno-associated virus (aav) vectors, due to their non-toxic and non-pathogenic nature. taking into account the possibility of mutagenesis in the body, it is essential that the viral vector must possess these two qualities. researchers identified around 100 av variants with a range of 13 serotypes; although multiple have been deemed adequate for experimentation, aav2 is used most frequently due to its high level of safety and sustained expression of the therapeutic gene within the neuron. along with the identified aavs, a genetically engineered aav capsid (aav-php.b) has been utilized in studies and expresses the ability to deliver a greater capacity of aav 12brain matters volume vi highly precise, gene-editing techniques and therapies have improved greatly as a result of this technology. comprised of a singular enzyme (cas9) and a single guide rna (sgrna), the target dna sequence is registered and recognized by the sgrna, and cleaved by the cas9 endonuclease, resulting in either a replacing of the mutated sequence or the insertion and deletion of sequences for inactivation. considering that genetic mutations only comprise around 1% of familial alzheimer's cases, crispr’s role in helping patients with ad may be limited to changing symptom expression by manipulating b-amyloid metabolism (bhardwaj, s., kesari, k. k., rachamalla, m., mani, s, et. al, 2021). while the variety of findings in regards to gene editing and the treatment of alzheimer’s disease are promising, much work is needed to ensure the safety of procedures on the human brain and their efficacy. host responses to viral vectors may prove to be dangerous, as is the concern of patients with high-functioning immune systems creating antibodies with the purpose of neutralizing the inserted vectors. additionally, the ethics and viability of a supposed treatment must be taken into consideration; factors such as cost, effectiveness, and availability all must be regarded. improved knowledge of the mechanisms behind alzheimer’s and their connection to various parts of the human body will undoubtedly improve the potential prospects for treatment. in combination with the continued efforts to find suitable vectors and outline target genes, many scientists and doctors are hopeful that gene-editing techniques may be a potential means to find a conclusive treatment to a disease that has affected millions of people worldwide. brain matters volume vi genomes to the central nervous system (cns) and convert more than 50% of astrocytes and neurons (chen, w., hu, y., & ju, d, 2020). while the selection of a vector is critical, researchers globally have experimented with aav vectors and various targets in the body to treat alzheimers; without choosing the proper target, the therapeutic gene may simply diminish symptoms slightly while possessing no contribution to the treatment and root cause of alzheimers. endoplasmic reticulum (er) stress and the unfolded protein response (upr) has been extensively studied, as the majority of neurodegenerative diseases are correlated with an accumulation of misfolded proteins, which contributes to stress and eventual breakdown of the er. additionally, beta-amyloid oligomers are a source of destabilization to the calcium of the er and its homeostasis, resulting in the death of neurons. by potentially being able to reduce the amount of stress affecting the er, researchers have begun to experiment with a method to target the unfolded protein response (upr) signaling in the hopes that the signaling pathway may be amplified for improvement in protein folding through gene editing. notably, a positive correlation between the overregulation of the upr pathway and glioblastoma invasion has been discovered, therefore being a safety concern when experimenting with this pathway. another potential target for researchers has been the mtor pathway, which deals with the regulation of mammalian metabolism and has also been known to play a role in neurodegeneration; when being abnormally regulated, protein accumulation is unable to be removed. in 2017, chen et. al previously demonstrated that the delivery of mtor positive regulators to the retina via the aav vector resulted in a decrease of ganglion cell death and cns axon regeneration; a variety of other studies have also reported positive effects on neuron regeneration in mouse models, highlighting the potential for the mtor pathway to be an ideal target. researchers have also devised methods for autophagy to be used through gene editing; in 2012, gorbatyuk et. al demonstrated that the overexpression of a kinase through aav2 resulted in the autophagy of dysfunctional mitochondria. in doing so, mitochondrial function that was lost as a result of b-amyloid oligomers was regained (chen et.al, 2020). similarly, microglia and astrocyte function has been brought to light as potential targets, considering the great importance of microglia within the neuroimmune system, and the damaging of their functions resulting in the neuron destruction witnessed in alzheimers. the re-regulation of microglia function has been considered a potential treatment; multiple studies have reviewed the ability of the overexpression of the receptor trem2 on myeloids to assist beta amyloid destruction and microglial movement. through this process, the plaque formation and eventual disruption of neurons caused by bamyloids is reduced, and spatial memory abilities are increased. in recent years, studies with clustered, regularly interspaced short palindromic repeats and the crispr-associated protein 9 (crispr-cas9) have increased significantly, and yielded optimistic results. targeted to specific genes and figure 1. proposed crispr cas-9 gene editing approaches to types of alzheimer’s disease. adapted from “crispr-cas9 gene editing : new hope for alzheimer’s disease therapeutics,” by bhardwaj, s. et al, 2021, journal of advanced research (https://doi.org/10.1016/j.jare.2021.07.001). cc by 4.0. 13 bhardwaj, s., kesari, k. k., rachamalla, m., mani, s., ashraf, g. m., jha, s. k., kumar, p., ambasta, r. k., dureja, h., devkota, h. p., gupta, g., chellappan, d. k., singh, s. k., dua, k., ruokolainen, j., kamal, m. a., ojha, s., & jha, n. k. (2021). crispr/cas9 gene editing: new hope for alzheimer's disease therapeutics. journal of advanced research. https://doi.org/10.1016/j.jare.2021.07.001 chen, w., hu, y., & ju, d. (2020). gene therapy for neurodegenerative disorders: advances, insights and prospects. acta pharmaceutica sinica b, 10(8), 1347– 1359. https://doi.org/10.1016/j.apsb.2020.01.015 gaj, t., sirk, s. j., shui, s.-lan, & liu, j. (2016). genome-editing technologies: principles and applications. cold spring harbor perspectives in biology, 8(12). https://doi.org/10.1101/cshperspect.a023754 warnock, j. n., daigre, c., & al-rubeai, m. (2011). introduction to viral vectors. methods in molecular biology, 1–25. https://doi.org/10.1007/978-1-61779-0959_1 u.s. department of health and human services. (n.d.). what happens to the brain in alzheimer's disease? national institute on aging. retrieved april 25, 2022, from https://www.nia.nih.gov/health/what-happens-brainalzheimers-disease references 1. 2. 3. 4. 5. 14brain matters volume vi there are many common misconceptions between differentiating adhd brains and non adhd brains, the cause of which largely stems from the stigmatization of mental health disorders. though it is still debated whether or not adhd is classified to be a disorder of the brain, inaccurate assumptions are often formed, leading to much confusion in the understanding of the disorder. adhd includes symptoms such as forgetfulness, hyperactivity, irritability, impulsivity, and difficulty paying attention to details. researchers have gathered evidence through scrutinizing various brain images and identifying structural differences that strongly convey the substantial differences between people who have adhd in comparison to those who do not. these differences will be investigated throughout this paper. today, the reports estimate approximately eleven percent of children and five percent of adults to be diagnosed with adhd in the united states. alongside this, there is increased difficulty while completing tasks such as listening during a class period or during brief moments of instructions. adhd stands for attention deficit hyperactivity disorder, and is classified as a common neuropsychiatric disorder. adhd is not a severely rare disorder, but still “affects more than one in 20 people under 18 years old” (radboud university nijmegen medical centre 2017). it is important to note that about two-thirds of the people diagnosed with adhd early on such as during their childhood continue to experience the symptoms of adhd as adults. the main part of the brain that researchers are examining is the basal ganglia, a part of the brain that controls emotion, voluntary movement, and cognition. researchers have “... found that the caudate and putamen regions within the ganglia are smaller in people with adhd” (radboud university nijmegen medical centre 2017). both the putamen and caudate make up the dorsal striatum, a functional structure that is directly involved in the decision-making process. more specifically, the things that encompass this would be action selection and initiation. the basal ganglia makes up the caudate, putamen, globus pallidus in the cerebrum, the substantia nigra in the midbrain, and the subthalamic nucleus in the diencephalon. it is important to note that the basal ganglia is known for its prominent role in movement, a critical aspect to pay attention to because many people with adhd have issues with staying still. therefore, the basal ganglia can be used as a strong indicator and an identifier of those who have adhd. to add on to this finding, international studies are interested in examining the differences in the brain structure and density involving 1,713 people with a diagnosis of adhd and 1,529 without the diagnosis. the age ranges for this study was between four and 63 years old. the purpose of the mri scan was to measure the overall brain volume of each person. the scientists took specific percentages of each region of the brain and measured the density of each person’s brain. alongside this, the size of the seven regions of the brain that were associated with a possible linkage to adhd are: the pallidum, thalamus, caudate nucleus, putamen, nucleus accumbens, amygdala, and hippocampus. through the analysis of measuring the regions, scientists can use the differences in brain volume percentages to better understand how an individual’s brain with adhd differs from an individual’s brain without adhd. scientists put more emphasis on scrutinizing the differences in each individual brain region in order to get a better idea on which regions are affected the most and the correlation they share with adhd. the conclusive results from this study were that people with adhd had slightly smaller overall brain volumes, thus not allowing for some expansion of certain brain regions and therefore limiting the ability to concentrate. alongside this, the regions that reported differences in size were the caudate nucleus, putamen, nucleus accumbens, amygdala, and hippocampus. the list is notably narrowed down because these were the regions that reported the most significant differences and were shown to have slightly smaller volumes in people with adhd as opposed to the other regions. another study identified specific locations of the differences in volumetric abnormalities within the basal ganglia through the use of lddmm, which stands for large deformation diffeomorphic metric mapping. the anatomy of the basal ganglia is illustrated in figure 1. the lddmm mapping’s purpose revolves around, “the effects of adhd, sex, and their interaction on basal ganglia shapes” (qiu 2009). the lddmm mappings generated basal ganglia templates and laplace-beltrami basis functions in the template coordinates was used to demonstrate shape variations within each structure in relation to the template. the shape variations, “were modeled for each subject as a random field” (qiu 2009). the results from this study encompassed that girls with adhd did not depict any differences in terms of volume or shape. in contrast, “boys with adhd showed significantly smaller basal ganglia volumes compared with typically developing boys, and lddmm revealed the groups the differences between adhd brains vs. non adhd brains julia gainski 3 brain matters volume 2 figure 1: this image demonstrates the anatomy of the basal ganglia. remarkably differed in basal ganglia shapes” (qiu 2009). one study encompassed the stigma behind adhd not being classified as a real disorder of the brain. the study makes the argument that adhd should not be treated differently than other disorders because of the similarities that adhd presents and the similarities it shares with other disorders such as learning disorders. the brain images were collected from 3,200 people. roughly half of the participants had some sort of diagnosis to adhd in the past and half of the participants were never diagnosed with adhd. the national institutes of health (nih) worked with enigma consortium, an international multidisciplinary group that specializes in psychiatric disorders, to conduct this study. in a like manner, figure 2 denotes an image that is superimposed on an icbm (international consortium for brain mapping) standardized anatomical template. one might wonder what these differences look like, and the answer is that on average, differences in brain volumes only range by a few percent between individuals who have adhd with those who do not. adhd is a disorder of the brain that primarily affects behavior and attention. other brain disorders, such as bipolar disorder, affect mood. one study used an mri scan, in which 455 people with adhd received psychostimulant medication. since there were[1] different volumes demonstrated within the five brain regions, it goes to say that adhd is present regardless of the fact that people had taken medication. in essence, this suggests that differences in brain volumes had no correlation to the presence of psychostimulants. [1] a psychostimulant medication is used to treat adhd and narcolepsy. the purpose of psychostimulant is to increase alertness, attention, and energy. therefore, this study had a primary focus on measuring more of the effects of psychostimulants than adhd. this finding presents the phenomenon that psychostimulants are not always proven to be effective as they have failed to produce any significant differences, if any. in terms of the amount of individuals who took them, there were 62 participants in each of the three trials. in a like manner, several studies encompassing the use of psychostimulants, used for treating individuals with depression, have shown how multiple trials and groups of participants have reported no significant differences with the use of psychostimulants (candy 2008). it is important to weigh the benefits and costs before deciding if one should take psychostimulants. not every individual who decides to take them will benefit and some ultimately face negative side effects such as mood swings and headaches. it is vital for an individual to note the progress he or she feels when taking psychostimulants. in order for this person to see if taking psychostimulants a good path for them to take, they should closely monitor their progress and check in with themselves everyday and then make the conclusion with their doctor on if they saw a consistent trend of improvement. as previously mentioned earlier in the article, the study conducted by a team of dutch neuroscientists also analyzed over 3,200 mri scans of the brains of people aged between four and 63 years old. around half of the participants had a diagnosis of adhd and the study analyzed overall brain volumes and inspected the regions most likely to be linked to adhd. they meticulously differentiate between genetics and the differences between brain imaging. the study’s results in brain scans “...revealed that five brain regions were smaller in people with adhd” (gregoire 2017). the study showed that the differences were more drastic in children in comparison to adults, leading the authors to derive that adhd is associated with delayed brain development. the study illustrates that differences are seen to be much more significant in children rather than adults. this is because as an adult brain matures, the brain regions more closely resemble the brains of people who do not have adhd. these differences become less and less distinct over time as opposed to the drastic differences seen between children with adhd brains in comparison to children who do not have adhd. within the study, analyzing different brain volumes and different amounts of psychostimulants, 455 people with adhd took a psychostimulant such (adderall, for example), and then another 600 participants were not currently on any medication but had a history with taking the medication. the mri imaging results demonstrated that the role of the stimulants did not at all correlate to the differences in brain volume. one researcher, dr. martine hoogman, studying the effects of adhd on the human brain, states her take on the role that the brain disorder plays in society: “the results from our study confirm that people with adhd have differences in their brain structure and therefore suggest that adhd is a disorder of the brain. we hope that this will help to reduce stigma that adhd is just a label for difficult children or caused by poor parenting” (paddock 2017). in essence, in today’s world, mental health is constantly being stigmatized and overlooked. in a like manner, brain disorders are being looked at as a rather secondary importance, which ignites the need for more conversations surrounding mental health. as seen in the studies described, certain paths and solutions work better for some than others. individuals with adhd must brain matters volume 2 4 figure 2. differences in neural activity and functional brain patterns between controls and children who have never been medicated with adhd.this image is superimposed on an icbm (international consortium for brain mapping). be mindful of this when deciding on their personalized path in order to treat what they are experiencing, because one solution cannot fix all issues. solutions ought to be approached with the mindset of needing to make collective changes such as dietary selections, having a conversation with a doctor on if psychostimulants are a promising option, and prioritizing the amount of exercise that is sufficient on a daily or weekly basis. on top of making lifestyle changes, one must begin to make internal changes as well, and adapt positive thinking patterns in order to better cope with their disorder. alongside this, it is important to remain optimistic in the midst of daily obstacles; as a society, we must work together to break down these barriers and pay closer attention to how we can accommodate those who need extra assistance. references candy, bridget, et al. “psychostimulants for depression.” cochrane database of systematic reviews, 23 apr. 2008, doi:10.1002/14651858.cd006722.pub2. gregoire, carolyn. “people with adhd have different brains.” huffpost, huffpost, 24 feb. 2017, www.huffpost.com/entry/adhd-brain-disorderstudy_n_58af2326e4b060480e05c139? guccounter=1&amp;guce_referrer=ahr0chm6ly93d3cuz294vz2xllmnvbs8&amp;guce_referrer_sig=aqaaakg_u1nifc2v31ycvjvkmpxjxqitdtj7irjnydrmrtvilvvfsvx3smpetob003vaxd9i3m-o3ken_lzd4lzosg026mf2a_cj_ tfa5pmikvwizma3brdcwc21x-ap3t2nt8_vw-rlvclghy5xlf4fi9kot8bmcjc5nvntez0lnlwa. https://doi.org/10.1371/journal.pone.0049392.g001 lim s-j, fiez ja and holt ll (2014) how may the basal ganglia contribute to auditory categorization and speech perception? front. neurosci. 8:230. doi: 10.3389/ fnins.2014.00230 http://journal.frontiersin.org/article/10.3389/fnins.2014.00230/ full paddock, catharine. “adhd: large imaging study confirms differences in several brain regions.” medical news today, medilexicon international, 16 feb. 2017, www.medicalnewstoday.com/articles/315884.php. qiu, anqi, et al. “basal ganglia volume and shape in children with attention deficit hyperactivity disorder.” american journal of psychiatry, vol. 166, no. 1, 1 jan. 2009, pp. 74–82., doi:10.1176/appi.ajp.2008.08030426. radboud university nijmegen medical centre. &quot;brain differences in adhd.&quot; sciencedaily. sciencedaily, 16 february 2017. &lt;www.sciencedaily.com/releases/2017/02/170216105919.htm&gt;. 5 brain matters volume 2 16 address and contact information here: uiucundergradneurosociety@gmail.com about undergraduate neuroscience journal and undergraduate neuroscience society the undergraduate neuroscience society (uns) is an academic student organization that strives to promote, educate, and hold events that help undergraduates gain a deeper understanding and appreciation for the field of neuroscience. events such as brain awareness week and fundraisers for the brain and behavior research foundation are held. the neuroscience journal committee, a subsidiary of uns, has created a journal entitled “brain matters”. this journal promotes a neuroscience dialogue on campus by publishing student research about topics from neuroscience, psychology, and biology. 10 neurological benefits of mindfulness victoria wu rené descartes was a 17th-century philosopher who popularized the idea of cartesian dualism, an abstract separation between the body and the mind, heavily influencing modern thought. people tend to think of their mind as separate from their brain and body, hence the term “mind over matter”. descartes believed that the connection between the mind and brain occurred at the pineal gland, which he called the “seat of the soul”. because we now know that the pineal gland is responsible for secretion of melatonin, a chemical that contributes to the regulation of our circadian rhythm, we can now understand that this differs from the definition that it was the area where all our thoughts are formed. additionally, from a biological standpoint, the “mind” as thought and abstract ideas originate from electrical and chemical signals in the brain (lockhorst, 2013). there is no separation between mind and body, for the brain works independently and outside of the body. the brain is simply another organ that functions as a piece of a machine, though the mechanisms are anything but simple. as a small error in syntax could lead to a myriad of unforeseen malfunctions in a computer program, minor changes in brain chemistry could lead to serious defects in the rest of the body. studies have shown that chronic stress strongly correlates to psychological disorders, decreased function in learning and attention, and weakening of the immune system (schneiderman, ironson, & siegel, 2008). however, for every action there is an equal and opposite reaction the opposing process is mindfulness meditation, a technique that correlates with improvement in health. effects have been most notable in patients with anxiety and depression, enhancing attention and reducing the risk of future cardiac ailments. mindfulness has proven to be quite an effective remedy in western medicine, despite its distant origin in eastern culture over two millennia ago. the practice of mindfulness, nonjudgmentally focusing the attention on the present moment to achieve mental clarity, originated in the hindu traditions of vedantism. other methods of practicing mindfulness later developed with buddhism around 400 b.c.e. the practice traveled west when jon kabat-zinn, a medical professor, started the mindfulnessbased stress reduction clinic in massachusetts. mindfulness plays a large role in positive psychology, which focuses on people’s strengths and needs for fulfillment. once mindfulness and detailed brain-imaging technology became prevalent in medicine, the door for research was opened. (joaquin, 2017) when researching emotion, fear is the easiest to observe. this is because behaviors associated with fear, such as cowering or running away, are physically exhibited. fear is a strong emotion and necessary for survival, although it can become pervasive and interfere with everyday functioning. when this happens, it is a sign that a person may be suffering from an anxiety disorder. according to the national comorbidity survey by harvard medical school (harvard medical school, 2007), anxiety disorders are the most common psychological disorders in the united states. many medications and treatments for anxiety disorders are used to avoid feelings of fear, but mindfulness takes the approach of confronting and accepting them. some people believe that focusing on the inner experience in a nonjudgmental way can ease discomfort and promote a positive relationship with emotion. (greeson & brantley, 2009) studies have found that it is very likely these people are correct in their hypothesis. according to hofmann, practicing mindfulness over the short course of two months was found to reduce symptoms of panic and anxiety (hedges’ g=.97). mindfulness therapy could be another option as an alternative or addition to medication for anxiety and panic disorders. in a 3-year follow-up, 22 patients who had undergone an 8-week mindfulness-based stress reduction outpatient study were found to have maintained their stress reduction, measured on the hamilton anxiety scale (f(2,32) = 13.22; p < 0.001) (miller, fletcher, & kabat-zinn, 1995). the anterior cingulate cortex (acc), associated with attention, is the brain area most consistently related to mindfulness during studies. the acc functions to filter out distractions and direct attention to the object of focus. it was also found that the acc is responsible for sustained attention (wu et al, 2017). the fronto-limbic structures of the brain that control stress reduction and emotional regulation are also involved. areas associated with attention and emotional regulation in the cerebral cortex were thicker in mindfulness practitioners compared to those who had never practiced this form of meditation. (tang, holzel, & posner, 2015). depression is the second most prevalent psychological disorder the us population faces. incredibly, mindfulness meditation not only lowers the feelings of fear in those with anxiety disorders but also raises the quality of life in patients with depression. as with anxiety, mindfulness meditation is helpful in symptom reduction, it’s unclear as to what neural mechanisms are responsible. more research is needed in these areas for full comprehension, but we do know a few of the brain areas involved as of now. the insula was found to have reduced activation during exposure to negative stimuli in those who practiced mindfulness. this brain area plays a large role in emotional experience and the decrease in activity corresponds to a decrease in rumination, a symptom of depression (paul, stanton, greeson, smoski, & wang, 2012). mindfulness-based cognitive therapy has been shown to reduce symptoms and prevent relapse of depression (p=0.04), though more research needs to be done on the neurological basis of these results (barnhofer et al, 2009). a benefit of mindfulness that is relatively well established is that the practice enhances attention (tang et al, 2015). according to lin et. al., “results reveal that mindfulness as a meditative practice produced a reduction in the difference between the lpp response to negative high arousing and neutral stimuli across time” (lin, fisher, roberts, & moser, 2016). this means attention will be higher for more menial tasks, like studying, in addition to ones that automatically capture our attention, like video games. studies have shown improved attention in long-term meditators. the cognitive decline that comes with age is reduced in these people, due to maintenance of the anterior cingulate cortex through meditation (zanesco, king, maclean, & saron, 2018). there is a strong connection to regulating breath and regulating attention. focused breathing is a method of mindfulness meditation that requires sustained attention to the body and present moment. this is likely the most practiced form of meditation and it has long-term benefits 11 on attention and stress. emotions, focus, and memory become clearer with this practice. breathing directly affects our attention, which cycles with each inhalation and exhalation. inhaling correlates to higher attention, exhaling to lower. mindful breathing works to reduce noradrenaline to a “sweet spot.” too much noradrenaline can cause a jittery, nervous feeling while feelings of sluggishness may result when insufficient amounts are present. this mechanism reduces stress long-term, which benefits other areas of the body (melnychuck et al, 2018). stroke is the fifth biggest killer in the us and heart disease is number one. chronic stress is a risk factor for both. those who suffer from chronic stress have high levels of cortisol, a stress hormone, which increases blood pressure. increased blood pressure for long periods of time increases the risk of heart disease and stroke. corticosteroid is another stress hormone as it. it suppresses the immune system by blocking the transcription of cytokines, proteins which regulate inflammation and immunity. immunosuppression is the result of this chain of events, leading to adverse health issues over time. suppression of the immune system impacts every system of the body and is linked to diseases like osteoporosis and obesity (barshes, goodpastor, & goss, 2004). acute, short-term stress is adaptive and will increase immune function, but chronic stress suppresses it (dhabhar, 2009). mindfulness meditation and focused breathing can be preventative for chronic stress, thereby reducing the risk of stroke and heart disease. although there is a need for more research on the neurologic mechanisms behind the benefits of mindfulness meditation, the studies given here show evidence that some benefits may exist. with age, decline in the ability to learn, solve problems, and reason is an issue common throughout all of humanity. depression and anxiety are the most common mental disorders in the us. stroke and heart disease are some of the top killers in our country. mindfulness meditation is a method that has been found to reduce the symptoms of or prevent these ailments entirely. additionally, it has been around for thousands of years due to its health benefits. combined with new technology, increased understanding of the brain, and modern approaches to medicine, this practice could become more prevalent as a simple, natural treatment for many diseases. notes 1 llp stands for late positive potential. it is an electrophysiological measure of attention given to emotional stimuli. 2 hedges’ g is a statistical test measuring size of an effect, or how much one group differs from another. g is indicative of the number of standard deviations the groups differ by. for reference, g=.2 is considered a small effect and g=.8 is considered a large effect. references barnhofer, t., crane, c., hargus, e., amarasinghe, m., winder, r. j., & williams, m. g. (2009, february 05). mindfulnessbased cognitive therapy as a treatment for chronic depression: a preliminary study. retrieved from https://www.sciencedirect. com/science/article/pii/s0005796709000333 barshes, n. r., goodpastor, s. e., & goss, j. a. (2004, january 01). pharmacologic immunosuppression. retrieved from https:// www.ncbi.nlm.nih.gov/pubmed/14766378 dhabhar, f. s. (2009, june 29). enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. retrieved from https://www.karger.com/ article/abstract/216188 greeson j., brantley j. (2009) mindfulness and anxiety disorders: developing a wise relationship with the inner experience of fear. in: didonna f. (eds) clinical handbook of mindfulness. springer, new york, ny harvard medical school, 2007. national comorbidity survey (ncs). (2017, august 21). retrieved from https://www.hcp.med. harvard.edu/ncs/index.php. data table 1: lifetime prevalence dsm-iv/wmh-cidi disorders by sex and cohort. hofmann sg, sawyer at, witt aa, oh d. the effect of mindfulness-based therapy on anxiety and depression: a metaanalytic review. j consult clin psychol. 2010;78(2):169–183. j. (2017, march 13). history of mindfulness: from east to west and from religion to science. retrieved from https:// positivepsychologyprogram.com/history-ofmindfulness/#hinduism-mindfulness lin, y., fisher, m. e., roberts, s. m., & moser, j. s. (2016, august 26). deconstructing the emotion regulatory properties of mindfulness: an electrophysiological investigation. retrieved from https:// www.frontiersin.org/articles/10.3389/ fnhum.2016.00451 lokhorst, g. (2013, september 18). descartes and the pineal gland. retrieved from https:// plato.stanford.edu/entries/pineal-gland/ melnychuk, m. c., dockree, p. m., o’connell, r. g., murphy, p. r., balsters, j. h., & robertson, i. h. (2018, april 22). coupling of respiration and attention via the locus coeruleus: effects of meditation and pranayama. retrieved from https:// onlinelibrary.wiley.com/doi/epdf/10.1111/ psyp.13091?referrer_access_token=t9lstfepl dgu6joveu3ylita6br2k8jh0krdpfoxc65 t4ao_i-grzhs0tmvptud527u1llrrf9izg5qu bsqljtej9qnmg00jjkvofg4ngod_0q1kkv dbgbenwnq_nrgs miller, j. j., fletcher, k., & kabat-zinn, j. (1999, december 28). three-year follow-up and clinical implications of a mindfulness meditation-based stress reduction intervention in the treatment of anxiety disorders. retrieved from https:// www.sciencedirect.com/science/article/ pii/016383439500025m paul, n. a., stanton, s. j., greeson, j. m., smoski, m. j., & wang, l. (2012, october 14). psychological and neural mechanisms of trait mindfulness in reducing depression vulnerability. retrieved from https://academic.oup.com/scan/ article/8/1/56/1696427 schneiderman, n., ironson, g., & siegel, s. d. (2008, october 16). stress and health: psychological, behavioral, and biological determinants. retrieved january 30, 2019, from https://www.ncbi.nlm.nih.gov/pmc/ articles/pmc2568977/ tang, y., hölzel, b. k., & posner, m. i. (2015, march 18). the neuroscience of mindfulness meditation. retrieved from https://www. nature.com/articles/nrn3916 wu, dingcheng & deng, hanfei & xiao, xiong & zuo, yanfang & sun, jingjing & wang, zuoren. (2017). persistent neuronal activity in anterior cingulate cortex correlates with sustained attention in rats regardless of sensory modality. scientific reports. 7. 43101. 10.1038/srep43101. zanesco, a. p., king, b. g., maclean, k. a., & saron, c. d. (2018, march 28). cognitive aging and long-term maintenance of attentional improvements following meditation training. retrieved from https:// link.springer.com/article/10.1007/s41465018-0068-1 language acquisition device and the origin of language briana sobecks in the early twentieth century, psychologists realized that language is not just understanding words, but also requires learning grammar, syntax, and semantics. modern language is incredibly complex, but young children can understand it remarkably well. this idea supports chomsky’s idea that language learning is innate. according to his hypothesis, young children receive “primary linguistic data” from what is spoken around them, which helps them develop knowledge of that specific language (cowie 2008). children passively absorb language from adults, peers, and exposure to media. however, this data is not sufficient to explain how children can learn unique constructions of words and grammar patterns. previously structuralists created a list of “phrase structure rules” to generate all possible grammar patterns. however, chomsky argued that grammar must also include “transformations” that combine old sentence patterns and reorganize them. he called these patterns “generative grammars.” for a child to understand patterns of this complexity, their language ability must be well developed. the primary linguistic data they’re exposed to isn’t enough to give them this complexity. the complexity of language allows chomsky to refute b.f. skinner’s hypothesis that grammar is developed through operant conditioning. too many usages of each individual word are needed for conditioning to be a viable option. since people can say and understand unique sentences, language ability must transcend pure conditioning. furthermore, the mechanism for operant conditioning is unlikely to take place in a child’s language development. if a child is trying to learn a new grammar pattern and makes a mistake, he or she could either be corrected by their parents or hear the sentence said by a more competent speaker. however, parents may not correct the child, and even if one child hears the correct sentence, it is unlikely that all children will hear a similar phrase. this does not prove that an innate language learning faculty exists, but it does strongly disregard operant conditioning’s role in language development. chomsky proposed a theory of “universal grammar,” in which all grammar follows certain rules that humans implicitly understand. since the data that a child is exposed to is finite, but the number of expressions possible in language is infinite, there must be a way for a child to generate new ideas independent of the vocabulary they have encountered. when first developing the theory, chomsky thought that children would do a “scientific inquiry” to investigate the working patterns of language. later, psychologists created a “parameter setting” model, saying that the device is a normal part of development, and as children grow, “switches” are activated to further their learning (cowie 2008). depending on the more specific patterns of a particular language, the universal grammar can be refined to fit a specific language. even if some children may hear a specific language pattern more than others, the fact that all children know it indicates a poss ble innate language sense. one of chomsky’s main tenants in his lad theory is the poverty of stimulus argument. though children do collect data to learn a language, it is unlikely that the data they are exposed to is enough to master an entire language. instead, they must infer grammatical rules through an internal sense. there are several cognitive factors that support this argument. underdetermination states that the finite data is applicable in infinite situations. in context, this means that children utilize the finite amount of data they hear to generate any possible sentence. degeneracy is another important factor. in regular speech, people often use abbreviated or grammatically incorrect sentences, yet children still learn proper grammar. idiosyncrasy is a third concept. every child is exposed to a different sample of sentences, yet they all develop the same language abilities. this points to the idea that children possess an innate way to interpret these sentences and generate grammatical patterns. fourth is positivity, which states that children only learn correct examples, and do not learn that “nonexample” sentences are incorrect, since they are not exposed to incorrect sentences. in other types of learning, examples are paired with counterexamples to ensure full understanding of a concept. in addition, children do not receive feedback for their sentence usage in most cases, which contrasts most learning from parents or teachers, in which feedback is used to reinforce or correct behavior (cowie 2008). aside from cognitive factors, biological evidence supports the lad hypothesis, since data suggests localization of language ability to certain regions of the brain. broca’s area is a section of the brain that is used for speech production. if this portion of the brain is impaired, then people are unable to utilize complex grammatical paterns. this indicates that broca’s area could contain a cognitive faculty for language development (cowie 2008). all these observations indicate the validity of the lad hypothesis. though b.f. skinner’s theory of cognitive development of figure 1: chomsky’s lad theory corresponds with the localization of language skills in several brain regions, including broca’s and wernicke’s areas. 9 brain matters volume 2 grammar because they can pick up on semantics and put information into the correct context. according to supporters of cognitive language development, children use innate perceptual and cognitive skills to learn language, but these skills are not language-specific, since they allow children to earn other interpersonal communication skills. when children learn languages, their early linguistic abilities are constrained by their overall cognitive function. as a child increases their overall cognitive function, their language ability increases as well. like the innate language theory, the cognitive language theory states that language learning ability increases from input data (behme 2008). however, unlike the innate language theory, cognitive language theory states that children do receive negative evidence in language learning. if a child says a sentence that others do not understand, then the child will realize that their sentence does not make sense. in addition, if a child expects a certain grammar pattern but never hears it, they will realize that this pattern is probably incorrect. parental feedback also shapes a child’s linguistic ability. demetras, post, and snow found that parents will repeat entire correct sentences from their child, but will not fully repeat incorrect ones. if they do repeat an incorrect sentence, they will say the correct version instead. children are more likely to repeat their parent’s corrections of incorrect sentences than to say the incorrect sentence again. according to cognitive psychologists, cognitive development allows young children to learn complex grammar patterns because the development process starts early, even before birth. fetuses can respond to sound at only 22 weeks old, and will postnatally recognize passages that were read to them while in the womb (behme 2008). newborn infants pick up on their own language more than other ones only a few days after birth. they are able to discriminate between languages with different rhythmic patterns, and can discriminate their own language from others after several months. since this ability takes time to develop, it suggests that language learning is not innate in itself. instead, it develops out of their innate auditory ability. studies have indicated that very young babies can learn patterns of speech, suggesting that the language learning process follows the same process of learning other things. though young children learn language at an early age, it takes time for them to refine it and produce meaningful words. children start by babbling in sounds from all languages, but narrow down to sounds from only their languages as they grow and mature. however, infants aren’t necessarily corrected in their babbling, so the exact reason why theynarrow down is unclear. one explanation may be the exposure to their parents’ grammar and speech patterns. this data can lead to their cognitive development of language. when parents speak to children, they use simpler grammar patterns that are easier for them to learn and comprehend. researchers found that most of children’s verbalizations are things they have previously said, suggesting that they practice these phrases to encode them in their brains. just as cognitive linguistic ability is an application of auditory learning, it could also be an application of statistical learning. statistical learning is a general ability that has been observed in other primates, not simply a separate, innate ability in humans. in a study done by jenny saffran, young children were able to sense the boundaries between words and the distribution of speech sounds (behme 2008). they track that some words correspond to certain objects even before they know the meaning of the words, which would not have to occur if language learning was innate. babies can also sense patterns in sounds that appear frequently at the beginning or the end of a word, which is another way for them to learn words. however, the lad theory is not without problems. it states that language is too complex for its syntax to be learned, but this research indicates that children can observe these differences through statistical information. even young children pick up on patterns like verb endings that distinguish different parts of speech. though this does not disprove the lad theory, it does act against the poverty of stimulus argument. another theory of cognitive development, posed by john macnamara, suggests that an infant learns meaning and language independently, and later combines them as they mature. macnamara defines meaning as any idea that a person can express through language, while the language itself is a collection of rules and structures that are used to convey this meaning. speech is a way to convey this meaning (macnamara 1972). language and meaning are almost always combined, but they are two separate ideas.for example, individuals with underdeveloped cognitive function are still able to use other cognitive facilities. assigning words and objects is more complicated than one expects, since there are often figuer 3: a young boy plays with a toy truck. the boy knows that this is a “truck,” but cannot recognize it as a “toy.” brain matters volume 2 10 figure 2: a mother reads to her child. as she reads sentences out loud, her daughter starts to pick up on patterns in the speech rhythms and grammar. multiple words for objects, and it would be difficult to identify which word is being referenced. if an adult references a specific object by name directly, the infant will interpret this as the object’s name. this also occurs even when the word is not the object name, but is used in the same context. for example, if a parent tells their child not to touch an object because “it’s hot,” the child will think the object is called “hot.” after learning names of objects or other nouns, children tend to learn conditional attributes of an object, and finally, they learn permanent attributes. children initially cannot discriminate between more and less descriptive words. for example, a child will know the word “truck,” but will not recognize that his truck is also a “toy.” however, he will also realize that a collection of toys are called “toys.” he treats “toys” as a separate idea from his truck. children learn more abstract words like “and” at a young age, suggesting that they need this word to give meaning to their thought processes. many grammar patterns can express multiple ideas based on context, and many times, the same ideas can be expressed through multiple grammar patterns. children can learn which patterns work in which contexts if they discover what the sentences mean independent of learning the grammar patterns. overall, there is compelling evidence for both the innate and cognitive theories of development. there is heavy evidence showing the development of linguistic ability through cognitive processes. yet these processes do not disprove the existence of a language acquisition device. however, the poverty of stimulus argument does not prove its existence, either. whether or not there is an innate language device in humans, it is clear that humans possess a remarkable ability to understand and produce complex grammar patterns and meaningful sentences. references behme, christina, and s. hélène deacon. “language learning in infancy: does the empirical evidence support a domain specific language acquisition device?” philosophical psychology, vol. 21, no. 5, 2008, pp. 641–71. crossref, doi:10.1080/09515080802412321. cowie, fiona, “innateness and language”, the stanford encyclopedia of philosophy (fall 2017 edition), edward n. zalta (ed.), url = <https://plato.stanford.edu/ archives/fall2017/entries/innateness-language/>. dirven, rené; verspoor, marjolyn. “the cognitive basis of language.” introduction to linguistics, universität koblenz-landau. 2017. course handout. macnamara, john. “cognitive basis of language learning in infants.” psychological review, vol. 79, no. 1, 1972, pp. 1–13. crossref, doi:10.1037/h0031901. images: “mother reading book to child.” pickpik, pickpik.com, 2019, https://www.pickpik.com/mother-and-daughter-mother-daughter-blue-child-love-52016. offringa, reid. “basic sketch of brain areas involved in language.” wikimedia commons, 9 jan. 2006, commons.wikimedia.org/wiki/file:surfacegyri.jpg. “young child playing with toy truck.” pickpik, pickpik.com, 2019, www.pickpik. com/young-girl-child-playing-outside-toys-150243. 11 brain matters volume 2 for quite a while, people considered the mind and body separate. rené descartes himself proposed the idea of what is called the cartesian dualism, that whatever happens to our body leaves our minds untouched. it was believed only the mind can truly affect itself, and thus was born “i think, therefore i am.” more recent scientific advances proved quite the opposite. our minds come from intricate neural connections in our brains. both our bodies and outside influences affect the flow of messenger molecules in our brains analogously to the way our livers or muscles can be affected, to name a few. if anything, our minds could just be an extension of our body, rather than its own separate entity. for example, one of the best ways to improve our brain function is through exercise. while research is still discovering the complete effects of exercise on the brain, many molecular and cellular mechanisms have already been elucidated. exercise is known to improve neural plasticity, increase neurotransmitter efficiency, expand neuron counts, and even prevent cognitive diseases. one of the most significant findings of exercise on brain health was elucidated through neurotrophic factors. these molecules act as growth factors for brain cells, increasing cell growth, signaling, and neural wiring. despite the importance of these factors for our brain, their expression depends on physical exercise. one of the most important neurotrophins is brain-derived neurotrophic factor (bdnf). this molecule can interact with synaptic development of dendrites and axons, allowing them to form specialized connections for specific neuron communication. in turn, better neural communication can aid in learning (cohencory et al., 2011). improved learning can occur immediately after exercise. human subjects were able to improve cognitive performances in learning new material after running on a treadmill. the increase in memory is correlated with bdnf concentration in the bloodstream that also spikes during exercise (winter et al., 2007). it is also shown that consistent exercise can increase bdnf levels compared to sedentary behavior in rats (berchtold et al., 2005). conversely, blocking bdnf contributes to decreased synaptic efficacy and decreased vesicle proteins, both directly harming communication between neurons (vaynman et al., 2006). abstract exercise is seen to physically improve the health and function of the brain. this involves a variety of molecular and cellular mechanisms, including significant increases of beneficial neurotrophic factors like bdnf. in addition, neurogenesis in the hippocampus is also increased after exercise. hippocampal vascular structures, like blood flow, are improved. plasticity is also improved. additional molecular mechanisms can contribute to alleviate symptoms of aging and more serious neuropathic diseases. negative factors like inflammation and reactive oxygen species are mitigated. outline on exercise and brain function andrew zhang figure 1a: axon expressing bdnf-gfp (in green) superimposed with dendrites of second neuron, stained with map2 (in red) (kohara, 2001). figure 1b: movement of bdnf-gfp in axon (kohara, 2001). 1 (other hormones, like the catecholamines dopamine, epinephrine, and norepinephrine were shown to increase through exercise. these hormones are thought to be associated with learning, as they increase signaling in the brain. it is also shown that increased levels of bdnf correlate with physical activity (winter et al., 2007). there are also other neurotrophins with levels that increase with exercise. an example is igf-1, which increases neuron counts in the hippocampus. (trej et al., 2001). nmda receptors, which are responsible for the health and function of neurons, also increase with exercise (farmer et al., 2004). other molecules include tnf-α and vascular endothelial growth factor (vegf). both these molecules improve vascular health, including blood vessel growth and differentiation throughout the body. tnf-α can also increase integrin protein production, which helps cells bind to extracellular structures. these activities can directly impact the vascular supply of nutrients in the brain (ding et al., 2006). because exercise can promote neurotrophic factors and hormones to signal in the brain, all of these effects can lead to a much healthier brain. while the human brain’s overall structure remains stable over adulthood, it can undergo slight changes for the better. exercise can induce these modifications to physical structures. for example, exercise appears to promote neurogenesis, the creation of new neurons. while in most of the brain, the number of neurons stays the same throughout life, the number of neurons can increase in the hippocampus. most of the newly generated neurons appear in the hippocampal dentate gyrus, a region highly responsible for learning and storing long-term memories (cho et al., 2013). higher rates of cell growth appeared in these regions for rats performing consistent treadmill exercise (heo et al., 2014). brain scans in animal studies have also shown improvement from exercise in vascular structures in the brain, like increased blood flow and permeability of the blood brain barrier (yau et al., 2014). these are all correlated with supplying nutrients and cleansing factors to grow and protect neurons. brain scans in mice have also confirmed greater growth in hippocampal areas after consistent exercise. similarly, brain scans in humans have shown analogous changes in the hippocampus as well. the same human subjects were tested in cognitive trials like delayed recall, recognition, and source memory. higher cognitive performance correlated significantly with more exercise (peirera et al., 2007). additionally, young neurons appear to contribute a greater learning potential. new neurons generate faster calcium and sodium concentration spikes, affecting action potentials and signal transduction to neighboring neurons. these neurons also change their behaviors more permanently to signals, compared to older neurons. (schmidt-hieber et al., 2004). these neurons are able to express greater responses to lower levels of signal as they mature, exhibiting long term potentiation. older neurons are more resistant to these changes (ge et al., 2007). long term potentiation indicates increased plasticity, the ability to rewire neural circuits. plasticity in the brain allows it to encode new information and boosts learning. therefore, as consistent exercise increases new neurons, it ultimately leads to more plasticity to the brain and thus increased learning. 2 figure 2a: heat map showing neurogenesis activity in mice, based on cerebral blood volume (peirera et al., 2007). figure 2b: heat map showing neurogenesis activity in humans, based on cerebral blood volume (peirera et al., 2007). exercise is associated with broader health effects as well. even though neurological decline is correlated with aging, exercise has been shown to minimize and reverse these trends. for example, for older subjects, aerobic fitness has been associated with better performances on cognitive tasks, as well as retaining larger hippocampal sizes in the brain (erickson et al., 2009). these trends also extend to symptoms of neurodegenerative diseases that tend to amplify in older age. for example, as exercise promotes neurogenesis in the hippocampus, it helps combat neuron loss in many diseases like alzheimer’s (yau et al., 2014). exercise is also seen to alleviate symptoms of diseases. in rats exhibiting symptoms of parkinson’s disease, consistent exercise appears to reduce short term memory damage (cho et al., 2013). similar findings are shown for rats exhibiting alzheimer’s symptoms, with exercise correlated with better performance in spatial learning (heo et al., 2014). while exercise cannot cure neurodegenerative diseases, they can alleviate symptoms and improve quality of life for people with these diseases. in addition to preventing neurodegenerative conditions, exercise also protects against physical damage to the brain. for example, exercise is shown to protect against stroke-like symptoms in the brain. in stroke, blood flow is deficient in the brain, which can cause swelling and cell death. in animal studies, these symptoms are reduced in animals who performed consistent exercise (ding et al., 2006). other physical damages to the brain come from reactive oxidative species (ros), for example. brain matters・volume v issue ii these are molecules that can originate as byproducts of metabolic reactions. however, ros react inappropriately with other molecules in cells, stopping proper pathways for normal function. this can even affect signaling and cell survival. exercise increases the amount of antioxidant enzymes in cells, protecting cellular function (radak et al., 2016). in animal studies, the rat brain showed an increase in protease activity in cells in response to exercise. these proteases are responsible for breaking down proteins, including misfolded and damaged proteins that act as ros (ogonovsky et al., 2005). exercise provides increased antioxidant protection, which protects the overall health and function of the brain. overall, exercise appears to play an overwhelmingly positive influence on the brain. neurotrophins increase their function after exercise, promoting brain health and learning. structures of the brain responsible for learning also change. neurons increase their potential for efficient communication. exercise also alleviates aging and neurodegenerative symptoms. despite the knowledge already known about exercise, there is still much more to learn about its effects on the brain. exercise also improves the rest of the body, in addition to the brain. based on current knowledge of physical activity, consistent exercise would be a wise choice for improving quality of life. references 1. berchtold, n. c., et al. “exercise primes a molecular memory for brain-derived neurotrophic factor protein induction in the rat hippocampus.” neuroscience, vol. 133, no. 3, pp. 853-861, elsevier, 2005, doi: 10.1016/j.neuroscience.2005.03.026 2. cho, han-sam, et al. “treadmill exercise alleviates shortterm memory impairment in 6-hydroxydopamine-induced parkinson’s rats.” journal of exercise rehabilitation, vol. 9, no. 3, pp. 354-361, korean society of exercise rehabilitation, 30 jun. 2013, doi: 10.12965/jer.130048 3. cohen-cory, s., et al. “brain-derived neurotrophic factor and the development of structural neuronal connectivity.” developmental neurobiology, vol. 70, no. 5, pp. 271-288, wiley, 22 feb. 2010, doi: 10.1002/dneu.20774 4. cotman, carl w., et al. “exercise builds brain health: key roles of growth factor cascades and inflammation.” trends in neurosciences, vol. 30, no. 9, pp. 464-472, sciencedirect, sept. 2007, doi: 10.1016/j.tins.2007.06.011 5. ding, y. h., et al. “exercise preconditioning upregulates cerebral integrins and enhances cerebrovascular integrity in ischemic rats.” acta neuropathologica, vol. 112, no. 74, springerlink, 16 may 2006, doi: 10.1007/s00401-006-0076-6 6. erickson, kik i., et al. “aerobic fitness is associated with hippocampal volume in elderly humans.” hippocampus, vol. 19, no. 10, pp. 1030-1039, wiley, oct. 2009, doi: 10.1002/hipo.20547 7. farmer, j., et al. “effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male sprague-dawley rats in vivo.” neuroscience, vol. 124, no. 1, pp. 71-79, elsevier, 2004, doi: 10.1016/j.neuroscience.2003.09.029 8. ge, shaoyu, et al. “a critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain.” neuron, vol. 54, no. 4, pp. 559-566, cell press, 24 may 2007, doi: 10.1016/j.neuron.2007.05.002 9. heo, yu-mi, et al. “treadmill exercise ameliorates disturbance of spatial learning ability in scopolamine-induced amnesia rats.” journal of exercise rehabilitation, vol. 10, no. 3, pp. 155-161, korean society of exercise rehabilitation, 30 jun. 2014, doi: 10.12965/jer.140110 10. kohara, k., et al. “activity-dependent transfer of brainderived neurotrophic factor to postsynaptic neurons.” science, vol. 291, no. 5512, pp. 2419-2423, science, 23 mar. 2001, doi: 10.1126/science.1057415 11. ogonovsky, h., et al. “the effects of moderate-, strenuousand over-training on oxidative stress markers, dna repair, and memory, in rat brain.” neurochemistry international, vol. 46, no. 8, pp. 635-640, elsevier, jun. 2005, doi: 10.1016/j.neuint.2005.02.009 12. pereira, ana c., et al. “an in vivo correlate of exerciseinduced neurogenesis in the adult dentate gyrus.” pnas, vol. 104, no. 13, pp. 5638-5643, national academy of sciences, 27 mar. 2007, doi: 10.1073/pnas.0611721104 13. petzinger, giselle m., et al. “exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in parkinson’s disease.” neurology, vol. 12, no. 7, pp. 716-726, the lancet, 01 jul. 2013, doi: 10.1016/s14744422(13)70123-6 14. radak, z., et al. “physical exercise, reactive oxygen species and neuroprotection.” free radical biology and medicine, vol. 98, pp. 187-196, elsevier, sept. 2016, doi: 10.1016/j.freeradbiomed.2016.01.024 15. schmidt-hieber, christoph, et al. “enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus.” nature, vol. 429, pp. 184-187, nature, 25 apr. 2004, doi: 10.1038/nature02553 16. trejo, josé l., et al. “circulating insulin-like growth factor i mediates exercise-induced increases in the number of new neurons in the adult hippocampus.” journal of neuroscience, vol. 21, no. 5, pp. 1628-1634, society for neuroscience, 01 mar. 2001, doi: 10.1523/jneurosci.2105-01628.2001 3 4 17. vaynman, shoshanna s., et al. “exercise differentially regulates synaptic proteins associated to the function of bdnf.” brain research, vol. 1070, no. 1, pp. 124-130, elsevier, 27 jan. 2006, doi: 10.1016/j.brainres.2005.11.062 18. winter, b. “high impact running improves learning.” neurobiology of learning and memory, vol. 87, no. 4, pp. 597-609, elsevier, may 2007, doi: 10.1016/j.nlm.2006.11.003 19. yau, suk-yu, et al. “physical exercise-induced adult neurogenesis: a good strategy to prevent cognitive decline in neurodegenerative diseases?” biomed research international, vol. 2014, no. 403120, hindawi, 09 apr. 2014. doi: 10.1155/2014/403120 brain matters・volume v issue ii copy of volume 6 publication abstract autism spectrum disorder (asd) is a disorder with many symptoms ranging from a lack of social skills and communication to repetitive actions and behaviors. . the disorder is characterized by a large spectrum, making it difficult to diagnose, due to the wide variety of symptoms it can portray in affected people. asd poses a challenge on a worldwide scale due to lack of information regarding causes or curative treatment. though there are no acknowledged cures, there are many types of therapies for children with asd all aimed at improving their symptoms (“autism spectrum disorder”, 2022). one possible treatment option that is being researched is ‘oxytocin therapy’. oxytocin therapy utilizes oxytocin -a hormone/chemical messenger that promotes qualities of recognition, trust, and bonding which leads to its positive enforcement of social interactions in people (deangelis, 2008). these qualities are what led to the development of a hypothesis that this hormone could be administered in a therapeutic form to improve the social functioning in those diagnosed with asd (ford, n.d.). this neuropeptide is administered intranasally and has been researched mostly in young children and teenagers. the results from these studies prove to be controversial as they display both positive as well as negative findings. hence, further research needs to be conducted on oxytocin therapy before a comprehensible conclusion can be made on its outcome. using oxytocin as a therapy for individuals with autism spectrum disorder alisha babu introduction in 2018 it was established that an average of 1 in 4 children are diagnosed with autism spectrum disorder by the cdc (“data and statistics”, 2022). autism spectrum disorder (also known as asd) is a neurodevelopmental disorder characterized by difficulties in social communication and interaction (“autism spectrum disorder”, 2022). patients diagnosed with autism have a large number of symptoms and behavioral abnormalities. these symptoms include: social impairment with communication difficulties along with repetitive and characteristic behaviors. specifically, signs of this include attention deficits such as failing to respond to one’s name when called, lack of eye contact, and an abnormal range of speech (no speech or fluent speech that may be awkward or inappropriate). repetitive behaviors may include certain bodily or speech ticks as well as an obsessive/deep interest in ideas or concepts which are intriguing to the patient(“autism spectrum disorder”, 2022). doctors and clinicians categorize the disorder into different types based on these symptoms. one type of asd is known as high functioning autism (hfa) which is also known as level 1 autism, and another type is known as low functioning autism (lfa) which is also called level 3 autism. (fredericks, 2008). patients with high functioning autism are able to read, write, and speak efficiently and are able to perform basic life skills such as eating and getting dressed. they show incredible persistence, can recognize patterns, and pay attention to detail. however, they experience difficulties with social interaction, are hypersensitive to their environment, display uncoordinated movements, and lack desire for a routine. (“what is asperger syndrome?”, n.d.). level 2 includes the same symptoms, but more severe, with marked deficits in social interaction and verbal display. level 3 is characterized by the most prevalent symptoms which characterizes it as low functioning autism. these symptoms include severe deficits in social interaction and verbal communication (“autism diagnosis criteria”, n.d.). patients diagnosed with level 3 asd are typically in need of full time aides and/or intensive therapy (holland, 2018). children and adults with low functioning autism (lfa) will commonly show pronounced symptoms including limited social abilities, repetitive behaviors, and restrained communication skills. research indicates that 25-50 percent of individuals with lfa will never be able to achieve the skill of functional speech in their lifetime. patients diagnosed with lfa also tend to have more memory impairments as compared to patients with hfa (ni chuileann & quigley, 2012). typically, asd is diagnosed during childhood. if symptoms are very apparent, diagnoses can be made at the early age of 18 months of age. this early diagnosis can be sought if the child shows signs of asd at the age of 6 to 12 months. however, it is also possible for autistic symptoms to emerge and subside by the age of 24 months (webmd editorial contributors, n.d.). although asd is not curable, there are many treatments (including medications and a variety of different therapies) that can alleviate its symptoms. one new type of therapy known as oxytocin therapy has been recently researched and is considered effective in treating individuals with asd. oxytocin also known as alpha-hypophamine is a hormone/chemical messenger that is produced in the hypothalamus and is transported and stored in the posterior pituitary gland. subsequently, the pituitary releases the hormone into the bloodstream in response to a trigger. the secretion of oxytocin from the pituitary gland relies on the activity of neurons within the hypothalamus excitation of these neurons leads to the release of oxytocin into the 1brain matters volume vi bloodstream (“oxytocin”, n.d.). the roles of oxytocin span in variety. one significant role of the hormone is specifically to trigger contractions of the uterine wall and lactation during childbirth. not only does oxytocin stimulate the muscles within the uterus to contract but also boosts production of prostaglandins which sustain these contractions. the psychological effects of these increased levels of oxytocin during childbirth can lead to “reducing pain and anxiety, enhancing well-being, and promoting interaction and bonding with the child” (doherty, n.d.). oxytocin is also known to play a role in facilitating social-interactions with others and can encourage their ability to affiliate with others. stressful situations can also boost levels of oxytocin in the body. this response has been linked with low norepinephrine levels, blood pressure, and heart rate (deangelis, 2008). the hormone is capable of enhancing trust or suspicion, affiliation or aggression, sexual arousal, and learning and memory (ford, n.d.). the role oxytocin has within social bonding and stress regulation is what led researchers to hypothesize that oxytocin could be utilized as an effective therapy for those with asd (deangelis, 2022). oxytocin therapy for autism spectrum disorder oxytocin therapy aims to optimize the circuits that underlie social deficits in those with asd while improving reward, motivation, and learning in them (guastella, 2016). nature reviews neurology states that, “oxytocin increases the salience of social stimuli and fine-tunes neural processes so that an organism can better attend and respond to those stimuli”(ford, n.d.). specifically, oxytocin facilitates the flow of social information from incoming sensory signals. this information is encoded in the regions involved with cognitive processes such as reward, learning, and memory. the method of administration of this treatment would be through a nasal spray. this method of therapy was observed and analyzed through many different studies and trials. one randomized double-blind clinical trial studied oxytocin’s effect on children with asd conducted by yatawara et al. in this trial, 31 children aged 3-8 and affected with asd were used as participants. these participants were randomly assigned drug kits which either had an oxytocin nasal spray or a placebo spray. the first dose started with 3 iu (international units) twice a day and gradually increased to 12 iu twice a day (full dose) by day 7. 15 of the participants had ‘oxytocin then placebo’ and 16 had ‘placebo then oxytocin’. this treatment lasted for a total of 5 weeks. the participants’ oxytocin levels were measured before and after the treatment and their behavior was observed (yatawara et al., 2015). results of this experiment revealed that children aged 3-8 with autism had an improved social responsiveness as rated by their care-giver over a 5 week course of oxytocin treatment. this study shows how there can be significant improvements caused by this new form of therapy, however another study experimenting with the effects of oxytocin with individuals with autism did not show as promising results. brain matters volume vi another study published in the new england journal of medicine was conducted using 290 participants aged 3-17 years diagnosed with autism spectrum disorder. these participants were administered 24-40 international units of intranasal oxytocin or placebo twice a day for a maximum of 24 weeks. clinical questionnaires were completed by the parents/guardians of the participants in 4 week intervals. the data provided by 277/290 participants had shown that the administration of oxytocin had no effect on asd symptoms (sikich et al., 2021). the ability of oxytocin to penetrate through the blood/brain barrier and diffuse intracerebrally has been questioned due to its short half-life. instead of the chronic supplementation route, researchers wonder if enhancing oxytocin signaling could be a promising treatment. in addition to solely supplying the participants with doses of oxytocin, researchers speculate whether pairing this intranasal dose with cognitive and behavioral therapy would prove to be an effective method (ford, n.d.). another randomized, double-blind, placebo-controlled study utilized 19 adult participants diagnosed with high functioning autism or asperger’s disorder 16 males. these participants were aged 33 years with a standard deviation of 13. the subjects were randomized to a dose of 24 iu (6 puffs) intranasal oxytocin twice daily for 6 weeks. their social and cognitive function was measured using the diagnostic analysis of nonverbal accuracy, and repetitive behaviors were measured through repetitive behavior scale revised. molecular autism states that “secondary measures included the social responsiveness scale, reading-the-mind-in-theeyes test and the yale brown obsessive compulsive scale – compulsion subscale and quality of life (world health organization quality of life questionnaire – emotional/social subscales). these tests were conducted every 2 weeks. results showed that based on the scores of the measurement scales, improvements occurred in social cognition and quality of life after the full 6 weeks of dosage (anagnostou et al., 2012). conclusion the skewed results obtained from the research conducted so far indicates that utilizing oxytocin as a therapy needs to continue being researched. a multi-level meta-analysis conducted by huong et al and published in the journal of neuroscience and biobehavioral reviews highlights the promise of using oxytocin as a new generation therapeutic to address core social impairments in asd (huang, 2021). there is still much that needs to be studied about the direct effects of oxytocin on one’s actions and attitudes before a clear determination can be made on whether this therapy will be useful in improving the symptoms in those diagnosed with asd. future studies should involve larger numbers of participants with wider spectrums of race, age, and gender represented in order to see if these traits affect the results oxytocin therapy can have on its user with asd. there must be a wider pool of participants with diversity in age as well as gender to see if these traits affect the results oxytocin can have on its user with asd. 2 anagnostou, e. (2012, december 12). intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. molecular autism. retrieved may 1, 2022, from https://molecularautism.biomedcentral.com/articles/10.11 86/2040-2392-3-16 chuileann, s. n. (2012, october 30). assessing recollection and familiarity in low functioning autism. springer link. retrieved may 1, 2022, from https://link.springer.com/article/10.1007/s10803-0121697-3 deangelis, t. (2008, february). the two faces of oxytocin. american psychological association. retrieved march 26, 2022, from https://www.apa.org/monitor/feb08/oxytocin doherty, c. (2021, january 7). what is oxytocin? verywell health. retrieved march 23, 2022, from https://www.verywellhealth.com/what-is-oxytocin5090160 ford, c. l. (n.d.). refining oxytocin therapy for autism: context is key. nature reviews neurology. retrieved april 29, 2022, from https://www.nature.com/articles/s41582-021-00602-9 guastella, a. j. (2016, february). oxytocin treatment, circuitry, and autism: a critical review of the literature placing oxytocin into the autism context. science direct. retrieved march 27, 2022, from https://www.sciencedirect.com/science/article/pii/s00063 22315005430 hoffman, m. (2020, december 6). what are the types of autism spectrum disorders? webmd. retrieved april 28, 2022, from https://www.webmd.com/brain/autism/autismspectrum-disorders holland, k. (n.d.). high-functioning autism. healthline. retrieved april 28, 2022, from https://www.healthline.com/health/high-functioningautism#asperger's-syndrome. huang, y. (2021). intranasal oxytocin in the treatment of autism spectrum disorders: a multilevel meta-analysis. neuroscience & biobehavioral reviews, 122, 18-27. https://doi.org/10.1016/j.neubiorev.2020.12.028 low functioning autism ? symptoms, signs, treatments, and more. (n.d.). angelsense. retrieved may 1, 2022, from https://www.angelsense.com/blog/low-functioningautism/ oxytocin. (n.d.). you and your hormones. retrieved march 23, 2022, from https://www.yourhormones.info/hormones/oxytocin/ sikich, l. (2021). intranasal oxytocin in children and adolescents with autism spectrum disorder. new england journal of medicine, 385(16), 1462-1473. https://doi.org/10.1056/nejmoa2103583 quigley, j., and s. ni chuileann. "assessing recollection and familiarity in low functioning autism." journal of autism and developmental disorders, vol. 23, pp. 140622. medline with full text, eds.a.ebscohost.com/eds/detail/detail? references 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. vid=5&sid=de746ea2-cccd-4198-b3097cdc1d3e060d%40sessionmgr4007&bdata=jkf1dghuex blpwnvb2tpzsxnzw8sdxjslglwjmdlb2n1c3rpzd1zod q3ntc0mszzaxrlpwvkcy1saxzljnnjb3blpxnpdgu%3 d#db=mnh&an=23108988. accessed 1 may 2022. sikich, l. (2021). intranasal oxytocin in children and adolescents with autism spectrum disorder. new england journal of medicine, 385(16), 1462-1473. https://doi.org/10.1056/nejmoa2103583 what is asperger syndrome? (n.d.). what is asperger syndrome? retrieved april 30, 2022, from https://www.autismspeaks.org/types-autism-whatasperger-syndrome yatawara, c. j. (2015, october 27). the effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial. nature. retrieved march 27, 2022, from https://www.nature.com/articles/mp2015162 14. 15. 16. 3brain matters volume vi https://www.verywellhealth.com/what-is-oxytocin-5090160 https://doi.org/10.1056/nejmoa2103583 https://doi.org/10.1056/nejmoa2103583 2 contents • editor’s note 3 • a brief review on the nutrient effects on the brain and implications by do yeon (jason) kim 4 • brain development of schizophrenic patients by bailey s. zinger 6 • neural pathways of anxiety by luke lalonde 8 • neurological benefits of mindfulness by victoria wu 10 • the origin, history and science of memory by neil doherty 12 • writer’s bio 15 cc image courtesy by balapagos on flickr on the cover: a beautiful brain with augumenter colors. cc image courtesy by _dj_ on flickr. bilingualism in young children has several cognitive benefits that lead to increased academic performance. between monolingual and bilingual children, behavioral differences can be observed as early as infancy. studies show that bilingualism influences the development of executive control, which includes cognitive abilities such as problem-solving, memory, and inhibition control. this early cognitive advantage carries into the classroom where skills such as problem solving and adapting to new information are critical for educational success. learning a second language trains the mind to better recognize linguistic patterns that can be applied to increased reading skill. infancy is a stage for critical lingual development in children. although their behavior may seem relatively simple, infants are constantly making observations that will guide their cognitive development. for example, newborn babies can sense a difference between their mother’s voice and a stranger’s voice (winkler et al., 2003). babies must learn to recognize the unique phonemes in the languages surrounding them before they can learn how to speak. in her book train your mind, change your brain, author sharon begley discusses how the neuroplasticity of infant brains is the basis for forming lifelong neural circuits in parts of the brain that are responsible for language (2008). in babies, hearing a language exercises the neural circuits in the brain that will encode the unique phonemes required for fluency. thus, sounds heard in the earliest years of life structure language-related brain tissue. neuroplasticity involves the relationship between an individual’s brain and external environment. for bilinguals, the additional language-learning practice changes the physical composition of white and grey matter in their brains. white matter refers to the myelinated nerve axons in the brain while grey matter represents the unmyelinated nerve cell bodies (mercadante & tadi, 2020). through vbm brain imaging, mechelli et al. found that bilinguals have a higher amount of grey matter in the left inferior parietal cortex, a region responsible for language processing, than monolinguals (2004). furthermore, they compared grey matter composition between “early bilinguals” who learned their second language before age five and “late bilinguals” who learned their second language during adolescence. the researchers showed that early bilinguals have a stronger increase in grey matter than late bilinguals. additionally, bilinguals completed tests to measure skill level in their second language, and imaging analysis concluded that subjects with higher test scores had increased grey matter than those with lower scores. overall, the evidence of increased grey matter in bilinguals could explain the observed differences in executive function between bilinguals the academic advantages of a bilingual brain emma ibanez and monolinguals. researchers, agnes melinda kovács and jacques mehler (2009), designed an experiment to assess the effect of bilingualism on the executive function in babies. the researchers placed 7-month-old monolingual and bilingual babies in front of a screen divided into right and left sections. to begin each trial, a predetermined word was said to the baby. right after the baby heard the word, a picture of a puppet appeared on the left or right side of the screen. the puppet appeared on the same side of the screen for the first part of the experiment, and trials were repeated so that the baby learned to expect the puppet after hearing the word. for the 2nd phase of the experiment, the researchers changed the location of the puppet to the opposite side of the screen and measured how many rounds were necessary for the baby to adapt to the change. the experimental data showed that bilingual babies relearned the puppet location faster than monolingual babies (kovács & mehler, 2009). this ability to adjust to a new stimulus is a measurable indication of executive control, proving that bilingual babies have better executive control than monolingual babies. cognitive gains from bilingualism represented by similar studies signal language development in infancy as the foundation for enhanced academic performance observed in older age. as children learn how to speak, executive control is measured using a wide variety of tests because they can respond to verbal or written instructions. one commonly explored cognitive advantage in bilinguals is the idea of “conceptual inhibition,” which measures the ability of the participant to redirect their focus to a new stimulus after having learned to associate a predetermined sensory cue with an old stimulus (carlson & meltzoff, 2008). this method of measuring inhibition was also the premise for the infant study that assessed the babies’ ability to relearn which side to expect the puppet picture. researchers, stephanie m. carlson and andrew n. meltzoff, measured executive control in groups of bilingual and monolingual children to better understand the relationship between bilingualism and conceptual inhibition. one experiment--the advanced dimensional change card sort (dccs) test--required the children to separate a stack of cards. various shapes and colors were pictured on all the cards, but a portion of the cards also had a star next to the shape. then, the children were told to organize the cards by shape unless the card had a star. instead, cards with stars were categorized based off the card’s color. the children had to inhibit the instruction to separate by shape each time they pulled out a card with a star. inhibition tests like the advanced dccs from the carlson and meltzoff study found that bilingual children were better than monolingual children in evaluating conflicting information through suppression of a previously learned 8brain matters・volume v issue ii concept to adapt to the new requirements of a task. thus, organizing one’s own brain around two languages induces early problem-solving practice that can be applied in academic environments. bilinguals also have an advantage in developing metalinguistic awareness, which is a skill involved in learning how to read. metalinguistic awareness is “the metacognitive ability that consciously reflects on the structure of linguistic knowledge and the cognitive processes engaged in literacy learning” (sun 1, 2016). therefore, an individual with high metalinguistic awareness can effectively analyze their language’s rules for grammar, syntax, etc. in a study conducted by lichao sun, monolingual and bilingual children were given the same exercises that measured metalinguistic awareness. one exercise, called the “zoo game,” involves a similar premise of conceptual inhibition used in the other studies. children had to choose whether to press a button depending on what animal appeared on screen i.e., clicking the button when an orangutan appeared was considered an incorrect response. in the collected data, bilingual children made fewer mistakes than monolingual children in choosing the right response, meaning that they were better able to inhibit a conflicting response by remembering the game rules and applying them to the provided stimulus. additionally, the bilingual children gave their responses quicker than the monolingual children. although bilingualism lends its cognitive advantages to the classroom environment, secondary factors like socioeconomic status influence greatly to the extent of an individual’s academic performance. for example, the carlson and meltzoff study included participants from various socioeconomic backgrounds, which is an extra variable during data analysis. bilinguals of different socioeconomic backgrounds might display different characteristics of executive control due to individual access to books, libraries, teachers, and other resources involved in language development. ultimately, carlson and meltzoff were able to adjust for variability in socioeconomic status in order to isolate differences in executive function that were directly related to monolingualism and bilingualism. in addition, the sun study was able to compare monolingual and bilingual children of similar socioeconomic backgrounds and conclude that bilinguals had a metalinguistic advantage over monolinguals. in the united states, a 2010 survey found that 22% of school-going children speak another language within their household (national center for education statistics, 2012). thus, bilingual children make up a significant portion of classrooms where their enhanced executive control and metalinguistic awareness can be essential assets for problem solving and literacy development. socioeconomic conditions can help or hinder the overall academic performance of both bilingual and monolingual students, so specialized attention from educators may vary across individual needs within the classroom. beyond childhood, bilingualism provides an increased communication capacity that is helpful for pursuing job opportunities. therefore, individuals can benefit from their bilingualism at each stage of life. references 1. begley, s. (2008). train your mind, change your brain: how a new science reveals our extraordinary potential to transform ourselves. ballantine books. 2. carlson, s. m., & meltzoff, a. n. (2008). bilingual experience and executive functioning in young children. developmental science, 11(2), 282–298. https://doi.org/10.1111/j.1467-7687.2008.00675.x 3. kovács, a. m., & mehler, j. (2009). cognitive gains in 7month-old bilingual infants. proceedings of the national academy of sciences, 106(16), 6556-6560. https://doi.org/10.1073/pnas.0811323106 4. mechelli, a., crinion, j. t., noppeney, u., o'doherty, j., ashburner, j., frackowiak, r. s., & price, c. j. (2004). structural plasticity in the bilingual brain. nature, 431(7010), 757-757. https://doi.org/10.1038/431757a 5. mercadante, a. a., & tadi, p. (2020, january). neuroanatomy, gray matter. national center for biotechnology information. https://www.ncbi.nlm.nih.gov/books/nbk553239/ 6. national center for education statistics. (2012, august). higher education: gaps in access and persistence study – executive summary https://nces.ed.gov/pubs2012/2012046/summary_1.asp 7. sun, l. (2016). analyzing bilingual advantage in metalinguistic awareness: the roles of executive functioning and vocabulary knowledge on metalinguistic tasks. [master’s thesis, university of california los angeles]. https://escholarship.org/uc/item/5wn18640 8. winkler, i., kushnerenko, e., horvath, j., ceponiene, r., fellman, v., huotilainen, m., naatanen, r., & sussman, e. (2003). newborn infants can organize the auditory world. proceedings of the national academy of sciences, 100(20), 11812-11815. https://doi.org/10.1073/pnas.2031891100 9 a prelude to modular theory few can contest the complicated and interdisciplinary origins of neuroscientific study, as its precise date of birth is obscure. however, it is important to place the first true and deliberate neuroscience studies in proper historical context so we can fully appreciate and understand why topics were studied through the lens of modular theory. ancient egyptians considered the brain and its organic projections to be little more than waste, instead believing that the true “seat of the soul” was the heart (chudler, n.d.). this view was replicated in early greek and biblical texts but represented the consolidation of personality and human character into physiological terms. later, hippocrates and his followers rebuked this dogma in early physiology, instead arguing that the brain was the major control center for the body and possessed three ventricles, each of which was responsible for a different mental faculty: imagination, reason, and memory (chudler, n.d.). this view was supported by the greek physician galen who wrote extensively on the subject and had a profound influence on enlightenment philosophers such as rene descartes (chudler, n.d.). hippocrates, galen, and descartes’ collective writings emphasized an increasingly compartmentalized view of brain structure and function, a sentiment that came to a head in the early 19th century under the directorship of the german physiologist franz joseph gall, the founder of the study of phrenology (fodor, 1983). phrenology borrowed major tenets of previous neurophysiological literature such as continuing to support the notion that the brain was the principal organ of the mind. gall took those previous ideas to new maxims, claiming that the brain represented a collection of precisely localized cerebral organs with specific functions (figure 1). the strength and proficiency of those particular functions, he argued, were proportional to the relative sizes and geometries of their respective skull regions. many would correctly conclude this understanding of neurophysiology to be akin to pseudoscience, but the dangerous influence phrenology has had on research in neuroscience must not be understated. the writings and lectures of gall, his collaborators, and his students spread throughout the english-speaking world during the 19th century and fomented a number of debates about the methods employed to justify the major principles of phrenology (yildirim & sarikcioglu, 2004). physiologist jean pierre flourens performed experimental brain excisions on pigeons and observed their consequential behavior to demonstrate that the defined brain regions in phrenology had little experimental backing. these ablations, however, caused varied deficiencies and behavioral abnormalities suggesting that some interplay did still exist between brain regions and behavior (yildirim & sarikcioglu, 2004). an avalanche of research soon followed, characterizing and qualifying these interactions, along with the functions of a number of other brain and nerve components (figure 2). were it not for the early writings and claims of phrenology, the brain might have not been drawn into so many distinct components over the next two centuries. modular theory comes under scrutiny significant progress has been made over the last several decades in analyzing and characterizing brain regions and tissues. our predecessor neurophysiologists of the late 1700s and 1800s lacked the sophisticated imaging technology we use today. our imaging techniques provide a far more nuanced view of the brain, permitting us to see individual cells with profound resolution as seen in the golgi staining technique (finger, 2004). golgi staining, developed by camillo golgi in 1873, entails the perfusing of silver nitrate into the cell bodies of neurons, the functional unit outcomes in neuroscience education: modular theory and network theory thomas romanchek figure 1: phrenology chart [jpg]. (1920). retrieved from https:// www.sciencephoto.com/media/1002821/view/phrenology-chart figure 2: blausen.com staff (2014). medical gallery of blausen medical 2014 [png]. retrieved from https://en.wikipedia.org/wiki/human_brain#/media/file:blausen_0102_ brain_motor&sensory_(flipped).png figure 3: methoxyroxy (2005). pyramidal hippocampal neuron [jpg]. retrieved from https:// commons.wikimedia.org/wiki/file:pyramidal_hippocampal_neuron_40x.jpg 1 brain matters volume 2 of the nervous system. the resulting stains depict darkened cell bodies and axons, the cellular projections that neurons use to communicate with one another (figure 3). this advent in imaging technology allowed scientists to observe the actual connections and highways of communication between distant regions within the nervous system (finger, 2004). modular theory was beginning to be forced on the defense for the first time since its birth two centuries prior. cell imaging had its uses but had fairly limited applications when it came to in-vivo study of the brain and its operations. cell and tissue isolation required the sacrifice of animal subjects and the collection of brain matter from cadavers. the first in-vivo studies of brain function and organization came about as the result of the invention of the x-ray in 1895 by wilhelm konrad roentgen. the first images from this technology gave researchers a valuable opportunity to observe naturally-occurring brain deterioration in living human subjects and to relate the damage location and intensity with the behaviors and actions the subjects expressed (finger, 2004). early work demonstrated the lack of uniformity in brain tissue between humans. regions thought to be related to language comprehension and speech production were found to differ in size and location between subjects. furthermore, the degree of gyration of those and other brain regions was unique for everyone who was imaged (triarhou, 2017). overt dissimilarities in brain appearance began to give way to mounting criticism of the well-defined module mold of brain organization. both cell and brain imaging had important implications in research, but limited potential because each perspective provided only a snapshot of activity at a single given moment. it was not until the invention and implementation of imaging and even neurostimulator technologies that such a feat was possible. positron emission tomography (pet) and magnetic resonance imaging (figure 4) allowed scientists to observe the brain in action and directly measure the activity of brain regions through the circulation and exchange of blood and oxygen. these were complemented with experimental chemical stimulation, light stimulation through optogenetics, and transcranial magnetic stimulation (figure 5) to directly test relationships of stimulation and inhibition with brain activity (badcock et al., 2019). these technologies revealed the limited importance of clusters of cells and tissues in action execution, and the greater relevance of their overarching and interconnected communication networks. however, a substantial disconnect still exists between what research has managed to reveal about the merits of network theory and what is being actively taught in classrooms. referencesreferences badcock, p. b., friston, k. j., ramstead, m. j. d., ploeger, badcock, p. b., friston, k. j., ramstead, m. j. d., ploeger, a., & hohwy, j. (2019, may 21). the hierarchically mechanistic mind: an evolu-a., & hohwy, j. (2019, may 21). the hierarchically mechanistic mind: an evolutionary systems theory of the human brain, cognition, and behavior. retrieved tionary systems theory of the human brain, cognition, and behavior. retrieved from https://doi.org/10.3758/s13415-019-00721-3from https://doi.org/10.3758/s13415-019-00721-3 bassett, d. s., & sporns, o. (2017). network neuroscience. nature neuroscience, bassett, d. s., & sporns, o. (2017). network neuroscience. nature neuroscience, 20(3), 353–364. doi:10.1038/nn.450220(3), 353–364. doi:10.1038/nn.4502 blackmore, d.g. (2013). massive modularity: why it is wrong, and what it can blackmore, d.g. (2013). massive modularity: why it is wrong, and what it can teach us anyway.teach us anyway. chudler, e. h. (n.d.). milestones in neuroscience research. retrieved from chudler, e. h. (n.d.). milestones in neuroscience research. retrieved from https://faculty.washington.edu/chudler/hist.htmlhttps://faculty.washington.edu/chudler/hist.html finger, stanley (2004). minds behind the brain: a history of the pioneers finger, stanley (2004). minds behind the brain: a history of the pioneers and their discoveries. new york: oxford university press. p. 29. isbn 978-and their discoveries. new york: oxford university press. p. 29. isbn 97801951818210195181821 fodor, j. a. (1983). the modularity of mind. cambridge, ma: the mit press.fodor, j. a. (1983). the modularity of mind. cambridge, ma: the mit press. national institutes of health. (2018, november 2). nih greatly expands invest-national institutes of health. (2018, november 2). nih greatly expands investment in brain initiative. retrieved from https://www.nih.gov/news-events/ment in brain initiative. retrieved from https://www.nih.gov/news-events/ news-releases/nih-greatly-expands-investment-brain-initiative.news-releases/nih-greatly-expands-investment-brain-initiative. sporns, o., & betzel, sporns, o., & betzel, r. f. (2016). modular brain networks. annual review of psychology, 67, 613–640. doi:10.1146/annurev-psych-122414-033634 triarhou l. c. (2017). the comparative neurology of neocortical gyration and the quest for functional specialization. frontiers in systems neuroscience, 11, 96. doi:10.3389/fnsys.2017.00096 white house office of the press secretary. (2013, april 2). fact sheet: brain initiative. retrieved from https://obamawhitehouse.archives.gov/the-press-office/2013/04/02/fact-sheet-brain-initiative yildirim, f. b., & sarikcioglu, l. (2007). marie jean pierre flourens (1794 1867): an extraordinary scientist of his time. journal of neurology, neurosurgery, and psychiatry, 78(8), 852. doi:10.1136/jnnp.2007.118380 figure 4: leblanc, r. (2009). sagittal t1 midline mri scan of reigh’s brain [jpg]. retrieved from https://www.flickr.com/photos/reighleblanc/3854685038. figure 5: us national institute on aging, alzheimer’s disease education and referral center (2008). pet scan of a normal human brain [jpg]. retrieved from https://commons.wikimedia.org/wiki/ file:pet_normal_brain.jpg. brain matters volume 2 2 copy of brain matters template final abstract procrastination is defined as the voluntary postponement of important tasks while being aware of the negative consequences. this phenomenon is found to be very common in undergraduate students with over 70% claiming to be frequent procrastinators. the origin of procrastination can vary from person to person, however in general this behavior is the result of many biological and psychological factors. thankfully, through specific training methods we can adjust our behavior and increase our behavior. procrastination is to put off something intentionally and habitually. in most contexts people procrastinate on work tasks, school tasks, home chores or any other work that people find difficult/ inconvenient. procrastination has a negative connotation as it implies that someone is too lazy to complete a task and they deliberately push away from doing the task in favor of something less important. procrastination affects the majority of the global adult population to some degree with the main demographic being college students and young adults. according to an article titled “the nature of procrastination”, approximately 80-90 percent of college students procrastinate regularly with 50 percent admitting that habitual procrastination negatively impacts their academics. (steel, 2007). habitual procrastination in students can not only lead to poor academic performance but can lead to many mental and physical problems such as self-induced stress, low self-esteem, weight gain any many other negative side effects caused by the loss of time due to procrastination. because of its harmful nature, it would make sense for students to avoid this behavior; however, there are many inherent biological and psychological factors that leave some students to be more or less likely to procrastinate (klassen et. al., 2008). a college student deliberately not doing their homework or studying in favor of hanging out with friends for a single night is not very problematic. the issue that many students have is a consistent inability to do tasks in a timely and organized manner, leading to assignments and other work to be done last minute and result in lower quality. this may be attributed to many things such as social media, social events, decreasing attention span, etc. all of which are due to short term distractions and can be easily remedied (klassen et. al., 2008). however, there are also other phenomena such as the procrastination paradox that can cause habitual procrastination (whitbourne, 2012). susan whitbourne, a phd professor of psychological and brain sciences at the university of massachusetts amherst explains the phenomena in her article “the paradox of procrastination”. the overall concept of the paper is that when faced with a daunting task such as studying for a difficult exam, students will be dismayed from studying because of the high difficulty. because they don’t want to study, they are likely to procrastinate, the procrastination leads to last minute exam preparation and thus a poor exam grade. because of the poor grades, students will believe that they are unable to do well in their class which then makes studying for the next exam even harder and thus leads to chronic procrastination. this constant cycle can result in more than just wasted time, overtime poor academic performance and lack of confidence and motivation can lead to decline in mental health because of self-induced stress. high stress levels can then make many other aspects of a student’s life more difficult. for example, high stress can lead to many physical complications such as heart disease, obesity and other unwanted physical effects on students (witbourne, 2012). because of the very negative effects that procrastination has on students it would make sense to avoid it all costs. initially it would seem that the cause for procrastination would be completely psychological, with behavioral factors like motivation and self-regulation being the only explanation (harris, 2019). however, there are physical predispositions in the brain that cause some students to be more likely to procrastinate than others (jaffe, 2013). the biggest physical culprit for chronic procrastination is the interaction between the limbic system and prefrontal cortex in our brain. the limbic system and prefrontal cortex are two regions of our brain assigned to regulate completely opposite functions. the limbic system is the part of our brain associated with emotion and other more primitive functions such as eating, pleasure/reward system, reproducing and controlling of chemicals such as dopamine and serotonin. the prefrontal cortex is associated with controlling more intelligent functions such as reasoning and logic. in the context of procrastination, the limbic system leans toward seeking short term pleasure and the prefrontal cortex is more rational and leans toward getting tasks done early to reduce stress. because all students are unique it is possible for some students to have a stronger acting prefrontal cortex that allows them to better act off rational decisions and make them less likely to habitually procrastinate. on the opposite side there are also students that have a stronger limbic system making their emotional/ thrill seeking side stronger than their rational decisionmaking side, thus leading to students that are more likely to procrastinate regardless of psychological aspects such as willpower or motivation. although there are physical predispositions that make some students more susceptible to procrastinating, the main reasons behind procrastination are psychological. some factors that affect how well a student performs are selfregulation and self-esteem. a study done by robert m. klassen in the journal “contemporary ducational psychology,” klassen takes many psychological factors why do we procrastinate? apil mahat 19 such as self-regulation, academic self-efficacy and selfesteem and surveys students to see if factors that affect procrastination rates also affect gpa (klassen, 2008). in the experiments 261 students were surveyed to rate how well they were able to self-regulate, their self-esteem, their academic self-efficacy (the definition of self-efficacy being one’s belief in themselves to succeed), and how often they procrastinate on a numeric scale. the values that the students gave were then compared to the student’s gpa. the results of this experiment show that when students that were unable to self-regulate their time, they struggled with procrastination and had lower gpa’s than students that identified as having good selfregulation of time. the demographics that had the most trouble with procrastination and had the lowest academic performance were those that lacked self-esteem and selfefficacy (klassen, 2008) . this shows that in some students procrastination has less to do with time management and laziness but more to do with their lack of self confidence in the ability to do a difficult task, making them less likely to want to do it and thus increasing their procrastination rates and decreasing their academic performance. now that we know procrastination is due to more than just laziness and distractions, we can begin to add more strategies for how to prevent procrastination (chrishildrew, 2015). the first common strategy is to remove all potential distractions such as phones or friends from your workspace. other strategies include properly managing time and creating a self-rewarding system to incentivize yourself to complete tasks. although these tips help with the self-regulation previously mentioned, they don’t address the self-esteem or self-efficacy that cause habitual procrastination. syeda batool, a researcher from govt. college university in lahore, also conducted research highlighting the correlation between self-esteem and educational performance. in her research paper “academic procrastination as a product of low selfesteem: a mediational role of academic self-efficacy” she comes to a similar conclusion, saying that “procrastination serves as an ego protecting mechanism, which is used as a defensive device by people with low self-esteem.”(batool, et. al., 2017). from her research she also concludes that selfesteem and self-efficacy are positively correlated, and selfefficacy is the strongest predictor of procrastination. she suggests that increased self-esteem will result in a decrease of procrastination habits. this means that the most effective way to reduce procrastination habits is to participate in academic activities that boost one’s self-esteem. this now raises the question of what effective strategies that improve one’s self-esteem and confidence in academic ability. michelle harris, author of “the link between self-esteem and social relationships: a meta-analysis of longitudinal studies” says “the metaanalytic finding that social relationships have a prospective effect on self-esteem provides support for central theories in the field of self-esteem, such as sociometer theory, reflected appraisals theory, and attachment theory." as outlined in the introduction, all of these theories highlight the key role of positive social relationships, social support, and social acceptance in shaping the development of self-esteem in all phases of the human life span.”(harris, 2019).”. in this quote harris talks about her experiment comparing selfesteem with social relationships, the important part being that she concludes positive social experiences are an important part in developing one’s self-esteem. for a student these social interactions would be are going to office hours, seeking study groups, and opening up to friends about academic stress. these strategies at face value may not seem to prevent procrastination, but talking to others and hearing about their difficulties and getting reassurance from others can help make stressful classes seem less daunting and easier to work on, these strategies are all effective in helping students study whilst also developing their social relationships, which further develop their self-esteem, lowering procrastination and increasing academic success and a false sense of hopelessness that lead students to avoid doing certain tasks and spiraling into a chronic problem of ones perception of what they are capable of doing rather than just being too lazy to study. references batool, s.s., khursheed, s., & jahangir, h. (2017). academic procrastination as a product of low selfesteem: a mediational role of academic self-efficacy. pakistan journal of psychological research, 32. chrishildrew. (2015). assembly: procrastination. teaching: leading learning. retrieved april 23, 2022, from https://chrishildrew.wordpress. com/2015/02/07/assembly-procrastination/ harris, m. ( 2019) positive relationships boost selfesteem, and vice versa. american psychological association, american psychological association, https:// www.apa.org/news/press/releases/2019/09/ relationships-self-esteem#:~:text=the%20 authors%20found%20that%20positive,effect%20in%20t he%20reverse%20direction. jaffe, e. (2013) “why wait? the science behind procrastination.” association for psychological science aps, association for phycological science , 29 mar. 2013, https:// www.psychologicalscience.org/observer/ why-wait-thescience-behind-procrastination. klassen, r.m., krawchuk, l.l., rajani s. (2008) “academic procrastination of undergraduates: low selfefficacy to self-regulate predicts higher levels of procrastination.” contemporary educational psychology, vol. 33, no. 4, 2008, pp. 915–931., https://doi.org/10.1016/j. cedpsych.2007.07.001. steel p. (2007). the nature of procrastination: a metaanalytic and theoretical review of quintessential selfregulatory failure. psychological bulletin, 133(1), 65–94. https://doi.org/10.1037/0033-2909.133.1.65 brain matters・volume v 20 novotney, a. (2010) “procrastination or ‘intentional delay’?” american psychological association, american psychological association. https://www.apa.org/ gradpsych/2010/01/procrastination. steel, plers. “the original myth.” psychology today, sussex publishers, 8 apr. 2016, https://www.psychologytoday.com/us/ blog/theprocrastination-equation/201604/ the-original-myth. whitbourne, s.k. (2012) “the paradox of procrastination.” psychology today, sussex publishers,10apr.2012, https:// www.psychologytoday.com/us/blog/fulfillment-anyage/201204/the-paradoxprocrastination#:~:text=so%20far%2c%20you%20 may%20be,no%20surprises%20there. 21 copy of brain matters template final table of contents life cycle of neurons nabiha javed 01 brain matters・volume v ii 07 19 09 11 14 antisense oligonucleotides mediated therapy for neurodegenerative disease apurva nayak impact of gestational period stress and early life stressors on child development karishma patel why do we procrastinate? apil mahat how to improve memory andrew zhang brain matters board 05 brain matters writers meet the writers thomas romanchek writer thomas is a junior double majoring in bioengineering and psychology and does research with the cellular neuroscience imaging lab on campus. he is an editor for ijois and an active member of the beckman journal club, two experiences which inspired him to start this journal. he is very excited to introduce “brain matters” to the uiuc community and hopes to broaden undergraduate interest in neuroscience and other brain topics. julia gainski writer julia gainski is a sophomore majoring in integrative biology with a minor in german. during the school year, she works as a personal assistant for students with physical disabilities. she is a part of the illini club tennis team and the secretary and a mentor of the pre-physician assistant club. she also works as a research assistant in the carla cáceres lab on campus. she is very excited to have her first article published in brain matters! chloe kim writer chloe (chaeyeon) kim graduated u of i in 2019 with b.s. in chemical engineering and minor in psychology. she worked as an undergraduate researcher in kong lab from 2016 to 2018 to develop her interest in clinical neuroscience research. she looks forward to sharing interesting topics in the field of neuroscience through brain matters. briana sobecks writer major: chemical engineering activities: american chemical society, newman center choir, campus honors student council 13 brain matters volume 2 julia gainski is a junior majoring in integrative biology with a minor in german. she is the public relations chair and a writer for brain matters. she is a research assistant at the control & network connectivity team (connectlab) at the beckman institute of advanced science and technology, where she assists with an eeg procedure in a concurrent eeg-fmri study. additionally, she is a personal assistant for students with physical disabilities at beckwith residential support services at nugent hall on campus, the secretary and a mentor of the pre-physician assistant club, and a member of the illini club tennis team. research in the psychological and brain sciences are constantly reevaluating the embodiment of human intelligence, seeking to better understand the convergence of the diverse array of differences in intellectual abilities and the variety of neurobiological mechanisms that drive this overall impact on an individual. the network neuroscience theory of human intelligence, brain networks, differences between fluid and crystalized intelligence, pattern separation, memory encoding, and how a person’s genetics intersects with their environment are all critical components that drive the overall impact on an individual’s intelligence. the network neuroscience theory prompts a discussion of how the brain network topology translates to general intelligence and differences at the individual level. the human brain’s community structure alongside the functional topology heavily utilizes resting-state functional mri (fmri) in which neurologists have the ability to extract information such as the spontaneous low frequency fluctuations of the blood oxygen-level dependent (bold) signal (barbey 2017). the bold imaging technique utilizes the regional differences in cerebral blood flow to describe regional activity and consequently produces images in fmri studies. the capability for network states to efficiently and easily transition amongst one another lays the foundation for the general intelligence, also known as the g factor and denoted as g, which delegates the instantaneous exchange of information across networks and depicts individual variations of information on a global scale (barbey 2017). an individual’s general intelligence consists of a wide array of cognitive abilities that avail them in gaining knowledge and solving complex problems. in essence, g allows researchers to better understand individual distinctions on the premises of studying brain network topology and dynamics (barbey 2017). this imaging method displays consistency across spatially distributed regions that further impart intrinsic connectivity networks. to its core, intrinsic connectivity networks (icns) serve as a foundational aspect for organizational elements of the human brain architecture. in a like manner, icns have been used in multivariate decompositions of fmri data alongside the use of independent component analysis. independent component analysis is particularly useful for the field of digital imaging as it serves as a statistical and computational technique that bestows various subcomponents derived from the separation of multivariate signals. this method concludes that the subcomponents are classified as non-gaussian signals and that they remain statistically independent of each other. furthermore, independent component analysis falls under the category of blind source separation. blind source separation is the process of differentiating between mixed signals and a set of source signals whilst having none or next to a limited amount of information in regards to the mixing process and source signals. to put source separation into a real world application, the human “cocktail party problem” describes a phenomenon where the brain has the ability to focus on one stimulus in the midst of a noisy social setting (bee and micheyl 2009). icns ultimately encapsulate how task-based neuroimaging and resting state data portrays resting state networks. these networks are areas of the brain that delineate discrete compositions of brain function. additionally, resting state networks incorporate the selection of large-scale functionality connected brain networks. these networks are a collection of widespread brain regions that utilize statistical analysis through the use of methods such as the fmri bold signal, pet, and eeg (laird et al. 2011). the network neuroscience theory additionally suggests that the g arises “from individual differences in the system-wide topology and dynamics of the human brain” (barbey 2017). this new found perspective stimulates the conversation that the small-world topology of brain networks composes an instantaneous rearrangement of their modular community structure. unraveling human intelligence in this image, figure (a) is representative of the axial view and presents the superior frontal activation. figure (b) displays a lateriles fef activation of the left hemisphere. figure (c) presents an axial image of the bilateral ifg a7tivation. in figure (d) there is an axial view that presents the superior frontal activation alongside a lateralized fef activation on the right hemisphere. figure (e) illustrates a sagittal view that depicts a centered position of the superior and medial frontal regions. figure (f) depicts a sagittal view that is centered on the left. 15 in essence, globally interrelated mental representations are generated in addition to the events that need to be carried out in order to attain the desired goal-state (barbey 2017). in the light of analyzing the interactions between brain networks, stanford scientists have conducted research encompassing the complex fluctuations in our brain networks and how the oscillating patterns begs the question on why certain tasks are learned at a more rapid pace in some individuals in comparison to others. researchers utilized pupil size measurements to gauge at how the brain reacts to shifts in connectivities. the significance of pupil size is that it measures the activity of the locus coeruleus, which is located in the upper region of the brainstem and is responsible for brain synthesis of the noradrenaline as well as regulating signals throughout the brain. adding more power to the amplification of strong signals alongside the muting of weak signals across the brain are characteristic of an increase in pupil size (kubota 2016). in essence, the researchers derived a link between changes in brain connectivity during rest and pupil size and found that larger pupils were linked to greater connectedness. this erudite finding ultimately led to the proposal that the noradrenaline is the impeccable impetus that makes the brain more cohesive in the midst of demanding cognitive tasks, which overall benefits the individual as they perform their task efficiently (kubota 2016). fluid intelligence denotes a higher dynamic connectivity and network flexibility than crystallized intelligence, because of this, it exhibits more inconsistencies on the topic of age and over the course of generations. intelligence goes beyond the scope of being able to recollect and recite vast amounts of information. it epitomizes one’s ability to digest new information and use it in various applications. intelligence encapsulates being able to solve problems through the convergence of a multitude of abilities such as memory, learning, perception, problem solving, and reasoning. crystalized intelligence stems from knowledge that is acquired through the basis of past experiences and previous information learned. as a person gets older, they will gain more knowledge and develop a stronger understanding of various subject matters. therefore, crystalized intelligence and age display a positive and linear trend. with that, the older a person is in age, the stronger their crystallized intelligence will become. fluid intelligence demonstrates the ability to solve problems through abstract thinking and reasoning. fluid intelligence does not involve any prior experience or education and is solely based on one’s ability to reason and solve complex problems upon initial exposure to them. fluid intelligence forces an individual to adapt and think abstractly when faced with a new problem that he has never seen before. when scrutinizing the network states concerned in both fluid and crystallized intelligence, crystallized intelligence recruits easy-to-reach network states, which retrieve experiences and previous knowledge gained. in contrast, fluid intelligence assembles difficult-to-reach network states that this graph illustrates how the magnitude of effect in terms of fluid intelligence declines over the course of infancy to old age. the opposite is seen here when the magnitude of effect in terms of crystalized intelligence continuously increases until it begins to level off when an individual reaches old age. are responsible for aiding in cognitive function, versatile reasoning, and problem-solving (barbey 2017). unlike crystallized intelligence, fluid intelligence declines during late adulthood as these critical cognitive abilities decrease with age. accordingly, crystallized intelligence reaches its apex typically between the age range of 60 to 70 years old while fluid intelligence has the potential to reach its climax around the age of 20 years old and consequently begin to level off following this age (trafton 2015). on the contrary, a study encompassing the peak of cognitive abilities in an individual’s lifetime in the psychological science journal denotes that subjects are capable of reaching the peak of their fluid intelligence well into their 40s or later (hartshorne and germine 2015). there has also been increasing evidence that engenders the idea that individual differences in crystallized and fluid intelligence emulate vast differences in terms of the ability of each icn to transition between network states. to extend, population studies have revealed that generational changes, in addition to a decrease in cognitive abilities, have a larger effect on fluid intelligence as opposed to crystallized intelligence. in a like manner, the network neuroscience theory adjudges these results in terms of global network dynamics. global network dynamics showcase correlation patterns that are suited in accordance to the empirical bold functional connectivity (cabral 2014). in a like manner, memory encoding plays a substantial role in emphasizing human intelligence and furthermore distinguishing humans from all other organisms. one study gave each of their subjects standardized neuropsychological tests which were used to measure intelligence, and language and memory functionality (morcom 2003). the experiment was designed to administer the exams in an hour and a half session before the mri scanning session was set to begin this diagram illustrates the anatomy of the locus coeruleus. 16 (morcom 2003). the folstein mini mental state test (mms) was the first exam given to the older participants and the national adult reading test (nart) was utilized to measure crystallized verbal intelligence. the raven’s advanced progressive matrices ii was used to measure ‘fluid’ non-verbal intelligence and the subjects were not timed when taking this exam. the results of the neuropsychological test performance demonstrated that the older subjects displayed a higher verbal iq based off of their performance on the national adult reading test. in contrast, the older participants displayed a much lower fluid iq which was measured by the raven’s advanced progressive matrices and a much worse long-term memory in respect to the younger subjects. it is unreasonable to delineate an exact or approximate age at which an individual’s cognitive abilities will peak or begin to decline as several cognitive functions differ drastically from each other and are independent from one another. joshua hartshorne, a postdoc in mit’s department of brain and cognitive sciences, states the discrepancies between being able to pinpoint ages throughout a lifespan, “at any given age, you’re getting better at some things, you’re getting worse at some other things, and you’re at a plateau at some other things. there’s probably not one age at which you’re peak on most things, much less all of them” (trafton 2015). this discovery changed the way that psychology and neuroscience tracks the progress of cognitive abilities and drastically contradicts the conventional perspectives. the study of neurons and their role in memory storage in mehumans ultimately lays the foundation and epitomizes human intelligence such as creative thinking and generalization. the hippocampus is the brain region responsible for memory storage and ensures that memories are independent of one another by storing them into separate groups of neurons (university of leicester 2020). pattern seperation is a fundamental principle of neuronal coding that discerns the differences between memories and experiences in the hippocampus (university of leicester 2020). several studies have put a primary focus on examining pattern separation in individuals well into their late adulthood. one laboratory conducted several experiments on the basis of behavioral pattern separation and configured recognition tasks that prompted regions within the parahippocampal gyrus to either reject or recall the tasks (kirwan and stark 2007). the recall-to-reject process is commonly used in associative-recognition tasks and gives an individual plenty of time during the recall process when imparting recognition judgements (rotello et al. 2000). during the task, pictures of objects were repeatedly shown or shown once to the individual throughout the duration of the task. some objects heavily resembled the ones previously shown and this conjoining aspect of the study encouraged pattern separation processes. functional magnetic resonance imaging (fmri) was used to monitor activity in the dentate gyrus (dg). this particular brain region was sensitive to the lures used throughout the tasks and this demonstrated a critical contribution to pattern separation in both an indirect and direct rendition of the task (stark et al. 2010). researchers chelsea k toner, eva pirogovsky, c brock kirwan, and paul e gilbert presented the idea that older adults have a greater likelihood of categorizing the lures as repeated in comparison to younger adults in the experiments (stark et al. 2010). when we think of intelligence, some may automatically direct attention to natural born capabilities or genetic influences, but intelligence is rather a combination of environmental and genetic factors that drive an individual’s overall intelligence. likewise, the heritability of traits is measured on a scale of 0 to 1.0. eye color is highly genetic with a heritable score of 0.99. intelligence depicts a heritability score of 0.8 which is considerably high but researchers frequently point out the misconceptions centered around this score and misconstruing the significance that the environment plays in determining an individual’s overall intelligence. an individual’s intelligence is most malleable when he/she begins early elementary school. opportunities within their schooling system and community will ultimately reinforce the prosperity of cognitive abilities over time. louis matzel, a professor of psychology at rutgers-new brunswick, speaks to the importance of an individual’s environment by stating, “the environment is the critical tool that allows our genetic equipment to prosper” (branson 2018). dana charles mccoy, assistant professor at the harvard graduate school of education, led the examination of the influence of classroom-based early childhood education (ece) specifically focused on grade retention, high school graduation, and special education placement (walsh 2017). the main takeaway stands that children attending high-quality ece programs are less likely to be held back in a grade level, less likely to be put into special education, and have a higher chance of graduating from high school than individuals not placed in these programs over the course of the last 40 years (walsh 2017). special education is defined as instruction that is specifically tailored to the individual in order to meet their unique needs of an individual with a disability (u.s. department of education 2017). numerous opportunities presented during a child’s early education are the cornerstone at which they can grow tremendously. taking full advantage of these endless possibilities is an excellent way for children to excel early on in their lives. mccoy calls attention to families and encourages them that their child’s education is a valuable investment as she states, “...it plays an important role in supporting children’s cognitive ability in language, literacy, and math, as well as social skill development and emotional growth” 17 (walsh 2017). intelligence is a pliable ability that can improve with time given that an individual is continuously promoting healthy lifestyle habits for themselves such as exercising regularly, which promotes the growth of neurons, augmenting brain function and structure and increasing the volume of the hippocampus (brinke et al. 2015). in addition to being physically active, getting an adequate amount of sleep is another key method in promoting prime cognitive function and ensuring that one is ready to learn something new. through the power of generalization and epitome of creative thought, humans cultivate the true meaning of intelligence and within their unique abilities in memory storage. although genetics play a substantial role in intelligence, the opportunities and an individual’s upbringing can create a significant impact as well. through the network neuroscience theory, one can utilize the brain network topology to decipher between intellectual differences at the individual level. references aron k. barbey. (2018) network neuroscience theory of human intelligence, trends in cognitive sciences, volume 22, issue 1, pages 8-20, issn 1364-6613, https://doi.org/10.1016/j. tics.2017.10.001. bee, mark a, and christophe micheyl.(2008) “the cocktail party problem: what is it? how can it be solved? and why should animal behaviorists study it?.” journal of comparative psychology (washington, d.c. : 1983) vol. 122,3: 235-51. doi:10.1037/07357036.122.3.235 branson, ken.17 jan. 2018, “inherited iq can increase in early childhood.” rutgers university, www.rutgers.edu/news/inherited-iq-can-increase-early-childhood. davies, huw. “functional magnetic resonance imaging [fmri].” ebme, ebme, www.ebme.co.uk/articles/clinical-engineering/ functional-magnetic-resonance-imaging-fmri. hartshorne, joshua k, and laura t germine. 4 (2015), “when does cognitive functioning peak? the asynchronous rise and fall of different cognitive abilities across the life span.” psychological science vol. 26: 433-43. doi:10.1177/0956797614567339 joana cabral, morten l. (2014) kringelbach, gustavo deco,exploring the network dynamics underlying brain activity during rest, progress in neurobiology, volume 114, pages 102-131, issn 03010082, https://doi.org/10.1016/j.pneurobio.2013.12.005. (http://www. sciencedirect.com/science/article/pii/s0301008213001457) kirwan, c brock, and craig e l stark. 6 sep. 2007, “overcoming interference: an fmri investigation of pattern separation in the medial temporal lobe.” learning & memory (cold spring harbor, n.y.) vol. 14,9 625-33. doi:10.1101/lm.663507 kubota, taylor. 30 sept. 2016, stanford scientists uncover how a fluctuating brain network may make us better thinkers, stanford news service, news.stanford.edu/press-releases/2016/09/30/ fluctuating-brai-better-thinkers/. laird, angela r et al. (2011) “behavioral interpretations of intrinsic connectivity networks.” journal of cognitive neuroscience vol. 23,12: 4022-37. doi:10.1162/jocn_a_00077 “sec. 300.39 special education.” 2 may 2017, individuals with disabilities education act, individuals with disabilities education act, sites.ed.gov/idea/regs/b/a/300.39. https://sites.ed.gov/idea/regs/ b/a/300.39 stark, shauna m et al. 21 may. 2010, “individual differences in spatial pattern separation performance associated with healthy aging in humans.” learning & memory (cold spring harbor, n.y.) vol. 17,6 284-8 doi:10.1101/lm.1768110 ten brinke, lisanne f et al. 4 (2015), “aerobic exercise increases hippocampal volume in older women with probable mild cognitive impairment: a 6-month randomised controlled trial.” british journal of sports medicine vol. 49: 248-54. doi:10.1136/ bjsports-2013-093184 trafton, anne. 6 mar. 2015, “the rise and fall of cognitive skills.” mit news | massachusetts institute of technology, massachusetts institute of technology, news.mit.edu/2015/brain-peaksat-different-ages-0306. https://news.mit.edu/2015/brain-peaks-at-different-ages-0306 laird, angela r et al. (2011) “behavioral interpretations of intrinsic connectivity networks.” journal of cognitive neuroscience vol. 23,12: 4022-37. doi:10.1162/jocn_a_00077 “sec. 300.39 special education.” 2 may 2017, individuals with disabilities education act, individuals with disabilities education act, sites.ed.gov/idea/regs/b/a/300.39. https://sites.ed.gov/idea/regs/ b/a/300.39 stark, shauna m et al. 21 may. 2010, “individual differences in spatial pattern separation performance associated with healthy aging in humans.” learning & memory (cold spring harbor, n.y.) vol. 17,6 284-8 doi:10.1101/lm.1768110 ten brinke, lisanne f et al. 4 (2015), “aerobic exercise increases hippocampal volume in older women with probable mild cognitive impairment: a 6-month randomised controlled trial.” british journal of sports medicine vol. 49: 248-54. doi:10.1136/ bjsports-2013-093184 trafton, anne. 6 mar. 2015, “the rise and fall of cognitive skills.” mit news | massachusetts institute of technology, massachusetts institute of technology, news.mit.edu/2015/brain-peaksat-different-ages-0306. https://news.mit.edu/2015/brain-peaks-at-different-ages-0306 university of leicester. 5 november 2020 ,“human intelligence just got less mysterious.” sciencedaily. sciencedaily. <www. sciencedaily.com/releases/2020/11/201105113006.htm>. caren m rotello, neil a macmillan, gordon van tassel, recall-to-reject in recognition: evidence from roc curves, journal of memory and language, volume 43, issue 1, 2000, pages 67-88, issn 0749-596x, https://doi.org/10.1006/jmla.1999.2701. https://www.sciencedirect.com/science/article/pii/s0749596x99927018?via%3dihub 18 table of contents how to improve memory.....................................................................................................................1 andrew zhang consumer neuroscience: the use of neuroscience techniques to create better advertising..............................................................6 nicole chilibovytsch origins of excersize-induced neurogenisis...............................................................................9 sanjana venkatarman the relationship between sleep deprivation and brain health................................14 emma ibanez unraveling human intelligence.....................................................................................................17 julia gainski 3 editor’s note thomas romanchek chief-editor thomas is a sophomore double majoring in bioengineering and psychology and does research with the cellular neuroscience imaging lab on campus. he is an editor for ijois and an active member of the beckman journal club, two experiences which inspired him to start this journal. he is very excited to introduce “brain matters” to the uiuc community and hopes to broaden undergraduate interest in the field! fiza bukhari assistant chief-editor fiza is a freshman majoring in molecular and cellular biology on the pre-med track. in addition to her involvement in the neuroscience journal committee, she communicates her illinois experience by writing for the uiuc admissions blog. just like her blog, she is thrilled to promote a neuroscience dialogue on campus! neil doherty editor neil is a freshman molecular and cellular biology major hoping to achieve the mcb certificate in neuroscience. he is a writer and editor for the “brain matters”, as well as a member of the undergraduate psychology association and the philosophy club at uiuc. he hopes to engage and inform the public about new advances in neuroscience, providing the foundation for sustained progress in science and medicine while also inspiring interest in the field in the student body of uiuc. laura kilikevicius editor laura is a freshman majoring in biology and hopes to one day move into work in genetics. she is thrilled to be working on “brain matters” and hopes to broaden the knowledge of current neuroscience research across campus. outside of the journal, she is an orientation leader on campus and is a catholic illini and lithuanianamerican club member. emerson fister editor emerson is a junior majoring in psychology with a concentration in behavioral neuroscience and a minor in integrative biology. outside of learning about neuroscience, she is passionate about human-centered design and is an active member of the university of illinois design for america studio. she is delighted to collaborate and learn with the other students behind “brain matters”. neelima valluru editor neelima valluru is a freshman at uiuc double majoring in computer science and biology. she is currently interning at the catchen lab on campus and is working on a computational genomics project. she is also a member of the bmes and esaa clubs on campus. she is very passionate about neuroscience and hopes to share current research in this fascinating field. quentin bu chief of design quentin bu is a junior majoring in intradisciplinary psychology with a minor in creative writing. in addition to her interest in cognitive neuroscience, she has past experiences in art, poster and graphic design. quentin hopes “brain matters” can provide a platform for an academic discussion about the field of study at uiuc. she also wishes readers will have an enjoyable reading experience. andrew zhang is a sophomore majoring in molecular and cellular biology. currently, he is a research assistant in dr. huimin zhao’s lab and also part of uiuc’s american chemistry society and react. how to improve memory our abilities to handle novel situations and utilize critical thinking depends heavily on our ever-expanding memory. while activities like problem solving and learning require persistence and effort, studies suggest there are ways to optimize our time and increase our efficiency to remember new things. since the late 1800’s, research has been uncovering how our memory works. psychological theories on memory paved the road for our understanding of memory, and many classrooms conducted applied research to test the efficacy of different learning techniques. recently, neurological studies on memory are also corroborating the evidence seen in older psychological studies. a prominent method for learning is the testing effect, which indicates that practicing knowledge with test-based questions improves learning significantly. while exams may serve as a gauge for people’s knowledge in the classroom, researchers have begun to realize their potential as an effective and robust learning method. the testing effect is seen through improved long-term memory, when the memory is retrieved during studying. studies have shown that short answer questions enhance long-term memory the best, while other testing methods like multiple choice questions or simple recall were not as effective (mcdaniel et al., 2007). methods like repeated studying and rereading proved less valuable than just one intermittent test (carpenter, 2009). recent neurological studies show increased activity in the brain from the testing effect, more so than other studying methods. for example, in learning dutch-swahili translations through the testing effect, participants’ left inferior parietal and left middle temporal lobes activated in fmri (van den broek et al., 2013). the same activity was not seen in traditional studying strategies, like repeating the lesson (van den broek et al., 2013). in another study, for learning associations between nouns, the testing effect activated hippocampal regions, the prefrontal cortex, and the posterior cingulate cortex, which are brain regions involved in memory retrieval cues (wing, 2013). on the other hand, these brain regions were much less active in the restudy condition, suggesting that the testing effect is more effective at utilizing brain resources to encode memory (wing, 2013). the testing effect proved robust in many different kinds of examinations and different subjects (agarwal et al., 2008). even tests that are quite different from the actual examination proved beneficial for memory (carpenter, 2009). evidence led many experts to believe the testing effect’s ability to improve learning and problem solving in addition to memory. when it comes to learning and memorizing new things, a simple test or two can be very helpful. the important implication is that even a bad testing session is more effective than rereading notes or textbooks. while tests may substantially improve memory, it is not necessary to overload oneself with large exams. researchers would most likely suggest the opposite, that by spacing material into reasonable learning sessions we can achieve a higher retention for the particular subject. this idea was first proposed by hermann ebbinghaus, who suggested that memory follows a forgetting curve, when information fades from memory over time. this loss of retention is best counteracted by learning and reviewing during separate occasions, rather than learning in only one sitting (ebbinghaus, 1913). this strategy for maximum retention became known as the spacing effect the relationship between memory acquisition and the spacing of time to review the material. when studying is spaced out, information tends to encode better in long term memory. in other words, memory is improved significantly with the help of spacing. spacing has seen success in a variety of practical situations, especially the classroom setting. for example, in a study conducted on 5th graders, students were required to learn difficult english vocabulary in one of two strategies: one taught in mass study (everythinig at once) while the other re-taught after a 7-day gap (spaced repetition) (sobel & kapler, 2010). the students performed equally well after figure 1. a schematic of the forgetting curve. the curve gradually lengthens with each review session, representing better retention with each review (chung & heo, 2018). 1 the first session of learning, but 5 weeks after the last learning session, the those with spaced repetition performed significantly better (sobel & kapler, 2010). another example was seen in a study with children who were tasked to remember certain toys. children who were allowed to play in between learning each toy were able to memorize the toys at a significantly better rate compared to children who learned the toys all at once (vlach et al., 2008). recently, neurologists have studied memory, like the forgetting curve and the spacing effect, in the brains of animals. the hippocampus appears to be crucial in retaining memory. in one experiment (sisti et al., 2007), rats were tested on a water maze, where they were required to learn and memorize the location of a platform in the maze. rats were also injected with 5-bromo-2-deoxyuridine (brdu), which labels newly synthesized cells. compared to normal rats, those with their hippocampus damaged through irradiation performed significantly worse in the water maze only after a few weeks, and showed decreases in brdu in neurons, meaning less formation of new neurons (snyder et al., 2005). it is hypothesized that new neurons in the hippocampus were not necessary for learning, since mice with a damaged hippocampus performed equally well with normal rats. however, new neurons are necessary for retention of memory, as seen by a drastic forgetting curve without them. a second experiment was conducted, where two groups of rats learned a water maze in either a single mass session (all at once) or with spacing. the rats with spaced learning performed significantly better than those without and were correlated with more brdu labeled cells in the hippocampus, suggesting neurological changes due to the spacing effect (sisti et al., 2007). overall, these studies point to the impact of the spacing effect on the preservation of new neurons, which in turn helps retain more information. and also outperforming the previous two groups (kang & pashler, 2011). based on these findings, it appears the spacing effect was not responsible for improving in associations. rather, interleaving is responsible for improving the ability to differentiate and associating pieces of information. not only does interleaving improve associations and differentiations, it has been shown to improve test performance in a practical setting. for example, in the following study (rohrer & taylor, 2007), interleaving improved math scores for students practicing math problems. spacing was not controlled for (students were not doing multiple math problems at the same time), which resembles more a practical classroom setting. the students were split into three groups. one group learned and practiced math through mixed topics (interleaving). another group practiced through blocked review, practicing one concept at a time. a third group also used a blocked review but included overlearning, meaning they completed multiple problems testing a single concept at a given time. referred to the masser group, they did twice as many problems as the original block group. the interleaving group overall did the same amount of problems as the masser group but spread at intervals the same size as the original block review. when tested, the masser group performed only slightly better than the original block group. however, the interleaving group performed significantly better than both groups. this suggests that additional practice is only useful for learning if spaced and mixed. studies on the neurological basis of interleaving are novel. in one study, (lin et al., 2011) participants were required to perform serial (ordering) tasks, requiring some but minimal upper body motion. in order to do so, participants must learn a specific sequence. one group learned through block training, and another through interleaving. the participants figure 2. learning correlated with brdu-labeled cells (sisti et al., 2007). in recent years, it is found that even the spacing effect can be further improved upon in strategies that make learning and memory consolidation more efficient. a similar but relatively new approach of learning is interleaving, or mixing subjects together while learning. for example, one can learn both math and english concepts in the same hour, alternating between the two subjects every couple of minutes. many interleaving techniques inevitably introduce spacing effects. concepts from one subject are separated in time in order to sandwich concepts from a different subject. however, even in controlling for spacing, studies suggest that interleaving promotes stronger associations with similar concepts and stronger differentiation between different concepts (kang & pashler, 2011). basically, interleaving helps improve and sharpen memory. in one study, subjects were tasked to learn and identify paintings by the artists. one group was shown 6 paintings of each painter all at once. a second group had mixed the orders of paintings. both groups were then administered distractor tasks to perform. when tested for the paintings later, the mixed group performed significantly better at identifying painters (kornell & bjork, 2008). another study followed up with a similar setup. this time, the two groups were tested with no mixed order, but the spacing of time between each painter and painting pair learned was changed. this resulted in no significant difference in performance. in the same study, another setup included mixed orders, which were shown either simultaneously or spaced with time. again, the two groups performed equally well 2 were studied under fmri blood-oxygen-level-dependent signals (bold) and excitability in the primary motor cortex (m1) through transcranial magnetic stimulation. during retention (learning phase), bold in prefrontal and sensorimotor regions and m1 excitability were higher in the interleaving group. initially, the interleaving group performed tasks with slower reaction time than the block training. however, after 5 days, the interleaving group experienced faster reaction times. m1 excitability was still higher, but bold in prefrontal regions were weaker compared to the block training group. these results suggest that interleaving produces higher activity in parts of the brain for learning, as seen by bold. over time, the brain incorporates the information. this makes retrieval more efficient, requiring less activity in brain regions as seen by decreased bold. m1 excitability shows higher activation of relevant brain regions in completing tasks. it is plausible other areas of the brain are also easily excitable when activated through interleaving. the incorporation of ideas and information inro long term memory is incredibly important. to effectively use one’s memory, one must also be able to retrieve information and use it. much of that brain power relies on working memory, which is closely tied to short term memory. additionally, any new pieces of information must first go through the short term memory before it can be stored in the long term memory. the working memory allows the brain to act on or even modify information. for example, the brain can imagine breaking a chair without one actually breaking the chair in real life. short-term memory cannot incorporate an infinite amount of information at the same time, however. in a very famous historical paper, george miller estimates the limit to be 7±2 pieces of information (miller 1956). however, the limit is actually not definite. some pieces of information themselves contain information, which are known as chunks. the chunk does not yet have a rigorous definition in the scientific community, but it is thought to be a group of information that the brain handles as one entity. in other words, a single chunk will consist of many pieces of information while taking less space in working memory. however, chunks do not completely bypass miller’s estimate. further studies have shown the capacity of the brain to handle up to 4±1 chunks (crowan, 2010), which is less than miller’s original estimate. because chunks themselves contain more information, each chunk takes up more space in working memory than a single item. in a recent study conducted, participants were required to memorize a sequence of numbers. depending on how many numbers were contained in each chunk, the maximum chunks the brain can handle varied. when chunks were only one number each, the limit was about 7. when chunks became very long, around 5 numbers each, the brain could only handle about 3-4 chunks (mathy & feldman, 2012). this corroborates the idea that the brain has a capacity for working memory, even when chunking. despite this, chunking still helps carry more information in working memory than individual pieces of information alone. the ability to use chunking effectively improves memory usage and memory consolidation dramatically. for example, studies conducted show that chess players rely on chunking entire movesets in a given board, like helping players remember where individual pieces are on a board, given only a few seconds to see the board (linhares & brum, 2007). it is also shown that pattern recognition in games like chess correlates with skill (linhares & brum, 2007). some neurological insights into chunking have corroborated with previous studies on its efficacy. for example, in one study (bor et al., 2003), participants were required to memorize spatial patterns. one group had a disruption in learning at a random point in time. another had a disruption specifically in between two different sets of information, establishing meaningful chunks in the participants’ memory. the second group performed better, and in fmri brain scans, their prefrontal cortex was also lit up more (bor et al., 2003). chunking produces higher activity in brain regions important for processing information, and chunking can improve short term memory. ultimately, with chunking, higher activity allows for better consolidation of information. while most memory and learning techniques were developed recently, there are some ancient techniques still used today, like the method of loci. also known as the “memory palace,” people would imagine putting pieces of information in each “room” of a building they are familiar with. retrieval of memory simply requires finding the right “room.” the technique was first used by ancient greeks to memorize speeches, and now it is used in memory competitions, allowing people to effectively memorize large chunks of information (dresler et al., 2017). additionally, the memory technique is just as effective when usifigure 3. increased blood flow was higher during practice in individuals with interleaving (top image, bottom row). during the retention phase, interleaving showed less blood flow activity compared to the control (bottom image, bottom row). presumed that interleaving is more efficient, requiring less effort during retention (lin et al. 2011). figure 4. basic schematic of encoding and retaining memory (esteve 2016). 3 ng locations in virtual reality as in with real locations (legge et al., 2012). the memory technique is uniquely a mental construct, but it provides tangible improvements for information consolidation. using the method of loci effectively requires practice and training (legge et al., 2012). to test for the effectiveness of the memory palace, a study was conducted on older subjects to practice memorizing a list of words. the subjects were trained in the method of loci during the study. the adults who were asked to utilize the memory palace technique performed significantly better at remembering words compared to the control (gross et al., 2014). on pieces of paper, those who used the method of loci remembered words in the correct order, and even left spaces in between for words they forgot (gross et al., 2014). neurological correlates also indicate the effectiveness of the method of loci. for example, in a neurological study conducted on memory atheletes and control participants, those who utilized the method of loci performed significantly better than other strategies, like active or passive learning, even up to at least 4 months later (dresler et al., 2017). in an fmri scan done on the participants, during memory consolidation and retrieval, those who trained with memory of loci had heightened activity between visual lobes, temporal lobes, and default mode networks (dresler et al., 2017). it is believed that the method of loci promotes increased connectivity between different parts of the brain, promoting memory consolidation. evidence-based research in effective memory techniques is relatively new. while some methods were well-known since ancient times, most have only been uncovered recently. neurological studies on the effects of memory techniques are currently ongoing but already substantiate the techniques. despite the significantly improved performances from these techniques, many participants in these studies believed traditional studying strategies were more effective. as researchers begin to understand more of these memory techniques, it is crucial that people will also learn to understand the importance of these techniques as well. learning new material can require effort, but there are always strategies to make learning and memorizing easier and more efficient. references agarwal, pooja k., et al., 19 sept. 2008, “examining the testing effect with openand closeboot tests.” applied cognitive psychology, vol. 22, no. 7, pp. 861-876, john wiley & sons, doi: 10.1002/acp.1391. bor, daniel, et al., 23 jan. 2003, “encoding strategies dissociate prefrontal activity from working demand.” neuron, vol. 37, no. 2, pp. 361-357, cell press, doi: 10.1016/s0896-6273(02)01171-6. carpenter, s. k., 2009, “cue strength as a moderator of the testing effect: the benefits of elaborative retrieval.” journal of experimental psychology: learning, memory, and cognition, vol. 35, no. 6, pp. 1563-1569, american psychological association, doi: 10.1037/ a0017021. chung, bo a., and heo, hae j., jan. 2018, “the effect of flipped learning on academic performance as an innovative method for overcoming ebbinhaus’s forgetting curve.” international conference on information and education technology, vol. 6, pp. 56-60, association for computing machinery, doi: 10.1145/3178158.3178206. crowan, n., 2 mar. 2021,“the magical mystery four: how is working memory capacity limited, and why?” current directions in psychological science, vol. 19, no. 1, pp. 51-57, sage publications,doi: 10.1177/0963721409359277. dresler, martin, et al., 8 mar. 2017, “mnemonic training reshapes brain networks to support superior memory.” neuron, vol. 93, no. 5, pp. 1227-1235, cell press, doi: 10.1016/j.neuron.2017.02.003. crowan, n., 2 mar. 2021,“the magical mystery four: how is working memory capacity limited, and why?” current directions in psychological science, vol. 19, no. 1, pp. 51-57, sage publications,doi: 10.1177/0963721409359277. dresler, martin, et al., 8 mar. 2017, “mnemonic training reshapes brain networks to support superior memory.” neuron, vol. 93, no. 5, pp. 1227-1235, cell press, doi: 10.1016/j.neuron.2017.02.003. ebbinghaus, hermann., 1913. “memory: a contribution to experimental psychology.” translated by ruger, henry a. and bussenius, clara e. `esteve, clàudia y., 2016., “very young learners’ vocabulary development in english : a case study with 4 and 5 year-old children.” gross, alden l., et al.,13 mar. 2014, “do older adults use the method of loci? results from the active study.” experimental aging research, vol. 40, no. 2, pp. 140-163, routledge,doi: 10.1080/0361073x.2014.882204. kang, sean h. k., et al., 02 may 2011, “learning painting styles: spacing is advantageous when it promotes discriminative contrast.” applied cognitive psychology, vol. 26, no. 1, pp. 97-103, john wiley & sons, doi: 10.1002/acp.1801. kornell, nate, and bjork, robert a.,1 jun. 2008, “learning concepts and categories is spacing the ‘enemy of induction’?” psychological science, vol 19, no. 6, pp. 585-592, sage publications, doi: 10.1111/j.1467-9280.2008.02127.x. legge, eric l. g., et al. 2012.09.002.,“building a memory palace in minutes: equivalent memory performance using virtual versus conventional environments with the method of loci.” acta psychologica, vol. 141, no. 3, pp. 380-390, elsevier, nov. 2012, doi: 10.1016/j.actpsy. lin, chien-ho (janice), et al., 1 jun. 2011, “brain-behavior correlates of optimizing learning through interleaved practice.” neuroimage, vol. 56, no. 3, pp. 1758-1772, elsevier, doi: 10.1016/j. neuroimage. linhares, alexandre, and brum, paulo., 10 jan. 2010 “understanding our understanding of strategic scenarios: what role do chunks play?” cognitive science, vol. 31, no. 6, pp. 989-1007, john wiley & sons, doi: 10.1080/03640210701703725. mathy, fabien, feldman, jacob., 2011.11.003. “what’s magic about magic numbers? chunking and data compression in short-term memory.” cognition, vol. 122, no. 3, pp. 346-362, elsevier , doi: 10.1016/j.cognition. mcdaniel, mark a., et al., 02 jul. 2007, “testing the testing effect in the classroom.” journal of cognitive psychology, vol 19, no. 4-5, pp. 494-513, routledge, doi: 10.1080/09541440701326154. miller, george., mar. 1956. “the magical number seven, plus or minus two: some limits on our capacity for processing information.” the psychological review, vol. 63, no. 2, american psychological association, rohrer, doug, and taylor, kelli. 19 apr. 2007, “the shuffling of mathematics problems improves learning.” instructional science, vol. 35, no. 6, pp. 481-498, springerlink, doi: 10.1007/s11251007-9015-8. sisti, helene m., et al. 19 apr. 2007 “neurogenesis and the spacing effect: learning over time enhances memory and the survival of new neurons.” learning & memory, vol. 14, no. 5, pp. 368-375, cold spring harbor laboratory press, doi: 10.1101/lm.488707. sobel, hailey s., et al. “spacing effects in real-world classroom vocabulary learning.” applied cognitive psychology, vol. 25, no. 5, pp. 762-767, john wiley & sons, 22 sep. 2020, doi: 10.1002/ acp.1747. van den broek, gesa s. e., et al. sep. 2013, “neural correlates of testing effects in vocabulary learning.” neuroimage, vol. 78, pp. 94-102, elsevier,doi: 10.1016/j.neuroimage.2013.03.071. vlach, haley. a., et al. 2008.07.013.“the spacing effect in children’s memory and category induction.” cognition, vol. 109, no. 1, pp. 162-167, elsevier, oct. 2008, doi: 10.1016/j.cognition. wing, erik a., et al. oct. 2013, “neural correlates of retrieval-based memory enhancement: an fmri study of the testing effect.” neuropsychologia, vol. 51, no. 12, pp. 2360-2370, elsevier, oct. 2013, doi: j.neuropsychologia. 4 copy of brain matters template final abstract memory is important in learning and is built over time and practice. not all memory strategies are built equally. recent evidence in both neurological and practical settings suggests that specific strategies can increase memory performance. compared to traditional block studying, strategies such as the testing effect, spacing effect, interleaving, chunking, and the method of loci significantly improve the efficiency of encoding new memories. our abilities to handle novel situations and utilize critical thinking depends heavily on our ever-expanding memory. while activities like problem solving and learning require persistence and effort, studies suggest there are ways to optimize our time and increase our efficiency to remember new things. since the late 1800’s, research has been uncovering how our memory works. psychological theories on memory paved the road for our understanding of memory, and many classrooms conducted applied research to test the efficacy of different learning techniques. recently, neurological studies on memory are also corroborating the evidence seen in older psychological studies. a prominent method for learning is the testing effect, which indicates that practicing knowledge with test-based questions improves learning significantly. while exams may serve as a gauge for people’s knowledge in the classroom, researchers have begun to realize their potential as an effective and robust learning method. the testing effect is seen through improved long-term memory, when the memory is retrieved during studying. studies have shown that short answer questions enhance long-term memory the best, while other testing methods like multiple choice questions or simple recall were not as effective (mcdaniel et al., 2007). methods like repeated studying and rereading proved less valuable than just one intermittent test (carpenter, 2009). recent neurological studies show increased activity in the brain from the testing effect, more so than other studying methods. for example, in learning dutch-swahili translations through the testing effect, participants’ left inferior parietal and left middle temporal lobes activated in fmri (van den broek et al., 2013). the same activity was not seen in traditional studying strategies, like repeating the lesson (van den broek et al., 2013). in another study, for learning associations between nouns, the testing effect activated hippocampal regions, the prefrontal cortex, and the posterior cingulate cortex, which are brain regions involved in memory retrieval cues (wing, 2013). on the other hand, these brain regions were much less active in the restudy condition, suggesting that the testing effect is more effective at utilizing brain resources to encode memory (wing, 2013). the testing effect proved robust in many different kinds of examinations and different subjects (agarwal et al., 2008). even tests that are quite different from the actual examination proved beneficial for memory (carpenter, 2009). evidence leads many experts to believe that the testing effect can improve learning and problem solving in addition to memory. when it comes to learning and memorizing new things, a simple test or two can be very helpful. the important implication is that even a bad testing session is more effective than rereading notes or textbooks. while tests may substantially improve memory, it is not necessary to overload oneself with large exams. researchers would most likely suggest the opposite, that by spacing material into reasonable learning sessions we can achieve a higher retention for the particular subject. this idea was first proposed by hermann ebbinghaus, who suggested that memory follows a forgetting curve, when information fades from memory over time. this loss of retention is best counteracted by learning and reviewing during separate occasions, rather than learning in only one sitting (ebbinghaus, 1913). this strategy for maximum retention became known as the spacing effect. it is the relationship between memory acquisition and the spacing of time to review the material. when studying is spaced out, information tends to encode better in long term memory. in other words, memory is improved significantly with the help of spacing. figure 1. a schematic of the forgetting curve. the curve gradually lengthens with each review session, representing better retention with each review (chung & heo, 2018). spacing has seen success in a variety of practical situations, especially the classroom setting. for example, in a study conducted on 5th graders, students were required to learn difficult english vocabulary in one of two strategies: one taught in mass study (everything at once) while the other retaught (spaced repetition) after a 7-day gap (sobel & kapler, 2010). the students performed equally well after the first session of learning, but 5 weeks after the last learning session, those with spaced repetition performed significantly better (sobel & kapler, 2010). another example was seen in a study with children who were tasked to remember certain toys. how to improve memory andrew zhang 14 however, even while controlling for spacing, studies suggest that interleaving promotes stronger associations with similar concepts and stronger differentiation between different concepts (kange & pashler, 2011). basically, interleaving helps improve and sharpen memory. in one study, subjects were tasked to learn and identify paintings by the artists. one group was shown 6 paintings of each painter all at once. a second group had mixed the orders of paintings. both groups were then administered distractor tasks to perform. when tested for the paintings later, the mixed group performed significantly better at identifying painters (kornell & bjork, 2008). another study followed up with a similar setup. this time, the two groups were tested with no mixed order, but the spacing of time between each painter and painting pair was changed. this resulted in no significant difference in performance. in the same study, another setup included mixed orders, which were shown either simultaneously or spaced with time. again, the two groups performed equally well and also outperformed the previous two groups (kang & pashler, 2011). based on these findings, it appears the spacing effect was not responsible for improving in associations. rather, interleaving is responsible for improving the ability to differentiate and associate pieces of information. not only does interleaving improve associations and differentiations, it has been shown to improve test performance in a practical setting. for example, in the following study (rohrer & taylor, 2007), interleaving improved math scores for students practicing math problems. spacing was not controlled for (students were not doing multiple math problems at the same time), which resembles a more practical classroom setting. the students were split into three groups. one group learned and practiced math through mixed topics (interleaving). another group practiced through blocked review, practicing one concept at a time. a third group also used a blocked review but included overlearning, meaning they completed multiple problems testing a single concept at a given time. referred to as the masser group, they solved twice as many problems as the original block group. the interleaving group overall did the same amount of problems as the masser group but spread at intervals the same size as the original block review. when tested, the masser group performed only slightly better than the original block group. however, the interleaving group performed significantly better than both groups. this suggests that additional practice is only useful for learning if spaced and mixed. studies on the neurological basis of interleaving are novel. in one study, (lin et al., 2011) participants were required to perform serial (ordering) tasks, requiring some but minimal upper body motion. in order to do so, participants must learn a specific sequence. one group learned through block training, and another through interleaving. the participants were studied under fmri blood-oxygen-level-dependent signals (bold) and excitability in the primary motor cortex (m1) through transcranial magnetic stimulation. during retention (learning phase), bold in prefrontal and sensorimotor regions and m1 excitability were higher in the interleaving group. initially, the interleaving group performed tasks with slower children who were allowed to play in between learning each toy were able to memorize the toys at a significantly better rate compared to children who learned the toys all at once (vlach et al., 2008). despite greater distraction for children playing between each learning session, their brains were able to consolidate information better (vlach et al., 2008). recently, neurologists have studied memory, like the forgetting curve and the spacing effect, in the brains of animals. the hippocampus appears to be crucial in retaining memory. in one experiment (snyder et al., 2005), rats were tested on a water maze. they were required to learn and memorize the location of a platform in the maze. rats were also injected with 5-bromo-2-deoxyuridine (brdu), which labels newly synthesized cells. compared to normal rats, those with their hippocampus damaged through irradiation performed significantly worse in the water maze only after a few weeks, and showed decreases in brdu in neurons, meaning less formation of new neurons (snyder et al., 2005). it is hypothesized that new neurons in the hippocampus were not necessary for learning, since mice with a damaged hippocampus performed equally well with normal rats (snyder et al., 2005). however, new neurons are necessary for retention of memory, as seen by a drastic forgetting curve without them. a second experiment was conducted, where two groups of rats either learned a water maze in either a single mass session (all at once) or with spacing. the rats with spaced learning performed significantly better than those without, and spaced repetition were correlated with more brdu labeled cells in the hippocampus, suggesting neurological changes due to the spacing effect (sisti et al., 2007). overall, these studies point to the impact of the spacing effect on the preservation of new neurons, which in turn helps retain more information. figure 2. learning correlated with brdu-labeled cells (sisti et al., 2007). in recent years, it is found that even the spacing effect can be further improved upon in strategies that make learning and memory consolidation more efficient. a similar but relatively new approach of learning is interleaving, or mixing subjects together while learning. for example, one can learn both math and english concepts in the same hour, alternating between the two subjects every couple of minutes. many interleaving techniques inevitably introduce spacing effects. concepts from one subject are separated in time in order to sandwich concepts from a different subject. brain matters・volume v 15 estimate. further studies have shown the capacity of the brain to handle up to 4±1 chunks (crowan, 2010), which is clearly less than miller’s original estimate. because chunks themselves contain more information, each chunk takes up more space in working memory than a single item. reaction time than the block training. however, after 5 days, the interleaving group experienced faster reaction times. m1 excitability was still higher, but bold in prefrontal regions were weaker compared to the block training group. these results suggest that interleaving produces higher activity in parts of the brain for learning, as seen by bold. over time, the brain incorporates the information. this makes retrieval more efficient, requiring less activity in brain regions as seen by decreased bold. m1 excitability shows higher activation of relevant brain regions in completing tasks. it is plausible other areas of the brain are also easily excitable when activated through interleaving. figure 3. increased blood flow was higher during practice in individuals with interleaving (top image, bottom row). during the retention phase, interleaving showed less blood flow activity compared to the control (bottom image, bottom row). presumed that interleaving is more efficient, requiring less effort during retention (lin et al. 2011). the incorporation of ideas and information into long term memory is incredibly important. to effectively use one’s memory, one must also be able to retrieve information and use it. much of that brain power relies on working memory, which is closely tied to short term memory. additionally, any new pieces of information must first go through the short term memory before it can be stored in the long term memory. the working memory allows the brain to act on or even modify information. for example, the brain can imagine breaking a chair without one actually breaking the chair in real life. short-term memory cannot incorporate an infinite amount of information at the same time, however. in a very famous historical paper, george miller estimates the limit to be 7±2 pieces of information (miller 1956). however, the limit is actually not definite. some pieces of information, known as chunks, contain multiple pieces of information together as one group. the chunk does not yet have a rigorous definition in the scientific community, but it is thought to be a group of information that the brain handles as one entity. in other words, a single chunk will consist of many pieces of information while taking less space in working memory. however, chunks do not completely bypass miller’s figure 4. basic schematic of encoding and retaining memory (esteve 2016) in a recent study conducted, participants were required to memorize a sequence of numbers. depending on how many numbers were contained in each chunk, the maximum chunks the brain can handle varied. when chunks were only one number each, the limit was about 7. when chunks became very long, around 5 numbers each, the brain could only handle about 3-4 chunks (mathy & feldman, 2012). this corroborates the idea that the brain has a capacity for working memory, even when chunking. despite this, chunking still helps carry more information in working memory than individual pieces of information alone. the ability to use chunking effectively improves memory usage and memory consolidation dramatically. for example, studies conducted show that chess players rely on chunking entire movesets in a given board, like helping players remember where individual pieces are on a board, given only a few seconds to see the board (linhares & brum, 2007). it is also shown that pattern recognition in games like chess correlates with skill (linhares & brum, 2007). some neurological insights into chunking have corroborated with previous studies on its efficacy. for example, in one study (bor et al., 2003), participants were required to memorize spatial patterns. one group had a disruption in learning at a random point in time. another had a disruption specifically in between two different sets of information, establishing meaningful chunks in the participants’ memory. the second group performed much better, and in fmri brain scans, their prefrontal cortex was also lit up more (bor et al., 2003). chunking produces higher activity in brain regions important for processing information, chunking and improving short term memory. ultimately, with chunking, higher activity allows for better consolidation of information. while most memory and learning techniques were developed recently, there are some ancient techniques still used today, like the method of loci. also known as the “memory palace,” people would imagine putting pieces of information in each “room” of a building they are familiar with. retrieval of memory simply requires finding the right “room.” the technique was first used by ancient greeks to memorize speeches, and now it is used in memory competitions, allowing people to effectively memorize large chunks of information (dresler et al., 2017). additionally, the memory 16 chung, bo a., and heo, hae j. “the effect of flipped learning on academic performance as an innovative method for overcoming ebbinhaus’s forgetting curve.” international conference on information and education technology, vol. 6, pp. 56-60, association for computing machinery, jan. 2018, doi: 10.1145/3178158.3178206. esteve, clàudia y. “very young learners’ vocabulary development in english : a case study with 4 and 5 year-old children.” 2016. crowan, n. “the magical mystery four: how is working memory capacity limited, and why?” current directions in psychological science, vol. 19, no. 1, pp. 51-57, sage publications, 2 mar. 2021, doi: 10.1177/0963721409359277. dresler, martin, et al. “mnemonic training reshapes brain networks to support superior memory.” neuron, vol. 93, no. 5, pp. 1227-1235, cell press, 8 mar. 2017, doi: 10.1016/j.neuron.2017.02.003. ebbinghaus, hermann. “memory: a contribution to experimental psychology.” translated by ruger, henry a. and bussenius, clara e., 1913. gross, alden l., et al. “do older adults use the method of loci? results from the active study.” experimental aging research, vol. 40, no. 2, pp. 140-163, routledge, 13 mar. 2014, doi: 10.1080/0361073x.2014.882204. kang, sean h. k., and pashler, h. “learning painting styles: spacing is advantageous when it promotes discriminative contrast.” applied cognitive psychology, vol. 26, no. 1, pp. 97-103, john wiley & sons, 02 may 2011, doi: 10.1002/acp.1801. kornell, nate, and bjork, robert a. “learning concepts and categories is spacing the ‘enemy of induction’?” psychological science, vol 19, no. 6, pp. 585-592, sage publications, 1 jun. 2008, doi: 10.1111/j.14679280.2008.02127.x. legge, eric l. g., et al. “building a memory palace in minutes: equivalent memory performance using virtual versus conventional environments with the method of loci.” acta psychologica, vol. 141, no. 3, pp. 380-390, elsevier, nov. 2012, doi: 10.1016/j.actpsy.2012.09.002. lin, chien-ho (janice), et al. “brain-behavior correlates of optimizing learning through interleaved practice.” neuroimage, vol. 56, no. 3, pp. 1758-1772, elsevier, 1 jun. 2011, doi: 10.1016/j.neuroimage.2011.02.066 linhares, alexandre, and brum, paulo. “understanding our understanding of strategic scenarios: what role do chunks play?” cognitive science, vol. 31, no. 6, pp. 989-1007, john wiley & sons, 10 jan. 2010, doi: 10.1080/03640210701703725. technique is just as effective when using locations in virtual reality as in with real locations (legge et al., 2012). the memory technique is uniquely a mental construct, but it provides tangible improvements for information consolidation. using the method of loci effectively requires practice and training (legge et al., 2012). to test for the effectiveness of the memory palace, a study was conducted on older subjects to practice memorizing a list of words. the subjects were trained in the method of loci during the study. the adults who were asked to utilize the memory palace technique performed significantly better at remembering words compared to the control (gross et al., 2014). on pieces of paper, those who used the method of loci remembered words in the correct order, and even left spaces in between for words they forgot (gross et al., 2014). neurological correlates also indicate the effectiveness of the method of loci. for example, in a neurological study conducted on memory athletes and control participants, those who utilized the method of loci performed significantly better than other strategies, like active or passive learning, even up to at least 4 months later (dresler et al., 2017). in an fmri scan done on the participants during memory consolidation and retrieval, those who trained with memory of loci had heightened activity between visual lobes, temporal lobes, and default mode networks (dresler et al., 2017). it is believed that the method of loci promotes increased connectivity between different parts of the brain, promoting memory consolidation. evidence-based research in effective memory techniques is relatively new. while some methods were wellknown since ancient times, most have only been uncovered recently. neurological studies on the effects of memory techniques are currently ongoing but already substantiate the techniques. despite the significantly improved performances from these techniques, many participants in these studies believed traditional studying strategies were more effective. as researchers begin to understand more of these memory techniques, it is crucial that people learn to understand the importance of these techniques as well. learning new material can require effort, but there are always strategies to make learning and memorizing easier and more efficient. references agarwal, pooja k., et al. “examining the testing effect with openand closeboot tests.” applied cognitive psychology, vol. 22, no. 7, pp. 861-876, john wiley & sons, 19 sept. 2008, doi: 10.1002/acp.1391. bor, daniel, et al. “encoding strategies dissociate prefrontal activity from working demand.” neuron, vol. 37, no. 2, pp. 361-357, cell press, 23 jan. 2003, doi: 10.1016/s08966273(02)01171-6. carpenter, s. k. “cue strength as a moderator of the testing effect: the benefits of elaborative retrieval.” journal of experimental psychology: learning, memory, and cognition, vol. 35, no. 6, pp. 1563-1569, american psychological association, 2009, doi: 10.1037/a0017021. brain matters・volume v 17 linhares, alexandre, and brum, paulo. “understanding our understanding of strategic scenarios: what role do chunks play?” cognitive science, vol. 31, no. 6, pp. 989-1007, john wiley & sons, 10 jan. 2010, doi: 10.1080/03640210701703725. mathy, fabien, feldman, jacob. “what’s magic about magic numbers? chunking and data compression in short-term memory.” cognition, vol. 122, no. 3, pp. 346-362, elsevier, mar. 2012, doi: 10.1016/j.cognition.2011.11.003. mcdaniel, mark a., et al. “testing the testing effect in the classroom.” journal of cognitive psychology, vol 19, no. 4-5, pp. 494-513, routledge, 02 jul. 2007, doi: 10.1080/09541440701326154. miller, george. “the magical number seven, plus or minus two: some limits on our capacity for processing information.” the psychological review, vol. 63, no. 2, american psychological association, mar. 1956. rohrer, doug, and taylor, kelli. “the shuffling of mathematics problems improves learning.” instructional science, vol. 35, no. 6, pp. 481-498, springerlink, 19 apr. 2007, doi: 10.1007/s11251-007-9015-8. sisti, helene m., et al. “neurogenesis and the spacing effect: learning over time enhances memory and the survival of new neurons.” learning & memory, vol. 14, no. 5, pp. 368375, cold spring harbor laboratory press, 10 may 2007, doi: 10.1101/lm.488707. snyder, jason s., et al. “a role for adult neurogenesis in spatial long-term memory.” neuroscience, col 130, no. 4, pp. 843-852, elsevier, 2005, doi: 10.1016/j.neuroscience.2004.10.009. sobel, hailey s., et al. “spacing effects in real-world classroom vocabulary learning.” applied cognitive psychology, vol. 25, no. 5, pp. 762-767, john wiley & sons, 22 sep. 2020, doi: 10.1002/acp.1747. van den broek, gesa s. e., et al. “neural correlates of testing effects in vocabulary learning.” neuroimage, vol. 78, pp. 94102, elsevier, sep. 2013, doi: 10.1016/j.neuroimage.2013.03.071. vlach, haley. a., et al. “the spacing effect in children’s memory and category induction.” cognition, vol. 109, no. 1, pp. 162-167, elsevier, oct. 2008, doi: 10.1016/j.cognition.2008.07.013. wing, erik a., et al. “neural correlates of retrieval-based memory enhancement: an fmri study of the testing effect.” neuropsychologia, vol. 51, no. 12, pp. 2360-2370, elsevier, oct. 2013, doi: j.neuropsychologia.2013.04.004. 18 https://doi.org/10.1007/s11251-007-9015-8 therapeutic techniques for neural regeneration in the central nervous system chloe kim scientists have studied multiple approaches that have been thought to enhance neural regeneration. these approaches have led to the development of groundbreaking treatment for age-related diseases and nerve injuries. the development and use of these treatments are vital because spinal cord injuries and traumatic brain injuries alone affect 90,000 people every year; approximately 10,000 mostly young individuals are affected by acute spinal cord injury and 50,000 die from traumatic brain injury each year (stabenfeldt et al., 2006). it is also important to note that neurodegenerative diseases, such as alzheimer’s or parkinson’s disease, are affecting a large portion of the aged population worldwide. as the average human lifespan is expected to increase over time, the number of people within the population affected by such diseases is projected to grow by mid-century (alzheimer's association, 2016). thus, by recovering nerve functionality after injury, nerve regeneration techniques have great potential to conquer the problems that are projected to affect a significant amount of the general population. therefore, techniques such as neural tissue engineering is a rapidly growing field of research that has the potential to achieve efficient nerve regeneration. nevertheless, most clinical treatments are limited to symptomatic methods, as in vivo approaches in neural regeneration are yet to be utilized. in this article, current limitations and newly developed methods of neural regeneration are to be introduced, as well as suggestions on possible future improvements for clinical adaptations. one of the greatest problems in neural injuries is that, in contrast to the peripheral nervous system, the central nervous system (cns) is generally incapable of self-repair or regeneration. spontaneous regeneration of the cns is mainly due to functions of inhibitory factors, and little is uncovered about this mechanism of inhibition. yet in the late twentieth century, an explanation for the functional recovery of the cns was introduced based on the concept of neuroplasticity, the cns’s ability to anatomically and functionally adapt to changes. in addition, the concept of reactive synaptogenesis was also proposed in 1979. reactive synaptogenesis is the process in which neighboring neurons form new synaptic contacts to replace those lost, contributing to a restoration of function following brain injury. as a result, several methods, including the use of stem cells, brain drug delivery, and implanting degradable biomaterial, have been actively researched to enhance regeneration in cns. studies have found that specific brain regions including the subventricular zone (svz), the adjacent rostral migratory stream (rms), and the circumventricular organs (cvos) might be responsible for modulating the regenerative ability of neural stem or progenitor cells. neural stem cells that are possibly responsible for neurogenesis are expressed by filament proteins, nestin, vimentin, gfap, and transcription factor sox2 in the svz of the anterolateral ventricle and subgranular zone of the hippocampus. similarly, studies using rat models identified sox2 and the cell cycle-regulating protein ki67 in cvos, and therefore proposed that cvos play important roles in stem-cell based neurogenesis as well as svz and rms (bennett et al., 2009). svz, rms, and cvos share the common trait of lacking protection provided by the blood-brain barrier (bbb) compared to other parts of the brain. bbb is a unique form of cellular membrane that is relatively impermeable compared to the membranes of other body parts because its capillary walls have no pores and the capillaries are lined by astrocytes. limited permeability of bbb has been one of the most limiting restrictions in brain drug delivery research. however, because svz, rms, and cvos have more “leaky” bbbs, they are more likely to perceive damage and engage in brain repair by producing new neurons which cross to other parts of the brain. in addition, several neuroprotective and neuroregenerative drugs have been developed to treat neurodegenerative diseases. nevertheless, most of them are not utilized because they are generally incapable of crossing the bbb, followed by rapid clearance from the blood circulation by the reticuloendothelial system (res). for example, molecules like z-devd-fmk and basic fibroblast growth factor (bfgf) were found to significantly induce neuroregeneration in in vitro studies. however, neither can pass the bbb in their free form or do so in very low amounts, displaying limited efficacy in potential clinical uses (yemisci et al, 2015). thus, to stimulate these brain regions and to utilize the drug molecules that have been found to contribute to neurogenesis, intravenous injection of nanoparticles (np) figure 1. locations of svz and rms (chang et al., 2016). these regions are located near the occipital lobe of the brain and serve as possible sources of stem cell regulation. figure 2. nanoparticles delivered into brain regions (long et al., 2017). the msc and nscs are types of stem cells that can carry nanoparticles into the brain and allow for transfusion and delivery of the desired drug, which has been experimented with for in vivo studies. brain matters volume 2 6 through. nps are well-defined particles ranging in sizes of approximately 10 to 1000 nm (1 μm) with a core-shell structure (nanocapsules) or a continuous matrix structure (nanospheres) (kreuter, 2014). researchers have uncovered that specific forms of np (angiopep-conjugated poly(ethylene glycol)-copoly(ɛ-caprolactone) nanoparticles or ang-peg-nps) pass through the bbb and accumulate in certain brain areas such as the ventricles, hippocampus, and cortical layer. also, chitosan nps and cationic bovine serum albumin-conjugated tanshinone iia pegylated nps showed promising results in crossing the bbb and therefore increase drug efficacy. moreover, these nps have the inherent ability to elicit neuroprotective effects by themselves. for example, by down-regulating pro-inflammatory cytokines, up-regulating anti-inflammatory cytokines and transforming growth factor-β1 (tgf-β1) these nps modulate inflammatory processes and neuronal signaling pathways (saraiva et al., 2016). more specifically, among other np formulations, solid lipid nanoparticles (slns) are expected to enhance efficiency in brain-targeted drug delivery system. in the late 1900s, researchers found that surfactant coating on nps increases blood np level along with the total np brain amount in in vivo studies. several mechanisms were proposed to explain this increase, one being that increased np retention in the brain blood capillaries, and their absorption into the capillary walls may create a higher concentration gradient, which enhances transportation across the bbb, leading to brain drug accumulation. another explanation may be that np endocytosis by endothelial cells can permit the drug release within these cells and the following drug diffusion in the brain parenchyma, or the transcytosis of nps with the bound drug can release directly into the brain parenchyma, along with multiple other possible explanations. although these mechanisms are still being studied, previous experimental results have shown that the use of surfactant-coated slns plays a role in brain-targeting drug delivery that induces neural regeneration as a possible treatment to neurodegenerative diseases (blasi et al., 2007). another way to induce enhance neuroregeneration is to directly implant active biomaterials such as hydrogels. hydrogels are used in the same drug delivery system as nps but act differently through inducing neurogenesis by mimicking neural growth conditions. biomaterials can be useful because the systemic delivery of pharmaceuticals usually results in reduced efficacy over time. this is predominantly due to failure to meet the needs for continuous drug delivery, along with possible side effects followed by repeated drug administration (gerndt et al., 1997). in treatments of spinal cord injury (sci), the drug-releasing biomaterial has been proposed as a new solution to overcome these obstacles. polymer-based materials, including hydrogels, particles, and fibers/conduits, are implantable or sometimes injectable; they can prevent detrimental side effects of drugs delivered systemically, such as a compromised immune system. such biomaterials are targeted to provide structural support to regenerating axons and glia migrating into the injury site. they also aim to provide a similar mechanical and biological environment as those of the nerve tissue matrix and degrade over time to be replaced by regenerating tissue. for instance, hydrogels are injected into the intrathecal space of the spinal cord, most commonly in treatments of contusive sci. for an acute injury, hydrogels are injected onto the contusion injury site, and solidified gels onto the hemisection injury site. for secondary injury, hydrogels incorporating particles are injected onto the contusion injury site, and solidified gels with particles onto the hemisection injury site. a small cavity grows within the contusion injury during the proliferation and chronic injury phases. fibers are positioned below the dura within the contusion injury space, while the conduit scaffolds within the hemisection injury connect to the healthy tissue. in a study conducted in 1995, arg-gly-asp peptide-functionalized phpma hydrogels promoted angiogenesis and extension of axons and glial cells (woerly et al., 1995). in addition, agarose is another injectable biodegradable material as it solidifies following injection according to changes in the environment such as temperature and ph. brain-derived neurotrophic factors (bdnf)-formulated agarose can solidify when cooled post-injection; nevertheless, the appropriate mechanism to cool the material in situ should still be concerned (nguyen & lee, 2010). regenerative capability of biomaterials is based on figure 3. mechanism of hydrogel-induced neural regeneration (liu et al., 2018). the cell grafts and neurotrophic factors are injected via a hydrogel into the muscle scaffolding. the integration of the cells + neurotrophic factors lead to activation of astrocytes, microglia, and a variety of other neurons that are involved with the repair mechanism within the tissue. 7 brain matters volume 2 its ability to deliver appropriate growth factors or critical components of the extracellular matrix (ecm), bind the same receptor as their natural counterpart to promote cell attachment, spreading, and proliferation. these peptides, such as the most common examples, tripeptide rgd and multidomain peptide (mdp), are attached to syringe-deliverable hydrogels and are subcutaneously implanted into the injury site to provoke neurogenesis and angiogenesis resulting in the dense vascular network. as discussed above, these biomaterials predictably degrade over time and replaced with the regenerating cellular matrix. one of the greatest concerns in this approach is the immune response to the implanted biomaterials. injections generally lead to an acute inflammatory response as hydrogels are frequently recognized as foreign material (moore et al., 2018). several aspects such as the local context of biomaterials influence the innate properties of the implanted biomaterials that form the extent of the immune response (sadtler et al., 2016). thus, multiple approaches are being discovered to minimize the potentially harmful immune response in treatments involving biomaterial injection. as both approaches, drug delivery via nanoparticles and direct injection of biomaterials, have distinct compatibility in treating different neuroregeneration-related diseases or injuries, combining these techniques can be a possible solution to overcome inherent problems in these methods (schmidt & leach, 2003). followed by more extensive research in individual techniques, an appropriate combination of these could result in significant improvements of multiple neurological illnesses by inducing neural regeneration in different situations as needed. references adekoya, n., thurman, d. j., webb, k. w., & white, d. d. (2002). surveillance for traumatic brain injury deaths--united states, 1989-1998. alzheimer’s association. (2016). 2016 alzheimer’s disease facts and figures. alzheimer’s & dementia, 12(4), 459-509. blasi, p., giovagnoli, s., schoubben, a., ricci, m., & rossi, c. (2007). solid lipid nanoparticles for targeted brain drug delivery. advanced drug delivery reviews, 59(6), 454-477. bennett, l., yang, m., enikolopov, g., & iacovitti, l. (2009). circumventricular organs: a novel site of neural stem cells in the adult brain. molecular and cellular neuroscience, 41(3), 337-347. chang, e. h., adorjan, i., mundim, m. v., sun, b., dizon, m. l., & szele, f. g. (2016). traumatic brain injury activation of the adult subventricular zone neurogenic niche. frontiers in neuroscience, 10, 332. cotman, c. w., & scheff, s. w. (1979). compensatory synapse growth in aged animals after neuronal death. mechanisms of ageing and development, 9(1-2), 103-117. gerndt, s. j., rodriguez, j. l., pawlik, j. w., taheri, p. a., wahl, w. l., micheals, a. j., & papadopoulos, s. m. (1997). consequences of high-dose steroid therapy for acute spinal cord injury. journal of trauma and acute care surgery, 42(2), 279-284. huang, l., su, t., & li, x. (2013). natural products as sources of new lead compounds for the treatment of alzheimer’s disease. current topics in medicinal chemistry, 13(15), 1864-1878. kreuter, j. (2014). colloidal drug delivery systems (vol. 66). crc press. liu, s., schackel, t., weidner, n., & puttagunta, r. (2018). biomaterial-supported cell transplantation treatments for spinal cord injury: challenges and perspectives. frontiers in cellular neuroscience, 11, 430. long, w., yi, y., chen, s., cao, q., zhao, w., & liu, q. (2017). potential new therapies for pediatric diffuse intrinsic pontine glioma. frontiers in pharmacology, 8, 495. moore, a. n., silva, t. l. l., carrejo, n. c., marmolejo, c. a. o., li, i. c., & hartgerink, j. d. (2018). nanofibrous peptide hydrogel elicits angiogenesis and neurogenesis without drugs, proteins, or cells. biomaterials, 161, 154-163. nguyen, m. k., & lee, d. s. (2010). injectable biodegradable hydrogels. macromolecular bioscience, 10(6), 563-579. prang, p., müller, r., eljaouhari, a., heckmann, k., kunz, w., weber, t., ... & weidner, n. (2006). the promotion of oriented axonal regrowth in the injured spinal cord by alginate-based anisotropic capillary hydrogels. biomaterials, 27(19), 3560-3569. sadtler, k., singh, a., wolf, m. t., wang, x., pardoll, d. m., & elisseeff, j. h. (2016). design, clinical translation and immunological response of biomaterials in regenerative medicine. nature reviews materials, 1(7), 16040. saraiva, c., praça, c., ferreira, r., santos, t., ferreira, l., & bernardino, l. (2016). nanoparticle-mediated brain drug delivery: overcoming blood–brain barrier to treat neurodegenerative diseases. journal of controlled release, 235, 34-47. schmidt, c. e., & leach, j. b. (2003). neural tissue engineering: strategies for repair and regeneration. annual review of biomedical engineering, 5(1), 293-347. schwab, m. e. (2002). repairing the injured spinal cord. science, 295(5557), 10291031. stabenfeldt, s. e., garcía, a. j., & laplaca, m. c. (2006). thermoreversible laminin‐functionalized hydrogel for neural tissue engineering. journal of biomedical materials research part a: an official journal of the society for biomaterials, the japanese society for biomaterials, and the australian society for biomaterials and the korean society for biomaterials, 77(4), 718-725. tröster, s. d., & kreuter, j. (1988). contact angles of surfactants with a potential to alter the body distribution of colloidal drug carriers on poly (methyl methacrylate) surfaces. international journal of pharmaceutics, 45(1-2), 91-100. woerly, s., laroche, g., marchand, r., pato, j., subr, v., & ulbrich, k. (1995). intracerebral implantation of hydrogel-coupled adhesion peptides: tissue reaction. neural plasticity, 5(4), 245-255. yemisci, m., caban, s., gursoy-ozdemir, y., lule, s., novoa-carballal, r., riguera, r., ... & dalkara, t. (2015). systemically administered brain-targeted nanoparticles transport peptides across the blood—brain barrier and provide neuroprotection. journal of cerebral blood flow & metabolism, 35(3), 469-475. brain matters volume 2 8 copy of brain matters template final abstract neurobiological/neuroanatomical differences that impact development often manifest from physical defects, genetic diseases, physical trauma, and other internal factors. however, external factors have also been discovered to have a significant effect on brain structure, brain function, cognition, and emotion. this paper in particular will focus on the way gestational period stress on the mother can negatively impact a child’s development in connection with the increased neurotrophic factors, depressed development, and social anxiety that forms within the child. to continue, children who undergo early life stressors, whether that be in the form of a traumatic disorder or the struggles of low socioeconomic standing show developmental changes in brain anatomy that hinder memory, emotional control, and reward pathways. furthermore, the consequences of early childhood/prenatal stressors on development are most modulated by maternal nurturing. impact of gestational period stress and early life stressors on child development karishma patel introduction prenatal stressors are experienced by the fetus through the intermediate of the placenta, a fetal organ with dramatic endocrine properties. while prenatal stress can enhance child development, it is the nature, magnitude, chronicity, timing of the stress, and the pregnant mother’s biological/psychological response to the stress that will determine it as deleterious or not (buss et al., 2012). during a high stress pregnancy, an increased presence of maternal cortisol can lead to a dysregulation of a placental enzyme by the name of 11-b hydroxysteroid dehydrogenase type 2 (11b-hsd2). this enzyme converts the cortisol to cortisone, thus inhibiting the amount of cortisol that crosses the placenta and reaches the developing fetus. thus, dysregulation of this enzyme can expose the developing fetus to greater levels of cortisol (nieves et al., 2020). furthermore, these elevated cortisol levels that not only influence the developing fetus, but also young children who are exposed to high stress environments, act on glucocorticoid receptors that are richly abundant in areas of prolonged postnatal development, such as the hippocampus and prefrontal cortex (pechtel et al., 2010). the glucocorticoid receptors can impair neural plasticity in these specialized brain structures, leading to deficits in cognition in specialized areas such as language, aspects of memory, executive function and emotions (katsnelson, 2015). the relationship that children have with their caregivers is also imperative in modulating stress hormones in the early years of life. discussion to begin, mothers who suffer from high stress levels in the gestational period tend to release increased placental corticotropin releasing hormone (crh) and maternal cortisol, which in turn results in impaired fetal maturation, infant mental/motor development, and infant temperament (buss et al., 2012). these damaging impairments include neuroendocrine dysregulation, social anxiety, and internalizing behaviors (problematic internal feelings, such as anxiety, sadness, reticence, fearfulness, and oversensitivity). a reduction in gray matter volume due to high levels of cortisol inhibiting the growth and differentiation of the developing nervous system, consequently leading to detriments in executive function, attention, learning, memory, motor control, balance, precision, coordination, is further examined in fetuses whose mothers experienced high levels of anxiety in the second trimester of pregnancy (buss et al., 2012). the children of women who experienced high pregnancy specific anxiety levels during the early second trimester showed volume reductions in the prefrontal cortex, premotor cortex, medial temporal lobe, lateral temporal cortex, and cerebellum. these brain structures are imperative for a variety of cognitive functions such as reasoning, planning, attention, working memory, some aspects of language, and social and emotional processing including recognition and semantic memory (buss et al., 2012). furthermore, a study by francheska m. merced nieves and colleagues suggest a potential disadvantageous effect of maternal stress on visual attention. increased neuroendocrine responses might also condition the fetus and eventual child to have heightened enhancement for predator detection and avoidance mechanisms. while this response can prepare the fetus for any external socioeconomic stressors it may face, such as an unstable family and dangerous neighborhood, it can also increase a child’s susceptibility to mental disorders such as ptsd and depression (buss et al., 2012). to continue, elevated levels of maternal anxiety and depression have been related with an increased prevalence of fearful temperament among infants (buss et al., 2012). while maternal stress can negatively impact the developing fetus in a plethora of ways, stress experienced in childhood, whether due to severe traumatic events or socioeconomic standing, can also be detrimental to development. the amygdala, in particular, is highly susceptible to sensitivity due to early life stressors that these children experience. furthermore, children who experience early life stressors show significant deficits in the affective domain and in brain regions with extended postnatal development such as the hippocampus, amygdala, and prefrontal cortex (pechtel et al., 2010). early life stressors seem to interfere with the neurogenesis, synaptic overproduction, and pruning of synapses/receptors, thus impairing neural plasticity and growth in the critical brain areas listed above 9 (pechtel et al., 2010). to continue, dopamine cell bodies in the ventral tegmental area project to the nucleus accumbens, therefore firing reward and unpredictable rewards. chronic stressors and early hostile rearing environments contribute to anhedonia-like behavior, low energy, and apathy in a child, and in turn resulting in blunted mesolimbic dopamine transmission. this disrupted mechanism leads to dysfunction in reward related brain activation in children exposed to early life stress (pechtel et al., 2010). researchers also recognized deterioration in the cerebellum as a result of early life stress to children, resulting in impaired motor learning, balance, coordination, language, visual spatial learning, and working memory (pechtel et al., 2010). to continue, maternal love/caregiving support has an extreme impact on reducing stress levels in young children and in preventing adverse brain changes. the detrimental effects of poverty on a child’s hippocampus can be mediated by this caregiving support. reduced hippocampal volume in children can also be attributed to a lack of maternal compassion and love (luby et al., 2013). to continue, children with a healthy and stable relationship with their caregivers have a controlled stress hormone reaction to frightening or upsetting stimuli. contrarily, children who are devoid of such stability and are subject to an insecure and disorganized relationship with their parents experience high cortisol levels even after the incidence of mild stressors. to continue, those who live in conditions of chronic poverty and thus experience a culmination of unfortunate conditions (such as separation from parents, family turmoil, etc.) show even more elevated stress hormone levels. even after moving to a safer home, young children who are neglected and abused still show abnormal patterns of cortisol production. certain components of prenatal care, including parental discipline, parent child verbal communication, and sensitivity to the needs of the child can mediate the effects of socioeconomic standing on emotional and cognitive functioning in children. conclusion the detrimental effects of gestational stress on the developing fetus, and external stress on young children (as represented by early life stressors, trauma, or socioeconomic conditions), have intense adverse effects on emotional regulation, reward response, memory, brain plasticity, and gray volume matter in the brain. however, these negative consequences can be overturned with proper maternal/parental care, support, and nurturing. therefore, it is essential that resources to inspire and endorse support for both expectant mothers and parents that are in impoverished communities are readily available to create an enriching and supportive environment for the healthy development of the fetus and child. references buss, c., davis, e. p., hobel, c. j., & sandman, c. a. (2011, november 23). maternal pregnancy-specific anxiety is associated with child executive function at 6-9 years age. stress (amsterdam, netherlands). https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3222921/. buss, c., davis, e. p., shahbaba, b., pruessner, j. c., head, k., & sandman, c. a. (2012, april 23). maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems. proceedings of the national academy of sciences of the united states of america. https://pubmed.ncbi.nlm.nih.gov/22529357/. katsnelson, a. (2015, december 22). news feature: the neuroscience of poverty. pnas. https://www.pnas.org/content/112/51/15530. luby, j., belden, a., & botteron, k. (2013, december 1). effects of poverty on childhood brain development. jama pediatrics. https://jamanetwork.com/journals/jamapediatrics/fullarticle/176 1544. nieves, g. m., bravo, m., baskoylu, s., & bath, k. g. (2020, july 21). early life adversity decreases pre-adolescent fear expression by accelerating amygdala pv cell development. elife. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7413666/. pechtel, p., & pizzagalli, d. a. (2010, september 24). effects of early life stress on cognitive and affective function: an integrated review of human literature. psychopharmacology. https://pubmed.ncbi.nlm.nih.gov/20865251/ brain matters・volume v 10 https://pubmed.ncbi.nlm.nih.gov/20865251/ since the late 1700s, various physicists, electrophysiologists, biologists, and, eventually, neuroscientists have set out to create a faithful, functional understanding of the nervous system and its many components. early physiologists related physically observable behavioral abnormalities to damage or dysregulation of specific tissues of the brain; these findings promoted an increasingly modular view of brain function. this theory held that the brain was organized into discernible parts or “modules” that correlated to particular regulatory and functional tasks (blackmore, 2013). as a consequence, modular theory has been at the heart of research and scientific investigation in the field of neuroscience for centuries. the advent and introduction of more sophisticated brain imaging and stimulatory technologies such as fmri and tem, along with the development of more precise methodology for experimental lesion induction and neuron inhibition, have cast doubt on traditional modular theory (badcock et al., 2019). instead, new findings support a more unified, network-based theory of neural organization and function (sporns & betzel, 2016). despite our growing understanding of the more accurate nature of a network approach to brain study, many universities and classrooms still rely on either a predominantly or exclusively modular approach to neuroscience education. it is the goal of this article to inform the reader about the current state of debate between modular and network brain theories of brain organization and function, to elucidate the profound bias in education particularly undergraduate education toward the use and exploration of modular theory, and an examination of the benefits of readapting neuroscience education to give either commeasurable or greater coverage of the alternative network theory in neural organization and function. there are several different approaches to understanding the differences between adhd brains and non adhd brains. through the analysis of brain imaging, mri scans, as well as more techniques used, researchers are able to identify which regions in particular have comparable differences to a person without adhd. the article explains various techniques used and extensively covers the different studies conducted and their corresponding results. all of the studies found that certain regions such as caudate nucleus, putamen, nucleus accumbens, amygdala, and hippocampus illustrate the biggest differences in brain volume. a key point that was addressed within the article is that there needs to be a greater push for putting emphasis on mental health and the importance of staying positive in the midst of these difficulties. it is crucial that those who have disorders such as adhd, make lifestyle changes that are best suited to them in order to manage the disorder in the most efficient way. outcomes in neuroscience education: modular theory and network theory 1 thomas romanchek the differences between adhd brains vs. non adhd brains 3 julia gainski therapeutic techniques for neural regeneration in the central nervous system 6 chloe kim table of contents table of contents brain matters volume 2 neural regeneration is a rising topic in the field of clinical neuroscience. although several practical restrictions hinder neural regeneration in central nervous systems, researchers are actively working to develop different ways to promote cns regeneration in order to aid the population suffering from cns disease or injury. in this article, diverse approaches that are proposed to enhance cns regeneration will be listed and reviewed. the origin of language in humans has been a subject of considerable debate in psychology. noam chomsky was a pioneer of the language acquisition device theory, in which he states that humans have an innate ability to learn language. language is a highly complex faculty, and since even small children can grasp its principles, chomsky argues that they must be born with the ability to process and produce language. since children are able to compose unique, grammatically correct sentences, their faculty goes beyond what could be achieved by replicating learned behavior. top cognitive psychologists, including michael tomasello and john macnamara, posit that language ability in children mirrors other learned behaviors. children interpret statistical information to form grammatically correct sentences, adjusting their speech patterns using corrections from their parents. there is compelling evidence for both theories, but more work must be done to fully understand the development of this incredible human ability. language acquisition device and the origin of language 9 briana sobecks table of contents about brain matters & meet the editorial board 12 meet the writers 13 brain matters volume 2 table of contents copy of brain matters template final laura is a junior majoring in molecular and cellular biology and is pursuing a minor in food science. she is very excited to showcase the new volume and hopes to expand the journal to new horizons. aside from working on the journal, she is an assistant researcher in the robinson lab, is an mcb leader, an orientation leader, a member of bioscience journal club, and an executive board member of the undergraduate neuroscience society. fiza is a junior majoring in molecular and cellular biology on the pre-med track. in addition to her involvement in the neuroscience journal committee, she has communicated her illinois experience by being a former uiuc admissions blogger and enjoys science through volunteering at a local free clinic and doing research at vet med. she is thrilled to promote a neuroscience dialogue on campus! chief editor assistant chief editor julia gainski is a junior majoring in integrative biology with a minor in german. she is the public relations chair and a writer for brain matters. she is a research assistant at the control & network connectivity team (connectlab) at the beckman institute of advanced science and technology, where she assists with an eeg procedure in a concurrent eeg-fmri study. additionally, she is a personal assistant for students with physical disabilities at beckwith residential support services at nugent hall on campus, the secretary and a mentor of the pre-physician assistant club, and a member of the illini club tennis team. public relations chair brain matters board 1 br ai n m at te rs b oa rd carolyn is a junior majoring in molecular and cellular biology and is currently conducting research in neurochemistry in dr. jonathan v. sweedler’s lab. outside of academics, she is passionate about illinithon, the university of illinois’ dance marathon program that fundraises for st. john’s children’s hospital in springfield, il. she is excited to collaborate with the other students behind “brain matters” and promote brain awareness on campus. samantha is a junior majoring in journalism with a minor in astronomy. outside of academics, samantha photographs and models for the fashion network. she is excited about mixing her skills of writing and photography to promote brain awareness and neuroscience knowledge on campus. eva is a junior majoring in molecular and cellular biology and minoring in creative writing. aside from her passion for mental health and neuroscience awareness, she enjoys writing and dancing, and is a proud member of uiuc’s legend dance company. she is so excited to work with her fellow students to expand our campus’s appreciation for neuroscience through brain matters! editors rajvi javeri is a sophomore pursuing a major in psychology with a concentration in behavioral neuroscience and a minor in music. apart from being a part of the undergraduate neuroscience society, she helps out as a research assistant at the cognitive neuroimaging laboratory at the beckman institute. in her free time. she likes to practice guitar and sing. she also loves drinking infused teas and reading books whenever she can. she loves going on treks and any outdoor activities in general and is also a part of the uiuc archery club! brain matters・volume v 2 sarah is a junior majoring in biochemistry and intradisciplinary psychology. in addition to editing for brain matters, sarah works in dr. auinash kalsotra’s biochemistry lab as a research assistant and in dr. kara federmeier’s cognitive neuroscience lab. in the future, sarah hopes to pursue an md-phd in biochemistry to study the mechanisms of neurodegenerative disorders. in her free time, sarah loves to play soccer, go hiking, watch television, and spend time with friends. apil is a sophomore majoring in molecular and cellular biology with interests in neuroscience research. outside of studying biology, he volunteers at both riverside hospital and riverside senior life center where he works with alzheimer patients. his other hobbies include playing basketball and soccer. jade is a third year undergraduate in cognitive science with a concentration in linguistics. she is passionate about voice technology and its effects on human behavior. in her free time she sings, plays guitar and piano, and loves trying new foods. she also enjoys traveling and immersing herself in other cultures. her love of writing and editing is shown through her work for the illinimedia company and article written for soundhound inc’s speech-to-meaning blog. she is happy to be editing and designing for the “brain matters” journal. manan is a junior majoring in brain and cognitive sciences and is pursuing a minor in chemistry. apart from being a pre-dental student, manan has previously been an orientation leader at uiuc. last summer, manan worked with people of determination and designed thinking modules for underprivileged students in india. outside of class, manan is deeply interested in reading books that pertain to cognitive psychology and productivity, engaging in insightful scientific dialogue and community service. he looks forward to making brain matters an inclusive and engaging scientific committee on campus design board* 3 br ai n m at te rs b oa rd *due to publishing delays, volume 5 was designed by the design board team from the 2022-2023 academic year katy is a junior in brain in cognitive science, soon to be an mcb major with a certificate in neuroscience! she is interested in cellular neuroscience and neuropathology. apart from her role in brain matters as a writer, and recently appointed design team member and editor, she is a research assistant in the physical activity and neurocognitive health lab, as well as the evolutionary immunology and genomics laboratory. after undergrad, she plans to attend grad school to conduct her own research in cellular neuroscience! zainab hashmi is a sophomore pursuing a dual degree in psychology and information science with a minor in computer science. previously a writer for brain matters, she joined the design board this year. she’s involved in research at the adaptive cognition and interaction design lab at uiuc, is design chair of muslim student association, and also works as a graphic designer at spurlock museum on campus. she is excited to be a part of the journal and to make the vast topics of neuroscience more accessible to everyone. brain matters・volume v 4 sleep deprivation is a national issue affecting teenagers and adults. the center for disease control and prevention (cdc) reports that 35.2% of adults and 68.8% of teenagers get less than the recommended amount of sleep per night (2017). ideally, teens should get around 9.5 hours of sleep, while adults should get 7-9 hours (“national institute of neurological disorders and stroke,” 2019). sleep deprivation is measured considering both the quality and the amount of sleep an individual obtains per night. thus, people who wake up several times throughout the night are considered sleep deprived. the causes of sleep deprivation can be voluntary or involuntary. while some people may choose to stay awake, others may have sleep disorders that prevent them from falling asleep. in both cases of sleep deprivation, people face decreased cognitive capacity and increased risk for neurological disorders. sleep-related neurons are located in the brainstem, pineal gland, basal forebrain, amygdala, hypothalamus, and thalamus (“national institute of neurological disorders and stroke,” 2019). the ninds explains that the suprachiasmatic nuclei in the hypothalamus process light signals to regulate sleep, so that sleepiness aligns with nighttime darkness as part of the body’s circadian rhythm. the circadian rhythm is the body’s regulatory system that synchronizes sleep-wake cycles with daytime and nighttime and functions through hormone regulation. for instance, the pineal gland releases melatonin a well-known hormone used in the signaling pathway for inducing sleep. the timing of hormones and neurological activity is essential for the body to induce and maintain sleep. a dark environment causes the body to secrete melatonin because the circadian rhythm coordinates sleepiness with nighttime. then, the circadian rhythm halts production of melatonin and increases secretion of other hormones when the body needs to wake up from sleep during the daytime. sleep consists of nonrapid eye movement (nrem) and rapid eye movement (rem) cycles (jacobson, 2020). nrem is the first sleep cycle, and people spend most of their time in this cycle. nrem also consists of three phases: n1, n2, and n3. an article by kate jacobson explains that the nrem cycle synthesizes atp energy for the brain, decreases heart rate and internal temperature, and heals the body of toxic metabolites. then, the production of acetylcholine transitions the brain into the rem cycle. rem sleep is the cycle that features peak brain stimulation and the occurrence of dreams. research also suggests that rem sleep has cognitive benefits and can decrease feelings of depression or anxiousness. thus, losing the recommended amount of rem sleep could have negative consequences on the brain. a sleep survey asked teenagers to assess the importance of getting enough sleep each night and to report behavior leading to sleep loss. the respondents cited social media, video game, and tv usage as major factors of their sleep deprivation (quante et al., 2019). along with acting as a sleep distraction, electronic devices have light-emitting diodes (led) with blue light, which interferes with sleep. in nature, sunlight is necessary for healthy sleep cycles so that the hypothalamus can establish the body’s circadian rhythm. researchers wu et al. conducted a study to examine the effects of blue light exposure on sleep in mice (2021). mice were split into a white group and a blue group. the white group was exposed to an hour of white light per day, while the blue group was exposed to an hour of blue light per day. the results showed that the blue light group mice slept and the relationship between sleep deprivation and brain health caption: left side view of the brain locates regions of the brain involved in sleep-related functions. emma ibanez is a junior majoring in mcb with a minor in chemistry. she is an undergraduate research assistant in the rhodes lab, which studies the blood, brain, and gonads of sex-changing clownfish. through the brain matters journal, emma wants to help other students get excited about neuroscience and its research. after graduation, she plans to attend graduate school to research neuroscience or a related field. 12 woke at later times than the white light group. in humans, electronic use before bedtime prevents the onset of sleep and promotes feelings of tiredness in the morning. in addition to individual habits, sleep disorders are also a major factor in sleep deprivation. insomnia is a sleep disorder that makes it hard for a person to fall asleep. a medical study estimates that 33% of adults have chronic insomnia (bhaskar et al., 2016). additionally, the researchers found that 27% of respondents that had insomnia were previously undiagnosed, suggesting that insomnia may be an underdiagnosed condition. a paper from levenson et al. characterizes insomnia as a “hyperarousal” of the mind, meaning that overstimulation of the brain before bedtime prevents someone from falling asleep (2015). currently, little is known about the specific chemical and cellular processes behind insomnia, but theories suggest that a region or family of neurons may be primarily responsible for it. for example, damage or removal of the thalamus, raphe nuclei, and mediobasal preoptic area caused insomnia in experiments with nonhuman subjects. other experiments show that the hypothalamus and left dorsomedial frontal cortex led to insomnia in several human patients suffering from brain damage. causes of sleep deprivation can be voluntary or involuntary, but the effects of sleep deprivation can be similar in both groups. sleep deprivation may cause a decreased attention span, which is an important trait for participating in work or school activies (alhola and polo-kantola, 2007). several sleep deprivation studies use “speed and accuracy” to define an individual’s attention span, and many of those studies concluded that sleep deprivation decreases speed, accuracy, or both during the experiment. these findings imply the detrimental effects of sleep loss on test performance in students: an inability to work fast and accurately during a test could result in a lower score. sleep deprivation also negatively impacts memory capacity, which can disrupt learning. a study by heckman et al. analyzed the effects of sleep deprivation on memory in mice (2020). the sleep-deprived mice were put in a testing cage to accustom them to their new surroundings. two items were placed randomly in the cage so that the mice could learn the items’ positions. after 10 minutes, the mice were taken out of the testing cage and put into their holding cage. then, the researchers moved one of the objects in the testing cage to a new location to test the amount of time needed for the mouse to notice the change. compared to rested mice, the researchers concluded that the sleep-deprived mice had a lower capacity for creating and using their memory in navigating the cage. in addition to cognitive deficits, sleep deprivation is associated with depression. the cdc sleep survey shows that 22.9% of sleep-deprived adults reported having depression while 14.6% of well-rested adults reported having depression (2017). an article from harvard health publishing also reports that 65% to 90% of depressed adults have a sleep disorder, implying that sleep disorders, like insomnia, can put an individual at risk for developing depression (2019). the development of alzheimer’s disease has also been linked to sleep deprivation (bishir et al., 2020). alzheimer’s disease involves the deterioration of neurons and cognitive decline. stress leads to an increased risk of alzheimer’s disease, and sleep deprivation can lead to increased stress, indicating that prolonged sleep deprivation may increase an individual’s risk of alzheimer’s disease. sleep deprivation also decreases the activity of proteins that keep neurons alive, which would lead to neural degeneration and inflammation. neuron inflammation is involved with stroke onset, so extensive sleep loss can have fatal consequences. sleep deprivation may lead to health issues, so scientists have made extensive progress in treating sleep-related problems. doctors are equipped to diagnose and treat sleep disorders in patients that show symptoms. diagnostic tests may include monitoring the patient’s brain or heart activity during sleep, or inquiring into the patient’s family history of sleep disorders (abad and guilleminault, 2003). treatments vary depending on the type and severity of the disorder: some patients need drugs, like melatonin, for healthy sleep while others require nonmedicinal therapy. other lifestyle changes, such as decreasing the use of stimulants like caffeine, limiting blue light exposure before bedtime, and maintaining a consistent sleep schedule can help prevent sleep deprivation. in conclusion, sleep deprivation can be detrimental to overall brain health. short-term effects include symptoms like reduced cognition, but long-term effects like depression and alzheimer’s disease are life-altering. sleep deprivation is widespread among adults and teenagers alike, so the effects of sleep deprivation can also negatively impact performance in school and work settings. fortunately, recognition of sleep deprivation is the first step to changing sleep habits, caption: light and eye receptors regulate the circadian rhythm. darkness causes the pineal gland to produce melatonin and induce sleep. artificial blue light can delay the production of sleep promoting hormones and prevent sleep onset. caption: the pet scans demonstrate the difference between a healthy brain and a brain with alzheimer’s disease. alzheimer’s disease causes neural degradation and increases risk for sleep deprivation. 13 such as minimizing blue light before bedtime, or working with a doctor to overcome sleep disorders. references abad, v. c., & guilleminault, c. (2003). diagnosis and treatment of sleep disorders: a brief review for clinicians. dialogues in clinical neuroscience, 5(4), 371–388. https://doi.org/10.31887/ dcns.2003.5.4/vabad alhola, p., & polo-kantola, p. (2007). sleep deprivation: impact on cognitive performance. neuropsychiatric disease and treatment, 3(5), 553–567. bhaskar, s., hemavathy, d., & prasad, s. (2016). prevalence of chronic insomnia in adult patients and its correlation with medical comorbidities. journal of family medicine and primary care, 5(4), 780–784. https://doi.org/10.4103/2249-4863.201153 bishir, m., bhat, a., essa, m. m., ekpo, o., ihunwo, a. o., veeraraghavan, v. p., mohan, s. k., mahalakshmi, a. m., ray, b., tuladhar, s., chang, s., chidambaram, s. b., sakharkar, m. k., guillemin, g. j., qoronfleh, m. w., & ojcius, d. m. (2020). sleep deprivation and neurological disorders. biomed research international, 2020, 5764017. https://doi.org/10.1155/2020/5764017 centers for disease control and prevention. data and statistics. (2017, may 2). https://www.cdc.gov/sleep/data_statistics.html harvard health publishing. (2019, september 24). sleep and mental health. https://www.health.harvard.edu/newsletter_article/ sleep-and-mental-health heckman, p. r., roig kuhn, f., meerlo, p., & havekes, r. (2020). a brief period of sleep deprivation negatively impacts the acquisition, consolidation, and retrieval of object-location memories. neurobiology of learning and memory, 175. https://doi.org/10.1016/j. nlm.2020.107326 health and human services department. (2013, march 19). pet scan-normal brain-alzheimers disease brain [image]. wikimedia commons. https://commons.wikimedia.org/wiki/file:pet_scan-normal_brain-alzheimers_disease_brain.png jacobson, k. (2020, may 1). stages of sleep: nrem sleep vs rem sleep. american association of sleep technologists. https:// www.aastweb.org/blog/stages-of-sleep-nrem-deep-sleep-vs-rem-sleep levenson, j. c., kay, d. b., & buysse, d. j. (2015). the pathophysiology of insomnia. chest, 147(4), 1179–1192. https://doi. org/10.1378/chest.14-1617 ma, z., yang, y., fan, c., han, j., wang, d., di, s., hu, w., liu, d., li, x., reiter, r., & yan, x. (2016, april 18). melatonin as a potential anticarcinogen for non-small-cell lung cancer [illustration]. oncotarget. https://doi.org/10.18632/oncotarget.8776 national institute of neurological disorders and stroke. brain basics: understanding sleep. (2019, august 13). https:// www.ninds.nih.gov/disorders/patient-caregiver-education/understanding-sleep#:~:text=sleep%20is%20important%20to%20a,up%20 while%20you%20are%20awake national institutes of health. (2016, january 21). brain side view [illustration]. flickr. https://www.flickr.com/photos/nihgov/24414866102/in/album-72157662951050375/ quante, m., khandpur, n., kontos, e. z., bakker, j. p., owens, j. a., & redline, s. (2019). “let’s talk about sleep”: a qualitative examination of levers for promoting healthy sleep among sleep-deprived vulnerable adolescents. sleep medicine, 60, 81–88. https://doi. org/10.1016/j.sleep.2018.10.044 wu, f., wu, s., gui, q., tang, k., xu, q., tao, y., chen, m., cheng, j., wang, l., & zhang, l. (2021). blue light insertion at night is involved in sleep and arousal-promoting response delays and depressive-like emotion in mice. bioscience reports, 41(3). https://doi. org/10.1042/bsr20204033 14 copy of volume 7 publication meet the writers brain matters writers writer rajvi javeri is a sophomore pursuing a major in psychology with a concentration in behavioral neuroscience and a minor in music. apart from being a part of the undergraduate neuroscience society, she helps out as a research assistant at the cognitive neuroimaging laboratory at the beckman institute. in her free time. she likes to practice guitar and sing. she also loves drinking infused teas and reading books whenever she can. she loves going on treks and any outdoor activities in general and is also a part of the uiuc archery club! writer michael is a sophomore majoring in molecular and cellular biology honors on the pre-med track. he is currently working on campus as an undergraduate researcher in the nelson lab. in addition to writing for brain matters, michael is a member of the illinois medical screening society and plays trumpet for the marching illini. michael hopes to inspire new advances in the field of neuroscience by writing about new and interesting research. writer juan bautista: political science major; molecular cellular biology minor, senior. extracurricular organizations besides brain matters at uns, include professional development chair at minorities in health sciences and founder of bandside uiuc a platform for student rock bands. neuroscience is probably the only real thing there is from a metaphysical perspective so why not study it. brain matters and uns provide a great commons area for discussion on neurological topics. writer my name is dominick ramirez, i am currently a sophomore looking to major in psychology. rsos i’m involved in are blood club, illini classics club, and illini world taekwondo. i’m interested in neuroscience because i want to learn more about the physiology behind mental disorders. writer hari is a junior majoring in chemical engineering. aside from brain matters, hari is also involved in other illinois rso’s such as illini biodiesel initiative, and the american institute of chemical engineers. outside of academics, hari also works as a tutor, teaching sat prep courses to both middle and high school students. he is excited to see interest and outreach in neuroscience topics increase through “brain matters”. meet the writers brain matters staff chief-editor laura is a junior majoring in molecular and cellular biology and is pursuing a minor in food science. she is very excited to showcase the new volume and hopes to expand the journal to new horizons. aside from working on the journal, she is an assistant researcher in the robinson lab, is an mcb leader, an orientation leader, a member of bioscience journal club, and an executive board member of the undergraduate neuroscience society. assistant chief-editor fiza is a junior majoring in molecular and cellular biology on the pre-med track. in addition to her involvement in the neuroscience journal committee, she has communicated her illinois experience by being a former uiuc admissions blogger and enjoys science through volunteering at a local free clinic and doing research at vet med. she is thrilled to promote a neuroscience dialogue on campus! editor carolyn is a junior majoring in molecular and cellular biology and is currently conducting research in neurochemistry in dr. jonathan v. sweedler’s lab. outside of academics, she is passionate about illinithon, the university of illinois’ dance marathon program that fundraises for st. john’s children’s hospital in springfield, il. she is excited to collaborate with the other students behind “brain matters” and promote brain awareness on campus. editor samantha is a junior majoring in journalism with a minor in astronomy. outside of academics, samantha photographs and models for the fashion network. she is excited about mixing her skills of writing and photography to promote brain awareness and neuroscience knowledge on campus. editor and designer jade is a third year undergraduate in cognitive science with a concentration in linguistics. she is passionate about voice technology and its effects on human behavior. in her free time she sings, plays guitar and piano, and loves trying new foods. she also enjoys traveling and immersing herself in other cultures. her love of writing and editing is shown through her work for the illinimedia company and article written for soundhound inc’s speech-to-meaning blog. she is happy to be editing and designing for the “brain matters” journal. designer and writer apil is a sophomore majoring in molecular and cellular biology with interests in neuroscience research. outside of studying biology, he volunteers at both riverside hospital and riverside senior life center where he works with alzheimer patients. his other hobbies include playing basketball and soccer. editor eva is a junior majoring in molecular and cellular biology and minoring in creative writing. aside from her passion for mental health and neuroscience awareness, she enjoys writing and dancing, and is a proud member of uiuc’s legend dance company. she is so excited to work with her fellow students to expand our campus’s appreciation for neuroscience through brain matters! editor sarah is a junior majoring in biochemistry and intradisciplinary psychology. in addition to editing for brain matters, sarah works in dr. auinash kalsotra’s biochemistry lab as a research assistant and in dr. kara federmeier’s cognitive neuroscience lab. in the future, sarah hopes to pursue an md-phd in biochemistry to study the mechanisms of neurodegenerative disord brain matters staff copy of volume 6 publication hippocampus structure and functions violet wang the distinction and consistency of the dorsal and ventral hippocampus's functions. "what is the name of the mythical creature with the upper body of a horse and the lower body of a fish that came with poseidon?" "it is hippokampos!" in greek mythology, hippokampos means seahorse, and it was later morphed into the english word hippocampus. hippocampus, a part of the brain, gets its name because of its shape. bottom (moser & moser, 1998). moreover, previous studies of anatomy revealed that the input and output connections of the dorsal hippocampus and ventral hippocampus are different (swanson & cowan, 1977). figure 1. comparison of the human hippocampus and seahorse the hippocampus is a small seahorse-shaped structure located in the medial temporal lobe of the brain. as part of the limbic system, it is well known for its function of declarative memory formation, consolidation, and retrieval (squire, 1992). damage or dysfunction of the hippocampus can lead to a variety of memory impairments, such as amnesia (zola-morgan et al., 1986). the hippocampus is a highly intricate and multifaceted brain region that is not limited to memory processing, but also encompasses a range of other important human functions, including emotional regulation. let's go back to the structure of the hippocampus. according to the analysis by moser and moser (1998), the hippocampus may not be a single entity, but rather, the dorsal and ventral regions may have different roles. dorsal and ventral are anatomical terms used to describe the relative positions of structures in the body or brain. dorsal refers to the upper or back side, while ventral refers to the lower or front side. in the hippocampus, the dorsal portion is the septal pole, which is closer to the top of the brain, while the ventral portion is the temporal pole, which is closer to the figure 2. the diagram of the hippocampus. the hippocampus is divided in the middle into dorsal hippocampus and ventral hippocampus. the dorsal hippocampus is associated with episodic memory and spatial navigation. in a study by maguire et al. (1997), taxi drivers recalling complex routes through the city showed different activation patterns in the right posterior hippocampus compared to the anterior hippocampus, while language materials preferentially activated the human posterior hippocampus over the anterior hippocampus, with greater activation in the left side (greicius et al., 2003). anatomically, the dorsal ca1 is linked to the postpressive and anterior cingulate cortex (cenquizca & swanson, 2007; vogt & miller, 1983), two cortical regions primarily involved in cognitive processing of visuospatial information and memory, and environmental exploration (maguire et al., 2006; spiers & maguire, 2006). overall, the dorsal region of the hippocampus is more associated with cognitive processes. the ventral hippocampus is responsible for emotions, such as anxiety and fear. kjelstrup et al. (2002) found that lesions to the most ventral quarter of the rats‘ hippocampus led to reduced defecation in brightly lit chambers, indicating a reduction in anxiety. additionally, studies indicate that animals with the ventral hippocampus removed tend to disregard cues associated with fear (koh et al., 2009). in human research, the ventral hippocampus is involved across conditions of threat, safety, and conditioned inhibition, using the pairing of threat and safety cue (meyer et al., 2019) . in terms of neuronal connectivity of the ventral hippocampus, it communicates bidirectionally with the amygdala via glutamate signaling, projecting responses to fear cues (jimenez et al., 2018). due to this anatomical feature, the ventral hippocampus is more associated with emotions. 39brain matters volume vi although the dorsal hippocampus is thought to be more important for spatial processing and memory, and the ventral hippocampus is primarily responsible for fear and anxious behavior, anatomical connections suggest a flow of information between the dorsal and ventral regions (lee et al. 2019). it was found that in spatial performance, the dorsal hippocampus was mainly involved in the formation of spatial maps, while the ventral hippocampus was involved in spatial flexibility and the ability to update spatial maps (lee et al. 2019). when dealing with fear, the dorsal ca3 results in the formation of a generalized fear response; the ventral ca3 leads to fear discrimination between the fear-inducing and safe contexts (besnard et al.,2020). in practice, the dorsal and ventral hippocampus function as a single integrated structure. in summary, both the dorsal and ventral regions of the hippocampus, which are “the head and tail” of the hippocampus, work separately and together to facilitate various cognitive functions to enhance quality of life. besnard, a., miller, s. m., & sahay, a. (2020). distinct dorsal and ventral hippocampal ca3 outputs govern contextual fear discrimination. cell reports, 30(7), 23602373. cenquizca, l. a., & swanson, l. w. (2007). spatial organization of direct hippocampal field ca1 axonal projections to the rest of the cerebral cortex. brain research reviews, 56(1), 1-26. fanselow, m. s., & dong, h. w. (2010). are the dorsal and ventral hippocampus functionally distinct structures?. neuron, 65(1), 7-19. greicius, m. d., krasnow, b., boyett‐anderson, j. m., eliez, s., schatzberg, a. f., reiss, a. l., & menon, v. (2003). regional analysis of hippocampal activation during memory encoding and retrieval: fmri study. hippocampus, 13(1), 164-174. jimenez, j. c., su, k., goldberg, a. r., luna, v. m., biane, j. s., ordek, g., ... & kheirbek, m. a. (2018). anxiety cells in a hippocampal-hypothalamic circuit. neuron, 97(3), 670-683. kjelstrup, k. g., tuvnes, f. a., steffenach, h. a., murison, r., moser, e. i., & moser, m. b. (2002). reduced fear expression after lesions of the ventral hippocampus. proceedings of the national academy of sciences, 99(16), 10825-10830. koh, m. t., wheeler, d. s., & gallagher, m. (2009). hippocampal lesions interfere with long-trace taste aversion conditioning. physiology & behavior, 98(1-2), 103-107. lee, s. l., lew, d., wickenheisser, v., & markus, e. j. (2019). interdependence between dorsal and ventral hippocampus during spatial navigation. brain and behavior, 9(10), e01410. references 1. 2. 3. 4. 5. 6. 7. 8. maguire, e. a., nannery, r., & spiers, h. j. (2006). navigation around london by a taxi driver with bilateral hippocampal lesions. brain, 129(11), 2894-2907. meyer, h. c., odriozola, p., cohodes, e. m., mandell, j. d., li, a., yang, r., ... & gee, d. g. (2019). ventral hippocampus interacts with prelimbic cortex during inhibition of threat response via learned safety in both mice and humans. proceedings of the national academy of sciences, 116(52), 26970-26979. moser, m. b., & moser, e. i. (1998). functional differentiation in the hippocampus. hippocampus, 8(6), 608-619. moser, m. b., moser, e. i., forrest, e., andersen, p., & morris, r. (1995). spatial learning with a minislab in the dorsal hippocampus. proceedings of the national academy of sciences, 92(21), 9697-9701. spiers, h. j., & maguire, e. a. (2006). thoughts, behaviour, and brain dynamics during navigation in the real world. neuroimage, 31(4), 1826-1840. squire, l. r. (1992). memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. psychological review, 99(2), 195–231. swanson, l. w., & cowan, w. m. (1977). an autoradiographic study of the organization of the efferent connections of the hippocampal formation in the rat. journal of comparative neurology, 172(1), 49-84. vogt, b. a., & miller, m. w. (1983). cortical connections between rat cingulate cortex and visual, motor, and postsubicular cortices. journal of comparative neurology, 216(2), 192-210. zola-morgan, s., squire, l. r., & amaral, d. g. (1986). human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field ca1 of the hippocampus. the journal of neuroscience : the official journal of the society for neuroscience, 6(10), 2950–2967. 9. 10. 11. 12. 13. 14. 15. 16. 17. 40brain matters volume vi fiza bukhari chief editor fiza is a sophmore majoring in molecular and cellular biology on the pre-med track. in addition to her involvement in the neuroscience journal committee, she communicates her illinois experience by writing for the uiuc admissions blog. just like her blog, she is thrilled to promote a neuroscience dialogue. laura kilikevicius assistant-chief editor laura is a sophomore majoring in biology and hopes to one day move into work in genetics. she is thrilled to be working on “brain matters” and hopes to broaden the knowledge of current neuroscience research across campus. outside of the journal, she is an orientation leader on campus and is a member of catholic illini. emerson fister chief of design/editor emerson is a senior majoring in psychology with a concentration in behavioral neuroscience and a minor in integrative biology. outside of learning about neuroscience, she is passionate about human-centered design and is an active member of the university of illinois design for america studio. she is delighted to collaborate and learn with the other students behind “brain matters”. carolyn oh editor carolyn is a sophomore majoring in molecular and cellular biology and is currently conducting research in neurochemistry in dr. jonathan v. sweedler’s lab. outside of academics, she is passionate about illinithon, the university of illinois’ dance marathon program that fundraises for st. john’s children’s hospital in springfield, il. she is excited to collaborate with the other students behind “brain matters” and promote brain awareness on campus. eva cornman editor eva is a sophomore majoring in molecular and cellular biology and minoring in creative writing. aside from her passion for mental health and neuroscience awareness, she enjoys writing and dancing, and is a proud member of uiuc’s legend dance company. she is so excited to work with her fellow students to expand our campus’s appreciation for neuroscience through brain matters! about brain matters & meet the editorial board the undergraduate neuroscience society (uns) is an academic student organization that strives to promote, educate, and hold events that help undergraduates gain a deeper understanding and appreciation for the field of neuroscience. the neuroscience journal committee, a subsidiary of uns, has created a journal entitled brain matters. this journal promotes a neuroscience dialogue on campus by publishing student research about topics ranging from neuroscience, psychology, and biology. brain matters volume 2 12 article 2 progression in understanding combat induced mental disorders dominick ramirez many names have been created to describe the combination of symptoms that soldiers face after returning from combat. until recent advancements in science, there has not been much consensus as to the cause and proper treatment of disorders that had medical symptoms but had no visible injuries to cause them. during world war i, the large amount of manpower involved in the conflict, along with the corresponding large numbers of soldiers that became afflicted, made these disorders unignorable for governments and the medical community. during this time, there was a disagreement within the medical community as to whether the symptoms were caused by physical injuries to the brain or were psychological. the term shell-shock was coined by psychologist charles samulel myers in 1915 to describe the disorder but had no concrete definition. presently, the term post-traumatic stress disorder (ptsd) has been developed to describe the mental condition that develops in response to experiencing or witnessing an event that has the potential to cause death or great bodily harm. unlike shell-shock, ptsd is a more generalized term, applied to events such as natural disasters, sexual assault, war, and automobile accidents as opposed to exclusively experiences in war. during a traumatic event, the brain causes the body to enter a state of self-preservation during which the sympathetic nervous system. this is the division of the nervous system responsible for regulating involuntary body functions such as sweat secretion and reflex adjustments of the cardiovascular system. in a stressful or dangerous situation, it releases large quantities of epinephrine from the adrenal gland, which causes an increase in heart rate, the widening of skeletal muscle blood vessels, and other effects which prepare the body to either fight, flee or freeze. ptsd occurs when the transition from this state to a responsive state brought about by the parasympathetic nervous system fails to happen. the symptoms of ptsd fall within the realm of intrusive memories, avoidance of reminders of the traumatic event, adverse changes in thinking and mood, and changes in physical and emotional reactions. in a military context, ptsd is often seen as the leading cause of mental ailments, and thus, these injuries are described as solely psychiatric. however, some research suggests that this is not always the case. besides ptsd, another affliction, blast-induced traumatic brain injury (btbi), is another prevalent injury among troops. while these conditions often exist simultaneously and have similar symptoms, btbi is a form of traumatic brain injury which is currently not very well understood and, therefore, more difficult to detect and treat. a common assumption in past years was that explosive blasts had similar effects to sports concussions and traffic accidents; however, recent studies have shown that there are physical differences in the brain that develop after experiencing a survivable blast (denes v agoston, md and alaa kamnaks 2015). in one case, scientists found that brains of deceased veterans that survived explosions and lived for years afterward had a unique honeycomb pattern of axonopathy or damage to nerve cells called axons, which are different damage patterns from other types of head injuries. these lesions were found in multiple areas of the brain, including the frontal lobe, which contains the parts responsible for personality expression and the execution of voluntary muscle movement. these findings could explain why the survivors went on to develop behavioral symptoms similar to those of athletes with concussions. (ryu, j., horkayne-szakaly, i., xu, l. et al. 2014). in another study that examined the brains of veterans post-mortem, dustlike scarring was found along the borders between grey matter and interconnecting white matter. this is different from the brain scarring caused by concussions in that it did not have a staining appearance on the tissue it affected. when compared to samples of people who had experienced ordinary concussions or had drug addictions (which have the potential to cause visible brain damage), it was found that the dust pattern was unique to bast survivors. (sharon baughman shively, md, iren horkayne-szakaly, md, robert v jones, md, et al. 2016) these and similar studies provide a foundation for further study in trying to understand the different types of mental injuries sustained in war as not much is currently understood as to how exactly blasts cause vol. 3 6 war were completely psychological; however, these advances have confirmed the existence of causes that, while previously suggested, were unable to be proven due to technological limitations. references kochanek, p. m., bauman, r. a., long, j. b., dixon, c. e., & jenkins, l. w. (2009). a critical problem begging for new insight and new therapies. journal of neurotrauma, 26(6), 813–814. doi: 10.1089/neu.2008.0893 agoston, denes, and alaa kamnaksh. “modeling the neurobehavioral consequences of blast-induced traumatic brain injury spectrum disorder and identifying related biomarkers.” brain neurotrauma frontiers in neuroengineering series, may 2015, pp. 309–328., doi:10.1201/b18126-28. “combat veterans’ brains reveal hidden damage from ied blasts 01/14/2015.” johns hopkins medicine, based in baltimore, maryland, www.hopkinsmedicine. org/news/media/releases/combat_veterans_brains_reveal_hidden_damage_from_ ied_blasts. goldstein, lee e, et al. “chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model.” science translational medicine, u.s. national library of medicine, 16 may 2012, www.ncbi.nlm.nih.gov/ pmc/articles/pmc3739428/. “is shell shock the same as ptsd?” psychology today, sussex publishers, www. psychologytoday.com/us/blog/what-doesnt-kill-us/201111/is-shell-shock-thesame-ptsd. jung, k. elan. “posttraumatic spectrum disorder: a radical revision.” psychiatric times, 1 nov. 2001, www.psychiatrictimes.com/antisocial-personality-disorder/ posttraumatic-spectrum-disorder-radical-revision. kochanek, patrick m., et al. “a critical problem begging for new insight and new therapies.” journal of neurotrauma, vol. 26, no. 6, 2009, pp. 813–814., doi:10.1089/ neu.2008.0893. ryu, jiwon, et al. “the problem of axonal injury in the brains of veterans with histories of blast exposure.” acta neuropathologica communications, vol. 2, no. 1, 2014, doi:10.1186/s40478-014-0153-3. schwarz, alan. “research traces link between combat blasts and ptsd.” the new york times, the new york times, 9 june 2016, www.nytimes. com/2016/06/10/us/ptsd-blast-waves-research.html. shively, sharon baughman, et al. “characterisation of interface astroglial scarring in the human brain after blast exposure: a post-mortem case series.” the lancet neurology, vol. 15, no. 9, 2016, pp. 944–953., doi:10.1016/s1474-4422(16)30057-6. “traumatic brain injury.” mayo clinic, mayo foundation for medical education and research, 29 mar. 2019, www.mayoclinic.org/diseases-conditions/traumatic-brain-injury/symptoms-causes/syc-20378557. “va.gov: veterans affairs.” what is polytrauma?, 9 july 2014, www.polytrauma. va.gov/understanding-tbi/definition-and-background.asp. worth, robert f. “what if ptsd is more physical than psychological?” the new york times, the new york times, 10 june 2016, www.nytimes.com/2016/06/12/ magazine/what-if-ptsd-is-more-physical-than-psychological.html. vol. 3 7 laura is a junior majoring in molecular and cellular biology and is pursuing a minor in food science. she is very excited to showcase the new volume and hopes to expand the journal to new horizons. aside from working on the journal, she is an assistant researcher in the robinson lab, is an mcb leader, an orientation leader, a member of bioscience journal club, and an executive board member of the undergraduate neuroscience society. fiza is a junior majoring in molecular and cellular biology on the pre-med track. in addition to her involvement in the neuroscience journal committee, she has communicated her illinois experience by being a former uiuc admissions blogger and enjoys science through volunteering at a local free clinic and doing research at vet med. she is thrilled to promote a neuroscience dialogue on campus! chief editor assistant chief editor julia gainski is a junior majoring in integrative biology with a minor in german. she is the public relations chair and a writer for brain matters. she is a research assistant at the control & network connectivity team (connectlab) at the beckman institute of advanced science and technology, where she assists with an eeg procedure in a concurrent eeg-fmri study. additionally, she is a personal assistant for students with physical disabilities at beckwith residential support services at nugent hall on campus, the secretary and a mentor of the pre-physician assistant club, and a member of the illini club tennis team. public relations chair brain matters board 24brain matters・volume v issue ii br ai n m at te rs b oa rd carolyn is a junior majoring in molecular and cellular biology and is currently conducting research in neurochemistry in dr. jonathan v. sweedler’s lab. outside of academics, she is passionate about illinithon, the university of illinois’ dance marathon program that fundraises for st. john’s children’s hospital in springfield, il. she is excited to collaborate with the other students behind “brain matters” and promote brain awareness on campus. samantha is a junior majoring in journalism with a minor in astronomy. outside of academics, samantha photographs and models for the fashion network. she is excited about mixing her skills of writing and photography to promote brain awareness and neuroscience knowledge on campus. eva is a junior majoring in molecular and cellular biology and minoring in creative writing. aside from her passion for mental health and neuroscience awareness, she enjoys writing and dancing, and is a proud member of uiuc’s legend dance company. she is so excited to work with her fellow students to expand our campus’s appreciation for neuroscience through brain matters! editors rajvi javeri is a sophomore pursuing a major in psychology with a concentration in behavioral neuroscience and a minor in music. apart from being a part of the undergraduate neuroscience society, she helps out as a research assistant at the cognitive neuroimaging laboratory at the beckman institute. in her free time. she likes to practice guitar and sing. she also loves drinking infused teas and reading books whenever she can. she loves going on treks and any outdoor activities in general and is also a part of the uiuc archery club! 25 sarah is a junior majoring in biochemistry and intradisciplinary psychology. in addition to editing for brain matters, sarah works in dr. auinash kalsotra’s biochemistry lab as a research assistant and in dr. kara federmeier’s cognitive neuroscience lab. in the future, sarah hopes to pursue an md-phd in biochemistry to study the mechanisms of neurodegenerative disorders. in her free time, sarah loves to play soccer, go hiking, watch television, and spend time with friends. design board* manan is a junior majoring in brain and cognitive sciences and is pursuing a minor in chemistry. apart from being a pre-dental student, manan has previously been an orientation leader at uiuc. last summer, manan worked with people of determination and designed thinking modules for underprivileged students in india. outside of class, manan is deeply interested in reading books that pertain to cognitive psychology and productivity, engaging in insightful scientific dialogue and community service. he looks forward to making brain matters an inclusive and engaging scientific committee on campus zainab hashmi is a sophomore pursuing a dual degree in psychology and information science with a minor in computer science. previously a writer for brain matters, she joined the design board in 2022. she’s involved in research at the adaptive cognition and interaction design lab at uiuc, is a ux designer for design innovation, design chair of muslim student association, and also works as a graphic designer at spurlock museum on campus. she is excited to be a part of the journal and to make the vast topics of neuroscience more accessible to everyone. katy simmons is an mcb major pursuing a certificate in neuroscience! her interests include cellular neuroscience and neuroimmunology. she is involved in brain matters as a design team member, editor, and former writer. her favorite thing about being a part of the journal is meeting and engaging with others that are passionate about neuroscience. apart from her role in brain matters, she is a research assistant in the physical activity and neurocognitive health lab, as well as the evolutionary immunology and genomics laboratory. after undergrad, she plans to attend grad school to conduct her own research in cellular neuroscience! 26brain matters・volume v issue ii br ai n m at te rs b oa rd 27 apil is a sophomore majoring in molecular and cellular biology with interests in neuroscience research. outside of studying biology, he volunteers at both riverside hospital and riverside senior life center where he works with alzheimer patients. his other hobbies include playing basketball and soccer. jade is a third year undergraduate in cognitive science with a concentration in linguistics. she is passionate about voice technology and its effects on human behavior. in her free time she sings, plays guitar and piano, and loves trying new foods. she also enjoys traveling and immersing herself in other cultures. her love of writing and editing is shown through her work for the illinimedia company and article written for soundhound inc’s speech-to-meaning blog. she is happy to be editing and designing for the “brain matters” journal. *due to publishing delays, volume v issue ii was designed by the design board from the 2022-2023 academic year the future of neuroregeneration hanifa mohammed neurodegenerative diseases are disorders in which the structure and function of the central nervous system (cns) and/or the peripheral nervous system (pns) are degraded. neurodegenerative diseases arise in mid to late life, and with the increasingly aging population in the world it’s predicted that more than 12 million americans will have neurodegenerative diseases by 2030 (the challenge of neurodegenerative diseases, n.d.). in mammals the neurons in the cns do not spontaneously regenerate which leads to multiple complications related to diseases that affect brain or spinal cord repair. these complications lead to disorders such as alzheimer’s disease (ad) and parkinson’s disease (pd) (huebner, e. a., & strittmatter, s. m. (2009)). currently there are multiple conceptual solutions to battle these disorders, all of which focus on replacement of lost neuronal cell bodies, or in other words neuroregeneration. studies have shown that the “lack of intrinsic regenerative ability of cns axons'' is due to the expression of adult neuronal genes (nagappan, p. g., chen, h., & wang, d. y. (2020)). neuroregenration of cns neurons requires tenascinbinding integrin to assist in the organization of the extracellular matrix glycoprotein, tenascin, which modulates cell adhesion (tucker & chiquet-ehrismann, 2015). the tenascin-binding integrin is not made in a fully differentiated adult neuron cell and thus adult neurons cannot undergo mitosis and produce more neurons (nagappan, p. g., chen, h., & wang, d. y. (2020)). embryonic axons can make tenascin-binding integrin as they remain undifferentiated, meaning they have better chances to grow new neurons in the cns than adult axons (nagappan, p. g., chen, h., & wang, d. y. (2020)). the use of pluripotent embryonic stem cells (esc) could be the answer to treat many conditions that often have only palliative care as a treatment. escs though come with ethical limitations since they are derived from human embryos. induced pluripotent stem cells (ipsc), are a novel system that can overcome this limitation by generating a pluripotent stem cell from a somatic cell, a cell that is not a gamete or an undifferentiated stem cell. they also have the added benefit of being created per-patient so that immune system rejection is minimized. in the laboratory, ipscs have shown great promise in regenerative medicine as they can give rise to any cell type in the body, including neurons (fig 1). with the growing interest in the possibilities ipscs provide to many neurodegenerative diseases, many researchers have begun to investigate how ipscs can mitigate the two most common neurodegenerative diseases alzhemier’s disease (ad) and parkinson’s disease (pd). ad is the most common neurodegenerative disease, with a predicted 6.2 million people in the us alone suffering from the disease (alzheimer’s disease questions and answers, n.d.). ad is sporadic and age-related and results in the gradual deterioration of cognitive functions . the brain of an ad patient has a noticeably reduced volume (fig 2). abstract as the average lifespan for humans is growing, neurodegenerative diseases are becoming more common. the two most common neurodegenerative diseases are alzheimer’s disease (ad) and parkinson’s disease (pd). both of these diseases cause the progressive degeneration of the central nervous system (cns). to combat the effects of these disorders it’s crucial to be able to regenerate the lost neurons. the issue is that cells in the brain reduce their plasticity as age increases, leading to little to no regeneration of the lost cells. induced pluripotent stem cell (ipsc) is a new avenue of research regarding neuroregeneration as the ability to specialize them into neurons provides a method to combat the progressive degenerative nature of neurodegenerative diseases. research in ad has shown successful experiments in specializing ipscs into glial cells and cholinergic neurons to improve memory loss in ad mice. research in pd has shown a method to specialize ipsc to neurons and thereby obtaining patient-specific transplants. the transplants and their effects have been successful in many animal models, leading to the potential of clinical trials in the near future. figure 1: cells can be gathered from the patient in concern. they can then be reprogrammed to ipscs and used to differentiate into the desired cell for treatment. this creates ipscs specifically tailored to the patient, thus reducing chances of immune rejection. image from vasic et al., 2019. 16brain matters・volume v issue ii this reduction in brain volume was particularly centered at the hippocampus, which is responsible for learning and memory, the loss in volume was attributed to death of neurons and degeneration of synapses. moreover, research suggests the unique occurrence of amyloid plaques, aggregated misfolded protein that cannot be broken down by the body, in the extracellular space of the ad brain is a causative factor in the development of this disease (vasic et al., 2019;cha m. y. et al. (2017)). in order to study how ipscs could reverse the effects of amyloid plaques, a study by fujiwara et al., treated transgenic mice with amyloid plaque build up with an ipsc therapy. firstly, amyloid plaques have been duplicated in pdgf promoter driven amyloid precursor protein (pdapp) transgenic mouse models. pdapp is a mutant of the human amyloid precursor protein (app) which results in the formation of amyloid plaques, and the buildup of amyloid plaques when mutated. now that the transgenic mice had a build up of amyloid plaques fujiwara et al. implanted human ipsc into these mice and attempted to regenerate cholinergic neurons, common nerve cells that serve as acetylcholine neurotransmitters, to ascertain the role ipsc cells may have in reversing the buildup phenotype. the ipsc cells that were injected had been specialized into neuronal precursors that would display a cholinergic neuron phenotype and were injected into the bilateral hippocampus of mice that had high levels of amyloid plaques (fig 3a-c) (fujiwara et al., 2013). as a control, some pdapp mice were injected with pbs (fujiwara et al., 2013). in order to measure neuroregeneration, the spatial memory function, a skill that utilizes the hippocampus, of the pdapp mice was measured prior to and after the injection at various intervals (fujiwara et al., 2013) (fig 3d-g). if the spatial memory function of the pdapp mice, with the transplanted ipsc cell, improves after the injection, it’s indicative of neuroregeneration in the hippocampal region which could point to reversal of ad phenotype (fujiwara et al., 2013). upon grafting the neuronal precursors into the mice, it was noticed that they dispersed throughout the hippocampus and became cholinergic and gabaergic neurons (fujiwara et al., 2013). gabaergic neurons are hypothesized to have similar growth conditions as cholinergic neurons and as a result have also regenerated (fujiwara et al., 2013). regardless, the spatial memory function of the mice with the ipsc transplantation was seen to improve after the grafting (fujiwara et al., 2013) (fig 3dg). the exact mechanisms involved in the improvement of spatial memory function in these mice are unknown. although, it is thought that the “neuronal precursors reconstruct neural networks essential for spatial memory function” (fujiwara et al., 2013). this implies that ipscs can be used to alleviate and delay the symptoms of ad. figure 2: the brain volume of an ad patient (top) as compared to the brain volume of a normal patient (bottom). image from: hersenbank. (2008). figure 3: ipscs were transplanted in the hippocampus as indicated by the black square on panel a and b. the neurons were fluorescently labelled by dapi to check for cell viability as seen n panel c. mean platform escape measures the time it takes for the mice to escape a maze, effectively measuring spatial memory. before the transplantation both the pdapp with the ipsc cell transplantation and the control with the pbs have similar, comparable spatial memory (d-e). within the second and third trial the pdapp with the cell transplantation shows an improved spatial memory (fg). image from fujiwara et al., 2013. 17 deleidi et al., used mauritian cynomolgus macaques (cm) to generate ipscs. cm has seven holtypes, so if ipscs can be generated by all seven haplotypes and still be able to regenerate neurons, then this process would indicate that individualized treatment for pd is plausible (deleidi et al., 2011). cm ipscs went through in vitro differentiation into dopaminergic neurons (deleidi et al., 2011). 400,000 differentiated ipscs were then transplanted into the striatum of 6-ohda rats (deleidi et al., 2011). 6-ohda rats is an animal model that has neurotoxin-induced neurodegeneration, behavioral deficits and motor dysfunction to model pd in a rat (simola et al., 2007). these models were used to examine how the pd phenotype would change after ipsc transplant. upon examining the dopaminergic neural graft after 4-16 weeks post-transplantation, it was found, through amphetamine and apomorphine responses, that the dopaminergic neurons were able to rebuild the connection between the striatum and snc that 6-ohda rats did not have (deleidi et al., 2011) (fig 4). the disconnection between the striatum and snc is a common cause of pd in humans so this finding implies the possibility that ipscs could be used to create dopaminergic neural grafts and combat the pathogenesis of pd (deleidi et al.). having successfully repeated this experiment on monkeys, human clinical trials are the next step in creating an adept treatment for pd (deleidi et al., 2011). kyoto, japan has begun clinical trials, which have shown both long-term survival and good integration into brain networks (elkouzi et al., 2019). to conclude, ipscs show great promise in neuroregeneration due to their autologous translatability and pluripotency. when it comes to treating neurodegenerative diseases, ipscs can be used to regenerate or restore lost and damaged brain networks. alzehimer’s disease, the most common neurodegenerative disease, is marked with amyloid plaques, which aid in progression of the disease. another study, cha et al., has shown that ipscs can be used to prevent neurodegeneration without regenerating neurons. research on neuron-astrocyte interactions has suggested that glial cells take part in regulating nerve activity and intracellular signalling by releasing neuromodulatory factors. (cha m. y. et al. (2017)). glial cells can be a causative factor to ad as their hyperactivation leads to formation of excess amyloid plaques (types of glia. (2016)). 5xfad is a transgenic mouse model that has five mutations that result in formation of amyloid plaques (shin et al., 2021). protein-ipscs are adult cells that were injected with the proteins of an esc, resulting in the adult cell gene expression being that of an esc. protein-ipscs is another method of obtaining ipscs. cha et al., injected protein-ipscs into 5xfad mice for the purpose of improving ad pathogenesis, and specifically focusing on their effect on amyloid plaques. to test the effects of protein-ipscs on the 5xad mice, spatial memory functions were tested. mice with the injected protein-ipscs displayed better spatial memory then those mice with no injected protein-ipscs (cha m. y. et al. (2017)). furthermore, these protein-ipscs were found to have become glial cells, mostly oligodendrocytes, implying that healthy oligodendrocytes, which create support for axons in the cns by producing myelin, may “improve memory function by maintaining axonal integrity” hence reducing the neurodegenerative effects of the ad (cha m. y. et al. (2017)). parkinson’s disease (pd) is another neurodegenerative disorder that affects more than 10 million people worldwide (statistics, n.d.). pd involves the degradation of the dopaminergic neurons of the substantia nigra pars compacta (snc) (elkouzi et al., 2019). this degradation of dopaminergic neurons cuts off the connection between the snc and the striatum, effectively reducing dopamine source. this results in the distinct tremors, rigidity, bradykinesia and postural instability that is noticeable in pd patients (elkouzi et al., 2019). the challenge with pd is the heterogeneity of the disease due to common genetic variants (greenland et al., 2019). this results in difficulty in finding one treatment that works for all pd patients, so to effectively treat pd a method to establish individualized treatments is necessary (elkouzi et al., 2019). while it’s possible to take esc and specialize them to dopaminergic neurons to replace lost dopaminergic neurons, it’s difficult to reach the desired level of specification that is required for an adept pd treatment (elkouzi et al., 2019). ipscs were used to establish a method to treat pd subtypes that arose from the common genetic variants. because ipscs can be generated from the patient, individualization of the treatment is possible. the blood of pd patients has been collected for research into the disease for a long period of time, resulting in a large data bank of different types of pd haplotypes (deleidi et al., 2011). this large data bank can be used to create ipsc lines specific to variants of pd. figure 4: the amphetamine and apomorphine levels were recorded between before transplantation of the ipscs and after the said translation at weeks 4, 8, 12, 16. it is clear that both amphetamine and apomorphine decrease after transplantation. image from deleidi et al., 2011. 18brain matters・volume v issue ii 19 the effect of these amyloid plaques can be removed by regenerating cholinergic neurons at the hippocampus, helping restore lost neurons and allowing the individual to retain their memory and learning skills. furthermore, the effect of amyloid plaques can also be mitigated by proteinipscs turned glial cells. glial cells, like oligodendrocytes, play a major role in regenerating axons in the cns. parkinson’s disease, another common neurodegenerative disease, is heterogenous and so no one treatment exists to help all those who are suffering from it. to develop a method for individualized and personalized treatment, ipscs were used to create custom dopaminergic neural grafts. these grafts could then be transplanted into the striatum where they rebuild the connection between the striatum and snc that many pd patients lack. this experiment yields high success rates in animals, and so it moves onto clinical trials. many researchers have been using ipscs to both regenerate neurons as well as other cells that slow down the degeneration of neurons. references 1.alzheimer’s disease questions and answers. (n.d.). texas department of state health services. retrieved april 18, 2021, from https://dshs.texas.gov/alzheimers/qanda.shtm neurodegeneration and neuro-regeneration-alzheimer's disease and stem cell therapy. international journal of molecular sciences, 20(17), 4272. https://doi.org/10.3390/ijms20174272 2. cha, m. y., kwon, y. w., ahn, h. s., jeong, h., lee, y. y., moon, m., baik, s. h., kim, d. k., song, h., yi, e. c., hwang, d., kim, h. s., & mook-jung, i. (2017). protein-induced pluripotent stem cells ameliorate cognitive dysfunction and reduce aβ deposition in a mouse model of alzheimer's disease. stem cells translational medicine, 6(1), 293–305. https://doi.org/10.5966/sctm.2016008 3. deleidi, m., hargus, g., hallett, p., osborn, t., & isacson, o. (2011). development of histocompatible primate-induced pluripotent stem cells for neural transplantation. stem cells (dayton, ohio), 29(7), 1052–1063. https://doi.org/10.1002/stem.662 4. elkouzi, a., vedam-mai, v., eisinger, r. s., & okun, m. s. (2019). emerging therapies in parkinson disease repurposed drugs and new approaches. nature reviews. neurology, 15(4), 204–223. https://doi.org/10.1038/s41582-019-0155-7 5. fujiwara, n., shimizu, j., takai, k., arimitsu, n., saito, a., kono, t., umehara, t., ueda, y., wakisaka, s., suzuki, t., & suzuki, n. (2013). restoration of spatial memory dysfunction of human app transgenic mice by transplantation of neuronal precursors derived from human ips cells. neuroscience letters, 557, 129–134. https://doi.org/10.1016/j.neulet.2013.10.043 6. greenland, j. c., williams‐gray, c. h., & barker, r. a. (2019). the clinical heterogeneity of parkinson’s disease and its therapeutic implications. european journal of neuroscience, 49(3), 328–338. https://doi.org/10.1111/ejn.14094 7. hersenbank. (2008). nederlands: gezonde hersenen (onder) versus hersenen van een donor met de ziekte van alzheimer. opvallend is de “verschrompeling” die is opgetreden bij de ziekte van alzheimer, waardoor de hersenen in omvang zijn afgenomen. own work. https://commons.wikimedia.org/wiki/file:ad_versus_co.jpg 8. huebner, e. a., & strittmatter, s. m. (2009). axon regeneration in the peripheral and central nervous systems. results and problems in cell differentiation, 48, 339–351. https://doi.org/10.1007/400_2009_19 9. nagappan, p. g., chen, h., & wang, d. y. (2020). neuroregeneration and plasticity: a review of the physiological mechanisms for achieving functional recovery postinjury. military medical research, 7(1), 30. https://doi.org/10.1186/s40779-020-00259-3 10. simola, n., morelli, m., & carta, a. r. (2007). the 6hydroxydopamine model of parkinson’s disease. neurotoxicity research, 11(3), 151–167. https://doi.org/10.1007/bf03033565 11. shin, j., park, s., lee, h., & kim, y. (2021). thioflavinpositive tau aggregates complicating quantification of amyloid plaques in the brain of 5xfad transgenic mouse model. scientific reports, 11(1), 1617. https://doi.org/10.1038/s41598-021-81304-6 12. statistics. (n.d.). parkinson’s foundation. retrieved april 18, 2021, from https://www.parkinson.org/understandingparkinsons/statistics 13. the challenge of neurodegenerative diseases. (n.d.). retrieved april 18, 2021, from https://neurodiscovery.harvard.edu/challenge 14. tucker, r. p., & chiquet-ehrismann, r. (2015). tenascinc: its functions as an integrin ligand. 15. the international journal of biochemistry & cell biology, 65, 165–168. https://doi.org/10.1016/j.biocel.2015.06.003 16. types of glia. (2016, november 22). https://qbi.uq.edu.au/brain-basics/brain/brain physiology/types-glia 17. vasic, v., barth, k., & schmidt, m. h. h. (2019). neurodegeneration and neuro-regeneration—alzheimer’s disease and stem cell therapy. international journal of molecular sciences, 20(17), 4272. https://doi.org/10.3390/ijms20174272 https://dshs.texas.gov/alzheimers/qanda.shtm https://doi.org/10.5966/sctm.2016-0081 https://doi.org/10.1016/j.neulet.2013.10.043 https://doi.org/10.1111/ejn.14094 https://doi.org/10.1186/s40779-020-00259-3 https://doi.org/10.1007/bf03033565 https://doi.org/10.1038/s41598-021-81304-6 https://www.parkinson.org/understanding-parkinsons/statistics https://neurodiscovery.harvard.edu/challenge https://doi.org/10.1016/j.biocel.2015.06.003 https://qbi.uq.edu.au/brain-basics/brain/brainhttps://doi.org/10.3390/ijms20174272 nicole chlibovytsch is a rising senior at uiuc majoring in psychology with a clinical concentration and minoring in molecular and cellular biology. nicole is involved in research on campus at sarah ward’s morality and motivation lab and has served as a peer mentor for the las honors program. nicole joined brain matters as a writer because she loves learning about and investigating the correlations between human neural activity and observable behaviors. for her it is fascinating to be able to trace human actions and choices back to the neuroscientific causes that take place within our brains. consumer neuroscience: the use of neuroscience techniques to create better advertising consumer neuroscience is a growing field that incorporates neuroscience-based research methods to meet the specific needs of different companies. while some companies utilize psychological and neuroscientific information to create an effective product, others choose to use such in formation in order to create persuasive advertisements. the three most common techniques used are eye tracking, eeg analysis, and fmri imaging. each technique exists as a valuable tool to gather specific information that helps build an accurate representation of what goes on in a potential consumer’s mind. while these techniques are useful in improving the effectiveness of an advertisement, they are limited by their ethical concerns, thus leaving many wondering how far is too far when using science to make sales. analysis of the techniques, their effectiveness, and what exactly they can do is important in determining where the boundaries of consumer neuroscience should lie. one of the easiest ways for neuroscientists to study consumers is through the use of eye tracking techniques. eye-trackers will monitor both the participant’s eye movements and pupil size throughout the time that they are engaged with the marketing material (harris et al., 247). eye-tracking monitors will record both a person’s saccades (quick jumps in visual fixation) and smooth pursuit (slower, more continual visual fixations along one object). tracking eye movement is useful in determining which parts of the advertisement the prospective consumers will be most attentive to and researchers can use this information to determine where the most interesting parts of the advertisement are. this is shown by image 1, in which the circle demonstrates where consumers were fixated within the webpage, and the lines show their saccades between fixations (gidlöf et al., 337). further information can be gathered by examining the ways in which a person’s pupils dilate while they are engaged with the material. if a participant is looking at something intriguing or startling, their autonomic nervous systems will automatically cause their pupils to dilate in an effort to take in more of the scene. dilation can also be caused when a participant is engaged in something that they perceive as challenging or puzzling. on the other hand, participants’ eyes will constrict upon seeing something displeasing or after having figured out something difficult (harris et al., 247). as a result of how easily eye tracking can be used across several types of advertisements (including but not limited to billboards, tv commercials, in-store promotional displays, and website ads), it has become an increasingly popular tool. another way for marketers to gauge how their advertisement will be perceived by the target audience is to perform an electroencephalography (eeg) analysis (harris et al., 2018). put simply, eegs use electrodes to measure the electrical currents in different areas of the brain. scientists can analyze the recorded electrical activity and use information about the relative location and timing of the currents to accurately estimate a person’s emotional and cognitive responses to what they just viewed. for example, if a marketer wants to convey feelings of personal relevance between the and the consufigure 1. list of major companies using neuromarketing and their reasons for doing so. (flores et al. 2014) fig 2. the use of eye-tracking and retrospective interviews to study teenagers’ exposure to online advertising (gidlöf et al. 2012) 5 mer, they may look for activity in broddman’s area 10, as this is the region that commonly shows activity when a subject engages with personal content. another important aspect to keep in mind when creating effective advertising is that the consumers should be actively engaged and attentive to the content they are viewing. for this reason, it’s also important for the eeg recordings to show activity in broddman’s areas 10/11, as activity here will demonstrate cognitive engagement. furthermore, left hemispheric activity in the prefrontal cortex is thought to be associated with positive reactions that result in behavior that is approach-focused, as opposed to withdrawal-focused behavior (ohme et al., 2010). eeg recordings are able to reveal how miniscule changes to advertisements can change the way in which the consumers’ brains will respond to the information. a famous commercial for sony bravia flat screen tvs involves an enormous amount of bouncy balls traveling down the streets of a small city; the commercial briefly shows a frog jumping out of a gutter while all of the balls are falling around it (shown in figure 3). while this moment was unplanned for and was not even very memorable, it made a big difference in the efficacy of the commercial conducted an eeg study which showed that the version of the commercial with the frog gave rise to more positive emotions (shown by more left hemispheric dominance) than the version without the frog (figure 3). this goes to show how eegs are used to determine how even the smallest of fragments from an advertisement may make a big impact (ohme et al., 2010). in contrast to the simplicity and convenience of eye tracking and eeg methods, fmri analyses go deeper into the brain to explore the meaning of patterns of blood flow. for example, stillman et al. conducted studies to test whether or not black and white images provoked the same levels of future-focused activities as those in color. (stillman et al., 2020). the results of both psychological and fmri testing suggest that a difference between the two does exist. when visualizing events 5 years into the future, the fmri scans of participants will show activity in the same regions which activate when looking a black and white images. in contrast, imagining events for the near future activates the same regions associated with colored images (stillman et al., 2020). these findings could prove useful to researchers who want to create an advertisement for products meant for the near future versus one that will be valuable to the consumer later in life (such as warranties or investments). another example of fmri being used for market research was shown in a study by plassman et al., participants were given two bottles of the same wine, but one was marked with a high price tag and one with a low price tag (428). despite these bottles of wine being exactly the same, the one with a higher tag was preferred by most participants. researchers analyzed participants’ brain scans during the experiment and discovered that putting a higher price tag literally makes the brain perceive the wine as tasting better, thus showing how neuroimaging can be used to measure the implicit processes that a consumer’s mind engages in. although many marketers may be interested in new techniques to create the most appealing products or advertisements, others have ethical concerns about using neuroscience to make a profit. questions must be asked about where to draw the line between harmless advertising techniques and intrusive techniques designed to scientifically convince the brain into purchasing a product it truly does not want nor need. in her book ethical dimensions of commercial and diy neurotechnologies, kimberely clark brings up the point that some demographics (typically adolescents) are disproportionately susceptible to the tactics of marketers. fmri research has shown that the brains of adolescents are increasingly vulnerable to activating their reward pathways, while being less susceptible to activity in inhibition pathways (clark, 42). this could have negative implications when marketers use aggressively accurate neuroscience tactics to persuade young consumers into buying potentially dangerous products, such as alcohol or trendy e-cigarettes. fmri imaging also shows that by pairing an already valued stimuli, for example the musical intro to a participant’s favorite tv show, with a novel product, the participant may transfer their positive feelings about the original stimulus to the new product. this is called the halo effect, a largely unconscious process, and can be used to persuade consumers into liking the product solely because of its connection to something they already enjoy, thus leading to worries that consumers may be manipulated into wanting to spend money on a product they’d otherwise find invaluable (clark, 2020). some critics also call into question the morality of using neuromarketing techniques for a profit. according to flores et al., neuromarketing is perceived by 68.7% of people as favorable when it is used by a for-profit business, but when used by a non-profit organization 84.2% of people think it’s favorable. this may be because non-profit organizations are typically viewed as more trustworthy and aim to help the public rather than use them to gain wealth (flores et al., 2014). all in all, consumer neuroscience is a broad and growing field that incorporates different research techniques in order to successfully market a product. different types of neurological/physiological studies can be done fig 3. version of the commercial with the frog gave rise to more positive emotions (shown by more left hemispheric dominance) than the version without the frog (ohme et al. 2010). 6 to draw conclusions about how well an advertisement will be perceived by its target audience. while there are accuracy benefits involved with consumer neuroscience, there are also possible ethical drawbacks in employing this type of research. in order to avoid crossing such ethical boundaries, careful consideration needs to be used when determining whether or not it is appropriate to use neuroscience in advertising. references clark, kimberly rose.(2020) “a field with a view: ethical considerations for the fields of consumer neuroscience and neuromarketing.” ethical dimensions of commercial and diy neurotechnologies 3. flores, jason, (2014). arne baruca, and robert saldivar. “is neuromarketing ethical? consumers say yes. consumers say no.” gidlöf, kerstin,11.3 (2012), nils holmberg, and helena sandberg. “the use of eye-tracking and retrospective interviews to study teenagers’ exposure to online advertising.” visual communication: 329-345. harris, joanne m., joseph ciorciari, and john gountas. 17.3 (2018), “consumer neuroscience for marketing researchers.” journal of consumer behaviour: 240-247. ohme, rafal, michal matukin, and tomasz szczurko. (2010) “neurophysiology uncovers secrets of tv commercials.” der markt 49.3-4: 133-142. plassmann, hilke, et al.(2015), “consumer neuroscience: applications, challenges, and possible solutions.” journal of marketing research 52.4: 428-429. sony. 11 february 2010,“sony bravia bouncy balls full hd 1080p” youtube, uploaded by 32cn32, https://youtu.be/0_bx8bncoiu. stillman, paul, et al.(2020), “examining consumers’ sensory experiences with color: a consumer neuroscience approach.” psychology & marketing. venkatraman, vinod, et al. 22.1 (2012), “new scanner data for brand marketers: how neuroscience can help better understand differences in brand preferences.” journal of consumer psychology: 143-153. a 7 symptoms and possible causes cures for parkinsons disease symptoms and possible causes cures for parkinsons disease michael mchenry parkinson’s disease is the world’s second most common neurodegenerative disorder, afflicting nearly 10 million people worldwide.1 while it is a fairly common disease, its exact causes are unknown and there is no known cure. since the early 1800s, parkinson’s disease has befuddled scientists. but now, cutting edge research has led scientists to believe that the solution to the parkinson’s puzzle may lie within our intestines. before delving into its interesting connection to the gut, one must first understand the basic symptoms of parkinson’s disease (pd). usually, parkinson’s disease most often affects individuals over the age of 60, but in some cases, symptoms can be seen in patients before they turn 50.1 the main symptoms associated with parkinson’s disease are uncontrollable shaking, slowed movements, impaired coordination, and body stiffness. these symptoms make life for those with the disease difficult, especially as they get older. the primary cause of those symptoms is the depletion of the brain’s dopaminergic neurons.1 dopaminergic neurons are responsible for releasing dopamine, a neurotransmitter that functions to facilitate communication between the substantia nigra and the basal ganglia. this interaction helps a human fine-tune his/her movement by helping the brain determine the energy cost of a particular movement.8 without dopamine-producing neurons, this interaction becomes impossible and results in the previously listed symptoms of the disease. currently, the most common treatments for parkinson’s are drugs that raise dopamine levels within the patient’s brain. the most common of those drugs is levodopa, a precursor molecule to dopamine. levodopa is converted by the cns into dopamine, thereby making up for the lack of dopamine produced by dopaminergic neurons. other therapies include drugs that mimic dopamine’s effects, drugs that slow the enzymatic breakdown of dopamine, and deep brain stimulation. while they are somewhat effective, today’s parkinson’s treatments are only able to lessen the symptoms of the disease, as they cannot attack the root causes of the disease. however, new studies have shed light on parkinson’s disease pathology. those studies indicate that parkinson’s pathology may begin in the enteric nervous system. the enteric nervous system (ens) is the largest part of the autonomic nervous system. it is made up of hundreds of millions of neurons and is responsible for regulating the function of the gastrointestinal system. because of its immense sophistication, the ens can regulate the complex gastrointestinal system on its own, independent from the central nervous system (cns). however, the ens and cns are linked by many afferent and efferent nerves that enable communication and the exchange of information between them. however, those same connections can also provide a pathway along which neurodegenerative diseases can spread. scientists have postulated that parkinson’s pathology may begin in the ens before spreading to the cns and causing the disease’s symptoms. the ens contains a unique type of neuron known as an enteric glial cell or egc. egcs can be found in the walls of the intestines and are crucial for the homeostatic regulation of many gi functions, including the regulation of the intestine’s neuroinflammatory response.2 under normal conditions, egcs in the mucosa myenteric plexus are not activated. however, if the intestinal wall of an individual is compromised in some way, it may become permeable to the bacteria that inhabit the lumen of the small intestine.7 if able to pass through the intestinal wall, those bacteria will cause the egcs of the small intestine to respond with a neuroinflammatory response. sustained activation of egcs results in an increase of the production of a misfolded protein known as α-synuclein. α-synuclein is a mysterious protein, as its true physiological function is not well known. however, it does play a crucial role in causing the dopaminergic cell death seen in pd patients. α-synuclein has been shown to build up in the dopa minergic neurons of parkinson’s patients, resulting in the death of those neurons.4 α-synuclein also can be seen forming protein deposits within neurons known as lewy bodies. in parkinson’s patients, lewy bodies are often found in neural tissue and have high concentrations of α-synuclein within them. the link between the production of α-synuclein within the enteric glial cells of the ens and the presence of α-synuclein within the brain suggests that α-synuclein may vol. 3 8 somehow migrate from the ens to the cns. the exact method by which this process could occur was unknown for a long time. however, a study by ahn et al. entitled “initiation of parkinson’s disease from gut to brain by δ-secretase” shows how it could occur in humans. researchers in this study looked to determine how α-synuclein could move from the ens to the cns, which would demonstrate how the gut could affect parkinson’s disease pathology. they utilized the pesticide rotenone to elicit parkinson’s-like symptoms in animal models. rotenone is known to cause symptoms like gut dysmotility and the aggregation of α-synuclein within the brains of animals. also, rotenone taken orally does not enter the circulatory system; instead, it solely acts on the ens when it crosses the membrane of the intestines.4 these factors make rotenone-treated mice good study subjects for parkinson’s. the first thing the researchers looked at was α-synuclein’s interactions with a protein known as tau. they found that α-synuclein and tau strongly bind to one another when they were cleaved by the protease asparagine endopeptidase (aep). aep cleaves the α-synuclein protein at n103 and the tau protein at n368. interestingly, overexpression of the α-syn n103 fragment in the brain has been shown to cause lewy body formation and motor dysfunctions.4 they also found that the complex created by the binding of tau n368 and α-synuclein n103 is highly cell permeable. being able to easily cross cell membranes makes it possible for the α-synuclein n103/tau n368 complex to potentially leave the digestive system to enter other organs, such as the brain. that possibility was proven by a later experiment where ahn et al. gave mice rotenone orally. after three months, immunofluorescence staining indicated that the α-syn n103/tau n368 complex was present in the vagus nerves of the mice treated with rotenone. this indicated that the complex moved from the ens through the vagus nerve to the brainstem. the vagus nerve was identified as the main passageway by which the lewy-body creating proteins traveled from the ens to the substantia nigra (sn) to cause the symptoms related to parkinson’s disease. however, once at the cns, scientists wanted to see if the α-syn n103/tau n368 could cause the endogenous production of α-syn n103 in the sn. to answer this question, ahn et al. injected mice the colons of mice with the α-syn n103/tau n368 complex. they found that once the complex got to the brain, it caused a local increase in the activation of aep. increased ahn et al. noted that the mice showed “substantially impaired” cognitive function when compared to the control mice, demonstrating that they were experiencing dopaminergic cell death. the findings of ahn et al. demonstrate how the proteins responsible for lewy body formation travel from the gut to the brain and cause dopaminergic cell death. the gut’s effect on parkinson’s pathology can now be explained. first, leaky gut dysbiosis causes bacteria in the intestinal lumen to move through the intestinal wall. those bacteria then cause a neuroinflammatory response from the intestine’s enteric glial cells. next, the egcs start to produce abnormal amounts α-synuclein, which builds up in the ens. then, the protease aep starts to cleave α-synuclein at n103 and tau at n368. those two fragments form a complex that can easily pass through cell membranes. complexes then exit the ens and travel to the brain via the vagus nerve. once in the brain, they cause endogenous production of α-syn n103 by activating locally activating aep. finally, α-synuclein builds up in the dopaminergic cells of the individual, causing lewy body formation and cell death. once in motion, this process would be difficult to stop due to the prion-like nature of the α-syn n103/tau n368 complex. however, it could be possible to create treatments targeted at preventing leaky gut itself. it has been postulated that parkinson’s pathogenesis could be prevented by using drugs to alter the gut microbiota to prevent leaky gut and maintain the solidity of the intestinal wall.2 by using eubacteria and antibiotics, doctors could theoretically control intestinal bacteria populations to prevent them from getting through the intestinal wall and inflaming the enteric glial cells. another possible treatment would involve the use of fecal microbiota transplant (fmt). fmt involves the transplantation of fecal matter from healthy individuals into individuals with abnormal gut bacteria compositions. 9 this method is aimed at helping to reestablish a stable gut microbiota and therefore prevent conditions like leaky gut. studies have shown that fmt has been effective in treating ulcerative colitis by helping to promote mucosal healing.9 given leaky gut dysbiosis’ role in parkinson’s progression, fmt could be a novel way to treat the disease. for years, parkinson’s disease has been clouded in mystery; its causes and pathology were a secret. however, new scientific discoveries have helped improve our understanding of the disease drastically. while we may not have all the information required to cure vol. 3 9 parkinson’s, these new discoveries have brought us closer to finding treatments that target the disease at its source rather than mitigate its symptoms. the future of parkinson’s treatment is a little brighter, which is great news for the 10 million people who suffer from it. vol. 3 10 6 brain development of schizophrenic patients bailey s. zinger in the distant past, the symptoms and characteristics of schizophrenia were considered the behavior of other worldly spirits or beasts dwelling within a host’s mind (“history cooperative”). although this idea is captivating, the symptoms of schizophrenia can be explained through scientific investigation. in 1910, swiss psychiatrist paul eugen bleuler coined the term “schizophrenia”, derived from the greek words “schizo”, meaning split, and “phren”, meaning mind (national institute of mental health, 2016). consequently, many people mistake schizophrenia for a form of dissociative identity disorder. a person who suffers from schizophrenia, however, does not change from one personality to another unrecognizable personality (national institute of mental health, 2016). schizophrenia is not a split personality disorder, nor is it the work of unseen spirits. although the disorder is enigmatic, studies have been conducted to elucidate some of its symptoms and characteristics. schizophrenia is a chronic and severe mental disorder that affects how an individual feels, thinks, behaves, and perceives reality (a brief history of schizophrenia, 2012). delusions and hallucinations are among the most common positive symptoms of the disorder, often resulting in experiences of derealization or depersonalization (cannon, t.d., 2015). derealization is a phenomenon in which the external world becomes seemingly unreal, for instance, a person experiencing derealization may describe it as a dream-like state in which sights and sounds are fuzzy and muted. depersonalization, one of the most common symptoms associated with schizophrenia, is a state in which one’s thoughts and feelings do not seem like his or her own (cannon, t.d., 2015). the onset of schizophrenia is typically progressive and presents itself between the ages of 12 and 35 (cannon, t.d., 2015). a young individual demonstrating stark changes in thought or perception that manifest into delusions is considered a prodromal or high-risk clinical case. schizophrenia is a disconnection between functional neural networks in the brain; since different psychotic symptoms of schizophrenia may involve different interactions amongst networks, high-risk clinical cases are of extraordinary importance to scientists as they can be marked and traced through the progression of the disorder (cannon, t.d., 2015). the complexity of schizophrenia is what makes the disorder so difficult to diagnose. the root causes of schizophrenia vary widely and may include genetic variants, social stress, and neurological complications during childbirth or early development (cannon, t.d.). due to the complex nature of the disorder, two leading theories of schizophrenia onset have been considered, but there is not yet one sure method to diagnose and treat individuals with the disorder. the two theories discussed in this article include the neurodevelopmental model and the excitation-inhibition imbalance model. brain disconnectivity due to *axonal pathology, such as disrupted myelination, and deficits in dendritic spines is thought to be the neurodevelopmental feature of schizophrenia (cannon, t.d., 2015). one condition includes disrupted myelin, the sheath of protective plasma membrane extensions along axons of the nervous system (snaidero, 2014). disrupted myelin prevents high specificity of nerve impulses along axons, indicating the possibility of miscommunication amongst cells in regards to perception and memory. this condition is likely to have been expressed at birth in schizophrenic patients, but in some cases, this disruption may progress above a threshold of exposed psychotic symptoms despite normal neurological developments (cannon, t.d., 2015). in other words, the neurological symptoms of schizophrenia are always present but are expressed later in life. the notion of postponed symptom expression means that the disorder may be progressive and a method of mapping the brain over time is pertinent to discovering the patterns of the disorder. thus, neuroimaging of highrisk clinical cases that did convert to the full psychosis of schizophrenia showed significantly greater thinning of the gray matter in the prefrontal cortex of the brain in comparison to healthy controls and those that did not convert (cannon, t.d., 2015). these tests included subjects that had not previously been exposed to antipsychotic medications, ensuring that the *axonal pathology refers to the laboratory tests conducted on samples of neural tissue including axons, the part of the nerve cell along which impulses are conducted. samples are tested for various conditions such as disrupted myelination. the myelin sheath is an insulating cover over the axons in the brain that increase the speed of nerve impulses. medications themselves were not stimulating the acceleration of gray matter loss (cannon, t.d., 2015). networks that involve the medial prefrontal cortex play critical roles in memory formation and retrieval. these networks also indicate whether a person experienced their own memory or imagined the experience of another person (cannon, t.d., 2015). this memory discrepancy can now be much better identified through the tracking of the thinning of gray matter in this region. “reality monitoring” is defined as the ability to assess the characteristics of memory representations. the characteristics of the memory representations may reflect the neurological processing activity that occurs when a memory becomes encoded. this includes the marking of perceptual or actual details about an event and/or the associated thoughts and feelings at the time (brandt, 2013). prefrontal cortex regions are primarily involved in memory recollection. to verify this, a study was performed focusing on the inhibition of memory retrieval. in this study, subjects suppressed retrieval of some items from a study list, showing that the ability to retrieve those items was impaired and the medial prefrontal cortex was active during retrieval suppression (peters, 1970). therefore, reality monitoring of action memories is predicted to provoke activity in medial prefrontal cortex regions (brandt, 2013) in specific structural variations, which correlate with differences in performance on reality monitoring tasks (cannon, t.d., 2015). schizophrenic patients are more likely to rely on familiarity-based mental processes, meaning activities and memories that are repetitive and easy to replicate due to prolonged exposure come more easily to them. this is due to the deficit in absolute or relational neural encoding, which reduces the ability to reference memories in context (cannon, t.d., 2015). considering this, disturbances in source monitoring during learning and memory encoding may cause disrupted belief evaluation (cannon, t.d., 2015), the sensation of having difficulty discerning a belief from a fact or actual circumstance. gray matter loss leading to disrupted belief in schizophrenia patients may explain why those with the disease become confused about what is real versus imaginary, and that the familiar begins to feel strange in the effect of derealization 7 or depersonalization. another theory of schizophrenia onset is the excitation-inhibition imbalance model. the basis of this model is derived from the neurological developments of drug abusers, particularly in phencyclidine and ketamine abusers. these drug abusers experience similar symptoms to schizophrenia sufferers; the abusers’ brains can be mapped and the findings applied to brains with schizophrenia. the effects of the drugs are driven by excitation of n-methyld-aspartate (nmda) receptors in the brain, and these receptors in turn are activated by the excited state of the amino acid transmitter glutamate (cannon, t.d., 2015). cells associated with glutamine, glutamatergic pyramidal cells, converge, or synapse, onto some neurons that express the inhibitory gamma-aminobutyric acid (gaba) transmitter. these cells in turn project back to the pyramidal cells, completing a set of regional neurological circuits (cannon, t.d., 2015). pyramidal cells function by transforming synaptic inputs into a patterned output of action potentials. they are special due to their abundance in the brain and that they are able to send their axons long distances throughout the brain (bekkers, n.d.). since some pyramidal cells ultimately activate nmda receptors, nmda receptor hypofunction may result in an imbalance of excitation and inhibition that could contribute to some symptoms of schizophrenia (cannon, t.d., 2015). for example, as nmda receptor function continues to weaken, the previously learned memory interpretations show a directly correlating positive linear relationship. this process creates an altered environment for the development of new explanations of experience and phenomena (cannon, t.d., 2015), such that an alien is controlling the patient’s thoughts or beliefs. another interesting aspect of the excitation-inhibition imbalance theory is that mismatch negativity (mmn) potential is dependent on nmda receptors. mmn is an electrophysiological potential generated when a stimulus occurs out of a series of standard stimuli that is different from the rest (a black dot amongst a series of white dots, for example) (national institute of mental health, 2016). since mmn is dependent on nmda receptors, reduced mmn in all stages of schizophrenia is consistent with the inhibition of nmdamediated synaptic activity, and in turn these deficits in nmda activity may drive the accelerated gray matter loss thought to be associated with schizophrenic cases (cannon, t.d., 2015). in all, the two theories discussed in this article describe some of the leading scientific evidence and speculation in the development of schizophrenia. however, many questions are still unanswered due to the complex nature of the disorder. what causes the process of gray matter deterioration? how does the inhibitionexcitation imbalance come to be? scientists and researchers are working toward answering these questions so that schizophrenics will receive more effective medical treatment. references a brief history of schizophrenia. (2012, september 08). retrieved january 04, 2019, from https://www.psychologytoday.com/us/ blog/hide-andseek/201209/brief-historyschizophrenia bekkers, j. m. (n.d.). pyramidal neurons. retrieved february 15, 2019, from https:// www.cell.com/current-biology/pdf/s09609822(11)01198-5.pdf brandt, v. c., bergstrom, z. m., buda, m., henson, r. n., & simons, j. s. (2013, august 6). did i turn off the gas? reality monitoring of everyday actions. retrieved january 6, 2019, from https://www.ncbi.nlm.nih.gov/ pmc/articles/pmc3969513/ cannon, t. d. (2015, october 19). how schizophrenia develops: cognitive and brain mechanisms underlying onset of psychosis. retrieved january 5, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/ pmc4673025/ history cooperative. (2016, september 19). divine madness – a history of schizophrenia. retrieved january 4, 2019, from https://historycooperative.org/divinemadness-a-history-of-schizophrenia/ national institute of mental health (2016). schizophrenia. retrieved january 4, 2019, from https://www.nimh.nih.gov/health/ topics/schizophrenia/index.shtml peters, g. j., david, c. n., & marcus, m. d. (1970, january 01). gregory j. peters. retrieved from http://learnmem.cshlp.org/ content/20/4/201.full.html snaidero, n., & simons, m. (2014, july 15). myelination at a glance. retrieved from http://jcs.biologists.org/content/127/14/2999 copy of volume 7 publication 8 neural pathways of anxiety luke lalonde what is anxiety? anxiety is a generalized term that can be used to describe feelings of worry or uneasiness that almost all people deal with intermittently in their lives. anxiety is a stress response to a potentially dangerous stimulus that causes an accelerated heartbeat and quickened breathing. while being stressed is uncomfortable, it’s not necessarily unhealthy if it does not disrupt daily life. an issue arises in those who face prolonged or recurring stress. this type of chronic stress has often been shown to predispose individuals to anxiety disorders (sanders, 2016), including various panic disorders, phobias, and social anxiety. another type of anxiety disorder, generalized anxiety disorder (gad), is characterized by constant and excessive uneasiness about routine life circumstances. gad often leads to symptoms such as difficulty sleeping or unsatisfying sleep, which can then lead to issues like irritability, muscle tension, general fatigue, and trouble concentrating (the national institute of mental health, 2018). there is no single cause for gad, but there are many associated risk factors including hormone imbalance, early-life trauma, exposure to repetitive, stressful stimuli, and a relatively slight genetic influence. key brain areas anatomically, gad involves abnormalities in the functioning of the limbic system, which is a phylogenetically ancient region of the brain that functions as a control center for emotions, mood, and drives (martin, 2009). more specifically, the hippocampus and the amygdala are the two primary structures in the limbic system that play a role in gad. the amygdala is an almond-shaped structure that transfers nerve impulses into hormonal signals, triggering emotional responses. it plays an important role in alerting the brain about potential threats. this is noteworthy because anxiety disorders, gad in particular, are a result of prolonged overactivity of the amygdala, which causes the brain to be in a constant state of fear or anxiety (patriquin, 2017). obviously, a constant state of fear would make it difficult to relax for those facing gad, ultimately resulting in the aforementioned symptoms of anxiety disorders such as fatigue and loss of sleep that eventually contribute to a multitude of additional symptoms. the other key brain region involved in gad, the hippocampus, is responsible for encoding threatening events into memory and relaying information to the amygdala during the process of retrieval for a rapid response to threatening stimuli (“the effects of stress & anxiety on the brain”, 2018). phylogeny it is important to note the phylogeny of the structures associated with gad. phylogeny refers to the evolutionary development of a particular feature of an organism. as mentioned before, the limbic cortex is ancient. this means that the limbic system was preserved through evolutionary history, and because of this, it is relatively autonomous, involving little voluntary action. anxiety disorders target the structures of the limbic system rather than higher cognitive centers of the frontal lobe such as the prefrontal cortex (responsible for decision making) or the orbitofrontal cortex (controls impulses). this means that anxiety disorders are not based on irrational thoughts but on threat assessment and an uncontrollable natural response to what part of the brain perceives to be a real threat, despite higher-order brain areas providing input that there is, in fact, no immediate danger (martin, 2009). this helps to explain the difficulty involved in controlling nervous feelings that come with anxiety disorders, as the problem is not solved by simply being cognizant of the fact that there is no real threat. instead, victims should take actions that will directly affect the sources of the problem, such as using medication to address neurochemical and hormonal imbalances. neurotransmitters and endocrine system anti-anxiety medication is useful in many cases as a way to counter the neurochemical imbalances associated with gad. there are a few ways in which neurotransmitter release can result in the overactivity of the limbic system. the first way is through decreased inhibitory signaling by the major mammalian inhibitory neurotransmitter, gamma-aminobutyric acid, also known as gaba. this would result in a greater amount of uninhibited nerve firings in the limbic cortex which would consequently lead to overactivity (martin, 2009). the second possibility is an excess of the excitatory neurotransmitter glutamate, which would result similarly with a greater amount of nerve firings and therefore overactivity of the amygdala. it is also possible that some combination of these two could be at play in contributing to overactivity. other chemical messengers that play a role in anxiety disorders are cortisol and norepinephrine, in this case acting as hormones. these two hormones are normally released in response to a threat for a limited period of time. they contribute to the accelerated heartbeat and quickened breathing that normally allow for faster movement and better perception when facing danger. (“the effects of stress & anxiety on the brain”, 2018). however, the brains of those with gad constantly perceive threatening stimuli, causing the extended production of these hormones that are only intended for short periods of time. there are trade-offs for the increased awareness these hormones provide over time. high cortisol levels contribute to weight gain, muscle weakness, and suppressed immunity as the body focuses on escaping momentary danger. (the national institute of mental health, 2018). another symptom of excess levels of both cortisol and norepinephrine is difficulty sleeping, which only exacerbates the stress response to real threats, perpetuating the release of these hormones. physical effects and ramifications the short-term effects caused by gad are apparent, as hormone imbalances and overactivity of nerves in the limbic system lead to sleep difficulties, lack of focus, weight-gain, and other symptoms (patriquin, 2017). however, these are merely side effects of what can be destructive functional abnormalities in and of themselves. it seems as though the constant activity of the limbic system could have some effect on the utility of the nerves themselves. in short, there are more direct and lasting effects caused by gad on the brain itself that should be 9 noted in order to view the full scope of damage caused by the disorder. one such effect is on the amygdala. as discussed, gad is linked to overactivity in the nerves of the limbic system, in particular those of the amygdala, as it is the system primarily responsible for perceiving potential danger. it has been found that the normally almond-shaped amygdala gets larger in pediatric patients with gad. this is likely to correspond with hypertrophy seen in the amygdala of lab animals, which correlates with expectation considering the abnormal activity of the amygdala in patients with gad (martin, 2009). different, yet also alarming, results have been observed in the form of hippocampal damage caused by limbic hyperactivity. while research is still in progress on the effects of gad on neurodegeneration within the limbic system, new research is showing that prolonged stress and anxiety can potentially cause structural degeneration of hippocampal nerves (“the effects of stress & anxiety on the brain”, 2018). this is especially concerning because the volume of the hippocampus and growth of new cells is directly related to stress resiliency in anxiety and mood disorders, suggesting that if there is structural damage to the hippocampus caused by gad, it is making the brain gradually less resilient to the stress as it persists (martin, 2009). another recent observation from fmri scans of gad patients is the ratio of grey to white matter in the brain. grey matter is the tissue of the central nervous system that contains the cell bodies, dendrites, and axon terminals of neurons, while white matter is made up of the connecting neuron axons (sanders, 2016). grey matter is found mostly in regions of the brain responsible for sensory perception, memory, and emotion, which is why it is possibly related to the hyperactivity of the amygdala, where an abnormally high ratio of grey to white matter has been found in studies of patients with gad. conversely, possibly related to neurodegeneration associated with gad, a greater ratio of white matter to grey matter has been found in hippocampal regions of patients with the disorder (hilbert, 2015). relevance as time goes on and the human brain becomes better understood, more information is uncovered regarding the side effects and neurological damage caused by gad. the good news is that neurodegeneration is not totally irreversible. the plasticity of the brain will allow for regeneration to some degree, but the earlier the damage can be reversed, the better (“the effects of stress & anxiety on the brain”, 2018). however, with more potential damages being uncovered, it is becoming apparent that relaxation and avoiding the risk factors of anxiety disorders should be emphasized in daily life. this is especially pertinent to those with stressful jobs and students that face difficult assignments, exams, and other stressors on a regular basis. the positive news for people that lead stressful lives is that there are ways to avoid gad, and the genetic contribution in gad is not as substantial as other anxiety disorders, so taking measures to stay away from avoidable stressful situations can be quite effective (martin, 2009). however, many people, especially students, still deal with gad. many face gad along with mdd (major depressive disorder), with which it has high comorbidity that ranges up to 98% in treatment studies (patriquin, 2017). it is important to not only know how to avoid gad, but to also be aware of the ways in which it can manifest itself in daily life, the damage it can cause, and its relationship to other mental illnesses like mdd. references hewitt, j. (2018, may 16). gaba, gaba, gaba, what does it actually do in the brain? retrieved from https://medicalxpress.com/ news/2018-05-gaba-brain.amp hilbert, k. (2015, october 13). gray and white matter volume abnormalities in generalized anxiety disorder by categorical and dimensional characterization. retrieved january 5, 2019, from https://www.ncbi.nlm. nih.gov/pmc/articles/pmc5103633/ martin, e. i. (2009, september). the neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. retrieved january 3, 2019, from https://www.ncbi.nlm. nih.gov/pmc/articles/pmc3684250/ patriquin, m. a. (2017, june 8). the neurobiological mechanisms of generalized anxiety disorder and chronic stress. retrieved january 4, 2019, from https:// www.ncbi.nlm.nih.gov/pmc/articles/ pmc5832062/ sanders, r. (2016, october 12). new evidence that chronic stress predisposes brain to mental illness. retrieved from https://news. berkeley.edu/2014/02/11/chronic-stresspredisposes-brain-to-mental-illness/ the effects of stress & anxiety on the brain. (2018, july 26). retrieved from https://www. neurocorecenters.com/blog/depressionanxiety-stresseffects-of-stress-anxiety-onbrain the limbic system. thinktankcentre.blogspot. com/2015/08/the-limbic-system.html t. (n.d.). anxiety disorders. retrieved january 3, 2019, from https://www.nimh.nih.gov/ health/topics/anxiety-disorders/index.shtml volume 8 (will be vol 7 on site) thank you! to the brain matters writers, editors, & executive board members, as well as the university of illinois university library & merinda kaye hensley for all of your hard work in making this journal possible. about brain matters brain matters discusses all things neuroscience, psychology, and biology written by uiuc’s very own. the journal welcomes all authors no matter their area of study or year, therefore, authors come from diverse backgrounds, from molecular and cellular biology & psychology, to computer science & engineering. this diversity allows volumes to have a wide range of articles. the journal is mainly written for the college community yet is accessible to anyone as brain matters is published in an open access format by the university library at the university of illinois urbanachampaign. alcoholic disruption of function in neurophysiological pathways and retrogressive development in size and capability of cognitive neurobiological structures throughcontinual exposure alcoholic disruption of function in neurophysiological pathways and retrogressive development in size and capability of cognitive neurobiological structures throughcontinual exposure juan bautista introduction alcohol (etoh) as a chemical disruptor that impedes on neural development, nutritional and hormone regulations, but has low salience amongst contemporary cultures as being such. in many societies alcoholic consumption is the universal pastime. it is a particularly popular form of socialization amongst young adults (18-22 years old). of full-time college students 54.9 percent admit to having drunk alcohol in the past month when surveyed in the 2018 national survey on drug use and health. out of those who drank in the previous group mentioned 36.9 percent also admitted to binge drinking (having 5 or more alcoholic drinks on a single occasion) []. the high prevalence among young adults is particularly dangerous because their brains are still developing and alcohol may accelerate some deleterious effects and disrupt synaptic rearrangement of the later stages of neural maturation. the factors behind the alcoholic trend within campus communities are numerous from a bacchanalian culture to emotional isolation. the general attraction to alcohol is that it releases inhibitions and psychological pressures. but, this article will take a glance at some of the immediate and long term effects of both continual and binge alcoholic consumption on the nervous system. from a molecular perspective, alcohol induced mechanisms create damaging toxic reagents that in turn cause cellular hypoxia and aggressive autoimmune responses in neural sensitive regions. as alcohol continues to be abused the effects of these faulty irregular pathways accumulate and structural brain damage, neuropathies, and even detriment to genetic viability become evident. ethanol and its metabolism alcohol is classified as a depressant drug because it reduces brain activity by blocking nmda, gaba, serotonin, and acetylcholine receptors from their corresponding neurotransmitters. the binding of etoh on gaba receptors in particular dims neural activity by oversaturating postsynaptic neurons with chloride anions. this elongated period of ion influx reduces the rate of action potentials delaying neural stimulation. the apparent changes in cognition following an episode of excessive alcoholic intake include: difficulty speaking (slurred), poor memory, slowed movements, loss of balance (vertigo), incapacitated motor coordination, stupor (unresponsiveness), and in some cases loss of consciousness. fig. 1 ethanol’s effect on neurotransmitters ethanol (ch3ch2oh) is primarily metabolized in the liver by the enzymes alcohol dehydrogenase (adh) and aldehyde dehydrogenase (aldh). alcohol dehydrogenase breaks down alcohol into acetaldehyde (ch3cho), nadh, and h+. then aldehyde dehydrogenase reacts with water to further break apart acetaldehyde into acetate (ch3coo-) and more nadh and h+ by products. the accumulation of nadh and h+ disrupt the natural pathway of gluconeogenesis. if gluconeogenesis does not proceed normally, an insufficient amount of bicarbonate would form and oxygen delivery would be set back. in addition to the hypoxia this case would also have acetate build up which would decrease the blood ph which may develop into metabolic acidosis. metabolic acidosis severely impairs breathing and requires medical attention. but, continuing on with our metabolism of alcohol, acetate can then be converted to acetyl coa through contribution of atp and coenzyme a in the mitochondria. progression stops here though, before completing the citric acid cycle, because the excess saturation of nadh from previous steps blocks regulatory enzymes (isocitrate dehydrogenase and α-ketoglutarate dehydrogenase). acetyl coa and atp are vol. 3 14 produced, and co2 is not released. the cells affected experience energy deficits and toxic retention which may lead to cellular death. over time these recurrent irregularities can lead to fatty liver, alcoholic hepatitis and lastly cirrhosis. each stage further weakens the liver’s ability to filter toxins as the organ dies. oxidative stress and cellular response if alcoholic intake exceeds the oxidation rate of the stomach and liver enzymes, alcohol dehydrogenase (adh) and aldehyde dehydrogenase (aldh) respectively, then other enzymes across the body will metabolize the alcohol and cause toxic products to linger in regions where they can do the most damage. the particular pace of oxidation in the average human body is roughly 100 milligrams of liquor for each hour per kilogram of body weight. to place this in context, about 8 grams of liquor will be discharged in an hour in the event that you weigh 180 pounds (81.6 kilograms), and 5 grams of liquor will be broken down in an hour if you weigh 110 pounds (50 kilograms). the oxidation rate is modified by sex, ethnicity/genetics, and health of the liver []. once consumed alcohol is rapidly absorbed into the bloodstream. 20 percent enters from the stomach and the other 80 percent seeps in through the linnings at the beginning of the small intestine []. because of this chemical’s high solubility in fat and water, it does not need to be broken down to readily circulate and permeate across the blood-brain barrier. the brain is 75% water by mass and the diffused alcohol has an almost immediate effect in it[ u.s. department of health and human services (1990)]. in the brain, the enzymes catalase and cyp2e1(cytochrome p450) metabolize alcohol; this pathway is therefore called the cytochrome p450-dependent pathway. this pathway creates aldehydes and acetates similar to the primary alcohol metabolism fig. 2 reactive oxygen species pathway in the liver but differs in that it converts nadph into nadp+ by implementing oxygen which forms oxidative free radicals in the brain. free radical-mediated interactions occur within proteins, lipids, and dna. oxidative degradation of omega 3 and omega 6 some polyunsaturated fatty acids undergo lipid peroxidation induced by ethanol intake (burke and ludden 1989). fig. 3 antioxidant treatment and alcoholism. in molecular aspects of alcohol and nutrition acute and chronic intoxication created acetaldehyde is very unstable and forms covalent adducts with the surrounding constituents. this should be done within the liver as it decreases enzymatic activity, inhibits microtubule assembly, and increases catabolism of proteins (lieber; sorrel and tuma). acetaldehyde condensates can incur detection by the immune responsive proteases and thereby damage the conjugated tissue (israel et al., lin et al). aldehyde also activates production of acetaminophen, benzene, ccl 4, halogenated hydrocarbon at toxic levels and pro-carcinogens (nitrosamines, and azo compounds) []. in an experiment sponsored by the university of texas southwerstern medical center, immunocytochemical localization of animal brains administered etoh discovered immunoglobulin antibodies, b-cells (interleukin-4), and t-cells (cd4-l) clustered in very high amounts (kozlowski and sterzl). the researchers predicted that cytokine il-4, recruited macromolecular immunoglobulin proteins into the brain that vol. 3 15 rallied with cd4-l and caused neuronal endocytosis in brain’s of the animals fed etoh. alcohol promotes inflammatory response in neuronal and glial cells by activating signalling pathways (mapks, ikk), increasing production of inflammatory mediators, cytokines, and transcription factors involved in apoptosis and injury response (ap-1, nf-kb) [alcohol and neuroinflammation: involvement of astroglial cells and il-1ri/tlr4 receptors vol. 25 num. 3/ 2006] malnutrition chronic alcohol use can cause malabsorption of important nutrients. health expert for bright hub magazine, kimberly roberts, offers insight into the unhealthy effect of alcohol in one’s diet “individuals that abuse alcohol also tend to fill their caloric needs with drinks, as opposed to food. when they do eat meals, they tend to be unhealthy. this is because alcohol is an addictive carbohydrate. consuming large amounts of this type of carbohydrate increases cravings for more unhealthy carbohydrates, as well as salts and sugars.” chronic alcoholic consumption can lead to a cycle of eating low nutrient foods. but long term alcohol malnutrition has a wide spread strain on many systemic organ functions. it inhibits secretions of digestive enzymes, neglects natural metabolic pathways (glycogenesis) and damages the cells lining the intestines and stomach impairing their ability to absorb nutrients into the bloodstream. vitamin b 6 (pyridoxine), 2 (riboflavin), 1 (thiamin), and folate are some of the nutrients crucial to brain health (nutrient transport, cell growth, homeostasis, which are in lowest proportion within alcoholics (leevy et al). alcohol is associated with cerebral deficiency of folate, a b vitamin soluble in water. folate is involved in metabolic processes such as that produce neurotransmitters (glutamate) and aid in dna synthesis. deficiency of folate and other b-vitamins contributes to accelerated neural degradation and initiation of disease (molero-luis m et al. 2015). for example fetal alcohol syndrome (fas) is prevalent disorder in which a pregnant woman (even at early stages in which she may not be aware of the pregnancy) consumes alcohol that suppresses nutritional flow (folate in particular) resulting in neuronal malformation (shibley ia jr, pennington 1997). thiamin deficiency for example is related to wernicke-korsakoff syndrome of ophthalmoplegia, cerebellar dysfunction, and cerebral degeneration. morphological changes in the brain cerebral cortex hippocampal formation -reduction in thickness reduction in the numerical density of granule cells prelimbic cortex -degradation of myelin sheaths cortical subcortical atrophy associated neuropathies -multiple sclerosis like symptoms genetic damage and heritability of alcoholic symptoms -predisposition -fetal as -lower iq unrelated to poor upbringing some regeneration is possible with abstinence of alcohol and lifestyle changes decrease or reverse the decline of brain matter references 1.fall semester-a time for parents to discuss the risks of college drinking. (2019, december 24). web retrieved from https://www.niaaa.nih.gov/publications/ brochures-and-fact-sheets/time-for-parents-discussrisks-college-drinking 2. heit, c., dong, h., chen, y., thompson, d. c., deitrich, r. a., & vasiliou, v. k. (2013). the role of cyp2e1 in alcohol metabolism and sensitivity in the central nervous system. in subcellular biochemistry (pp. 235–247). https://doi.org/10.1007/978-94-0075881-0_8 3. mcdonnell, pharmd, bcop, a.m., & dang pharmd, bcps, c.h. (2013). basic review of the cytochrom p405 system. jouranl of the advanced practitioner in oncology, 4(4). https://doi.org/10.6004/jadpro.2013.4.4.7 vol. 3 16 4.[1] substance abuse and mental health services administration. (2019). key substance use and mental health indicators in the united states: results from the 2018 national survey on drug use and health (hhs publication no. pep19-5068, nsduh series h-54). rockville, md: center for behavioral health statistics and quality, substance abuse and mental health services administration. retrieved from https://www. samhsa.gov/data/ 5. [2] johnson, s. b., blum, r. w., & giedd, j. n. (2009). adolescent maturity and the brain: the promise and pitfalls of neuroscience research in adolescent health policy. the journal of adolescent health : official publication of the society for adolescent medicine, 45(3), 216–221. https://doi.org/10.1016/j. jadohealth.2009.05.016 6. dynamic mapping of human cortical development during childhood through early adulthood. gogtay n, giedd jn, lusk l, hayashi km, greenstein d, vaituzis ac, nugent tf 3rd, herman dh, clasen ls, toga aw, rapoport jl, thompson pm proc natl acad sci u s a. 2004 may 25; 101(21):81749. 7. (n.d.). retrieved from https://www.usgs.gov/ special-topic/water-science-school/science/wateryou-water-and-human-body?qt-science_center_objects=0#qt-science_center_objects 8. ehlers cl, criado jr. adolescent ethanol exposure: does it produce long-lasting electrophysiological ef 9. allen cd, lee s, koob gf rivier c . immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitaryadrenal axis in adult and adolescent rats. brain behav immun. 2011 june;25(suppl 1):s50–s60 10. silva, c. s., portari, g. v., & vannucchi, h. (2016). antioxidant treatment and alcoholism. in molecular aspects of alcohol and nutrition (pp. 119–131). elsevier. https://doi.org/10.1016/b978-0-12-8007730.00010-0) 11. dervaux a, laqueille x. [thiamine (vitamin b1) treatment in patients with alcohol dependence]. presse med. 2017;46(2 pt 1):165-171. doi:10.1016/j. lpm.2016.07.025 12. tardelli vs, lago mppd, silveira dxd, fidalgo tm. vitamin d and alcohol: a review of the current literature. psychiatry res. 2017;248:83-86. doi:10.1016/j. psychres.2016.10.051 13. american addiction centers. the effects of alcohol on the pancreas. october 2019. 13. spector r, johanson ce. 2007. vitamin transport and homeostasis in mammalian brain: focus on vitamins b and e. j. neurochem. 103(2): 425–38 vol. 3 17 copy of volume 7 publication article 1 the use of virtual reality to treat anxiety-related disorders rajvi javeri virtual reality (vr) is defined as the computer-generated simulation of a three-dimensional image or environment that the user interacts with in seemingly real and physical ways using special electronic equipment such as a helmet with a screen inside or gloves fitted with sensors (oxford dictionary). when using vr, people’s senses including vision, hearing, touch, and even smell are stimulated. the head-mounted display system with binocular screens, stereo sound, and movement-tracking follows the user’s head movements and alters the virtual environment based on these movements. a scent machine that uses compressed air diffuses scented substances, making the experience even more life-like (strickland). for an individual to obtain the proper experience of vr, there must be an element of interaction involved. interactivity depends on three main factors: speed, range, and mapping. speed depends on how quickly the computer identifies the user’s actions and reflects them for the user to perceive. range refers to the number of possible outcomes resulting from any particular user action. mapping is how well the system provides natural results in response to a user’s actions (strickland). in virtual reality, the user has the freedom to navigate themselves through the environment as they please. however, these environments tend to include some other forms of interaction to provide a more exciting experience for the user. other than its recreational uses, one of the most significant uses for virtual reality technology is in the treatment of anxietyrelated disorders. current treatments for such disorders include cognitive behavioral therapy (which is a type of exposure treatment) and visualization and systematic desensitization. these treatment methods, however, take longer amounts of time in order to have some effect, and they are mainly used to treat phobias and not depressive disorders (mcleod). research in evaluating the use of virtual reality to treat anxiety disorders began in the 90s. in the later years, virtual reality exposure (vre) applications were broadened and applied to the treatment of cognitive, emotional and even physical disorders. in a metaanalysis of 13 studies, vre treatment was compared with in vivo treatments for social anxiety disorders and agoraphobia. the results were such that the magnitude of effect with vre was greater in the control groups (d=1.1, p<0.5) and lower with the use of in vivo methods (d=3.5, p<0.5). with vr, the therapist can apply exposure and mediate the stimuli to increase or decrease intensity depending on the patient that is being treated. for example, in treating patients who are afraid of heights or flying on airplanes, the therapist could use vr treatment to be able to manipulate aspectssuch as turbulence, take-off and landing, as well as repeated exposureall during the course of one consultation visit (rothbaum). vr also facilitates the evoking of memories that may be difficult for the patient to relive by forming associations between those mental images and sensory cues (rothbaum). lastly, it is noteworthy that in a world where technology has taken over most aspects of life, vre would be more attractive for the current generation. according to pmx agency, the current generation, or the “gen z,” consumers are going to become the single largest group of consumers in the technology market. according to studies conducted by the international data corporation, 8.1 million virtual reality headsets were shipped to consumers around the world in 2016, and this estimate is projected to rise to 60 million by 2021 (harrison). virtual reality therapy has been most effective in its use for exposure therapies as in the case of post-traumatic stress disorder (ptsd) and phobias. post-traumatic stress disorder is a mental health condition that is triggered by either experiencing or witnessing a terrifying event. such events could include a war, a terror attack or even a traumatic accident. the symptoms of ptsd do not usually occur until a month after the traumatic event. however, in some cases the symptoms can even surface years after the event. these symptoms typically include intrusive memories of the stressful event accompanied by upsetting dreams or nightmares, negative changes in mood, and changes in physical and emotional reactions, like being startled easily and always being on guard for danger (mayo foundation vol. 3 1 for medical education and research) the major brain regions that are affected by traumatic stress include the amygdala, hippocampus and the prefrontal cortex. findings from animal studies have concluded that ptsd leads to a decrease in hippocampal and anterior cingulate cortex volumes due to the change in the brain’s “circuits,” accompanied with an increase in the amygdala’s response. fig 1. diagram depicting the regions of the brain affected by ptsd there is also a spike in norepinephrine and cortisol response to stressors. the hippocampal volume in vietnam veterans was studied using magnetic resonance imaging, and it was found that they had 8% smaller right hippocampal volume relative to controls matched for a healthy brain (brenmer). to test the reliability of vr therapy, the department of psychiatry at the emory school of medicine in atlanta, georgia conducted a test on a participanta 50-year-old caucasian who served as a helicopter pilot in the vietnam war. “he met the dsm-iv criteria for current ptsd, and current major depressive disorder, and past alcohol abuse” (rothbaum 265). fig 2. comparison of a healthy brain (l) with a brain affected by ptsd (r) to depict the difference in brain volume of certain brain structures during the vr exposure treatment, the patient was equipped with a head mounted display containing two mini-television screens and earphones over each ear. the set up was connected to a computer whose graphics and audio were consistent with the orientation of the patient’s head and were computed in real time as the patient explored the surrounding environment. the therapist could communicate with the patient via a microphone attached to the headset. the treatment was delivered in 14, 90-minute sessions and the sessions increased in intensity as the weeks progressed. the participant could feel vibrations similar to those felt while seated in a helicopter through the vr set up. he was also shown virtual environments, such as those of a jungle clearing and was exposed to audio effects comprising noises that one would typically hear on the battlefield. in the later sessions, the participant’s most traumatic memories were triggered and prompted by the therapist. to do this, the therapist would ask the patient to recount those traumatic memories repeatedly in past tense until his anxiety decreased due to a process known as habituation. the therapist simultaneously viewed the virtual environments with which the patient was interacting and would comment appropriately while maintaining the exposure until the participant’s anxiety habituated. results from pre-treatment to post-treatment are positive (rothbaum). after the treatment, the values indicating arousal and depression, among others, appeared significantly lower, indicating a decrease in clinical severity. vol. 3 2 the scales used to measure the results included: the clinician administered ptsd scale (caps), the impact of events scale (ies), and the beck depression inventory (bdi). the patient’s caps total score was 64 (severe) before treatment, which dropped to 42 (moderate) after treatment, indicating a decrease in clinical severity. the patient’s pre-treatment ies score was 33 (1 standard deviation (sd) above the average of all veterans suffering from ptsd in his group) which decreased to 18, indicating a 2 sd move following therapy. his 6-month follow up indicated a total ies score of 0 which denoted a complete absence of intrusive symptoms related to the traumatic incident. lastly, his bdi score dropped from a 37 to a 30 which was still in the severe depression range. however, his 6-month follow up score of 21 fell into the moderate depression range (rothbaum). another effective use of virtual reality therapy is in the treatment of phobias. a phobia is an extreme and irrational fear or aversion to something, which may or may not have a grounding in reality. these phobias interfere with the day-to-day functioning of an individual and are often paired with anxiety. symptoms include panic attacks, elevated heart rate, trembling and feeling out of control or powerless (open path psychotherapy collective). one of the most common phobias is the fear of flying. about 10-40% of the population has a fear of flying, and the anxiety produced by flying is so intense that it can impede an individual’s daily functioning and can even influence the kind of job they settle for (price). people who have the disorder usually ingest some form of alcohol or sedative in order to deal with the fear. exposure therapy is the most common method used in the treatment of phobias. it involves exposing a patient to the stimulus that he/she fears, so that they can habituate to it. habituation is the diminishing of a psychological or emotional response to a frequently repeated stimulus (oxford dictionary). repeated exposure to the stimulus in a controlled manner for prolonged periods of time can help the patient cope with the phobia. virtual reality is itself a type of exposure therapy and this makes it an effective tool in combating phobias. in this type of therapy, patients learn how to identify the thoughts that are causing this anxiety and then learn how to overcome and replace these thoughts with more helpful ones (winerman). a study was conducted by price et al. to treat the fear of flying in a 42-year-old female who met the criteria for a situational type phobia according to the dsm-iv criteria. during the first half of the treatment, the female sat for seven sessions of anxiety management techniques which included: breathing relaxation, biotherapy, thought-stopping, cognitive restructuring and preparation for stressors*. after six weeks, the second part of the treatment was initiated in which there were six sessions of vre administered. each session lasted 30-45 minutes and exposed the patient to the simulation of taking off and landing along with various variables such as turbulence and adverse weather conditions. after this time period, the outcome of the therapy was evaluated with a self-report questionnaire and subjective unit of discomfort (suds) ratings. it was noticed that the patient experienced a decline in self-reported anxiety and could complete an actual flight with very little anxiety which indicates that the treatment was successful (price). research conducted at the university of california on the neural activity of rodents provides promising results relating to virtual reality therapy. experiments are being conducted on them in vr settings, wherein their brain signals from the *the anxiety reducing techniques employed in the first half of this study were to prepare the participant for the flight. the techniques were not a control of any sort. vol. 3 3 hippocampus are being recorded. being associated with memory and spatial mapping, the neurons in the hippocampus have a gps-like system, which helps them navigate their way through space. the purpose of this study was to find out whether vr could simulate the same type of brain mapping as in the hippocampus. interestingly, they found out that 60% of the neurons in the hippocampus stopped firing during the experiment. this is possible because vr is immersive, and this immersion can lead to changes in the way the brain processes stimuli. it has been speculated that vr’s ability to “shut down” the hippocampus could have rewired the brain and that the various pathways in the brain can be formed and reinforced through repetition (guillette, verizon). these findings indicate that the long-term use of vr on the brain can be an effective cure for phobias. as mentioned before, vrt is a type of exposure therapy. exposure therapy can change the fear circuitwhich involves the amygdala and the prefrontal cortexafter treatment. during habituation, the bilateral anterior medial temporal lobe and the amygdala show a decline in regional cerebral blood flow on repeated exposure to the feared stimuli. this results in a decrease in subjective anxiety ratings and a drop in the patient’s heart rate during stressful conditions (landowska). in this manner, vr proves to be effective against phobias. while analyzing the benefits of virtual reality therapy, it is equally important to keep in mind the drawbacks associated with it. the first major drawback is that vr interfaces have not been designed to be used as medical equipment yet. this means that the major challenge associated with vr therapy is the sterilizing of the equipment for its use on multiple patients. vr equipment has not yet been modified to accommodate people with disabilities and special needs, which limits the extent of its use. this can pose problems because a large number of war veteranswho need the treatment mostwill not be able to reap its benefits. additionally, cost is another hindrance in the use of vr therapy in a number of medical facilities. although equipment cost has reduced significantly in the previous years, schools and health centers are afraid to purchase equipment in the absence of subsidies. the cost of the equipment also limits the availability of the treatment, leading back to the issue that it will fail to satisfy the needs of most people (burdea). with the invention of technology, science has opened several opportunities that are proving to be necessary for the betterment of humanity. these opportunities are providing a better chance for us to adapt, and therefore we shouldn’t forgo them. when it comes to virtual reality therapy, its uses now encompass the treatment of anxiety-related disorders such as ptsd and phobias. according to the metaanalysis, when compared to other exposure therapies such as systematic desensitization, vr therapy appears to have a greater magnitude of effect. vr, when used to treat veterans of the vietnam war showed a significant reduction in the patient’s symptoms of depression and anxiety. the immersive quality of vr therapy allows it to be used for the treatment of phobias too. it achieves this by rewiring the brain’s circuitry – such as the fear circuitinvolving the amygdala and the prefrontal cortex. it also stimulates habituation, causing reduction in the cerebral blood flow in the amygdala and the bilateral anterior medial temporal lobe. further research and development in the use of virtual reality equipment in treatment, if encouraged, can prove to be immensely beneficial and can improve the standard of living for people who have experienced many hardships, helping them come close to leading a normal life. references 1. oxford dictionary. (n.d.). virtual reality: definition of virtual reality by oxford dictionary on lexico.com also meaning of virtual reality. https://www.lexico. com/definition/virtual_reality 2. strickland, j. how virtual reality works. 29 june 2007, https://electronics.howstuffworks.com/gadgets/other-gadgets/virtual reality.htm/printable 3. mcleod, s. systematic desensitization. 1 january 1970, https://www.simplypsychology.org/systematic-desensitisation.html#:~:text=systematic desensitization is a type,stimulus gradually using counter conditioning. 4. rothbaum, b. o., garcia-palacios, a., & rothbaum, a. o. treating anxiety disorders with virtual reality exposure therapy. 2012, revista de psiquiatría y salud mental (english edition), 5(2), 67–70. doi: 10.1016/j. rpsmen.2011.05.003 vol. 3 4 5. harrison, k. l. (2017, june 27). why vr is the perfect way to win gen z consumers. retrieved from https://www.inc.com/kate-l-harrison/why-vr-is-theperfect-way-to-woo-gen-zers.html 6. mayo foundation for medical education and research . (n.d.). symptoms and causes. retrieved from https://www.mayoclinic.org/diseases-conditions/ post-traumatic-stress-disorder/symptoms-causes/syc20355967?p=1 7. bremner, j. d. (2006). traumatic stress: effects on the brain . dialogues in clinical neuroscience, 8(4), 445–461. doi: 10.1002/9781118356142.ch13 8. rothbaum, b. o., hodges, l., alarcon, r., ready, d., shahar, f., graap, k., … baltzell, d. (1999). virtual reality exposure therapy for ptsd vietnam veterans: a case study. journal of traumatic stress, 12(2), 263– 271. doi: 10.1023/a:1024772308758 9. open path. (n.d.). phobias: open path psychotherapy collective. retrieved from https://openpathcollective.org/mental-health-topics/phobias/ 10. price, m., anderson, p., & rothbaum, b. o. (2008). virtual reality as treatment for fear of flying: a review of recent research. international journal of behavioral consultation and therapy, 4(4), 340–347. doi: 10.1037/h0100864 11. winerman, l. (2005). fighting phobias: a virtual cure. monitor on psychology, 36(7), 87. doi: 10.1037/ e411952005-043 12. verizon. (2019, december 3). virtual reality changes your brain. retrieved from https://www.verizon. com/about/our-company/fourth-industrial-revolution/ virtual-reality-changes-your-brain 13. landowska, a., roberts, d., eachus, p., & barrett, a. (2018). withinand between-session prefrontal cortex response to virtual reality exposure therapy for acrophobia. frontiers in human neuroscience, 12, 362. https://doi.org/10.3389/fnhum.2018.00362 14. burdea, g. c. (2003). virtual rehabilitation – benefits and challenges. methods of information in medicine, 42(05), 519–523. doi: 10.1055/s-0038-1634378 15. callan, a. c. (n.d.). effects of ptsd on functional circuitry involved in fear learning [illustration]. oxford handbooks online. https://www.oxfordhandbooks. com/oxford/fullsizeimage?imageuri=%2f10.1093%2foxfordhb%2f9780190635374.001.0001%2foxfordhb-9780190635374-e-12-graphic-001-full.gif&urichapter=%2f10.1093%2foxfordhb%2f9780190635374.001.0001%2foxfordhb-9780190635374-e-12 16. general electric (ge) news. (2015, april 22). mapping the ptsd brain [photograph]. https://www. ge.com/news/reports/21-04-2015mapping-the-ptsdbrain 17. ipser, j. c. i. (2013). regions activated in response to phobic stimuli in patients [photograph]. psychiatry and clinical neuroscience. https://onlinelibrary.wiley. com/doi/pdf/10.1111/pcn.12055 vol. 3 5 copy of volume 6 publication using cognitive therapy methods to treat musical performance anxiety sarah masud when it comes to exams, public speaking, and completing tasks in general, performance anxiety appears to be a common experience. however, it can cause significant distress and impairment, even to the point that some consider it to be a subtype of social anxiety disorder. the difference is that social anxiety is broadly concerned with embarrassment and humiliation in social situations while individuals with performance anxiety specifically fear the consequences of performing poorly. though they aren’t the same, applying cognitive behavioral therapy (cbt) shows promising results for both of them. in particular, people with musical performance anxiety (mpa) can benefit from adapted forms of cbt during private lessons. in evidence-based practice of cognitive-behavioral therapy, dobson and dobson (2017) discuss how therapists can help their patients work through their negative thoughts by simply educating them about the different types of cognitive distortions and negative thinking patterns. one of the most common distortions is overgeneralization, which involves making a broad judgment based on one bad experience. in the context of mpa, a musician may feel that their performances are never good because they performed poorly one time. a similar distortion is magnification, which is giving one factor more significance than it realistically has. for example, a musician may feel that an entire performance went badly because they messed up on one section. once these thought patterns are explained to patients, they are asked to record instances when they think these things along with the emotions and behaviors that follow them. these are thought patterns that can be addressed not only in a clinical setting but in private lessons as well. when teachers are able to pinpoint these cognitive distortions, they can help their students replace negative thoughts with positive ones. this is the goal of cbt, and an alternative thought is meant to be recorded next to each automatic negative thought for future application. an example of a negative thought would be that a student’s nerves will always take over and they will be unable to perform well no matter what. the associated emotions and behaviors are feelings of hopelessness and a lack of preparation for the next performance. this could be restructured into a positive thought if the student tries thinking that they’re in control of their own thoughts and that they’ll become less nervous as they gain more experience. so, the resulting situation is an increase in confidence and motivation to practice and take lessons. this is effective for less remarkably negative thoughts as well. even replacing the thought of “don’t rush this section” with “play slowly and calmly” creates more potential for a good experience. figure 1. a moderate amount of physiological arousal is optimal for strong performance, but excessive amounts deteriorate performance quality (wikimedia commons, 2020). performance anxiety has somatic, behavioral, emotional, and cognitive aspects. some psychologists view somatic symptoms—such as rapid heartbeat, sweaty hands, and muscle tension—as the most important ones. in fact, a study conducted by zinn et al. (2000) found that these physical symptoms create a chain reaction that leads to anxious thoughts. once an individual becomes aware that their heart is beating fast and their hands are shaking, it leads to more apprehension about their performance, which only heightens physiological arousal. in contrast, cognitive behaviorists argue that performance anxiety arises because of cognitive assessments of the perceived threatening situation (bruce & barlow, 1990). compared to individuals who don’t experience mpa, these judgments are largely negative and disproportional to the actual threat posed. many studies following bruce and barlow’s have reinforced that the cognitive and emotional symptoms of mpa are more significant than originally believed. these include a loss of concentration, anxious apprehension, and feelings of helplessness. this is where methods of cbt become helpful: in treating the thought processes associated with mpa. figure 2. an example of cognitive behavioral therapy working to restructure negative thought patterns and lead to new outcomes (wikimedia commons, 2022). 32brain matters volume vi cina, j. a. (2021). music performance anxiety and cognitive-behavioral therapy: some pedagogical insights. college music symposium, 61(2), 53–67. https://www.jstor.org/stable/48645698 file:hebbianyerkesdodson.svg. (2020, september 16). wikimedia commons. retrieved 18:33, april 18, 2023 from.https://commons.wikimedia.org/w/index.php? title=file:hebbianyerkesdodson.svg&oldid=460876838. file:rebt method albert ellis.png. (2022, march 4). wikimedia commons. retrieved 18:27, april 18, 2023.from.https://commons.wikimedia.org/w/index.php? title=file:rebt_method__albert_ellis.png&oldid=634699703. gaudiano b. a. (2008). cognitive-behavioral therapies: achievements and challenges. evidence-based mental health, 11(1), 5–7. https://doi.org/10.1136/ebmh.11.1.5 references 1. 2. 3. 4. brain matters volume vi however, it’s important to note that this approach won’t work for everyone and that cbt has its criticisms. opposers argue that the methods are too mechanistic and that they fail to consider the whole perspective. regarding mpa, cognitive appraisals are just one aspect, and addressing them won’t guarantee a reduction in anxiety and the physiological and behavioral symptoms associated with it. in a related study conducted by burns and spangler (2001), cbt didn’t show any significant treatment outcomes for 521 patients with dysfunctional attitudes. still, many studies show that efforts to reduce negative cognitive assessments may be effective in reducing mpa—one experiment even saw greater improvements in confidence using cbt alone compared to using a combination of cbt and buspirone, an anxiety medication (clark & agras, 1991). although this adapted form of therapy is a promising approach to treating mpa, further research needs to be done to conclude whether there are more effective treatment methods. based on current knowledge, it is effective in replacing negative thought processes to reduce the cognitive and emotional symptoms associated with mpa (cina, 2021). if applied during private music lessons, it could show favorable results that compare to clinical treatment. 33 https://commons.wikimedia.org/w/index.php?title=file:hebbianyerkesdodson.svg&oldid=460876838 https://commons.wikimedia.org/w/index.php?title=file:rebt_method_-_albert_ellis.png&oldid=634699703 copy of volume 7 publication introduction the thalamus remains a mysterious structure in neurobiology: arising from the diencephalon and playing numerous essential roles in human physiology. the diencephalon can be divided into four parts: the epithalamus, the dorsal thalamus, the ventral thalamus, and the hypothalamus. this review will focus primarily on the dorsal division, as this is the portion that innervates the cerebral cortex, which is most relevant to this discussion. the thalamus is a paired gray matter structure composed of an array of different nuclei each serving a specific purpose. it is conveniently located between subcortical structures and the cerebral cortex, which facilitates its relay function, filtering information about sensory inputs (i.e. taste, touch, sound, etc.) between the brain and the body. the thalamus’ advantageous location and specialized nuclei has given rise to speculation of whether the structure serves a more intricate function, one involved in cognition and consciousness. first order and higher order nuclei the anatomy of the thalamus is one of great complexity. brain nuclei, such as that which the thalamus is composed of, are collections of neuronal cell bodies and thus are classified as gray matter. thalamic-specific nuclei can be further classified as either ‘first-order’ (fo) or ‘higher-order’ (ho). ‘first-order’ thalamic nuclei correspond with earlier proposed functions of the thalamus, that is, with relaying sensory information from subcortical structures. alternatively, ‘higher-order’ thalamic nuclei receive inputs from cortical layer 5 instead of the periphery and are thus being implicated as potentially carrying out higher order function, as their name implies. this theory is also supported by the role of ho nuclei in cortico-thalamo-cortical pathways, as they allow communication between cortical areas. this information has given rise to speculation that ho nuclei play a more integrative role while fo nuclei solely facilitate sensory relay function. however, these theories are being challenged by new evidence suggesting that both system’s purposes are more complex and are both involved in higher order functions. the thalamic bridge to cognition and consciousness lina issa abstract from an evolutionary perspective, deeper brain structures are postulated as being more primitive than those that were developed later on. as such, the thalamus, being a deep brain structure, is generally believed to occupy one such primitive role: that of a ‘sensory relay station’. recent evidence, however, suggests that the thalamus is in fact responsible for more complex and higher order functions involving cognition and consciousness, processes previously attributed solely to the cerebral cortex. this review examines several of these emerging theories through the lens neural pathways, with particular focus placed on how the complex circuitry of the thalamus allows for the intricate connectivity between itself, the cerebral cortex, and other subcortical structures. both ho and fo nuclei may in fact represent a ‘thalamic bridge’, in which the thalamus occupies an integrative role between sensory perception and cognition. modulatory vs. driver input the differential properties of synapses also contribute a great deal to thalamic activity. it is postulated that two distinct forms of synaptic inputs exist: ‘driver input’ and ‘modulatory input’. drivers carry the message whereas modulators modify how driver inputs are processed through processes such as attenuation or amplification. this further promotes categorization of thalamic nuclei as either ‘first-order’ (fo) or ‘higher-order’ (ho) based on where they receive their driving input from. fo nuclei receive driver input from subcortical structures while ho nuclei are mainly innervated by descending corticothalamic inputs from layer 5. layer 6 cells provide modulatory feedback input to all thalamic nuclei, projecting to thalamic regions and providing thalamocortical input to the same cortical region from which they originate. modulatory inputs from the cortex thus reach both ho and fo thalamic nuclei and affect the functionality of thalamocortical neurons. figure 1: thalamic nuclei. image courtesy s bhimji md. 13 the md has been implicated in executive functions (involving planning, working memory, and decision-making) because of its significant interconnectivity with the prefrontal cortex (pfc) which is ultimately responsible for cognitive control functions. as discussed previously, the involvement of ‘higher-order’ thalamic nuclei in distributing efference copies of the cerebral cortex signals to other cortical areas through a mode termed transthalamic communication gives insight into the significance of thalamic connections. thus, using the example of the mediodorsal thalamic nucleus previously discussed, lesions to this structure would disrupt connections between the thalamus and cortex. as a result, the direct connections via different cortical areas and the transthalamic connections of different cortical areas would no longer be aligned, ultimately altering our internal perception of sensory stimuli. our senses of sound, taste smell, etc. would no longer properly feed into subsequent processes which rely on accurate information, consequently impacting mental processes such as thinking and learning. an evident manifestation of this pathology would be people demonstrating unexplained behaviors or verbalizing nonsensical thoughts. thus, it is evident that the mediodorsal nucleus of the thalamus is essential in this higher order cognitive scheme. the thalamus and consciousness in addition to the role of the thalamus in cognition, studies have shown that this structure may also be heavily affiliated with consciousness, which is also dependent on thalamocortical and corticocortical interactions. the higherorder thalamic nuclei which facilitate cortical communication may play a role in modulating corticocortical interaction across different conscious states. one specific region of the thalamus that has been highlighted in relation to consciousness is the central lateral thalamus (cl). consciousness is thought to involve feedforward and feedback interactions between cortical layers and areas and the cl is connected to both deep and superficial cortical layers. a study done on macaques shows promising evidence for cl function in consciousness. electrical stimulation of the cl in two anesthetized macaques produced behavioral indications of arousal. 14 the implications of this set-up are that sensory signals relayed via fo nuclei are processed in the cortex and then transmitted via ho to different cortical areas. this phenomena promotes a functional aspect of ho nuclei in trans-thalamic communication, one that allows cortical areas to communicate with each other outside of the direct connections between different cortical areas. it is also important to recognize that the inputs to both ‘first-order’ and ‘higher-order’ nuclei arrive via branching axons with extra thalamic branches innervating a motor center carrying a message that can be interpreted as an efference copy (an internal copy of an efferent). efference copies are neural representations of motor outputs that predict reafferent sensory feedback. this phenomena is observed in tickling, where efference copies are created when you attempt to tickle yourself, which allows for the prediction of the sensory consequences of the movement. yet, when other people tickle you, it is not predicted, and the sensation is much more intense. the cognitive thalamus the circuitry between the thalamus and cortex gives rise to a cognitive function of the thalamus, particularly in memory and learning. the link between the thalamus and memory has long been speculated in accordance with evidence indicating that damage to the thalamus invariably occurs in korsakoff syndrome, a chronic memory disorder. one prominent thalamic nucleus assumed to be linked to memory is the anterior nuclei of the thalamus (ant) which is located at the rostral end of the dorsal thalamus. the ant is a key component of the hippocampal system for episodic memory, connecting the anterior cingulate (which is implicated in complex cognitive function) and orbitomedial prefrontal cortex (which is involved in decision-making). early evidence shows a specific role of the anterior thalamus in pavlovian conditioning, a learning procedure that involves the pairing of a potent stimulus with a neutral one to ultimately elicit a potent response in the subject to the neutral stimulus. data indicate that the atn is specifically involved in the acquisition phase of pavlovian learning. one study on rats demonstrates that acquisition of contextual fear memory is delayed after atn lesions. another prominent thalamic nuclei involved in memory and learning is the mediodorsal nucleus of the thalamus (md). figure 2: thalamocortical circuitry (usrey & sherman, 2017. figure 3: corticocortical and transthalamic routes of transmission via the mediodorsal thalamus (ouhaz et al., 2018) brain matters・volume v issue ii it was also shown that sleep and anesthesia were associated with less activity in the cl, whereas cl stimulation reversed these changes. this finding can be explained by thalamic circuitry, one of these circuits carries sensory information from the thalamus to the cerebral cortex and another carries feedback about predictions, attention, etc., all of which are needed to facilitate consciousness in organisms. conclusion from this brief overview we can see that the thalamus is not a simple, crude structure but is instead involved in many dynamic processes that significantly alter the nature of the information relayed to the cortex. the distinct cell groups/nuclei in the thalamus provide insight into how such a structure is able to perform these broad range of functions. specifically, it is the ‘higher-order’ nuclei that allow for the cross talk between different cortical areas. as for the ‘firstorder’ nuclei, they provide a path for the outside world and the various subcortical structures to communicate with the cerebral cortex. this review also highlighted some key thalamic nuclei that have been specifically implicated in cognition and arousal. altogether, although a myriad of recent research is emerging looking at the thalamus and its sophisticated circuitry, we still have a long way to go to truly understand all the roles this alluring structure takes on. references 1. bickford, m. e. (2016). thalamic circuit diversity: modulation of the driver/modulator framework. frontiers in neural circuits, 9. 2. child, n. d., & benarroch, e. e. (2013). anterior nucleus of the thalamus: functional organization and clinical implications. neurology, 81(21), 1869–1876. 3. dupire, a., kant, p., mons, n., marchand, a.r., coutureau, e., dalrymple-alford, j., wolff, m., 2013. a role for anterior thalamic nuclei in affective cognition: interaction with environmental conditions. hippocampus 23, 392–404. 4. ouhaz, z., fleming, h., & mitchell, a. s. (2018). cognitive functions and neurodevelopmental disorders involving the prefrontal cortex and mediodorsal thalamus. frontiers in neuroscience, 12. 5. prasad, j. a., carroll, b. j., & sherman, s. m. (2020). layer 5 corticofugal projections from diverse cortical areas: variations on a pattern of thalamic and extrathalamic targets. the journal of neuroscience, 40(30), 5785–5796. 6. redinbaugh, m. j., phillips, j. m., kambi, n. a., mohanta, s., andryk, s., dooley, g. l., afrasiabi, m., raz, a., & saalmann, y. b. (2020). thalamus 7. sherman, s. m., & guillery, r. w. (1998). on the actions that one nerve cell can have on another: distinguishing “drivers” from “modulators.” proceedings of the national academy of sciences, 95(12), 7121–7126. 8. sherman, s. m., & guillery, r. w. (1996). functional organization of thalamocortical relays. journal of neurophysiology, 76(3), 1367–1395. https://doi.org/10.1152/jn.1996.76.3.1367 9. wolff, m., morceau, s., folkard, r., martin-cortecero, j., & groh, a. (2021). a thalamic bridge from sensory perception to cognition. neuroscience & biobehavioral reviews, 120, 222–235. 10. wolff, m., & vann, s. d. (2018). the cognitive thalamus as a gateway to mental representations. the journal of neuroscience, 39(1), 3–14. 15 copy of volume 6 publication katy simmons is an mcb major pursuing a certificate in neuroscience! her interests include cellular neuroscience and neuroimmunology. she is involved in brain matters as a design team member, editor, and writer. her favorite thing about being a part of the journal is meeting and engaging with others that are passionate about neuroscience. apart from her role in brain matters, she is a research assistant in the evolution of intelligent systems lab, as well as the evolutionary immunology and genomics laboratory. after undergrad, she plans to attend grad school to conduct her own research in cellular neuroscience! brain matters writers vyapti is a freshman majoring in psychology. she is interested in neurobiology and the workings of the mind and its connection to psychology. outside of the academic realm, she enjoys spending time reading books and sketching. she enjoys researching topics about the brain that are both fascinating and that help bring awareness, which the “brain matters’ organization allows her to do. she has currently written an article on the makings of the antisocial behavior type, which not only educates others on the situational and biological aspect of those with the antisocial behavior type, but also brings awareness, so that these cases can be better resolved, and prevented from causing chaos. my name is alisha, and i am a sophomore majoring in brain and cognitive sciences as well as minoring in chemistry and psychology. my major allows me to learn how intelligent systems work and this includes intelligent computer systems. i get to intertwine subjects of psychology with cs and learn how they can be used together to understand the world of artificial intelligence and the idea of "what is a mind". i am also a research assistant in the brain and cognitive development lab where we study the basic perceptual and cognitive abilities one is born with. we observe the development in children which can inform us on how early brain organization can inform theories of conceptual development. my personal interests in research delve into neurodivergent disorders such austism spectrum disorder in children and what could possibly be utilized as a therapy for them. saani kulkarni is a rising junior majoring in bioengineering with a minor in computer science. outside of academics, she is passionate about learning from different cultures and travel, choosing to further her knowledge by working as a global engineering ambassador for the school. she hopes to combine her interest in neuroscience with her skills in order to promote student awareness on campus in regard to neurodegenerative disorders. 46 br ai n m at te rs w ri te rs brain matters volume vi br ai n m at te rs w ri te rs bilal is an undergraduate student currently studying biomolecular engineering on a pre-med track. he is currently involved with a few organizations on campus: idea institute, cancer center at illinois, and the carle illinois college of medicine. his interests align with tissue engineering, translational sciences, and the use of health technology. additionally, he is pursuing a minor in computer science. bilal is active in the research community and hopes to use more of machine learning and artificial intelligence to further automate human interaction. he loves to run, hang with friends, and listen to podcasts in his spare time. you can usually catch him on the quad going for a nice stroll. shireen aydogan is a sophomore majoring in molecular and cellular biology on a pre-med track and exploring the possibility of an arabic and communications minor. she devotes time to teach english to refugees and volunteer at the free health clinic in the community throughout the school year as well. in her free time she enjoys playing the guitar, and spending time with her family. she also likes to stay active by playing basketball and snowboarding. she hopes to increase awareness in neuroscience through her writing and as social/advertising chair for brain matters. alex graduated from the university of illinois urbana-champaign in 2023, where he majored in psychology with a concentration in cognitive neuroscience. he was a member of the undergraduate psychology association and lgbtq+ kiki and is currently a research assistant in the learning and language lab at uiuc under dr. jon willits. in his free time, alex enjoys reading and local music. he is passionate about approaching science from a philosophically informed perspective and hopes that his writing in brain matters will spark an interest in this point of view for others interested in neuroscience. 47 michelle is a sophomore pursuing a major in chemistry and a minor in computer science. aside from being a part of the journal, michelle is currently working in the silverman lab as an undergraduate researcher. she is excited to explore the field of neuroscience by writing for brain matters. brain matters volume vi matthew babik is a sophomore in the biochemistry major. he is pursuing an md. ph.d. where he hopes to study neuronal mapping techniques as a scientist and perform in utero spina bifida treatments as a medical doctor. during the fall 2021 semester, matthew worked in uiuc’s roger adams laboratory where he researched yeast vacuole proteins and their potential use as homologous models for higher eukaryotic vesicles. since high school, he has been interested in the topic of dendritic nonlinearities and neuroscience as a whole. he found that writing for the journal was a great outlet for exploring this interest. sarah masud is a freshman pursuing a dual degree in psychology and information sciences. she also plans to minor in art & design. some of her academic interests include cognitive science, human-computer interaction, and psychiatric disorders. she enjoys drawing and visiting coffee shops as well! outside of brain matters, she is also involved in the undergraduate psychology association and stitching illini. she hopes to continue furthering her understanding of neuroscience through writing for the journal. hello! my name is celeste acosta and i’m a senior in molecular and cellular biology and psychology! i’m from cicero, illinois. i’m currently training to work at the physical and neurocognitive health lab with dr. dominika pindus and her team on campus. i love learning about the brain and it’s wonderful ability to constantly change itself even in the most challenging circumstances! in the future i’d like to apply what i’ve learned about neuroscience in a clinical setting as a child and adolescent psychiatrist. in my free time i like to take pictures, read, play animal crossing, and spend time with my family back home! ruibin (violet) wang is a senior student at the university of illinois urbanachampaign, where she is pursuing a major in psychology with a concentration in behavioral neuroscience. her passion for the field of neuroscience and psychology research is reflected in her various experiences, including her current role as an undergraduate research assistant in the juraska lab, where she studies the effect of phthalates on rats' hippocampus. brain matters volume vi 48 br ai n m at te rs w ri te rs br ai n m at te rs w ri te rs 49 neha bashir is majoring in mcb honors on the pre-med track, with a minor in business. her interests include neuroscience and cognitive health. she is a writer for brain matters, which allows her the opportunity to learn about pursue new information about the brain and nervous system. she first became interested with the brain in high school when she was provided the opportunity to hold a cadaver brain, and became inspired as she traced her fingers along the sulci and gyri. additional to being a writer in brain matters, she is involved in cultural and medical clubs at uiuc, as well as being an undergraduate research assistant in the physical activity and neurocognitive health lab. after graduating from uiuc, she hopes to attend medical school and achieve a career as a pediatric neurologist. brain matters volume vi copy of volume 7 publication copy of brain matters template final introduction many neurodegenerative diseases: alzheimer’s disease, huntingtion’s disease, duchenne’s muscular dystrophy, and spinal muscular atrophy, are linked to the aggregation of toxic proteins in the nervous system. although significant strides have been made in studying the mechanisms of neurodegenerative diseases, the consequent advancements in therapies for treating them have been slower. antisense oligonucleotide-based strategies (asos) are the most direct method of targeting gene expression. aso strategies utilize synthetic oligonucleotides which bind to the target mrna by watson-crick hybridization and can either promote or inhibit the degradation of this rna, leading to a knock down of gene expression. in 2016, two aso therapies for spinal muscular atrophy and duchenne muscular dystrophy were approved by the fda. this marked a shift in the direction of treatment strategies towards antisense oligonucleotides (asos). asos can target gene expression through a variety of mechanisms including altering the splicing of pre-mrna, blocking mrna translation or preventing the assembly of ribosomal complexes. the main complication in aso therapies is that oligonucleotides cannot cross the blood brain barrier and thus, require invasive forms of delivery. this article will discuss mechanisms of aso-therapy, challenges in its clinical applications, fda-approved aso therapies, and future development. mechanisms of aso-therapy many neurodegenerative diseases: alzheimer’s disease, huntingtion’s disease, duchenne’s muscular dystrophy, and spinal muscular atrophy, are linked to the aggregation of toxic proteins in the nervous system. although significant strides have been made in studying the mechanisms of neurodegenerative diseases, the consequent advancements in therapies for treating them have been slower. antisense oligonucleotide-based strategies (asos) are the most direct method of targeting gene expression. aso strategies utilize synthetic oligonucleotides which bind to the target mrna by watson-crick hybridization and can either promote or inhibit the degradation of this rna, leading to a knock down of gene expression. in 2016, two aso therapies for spinal muscular atrophy and duchenne muscular dystrophy were approved by the fda. abstract many neurodegenerative diseases like alzheimer’s disease, huntingtion’s disease, duchenne’s muscular dystrophy and spinal muscular atrophy are linked to aggregated, toxic proteins. antisense oligonucleotide-based strategies (asos) are the most direct method of targeting gene expression. synthetic oligonucleotides bind to the target mrna by watson-crick hybridization and can either promote the degradation of rna or inhibit it. in 2016, two aso therapies for spinal muscular atrophy and duchenne muscular dystrophy were approved by the fda. this marked a shift in the direction of treatment strategies towards antisense oligonucleotides (asos). asos can target gene expression through a variety of mechanisms including altering the splicing of pre-mrna, blocking mrna translation or preventing the assembly of ribosomal complexes. while maternal stress can negatively impact the developing fetus in a plethora of ways, stress experienced in childhood, whether due to severe traumatic events or socioeconomic standing, can also be detrimental to development. the amygdala, in particular, is highly susceptible to sensitivity due to early life stressors that these children experience. furthermore, children who experience early life stressors show significant deficits in the affective domain and in brain regions with extended postnatal development such as the hippocampus, amygdala, and prefrontal cortex (pechtel et al. 2010). early life stressors seem to interfere with the neurogenesis, synaptic overproduction, and pruning of synapses/receptors, thus impairing neural plasticity and growth in the critical brain areas listed above (pechtel et al. 2010). the corpus callosum, which connects various aspects of cognitive, motor, and sensory functioning at different stages across development, decreases in size due to early due to early life stressors. in addition to recruiting cellular enzymes, asos can also directly cleave target rna if they are designed with their own enzymatic activity. this is usually done by associating dnazymes and ribozymes with asos. asos can also modify rnas to alter their stability and promote or inhibit degradation. asos also participate in direct translation inhibition by sterically blocking ribosomes. this steric block is formed when asos bind to mrna and prevent the association of the 40s and 60s ribosomal subunits during translation. furthermore, asos can modulate the splicing of rna into mature mrna transcripts. asos destabilize splice sites by binding to intron-exon junctions thereby preventing the binding of splice factors. if the disorder is known to be caused by a splicing defect, it is suggested that asos with this mechanism of action are used to return to normal function. usage of asos in this case can either promote a return to the original reading frame or can simply exclude the mutated dna segment of the gene. current aso therapies as of 2019, the fda has approved only 3 aso-mediated therapies for neurodegenerative diseases: antisense oligonucleotides mediated therapy for neurodegenerative disease apurva nayak 11 modifications from 2’ to 4’ positions constrain the sugar and result in stronger binding as well. it is also important that long-term and side effects are studied before the therapies are implemented. there are two possible reasons for off-target effects, hybridization dependent or independent. as asos are streamlined to be more efficient and their effects become more widespread, the off-target effects are likely to pose a larger problem. for example, as aso sequences get shorter, the risk of mismatched complementary binding rises and this leads to a larger risk of influencing the expression of non-target rnas. future development as a new type of therapy, asos can still be refined and applied to a broad variety of diseases outside of the few known so far. for example, asos mediated by rnase h are the most common mechanism of aso therapies. however, target rna suppression can also be achieved by other mechanisms. the modulation of splicing is very promising as an alternative aso mechanism. in this case, attuning splicing can result in an out-of-frame deletion that consequently causes nonsense decay of the transcript which overall, results in protein knockdown. most of the current aso-mediated therapies work by degrading rna; the opposite, increasing rna expression, however, is a much more complicated endeavor. in vivo, increasing the levels of proteins is a delicate task because there are not many genes to which this strategy is applicable. gene therapy and targeting inhibitory antisense transcripts in a process called antisense-mediated derepression are mechanisms of achieving increased protein levels, in vivo. liang et al. (2016) used asos to increase the efficiency of mrna translation. this study used asos that targeted open reading frames upstream of the target sequence to increase translation and thus increase protein levels. after the approval of aso therapies for dmd and sma, the potential of asos has been significantly broadened. for example, ongoing studies are developing aso-mediated therapies for huntington’s and alzheimer’s. huntington’s disease is caused by repeats of the sequence cag in the gene htt that codes for a polyglutamine section in the protein huntingtin. this same polyglutamine section is the site of mutations that lead to a number of other neurodegenerative diseases like spinocerebellar ataxias. asos are being developed to silence the cag section of huntingtin, but the issue with this approach is that it may cause downregulation of nontarget sequences that contain cag. other approaches include using asos to target the mutated hd allele, specifically polymorphisms of individual nucleotides, that a large majority of hd patients have. with regard to alzheimer’s, asos can be used to target the protein tau. alzheimer’s falls under the category of tauopathies, where tau is hyperphosphorylated and accumulates to form tangles in neurofibers. aso-mediated approaches are being developed to silence tau by targeting a number of different points in the gene expression pathway. eteplirsen for duchenne muscular dystrophy, nusinersen for spinal muscular atrophy and inotersen for familial amyloid neuropathy. duchenne muscular dystrophy is caused by a mutation in the gene dmd (human duchenne muscular dystrophy) that codes for the protein dystrophin. usually, dmd mutations result in a premature truncation of dystrophin. the aso used by eteplirsen acts on the pre-mrna of dmd and excludes exon 51. this causes a re-establishment of the reading frame and results in partial restoration of dmd function. spinal muscular atrophy (sma) is the result of a deficiency of the ‘survival of motor neuron’ (smn) protein caused by a loss of function mutation in both copies of the smn1 gene located on chromosome 5. in the treatment of spinal muscular atrophy, the gene smn2 is targeted to offset the smn protein deficiency. smn2 is a homologous gene to smn1 except it does not contain exon 7. the severity of sma increases as the copy number of the smn2 gene decreases. the aso nusinersen prevents the splicing silencer that removes exon 7 from the smn2 gene. as a result, the smn2 gene produces the smn protein. challenges in clinical application while some successful therapies have been developed, one of the main issues in using aso-mediated therapies for neurodegenerative disorders is effective delivery of the drug to the brain. antisense oligonucleotides are too large to cross the blood brain barrier. in order to reach the brain, the therapy is delivered through the spinal cord by injection into the cerebrospinal fluid.the spinal cord is the pathway of delivery that must be used. cerebrospinal fluid (csf) is produced by the choroid plexus and is stored in cerebral ventricles in the brain as well as in the spinal cord. asos can be safely administered by injecting them directly into csf in the spinal cord. the first phase of human clinical testing of an aso targeting the gene sod1 showed that the drug was successfully and safely injected into the csf but only reduced the mutant sod1 protein expression by about 12%. there is also the issue of sustainability for long term usage of aso-mediated therapies. chemically modified asos can have longer half-lives. for example, the modification 2’o’methoxyethyl can be added to asos. this increases binding affinity to mrna and has a half life of 6 months or more. aso-mediated therapies are still relatively new and many improvements need to be made to existing therapies before they can be considered a standard treatment. improving the specificity to targets is very important to prevent any off-target effects. during the development of asos, two main methods are used to study and improve specificity. the first is quantitative pcr to appraise the mrna expression when treated with asos. this method can be used to study where mismatches occurred and whether or not the mismatched binding to the aso resulted in any changes in gene expression of the target. the second method is transcriptome analysis or rna-sequencing of mouse tissues. the tissues extracted from mice do not have the mrna target and are studied for expression changes when treated with the aso. aso-mediated therapies can also be modified to enhance their pharmacokinetic properties like binding affinity and resistance to endogenous nucleases. for example, brain matters・volume v 12 this includes binding and blocking the start codon, splice factors or sequences. so far, the most successful approach has involved using asos to create an out-of-frame deletion by skipping specific exons that ultimately reduces tau protein levels. concluding statements aso-mediated therapies have shown to be a novel approach to treating neurodegenerative diseases. a lot of development and further research needs to be done to broaden the scope of applications of this therapeutic strategy. asos, as a new therapy, have a lot of room for improving specificity, efficiency, and rates of activity. further research needs to be done on enhancing aso selectivity without increased offtarget binding. as asos become a more prominent method of treating neurodegenerative diseases, it is important to study its applications to non-neurological disorders. bibliography bennett, c. frank, and eric e. swayze. “rna targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform.” annual review of pharmacology and toxicology, vol. 50, no. 1, 2010, pp. 259–293., doi:10.1146/annurev.pharmtox.010909.105654. daniel r. scoles, eric v. minikel, stefan m. pulst, neurol genet apr 2019, 5 (2) e323. doi:: 10.1212/nxg.0000000000000323 liang, xue-hai, and wen shen. “translation efficiency of mrnas is increased by antisense oligonucleotides targeting upstream open reading frames.” nature biotechnology, vol. 34, 11 july 2016, pp. 875–880., doi:https://doi.org/10.1038/nbt.3589. rinaldi, c., wood, m. antisense oligonucleotides: the next frontier for treatment of neurological disorders. nat rev neurol 14, 9–21 (2018). https://doi.org/10.1038/nrneurol.2017.148 stein, c a, and y c cheng. “antisense oligonucleotides as therapeutic agents--is the bullet really magical?” science , vol. 261, no. 5124, 20 aug. 1993, pp. 1004–1012., doi:science.8351515. smith, r. a. “antisense oligonucleotide therapy for neurodegenerative disease.” journal of clinical investigation, vol. 116, no. 8, 2006, pp. 2290–2296., doi:10.1172/jci25424. uhlmann, eugen, and anusch peyman. “antisense oligonucleotides: a new therapeutic principle.” chemical reviews, vol. 90, no. 4, 1990, pp. 543–584., doi:10.1021/cr00102a001. wurster, claudia d, and albert c ludolph. “antisense oligonucleotides in neurological disorders.” therapeutic advances in neurological disorders vol. 11 1756286418776932. 23 may. 2018, doi:10.1177/1756286418776932 13 https://doi.org/10.1038/nbt.3589 copy of volume 7 publication about brain matters brain matters discusses all things neuroscience, psychology, and biology written by uiuc’s very own. authors come from diverse backgrounds, such as computer science and engineering majors. not to mention, the journal welcomes all authors no matter their area of study or year. this diversity allows volumes to have a wide range of articles. the journal is mainly written for the college community yet is accessible to anyone as brain matters is uploaded as an open access journal format by the university library. sponsors the undergraduate neuroscience society (uns) sponsors the brain matters journal. uns is a uiuc registered student organization that is dedicated to establishing and growing the neuroscience community on campus. copy of volume 7 publication copy of volume 7 publication 4 a brief review on the nutrient effects on the brain and implications do yeon (jason) kim abstract nutrients affect overall human health in various ways and their importance has been well-documented in numerous scientific articles. recently, new evidence has suggested that diet plays a role in altering brain functions. such findings have evoked speculation as to how diet can influence brain morphology and impact cognitive functions. data from mice with modified diets and interpolated results from human studies with specific ingredients suggest that nutrients may act as a signaling molecule when broken down by cells to directly affect the brain itself. from well-controlled single diets to varying supplemental diets, new information has been found of how different diets influence brain functions and aging of the brain. introduction the human brain is a collective structure consisting of a myriad of neurons constantly firing signals to create, store, and recall memories. the major functional anatomy of the human brain is divided into four key parts: the parietal, frontal, occipital and temporal lobes (hoffman, 2017). each part comes with distinct functions. although each part can be separated into its respective functions, it is important to note that brain structure as a whole is highly interactive. therefore, the interactions of inner connections are not trivial and many questions about the function and architecture of the brain remain unanswered. even with contrast to the remarkable complexity of the brain, scientists have used a relatively simple approach to determine the influence of nutrients on brain morphology and its function. brain function and mental illnesses have often been associated with factors like mental stress and emotionality. in fact, in one study, researchers suggested that chronic stress leads to changes in brain structure and function (chetty et al., 2014). however, at a molecular level brain functions can also be affected by tangible, physical factors such as nutrients. after all, the cellular make-up of the brain results from the fundamental building blocks received from foods in general. hence, it is not surprising that food itself can affect the mental and cognitive functions of the brain. in one study, researchers have verified that tweaking the diet of mice models altered brain cell density, count, weight, and tissue morphology of the brain, leading to the belief that cognitive function and emotionality can be an influence as well (lemon et al., 2016). it is believed that gut hormones affected by various foods can enter in and out of the brain, interacting with various receptors on the brain itself. nutrients affect aging of the brain aging of the brain is commonly associated with a variety of negative changes including cognitive decline, sensory function loss, and neurodegeneration at the cellular level. among the many symptoms of an aging brain, common characteristics include chronic oxidative stress, resistance to insulin, mitochondrial dysfunction, muscle, and neural atrophy, and increased levels of inflammatory processes; actual mechanisms behind these processes are complex and are the topic of another discussion in themselves. in general, mitochondrial dysfunction and oxidative metabolism are the two main sources of oxidative stress in the brain contributing directly to cognitive, motor and sensory damage (antier et al., 2004; wang and michaelis, 2010; yin et al., 2014). neurons in the brain require a great deal of energy which is supplied by the atp consumption occurring in membrane ionic pumps, synaptic transmission, and channel activity. as a result of such demand, this can lead to increased free radicals which may inhibit the enzyme nadh dehydrogenase and cause a defect in mitochondria. impaired production of atp from dysfunctional mitochondria increases reactive oxygen species in the brain which contribute to the commonly observed aging process (shigenaga et al., 1994, lenaz, 1998; sastre et al., 2003). a recent study according to lemon et al. (2016) has revealed the ways to prevent neural decline through the use of multi-ingredient dietary supplements (mds). to explore these options, researchers from the study carefully chose key ingredients that have been proven to slow down or completely eradicate each of the five processes associated with aging. the supplements in the study were prepared in a liquid form and a 0.4 ml volume was soaked in a 1 cm x 1.5 cm x 1 cm piece of bagel and allowed to dry. each mouse was given exactly one piece of the bagel with or without multi-dietary supplements every day. each piece was eaten within 20 minutes to ensure that the mice received the equivalent and full dosage required for the study. transgenic growth hormone (tgm) mice were used to model older specimens because the overexpressed growth hormone allows tgm to mature and age faster (lemon et al., 2016). this allows researchers to study the effects of aging in a shorter period. results of the experiment demonstrated that various improvements in brain function are due to the mds treatment in the tgm mice. however, simple somatosensory tests, which included (a) landing response, (b) visual placing, (c) negative geotaxis, and (d) pinch reflex, did not show significant improvement compared to normal, untreated mice. this shows how further improvement from supplementation alone did not occur. however, there are other areas that have been improved to a certain extent. mds treated tgm brain cells showed significantly greater density as opposed to the brain cells of 12-month-old untreated tgm mice, implying that mds indeed slowed down the deteriorating effects of aging on the brain (lemon et al., 2016). in terms of tissue morphology, supplemental mice had a 16% increase in the molecular layer (ml) and 18% increase in the granular layer (gl) of the brain (lemon et al., 2016). the mitrial cell layer also showed an increase of up to 29% in treated mice. loss of mitral cells in aging rodents has been documented and the increase in these cells in the mds suggests that treatment potentially prevented these neurons from agerelated atrophy. in terms of behavioral influence on mice, the effect on the supplemented mice was significantly different from dim light to bright light. this suggests that supplemented mice demonstrated improved contextual discrimination which implies that aging mds treated mice had stronger cognitive function than their counterparts. in motor coordination, the untreated 12-month tgm mice showed severely hindered coordination compared to same age untreated normal mice, but mds supplement mice showed significant progress in terms of motor coordination (lemon et al., 2016). this implies that nutrients play a critical role in the aging of the brain in various areas. gut to brain connection the human body consists of complex systems of connections that interact with different parts of the body. for example, the enteric nervous system (ens) 5 consists of more than 100 million nerve cells lining the gastrointestinal tract from esophagus to rectum. while the brain and gut may appear to be two different tissue systems with little interaction, it is highly probable that events in the gut can trigger reactions in the brain and vice-versa. a piece of great evidence about the gut-to-brain connection can be found in the interaction between insulin and specific signal transduction receptors located in the hippocampus. insulin has been known to be a gut hormone produced in the pancreas and involved in changes in cognitive processing in the brain. as discussed above, the brain to gut connection plays a significant role in shaping the brain and further verifies the importance of nutrients. effects of specific nutrients on cognition there is a belief that a deficiency of omega-3 fatty acids in rodents results in impaired learning and memory. in addition, even in humans, omega-3 deficiencies have been linked with increased risk of mental disorders such as bipolar disorder, schizophrenia, dementia and dyslexia (peet, laugharne, mellor & ramchand, 1996). according to current data, a diet rich in omega-3 fatty acids can promote brain health. on the other hand, high contents of trans and saturated fats adversely influence brain cognition as described below. in rodent studies, so-called “junk food” with high trans and saturated fat content led to a decline in cognitive performance in rats as well as reduced hippocampal levels of bdnf related synaptic plasticity in only three weeks of such treatment. this once again implies that nutrients have a huge role in brain health (molten, barnard, ying, roberts, & gomezpinilla, 2002). at a molecular level, broken down foods can become building blocks for signaling molecules to promote neural synaptic plasticity. antioxidants and micronutrients, in particular, are other great examples known to influence learning capacity and memory performance of the brain. various micronutrients with an antioxidant capacity can influence these functions. however, constituents that make up an “antioxidant” substance are great in number and only a few of them has been extensively evaluated separately. two tannins (procyanidin and prodelphinidin), anthocyanins, and phenolics are well-known compounds with antioxidant properties commonly found in grapes, tea leaves, and seeds. researchers evaluated their influence on mice, and polyphenols have been shown to increase hippocampal plasticity to enhance learning and memory performance (casadesus et al., 2004). for example, alpha lipoic acid, which is found in meats such as the kidney, heart, and liver, and vegetables like spinach, broccoli, and potatoes, is a coenzyme important for energy homeostasis in mitochondria (liu, 2008). another example is a curcumin, curry spice, which has been shown to reduce memory deficits in animal models, implying that nutrients indeed have a positive effect on cognitive functions in the brain (frautschy sa, et al 2001). high salt diet on the brain it is an accepted fact that the human body requires a sufficient amount of sodium to stay healthy and maintain functioning. however, a high sodium diet is detrimental to cognitive function and seems to have a role in a variety of cardiovascular disorders (nwanguma and okorie, 2013). a high salt diet undeniably has a critical role in shaping human health, yet the exact mechanism with which a high salt diet impairs cognitive function and learning remains unknown. however, it is well-documented that excessive salt intake has undesirable physiological effects. various studies on animals have shown that such cases are true. increased oxidative stress in cells, as well as the generation of reactive oxygen species which can turn into free radicals, can damage the brain over time. however, according to a study where scientists compared 4-week and 7-week highsalt diets in mice, it was found that the more salt was consumed, the more weight the mice lost. it is also important to note that in the same study, it is mentioned that the mice consumed a gradual increase in food and water (ge et al., 2017). however, both short-term and long-term memories with mice treated with 7-week long high salt diets were impaired. the high 7-week salt group had disturbances in the hippocampal long-term potentiation (ltp). in addition, the same studied also showed that high salt diets induce oxidative stress and trigger metabolic reprogramming in the hippocampus (ge et al., 2017). high salt treatment is associated with neurotransmitter release, implying that nutritional diet specification such as a high salt diet can affect brain function. conclusion in-depth analyses have shown that by tweaking and controlling diet, even aging of the brain can be slowed down and functions can be restored to normal levels. further research is necessary to study the exact mechanism behind how specific nutrients can influence brain-cell interactions. both high and low levels of brain functioning are affected by nutrients as evidence shows, which is why it is crucial to research and modify other experimental diets in order to promote the health of the brain. references antier, d., carswell, h. v., julia brosnan, m., hamilton, c. a., mhairi macrae, i., groves, s., ... & dominiczak, a. f. (2004). increased levels of superoxide in brains from old female rats. free radical research, 38(2), 177183. casadesus, g., shukitt-hale, b., stellwagen, h. m., zhu, x., lee, h. g., smith, m. a., & joseph, j. a. (2004). modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. nutritional neuroscience, 7(5-6), 309-316. chetty, s., friedman, a. r., taravosh-lahn, k., kirby, e. d., mirescu, c., guo, f., ... & tsai, m. k. (2014). stress and glucocorticoids promote oligoden drogenesis in the adult hippocampus. molecular psychiatry, 19(12), 1275. frautschy, s. a., hu, w., kim, p., miller, s. a., chu, t., harris-white, m. e., & cole, g. m. (2001). phenolic anti-inflammatory antioxidant reversal of aβ-induced cognitive deficits and neuropathology. neurobiology of aging, 22(6), 993-1005. gómez-pinilla, f. (2008). brain foods: the effects of nutrients on brain function. nature reviews neuroscience, 9(7), 568. lemon, j. a., aksenov, v., samigullina, r., aksenov, s., rodgers, w. h., rollo, c. d., & boreham, d. r. (2016). a multiingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice. environmental and molecular mutagenesis, 57(5), 382-404. lenaz, g., bovina, c., d’aurelio, m., fato, r., formiggini, g., genova, m. l., ... & ventura, b. (2002). role of mitochondria in oxidative stress and aging. annals of the new york academy of sciences, 959(1), 199-213. liu, j. (2008). the effects and mechanisms of mitochondrial nutrient α-lipoic acid on improving ageassociated mitochondrial and cognitive dysfunction: an overview. neurochemical research, 33(1), 194-203. mcnay, e. c. (2007). insulin and ghrelin: peripheral hormones modulating memory and hippocampal function. current opinion in pharmacology, 7(6), 628-632. molteni, r., barnard, r. j., ying, z., roberts, c. k., & gomez-pinilla, f. (2002). a highfat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. neuroscience, 112(4), 803-814. nwanguma, b. c., & okorie, c. h. (2013). salt (sodium chloride) content of retail samples of nigerian white bread: implications for the daily salt intake of normotensive and hypertensive adults. journal of human nutrition and dietetics, 26(5), 488-493. peet, m., laugharne, j. d. e., mellor, j., & ramchand, c. n. (1996). essential fatty acid deficiency in erythrocyte membranes from chronic schizophrenic patients, and the clinical effects of dietary supplementation. prostaglandins, leukotrienes and essential fatty acids, 55(1-2), 7175. sastre, j., pallardó, f. v., & viña, j. (2003). the role of mitochondrial oxidative stress in aging. free radical biology and medicine, 35(1), 1-8. shigenaga, m. k., hagen, t. m., & ames, b. n. (1994). oxidative damage and mitochondrial decay in aging. proceedings of the national academy of sciences of the united states of america, 91(23), 10771-8. wang, x., & michaelis, e. k. (2010). selective neuronal vulnerability to oxidative stress in the brain. frontiers in aging neuroscience, 2, 12. yin, f., boveris, a., & cadenas, e. (2014). mitochondrial energy metabolism and redox signaling in brain aging and neurodegeneration. antioxidants & redox signaling, 20(2), 353-371. my name is sanjana venkataraman and i am a senior majoring in psychology. apart from my work with brain matters, i enjoy photography and have been a part of the flashpoint photography club. i also enjoy travel and singing. i have worked as a research assistant at the rhodes lab since i was a freshman and enjoy doing research in behavioural neuroscience. my research experience and interest in playing an active role in the communication of neuroscience motivated me to write for brain matters. there are numerous widely accepted short-term and longitudinal benefits of exercise. established health benefits include the prevention of several diseases and illnesses, lowering the risk of cardiovascular disease, diabetes, and certain kinds of cancers (clague and bernstein, 2012; chapman et al., 2013). exercise also positively impacts mental health by reducing likelihoods of developing depression and anxiety, and generally improving overall quality of life. these positive effects of exercise make it a rich, constructive area of study in the fields of psychology and neuroscience (mandolesi et. al., 2018). moreover, physical exercise has been known to positively impact the process of acquiring knowledge, or cognition in humans as well as rodents. there is evidence to support the idea that voluntary exercise has aided in combating some biological symptoms of diseases associated with the degeneration of the brain and nervous system (adlard, et al., 2005; voss et al., 2013). apart from studies that show improved cognitive ability in older adults, exercise has also shown to improve cognitive health across the lifespan (voss et al., 2011). this has been further established by examining different regions of the brain and their relationship with physical activity. a diverse variety of research has examined the changes in brain regions associated with exercise, with the most outstanding being those that take place in the region widely known to be responsible for learning and memory, the hippocampus. studies in humans have consistently corroborated this, with randomized clinical trials demonstrating increased volume and blood flow to the hippocampus (chaddock–heyman et al., 2016; erickson et al., 2009). across all brain regions that have been studied, the hippocampus is considered to be the most robust in its association with exercise. hippocampal activity has also been correlated with the speed of running (li et al., 2012; chen et al., 2011). neuronal indicators of hippocampal activity when mice voluntarily run on wheels have also raised the question of whether the activity generated by exercise is chiefly responsible for the observed survival of new cells in the dentate gyrus, a sub region of the hippocampus (clark et al., 2010, 2011), adding another dimension to the improved cognitive effects of exercise. given the abundance of research on exercise induced neurogenesis and its effects on improved cognitive behaviour and function, it is important to scrutinize the crucial connection between the hippocampus and physical activity, so that we better understand the origins of the brain and behaviour related benefits of exercise. by doing so with recent and well established lines of research that have pervaded the neuroscientific community, upcoming research can be contextualized appropriately and appreciated for its relevance to our own daily lives. neurogenesis is the growth of new neurons in the brain and has been studied substantively over the last two decades. rodent models have consistently supported the relationship between exercise and neurogenesis, suggesting that exercise increases the total number of neurons in the hippocampus by two to six-fold (mustroph et al., 2012.; rhodes et al., 2003). there are two primary hypotheses that address the origins of hippocampal neurogenesis. the first one is the muscle hypothesis that postulates signals associated with this neurobiological change originates from contracting muscles that are actively engaged during exercise (wrann et. al. 2013). the second leading hypothesis, which will be the focus of this review, suggests that the signals are generated from within the brain itself. this hypothesis holds that interactions within the central nervous system rather than the peripheral are associated with increased hippocampal plasticity, neurogenesis, and improved cognitive performance. running results in the immediate activation of the brain that lasts for the duration of the exercise. this can be seen through the lenses of theta oscillations and gamma oscillations as well as immediate early gene (ieg) induction. immediate early genes are genes that are activated briefly in response to external stimuli thus becoming markers of neuronal activity. theta oscillations are neural oscillations that occur in the brain and are best viewed through an electroencephalogram (eeg). theta waves have been rigorously studied in relation to the hippocampus. hippocampal theta activity is observed during several different tasks, an important one being motor activity. theta activations have been related to several different functions origins of exercise-induced neurogenesis 8 like memory, motor behavior, and attention. studies have demonstrated the positive correlation between voluntary movements and theta oscillation in the hippocampal formation or hpc (the hippocampus and related structures of the dentate gyrus and subiculum). in a running wheel experiment, the speed of running initiation was directly related to the onset frequency of hpc theta oscillations (bland and oddie, 2001, vanderwolf, 1969). correlations between speed and hippocampal theta have been reported in several different studies. li et al. (2012) reported that theta frequency is correlated with speed during the preparatory and initiation phases of wheel running while theta rhythms of middle frequency (6.5-9.5 hz) are correlated with speed consistently throughout an entire wheel running episode. hippocampal gamma waves mirror this speed-dependent effect. gamma waves are a neural oscillatory pattern implicated in working memory and attention. disruptions in gamma rhythm are commonly seen in disorders such as epilepsy and alzheimer’s disease which further validate its significance and its role in exercise and hippocampal activity. mice running on linear and y-shaped paths showed speed modulated increases in gamma frequencies. interestingly, theta-gamma coupling – the process whereby low frequency that oscillations modulate high frequency gamma oscillations – was also observed to increase with speed (chen et al., 2011; ahmed and mehta, 2012). moreover, research into iegs corroborates the phenomenon of activation in the brain following an acute bout of exercise. ieg-positive cells in the dentate gyrus and other regions of the hippocampus are significantly positively correlated with average running speed over an acute 90-minute period prior to euthanasia (rhodes et al., 2003). a study using the ieg c-fos (an indicator for neuronal activity) demonstrated that rodents running on treadmills at higher speeds showed greater c-fos expression or neuronal activity in sub-regions of the hippocampus, specifically the dentate gyrus and ca1 and ca3 areas (lee et al., 2003). wheel running is a commonly used model of exercise and has been implemented extensively in the study of exercise-induced neurogenesis. early studies established that voluntary running in mice given access to wheels was enough to increase neurogenesis. mice injected with brdu, an analog for thymidine that incorporates itself into the cellular dna and acts as a marker for neurogenesis, demonstrated twice as many surviving proliferating cells after being given access to a wheel for an extended period of time (mustroph et al., 2012; van praag et al., 1999). in a study by clark et al. (2010), we see an even clearer direct connection between ieg expression and neurogenesis in wheel running mice. the study examined the induction of the c-fos and neurogenesis in terms of cell proliferation and survival of new neurons in the dentate gyrus. results indicated that cell survival at the 25-day mark after the last brdu injection appeared to double in wheel running mice. exercise-induced c-fos expression also appeared to elevate and attenuate in accordance with cell survival, corresponding with peak levels of neurogenesis in the initial days of running. it is worth noting that elevations in exercise-induced c-fos expression and cell survival coincided with one another, adding another dimension to neuronal activity and the abundance of evidence in support of the central hypothesis makes it hard to dispute the role of endogenous brain activity in hippocampal neurogenesis. recent research has investigated a new perspective on exercise brain interactions, focusing on the idea that factors released from the muscles in the peripheral nervous system themselves travel across the blood brain barrier, and form the basis for hippocampal neurogenesis. among the initial molecules studied were insulin-like growth factor (igf) and vascular endothelial growth factor (vegf) (rendeiro and rhodes, 2018). the recently studied fndc5, is a protein that has its expression regulated by pgc-1α, another protein released from contracting skeletal muscles. a study demonstrated that fndc5, when delivered through peripheral injections, results in increased levels of the cleaved product of fndc5, a protein called irisin (wrann et al., 2013). several other studies have corroborated the role of irisin/fndc5 in the muscle hypothesis, some in conjunction with the neurotrophic factor brain derived neurotrophic factor (bdnf) (delezie and handschin, 2018; lourenco et al., 2018). bdnf, a member of the neurotrophin family, is among the most robustly researched factors that are associated with exercise induced hippocampal neurogenesis. bdnf has been demonstrated to peak in its expression a few schematic coronal view of a rodent brain section outlining the hippocampus, and within it, the dentate gyrus, ca1 and ca3 regions. adapted from “reovirus infection and tissue injury in the mouse central nervous system are associated with apoptosis by oberhaus,” s. m. et al., 1997, journal of virology, 71(3), 2100–2106 graphic illustrating the effect of exercise on the relationship between bdnf, fndc5 and pgc-1α, and their collective influence on neurogenesis and learning. adapted from “exercise induces hippocampal bdnf through a pgc-1α/fndc5 pathway,” wrann, c. d. et al., 2013, cell metabolism, 18(5), 649–659 9 weeks after birth, during the change from embryonic phase to adult phase in neurogenesis in mice. it is also shown to increase through gene expression in the hippocampus from treadmill and aerobic exercise (liu and nusslock, 2018). in wheel running mice, levels of bdnf mrna within the dentate gyrus of the hippocampus increased within a few days of exercise itself (neeper et al, 1995). further, hippocampal plasticity is also seen as an outcome of the administration of aicar. aicar can be defined as an agonist of the enzyme amp-activated protein kinase, (ampk) which works by restoring cellular energy levels, i.e. atp, when they are low by transporting glucose-oxidizing fatty acids in response to muscle contractions such as those that occur during exercise (schimmack et al., 2006). in a study by guerrieri and van praag (2015), mice were administered with aicar while remaining sedentary or tasked to run with a vehicle (control substance) injection for varying periods of time. mice in the group that were administered with aicar and that were made to run for 14 days showed significant increases in ampk levels compared to the control group. furthermore, both 7 and 14-day running groups showed a higher number of brdu positive cells compared to controls, indicating neurogenesis (guerrieri and van praag, 2015). ampk is also implicated in research aiming to establish the role of the myokine cathepsin b (ctsb) in exercise brain interactions. in a simulation of exercise conditions, aicar was administered in vitro to muscle cells. ctsb protein levels in the cultured cells increased significantly at 6 hour and 12 hour time points when treated with aicar as compared to controls. the same study also reported elevated levels of ctsb plasma levels due to running as well as elevated ctsb expression in the hippocampus (moon et al., 2016). the extent to which several of these factors, when isolated or operating in combination with one another can solely be considered responsible for the benefits of running and exercise is very much in dispute. more research in this area is needed for a cause-and-effect relationship to be formed between circulating myokines and effects of exercise (rendeiro and rhodes, 2018). having now established the consistency with which we see neurogenesis due to wheel running and myokines, as well as concomitant with hippocampal activity, it is important to revisit one of the driving forces behind this area of study. neurogenesis has several important implications for behaviours demonstrating learning and memory and cognitive performance in general. tasks like novel environment exploration and the morris water maze form an important part of the repertoire of measures that aim to assess learning and memory in rodents. mice with running wheels had twice the number of new neurons compared to sedentary mice and hence displayed a two-fold increase in the number of zif268+ (protein product of an ieg) cells following tasks like novel environment exploration and the morris water maze, both of which are tests to gauge spatial learning and memory. this suggests that the neurons generated by running are recruited in hippocampus-engaging tasks and behaviours. therefore, wheel running-induced neurogenesis can potentially play a functional role in behaviours that engage the hippocampus (clark et al., 2012). these findings with improved measurable behaviour are also supported by studies exploring the subject from a muscle-brain axis perspective. wild type mice treated with aicar demonstrate improved spatial memory (kobilo et al., 2011). the study by moon et al. (2016) found that ctsb knockout mice that were made to run did not display improvements in spatial memory as gauged by the morris water maze task. recent advances in molecular biology, such as optogenetics (the use of light to manipulate cellular activity through micro-led implants) and cellular tracing techniques, have enabled us to identify and localize cells within the hippocampus that play significant roles in memory. furthermore, cells responsible for particular brain functions like those relating to memory, can be manipulated to recapitulate an experience as if it were happening in real time (liu et. al., 2014). artificial recapitulation of complex experiences like exercise would allow us to assess the role of brain activity in neurogenesis. moreover, attempts are being made to isolate the main physiological constituents of exercise. the novel e-stim model attempted to evaluate the extent to which electric stimulation of hindlimb muscles in mice while they are anaesthetized or do not have their hippocampus activated, is sufficient to increase hippocampal neurogenesis. interestingly, there was a greater proportion of brdu positive cells in the dentate gyrus of the e-stim mice compared to a control group that was given a sham treatment, but the cells were identified as astrocytes, cells that support and nourish neurons (gardner et al., 2020). this brings us closer to delineating the causal mechanisms that are at play and other processes like astrogliogenesis (formation of new astrocytes) that may occur as a result of exercise. the growing body of research on the relationship between exercise like hippocampal activation as well as i) representative images of ieg cfos indicating neuronal activity in the dentate gyrus during control, mild, moderate and severe treadmill exercise. a = control group; b = mild-exercise group; c = moderate exercise group; d = severe-exercise groupgreater number of black dots indicate more cfos+ cells in the dentate gyrus of the hippocampus. ii) c-fos positive cells in each group. adapted from “dependence of rat hippocampal c-fos expression on intensity and duration of exercise.” by lee, t.h., et. al, 2003, life sciences, 72(12), 1421–1436. 10 skeletal muscle contraction, and improved cognitive behaviour is vital for therapeutic interventions for neurodegenerative diseases like alzheimer’s disease and their symptomatology. localizing the specific effects of muscle contractions, myokines and hippocampal activation are key to giving our understanding of exercise-brain interactions more depth and progressing towards clinical interventions in human research. references adlard, p. a., perreau, v. m., pop, v., & cotman, c. w. (2005). voluntary exercise decreases amyloid load in a transgenic model of alzheimer’s disease. the journal of neuroscience : the official journal of the society for neuroscience, 25(17), 4217–4221. https://doi. org/10.1523/jneurosci.0496-05.2005 ahmed, o. j., & mehta, m. r. (2012). running speed alters the frequency of hippocampal gamma oscillations. the journal of neuroscience : the official journal of the society for neuroscience, 32(21), 7373–7383. https://doi.org/10.1523/jneurosci.5110-11.2012 bland, b. h., & oddie, s. d. (2001). theta band oscillation and synchrony in the hippocampal formation and associated structures: the case for its role in sensorimotor integration. behavioural brain research. https://doi.org/10.1016/s0166-4328(01)00358-8 chaddock-heyman l, erickson ki, chappell ma, johnson cl, kienzler c, knecht a, drollette es, raine lb, scudder mr, kao sc, hillman ch, kramer af (2016) aerobic fitness is associated with greater hippocampal cerebral blood flow in children. developmental cognitive neuroscience 20:52-58. https://doi.org/10.1016/j. dcn.2016.07.001 chen, z., resnik, e., mcfarland, j. m., sakmann, b., & mehta, m. r. (2011). speed controls the amplitude and timing of the hippocampal gamma rhythm. plos one, 6(6), e21408. https://doi.org/10.1371/journal.pone.0021408 clague, j., & bernstein, l. (2012). physical activity and cancer. current oncology reports, 14(6), 550–558. https://doi. org/10.1007/s11912-012-0265-5 clark, p. j., bhattacharya, t. k., miller, d. s., & rhodes, j. s. (2011). induction of c-fos, zif268, and arc from acute bouts of voluntary wheel running in new and pre-existing adult mouse hippocampal granule neurons. neuroscience, 184, 16–27. https://doi. org/10.1016/j.neuroscience.2011.03.072 clark, p. j., kohman, r. a., miller, d. s., bhattacharya, t. k., haferkamp, e. h., & rhodes, j. s. (2010). adult hippocampal neurogenesis and c-fos induction during escalation of voluntary wheel running in c57bl/6j mice. behavioural brain research, 213(2), 246–252. https://doi.org/10.1016/j.bbr.2010.05.007 clark, p. j., bhattacharya, t. k., miller, d. s., kohman, r. a., deyoung, e. k., & rhodes, j. s. (2012). new neurons generated from running are broadly recruited into neuronal activation associated with three different hippocampus-involved tasks. hippocampus, 22(9), 1860–1867. https://doi.org/10.1002/hipo.22020 delezie, j., & handschin, c. (2018). endocrine crosstalk between skeletal muscle and the brain. frontiers in neurology, 9(aug). https://doi.org/10.3389/fneur.2018.00698 erickson, k. i., prakash, r. s., voss, m. w., chaddock, l., hu, l., morris, k. s., white, s. m., wójcicki, t. r., mcauley, e., & kramer, a. f. (2009). aerobic fitness is associated with hippocampal volume in elderly humans. hippocampus, 19(10), 1030–1039. https:// doi.org/10.1002/hipo.20547 gardner, j. c., dvoretskiy, s. v., yang, y., venkataraman, s., lange, d. a., li, s., boppart, a. l., kim, n., rendeiro, c., boppart, m. d., & rhodes, j. s. (2020). electrically stimulated hind limb muscle contractions increase adult hippocampal astrogliogenesis but not neurogenesis or behavioral performance in male c57bl/6j mice. scientific reports, 10(1), 19319. https://doi.org/10.1038/s41598-020-76356-z guerrieri, d., & van praag, h. (2015). exercise-mimetic aicar transiently benefits brain function. oncotarget, 6(21), 18293–18313. https://doi.org/10.18632/oncotarget.4715 kobilo, t., guerrieri, d., zhang, y., collica, s. c., becker, k. g., & van praag, h. (2014). ampk agonist aicar improves cognition and motor coordination in young and aged mice. learning & memory (cold spring harbor, n.y.), 21(2), 119–126. https://doi. org/10.1101/lm.033332.113 lee, t. h., jang, m. h., shin, m. c., lim, b. v., kim, y. p., kim, h., choi, h. h., lee, k. s., kim, e. h., & kim, c. j. (2003). dependence of rat hippocampal c-fos expression on intensity and duration of exercise. life sciences, 72(12), 1421–1436. https://doi.org/10.1016/ s0024-3205(02)02406-2 liu, x., ramirez, s., & tonegawa, s. (2013). inception of a false memory by optogenetic manipulation of a hippocampal memory engram. philosophical transactions of the royal society of london. series b, biological sciences, 369(1633), 20130142. https://doi. org/10.1098/rstb.2013.0142 liu, p. z., & nusslock, r. (2018). exercise and hippocampal neurogenesis: a dogma re-examined and lessons learned. neural regeneration research, 13(8), 1354–1355. https://doi. org/10.4103/1673-5374.235225 lourenco, m. v., guerra, l. a., wilcock, d. m., kincheski, g. c., alves-leon, s., zhang, h., … beckman, d. (2018). exercise-linked fndc5/irisin rescues synaptic plasticity and memory defects in alzheimer’s models. nature medicine, 25(1), 165–175. https://doi.org/10.1038/s41591-018-0275-4 mustroph, m. l., chen, s., desai, s. c., cay, e. b., deyoung, e. k., & rhodes, j. s. (2012). aerobic exercise is the critical variable in an enriched environment that increases hippocampal neurogenesis and water maze learning in male c57bl/6j mice. neuroscience, 219, 62–71. https://doi.org/10.1016/j.neuroscience.2012.06.007 moon, h. y., becke, a., berron, d., becker, b., sah, n., benoni, g., janke, e., lubejko, s. t., greig, n. h., mattison, j. a., duzel, e., & van praag, h. (2016). running-induced systemic cathepsin b secretion is associated with memory function. cell metabolism, 24(2), 332–340. https://doi.org/10.1016/j.cmet.2016.05.025 neeper, s. a., gómez-pinilla, f., choi, j., & cotman, c. w. (1996). physical activity increases mrna for brain-derived neurotrophic factor and nerve growth factor in rat brain. brain research, 726(1-2), 49–56. https://doi.org/10.1016/0006-8993(96)00273-9 oberhaus, s. m., smith, r. l., clayton, g. h., dermody, t. s., & tyler, k. l. (1997). reovirus infection and tissue injury in the mouse central nervous system are associated with apoptosis. journal of virology, 71(3), 2100–2106. https://doi.org/10.1128/jvi.71.3.21002106.1997 rendeiro, c., & rhodes, j. s. (2018). a new perspective of the hippocampus in the origin of exercise-brain interactions. brain structure & function, 223(6), 2527–2545. https://doi.org/10.1007/ s00429-018-1665-6 rhodes, j. s., garland, t., jr, & gammie, s. c. (2003). patterns of brain activity associated with variation in voluntary wheel-running behavior. behavioral neuroscience, 117(6), 1243–1256. https://doi.org/10.1037/0735-7044.117.6.1243 schimmack, g., defronzo, r.a., musi, n. (2006) amp‐activated protein kinase: role in metabolism and therapeutic implications. diabetes, obesity and metabolism, 8(6), 591-602. https://doi.org/10.1111/j.1463-1326.2005.00561.x vanderwolf ch (1969) hippocampal electrical activity and voluntary movement in the rat. electroencephalogr clin neurophysiol 26(4):407–418. https://doi.org/10.1016/0013-4694(69)90092-3 van praag, h., shubert, t., zhao, c., & gage, f. h. (2005). exercise enhances learning and hippocampal neurogenesis in aged mice. the journal of neuroscience : the official journal of the society for neuroscience, 25(38), 8680–8685. https://doi.org/10.1523/ jneurosci.1731-05.2005 voss, m. w., nagamatsu, l. s., liu-ambrose, t., & kramer, a. f. (2011). exercise, brain, and cognition across the life span. journal of applied physiology (bethesda, md. : 1985), 111(5), 1505–1513. https://doi.org/10.1152/japplphysiol.00210.2011 voss, m. w., vivar, c., kramer, a. f., & van praag, h. (2013). bridging animal and human models of exercise-induced brain plasticity. trends in cognitive sciences, 17(10), 525–544. https://doi. org/10.1016/j.tics.2013.08.001 wrann, c. d., white, j. p., salogiannnis, j., laznik-bogoslavski, d., wu, j., ma, d., spiegelman, b. m. (2013). exercise induces hippocampal bdnf through a pgc-1α/fndc5 pathway. cell metabolism, 18(5), 649–659. https://doi.org/10.1016/j.cmet.2013.09.008 11 introduction one of the negative consequences of cancer is the continuous and unregulated proliferation of cancer cells. unlike regular cells which grow to appropriately regulated signals, cancer cells grow and divide “uncontrollably”, spreading to normal tissues and organs throughout the body by a process called metastasis. (cooper, 2000) the unregulated growth of cancer cells is the result of an accumulation of abnormalities within multiple cell regulatory systems and is reflected in a manner that distinguishes cancer cells from their counterparts. these abnormalities can range from various types of mutations in the dna sequence that can either cause issues with tumor suppressor genes or activating cancer promoting genes. with respect to cancer pathology, the most important issue is the distinction between malignant and benign tumors. (cooper, 2000) a tumor is any abnormal proliferation of cells. a benign tumor such as a skin wart remains stagnant in a specific location and does not spread to other tissues and parts of the body. a malignant tumor can spread to nearby tissues as well as throughout the body via the circulatory and lymphatic systems through metastasis. (cooper, 2000). brain tumors are a collection of neoplasms that arise either from within the brain itself, or from systemic tumors that have metastasized to the brain. symptoms of brain tumors include seizures, headaches, fatigue and cognitive dysfunction. (butowski, 2015) there are currently over 120 types of cancers and tumors that effect the brain, however some of the more common ones are pilocytic astrocytoma’s, ependymomas, and medulloblastomas in children, and the diffuse astrocytic tumours (including astrocytoma, anaplastic astrocytoma’s, and glioblastomas), oligodendroglia’s, and meningioma’s in adults. (collins, 2004) . ependymomas are glial cell tumors that typically arise from the lining cells of the blood vessels of the brain and are less known to be found outside of the central nervous system. these tumors are genetically distinct from each other and affect children more than adults. (zamora, 2020) ependymoma tumor diagnosis: pathophysiology and prognosis of pediatric and adult patients christopher jones ependymomas are a rare type of tumor that affects the central nervous system (cns) of adolescents and adults. the tumor derives from the ependymal cells which are responsible for lining the ventricles containing cerebrospinal fluid within the brain and spinal cord. while pediatric patients are more likely to develop the tumor in the brain, adult patients mainly develop the tumor in the spinal cord region. (gerstner, 2018). ependymomas range from being slow growing grade i tumors to malignant and fast growing grade iii tumors which are known as anaplastic. current medical treatments for this tumor provide more positive outcomes for adult patients versus pediatric patients. this paper will explore the pathophysiology of the disease in both patient types in order to provide insight into possible differences that better explain the clinical outcome abstract ependymomas explained since ependymomas rarely spread outside the central nervous system, they do not follow the typical classification system. the classification starts with grade i tumors which are slow growing and are often considered benign, including subependymomas and myxopapillary ependymomas. this means they are less likely to be fatal. subependymomas arise in the ventricular walls and are common in the fourth or lateral ventricles. they are histologically characterized by a hypocellular tissue presenting clusters of cells with a bland nucleus surrounded by glial matrix. myxopapillary ependymomas arise in the cauda equina, filum terminale or conus medullaris, and present histologically as pseudopapillary structures with mucin-rich microcysts, the cells are cuboidal and radially arranged surrounding a myxoid stroma. these regions are in the tailbone or the base of the spinal cord. these tumors would occur in mostly the adult patient subtype. grade ii ependymomas are present in papillary structures. cells are arranged regularly and present a clear cytoplasm. grade iii, are anaplastic ependymomas, presenting with abundant mitotic cells with pseudopalisading necrosis. this type is more deadly (zamora, 2020). ependymomas develop in all age groups but occur mostly in children and rarely in adults. according to the 2014 report published by the central brain tumor registry of the united states, ependymomas account for 5.2% of all brain and cns imaging of a pediatric brain tumor (2020). 5 6 tumors in children and adolescents aged 0–19 years. with regards to ethnicity, the incidence rate per 100,000 is 0.40 in caucasians versus 0.27 in african american (wu 2016). the survival rate is the highest for those aged 20–44 years and gets lower with increasing age at the time of the diagnosis. the 10-year survival rate is only 28.1% in those aged older than 75 years. in children and adolescents aged 0–19 years, the 10-year survival rate is 66%. (wu 2016) the prognosis of this tumor type is mainly based on the location of the tumor as well as the age of the patient. a study conducted by rodriguez analyzed 2408 ependymoma cases2132 belonging to the grade 2 category and 276 belonging to the grade 3 category from the surveillance, epidemiology and end results database 1997–2005. some of the factors that contributed to poor clinical outcomes were younger age, male sex, higher tumor grade, intracranial location, and failure to undergo surgical resection. even with these findings, the use of the central registry does suggest possible issues with diagnosis. analysis of ependymoma cases in a single institution found that nearly 20% of cases had been misdiagnosed as another histological type of neoplasm prior to expert review. ( wu, 2016) in order to understand how the prognostic factors for pediatric patients are different from those of adults, (amirian et al, 2016) the ependymoma cases from the seer database are analyzed separately for pediatric and adult patients. anaplastic and infratentorial location of tumors were associated with increased mortality rate in pediatric cases, while a supratentorial location was associated with higher mortality rate in adult patients. surgical resection proved to be beneficial for both pediatric and adult patients. ( wu, 2016) the unfavorable prognostic impact of a supratentorial location was shown by analysis from a study involving seventy patients aged older than 17 years. however, only older age, and not supratentorial location, was found to be an unfavorable prognostic factor by multivariate analysis from the study. ( wu, 2016) a single institution study of 123 adult ependymoma patients was conducted at the university of texas md anderson cancer center. forty patients had tumors in the brain, 80 in the spinal cord, and 3 at both locations. although most of the tumors were grade i or ii, the study showed that brain location (versus spinal cord) and tumor anaplasia were associated with a worse outcome in adults measured by both overall survival (os) and progression-free survival (pfs) (wu 2016). ependymal tumors have a rare occurrence, comprising 1.7% of all brain tumors, as reported in the cbtrus statistical report. it has been difficult to find an effective treatment for the disease due to the low percentage of occurrence of these tumors (zamora, 2020). studies have shown an improved survival for patients who undergo resection with adjuvant radiation therapy. there is minimal and limited evidence supporting chemotherapy for adult ependymomas (zamora, 2020). currently none of the established guidelines use the molecular subgroups to guide treatment of ependymoma. the current consensus recommends that patients with pf-epn-a positive ependymoma, who are older than 12 months undergo maximal safe micro-neurosurgical removal in addition to local radiotherapy. (zamora, 2020). for intracranial ependymomas, surgery is the main treatment. complete resection without residual disease has presented better clinical outcomes and better overall survival rate than partial resection. ( zamora, 2020) as discussed previously, there is insufficient evidence to support the use of chemotherapy. patients who are long term survivors from central nervous system tumors present a diverse array of complications, including neurological deficits, cognitive limitations, hearing loss, endocrine and growth abnormalities, and secondary malignancies. adult patients may present long term complications, most commonly fatigue, numbness and tingling, pain, and disturbed sleep. ( zamora, 2020)childhood intracranial ependymoma has a poor prognosis, especially in young children when a gross total resection cannot be performed. even without radiologically proven residuum, around two-thirds of these young children will have a relapse. (grill, 2003). adjuvant therapy is necessary for most, if not all, patients. craniospinal irradiation combined with posterior fossa boost has deleterious effects on cognition. pediatric oncology teams have tried to use chemotherapy to avoid irradiation and reduce irradiation fields to the tumor bed without altering the prognosis. cisplatin, at a dose of 120 mg is the only single agent that has reproducibly shown some efficacy in ependymoma. (grill, 2003) despite some combinations showing efficacy in the adjuvant setting, childhood intracranial ependymomas can be considered chemo resistant. the overexpression of the multidrug resistance-1 gene and the 06-methylguanine-dna methyltransferase have been implicated as possible mechanisms for this phenomenon. as the use of chemotherapy with current agents is questionable, phase ii studies with new agents and combinations become necessary. (grill, 2003) since the main problem of this disease is local relapse, it may not be necessary to irradiate the whole posterior fossa region. however, local control of the disease by irradiation must be improved. in this respect, hyperfractionation or radio sensitizers may be valuable therapeutic options. the treatment of children with ependymoma is a challenge for all caregivers. there is no doubt that any possible improvement in the management of this rare tumor will only be the result of well-designed cooperative trials (grill 2003). a mri image of an ependymoma tumor in the spinal cord (n.c.i, 2021). conclusion ependymomas are a very aggressive type of brain tumor that occur in both pediatric and adult patient types. brain matters・volume v issue ii while most cases of this tumor type effect pediatric patients in the brain with very little metastasis from other regions of the body, it still has a worse prognosis compared to adult patients. the common treatment for these tumors include surgery as well as chemotherapy, however the tumor has shown to be chemo resistant. typically when a tumor is chemo resistant it will end up growing back not too long after the chemotherapy and continue to spread. there has been research conducted that shows chemotherapy may not be the best treatment due to its lasting complications it may cause. therefore, upon initial surgery, it is recommended that the surgeons remove most of the tumor in order to try and eliminate as much as possible. more research needs to be done to understand ependymomas on a molecular level in order to offer a more effective treatment for pediatric “patients”. references 1. butowski n. a. (2015). epidemiology and diagnosis of brain tumors. continuum (minneapolis, minn.), 21(2 neurooncology), 301–313. https://doi.org/10.1212/01.con.0000464171.50638.fa 2. collins v. p. (2004). brain tumours: classification and genes. journal of neurology, neurosurgery, and psychiatry, 75 suppl 2(suppl 2), ii2–ii11. https://doi.org/10.1136/jnnp.2004.040337 3. cooper gm. the cell: a molecular approach. 2nd edition. sunderland (ma): sinauer associates; 2000. chapter 15, cancer. available from: https://www.ncbi.nlm.nih.gov/books/nbk9878 4. gerstner, e. r., & pajtler, k. w. (2018). ependymoma. seminars in neurology, 38(1), 104–111. https://doi.org/10.1055/s-0038-1636503 5. grill, j., pascal, c., & chantal, k. (2003). childhood ependymoma: a systematic review of treatment options and strategies. paediatric drugs, 5(8), 533–543. https://doi.org/10.2165/00148581-200305080-00004 6. wu, j., armstrong, t. s., & gilbert, m. r. (2016). biology and management of ependymomas. neuro-oncology, 18(7), 902–913. https://doi.org/10.1093/neuonc/now016 7. zamora ea, alkherayf f. ependymoma. [updated 2020 jun 30]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2021 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk538244/ 8. rare pediatric brain cancer. (2020). [photograph]. pediatric brain cancer. https://www.google.com/url? sa=i&url=https%3a%2f%2fwww.soundhealthandlastingweal th.com%2fhealth-news%2finsights-into-diagnosis-andtreatment-of-rare-pediatric-braincancer%2f&psig=aovvaw09kfbxnwob0y4sv0nkcmv&ust=1624466974403000&source=images&cd=vfe&ve d=0caoqjrxqfwotcpjwujzzq_ecfqaaaaadaaaaaba 9. n.c.i. (2021). ependymoma diagnosis and treatment [photograph]. national cancer institute. https://www.google.com/url? sa=i&url=https%3a%2f%2fwww.cancer.gov%2frare-brainspinetumor%2ftumors%2fependymoma&psig=aovvaw1v6ss0v kdrdacfalss7ox0&ust=1624467375953000&source=imag es&cd=vfe&ved=0caoqjrxqfwotcpi72tnaq_ecfqaaaaad aaaaabad 7 https://doi.org/10.1212/01.con.0000464171.50638.fa https://doi.org/10.1136/jnnp.2004.040337 https://www.ncbi.nlm.nih.gov/books/nbk9878 https://doi.org/10.1055/s-0038-1636503 https://doi.org/10.1093/neuonc/now016 https://www.ncbi.nlm.nih.gov/books/nbk538244/ copy of volume 6 publication social media effect on brain plasticity neha bashir the school bell rings amongst the sounds of high-pitched chattering of a suburban high school. lucy, a young freshman, was the type of student to arrive to class five minutes early, already starting the assigned homework for the day. hardworking and persistent, lucy always achieved high grades in her studies. however, her infatuation for social media began to affect how well she was doing in class. every day, lucy scrolled through her social media feeds for hours on end. even if she had an exam the next morning, she would stay up late at night, hooked to the colorful apps of her phone. with no willpower to study anymore, her grades started to decline. she had trouble concentrating in class, and her schoolwork reflected her lack of motivation. lucy’s addiction to social media provides insight on brain plasticity and the effect social media exposure has on it. brain plasticity refers to the brain’s way of changing and adapting to new experiences, where it grows new networks of functional change from learning (cherry, 2022). national statistics show that the average person spends roughly 3 hours on social media every day, and teenagers spend about 8 hours of phone screen time (georgiev, 2023). by studying the correlation between excessive exposure to social media on brain plasticity we can possibly discern the real negative effects of mindlessly scrolling on attention and memory deficits. most high school students hone their ability to memorize facts quickly and efficiently in an effort to retain the most important information from a lesson. however, when social media excessively consumes a person’s thoughts, they try using their multitasking skills to accomplish all the requirements social media demands. studies have shown that multitasking leads to a decrease in concentration and reduction of absorption in experiences, causing memories to fade (tamir et al, 2018). similarly, social media has introduced the use of shorthand typing, where statements like “lol” take place of “laughing out loud.” these quick mnemonics are labeled “crutch” and are harmful in offloading relevant information and then forgetting the important information (tamir et al, 2018). memory has shown to have a negative relationship with social media, as it hinders people’s abilities to remember information. however, memory is not the sole victim of social media, as attention decreases just as easily from social media influence. a study was performed to determine the correlation between social media and psychological distress of attention control, where it was concluded that social media has a positive relationship with lower levels of attention control (mahalingham et al., 2021). using social media provides people access to control how long they want to pay attention to a certain video, picture, or text message. the brain then translates this control and applies it to other aspects of life, like being in a class where the information could be presented in a boring way. the brain can stop paying attention and focus on other things because the brain is already conditioned to be in control of how little time a person must spend on something. the figure below shows a decrease in memory consistent through the study, as well as an increase in mind wandering. as social media allows people control to swipe as fast away from a certain screen image, the brain shortens its attention span for all life events. figure 1. the figure above shows the correlation between social media use and memory and mind wandering. given three studies, a positive control of no media use, and two experimental of recording and sharing, it can be noted that there is a discrepancy between the three groups in memory and mind wandering. there is a decrease in memory for both experimental groups and an increase in mind wandering in recording group generally and in one case for sharing as well. social media platforms continue to enthrall millions of people, but it is important to note the detrimental effects it could have on brain plasticity. social media has proven to be a useful tool to remain connected, however excessive screen time has detrimental effects on the brain, but consider just the mechanisms behind social medias affect on memory and how to mitigate the outcome. 41brain matters volume vi cherry, kendra. (2022). “how brain neurons change over time from life experience.” verywell mind, https://www.verywellmind.com/what-is-brain-plasticity2794886. georgiev, deyan. (2023).“how much time do people spend on social media in 2023?” techjury, https://techjury.net/blog/time-spent-on-socialmedia/#gref. tamir, d, et al. (2018). “media usage diminishes memory for experiences.” journal of experimental social psychology, academic press, https://www.sciencedirect.com /science/article/pii/s002210311730505x. mahalingham, tamsin, et al. (2021). “attention control moderates the relationship between social media use and psychological distress.” journal of affective disorders, https://www.sciencedirect.com/science/article/pii/s0165 032721011563. references 1. 2. 3. 4. 42brain matters volume vi copy of volume 7 publication copy of volume 7 publication copy of volume 7 publication copy of volume 6 publication unlocking the inner genius within shireen aydogan introduction for much of his adolescence jason padgett, a college dropout, lived a typical party life and had no interest in education, especially mathematics. all of this changed when he suffered a blow to the back of his head during an attack outside a bar one night. padgett was rushed to the hospital and diagnosed with a concussion and a bleeding kidney. it was not long after his return home that he noticed his behavior drastically changed and that he was seeing everything from a different perspective. padgett stated, “water coming down the drain didn’t look like it was a smooth, flowing thing anymore, it looked like these little tangent lines” (keating, 2020). for the first time in his life, padgett was observing everything through a peculiar lens and he knew something was quite strange. he turned to the internet with hope of an explanation to the unique vision caused by his trauma, but was unsuccessful. oddly enough, he was finally able to explain what he was seeing with drawings, which are commonly known as fractals, or repeating geometric patterns. he realized that he acquired a rare talent for physics and mathematics in particular. most fascinatingly, he is the only person known to date who can not only see, but also draw fractals. savant syndrome jason padgett is believed to have acquired savant syndrome. savant syndrome is a rare condition in which people, typically who are mentally impaired, demonstrate remarkable talent. less than 1% of individuals have been diagnosed with savant syndrome, but it is estimated that 1 in 10 people who have autism have some level of savant abilities. the characteristics of acquired savant syndrome are parallel to people with autism who have savant syndrome. the major difference is that acquired savants discover a prodigious ability that laid dormant after suffering traumatic brain injury (tbi). a tbi is a disruption in the normal function of the brain caused by a sudden injury that causes acute and irreversible damage to the parenchyma (ng and lee, 2019). the most severe forms of tbi can cause permanent damage and lingering side effects. common side effects include headaches and loss of memory as well as consciousness (argawal et al., 2020). connection between traumatic brain injury and acquired savant syndrome while many side effects are common with tbis, it is a particularly high risk factor for developing frontotemporal dementia (ftd), a deterioration of the frontal and temporal lobes. the frontal and temporal lobes of the human brain are highly developed and serve as a major differentiator abstract people with savant syndrome are characterized by rare intellectual gifts in one or more specific areas. acquired savant syndrome occurs, in most cases, after a traumatic brain injury (tbi) and is associated with the development of frontotemporal dementia (ftd). specifically damage to the left temporal lobes caused by ftd has been linked to the acquisition of savant skills. the left-right compensation theory explains the process responsible for acquiring new abilities. it explains that the inhibition of pathways on the left side of the brain, specifically the temporal lobes, can cause compensatory growth on the right side of the brain. allan synder's experiment utilizing transcranial direct current stimulation (tdcs) demonstrates this theory utilizing low levels of electrical current targeting the left region of the brain to stimulate the formation of new neural connections on the right side. relatively new technologies and current research is promising to understanding acquired savant syndrome and gives light to possibilities of unlocking one's inner genius. figure 1. one of jason padgett’s hand drawn fractals, quantum nautilus. it describes the fact that all things in the universe are in constant motion and rotating around something else (padgett, 2006) figure 2. a comparison of coronal mri scans demonstrating the differences in a savant (right) (padmanaban et al., 2020) and a non savant (left) (corrigan et al., 2012), specifically in hippocampi. 25brain matters volume vi similar to acquired savants, participants of allan synders experienced discernible changes in their neural activity. the tdcs forced redistribution of electric circuits in the left hemisphere and in turn allowed stimulation of neurons on the right side. although for acquired savants, damage to the temporal lobes is what ultimately allows “rewiring” of neural pathways and domination of the right hemisphere (stanmissouri, 2019). the ability of the brain to empower neurons to form new connections is known as neuroplasticity. that is what neuroscientists believe is responsible for the expression of a new ability that otherwise was not present, or “hiding”. currently, tdcs is available online for a fairly cheap price and its popularity is steadily growing. in recent studies, tdcs constitutes a promising therapeutic intervention for psychiatric disorders such as people with major depressive disorder (bennabi and haffen, 2018). commercial headsets have become available as well and are just one click away from users. the headset’s stimulation encourages the brain to form new connections enhancing users' process of learning. professional skiers of the olympic national team train using electric stimulation headbands known as halo (yuhas, 2018). targeted audiences for companies selling tdcs also include the average student who wants to perform better in their next exam although neuroscientists have raised concerns about this practice. there are still many unknowns to what long-term side effects tdcs can have after repeated use as well as how the other regions of the brain will react. emiliano santarnecchi, a neurologist at harvard medical school, also emphasized that each brain is different and that individuals may react differently to the stimulation (yuhas, 2018). future research and outlook despite this remarkable technology, the tdcs has not allowed people to acquire prodigious capabilities similar to the abilities of people with savant syndrome. with this being said, there are still many things about savants that are yet to be fully elucidated. given the low prevalence rate of extraordinary savant skills, there have been limited studies including savants. while this is a setback, technology that is more sophisticated, like tdcs has allowed researchers to learn more about the brain functions, thus giving more insight to acquired savant syndrome. through a relatively new approach to the positron emission tomography (pet) called ambulatory microdose positron emission tomography (ampet) researchers have been able to understand more about brain activity during various activities (freeman, 2015). between the abilities that humans and non-humans have. ftd is typically a language or behavior disorder and affects the anterior temporal lobes (atls) which are the center for semantic knowledge or general information that one has acquired. the orbitofrontal cortex which is involved in social and emotional behavior is also targeted by this disease (young et al., 2017). this specific deterioration has been unexpectedly linked to the acquisition of savant-like talent (heaton & wallace, 2004). not only is ftd linked to savant syndrome, but it seems that patients with ftd affecting the left-temporal lobe are most likely to acquire savant syndrome. a research study which investigated patients with newly acquired savant-like skills in the early stages of ftd determined that 4 out of 5 patients had the left-temporal variant of ftd. in an earlier research study, the inhibition of certain signals, specifically from the left hemisphere of the temporal lobe, was found responsible for inducing savant-like capabilities (miller, 1998). a plausible explanation for this occurrence is the left-right compensation theory that states the inhibition of the left hemisphere can cause compensatory growth in the right side of the brain (snyder, 2009). the formation of the new connections in the right region of the brain fosters new abilities and causes a burst of creativity. although savant syndrome activates specific parts of the brain through formation of new neural connections, it destroys others. people who acquire savant syndrome are rare cases of geniuses, yet most have encountered behavioral disorders connected with tbi. in jason pagdett’s case, his tbi brought on obsessive compulsive disorder, specifically germaphobia and agoraphobia (keating, 2020). this presents the fundamental question of whether we can tap into and become geniuses without the side effects of tbi. looking into these possibilities, allan snyder, a neuroscientist at the university of sydney, conducted an experiment using transcranial direct current stimulation (tdcs) to induce changes to cortical excitability of the left hemisphere of the temporal lobe. the subjects were asked to solve a critical thinking puzzle known as the “nine-dot” puzzle before tdcs yet all were unsuccessful. during the tdcs, 40% of participants were able to solve the same intellectual challenge (chi & snyder, 2016). like people who acquired savant syndrome, the participants of this experiment expressed a unique ability that was not present before (piore, 2013). this experiment not only demonstrated the possibility of localizing regions of the brain responsible for savant-like talents, but it also shed light on the possibility of unlocking one's inner genius. figure 3. professor allan synder displays the device used to electrically stimulate the brain, commonly referred to as the “thinking cap” (wynne, 2011). figure 4. liftid, a commercial tdcs device available that recommends 20 minutes usage a day to maximize attention, focus, and alertness (rpw technology, 2022). 26brain matters volume vi emiliano santarnecchistann-missouri, eric. (2019, november 5). your brain can rewire itself after traumatic injury. futurity. retrieved january 3, 2022, from https://www.futurity.org/traumatic-injury-brains-2202932-2/ treffert, d. a. (2015, january 1). accidental genius. scientific american. retrieved november 17, 2021, from https://www.scientificamerican.com/article/accidentalgenius/ wynne, p. (2011, february 11). brain-zapping 'thinking cap' just might work. nbcnews.com. retrieved january 8, 2022, from https://www.nbcnews.com/id/wbna41534303 lindau m, almkvist o, kushi j, boone k, johansson se, wahlund lo, cummings jl, miller bl (2000). first symptoms--frontotemporal dementia versus alzheimer's disease. dement geriatr cogn disord. 5, 286-93. doi: 10.1159/000017251. takahata, k., & mimura, m. (2010). acquired savant syndrome in frontotemporal dementia. rinsho shinkeigaku, 50(11), 1017–1017. https://doi.org/10.5692/clinicalneurol.50.1017. ng, s. y., & lee, a. y. (2019). traumatic brain injuries: pathophysiology and potential therapeutic targets. frontiers in cellular neuroscience, 13. https://doi.org/10.3389/fncel.2019.00528 bennabi, d., & haffen, e. (2018). transcranial direct current stimulation (tdcs): a promising treatment for major depressive disorder?. brain sciences, 8(5), 81. https://doi.org/10.3390/brainsci8050081 yuhas, d. (2021, april 8). students are zapping their brains to get ahead in school but evidence for the practice is limited. the hechinger report. retrieved january 27, 2022, from https://hechingerreport.org/students-zapping-brains-getahead-school-evidence-practice-limited/ agarwal, n., thakkar, r., & than, k. (2020, march 2). traumatic brain injury. aans. retrieved december 18,2021,fromhttps://www.aans.org/en/patients/neurosurg ical-conditions-and-treatments/traumatic-brain-injury chi rp, snyder aw. (2002, may). brain stimulation enables the solution of an inherently difficult problem. neurosci lett, 515(2), 121-4. doi: 10.1016/j.neulet.2012.03.012. corrigan, n.m., richards, t.l., treffert, d.a. and dager, s.r. (2012) toward a better understanding of the savant brain. comprehensive psychiatry, 53, 706-717. https://doi.org/10.1016/j.comppsych.2011.11.006 freeman, t. (2015, october 28) “portable brain scanner allows pet in motion”. http://medicalphysicsweb.org/cws/article/research/63031 heaton p, wallace gl. (2004, july). annotation: the savant syndrome. j child psychol psychiatry, 45(5), 899911. doi: 10.1111/j.1469-7610.2004.t01-1-00284.x. keating, s. (2020, july 8). the violent attack that turned a man into a maths genius. bbc future. retrieved october 3, 2021, from https://www.bbc.com/future/article/20190411-the-violentattack-that-turned-a-man-into-a-maths-genius miller, l. k. (1999). the savant syndrome: intellectual impairment and exceptional skill. psychological bulletin, 125(1), 31–46. https://doi.org/10.1037/00332909.125.1.31. padmanaban, s., thiruvenkadam, k., thirumalaiselvi, m., & kumar, r. (2020). a role of medical imaging techniques in human brain tumor treatment. international journal of recent technology and engineering, 8(4s2), 565–568. https://doi.org/10.35940/ijrte.d1105.1284s219 piore, a. (2013, february 19). the master memories of savants. popular science. retrieved november 25, 2021, from https://www.popsci.com/science/article/201302/master-memories-savants/ snyder, a. (2009). explaining and inducing savant skills: privileged access to lower level, less-processed information. philosophical transactions of the royal society b: biological sciences, 364(1522), 1399–1405. https://doi.org/10.1098/rstb.2008.0290 the ampet is a wearable scanner that allows for imaging while the patient is able to freely move and perform various tasks. experiments and innovations like these are not only promising in understanding more about the brain functions but also savant syndrome and in helping people who suffer from brain damage. the possibilities are endless with new neurotechnology that is being developed. neuralink corporation founded by elon musk is currently testing implantable brain-machine interfaces. this chip's purpose is to help paraplegics perform simple tasks that they otherwise would not have been able to complete. clinical trials have shown promising results with rodents and monkeys and a study is ongoing with human participants. in the near future, this technology could be revolutionary and the missing piece to helping people “unlock their inner genius.” references 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 27brain matters volume vi https://www.scientificamerican.com/article/accidental-genius/ https://doi.org/10.5692/clinicalneurol.50.1017 https://doi.org/10.3390/brainsci8050081 https://psycnet.apa.org/doi/10.1037/0033-2909.125.1.31 copy of volume 7 publication brain matters vol. 8 no. 1 thank you! to the brain matters writers, editors, & executive board members, as well as the university of illinois university library & merinda kaye hensley for all of your hard work in making this journal possible. about brain matters brain matters discusses all things neuroscience, psychology, and biology written by uiuc’s very own. the journal welcomes all authors no matter their area of study or year, therefore, authors come from diverse backgrounds, from molecular and cellular biology & psychology, to computer science & engineering. this diversity allows volumes to have a wide range of articles. the journal is mainly written for the college community yet is accessible to anyone as brain matters is published in an open access format by the university library at the university of illinois urbanachampaign. copy of volume 6 publication table of contents using oxytocin as a therapy for individuals with autism spectrum disorder alisha babu...................................................................................1 the neurobiology behind the making of the antisocial personality type vyapti patel...................................................................................7 implications of gpcrs in alzheimer’s katilyn simmons...........................................................................4 can gene editing be the key to treating alzheimers? saani kulkarni ..............................................................................12 articles..............................................................................1 the mind-body problem and cognitive neuroscience: a brief history and outlook alex ball.......................................................................................15 deep brain stimulation advancements in clinical medicine, innovation in cutting-edge technology bilal karim...................................................................................19 the overlap between neuroscience and psychiatry: an exploration of the effectiveness of neurological applications in treating psychiatric disorders michelle bishka.............................................................................22 unlocking the inner genius within shireen aydogan............................................................................25 biochemical mechanisms of dendritic nonlinearities and their application in computational models matthew babik...............................................................................28 ibrain matters volume vi brain matters volume vi ii about the writers...................................................................46 meet the board......................................................................43 using cognitive behavioral therapy methods to treat musical performance anxiety sarah masud...................................................................................32 hippocampus structure & functions violet wang....................................................................................39 the neurobiological basis of the placebo effect and potential therapeutic applications celeste acosta.................................................................................34 alzheimer's and microbes casey meskovich.............................................................................36 social media effect on brain plasticity neha bashir....................................................................................41 micro-articles....................................................................32 volume 8 (will be vol 7 on site) editors macy is a freshman at uiuc majoring in brain and cognitive science with minors in integrative biology and music. she’s from evanston, illinois, and when she isn’t studying for yet another exam, she plays violin with the uiuc philharmonia and enjoys reading. she currently works for dr. husain at the auditory cognitive neuroscience (acn) lab. she loves editing for brain matters and is also a member of the undergraduate neuroscience society (uns). kamile aleksaite is a senior in bioengineering with a minor in health administration. she is the treasurer, co-social chair, and editor for the brain matters journal. her hobbies include playing volleyball and tennis, and she works as a lab technician at the evolutionary immunology and genomics laboratory. she plans to continue her studies at uiuc through the master’s program in bioengineering. meghan blomberg is a sophomore majoring in bioengineering and pursuing a minor in electrical engineering. she hopes to integrate her interests in electronic sensing into the neural space. apart from being an editor for the journal, she is involved in illinois microtech, where she learns about microfabrication of electronic devices. she is also a part of the illinois scholars for undergraduate research (isur) program. in her free time, she enjoys figure skating and competes on behalf of the university of illinois intercollegiate figure skating team. holly foskett is one of the editors for the brain matters journal and is currently a freshman at uiuc majoring in neuroscience. outside of the journal, holly loves to read, workout, and play tennis. she is also looking to conduct research of her own in the field of neuroscience in the future. brain matters・volume vii 90 br ai n m at te rs b oa rd br ai n m at te rs b oa rd megan lu is a sophomore majoring in brain & cognitive science with a minor in health administration and business. she is involved in various rsos on campus, including fhce (future healthcare executives) and alpha epsilon delta (a prehealth fraternity). she is also currently involved in research with the illinois alternative protein project. in her free time, megan spends most of her time at the gym working out, cooking new recipes, or listening to true crime podcasts. she hopes to deepen her understanding and appreciation of the brain through writing with brain matters. amy li is a freshman studying psychology at the university of illinois at urbana champaign. she got involved as a writer for this journal because she is interested in developmental and clinical psychology, and wanted to learn about the neuroscience behind those disciplines. in addition to writing for brain matters, amy is involved in women in psychology, women’s glee club, planned parenthood gen action, and girl gains on campus. praise kim is a freshman majoring in brain and cognitive science and spanish. her intellectual passions include the development of linguistic ability, mapping how the brain represents psychological phenomena, and environmental factors on intelligence. she joined brain matters as an editor to expand her knowledge on a variety of psychological and neurological processes. other organizations she is involved in include various language practice groups and nami. in her free time, she is with her church, working out, or reading. she plans on becoming an academic or psychologist in the future. copy of volume 7 publication copy of volume 6 publication the neurobiological basis of the placebo effect and potential therapeutic applications celeste acosta two patients, patient a and b, are diagnosed with the same chronic pain condition after a catastrophic car accident. both patients experience the same type of chronic pain around their neck and lower back. both patients receive the same prescription from the same doctor, except one bottle of pills does not contain any active drug. both patients experience pain relief from their symptoms in a few weeks and improve their condition drastically with the treatment. how is this possible if only one of the patients received an active drug compound? the placebo (pla-see-boh) effect, or placebo response, can be described as the “improvement of symptoms” in an individual after receiving a substance under a certain context that is supposed to have no real therapeutic effect (ortega et al., 2022). but what does this really mean? is there a neurobiological basis to the placebo effect? is there an opportunity for the usage of placebo treatments in a clinical setting? in the united states, a country largely influenced by big pharmaceutical companies, delving deeper into the biological basis and further therapeutic application might be seen as a potential threat but nevertheless, a necessary effort to make. the brain can, in fact, produce its own natural opioids called endogenous opioids, and they provide the same level of pain relief as exogenous opioids! from here the brain is releasing feel good chemicals and the placebo effect is in full speed. it can cause even greater changes in the immune system and hormone system (ortega et al., 2022) favorita1987/shutterstock let’s delve a little deeper into how a placebo effect works in the big complex blob that is the human brain. one of the most important factors for a placebo to work is context and setting (cai and he, 2019). for example, it’s more likely for someone to trust the words of a confident doctor in a white coat than your average joe in a sketchy alley. when you're in the appropriate setting, neurons in your dorsolateral prefrontal cortex begin to fire (ortega et al., 2022). this area of the brain, located right behind your forehead, is basically like the quality check controller of the brain. if the dorsolateral prefrontal cortex finds good quality information, that likely means it’s important! so this information gets sent off to other areas in the brain, specifically the areas responsible for releasing dopamine and self made opioids (bennedetti et al., 2005). figure 1. the context in which a placebo treatment is administered is crucial for the corresponding signals to activate the pathways starting from the prefrontal cortex (brainfacts/sfn). but if all it takes is to activate that prefrontal cortex, why don’t all placebo treatments work? well, that answer is a bit more complex but has a lot to do with the context the placebo is received in and the internal beliefs of the person receiving the placebo. belief also has a major influence on the placebo effect being successful. in fact, the main area of the brain that stores mental representations of the world in order to create our own internal beliefs is the prefrontal cortex (sathyanarayana rao et al., 2009). the prefrontal cortex is the area that starts to bring meaning to the signals and stimuli around us, something with meaning can be stored as an internal belief. a “stronger” belief can be correlated to more neurons firing in the prefrontal cortex, and when activated in the right setting, can produce the benefits of the placebo. the more we practice the same connection over and over, the stronger its effects (sathyanarayana rao et al., 2009). similarly, if the belief is negative, and those connections are strengthened, then there won’t be a perceived change overall (“this doesn’t work!”). so, in reality, we really do become what we think. benedetti, f., mayberg, h. s., wager, t. d., stohler, c. s., & zubieta, j.-k. (2005). neurobiological mechanisms of the placebo effect. the journal of neuroscience, 25(45),.10390–10402. https://doi.org/10.1523/jneurosci.3458-05.2005 references 1. 34brain matters volume vi brain matters volume vi cai, l., & he, l. (2019). placebo effects and the molecular biological components involved. general psychiatry, 32(5). https://doi.org/10.1136/gpsych-2019100089 ortega, á., salazar, j., galban, n., rojas, m., ariza, d., chávez-castillo, m., nava, m., riaño-garzón, m. e., díaz-camargo, e. a., medina-ortiz, o., & bermúdez, v. (2022). psycho-neuro-endocrine-immunological basis of the placebo effect: potential applications beyond pain therapy. international journal of molecular sciences, 23(8), 4196. https://doi.org/10.3390/ijms23084196 sathyanarayana rao, t. s., asha, m. r., jagannatha rao, k. s., & vasudevaraju, p. (2009). the biochemistry of belief. indian journal of psychiatry, 51(4), 239–241. https://doi.org/10.4103/0019-5545.58285 2. 3. 4. 35 copy of volume 6 publication alzheimer's and microbes casey meskovich introduction for twenty-five years, professor ruth itzhaki’s research on microbes as a possible cause of alzheimer’s diseases was dismissed and ridiculed. the idea that there could be a potential bridge between two starkly different fields–virology and neurodegeneration–seemed absurd at the time. now, itzhaki’s work is the backbone of an ongoing, cutting-edge trial on antiviral treatments for alzheimer’s at columbia university. microbes as triggers evidence supporting ithaki’s theory points to herpes simplex virus 1 (hsv-1) as a driving factor in alzheimer’s disease. hsv-1 is mainly transmitted orally, and causes what is commonly known as cold sores. the mechanism of invasion is as follows: the virus invades the body, burrows into the central nervous system, and remains latent within the brain (cox, 2023). when activated, it causes an acute inflammatory response. this activation can take place due to periods of stress, including head injuries, immunosuppression, and other comorbid infections. the multiple reactivations lead to sufficient brain damage and inflammation, facilitating the spread of the infection. while any pathogenic microbe can theoretically have a trigger role (and various bacteria have been suspected of this), there are shocking similarities in the brain regions affected by alzheimer’s disease and the herpes simplex virus 1, leading scientists to believe that it might be implicated in the pathogenesis of alzheimer’s disease. hsv1 was found in the temporal, frontal, and hippocampal regions of both ad individuals and individuals only infected with hsv (tyler, 2021). additionally, according to johns hopkins medicine, hsv-1 is very common, affecting up to fifty to eighty percent of american adults. the asymptomatic nature of the viral infection often renders it undetectable. hsv-1 was notably the first microbe to be detected in the human brain, in both patients who were diagnosed with alzheimer’s and those who were not. this is a clear indication that infection by the herpes simplex virus 1 alone is not enough to cause disease, and another factor can determine the degree of damage caused by the virus (itzhaki, 2022). the vzv pathway a study by tufts university suggests that another form of herpes virus, varicella zoster virus, may be one of the causative factors (blanding, 2015). as reported by the national institute of health, more than ninety-five percent of people have been infected with varicella zoster virus (abbreviated vzv) before the age of twenty, usually in the form of chickenpox (tyler, 2021). to better understand the relationship between hsv-1, vzv, and alzheimer’s disease, tufts researchers modeled the brain with sponges made of silk and collagen, and populated these sponges with neural stem cells. they found that neurons can be infected with vzv, but that wasn’t enough to produce the characteristics of alzheimer’s disease. interestingly, if hsv-1 was already present in a latent form, the exposure to vzv led to a reactivation of hsv-1 and a dramatic increase in both beta-amyloid proteins and tau proteins, a hallmark of alzheimer’s disease (cairns et al., 2022). amyloid v. microbial theory until now, researchers have widely accepted what many call the amyloid theory as the cause of alzheimer’s disease. the amyloid theory holds that the disease can result from a buildup of amyloid beta peptides in the space between brain cells. the peptides are then cleaved from this space, allowing them to float freely and aggregate. if left untreated, the clumps aggregate into plaques, one of the defining characteristics of the disease (cairns et al., 2022). recent research has proved that the amyloid theory and the microbial theory are not necessarily mutually exclusive. figure 1. herpes simplex virus (utmb home. n.d.). 36brain matters volume vi brain matters volume vi figure 2. a pet scan by revealing the difference in presence of amyloid plaques between patients with alzheimer’s and those without (yang, 2012). abbott, a. (2020, november 04). are infections seeding some cases of alzheimer’s disease? nature. are infections seeding some cases of alzheimer’s disease? a study by neurogeneticist tanzi and colleagues showed that amyloid-beta has antimicrobial properties. tanzi’s study showed that this peptide was able to kill eight common pathogenic microorganisms, such as streptococcus pneumoniae and escherichia coli (abbott, 2020). by glutinating and trapping various microbes, amyloid-beta is actually the brain’s first line of defense, and only poses an issue when allowed to aggregate into plaques. aging brings the decreased ability to clear amyloid aggregates from in between neurons, allowing them to trigger a cascade of neuroinflammation. furthermore, an age-associated waning immune system can allow microbes to proliferate more efficiently, catalyzing the development of the disease. similarly, lifestyle risk factors of alzheimer’s, such as lack of exercise and social isolation, can also weaken the immune system and further decrease the body’s ability to clear plaques (yang, 2012). conclusion although the cause of alzheimer’s disease remains largely elusive, recent research into potential microbial origins has offered much-needed insights. amyloid-beta plaques may be a side effect, rather than an actual cause of alzheimer’s, which could explain the relative ineffectiveness of amyloidtargeting drugs on patients. results of the study by columbia university on valacyclovir, an antiviral treatment for alzheimer’s, are expected in early 2024. however, various studies have already shown the effectiveness of antivirals in preventing alzheimer’s, such as a 2018 study from taiwan, which showed that people treated with antiviral drugs decreased risk of dementia ninefold. current research is now investigating the role of vaccinations in alzheimer’s. references 1. anti-herpetic medications and reduced risk of dementia in patients with herpes simplex virus infections-a nationwide, population-based cohort study in taiwan. (n.d.). pubmed. retrieved march 16, 2023, from https://pubmed.ncbi.nlm.nih.gov/29488144/ blanding, m. (2015, april 1). growing the stuff of life | tufts now. tufts now. retrieved march 16, 2023, from https://now.tufts.edu/2015/04/01/growing-stuff-life devanand, d. p., andrews, h., kreisl, w. c., razlighi, q., gershon, a., stern, y., mintz, a., wisniewski, t., acosta, e., pollina, j., katsikoumbas, m., bell, k. l., pelton, g. h., deliyannides, d., prasad, k. m., & huey, e. d. (2020). antiviral therapy: valacyclovir treatment of alzheimer’s disease (valad) trial: protocol for a randomised, double-blind,placebo-controlled, treatment trial. bmj journal, 10(2). 10.1136/bmjopen-2019032112 the innate immunity protein ifitm3 modulates γsecretase in alzheimer’s disease. (n.d.). youtube. retrieved march 16, 2023, from https://doi.org/10.1038%2fs41586-020-2681-2 itzhaki, r. (2022, november 15). my work investigating the links between viruses and alzheimer's disease was dismissed for years – but now the evidence is building. the conversation. retrieved march 16, 2023, from https://theconversation.com/my-work-investigating-thelinks-between-viruses-and-alzheimers-disease-wasdismissed-for-years-but-now-the-evidence-is-building184201 lay, p., & cox, d. (2023, february 19). could alzheimer's be caused by an infection? the guardian. retrieved march 16, 2023, from https://www.theguardian.com/society/2023/feb/19/couldalzheimers-be-caused-by-an-infection paired immunoglobulin-like type 2 receptor alpha g78r variant alters ligand binding and confers protection to alzheimer's disease. (2018, november 2). plos. retrieved march 16, 2023, from https://journals.plos.org/plosgenetics/article? id=10.1371/journal.pgen.1007427 potential involvement of varicella zoster virus in alzheimer's disease via reactivation of quiescent herpes simplex virus type 1. (n.d.). pubmed. retrieved march 16, 2023, from https://pubmed.ncbi.nlm.nih.gov/35754275/ silver, m. (2022, august 2). common viruses may be triggering the onset of alzheimer's disease. tufts now. retrieved march 16, 2023, from https://now.tufts.edu/2022/08/02/common-viruses-maybe-triggering-onset-alzheimers-disease tyler, k. l. (2021, september 3). the link between alzheimer disease and herpes simplex virus infection: better late than never, or better never than late? national library of medicine. https://doi.org/10.1007%2fs13311-021-01112-8 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 37 varicella-zoster virus disease | nih. (2022, september 7). clinical info hiv.gov. retrieved april 14, 2023, from https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinicalguidelines-adult-and-adolescent-opportunisticinfections/varicella-zoster viral role in alzheimer's disease discovered. (2022, august 2). university of oxford. retrieved march 16, 2023, from https://www.ox.ac.uk/news/2022-08-02-viralrole-alzheimers-disease-discovered yang, s. (2012, january 23). lifelong brain-stimulating habits linked to lower alzheimer's protein levels | research uc berkeley. research uc berkeley. retrieved march 16, 2023, from https://vcresearch.berkeley.edu/news/lifelong-brainstimulating-habits-linked-lower-alzheimers-protein-levels 12. 13. 14. 38brain matters volume vi copy of volume 6 publication biochemical mechanisms of dendritic nonlinearities and their application into computational models matthew babik introduction dendritic nonlinearities are a signaling method implemented by neurons in the prefrontal cortex (pfc) to increase the computational power of a single neuron. this type of signaling has been associated with learning-related mechanisms and higher-level cognitive functions, such as emotions (poirazi et al., 2014). dendrites utilizing nonlinearities tend to propagate incoming signals through vast integrative networks known as dendritic branches. the nonlinearities themselves occur directly at the spines of the dendrite which process the incoming signal and generate dendritic spikes alongside nearby spines (spruston, 2013). the tendency for a signal to propagate towards the soma occurs by spiking, which has the ability to elicit action potentials based on its strength (spruston, 2013). dendritic spikes are caused by the summation of incoming signals from multiple dendritic spines. these signals can be increased or decreased by subcellular memorization mechanisms that take into account previous depolarizations (poirazi et al., 2014). a variety of biochemical mechanisms mediate these signaling interactions and can occur locally or communally along a particular dendritic branch. nonlinear mechanisms that are isolated to particular spines tend to occur through interactions with na+, k+, ca2+ cation channels (poirazi et al., 2014). spatiotemporal relationships between spines regulate signals and the manner in which they are processed communally. these spatial relationships utilize nmethyl d-aspartate (nmda) receptors and their intracellular effects to regulate synaptic connections (poirazi et al., 2014). the cyclic adenosine monophosphate response elementbinding protein (creb) transcription factor also acts relative to local signals received by a synapse. this transcription factor helps to produce proteins that induce long-term potentiation at the spine that was depolarized. the coupling of all these biochemical reactions creates the pattern of nonlinearities experienced by the neuronal network. biochemical mechanisms of dendritic nonlinearities cation channels ion channels on the dendritic spines of pfc neurons exhibit unique biophysical properties and can be controlled by intracellular processes. certain mrna are trafficked by chaperone proteins into localized dendritic locations as a consequence of synaptic activity in the area (bramham & wells, 2007). dendritic spines contain the intracellular machinery to translate these messages, thus modifications are highly regulated and able to be localized to the environment near the postsynaptic area (bramham & wells, 2007). these mrna typically contain information to produce new ion channels in a dynamic system that may lead to the overexpression or underexpression of a particular channel protein. if the activity of an ion channel is increased within these locations, the neuron will actively modify the dendrite in response to synaptic activity (bramham & wells, 2007). depolarizations of particular channels are also important to maintain the integrity of the spines. the localized production of the arg protein expands the actin cytoskeleton, which underlies the morphology of the dendritic spine (bramham & wells, 2007; lo et al., 2020). this protein is transcribed locally in a spine after a depolarization event by ca2+ions via nmda receptor channels where it can then exert its effects (bramham & wells, 2007). all dendritic spines start from the actin cytoskeleton pushing on the cellular membrane to produce a small bubble. this bubble will begin to localize intracellular machinery and eventually produce a working abstract while dendritic spines make up only a small portion of the entire neuronal system, multiple intracellular mechanisms are localized to these points to trigger unique signaling pathways. biochemical interactions of membrane channels, intracellular protein cascades, and spine morphologies all give rise to nonlinear mechanisms of signal transduction. large branch summation events, in which multiple incoming signals are integrated towards the soma, are mediated by these mechanisms. information on this topic is utilized within computational studies to create accurate pyramidal neural networks. however, the methods to incorporate these nonlinear mechanisms into programs can be thoroughly debated. the purpose of this paper is to discuss the advantages and disadvantages of current approaches that incorporate nonlinear signal transduction into neuronal models. figure 1. the localization and simulation of mrna translation within a dendritic spine. (benita et al., 2020) 28brain matters volume vi those with ca2+, na+, and nmda, have been shown to elicit back and forward propagation of dendritic spikes (poizari, 2014). spatiotemporal associations of dendrites the morphological diversity of dendritic trees is capable of affecting signal conduction towards the soma. dendritic trees act as large summation devices that will properly conduct a signal once a certain threshold has been reached. this is opposed to linear dendritic signaling which acts through simple transmission pathways (poirazi et al., 2014). these mechanisms are developed through different voltagedependent conductance factors, particularly via voltagedependent ion channels (losonczy et al., 2008). although these factors are associated with a biophysical view of dendrites, the biochemical interplay inside the cell allows for nonlinearities to occur. the most notable biochemical system that creates these dendritic properties involves the activation of nmda spikes. nmda reception is tied to mechanisms of back and forward propagation of dendritic spikes (losonczy & magee, 2006). these methods of propagation assist in signal summation events and strengthen synaptic connections as a form of ltp induction (remy & spruston, 2007). however, this type of ltp induction is only performed by parvalbumin-expressing (pv+) gabaergic interneurons (remy & spruston, 2007; cornford et al., 2019). nmda reception can cause dendritic regenerative events known as nmda spikes. 1 these spikes have much higher amplitude and duration than spikes generated by na+, a-type k+, or ca2+ mediated potassium channels (poirazi et al., 2014). however, these spikes still have a lower amplitude than ca2+ channel spikes2(poirazi et al., 2014). nmda spikes are highly localized, being almost purely confined to the dendritic branch of the overall system (iacobucci, & popescu, 2019). as the spike acts both forwards and backwards on the system, it is capable of affecting all the spines of a branch (iacobucci & popescu, 2019). this effect is described as spatial coupling and has been investigated as a mechanism for intracellular detection of spines that form a synaptic connection (iacobucci & popescu, 2019). in addition to stimulation of the dendritic branch, receptor activation by nmda can affect the processing of signals purely within dendritic spines (iacobucci & popescu, 2019). spatial coupling influences the overall activity of all nmda receptors in a spine after a particular nmda receptor has allowed ca2+ions to pass through (iacobucci & popescu, 2019). this mechanism acts biochemically through interactions with calmodulin, calcium ions, and the local nmda receptors within the dendritic spine (iacobucci & popescu, 2019; shah 2010). this form of mediation is inhibitory towards nmda reception and serves as a method to autoinhibit the movement of ca2+ across the membrane and prevent oversaturation of the ion (iacobucci & popescu, 2019). creb transcription factor creb is a multipurpose transcription factor that enables nonlinear mechanisms in dendritic spines. this protein acts to stabilize long-term memory (particularly in amygdalarelated fear memorization engrams) and alters cellular machinery based on this stabilization (poirazi et al., 2014; dendritic spine. this unique production of the arg protein acts to maintain the stability of the spine through its interactions with the cytoskeleton and thus also maintains the synaptic connection (bramham & wells, 2007; lo et al., 2020). post-translational modifications of ion channels elicit unique activity-dependent responses that allow for nonlinear signal propagation. these changes depend on the type of protein and the mechanism it acts with intracellularly (shah et al., 2010). local depolarization and plasticity of the synapse cause changes in the phosphatases and kinases present within the postsynaptic area (shah et al., 2010). the involvement of cascade proteins creates mechanisms of biochemical backpropagation that tend to act on the ion channels. this type of backpropagation governs the activity of a particular synapse (shah et al., 2010). for example, in ca1 dendrites, activation of protein kinases a, c, mitogenactivated protein kinase (mapk), and extracellular signalregulated kinase (erk) modify a-type k+ion channels. modification of these channels can elicit enhanced ap propagation (hoffman & johnston, 1998; shah et al., 2010). a well-studied post-translational modification involves the attachment of the protein calmodulin to the ca2+ mediated potassium channel “kca2.2” (shah et al., 2010). calmodulin acts as an intermediate to attach ca2+ and activate the channel, allowing the affinity of the protein to be regulated in order to vary the activity of k+influx (allen et al., 2007; xia, 1998). the phosphorylated state of kca2.2-bound calmodulin is controlled by localized phosphatase (phosphatase 2a) and kinase ck2 (allen et al., 2007; shah et al., 2010). phosphorylation of calmodulin decreases the activity of the channel due to a lower affinity of ca2+for calmodulin (allen et al., 2007; shah et al., 2010; xia, 1998). likewise, the removal of this phosphate will increase the affinity for ca2+. this process leads to bidirectional activation of the channel. in all, the mechanisms presented have the ability to create unique depolarizations and allow for the retention of information relative to the inputs received. in addition, distributions of ion channels in spines also play a role in nonlinear processing (remy et al., 2009). the inactivation of na+ channels strongly regulates spike generation within ca1 pyramidal neurons (remy et al., 2009; poirazi et al., 2014). inactivation of these channels leads to increased dendritic excitability globally in the cell (remy et al., 2009). this feature thus aids in inducing synaptic plasticity relative to the surrounding neurons. local distributions of voltage-gated ion channels and their properties tend to be altered after long-term potentiation (ltp) induced excitatory stimulation (poirazi et al., 2014). these ltp stimulations decrease the peak depolarization required to elicit a dendritic spike. this change leads to a slow but permanent increase in the ability of a dendritic branch to influence the voltage of the soma (poirazi et al., 2014; losonczy et al., 2008). this effect is well understood and is known as branch strength potentiation (poirazi et al., 2014). overall, this phenomenon shows that if plasticity is induced on a spine, it will propagate to the surrounding dendrites via a-type currents (a-type currents occur via ca2+ mediated k+ channels) (poirazi, 2014) ionic conductances, particularly brain matters volume vi 29 these simulations can better account for the large degree of spinal interactions within the “tree-like” networks seen within in vivo cell lines (stöckel & eliasmith, 2021; poirazi & papoutsi, 2020). single neuron programs are more capable of modeling spatial and temporal interactions due to the greater ability to model spike firing. the summation of spike inputs is thus able to be based on the biochemical mechanisms mediating spine relationships (poirazi & papoutsi, 2020). due to this complexity on the single-cell level, a wide variety of methods have been proposed for creating multicellular models. in particular, the transformation functions utilized on the input vectors across neurons in these networks have used nonorthogonal basis functions (multiple correlated independent variables) (stöckel & eliasmith, 2021). networks that use these basis functions linearly combine them to create a processing unit so that the movement of signals is nonlinear (stöckel & eliasmith, 2021). overall, this type of transformation is an attempt to roughly model spikes created by incoming signals and their intracellular properties. current models also utilize varying degrees of pre-population versus post-population signal integration (stöckel & eliasmith, 2021; poirazi & papoutsi, 2020). this variation models biochemical mechanisms utilized for spike integration. dendritic spines formed by nmda stimulation produce synaptic clusters capable of being modeled by this population data (poirazi & papoutsi, 2020). as this form of integration is commonly utilized within nonlinear neural networks, these models take advantage of dendritic spike summation in order to produce a possible output (stöckel & eliasmith, 2021). this enables nonlinear functions to utilize the connections of the prepopulation along with those of the post-population, a property that is mediated by the biochemical mechanisms discussed (stöckel & eliasmith, 2021). overall, this approach of modeling utilizes operations of synaptic filtering to produce nonlinear relationships between somatic input currents and the neural response. a common challenge within computational neuroscience is building accurate models of the pyramidal tract that can properly integrate excitatory and inhibitory interactions into one signal. a recent method developed to navigate this issue is to separate the two pathways and afterward combine the resulting values using least squares regression optimization to find the updated weights during backpropagation (stöckel & eliasmith, 2021). previous methods utilized inhibitory interneurons that mediate the incoming excitatory signal before progressing. in the new program, the inhibition function is integrated alongside the other nonlinear connections established (stöckel & eliasmith, 2021; drix et al., 2020). the current method not only saves computational space but also prevents loss of signal integrity (stöckel & eliasmith, 2021). conclusion based on current models of dendritic nonlinearities, the ability of current computational models to accurately represent pyramidal neurons shows benefits as well as issues. while these models are capable of gaining insight into higher-order functioning based on the work of biophysical studies since the 1990s, accurate modeling of inhibition is still a problem. poirazi et al., 2019; zhou, 2009). creb enables the initiation of multiple cascade events which produce plasticity-related proteins when intracellular conditions permit such connections (zhou, 2009; poirazi, 2014). in particular, this transcription factor produces proteins involved in the mapk and mtor pathways (zhou, 2009). both of these cascades are involved in maintaining synaptic integrity after ltp induction. these plasticity-related proteins will eventually cause higher-level functional changes in the physiology of the amygdala by recruiting neuronal cells for the formation of fear engrams. as creb changes neuronal conformation, it also acts on particular spines to dictate temporal and spatial synaptic cluster formation (poirazi, 2014; poirazi, 2019; zhou, 2009). the formation of synaptic clusters by creb mechanisms also leads to the induction of the effects of nmda spikes within a particular space of the dendritic tree, further propagating methods of nonlinear integration. additionally, nmda ca 2+ channels are shown to influence the spatial dynamics of synaptic clusters during development (kastellakis & poirazi, 2019). the biochemical mechanisms elicited by the creb protein allow for compartmentalized dendritic spine generation (poirazi, 2014; kastellakis & poirazi, 2019). specifically, portions of dendritic branches utilize cluster formation as a method of localized spike induction to a particular section of the neuron (kastellakis & poirazi, 2019). in this interaction, the mapk signaling pathway involves the protein ras gtpase, which is known to increase spine volume after induction of the cascade (kastellakis & poirazi, 2019; kastellakis, 2015). the number of spines is increased by inducing actin molecules from the cytoskeleton in the dendritic branch to push the membrane upward and form a localized pocket (kastellakis & poirazi, 2019; kastellakis, 2015). an increase in spine volume is integral to synaptic cluster formation, although multiple processes are acting to produce this output (kastellakis, 2015; poirazi, 2014). modeling dendritic nonlinearities while mathematical modeling of nonlinear networks has been capable of creating simulations that can process information similar to neurons, networks utilizing functions that integrate known biochemical mechanisms are missing. higher-order statistical operations, while capable of creating unique integrations (structures beyond simple hebbian networks), still exhibit faults relative to the biochemical to biophysical interplay (cox & adams, 2009; stöckel & eliasmith, 2021). models that give further attention to nonlinear biochemical mechanisms tend to be modeled within single neuron simulations (poirazi et al., 2003). figure 2. the creation of dendritic spines from actin filaments. (miermans et al., 2017 30brain matters volume vi allen, d., fakler, b., maylie, j., & adelman, j.p. (2007). organization and regulation of small conductance ca2+activated k+ channel multiprotein complexes. j neurosci (9)2369-76. benita, t., cinzia, c., & j, cioni., (2020) molecular mechanisms behind mrna localization in axons open biol.10, 200177-200177 bramham, c. & wells, d. (2007). dendritic mrna: transport, translation, and function, nature rev neuroscience, 8(10), 776-89. cornford, j.h., mercier, m.s., leite, m., magloire, v., häusser, m., & kullmann, d.m. (2019) dendritic nmda receptors in parvalbumin neurons enable strong and stable neuronal assemblies, elife 8:e49872 doi: 10.7554/elife.49872 cox, k. & adams, p. (2009). hebbian crosstalk prevents nonlinear unsupervised learning, frontiers in computational neuroscience, 3(11). drix, d., hafner, v.v., & schmuker, m. (2020). sparse coding with somato-dendritic rule. neural networks, 131, 37-49. hoffman, d.a. & johnston, d. (1998). downregulation of transient k+ channels in dendrites of hippocampal ca1 pyramidal neurons by activation of pka and pkc. j neurosci, 18(10):3521-8. iacobucci, g. j., & popescu, g. k. (2019). spatial coupling tunes nmda receptor responses via ca2+ diffusion. j neurosci: the official journal of the society for neuroscience, 39(45), 8831–8844. kastellakis, g. (2015). synaptic clustering within dendrites: an emerging theory of memory formation. progress in neurobiology, 126, 19-35. kastellakis, g., & poirazi, p. (2019). synaptic clustering and memory formation. frontiers in molecular neuroscience, 12, 300. lo, l.h., dong, r., lyu, q., & lai, k. (2020). the protein arginine methyltransferase prmt8 and substrate g3bp1 control rac1-pak1 signaling and actin cytoskeleton for dendritic spine maturation. cell rep, 10(31). current neural engineering frameworks integrate inhibition functions with non-orthogonal functions in order to maintain the integrity of the signal. however, this only roughly approximates many of the mechanisms present within the postsynaptic cell. multiple variables exist on the biochemical level to create the observed patterns of dendritic nonlinearities. these biochemical processes exhibit temporal and spatial relationships relative to the induction of their intracellular mechanisms. these factors lead to variations and randomness that may not be fully accounted for in the final calculation of weights within neuronal models. due to insufficient information surrounding the biochemical mechanisms that underlie dendritic nonlinearities, it may be a better approach to utilize biophysical models for larger neuronal systems. strictly adhering to current biochemical knowledge may create limits on the ability of these simulations to portray higher-order functioning. references 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. brain matters volume vi losonczy, a. & magee, j.c. (2006). integrative properties of radial oblique dendrites in hippocampal ca1 pyramidal neurons. neuron. 50(2):291-307. losonczy, a., makara, j.k., & magee, j.c. (2008). compartmentalized dendritic plasticity and input feature storage in neurons. nature, 452(7186):436-41 miermans, c., kusters, r., hoogenraad, c., storm, c., (2017). biophysical model of the role of actin remodeling on dendritic spine morphology. plos one, 12(2): e0170113 poirazi, p., brannon, t., & mel, b., (2003) pyramidal neuron as two-layer neural network neuron, 37, 6, 989-999 poirazi, a., papoutsi, a., kastellakis, g., psarrou, m., & anastasakis, s. (2014). coding and decoding with dendrites, journal of physiology paris, 108, 18-27. poirazi, p., tzilivaki, a., & kastellakis, g., (2019) challenging the point neuron dogma: fs basket cells as 2-stage nonlinear integrators. nat commun, 10, 3664 poirazi, p. & papoutsi, a., (2020). illuminating dendritic function with computational models. nat rev neurosci, 21, 303–321. remy, s. & spruston, n. (2007). dendritic spikes induce single-burst long-term potentiation. proc natl acad sci usa. 104(43):17192-7. remy, s., beck, h., & yaari, y. (2009). plasticity of voltage-gated ion channels in pyramidal cell dendrites, current opinion in neurobiology, 20, 503-509. shah, m. m., hammond, r. s., & hoffman, d. a. (2010). dendritic ion channel trafficking and plasticity. trends in neurosciences, 33(7), 307–316. https://doi.org/10.1016/j.tins.2010.03.002 spruston, n. (2013). information processing in dendrites and spines, fundamental neuroscience (fourth edition), 231-260. stöckel, a. & eliasmith, c. (2021). passive nonlinear dendritic interactions as a computational resource in spiking neural networks, neural computation, 33 (1): 96–128. xia, x.m., fakler, b., rivard, a., wayman, g., johnsonpais, t., keen, j.e., ishii, t., hirschberg, b., bond, c.t., lutsenko, s., maylie, j., & adelman, j.p. (1998). mechanism of calcium gating in small-conductance calcium-activated potassium channels. nature. 395(6701): 503-7. zhou, y. (2009). creb regulates excitability and the allocation of memory to subsets of neurons in the amygdala. nature neuroscience, 12(11), 1438–1443. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 31 volume 8 (will be vol 7 on site) more inaccuracies than typ children. this suggests a lack of cognitive control for asd individuals may be more pronounced at earlier ages (solomon et. al, 2008). emotional control in asd emotional control refers to the management of an individual's emotions. people with asd often have strong emotions and struggle to control them, this is often referred to as emotional dysregulation. to put it into perspective, when placed in an overwhelming environment, typ individuals may try to calm down, while individuals with asd tend to react without a clear goal in mind (ghanouni and quirke., 2022). asd individuals usually have trouble understanding their own emotions and struggle to adjust their behavior depending on the situation. other factors such as bright lights and sounds can make it even more difficult for asd individuals to handle their emotions, leading to potential shutting down or avoidance of certain situations (mazefsky et al., 2013). this highlights the challenges individuals with asd face. with the difficulty of comprehending emotions coupled with heightened sensitivities, interventions or therapies are crucial to support asd individuals with navigating social situations and developing efficient coping mechanisms. the interplay of cognitive and emotional control in autism spectrum disorder kaitlyn tuvilleja abstract autism spectrum disorder (asd) is a condition that affects how an individual interacts, communicates, learns, and behaves (national institute of mental health). this can significantly impact two crucial areas for navigating our daily lives: cognitive and emotional control. the cognitive side aids decision-making and clear communication. they allow us to weigh various options logistically and predict the potential consequences of those decisions. the emotional side helps manage healthy relationships as these controls allow for attentive listening, clear communication, and disagreement navigation. multiple studies delve into the interplay between cognitive and emotional control between individuals with asd and typical adults (typ) without asd. by understanding how cognitive and emotional control affects individuals with asd, we can create a society that is more accessible and enthusiastic to help. cognitive control in asd cognitive control is managing your thoughts, feelings, and actions to adapt to various situations (miller and cohen 2001). in terms of attention and planning, cognitive control aids an individual's mental organization of information. it also contributes to decision-making and how to make logistical choices and predict the consequences. for example, most individuals can switch between tasks or even multi-task. however, these controls can be inhibited by physiological and psychological factors. brain structure and function abnormalities, such as neuroinflammation, oxidative stress, and gut-brain axis dysfunction are correlated to cognitive problems in asd, such as depression and aggression. even deficiencies in sensory perception, specifically visual processing, can contribute to the deficits of cognitive control in asd (al-mazidi, 2023). while typ individuals use cognitive control subconsciously, individuals with asd may find difficulties in using cognitive control abilities efficiently. most individuals with asd struggle with task-switching problems, which are theorized to be in coordination with a lack of behavioral control. to observe this, researcher marjorie solomon at the university of california, davis conducts a study observing whether cognitive and emotional controls work together. the study included children both younger and older than twelve years old. to examine cognitive control in asd, participants were given the “preparing to overcome prepotency” (pop) task. the pop task consisted of two easier and harder trials (i.e. requirement to inhibit a habitual response). reaction times were slowed throughout each task for both asd and typ groups regardless of age. as more attempts were made, the typ group eventually had more efficient performances. in contrast, the asd group showed more difficulty in suppressing habitual responses as tasks continued (fig. 1). these results suggest that children with asd may have deficits in cognitive control, particularly in predicting responses. further analysis shows that asd children under 12, though a small difference, tend to make figure 1. inaccuracies with harder trials between asd and typ group across participants younger than 12 (blue) and older than 12 (green) by age range (solomon et al.) the interplay between cognitive and emotional control researchers acknowledge that there may be interactions between systems managing cognitive and emotional control. the study involved a typ group and an asd group, both trained in cognitive reappraisal. individuals with asd are known to have trouble controlling their emotions. researcher richey and his team compared brains of asd and typ brain responses when they try to reinterpret situations in a more positive light to help regulate emotions, also known as reappraisal. during the fmri brain scan, participants were shown pictures of faces and asked to develop positive or negative thoughts about those faces. what the researchers found was that the asd group had weaker activity in two regions of the dorsolateral prefrontal cortex (dlpfc) and the amygdala. the dorsolateral prefrontal cortex (dlpfc) was involved more with motivation and reward, especially for social stimuli (fig. 2). this explains why asd individuals do not find social interactions or events as exciting or as rewarding as other people would since social events don't feel as rewarding to them. the amygdala, which was involved with suppressing negative emotions, isn’t as active in asd individuals. typ individuals are shown to activate the amygdala more when presented with tasks that require suppressing negative emotions. this would explain why asd individuals usually have difficulty calming down as the amygdala isn’t as active as typical individuals (richey et al., 2015). despite the different brain region strengths, both groups had similar changes in their emotional responses, suggesting people with asd might use different brain mechanisms to achieve emotional regulation (richey et al., 2015). conclusions and future implications understanding how cognitive and emotional controls affect individuals with asd is essential for developing effective interventions and fostering a more inclusive society. asd individuals struggle with social interactions due to their differences in brain activity. despite the challenges in cognitive and emotional control, individuals with asd possess unique strengths and capabilities. researchers can use this data to create techniques and therapies to support individuals with asd. by acknowledging these differences and fostering an environment of support, we can empower individuals with asd to thrive in all aspects of society. references 1. al-mazidi, s. h. (2023, october 6). the physiology of cognition in autism spectrum disorder: current and future challenges. cureus. https://www.cureus.com/articles/193026-the-physiology-ofcognition-in-autism-spectrum-disorder-current-and-futurechallenges#!/ 2. ghanouni, p., & quirke, s. (2022, january 25). resilience and coping strategies in adults with autism spectrum disorder. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8788904/ 3. mazefsky, c., et al. (2013, june 3). the role of emotion regulation in autism spectrum disorder. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3719386/ 4. miller, e., & cohen, j. (2001). an integrative theory of prefrontal cortex function. annual review of neuroscience. https://www.annualreviews.org/content/journals/10.1146/annu rev.neuro.24.1.167 5. national institute of mental health. (2024, february). autism spectrum disorder. national institute of mental health. https://www.nimh.nih.gov/health/topics/autism-spectrumdisorders-asd 6. poljac, e., & bekkering, h. (2012, october 5). a review of intentional and cognitive control in autism. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3481002/ 7. richey, j. a., et al. (2015, november). neural mechanisms of emotion regulation in autism spectrum disorder. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4515208/ 8. solomon, m., et al. (2008, november). cognitive control in autism spectrum disorders. international journal of developmental neuroscience. https://www.sciencedirect.com/science/article/pii/s073657480 700161x figure 2. highlighted right and left dorsolateral prefrontal cortex (dlpfc) in asd participants (richey et al.). brain matters・volume vii 40 https://www.cureus.com/articles/193026-the-physiology-of-cognition-in-autism-spectrum-disorder-current-and-future-challenges#!/ volume 8 (will be vol 7 on site) stimulating experiences. the last is background use, which involves listening to music while performing other tasks without getting distracted. using these three uses of music as a foundation, a study by sanseverino et al. (2022) sought to understand how emotional, cognitive, and background use of music affect perceptions of job satisfaction and performance. they hypothesized that (1) emotional use has a positive relationship to job satisfaction and performance, (2) cognitive use has a positive relationship to job satisfaction and no direct relationship to performance, and (3) background music has no direct relationship to job satisfaction or performance. to test this, 424 participants were instructed to complete a questionnaire about their music listening habits while working. 57.7% reported listening to music, 26.5% reported not listening to music because they could not, and 15.8% reported not wanting to listen to music. for this study’s purposes, only the 244 participants who stated that they listen to music while working were considered. music use was determined using fifteen questions from chamorro-premuzic and furnham’s 2007 study, which consisted of five questions for each use of music. respondents rated how they use music on a likert scale from 1 (“strongly disagree”) to 5 (“strongly agree”). job satisfaction was assessed with five questions on the same scale, and respondents rated their satisfaction in various areas such as relationships, physical conditions, and prospects. finally, job performance was measured using four questions. participants were asked to rate how effective they’ve felt regarding different aspects of their performance, such as, “how effective were you in performing without mistakes?” altogether, these measures would uncover whether different uses of music are correlated with different work outcomes. results and implications sanseverino’s 2022 study found that both job satisfaction and performance are positively correlated with emotional use of music, which confirms the first hypothesis. cognitive use showed non-significant relationships both with satisfaction and performance, disproving the second hypothesis. finally, background use had a negative correlation with job satisfaction, disproving the third hypothesis, and didn’t show any significant relationship with job performance. age, interestingly, showed a negative relationship to all three uses of music, indicating that music use during work may decrease as people grow older. another fascinating finding was that men were less likely to use background music and more likely to engage in cognitive use. symphonies vs. silence: how does music affect work performance? sarah masud introduction imagine this: you’re slouching at your desk, staring at the mountain of tasks you have yet to complete, and your productivity is at a minimum. how do you combat this? do you pull out your headphones and your favorite playlist, hoping they’ll get you in the groove to work? or do you cut out the distractions and try to focus without any bothersome background noise? the debate on whether music enhances or hinders work performance is a long one running with many studies reporting mixed results. some individuals say that listening to music uplifts their mood and boosts their productivity, while others insist that working in silence is the key to sustaining focus. while it is difficult to make a definite claim on how music affects work, one important consideration is that different ways of listening to music can lead to different outcomes. it is worth examining how emotional, cognitive, and background use of music impact job satisfaction and performance. previous findings: what’s the big debate? early studies investigating the effect of music on work performance have often posed contradictory findings. shih, huang, and chiang (2012) found that background music containing lyrics had a negative effect on attention and concentration. similarly, padmasiri and dhammika (2014) reported that listening to relaxing music decreased work performance. however, this study didn’t consider contexts where workers can choose music rather than just being exposed to it in their work environment. lesiuk (2010) found that people listening to their preferred music reported lower stress and better mood, as well as improved performance in situations with high cognitive demands. likewise, a study by haake (2011) indicated that music at work evokes positive emotions, resulting in feelings of inspiration, concentration, and stress reduction. it may be that workers prefer listening to music because it makes work more enjoyable and increases satisfaction and creativity. however, it’s evident that the content and context of music matter greatly. music genre and its impact chamorro-premuzic and furnham (2007) describe three ways that people use music in everyday life. the first is emotional use, which refers to evoking positive or negative moods, changing the emotional state, or expressing pleasure in experiencing an emotion that isn’t necessarily positive (e.g., finding comfort in sad music). the second is cognitive use, which entails listening to music for intellectual purposes and enjoying the technical aspects. an example of this is seeking out classical or jazz music—not because it’s unlikely to elicit emotions, but because its complexity allows for rational appreciation and suits those who like intellectually job satisfaction and performance. emotional use of music was found to be positively correlated with both job satisfaction and performance, suggesting that the emotions evoked by music can enhance perceptions of work satisfaction and task accomplishment. on the other hand, cognitive use of music did not show any significant relationships, and background use of music primarily demonstrated negative effects, particularly concerning job satisfaction. this suggests that excessive reliance on music as background noise could be a common reaction to feeling dissatisfied with work. however, it’s important to note that reasons for listening to music and the outcomes gained vary from person to person. by recognizing the different ways music is used and its varying effects on job satisfaction and performance, organizations can tailor strategies to support their employees' well-being and productivity. from creating designated quiet spaces to offering flexibility in music choices, accommodating different preferences is key to creating a productive and enjoyable workplace. references 1. chamorro‐premuzic, t., & furnham, a. (2007). personality and music: can traits explain how people use music in everyday life?. british journal of psychology, 98(2), 175185.https://doi.org/10.1348/000712606x111177 2. haake, a. b. (2011). individual music listening in workplace settings: an exploratory survey of offices in the uk. musicae scientiae, 15(1), 107-129.https://doi.org/10.1177/1029864911398065 3. lesiuk t. (2010). the effect of preferred music on mood and performance in a high-cognitive demand occupation. journal of music therapy, 47(2), 137–154. https://doi.org/10.1093/jmt/47.2.137 4. padmasiri, m. d., & dhammika, k. a. s. (2014). the effect of music listening on work performance: a case study of sri lanka. int. j. sci. technol. res, 3(6). 5. sanseverino, d., caputo, a., cortese, c. g., & ghislieri, c. (2022). "don't stop the music,"please: the relationship between music use at work, satisfaction, and performance. behavioral sciences, 13(1), 15. https://doi.org/10.3390/bs13010015 6. shih, y. n., huang, r. h., & chiang, h. y. (2012). background music: effects on attention performance. work, 42(4), 573–578. https://doi.org/10.3233/wor-2012-1410 in this study, emotional use of music was the only type associated with positive effects on both job satisfaction and performance. but why is this, and what aspects of emotional use could lead to more positive outcomes than other uses of music? it may be that enjoying the emotion elicited by music enhances perceptions of work satisfaction. in turn, this combination of a charged emotional state and increased satisfaction could contribute to more positive perceptions of tasks accomplished at work. cognitive use of music, which was more common in men than women in this sample, is surprisingly not related to job satisfaction. however, this could be explained by the participants that were recruited; this study intentionally excluded professional musicians who engage with this type of music more frequently, resulting in a sample that had low scores on cognitive use. another explanation for this low number could be that the positive emotions evoked from cognitive use were mistaken for emotional use, which would be far more common in this sample of non-musicians. future studies with more representative samples—including musicians and more women engaging in cognitive use— could further investigate why cognitive use is unrelated to job satisfaction. one possibility is that appreciating the technicality of music adds an extra requirement to work, so cognitive use distracts workers from pursuing more important tasks. therefore, this would counteract any positive activation they get from enjoying the structure of music. lastly, background use of music seemed to only have negative effects in this study, including a significant negative correlation with job satisfaction. however, this study cannot assume any causal relationships due to its cross-sectional design; that is, data on music habits and satisfaction was collected at a single point in time, so it’s unclear which came first. it’s possible that the effect is reversed and the more people feel dissatisfied with their work, the more they use music as background noise. this general rule that correlation is not causation is important to keep in mind for all three uses of music and their reported effects. to determine any causality, it would be necessary to conduct further longitudinal studies; that is, research that repeatedly measures effects over time rather than a single instance. future work could also apply this research to the real world and outline how organizations can use music as a resource. even an approach as simple as implementing quiet workspaces, where employees are free to engage with their chosen music or none at all, can increase performance and satisfaction across the board while accounting for individual preferences. conclusion the conversation surrounding the influence of music on work performance is nuanced, with various studies reporting different results. while some swear by the motivational power of their favorite songs to boost productivity, others find comfort in the tranquility of a silent workspace. the study conducted by sanseverino et al. (2022) sheds light on the multifaceted relationship between different uses of music and brain matters・volume vii 72 https://doi.org/10.1348/000712606x111177 https://doi.org/10.1177/1029864911398065 https://doi.org/10.1093/jmt/47.2.137 https://doi.org/10.3390/bs13010015 https://doi.org/10.3233/wor-2012-1410 copy of volume 6 publication the overlap between neuroscience and psychiatry: an exploration of the effectiveness of neurological applications in treating psychiatric disorders michelle bishka neuroscience and psychiatry have a historically complicated dynamic, originating as the unified field of neuropsychiatry and later diverging into two separate fields of study. neuroscience is the study of the nervous system and the brain. a critical branch of neuroscience that is concerned with the nervous system and brain-related diseases is neurology. psychiatry, like neurology, is also concerned with brain abnormalities, but, unlike neurology, psychiatry is the study of mental illnesses. mental illnesses differ from neurological disorders in that they cannot be solely identified and treated through somatic, physical, symptoms and their mediation. this is because mental disorders are often associated with environmentally-induced trauma. however, as research in neuroscience develops, there is evidence to suggest that certain psychiatric disorders can be linked to structural abnormalities, like chemical imbalances in the brain, intertwining the fields of neuroscience and psychiatry once again (baker et al., 2002). though a trend towards reunification between the two disciplines has been established, neuroscience and psychiatry remain distinct but work in tandem for the most effective treatment of psychiatric disorders. the treatment of psychiatric disorders in a neurological context could be seen in the 20th century with electroconvulsive therapy (ect). the first documented case of ect was recorded in the 1930s, known as shock therapy (shorter, 2008). as broken down by mayo clinic (2018), ect passes electrical currents through the brain to trigger a short seizure and reconfigure its chemistry in such a way that relieves the symptoms of certain mental illnesses. controversy around ect stems from its initial implementation, which unsafely sent high doses of electricity through the brains of patients without anesthesia, potentially leading to confusion, memory loss, broken bones, or heart complications in the patient. developments in anesthesia eventually made ect safer in treating psychiatric disorders, though the stigma of ect still remains. in contrast, modernday ect occurs in a highly-controlled environment where the brain, heart, blood pressure, and oxygen levels of the patient are monitored as they are under anesthesia (mayo clinic, 2018). ect is considered highly effective in patients who have severe depression that remained unaffected by other treatment methods, with more than 50% of severely depressed individuals experiencing improvement in their symptoms (khalid et al., 2008). ect has also been proven effective in treating schizophrenia, with 77% of schizophrenic individuals responding to ect (kaster et al., 2017). remission post-treatment is common, with many individuals undergoing a series of ect treatments to manage their symptoms over time (mckenna, 2021). ect may also be coupled with other methods of treatment, like medication. another conversation surrounding the application of neuroscience to psychiatry surfaced with irwin and miller’s (2007) “depressive disorders and immunity: 20 years of progress and discovery,” which developed the cytokine model of depression. in depression, it is found that signaling proteins that regulate immunity, cytokines, are produced in high concentrations in a pro-inflammatory form. large amounts of pro-inflammatory cytokines activate enzymes that convert tryptophan, an amino acid of serotonin, into a form that can no longer be used for serotonin synthesis (miller et al., 2013). the low levels of serotonin seem to be a cause of depression according to the “serotonin hypothesis” (albert et al., 2012). therefore, according to irwin and miller, a viable method of treating depression is to limit pro-inflammatory cytokine production through medication, as this would increase serotonin production. depression was first explained in terms of serotonin more than 50 years ago. with new findings, the “serotonin hypothesis” has been met with inconsistencies, as explained by paul albert’s analysis of it. individuals without mental disorders who had their serotonin levels experimentally reduced exhibited little to no change in mood. antidepressants that increase serotonin levels were found to not necessarily work for all individuals with depression, and antidepressants that do not raise serotonin levels can also aid in depression treatment (albert et al., 2012). this is not to say that the “serotonin hypothesis” is not credible. the most commonly prescribed antidepressants are selective serotonin reuptake inhibitors (ssris), which increase serotonin levels. these antidepressants are about as effective as their competitor, serotonin and norepinephrine reuptake inhibitors, which increase both serotonin and norepinephrine levels (u.s. national library of medicine, 2020). a study published by the u.s. national library of medicine (2020) evaluated the efficacy of antidepressants, revealing that 40 to 60 people out of the 100 who took antidepressants had their severe depression symptoms alleviated within six to eight weeks, while 20 to 40 people out of the 100 who took a placebo experienced the same result. although this suggests that antidepressants improve severe abstract neuroscience and psychiatry, once indistinguishable fields, had developed into their own disciplines over the course of the 20th century. by the end of the 20th century and the beginning of the 21st century, however, developments in neuroscience that enable psychiatric disorders to be treated in terms of structural abnormalities of the brain have led to a possible reunification between the two fields, though the fields still remain separate today. 22brain matters volume vi albert, p. r., benkelfat, c., descarries, l. (2012, september 5). the neurobiology of depression--revisiting the serotonin hypothesis. i. cellular and molecular mechanisms. philosophical transactions of the royal society of london. series b, biological sciences. retrieved december 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3405681/ baker, m. g., kale, r., menken, m. (2002, june 22). the wall between neurology and psychiatry. bmj (clinical research ed.). retrieved december 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc11234283. cuijpers, p., sijbrandij, m., koole, s. l., andersson, g., beekman, a. t., reynolds, c. f. (2013, june 4). the efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: a metaanalysis of direct comparisons. world psychiatry : official journal of the world psychiatric association (wpa). retrieved december 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3683266/ fansi, a., jehanno, c., lapalme, m., drapeau, m., bouchard, s. (2015). [effectiveness of psychotherapy compared to pharmacotherapy for the treatment of anxiety and depressive disorders in adults: a literature review]. sante mentale au quebec. retrieved december 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/27203537/ høglend, p. (1999). psychotherapy research: new findings and implications for training and practice. the journal of psychotherapy practice and research. retrieved december 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3330564/ irwin, m. r., miller, a. h. (2007, march 13). depressive disorders and immunity: 20 years of progress and discovery. brain, behavior, and immunity. retrieved december 24, 2021, from https://www.sciencedirect.com/science/article/pii/s08891 5910700027x kaster, t. s., daskalakis, z. j., blumberger, d. m. (2017, april). clinical effectiveness and cognitive impact of electroconvulsive therapy for schizophrenia: a large retrospective study. the journal of clinical psychiatry. retrieved december 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/28297593/ improve when ect treatment is coupled with medication (youssef & mccall, 2014) or psychotherapy (mcclintock et al., 2011), specifically in treating severe depression. still, further investigation is required to solidify this evidence, as it originated from studies with flawed designs that require refining. overall, all treatments of psychiatric disorders are helpful in mediating their symptoms, but their effectiveness depends on the individual and their mental illness. thus, it is important to note that psychiatry is multifaceted. the incorporation of neurological methods in the treatment of psychiatric disorders has proven to be effective for many, but it is overly simplistic to rely solely on medication or ect as treatment when addressing a disorder that can be better alleviated with psychotherapy or a combination of psychotherapy, medication, and ect. references 1. 2. 3. 4. 5. 6. 7. depression symptoms in about 20 people out of 100 within six to eight weeks, there are still a significant number of individuals who did not see any improvement in their severe depression symptoms despite taking antidepressants. as a result, depression is viewed to be caused by a conglomerate of environmental, psychological, biological, and chemical factors. thus, it is important to note that psychiatry is multidisciplinary and may utilize treatment methods that are not based in neurology. one such example of a psychiatric treatment method that is not neurologically-founded is psychotherapy, which primarily alleviates the symptoms of mental disorders that are not directly associated with complications in the physical or chemical structure of the brain. psychotherapy is an opportunity for an individual to learn coping mechanisms for difficult situations and relieve stress that can be amplified by mental illness (mayo clinic, 2016). unlike ect, the results of psychotherapy are heavily dependent on both the therapist and the patient. according to per høglend’s “psychotherapy research” (1999), an ideal therapist is able to apply psychiatric interventions to their patient and adjust these interventions according to their patient's response. a suitable patient is one that can verbalize their concerns and work well with others. the efficacy of psychotherapy is, therefore, highly contingent on the individuals involved. on average, 63 out of 100 individuals who continually participate in psychotherapy have seen progress with their psychiatric disorder, while only 38 out of 100 individuals under a placebo or minimal treatment experienced the same effect (høglend, 1999). this indicates that 25 out of 100 people who undergo psychotherapy report a successful outcome. the effectiveness of common psychiatric disorder treatments, ect, medication, and psychotherapy, vary among individuals. both neurologically and non-neurologically-based treatments have their benefits. in general, there is no large discrepancy between the effectiveness of medication and psychotherapy usage surrounding patients with moderate anxiety or depressive disorders, as seen in a study conducted by alvine fansi (2015). despite this, psychotherapy seems to have longer positive effects with a reduced likelihood of relapse (fansi 2015). according to a study led by pim cuijpers (2013), a similar pattern is seen in patients with panic disorder and seasonal affective disorder (seasonal depression), where the effectiveness of psychotherapy and medication parallel each other. a shift occurs with dysthymia, a severe form of chronic depression that is more effectively treated with medication than psychotherapy, and obsessive-compulsive disorder (ocd), a disorder that is more effectively treated with psychotherapy than medication (cuijpers et al., 2013). ect is often used as a last resort, to treat disorders that have not been improved by treatments that have lower risk and are easier to access. as demonstrated in a study led by eric ross (2018), ect, in comparison to medication and psychotherapy, is more effective in treating severe depression, but has extremely high relapse rates. there is potential evidence to suggest that the relapse rates and, thus, effectiveness of ect may brain matters volume vi 23 khalid, n., kirov, g., champney-smith, k., giles, m., tredget, j., atkins, m. (2008, june). the effectiveness of electroconvulsive therapy in treatment-resistant depression: a naturalistic study. the journal of ect. retrieved december 24, 2021, from https://pubmed.ncbi.nlm.nih.gov/18580559/ mayo foundation for medical education and research. (2016, march 17). psychotherapy. mayo clinic. retrieved december 24, 2021, from https://www.mayoclinic.org/testsprocedures/psychotherapy/about/pac-20384616 mayo foundation for medical education and research. (2018, october 12). electroconvulsive therapy (ect). mayo clinic. retrieved december 24, 2021, from https://www.mayoclinic.org/testsprocedures/electroconvulsive-therapy/about/pac20393894 mcclintock, s. m., brandon, a. r., husain, m. m., jarrett, r. b. (2011, september). a systematic review of the combined use of electroconvulsive therapy and psychotherapy for depression. the journal of ect. retrieved december 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3162076/ mckenna, j. (2021, february 21). electroconvulsive therapy (ect) and mental illness. webmd. retrieved december 24, 2021, from https://www.webmd.com/schizophrenia/electroconvulsive -therapy miller, a. h., haroon, e., raison, c. l., felger, j. c. (2013, march 6). cytokine targets in the brain: impact on neurotransmitters and neurocircuits. depression and anxiety. retrieved december 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4141874 ross, e. l., zivin, k., maixner, d. f. (2018, july 1). costeffectiveness of electroconvulsive therapy vs pharmacotherapy/psychotherapy for treatment-resistant depression in the united states. jama psychiatry. retrieved december 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6145669/ shorter, e. (2008, november 21). history of psychiatry. current opinion in psychiatry. retrieved december 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3714299/# r25 u.s. national library of medicine. (2020, june 18). depression: how effective are antidepressants? informedhealth.org [internet]. retrieved december 24, 2021, from https://www.ncbi.nlm.nih.gov/books/nbk361016/ youssef, n. a., mccall, w. v. (2014, november). relapse prevention after index electroconvulsive therapy in treatment-resistant depression. annals of clinical psychiatry: official journal of the american academy of clinical psychiatrists. retrieved december 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4420179/ 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 24brain matters volume vi copy of volume 7 publication 12 the origin, history and science of memory neil doherty throughout human history, much of the brain and its functioning has been unknown. at first, the theory of mind was articulated by ancient greek philosophers. plato, for instance, declared that the logistikon (interpretation of consciousness at the time) was, in fact, the thinking part of the soul. aristotle subsequently proposed that the mind was an extension of the soul that involved knowing and understanding. outside these two major contributions, not much else of the function of the human brain had been addressed, outside of its moral reasoning and decision making. although the studies at the time had been primitive and informal, they did tackle many of the critical concepts about consciousness, will, and memory. however, memory seemed more tangential and was treated teleologically as a means of understanding consciousness. up until the 20th century, very few people had questioned the extent, capacity, or mechanism of memory. it was lost in the deafening roar of debate over consciousness. however, in 1885, the first account of memory as a function of crystallized intelligence had been proposed, with the advent of the famous ebbinghaus curve from ebbinghaus’ über das gedächtnis (memory. a contribution to experimental psychology, 2016). though it seemed rather self-evident, the scientific data proving that memory decreased over time was revolutionary. as a direct result of ebbingahus’ contribution, the study of human memory was thrust to the forefront of both psychology and early neuroscience. eventually, richard semon proposed in his 1904 the mneme that memories created an engram, a seemingly permanent change in the physical structure of the brain that can be measured (12). later in 1949, psychology researcher donald hebb developed hebb’s rule, the notion that memories were stored in connections between neurons known as synapses (65). this forms the basis of our current understanding of memory, scientifically supported by the continued efforts of modern neuroscientists from the 1950’s onwards (most notably dr. karl lashley, who in 1950 gave empirical evidence of engrams by eliciting episodic memories by electrically stimulating different parts of the brain with electrodes (mastin, 2018). despite knowing about the nature of memory, there is little knowledge about what exactly constitutes memory, how it functions, and its relation to other cognitive processes. currently, our understanding of memory is split between two interpretations of neural functioning: the modular approach and the holistic approach. the modular approach (first proposed by jerry fodor in 1983 when he published the book modularity of mind (2-5)) proposes that memories function differently in different parts of the brain as a result of a neural anatomical process known as functional specialization (neurons being functionally assigned different roles based upon localization and necessity (wang, d. et al., 2014). to understand this approach, we must first understand how memories are formed. memories are formed by converting external stimuli into usable electrical signals. touch, for example, uses unmyelinated dorsal root ganglia (drg) neurons to detect pressure and proprioception (body orientation), allowing for afferent messages to be sent via the depolarization of action potentials -electrical signals created by electrochemical gradients (see figures 1.1 and 1.2 )(ch1_neuronv_biov2 8-26)once exteroreceptive (outer body) and/ or interoceptive (inner body) sensations have been detected. these messages then travel to the cortex via the gracilis muscle in the thigh, ascending up the spinal cord to the cunneatus, finally making their way to the second somatosensory cortex, which includes the amygdala and hippocampus (see figure 2.1). proponents of modular theory then propose that memories enter the hippocampus from the cerebral cortex through the perforant pathway, which leads to the entorhinal cortex. this data then flows to the dentate gyrus where it is transferred to the pyramidal neurons of the ca3 region of the hippocampus, which sends the information to the axons of the ca1 region. the subiculum then relays the information back to the entorhinal cortex, which pushes out the data back into the cerebral cortex, where different memories are then divided to be encoded; repressed and emotionally episodic memories are sent to the amygdala and limbic system in people with ptsd or emotional trauma, while semantic memory is stored in the neocortex. other information is mostly kept in the synapses between neurons via complex sequences of neurotransmitters stored in synaptic vesicles waiting to be released at depolarization into the synaptic cleft in both the hippocampus and the cerebral cortexes (see figure 3.1) (rolls, e.t., 1996). holists suggest the very same anatomy, however they maintain that memories are stored across the entirety of the cortex, meaning that all areas overlap with little specialization in memory storage beyond the distinction between the storage of explicit (conscious) memories in the cerebrum and implicit procedural (muscle) and episodic memories in the cerebellum and amygdala (ramachandran, 2009). in essence, holists posit that memory storage is almost completely indeterminate and generalized across the entire brain. both seemingly contrary theories have significant experimental support, meaning the prevailing theory is that memory is a mixture of both holism and modularity. as a result, more recent focus has been given to understanding the cellular mechanisms to better delineate between the two systems to determine their roles in very destructive disorders like alzheimer’s and ptsd. figure 1.1 diagram of neuron figure 1.2: image of the components of a synapse by which neurotransmitters are exchanged end signal transduction occurs. 13 after addressing the physiological distinctions for approaching memory, it’s important to note that current studies on the procedure of recall have shown that memory has not been properly delineated from other cognitive processes as was originally thought. for instance, according to tomita et al., functional magnetic resonance imaging tests (fmri) have determined that during voluntary recall, blood flow aggregation in regions of the frontal lobes associated with conscious thought increased, suggesting that feedback projections from prefrontal cortex to the posterior association cortex appear to serve the executive control of voluntary recall, not the previously believed sub-cortical regions responsible for unconscious activity. this implies that it is possible that memory and consciousness may not be separate at all. in addition, consciousness and memory have been discovered to emerge from the same cellular process. memory is allegedly stored in complex sequences of pyramidal neurons that scientists now believe are capable of quantum computing by mechanism of tau protein synthesis in microtubules from ribosomes in the pyramidal neurons (orchestrated objective reduction theory or orch-or, also known as the penrosehammerhoff model). the specific make up of proteases, tau proteins, and ubiquitin proteins forms a complex system by which signaling occurs to quantum level differences, in which electron transmission is specified to particle level accuracy. this is also now considered the main mechanism of consciousness, as such neurons also associate with other high gray matter areas of the prefrontal and cerebral cortexes. this makes the data stored infinitely complex due to the extensively minute degree of error and incredibly high intensity of specificity (atmanspacher, h., 2004). though the penrosehammerhoff model is a relatively new projection that is still being tested for validity, it does provide a possible explanation for why nonmemory based conscious-driven parts of the cortex activate during voluntary recall. it should also be noted that the previously mentioned synaptic model for memory does imply that the synaptic cleft, which is associated with memory, is also responsible for signal transduction via neurotransmitters, indicating that there is some physiological correlation between the process of signal transduction and memory encoding and storage. an interesting advancement in our current understanding of the connection between memory and consciousness can also be found in stroke victims, specifically those that suffer from cerebral ischemia -brain damage caused by lack of blood flow to the brain(mayo clinic, 2018) patients who have such debilitating strokes have the potential to develop a condition known as capgras syndrome, a unique disorder affecting a person’s ability to relate memory to emotional experience. this rare disorder preserves the pathways for visual recognition within the posterior occipital lobe and temporal lobe, along with emotional centers of the brain such as the amygdala, parts of the diencephalon, and the basal ganglia. however, the connection between the two in the parietal lobe (now believed to be the fusiform gyrus) is damaged, producing an inability to share the processed information between the limbic system and the occipital lobe. as a result, the ailing patients are incapable of recognizing loved ones or processing emotional memories properly. despite being able to recognize people of little significance in their lives and being able to experience emotion, these patients report being surrounded by impostors replacing their loved ones, hence the colloquial name “imposter syndrome”. (ramachandran 158-174) the problem, however, presents a surprising revelation: emotional memories are separable from conscious activity. in patients with capgras syndrome, there is a remarkable ability to consciously forget an individual within a short span of time; however, patients do exhibit an unconscious emotional response that is caused by an emotional “memory” of qualities of the individual. in other words, when someone with capgras syndrome catches up with an old friend, they fail to recognize the friend cognitively, however they unconsciously feel the typical emotions they would around said friend, indicating that emotional memory might be processed separately from conscious memory, only to interweave with consciously streamlined data in the fusiform gyrus. (ramachandran, 2009) similarly, people with severe anterograde amnesia who are incapable of forming new crystallized memories are reportedly able to retain unconscious emotional memory storage, sometimes even exhibiting consistent behavior in spite of not understanding why or how they started the behavior (sacks 23-43) post traumatic stress disorder, another debilitating neuropsychological condition, has revealed that the human brain is capable of altering its capacity of memory storage drastically. ptsd is a result of the overuse of corticotropin-releasing factor (crf) in the hypothalamic-pituitary-adrenal axis system. in the brain, the thalamus circulates crf to facilitate the release of adrenocorticotropic hormone (acth) from the pituitary gland, resulting in the adrenal gland releasing epinephrine. the epinephrine then operates in a negative feedback loop with norepinephrine by mechanism of auto-inhibition through presynaptic α2-adrenoceptors. this negative feedback loop prevents overproduction of cortisol and their consequent overstimulation of the pituitary gland, hypothalamus and hippocampus. (bremner, j.d. et al., 1970) normally, this noradrenergic response is used to maximize utility (more blood flow, more actin filaments prepared by ionized channels, more ready action potentials, and generally faster reflexes in physiological structures) in survival circumstances, increasing activity in the sympathetic nervous system in preparation for dealing with external threats. however, people with ptsd create crf in extreme excess due to both genetic and epigenetic influences. some people are born with more hypothalamic corticotropin-releasing factor mrna, meaning more glucocorticoid protein synthesis occurs (bremner, j.d. et al, 1970). others can have previously unexpressed genes triggered by the environmental factors causing the use of more telomeres which are responsible for cortisol production (yang, b.z. et al., 2013). this overabundance of crf and cortisol has been shown to cause some impairment of intellectual ability in both crystallized and fluid intelligence. according to dr. j. douglas bremner m.d et al., “brain imaging studies have shown alterations in a circuit including medial prefrontal cortex (including anterior cingulate), hippocampus, and amygdala in ptsd… stimulation of the noradrenergic system with yohimbine resulted in a failure of activation in dorsolateral prefrontal, temporal, parietal, and orbitofrontal cortex, and decreased function in the hippocampus.” interestingly, these studies show that not only are memory and verbal ability reduced, but the very process of accessing memory is completely altered during triggered episodes. during posttraumatic episodes, it seems that hippocampus activity is lower than normal while most brain activity is centered in the limbic system; specifically, the amygdala, posterior cingulate, gyrus, and parahippocampal gyrus are active in these periods. the reduced brain activity in areas associated with conscious memory retrieval explain the seemingly random and uncontrollable onset of traumatic episodes and most likely occur due to overstimulation of the sympathetic nervous system. in other words, the mechanism of ptsd is most likely related to an overstimulated fight-or-flight system exercising dominance over the less developed cognitive system of the brain. the dominance occurs due to the limbic system being a far more responsive and developed brain structure, one that operates on hormonal messaging that is longer lasting than simple synaptic signaling. ptsd thus shows that memories are in fact not entirely voluntary and occur due to several diverging mechanisms rather than one (bremner, j.d. et al., 1970). to summarize, memory has been a relatively uninvestigated subject. however, with the advent of modern neuroscience and growing prevalence of memory disorders, it has become a scientific phenomenon worth investigating. memory has been linked to many phenomena, branching emotion, consciousness, instinct, and genetics in a melting pot of complex neural functioning. memory may well be the key to understanding the connection between mind and matter, consciousness, intelligence and human emotion. figure 2.1: image of the path by which sensory information is sent figure 3.1: diagram of the hippocampus and position in the brain 14 references a., f. j. (1983). the modularity of mind. united states: mit press. abraira, v. e., & ginty, d. d. (2014, february 21). the sensory neurons of touch pubmed central (pmc). retrieved february 3, 2019, from https://www.ncbi.nlm.nih.gov/ pmc/articles/pmc3811145/ action potentials and synapses. (2017, november 09). retrieved february 3, 2019, from https://qbi.uq.edu.au/brain-basics/ brain/brain-physiology/action-potentialsand-synapses atmanspacher, h. (2004, november 30). quantum approaches to consciousness. retrieved february 3, 2019, from https:// plato.stanford.edu/entries/qt-consciousness/ bremner, j. d. (1970, january 01). traumatic stress: effects on the brain semantic scholar. retrieved february 3, 2019, from https://www.semanticscholar.org/paper/ traumatic-stress:-effects-on-the-brain-brem ner/9fb167ec76392d212cd303d49ac08e48bc 8230f1 ch1_neuronv_biov2[pdf]. (2018). chennai: indian institute of technology madras. ebbinghaus, h. (2016). memory: a contribution to experimental psychology. united states: scholar select. h, t. (1999, october 14). top-down signal from prefrontal cortex in executive control of memory retrieval. retrieved february 3, 2019, from https://www.ncbi.nlm.nih.gov/ pmc/articles/pmc3511853/ hebb, d. o., phd. (1949). the organization of behavior a neuropsychological theory. chapman hall, ny: john wiley and sons. m. (2018, october 26). stroke. retrieved february 3, 2019, from https://www. mayoclinic.org/diseases-conditions/stroke/ symptoms-causes/syc-20350113 mastin, l. (2018). the study of human memory. retrieved february 3, 2019, from http:// www.human-memory.net/intro_study.html ramachandran, v. s., & blakeslee, s. (2009). phantoms in the brain: probing the mysteries of the human mind. new york: harper perennial. rolls, e. t. (1996). a theory of hippocampal function in memory oxcns.org. retrieved february 3, 2019, from http://www.oxcns. org/papers/205_rolls96.pdf sacks, o. w., & self, w. (2015). the man who mistook his wife for a hat. london: picador. shields, c. (2000, january 11). aristotle’s psychology. retrieved from https://plato. stanford.edu/entries/aristotle-psychology/#7 wang, d. (2014, september 10). functional specialization in the human brain estimated by ... retrieved february 3, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/ pmc4160771/ yang, b. z. (2013, february). child abuse and epigenetic mechanisms of disease risk. retrieved february 3, 2019, from https:// www.ncbi.nlm.nih.gov/pmc/articles/ pmc3758252/ yang, b. z., phd. (2013, february). child abuse and epigenetic mechanisms of disease risk. retrieved february 3, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/ pmc3758252/ copy of volume 7 publication copy of volume 6 publication the mind-body problem and cognitive neuroscience: a brief history and outlook alex ball abstract cognitive neuroscience investigates the relationship between mental processes (such as perception, attention, thought, and memory) and physical states of the nervous system. this relationship gives rise to the mind-body problem, which has long been the subject of debate in philosophy. over the last century, discussion of the problem has been informed by a deluge of empirical evidence from brain and mind sciences. while promising as a method of inquiry, cognitive neuroscience runs into an exceptional difficulty in explaining how non-conscious physical systems gain the ability to have an internal, first-person conscious experience that is characteristic of a mind. the challenge of this gap in explanation is commonly known as the “hard problem” of consciousness. unlike the conceivably resolvable “easy problems” for cognitive neuroscience, such as merely correlating specific brain states with wakeful mental states, the “hard problem” does not have a readily apparent path to solving it. this article will explore early conceptualizations of consciousness, how cognitive neuroscience and related fields have changed how we think about conscious mental states, and what future possibilities there are for achieving a complete understanding of the conscious mind. the challenge of consciousness the mind-body problem is a long-standing question in philosophy: what exactly is the causal relationship between the properties of the mind, particularly conscious experience, and the physical brain? consciousness, while a notoriously contentious term, generally means possessing subjective experience with varying levels of wakefulness. a person, animal, or thing is said to be conscious when they are in some capacity phenomenally aware of the contents of their cognition, such as thoughts, perceptions, beliefs, and emotions. such contents are referred to as mental states in philosophy of mind, and a person possesses conscious mental states in wakeful life or when dreaming and is seemingly absent of them when in deep dreamless sleep, a coma (laureys, 2005), or under sufficient general anesthesia (alkire et al., 2008; pavel et al., 2020). conscious mental states are considered to be part of the mind; they are mental phenomena. for cognitive neuroscience, the challenge of the mind-body problem lies in explaining the precise relationship between such mental properties and the physical brain in an objective manner to establish a unified scientific understanding of both mind and body. intuitively, the mental is separate from the physical. there is an apparent difference between the third-person objectivity of the world examined by the sciences and the first-person subjective nature of conscious mental states, which has historically led to the mind and body being thought of as fundamentally separate (but related) phenomena. historical origin of the problem and mind-body dualism the mind-body problem may have earlier conceptual origins in western philosophy, but the most influential early attempt to resolve it came from rationalist philosopher rené descartes. descartes posited that mental and physical activity occurred in a fundamentally separate, but connected view called substance dualism. he claimed that there are two fundamental aspects to reality: the substance of matter, which is spatially extended in the world and includes the physical body, and the substance of mind (or soul), which is immaterial and non-spatial (descartes, 1641/1986). descartes speculated that the pineal gland, recognized today as a melatonin-secreting endocrine organ (axelrod, 1974), facilitated the interaction between mind and body as the “seat of the soul.” while research into the pineal gland has failed to support such a hypothesis of interaction, descartes’ idea of the body as a purely physical system paved the way for further objective scientific inquiry into human biology, as immaterial causes were localized to only mental activity and the body largely lost its sacred status (shapin, 2000). mindbody dualism continues to be a popular notion in folk psychology. regardless, the view has fallen out of favor as a viable theory of the mind due to the lack of a coherent explanation for interaction between substances and, chiefly, in light of our modern understanding of the nervous system. figure 1. schematic diagram of gpcr structure (neumann et al., 2014).figure 1. schematic diagram of gpcr structure (neumann et al., 2014). 15brain matters volume vi additionally, wm can be further explored at the genetic and molecular levels. for example, hsiao et al.’s (2020) findings suggest that boosting or hampering the expression of the gene gpr12, which encodes the g-protein-coupled receptor gpr12 in mammals, has substantial effects on wm. the researchers associated a higher concentration of gpr12 proteins in the thalamus of mice with better performance in wm tasks in mice, and found that performance suffered when the encoding gene was underexpressed. gpr12 is an orphan g-protein-coupled receptor, meaning its exact endogenous ligand is presently unidentified, but the path to a molecular understanding of wm is entirely conceivable. at first glance, it seems possible for cognitive neuroscience to provide an explanation of the entire causal relationship between particular states of the brain and the functioning of wm and countless other mental processes in the future. however, in the above scientific theories, something vitally important has been left out of the picture. wm is a conscious mental process, and the phenomenal awareness of mental content – one of the most basic properties that separate a conscious state from a non-conscious one – has managed to evade a reductive explanation. the explanatory gap physicalism is often thought of in its reductive form, in which a higher-level property (such as heat) can be functionally explained in the terms of its lower-level properties (molecular motion). a reductive physicalist theory of the mind maintains that the basic elements of consciousness, subjective conscious mental states, can be translated into lower-level properties. a completely reductive understanding of the mind needs to take mental phenomena and reduce them to the language of biology, which can be further translated to chemistry and physics, neatly fitting consciousness with our best scientific theories about the world. reductive physicalist theories of the mind have increasingly come under fire, including from other physicalists who propose that reducing subjective experience to physical terms is an impossible task. such perspectives emphasize the epistemological limits of science, irrespective of the ontological status of the mind as physical. nagel’s (1974) widely influential article “what is it like to be a bat?" argues that consciousness means there is “something that it is like” to undergo mental states for organisms, such as bats, and that such an internal experience is inaccessible to understanding from the outside. according to nagel, a human cannot understand what it is like to be a bat just by understanding every physical fact about the animal. levine (1983) highlights that while we can find certain biological correlates for conscious perceptions such as pain, a scientific explanation for the actual subjective feeling of something like the slow nociceptive pain that seems to result from the activation of c-nerve fibers is nowhere to be found. the central element to these arguments against reductive physicalism is the idea of qualia: a conscious mental state has a qualitative, subjective feeling that is experienced, such as the redness of an apple or the sourness of a lemon. perceptions like color can be reduced to physical explanations in the objective sense by understanding electromagnetism and how the nervous system converts photons into neural activity, but the the mind-body relationship today: contributions from cognitive neuroscience dominant philosophical theories of the underlying nature of consciousness, and the most relevant for cognitive neuroscience, are under the umbrella of physicalism: the doctrine that reality, including the mind, fundamentally consists of only physical things. contrary to substance dualism, only the material substance exists. the popularity of physicalist theories of the mind can be attributed to the empirical study of the brain indicating that the instantiation of the mind is dependent on physical systems, and that its mental processes can be disrupted by physical alteration. for descartes (1649/1989), the ability to think and to reason was a facet of an immaterial and rational soul. contrarily, conscious mental processes have been shown to be just as functionally indebted to the physical structure of the brain as the unconscious regulation of the heartbeat, respiration, and digestion. one such example is working memory (wm), which is critical for the conscious manipulation of information. neuroimaging techniques have discovered that the frontoparietal network and regions such as broca’s and wernicke’s areas, the basal ganglia, the thalamus, and the caudate nucleus variously activate depending on the wm tasks performed (chai et al., 2018). lesions following traumatic brain injury to such regions (often in the frontal lobe) consistently impair wm tasks (owen et al.,1990; barbey et al., 2013). figure 2. simplified illustration of baddeley’s (2010) multicomponent model of working memory, demonstrating multiple cortical structures thought to be involved in various tasks (chai et al., 2018). figure 3. highlighted regions of an fmri scan display activity during two different working memory tasks (graner et al., 2013). 16brain matters volume vi barbey, a. k., koenigs, m., & grafman, j. (2013). dorsolateral prefrontal contributions to human working memory. cortex, 49(5), 1195-1205. chai, w. j., abd hamid, a. i., & abdullah, j. m. (2018). working memory from the psychological and neurosciences perspectives: a review. frontiers in psychology, 9, 401. chalmers, d. j. (1995). facing up to the problem of consciousness. journal of consciousness studies, 2(3), 200-219. churchland, p. m. (1985). reduction, qualia, and the direct introspection of brain states. the journal of philosophy, 82(1), 8-28. https://doi.org/10.2307/2026509 dennett, d. c. (1988). quining qualia. in consciousness in modern science. oxford university press. descartes, r. (1986). meditations on first philosophy: with selections from the objections and replies (j. cottingham, trans). cambridge university press. (original work published 1641) descartes, r. (1989). passions of the soul. (s. voss, trans). hackett publishing. (original work published 1649) graner, j. l., oakes, t. r., french, l. m., & riedy, g. (2013). functional mri in the investigation of blastrelated traumatic brain injury. frontiers in neurology, 4, 16. hsiao, k., noble, c., pitman, w., yadav, n., kumar, s., keele, g. r., terceros, a., kanke, m., conniff, t., cheleuitte-nieves, c., tolwani, r., & rajasethupathy, p. (2020). a thalamic orphan receptor drives variability in short-term memory. cell, 183(2), 522536. jöhr, j., pignat, j. m., & diserens, k. (2015). neurobehavioural evaluation of disorders of consciousness. schweizer archiv für neurologie und psychiatrie, 166(5), 163-169. nagel, t. (1974). what is it like to be a bat? the philosophical review, 83(4), 435-450. https://doi.org/10.2307/ laureys, s. (2005). the neural correlate of (un) awareness: lessons from the vegetative state. trends in cognitive sciences, 9(12), 556-559. https://doi.org/10.1016/j.tics.2005.10.010 levine, j. (1983). materialism and qualia: the explanatory gap. pacific philosophical quarterly, 64(4), 354-361. owen, a. m., downes, j. j., sahakian, b. j., polkey, c. e., & robbins, t. w. (1990). planning and spatial working memory following frontal lobe lesions in man. neuropsychologia, 28(10), 1021-1034. pavel, m. a., petersen, e. n., wang, h., lerner, r. a., & hansen, s. b. (2020). studies on the mechanism of general anesthesia. proceedings of the national academy of sciences, 117(24), 13757-13766. shapin, s. (2000). descartes the doctor: rationalism and its therapies. the british journal for the history of science, 33(2), 131-154. alkire, m. t., hudetz, a. g., & tononi, g. (2008). consciousness and anesthesia. science, 322(5903), 876–880. https://doi.org/10.1126/science.1149213 axelrod, j. (1974). the pineal gland: a neurochemical transducer. science, 184(4144), 1341–1348. baddeley, a. (2010). working memory. current biology, 20(4), 136-140. https://doi.org/10.1016/j.cub.2009.12.014 explanation lacks subjective quality, instances of which are called qualia. trying to explain redness to a congenitally blind person is fruitless because there is, supposedly, no explanatory means to understand qualia without actually experiencing them. if non-reductive accounts of the mind are true, then the intractability of subjectivity is concerning for reductive physicalism and broader hopes that cognitive neuroscience can resolve the mind-body problem. the gap between explaining physical systems and explaining the capacity for qualia is an important point of the contemporary debate over the mind-body problem. some reject the commonsense idea of qualia, viewing the concept as a category mistake that requires further progress in neuroscience to truly understand (churchland, 1985; dennett, 1988); others posit that qualia are (however rudimentarily) a fundamental aspect of some or all physical things (strawson, 2017). regardless, bridging the explanatory gap is what chalmers (1995) has coined “the hard problem” of consciousness, which every complete theory of mind must address in some capacity. the “easy problems” of consciousness, according to chalmers, are those that are conceptually possible for a physicalist inquiry into the mind, such as a complete understanding of only the neural correlates of consciousness. as the above arguments from philosophy of mind have demonstrated, finding a place for the phenomenal awareness aspect of consciousness alongside our reductive explanations of the natural world seems to require a radical reconsideration of either qualia or reality itself. concluding remarks cognitive neuroscience has contributed to the debate surrounding the mind-body problem by narrowing the realm of possibility through the scientific study of the mind’s relationship with the body. when it comes to consciousness, cognitive neuroscience may only be capable of fully explaining the far from trivial “easy problems,” leaving the explanatory gap unbridged. the fundamental nature of the mind and consciousness may always remain an unsolvable mystery. alternatively, the present difficulty in reconciling reductive physicalism with certain properties of consciousness may open the door to entirely new ways of thinking about the mind that have yet to be known or even conceptualized. whether the mind-body problem can be ultimately solved or not, cognitive neuroscience and related fields provide valuable and practical insights into the mental processes of the elusive conscious mind. references 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 17brain matters volume vi strawson, g. (2017). physicalist panpsychism. in the blackwell companion to consciousness, 2nd edition. new york: wiley-blackwell, 374-90. 20. 18brain matters volume vi copy of volume 7 publication copy of volume 7 publication volume 8 (will be vol 7 on site) fine tuning alzheimer’s disease (ad) treatment with music-based interventions (mbi): an anatomical overview celeste acosta abstract music is as universal as language itself across human culture. music processing in the human brain is a dynamic and complex interplay of sensory, cognitive, and emotional functions that promotes healthy amounts of brain activity. the use of music as a nonpharmacological treatment is actively being researched for its potential in treating and managing symptoms associated with neurological disorders parkinson’s disease (pd), alzheimer’s disease (ad), and alzheimer’s disease-related dementias (adrd), or sudden brain injury such as a stroke. this paper will discuss the anatomical hallmarks of music processing, which sets the foundation for discussing the dynamic activation of other brain regions notably affected by alzheimer’s disease. we will discuss the imaging studies that engaged multiple brain regions that allowed researchers to conclude how music-based interventions (mbis) potentially contribute to the enhancement of networks and pathways involved in sensory and motor processes and ad patient psychopathological outcomes. music processing in the brain music, a ubiquitous aspect of the human experience, can transport us through a multitude of physical sensations in milliseconds, yet it begins as something we can’t see, touch or smell: tiny vibrations that swirl through the air. those unique vibrations form notes, which merge into something more complex. it starts as a tune, then a melody, and before you know it, you’re humming along to a song you first listened to at a cafe one afternoon many years ago. but your brain is tricked into thinking it’s back in that moment once again, reanimating the neurons that sparked vividly while the song kept playing, even giving you the same goosebumps that had emerged on your skin back then. music processing begins its journey in the inner ears, where acoustic data transforms into an electric signal via the cochlea. this signal travels through the auditory nerve to the brain stem, specifically to the inferior colliculus– the main area where fundamental sound features like periodicity and intensity undergo initial processing. then, auditory information is sent to the thalamus, where all sensory information is relayed except smell, to finally arrive at the auditory cortex (ac). the ac directly projects to limbic structures, i.e., amygdala and medial orbitofrontal cortex (ledoux, 2000). the primary ac also interacts with the superior temporal areas which further analyze acoustic cues, frequency, pitch, sound level, tempo changes, motion, and spatial locations. the left ac is more attuned to process temporal information, while the right ac in spectral resolution, contributing to the lateralization of speech in the left hemisphere and music right hemisphere (hall et al., 2003). these fundamental structures of the auditory cortex work are what make the most basic sound processing possible. however, music processing and further perception involves regions that go a bit beyond basic sound processing. neuroimaging, primarily fmri studies, have shown that music engages a larger network of cortical regions including the inferior and medial prefrontal cortex, premotor cortex, anterior and posterior parts of the superior temporal gyrus, and the inferior parietal lobe (janata et al., 2002) (patel, 2003). an emotion-inducing piece of music also activates the regions deep in the limbic system–such as the midbrain, the basal ganglia (primarily the nucleus accumbens of the striatum), the amygdala, and the aforementioned hippocampus and cingulate cortex which are also involved in the processing of memory. the group of researchers led by blood et al. in 2001, were the first to publish results that showed evidence of music producing intense pleasure via pet scans. the scans showed increased blood flow to the areas ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex (also involved in music memory), which were previously known to be activated during in response to “euphoria-inducing stimuli” (blood et al., 2001). moreover, the perception of music rhythm, synchronized movement to its beat, and music production via singing or playing an instrument engage the sensory-motor networks of the brain (grahn et al. 2009). these encompass regions in the cerebellum, basal ganglia, and the motor and somatosensory cortices (zatorre et al., 2007). based on comprehensive imaging data, researchers have developed an anatomical delineation of pivotal brain regions implicated in music processing, as illustrated in figure 1. this foundational knowledge is crucial to know in order to grasp the potential therapeutic advantages and outcomes of musicbased interventions. figure 1. key brain areas associated with music processing. adapted from särkämö and colleagues (sihvonen et al., 2017) structures affected by alzheimer’s disease as we delve into the complexities of alzheimer's disease (ad), it's important to keep in mind our ultimate focus: understanding how music-based interventions (mbis) can offer new pathways in ad treatment. the progression of ad, marked by distinct neuropathological stages, sheds light on why and how mbis might be uniquely poised to mitigate some of the cognitive and emotional deficits caused by this disease. alzheimer's disease (ad) unfolds in distinctive neuropathological stages which start with the early accumulation of beta-amyloid plaques and the formation of tau tangles within the cell. in the mild cognitive impairment (mci) stage, cognitive decline becomes noticeable, signaling dysfunction at the neuronal level. progressing to the moderate stage, tau pathology spreads, which eventually impacts deep limbic and cortical regions involved in memory processing, ensuing widespread neuronal cell death (ardent, 2009). at this point of ad, major deficits in memory, behavior, and emotions are noticeable and the major cause of decline in not just overall health but also quality of life (alzheimer’s association, 2023). with modern imaging techniques, researchers are now able to accurately map the structures of the brain that are affected by ad– which can aid the further development of therapeutic treatment options that can target these areas. using quantitative in vivo mri techniques comparing healthy and ad brains, researchers noted initial structural changes in the medial temporal lobe, specifically the entorhinal cortex (detoledo, 2000). further mri studies combined with a series of linear regression showed that dysfunction in the entorhinal cortex disrupts communication between hippocampus and the prefrontal cortex (pfc) of the medial temporal lobe, which leads to more noticeable loss of function in memory, behavior, and emotional regulation (killany et al., 2002). connecting what we know about the areas uniquely activated by music processing and the areas affected in the progression of ad, the use of mbi’s has potential to more directly stimulate areas deep within the cortex. more recent evidence also points to the limbic system regions–which include the amygdala, ventral striatum, and insular cortex–as playing a crucial role in the development of loss of memory and emotional regulation (peck, 2016). the amygdala, a crucial structure for emotional processing in the medial temporal lobe, is affected even in the early stages of ad according to poulin et al. in 2011. previous research shows that music can evoke a strong emotional response because it activates these areas of the limbic system as well. there are major overlaps between structures affected in ad and structures that involve music processing– this simple observation is what has propelled the development of mbis as a plausible form of therapeutic intervention for patients affected by ad and other dementias. music based interventions music based interventions (mbi’s) were first developed in a series of workshops sponsored by the nih in 2022 and have since published the nih music based intervention toolkit (edwards et al. 2023) which is a comprehensive paper delineating the main pillars of mbi’s and how to best integrate it as a non-pharmacological treatment for ad and other neurologic disorders. there is no current standard definition of an mbi because they are unique to each patient in regard to the music style, listening mode, cultural background, and personal significance. it is also important to recognize the current model of care for dementia and where mbi’s fit into the current “standard”. according to the alzheimer's association in 2018, there are a set of recommendations for each category of patient centered treatment models. the integration of mbi’s would be most appropriate under care of behavioral and psychological symptoms of dementia (bpsd), more specifically under the second recommendation of care developed by scales et al. in 2018, which states to “implement nonpharmacological practices that are person-centered, evidence-based, and feasible in the care setting” (fazio et al., 2018) despite the novelty of mbis, there is research from the past decade that has already explored the potential therapeutic effect of music that provides insight on the efficacy of mbis. särkämö et al. completed three different studies over the course of 2014-2016 regarding music listening versus music singing compared to standard care for dementia and ad. both music listening and singing groups showed improvements in behavioral disturbances and physical signs compared to the control group. while these effects weren't sustained after 6 months, singing notably enhanced working memory in mild dementia and maintained executive function and orientation in young people with dementia. music listening supported general cognition, working memory, and quality of life, particularly in moderate dementia without alzheimer’s in institutional care. both interventions alleviated depression, regardless of musical background. music listening improved mood, general orientation, episodic memory, attention, executive functions, overall cognitive performance, and quality of life.this was a decently sized, single blind study with a total of 83 participants. a slightly larger study (n=100) investigated the effects of group music therapy versus standard care alone, and these results showed group music therapy not only decreased depression but also delayed the deterioration of cognitive functions, especially recall. more importantly, these effects persisted 1 month after they stopped the intervention (chu et al., 2014). interestingly, music familiar to the listener distinctly activates the anterior cingulate and medial prefrontal cortex in a healthy brain, indicating their significance in musical memory (jacobsen et al., 2015). in ad individuals, the medial prefrontal cortex experiences a slower degeneration compared to other cortical areas. moreover, the regions responsible for encoding musical memory exhibit minimal atrophy or decline in glucose metabolism, despite similar amyloid-β deposition when compared to other cortical regions. these findings potentially explain why alzheimer's patients can still recognize and emotionally respond to familiar songs, even in advanced stages of the disease (jacobsen et al., 2015). brain matters・volume vii 10 conclusion music, in its simplest form, dynamically engages sensory, cognitive, and emotional functions in the human brain. understanding the neurological pathways of music processing in the brain is one of many facets that involve the further development of music-based interventions as a nonpharmacological treatment for neurological disorders. mbis show promise in enhancing networks crucial for sensory, motor processes, emotions, and memory. while there are still major improvements to be made in terms of further data collection process and understanding of the molecular dynamics of music processing in the human brain, the current exploration of music's therapeutic benefits represents a progressive shift toward addressing the complexities of brain disorders associated with different types of dementia. other limitations of mbis that could be addressed pertain to the duration of the effects of treatment and the factors that most influence the effects of the treatments to be sustained. overall, mbis emerge as an accessible and non-invasive treatment option in addition to traditional therapies, offering potential improvements in ad patient outcomes. references 1. arendt, t. (2009). synaptic degeneration in alzheimer’s disease. acta neuropathologica, 118(1), 167–179. https://doi.org/10.1007/s00401-009-0536-x 2. blood, a. j., & zatorre, r. j. (2001). intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. proceedings of the national academy of sciences, 98(20), 11818–11823. https://doi.org/10.1073/pnas.191355898 3. chen, w. g., iversen, j. r., kao, m. h., loui, p., patel, a. d., zatorre, r. j., & edwards, e. (2022). music and brain circuitry: strategies for strengthening evidence-based research for music-based interventions. the journal of neuroscience, 42(45), 8498–8507. https://doi.org/10.1523/jneurosci.1135-22.2022 4. chu, h., yang, c.-y., lin, y., ou, k.-l., lee, t.-y., o’brien, a. p., & chou, k.-r. (2014). the impact of group music therapy on depression and cognition in elderly persons with dementia: a randomized controlled study. biological research for nursing, 16(2), 209–217. https://doi.org/10.1177/1099800413485410 5. de toledo-morrell, l., goncharova, i., dickerson, b., wilson, r. s., & bennett, d. a. (2006). from healthy aging to early alzheimer’s disease: in vivo detection of entorhinal cortex atrophy. annals of the new york academy of sciences, 911(1), 240–253. https://doi.org/10.1111/j.17496632.2000.tb06730.x 6. edwards, e., st hillaire-clarke, c., frankowski, d. w., finkelstein, r., cheever, t., chen, w. g., onken, l., poremba, a., riddle, r., schloesser, d., burgdorf, c. e., wells, n., fleming, r., & collins, f. s. (2023). nih musicbased intervention toolkit: music-based interventions for brain disorders of aging. neurology, publish ahead of print. https://doi.org/10.1212/wnl.0000000000206797 7. fazio, sam, et al. “alzheimer’s association dementia care practice recommendations.” the gerontologist, vol. 58, no. 1, 18 jan. 2018, pp. s1–s9, https://doi.org/10.1093/geront/gnx182. 8. grahn, j. a., & rowe, j. b. (2009). feeling the beat: premotor and striatal interactions in musicians and nonmusicians during beat perception. journal of neuroscience, 29(23), 7540–7548.https://doi.org/10.1523/jneurosci.2018-08.2009 9. hall, d. a., hart, h. c., & johnsrude, i. s. (2003). relationships between human auditory cortical structure and function. audiology and neurotology, 8(1), 1–18. https://doi.org/10.1159/000067894 10. jacobsen, j.-h., stelzer, j., fritz, t. h., chételat, g., la joie, r., & turner, r. (2015). why musical memory can be preserved in advanced alzheimer’s disease. brain : a journal of neurology, 138(pt 8), 2438–2450. https://doi.org/10.1093/brain/awv135 11. janata, p. (2002). the cortical topography of tonal structures underlying western music. science, 298(5601), 2167–2170. https://doi.org/10.1126/science.1076262 12. janata, p., tillmann, b., & bharucha, j. j. (2002). listening to polyphonic music recruits domain-general attention and working memory circuits. cognitive, affective, & behavioral neuroscience, 2(2), 121– 140. https://doi.org/10.3758/cabn.2.2.121 13. killiany, r. j., hyman, b. t., gomez-isla, t., moss, m. b., kikinis, r., jolesz, f., tanzi, r., jones, k., & albert, m. s. (2002). mri measures of entorhinal cortex vs hippocampus in preclinical ad. neurology, 58(8), 1188–1196. https://doi.org/10.1212/wnl.58.8.1188 14. koelsch, s. (2014). brain correlates of music-evoked emotions. nature reviews neuroscience, 15(3), 170–180. https://doi.org/10.1038/nrn3666 15. ledoux, j. e. (2000). emotion circuits in the brain. annual review of neuroscience, 23(1), 155–184. https://doi.org/10.1146/annurev.neuro.23.1.155 16. lehericy, s., hirsch, e. c., cervera, p., hersh, l. b., hauw, j. j., ruberg, m., & agid, y. (1989). selective loss of cholinergic neurons in the ventral striatum of patients with alzheimer disease. proceedings of the national academy of sciences, 86(21), 8580–8584. https://doi.org/10.1073/pnas.86.21.8580 17. pando-naude, v., patyczek, a., bonetti, l., & vuust, p. (2021). an ale meta-analytic review of top-down and bottom-up processing of music in the brain. scientific reports, 11(1). https://doi.org/10.1038/s41598-021-00139-3 18. patel, a. d. (2003). language, music, syntax and the brain. nature neuroscience, 6(7), 674–681. https://doi.org/10.1038/nn1082 19. peck, k. j., girard, t. a., russo, f. a., & fiocco, a. j. (2016). music and memory in alzheimer’s disease and the potential underlying mechanisms. journal of alzheimer’s disease, 51(4), 949–959. https://doi.org/10.3233/jad-150998 20. platel, h., baron, j.-c., desgranges, b., bernard, f., & eustache, f. (2003). semantic and episodic memory of music are subserved by distinct neural networks. neuroimage, 20(1), 244–256. https://doi.org/10.1016/s10538119(03)00287-8 https://doi.org/10.1073/pnas.191355898 https://doi.org/10.1111/j.1749-6632.2000.tb06730.x https://doi.org/10.1111/j.1749-6632.2000.tb06730.x https://doi.org/10.1212/wnl.0000000000206797 https://doi.org/10.1093/brain/awv135 21. poulin, s. p., dautoff, r., morris, j. c., barrett, l. f., & dickerson, b. c. (2011). amygdala atrophy is prominent in early alzheimer’s disease and relates to symptom severity. psychiatry research: neuroimaging, 194(1), 7–13. https://doi.org/10.1016/j.pscychresns.2011.06.014 22. särkämö, t., tervaniemi, m., & huotilainen, m. (2013). music perception and cognition: development, neural basis, and rehabilitative use of music. wiley interdisciplinary reviews: cognitive science, 4(4), 441–451. https://doi.org/10.1002/wcs.1237 23. sihvonen, a. j., särkämö, t., leo, v., tervaniemi, m., altenmüller, e., & soinila, s. (2017). music-based interventions in neurological rehabilitation. the lancet neurology, 16(8), 648–660. https://doi.org/10.1016/s14744422(17)30168-0 24. zatorre, r. j., chen, j. l., & penhune, v. b. (2007). when the brain plays music: auditory–motor interactions in music perception and production. nature reviews neuroscience, 8(7), 547–558. https://doi.org/10.1038/nrn2152 25. zatorre, r., evans, a., & meyer, e. (1994). neural mechanisms underlying melodic perception and memory for pitch. the journal of neuroscience, 14(4), 1908–1919. https://doi.org/10.1523/jneurosci.14-04-01908.1994 brain matters・volume vii 12 copy of volume 7 publication volume 8 (will be vol 7 on site) once the information passes the optic chiasm, it continues to the lateral geniculate nucleus, which is a part of the thalamus. all sensory information passes through the thalamus, and then visual information is finally passed to the visual cortex. the visual cortex is where the images from the retina finally begin to be processed and are recognized by our brain (baskin 2021). the complexity of the visual processing pathway leads to the possibility of error at any point. different optical illusions target different parts of the pathway in order to have the effect that they do. hermann grid illusion one famous example of an optical illusion is the hermann grid illusion. as seen in figure 1, this illusion tricks the brain into believing there are gray circles located in the intersections of white lines. these circles are seen due to the posterior and anterior neuron connection. posterior neurons convert light stimuli into electrochemical messages. these messages are then sent to the anterior neurons, also known as ganglion cells. these ganglion cells are tasked with deciphering all the information they receive; the inputs that these ganglion cells receive are either excitatory or inhibitory. from there, they decide how best to transfer the information to other parts of the brain. their decisions result in the unique organization of ganglion cells, which is often known as center surround. when one views the hermann grid illusion, ganglion cells are activated. the first ganglion cell (referred to as ganglion one) has 10 out of 16 of its inputs exposed to light. optical illusions: what are they, and why do they occur? ananya sampathkumar abstract optical illusions are commonly used in psychology classes in order to show how the brain can be easily manipulated. these illusions all target different parts of the visual pathway. as a result, researchers are able to find the specific reasons for some illusions, such as the hermann grid. however, scientists currently have no specific reason that all illusions trick us. as further research is done, optical illusions will be better understood, and scientists will be able to use them to further understand the visual pathway. introduction very often, people will claim to see things that do not exist. whether that could be witnessing a mythical creature or losing track of a bug, our brain and eyes can often play tricks on us. one common trick played on our senses are optical illusions. optical illusions, also called visual illusions, are a phenomenon that occurs when the perception of something differs from the actual reality of it ( yoshimoto, et al. 2021). some commonly discussed optical illusions are the hermann grid illusion, the kanizsa triangle, and the lilac chaser. these visual illusions play differing tricks on your mind, making you see motion and shapes where there are neither. there are a multitude of possible reasons why optical illusions continue to play tricks on our mind. while each optical illusion is different in its effects on the brain, there are a few theories as to why these images fool our brains into seeing such differences from reality. visual cue pathway the visual processing system is an incredibly complex pathway with many different parts of the brain and the eye involved. it begins when light enters the eye. from the iris and lens, light will be projected onto the retina. the retina is a very important part of the visual system as it determines the type of image that will be seen. inside of the retina, there are two different types of photoreceptors: rods and cones. rods are located on the periphery of the retina, and assist in the processing of images in low light and in black and white. on the contrary, cones are found in the center of the retina and process images in higher light with different colors. from the retina, a cranial nerve known as the optic nerve receives the information. this information is passed through until it reaches the optic chiasm. the optic chiasm is the intersection between the two optic nerves that allows for information from the left eye field and right eye field to be sent to both sides of the brain. without it, our brain would only receive half of our visual information and would not be able to function as properly. figure 1. hermann grid illusion. black squares are separated by white lines. when staring at white lines, there seem to be gray circles in the intersection of the white lines where there are not (university of pittsburgh, 2019). brain matters・volume vii 36 of these 10 inputs, eight of them are excitatory and two are inhibitory. the two inhibitory inputs are canceled out by the excitatory inputs, leading to a net gain of six excitatory inputs. due to the increased amount of excitatory inputs in comparison to inhibitory inputs, the white line seems very bright. the second ganglion cell (referred to as ganglion two) has no excitement at all. due to not having any inhibitory inputs or excitatory inputs, the surround is repressed, and the center is not excited. as a result, the black background is shown as very dark. finally, the third ganglion cell (referred to as ganglion three) has 12 out of 16 inputs exposed to light. out of these 12, eight are excitatory and four are inhibitory. as a result, the net result is four excitatory inputs, so the intersections between the white lines seem darker than the lines themselves. as a result, they are processed as a light gray color, tricking our brains into believing that the intersections are a darker color than the rest of the lines (university of pittsburgh, 2019). while the hermann grid illusion is easily explainable, this is simply one example of an optical illusion. there are many different types of illusions that all affect different parts of the brain. despite this example, scientists still do not have specific answers as to why all optical illusions occur in the way that they do. theories on optical illusions while there is information regarding specific illusions, scientists do not know what truly causes optical illusions (van der berg 2019). however, scientists have a few theories. one reigning theory is the backward processing theory. this theory states that information travels through circuits of neurons. usually, all this information is processed through the visual pathway and then passed on to the prefrontal cortex for decision-making. however, scientists believe that not all the information stays on this path, and some neurons change course by sending information back to the first stage of processing. this theory accounts for the processing of the kanizsa triangle, specifically (duffy, 2016). another popular theory is that our brain simply misunderstands the signals it is being given by the eyes. sometimes the visual cues are not enough to provide the necessary information for the brain to function properly, so some assumptions are made in order to maintain normal processing. as a result, some scientists believe that optical illusions are caused by a lack of information or a misinterpretation of the visual cues by the brain (van der berg 2019). summary optical illusions occur when the brain incorrectly perceives images. these illusions manipulate different parts of the visual information pathway, and as a result, scientists are unable to figure out why exactly optical illusions occur. while researchers know how and where specific illusions like the hermann grid illusion occur, they have two reigning theories as to why these occur on a broader scale: the backwards processing theory and the misunderstanding theory. understanding optical illusions is crucial to the understanding of the visual pathway and all the issues that can occur during processing. with time, we will be able to better understand how the body perceives visual signals. references 1. baskin, k. (2023, may 30). the visual pathway from the eye to the brain. perkins school for the blind. https://www.perkins.org/the-visual-pathway-from-the-eye-tothe-brain/ 2. duffy, j. (2016, march 29). neuronal feedback could change what we “see”. carnegie mellon university. https://www.cmu.edu/news/stories/archives/2016/march/optic al-illusions.html 3. ross lab. (n.d.). making sense of the hermann grid illusion. university of pittsburgh. https://www.rosslab.neurobio.pitt.edu/making-sense-of-thehermann-grid-illusion/ 4. van der berg, c. (2022, august 16). how does an optical illusion work? queensland brain institute, university of queensland. https://qbi.uq.edu.au/blog/2019/10/how-does-optical-illusionwork#:~:text=optical%20ill 5. yoshimoto, s., & takeuchi, t. (2021, november). the mechanisms of the visual system behind visual illusions: from eye to brain. national library of medicine. https://pubmed.ncbi.nlm.nih.gov/34759062/#:~:text=higher% 20visual%20areas%20are %20responsible,a%20two%2ddimensional%20retinal%20im age. figure 2. hermann grid illusion. black squares are separated by white lines. when staring at white lines, there seem to be gray circles in the intersection of the white lines where there are not (university of pittsburgh, 2019). https://www.rosslab.neurobio.pitt.edu/making-sense-of-the-hermann-grid-illusion/ volume 8 (will be vol 7 on site) astrocytes and their role in psychiatric disorders pravika srivastava abstract astrocytes are the most abundant glial cells in the central nervous system. they are recognized as active participants in neurodevelopment, neurotransmission and synaptic plasticity. astrocytes are increasingly associated with the modulation of neuronal circuits and regulation of neurotransmitter balance. the dysregulation of these functions may contribute to the progression of psychiatric illnesses. the understanding of astrocytes and their relation to psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder is constantly evolving. targeting astrocytes in the development of therapeutic interventions for psychiatric disorders is an emerging avenue of exploration. this paper discusses the exact function of astrocytes, their part in synaptic plasticity and how they play a crucial role in the development and presence of psychiatric illnesses, specifically schizophrenia and mood disorders. what are astrocytes? one of the most integral components of one’s central nervous system are astrocytes. in the past, astrocytes were thought to act only as supporting cells for neurons; however, modern research suggests that they may play additional, multifaceted roles crucial to the proper functioning of the nervous system. structurally, astrocytes possess numerous fine processes extending from their cell bodies, which form intricate networks that wrap around neurons and their synapses. it is oftentimes said that astrocytes are in “close structural association with synapses” (notter, 2021). this feature in astrocytes greatly helps in regulating synaptic transmission. functionally, they contribute to the maintenance of neuronal health and homeostasis by regulating nutrient and ion levels, as well as participating in the formation and maintenance of the bloodbrain barrier. the role of astrocytes in neurotransmission and synaptic plasticity neurotransmission and synaptic plasticity are critical functions of astrocytes that are necessary for the nervous system's essential processes and function. by actively contributing to the control of neurotransmitter levels in the synaptic cleft (the narrow space between two neurons in which chemicals are exchanged), astrocytes have a significant impact on neurotransmission. the process by which neurotransmitters—chemical messengers in the brain —are reabsorbed into presynaptic neurons following their release into the synaptic cleft is known as neurotransmitter reuptake. ensuring appropriate neurotransmitter levels and controlling neuronal transmission depend on this mechanism. neurotransmitters like gamma-aminobutyric acid (gaba), a major inhibitory neurotransmitter, and glutamate (the most abundant neurotransmitter in the body), a major excitatory neurotransmitter, are taken up by astrocytes after their release into the postsynaptic cell. astrocytes assist in stopping the signaling between neurons by removing these neurotransmitters from the synaptic cleft, avoiding overstimulation and preserving the equilibrium of neuronal activity. in addition to neurotransmission, they also play a crucial role in synaptic plasticity. they release signaling molecules, such as gliotransmitters, which can modulate the strength of synaptic connections. synaptic connection is what controls the consistency of transmissions between two specific cells. the significance of these connections between two neurons can be influenced by various factors such as the frequency of activation, the relevance of information and neurotransmitter type, just to name a few. moreover, astrocytes control a process known as synaptic pruning, which strengthens and improves significant synaptic connections while removing less significant ones. (nimh. 2023, march). astrocytes influence long-term potentiation (ltp) and long-term depression (ltd), two forms of synaptic plasticity associated with learning and memory. ltp is the process by which synaptic connections strengthen and ltd involves weakening them. glutamate, atp and cytokines are all compounds that astrocytes regulate in the process of plasticity (ota, y., zanetti, a. t., & hallock, r. m. 2013). figure 1. visualization of astrocyte structure and some of its roles (research gate, 2016) these factors modulate ltp and ltd, influencing the persistence and strength of synaptic changes associated with memory formation. psychiatric disorders and their prevalence psychiatric disorders, also referred to as mental health disorders, are a broad category of problems that impact a person's thoughts, feelings, actions, and general state of health. these complicated illnesses are frequently caused by a mixture of biological, psychological, environmental, and hereditary variables. they impact a wide range of individuals and, as shown in a study from the world health organization in 2019, approximately 1 in 8 people suffered from some variation of mental illness. additionally, these numbers drastically increased after the covid-19 pandemic (world health organization, 2022). there are a broad range of categories for psychiatric disorders such as, depressive, anxiety, bipolar, neurodevelopmental, etc. are a few amongst the many different types of illnesses. the prevalence of psychiatric disorders varies upon many different factors such as which disorder it is, geographic location as well as cultural factors. mental illness encompasses many different conditions ranging from mild to moderate to severe. there are two distinct categories when it comes to mental illnesses: any mental illness (ami) and serious mental illness (smi). ami includes all recognized mental illnesses. smi is a smaller and more severe subgroup of ami. (national institute of mental health, 2023). schizophrenia & mood disorders schizophrenia is a serious and chronic mental disorder that greatly impacts a person's thinking, emotions and behavior. symptoms of schizophrenia can be characterized as either positive and negative. positive symptoms involve things that are physically/outwardly visible and add factors into one’s behavior, whereas negative symptoms are much more subtle, difficult to observe and tend to subtract a factor from one's behavior. (national library of medicine, 2019). mood disorders are another type of psychiatric illness. they significantly impact one’s mood regulation and can impact their daily tasks and overall mental well being. some common mood disorders include major depressive disorder and bipolar disorder. they also impact one’s emotions and behavior through a series of hallucinations, disorganized thinking, etc. however, mood disorders emphasize a persistent feeling of sadness and can eventually lead to a lack of interest in everyday activities that an individual once enjoyed (national library of medicine, 2019). how do astrocytes relate to these disorders? dysfunctional synaptic pruning has been observed in schizophrenia (sekar et al., 2016), which can lead to inflammation in the brain, disruption of balance of neural circuits as well as irregular brain connectivity (birnbaum & weinberger, 2017). these genetic variations in affecting astrocyte function can cause individuals to be more susceptible to this disorder. moreover, astrocytes play a critical role in neuroplasticity, which is commonly known as the brain’s ability to adapt and reorganize. neuroplasticity is oftentimes impaired in such psychiatric conditions (santello, m., 2019). in mood disorders, dysfunctional astrocytes can influence weak synaptic connectivity and prevent regulation in reuptake and release of neurotransmitters, leading to such disorders. in addition to this, it has been noted that astrocytes also help in regulating neurotransmitter levels which are typically dysregulated in the disordered brain. they play an intricate role in maintaining the balance of these neurotransmitters and dysfunction of this role may contribute to symptoms of such disorders (nimh, 2023). dopamine imbalance is highly common in schizophrenia (correll, c. 2020). if astrocytes are unable to undergo the process of neurotransmitter uptake and regulate their levels, it may lead to something similar to dopamine imbalance which eventually contributes to the symptoms of schizophrenia. conclusion the evolving understanding of astrocytes and their roles in the central nervous system emphasizes their importance to psychiatric disorders. through their regulation of neurotransmitter balance, synaptic transmission, and plasticity, they have exerted great influence over the neuronal circuits necessary for mood regulation. by investigating the complex relationship between astrocytes and psychiatric disorders, further research may lead to new approaches for managing complex conditions and improving treatment for individuals that suffer from such illnesses. thus, continued research and studies on astrocytes holds immense potential to advance and better our understanding and treatment of psychiatric disorders. references 1. birnbaum, r., & weinberger, d. r. (2017). genetic insights into the neurodevelopmental origins of schizophrenia. nature reviews neuroscience, 18(12), 727–740. https://doi.org/10.1038/nrn.2017.125 2. correll, c., & schooler, n. (2020). negative symptoms in schizophrenia: a review and clinical guide for recognition, assessment, and treatment. neuropsychiatric disease and treatment, 16(1), 519–534. https://doi.org/10.2147/ndt.s225643 figure 2. diagram of plasticity of structural interactions, synaptic elements and astrocytes (santello et al., 2019). brain matters・volume vii 2 3. figure 1: astrocytes have close morphological and functional. (n.d.). researchgate. https://www.researchgate.net/figure/astrocytes-have-closemorphological-and-functional-associations-withmicrovasculature-and_fig1_290479871 4. nimh. (2023, march). mental illness. national institute of mental health. https://www.nimh.nih.gov/health/statistics/mental-illness 5. notter, t. (2021). astrocytes in schizophrenia. brain and neuroscience advances, 5, 239821282110091. https://doi.org/10.1177/23982128211009148 6. samhsa. (2022, march 31). living well with serious mental illness. www.samhsa.gov. https://www.samhsa.gov/serious-mental-illness 7. santello, m., toni, n., & volterra, a. (2019). astrocytes function from information processing to cognition and cognitive impairment. nature neuroscience, 22(2), 154–166. https://doi.org/10.1038/s41593-018-0325-8 8. sekar, a., bialas, a. r., de rivera, h., davis, a., hammond, t. r., kamitaki, n., tooley, k., presumey, j., baum, m., van doren, v., genovese, g., rose, s. a., handsaker, r. e., daly, m. j., carroll, m. c., stevens, b., & mccarroll, s. a. (2016). schizophrenia risk from complex variation of complement component 4. nature, 530(7589), 177–183. https://doi.org/10.1038/nature16549 9. world health organization. (2022, june 8). mental disorders. world health organization. https://www.who.int/news-room/fact-sheets/detail/mentaldisorders 10. zhou, x., xiao, q., xie, l., yang, f., wang, l., & tu, j. (2019). astrocyte, a promising target for mood disorder interventions. frontiers in molecular neuroscience, 12. https://doi.org/10.3389/fnmol.2019.00136 brain matters・volume vii 4 copy of volume 6 publication about brain matters brain matters discusses all things neuroscience, psychology, and biology written by uiuc’s very own. authors come from diverse backgrounds, such as computer science and engineering majors. not to mention, the journal welcomes all authors no matter their area of study or year. this diversity allows volumes to have a wide range of articles. the journal is mainly written for the college community yet is accessible to anyone as brain matters is uploaded as an open access journal format by the university library. sponsors the undergraduate neuroscience society (uns) sponsors the brain matters journal. uns is a uiuc registered student organization that is dedicated to establishing and growing the neuroscience community on campus. copy of volume 6 publication deep brain stimulation advancements in clinical medicine, innovation in cutting-edge technology bilal karim introduction scientific innovation has been incredibly influential, leading to countless breakthroughs, especially in surgical technology. these discoveries have revolutionized access to quality patient care and adequate treatment. we have seen new creations and developments in artificial intelligence, leading to optimized support and management for triage, and efficient reviewing of electronic health records (ehr). however, a relatively new remedy called deep brain stimulation has become more prominent in the treatment of several debilitating neurological symptoms. this procedure is most commonly used to treat diseases like parkinsons, essential tremors, and epilepsy (especially focal epilepsy which originates in the frontal, occipital, temporal, and parietal part of the brain). these diseases are characterized by tremors, rigidity, stiffness, and slowed movement (national institute for health, 2017). dbs is considered a plausible treatment option for movement disorders, and is generally performed when medications have become less effective and begin interfering with daily life activities (ui hospitals). anatomy of deep brain stimulation dbs uses a surgically implanted, battery-operated medical device called the implantable pulse generator (ipg), which is placed deep into a central location in the brain. the ipg is similar to that of a heart pacemaker, and dimensions are approximately similar to that of a stopwatch. dbs is designed to deliver electrical stimulation to localized regions of the brain that control movement, which ultimately block or inhibit the nerve signals that cause the symptoms. dbs consists of three components: the lead, the extension and the ipg. the lead (commonly known as the electrode), is a thin, insulated wire that is inserted through a small opening in the skull and positioned in the brain. next, we have the extension component, which is an insulated wire that is passed underneath the skin, and connects the lead to the ipg. lastly, the ipg (our “battery pack”) is the third and final part that is implanted under the skin near the collarbone. the length of the wire and the distance between the electrode will determine the ideal placement at which the ipg can be planted. mechanisms of dbs implants have become widely accepted over the last few years and research has led to the development of several advanced designs and blueprints for them. all modern implantable pulse generators (ipg) contain a radiofrequency antenna, which leads to increased usability, and enables clinicians to deploy external programming devices to monitor for impedence and for editing stored data. in ‘closed-loop’ or ‘adaptive’ dbs, the stimulator is able to measure neural activity while synchronously stimulating the target zone. these devices are increasingly taking the form of ‘apps’ on consumer-grade mobile devices such as smartphones and tablets. ipgs use proprietary radio communication protocols. more recently, sumer-grade mechanisms such as bluetooth are being utilized in order to facilitate over-the-air modifications and remote connections. as for diagnoses, neurologists and other clinicians use powerful magnetic imaging to make a clear and concise decision regarding the exact target for surgical implantation within the brain. these regions include the subthalamic nucleus, the thalamus, and the globus pallidus. during the operation, surgeons are able to use microelectrode monitoring to improve the overall condition of the patient. in most circumstances, dbs has been approved for a wide variety of conditions and has shown to be remarkably safe and effective (cleveland clinic, 2020). while symptoms may not be eliminated, they can be reduced to a tolerable amount. the results are widely dependent on the appropriate selection of patients, stimulation of the correct brain region, and precise positioning of the electrode during surgery, and evidence-based programming and medical management. functionality & implementation parkinson’s disease is closely linked with a significant loss in functionality of dopaminergic cells within the substantia nigra pars compacta (snc). these dopaminergic cells also project to the striatum a major arc of the basal ganglia (american association of neurological surgery). dopaminergic regions primarily consist of motor, cognitive, and limbic loops. the snc has connections to locations of the brain that control both motor and non-motor functions. two important regions, the subthalamic nucleus (stn) and the globus pallidus internus (gpi) have proven to be powerful targets for managing abnormal electrical circuits. they alleviate the symptoms of bradykinesia, motor fluctuations, and dyskinesia (john gardner, sagepub, 2013). following activation, the lead and electricity it emits will work to normalize brain signals, resulting in a smoother response to medication. dbs has proven to be an exciting and effective tool for treating a large spectrum of conditions, but there is a good reason that the field is only beginning to recognize its full potential. subsequently, use of a powerful technology for modulation purposes will inevitably lead to dire consequences and serious negative risk in the case of poor implementation. 19brain matters volume vi deep brain stimulation (dbs). cleveland clinic. (n.d.). retrieved november 5, 2021, from https://my.clevelandclinic.org/health/treatments/21088deep-brain-stimulation deep brain stimulation. deep brain stimulation | uva health. (n.d.). retrieved november 7, 2021, from https://uvahealth.com/services/parkinsons-movementdisorders/deep-brain-stimulation nowadays, dbs systems rely on stimulation parameters set forth by a neurophysiologist, clinician, or even the patient. the system will remain static until manually modified. the rollout of dbs has been limited due to a wide variety of challenges in optimizing each component of the feedback (john gardner, sagepub, 2013). ipg designs have also improved in terms of their ability to network with other devices. this networking may occur between smartphones and tablets, leading to wider accessibility. nonetheless, the inherent cybersecurity risk does increase with wirelessly communicating electronic devices. attackers who could potentially gain access to the ipg could cause considerable harm to patients and their clinical state. potential advancements for treatment refinement of dbs gives way to changes in medical applications and furthers the spectrum of improved technology. in the future, technological advancements may allow the implantation of several electrodes in the brain. this can enable the treatment and diagnosis of multiple symptoms at once, or the synergistic treatment of one symptom via multiple apparatuses. currently, a few ipgs are highly capable of stimulating up to two different frequencies simultaneously. however, newer devices may allow new stimulation protocols to be established for each parameter that involves electrode contact with the respective region (cedars-sinai medical center, 2016). it is important to remember that dbs does not restore one’s previous quality of life; it will only allow one to achieve more independence in one’s daily life. conclusion & constraints as we strengthen our perspective surrounding neurophysiological contraptions, we gain a stronger perspective on how we can successfully target multiple structures in the brain for electrical modulation via dbs. dbs has single-handedly drawn out curiosity in both scientists and the general public by offering a humanitarian and scientific perspective. the indicators for dbs will continue to expand to cover a wider range of disorders. the development of more effective paradigms such as closed-loop simulations will enhance refractory movement disorders, resulting in stronger microelectrode mapping. the increase in fundamental knowledge concerning human health and mechanisms of disease have made it easier to invest in biological advancements and innovation. the next few years of modernization will be crucial, and should spark an uptick of growth, leading to a scientific revolution of sorts. references 1. 2. programming adjustment the programming of the stimulator system is usually performed in an outpatient setting, but in some circumstances, it may be activated before the patient’s discharge from the treatment facility. generally, there is an immediate improvement in some pd symptoms, however, some patients may take up to a week or a month to notice improvements. patients may also be admitted to a rehabilitation center, allowing clinicians to closely evaluate and monitor their response to dbs and adjust medication as needed. the endless combinations and configurations of dbs make it difficult to find a setting which is best suited to the individual. each dbs electrode has four leads within it, of which two are activated. the lifespan of the battery should last anywhere from two to five years. a dbs programmer should regularly check on the device to ensure that there is no loss of therapy efficacy. research obligations & ethical validity dbs faces several prominent concerns due to its widespread adoption and establishment. a complete investigation pointed to many complexities, which have acted as impediments to the continued progression of dbs. the successful translation and interpretation of research into clinical use is thwarted by obscurity in adopting suitable clinical trials. for most experiments, blinding is unachievable, as patients are actively awake during the stimulation. nonetheless, performing well blinded trials is easier to achieve in comparison to traditional ablation surgeries, as neurostimulators can be activated and manipulated without the need for unnecessary surgery. additionally, dbs is an expensive tool to use and maintain. dbs is game-changing and life-saving; however, it should only be used in extremely rare and heightened emergencies due to the non-trivial risks associated with surgery (university of virginia health, 2021). this expense is problematic in the real world, as very few people have the resources to afford the treatment and hardware, even if the treatment warrants consideration. increased production of low-cost ipgs would be logical, although the lack of surgical centers and providers still create barriers. 20brain matters volume vi gardner j. (2013). a history of deep brain stimulation: technological innovation and the role of clinical assessment tools. social studies of science, 43(5), 707– 728. https://doi.org/10.1177/0306312713483678 pycroft, l., stein, j., & aziz, t. (2018). deep brain stimulation: an overview of history, methods, and future developments. brain and neuroscience advances. https://doi.org/10.1177/2398212818816017 u.s. department of health and human services. (2017, june 20). a noninvasive deep brain stimulation technique. national institutes of health. retrieved november 11, 2021, from https://www.nih.gov/newsevents/nih-research-matters/noninvasive-deep-brainstimulation-technique spine, m. b. &. (n.d.). dbs. mayfieldclinic.com. retrieved november 12, 2021, from https://mayfieldclinic.com/pedbs.htm towards the next generation of deep brain stimulation therapies: technological advancements, computational methods, and new targets. frontiers. (n.d.). retrieved october 14, 2021, from https://www.frontiersin.org/research-topics/9483/towardsthe-next-generation-of-deep-brain-stimulation-therapiestechnological-advancements-computati update on current technologies for deep brain stimulation in parkinson's disease. journal of movement disorders. (n.d.). retrieved december 5, 2021, from https://www.ejmd.org/journal/view.php?number=302 m;, d. o. m. k. j. r. u. t. (2016, august 11). subthalamic nuclei deep brain stimulation improves color vision in patients with parkinson's disease. brain stimulation. retrieved january 2, 2022, from https://pubmed.ncbi.nlm.nih.gov/27591893/ 3. 4. 5. 6. 7. 8. 9. 21brain matters volume vi copy of volume 7 publication copy of volume 7 publication andrew zhang is a sophomore majoring in molecular and cellular biology. currently, he is a research assistant in dr. huimin zhao’s lab and also part of uiuc’s american chemistry society and react. he believes that neuroscience is a great field to learn about. there are so many things to learn about the brain especially ideas that can improve our lives. he is excited to be a part of brain matters in sharing neuroscience! brain matters writers my name is christopher jones. i am a community health-pre med major. as an undergraduate student i have been involved in several activities including minorities in medicine (maps), intramural basketball, as well as various volunteering opportunities throughout the champaign-urbana community. i am also a member of the omega psi phi fraternity inc. one of my most memorable moments thus far was belong selected to participate in the niams summer research fellowship at the national institutes of health in washington d.c. my goal is to attend medical school and become a neurosurgeon. emma ibanez is a senior majoring in mcb with a minor in chemistry. as an undergraduate research assistant in the rhodes lab, she genetically modifies clownfish for studying socially influenced sex change. emma also enjoys caring for her plant collection and learning how to play the piano. after graduation, she plans to attend graduate school for further research in neuroendocrinology. lina graduated from the university of illinois at urbana-champaign in 2021 and is now a first-year medical student at the university of illinois at chicago. she was previously doing research in an auditory neuroscience lab at the beckman institute on campus and was awarded the 2021 berkowitz summer fellowship for her work there. lina was also published in cells for her contributions in looking at age-related hearing loss and the distribution of serum lipidomic biomarkers as a means of predicting the development of alzheimer’s disease. outside of academics, she is involved in social justice work and volunteers through various organizations to serve in underserved communities. she is very excited to share her passion for neuroscience through brain matters! 28brain matters・volume v issue ii br ai n m at te rs w ri te rs 29 hanifa is a senior at the university of illinois majoring in molecular and cellular biology with honors concentration and minoring in philosophy. she has been interested in neuroscience after reading paul kalanithi's autobiography when breath becomes air. in addition to writing for brain matters, hanifa is currently researching the effect of avp on the brain's glymphatic system in dr. martha gillette's lab. she volunteers at carle, avicenna, salt and light, and the illini medical screening society. laura is a junior majoring in molecular and cellular biology and is pursuing a minor in food science. she is very excited to showcase the new volume and hopes to expand the journal to new horizons. aside from working on the journal, she is an assistant researcher in the robinson lab, is an mcb leader, an orientation leader, a member of bioscience journal club, and an executive board member of the undergraduate neuroscience society. copy of volume 6 publication implications of gpcrs in alzheimer’s katilyn simmons abstract g-protein coupled receptors, or gpcrs, are a large, diverse group of receptors found in all eukaryotes. gpcrs, as their name suggests, interact with g-proteins in the cell in order to carry out a variety of cellular responses. most of these cellular responses are related to sensory functions such as pheromone signaling, taste, light perception, and other processes in the brain (azam et al., 2020). for this reason, gpcrs are a very promising target for drugs that treat disorders affecting these processes. these disorders include many neurodegenerative cns disorders, such as alzheimer’s disease. while many current drugs and therapies treat symptoms of these disorders, drugs that target gpcrs more directly would focus on the cause of the disorders at their roots (huang et al., 2017). insight into the mechanisms involved in signal transduction pathways in disorders such as those in alzheimer’s would lead us to new discoveries that could alter the course of these and many other disorders of the cns. why are receptors important? the neurons in your brain, as well as other cells in your body, are constantly sending signals in all directions to any neuron that will listen and respond. these neighboring cells need a way to “listen” to these communications and interpret them in meaningful ways so that the cell can respond accordingly. an example of one way that the cell does this is through receptors. when a cell fires, it releases a signaling molecule – typically a hormone or a neurotransmitter – called a ligand, which then binds to the receptor. while some signals do result in direct cellular responses, such as in the case of a ligand binding to an intracellular receptor, signals usually initiate some type of cellular response through a series of steps called a signal transduction pathway (brooker et al., 2022). this pathway consists of a series of changes that lead to the production of a secondary signaling molecule which can lead to various cellular responses, such as altering enzymatic activity, altering protein function, or altering the function of transcription factors which activate gene expression – essentially turning a gene on or off. the proper functioning of any receptor is vital to the normal everyday bodily processes that are happening constantly in your body. what are gpcrs? one especially important group of receptors that are specifically relevant in the neuropathology realm are gpcrs, or g-protein coupled receptors. to put things into scope, there are over 370 non-sensory gpcrs currently identified, and 90% of those 370 receptors are expressed in the brain (azam et al., 2020). gpcrs are a remarkably diverse group of receptors that bind a vast variety of different signaling molecules, and therefore perform a variety of difference functions in your body and brain. in the brain, they are responsible for things like taste and appetite, pheromone signaling and mood, vision and light perception, immune regulation, and more general functions like cognition and synaptic transmission (huang et al., 2017). it is for this reason that regulation of gpcrs is a common target for drugs that treat disorders of such functions. how are gpcrs structured? being able to answer questions about how something is structured can often give us some clue as to how it works. gpcrs typically have seven domains, or segments, that are membrane-spanning, meaning that they wind back and forth across the plasma membrane of the cell. they also contain extracellular loops that contain components that stabilize the structure. gpcrs interact with g-proteins, named for their ability to bind to gtp and gdp. the g-protein is a lipidanchored protein, which means that it is attached to the intracellular side of the membrane and consists of an alpha subunit and a β/gamma dimer. in its inactivated state, the gprotein binds gdp (brooker et al., 2022). how do gpcrs function? now that we have a basic understanding of how the gpcr and g-protein are structured, let us examine how they function to carry out cellular responses when they are functional. to begin the signal transduction pathway, a ligand, or signaling molecule such as a hormone, peptide, or growth factor binds to the extracellular portion of the receptor. this causes a conformational change which allows the receptor to bind to a g-protein. once bound to the receptor, the g-protein a subunit and β/g dimer separate, releasing gdp. this allows the alpha subunit to bind gtp. figure 1. schematic diagram of gpcr structure (neumann et al., 2014). 4brain matters volume vi the two components of the g-protein can both play separate, very important roles in eliciting cellular responses. for example, the a subunit can activate enzymes in the cell that lead, in a chain reaction, to the increased or decreased production of important energy sources such as glucose. the b/g dimer is also important, as it can play a role in the regulation of ion channels (brooker et al., 2022). how do gpcrs relate to alzheimer’s? alzheimer’s disease (ad) is a neurodegenerative disorder associated with reduced cognitive function, loss of synapses, and neurofibrillary degeneration, or the formation of tangles of fibers within nerve cells, due to a buildup of plaques in the brain. these plaque buildups are accumulations of β-amyloid peptide (aβ), which is formed from a protein called amyloid protein precursor (app) (zhao et al., 2016). as stated before, gpcrs are involved in the normal functioning of many important cellular processes in the brain. one example of this is demonstrated in gpcrs’ role in the development of ad through the processing of app. gpcrs and the regulation of app through bace1 downregulation bace1 is an enzyme that is essential for the processing of app and generation of b-amyloid. in patients with ad, bace1 has been found to be overactive, but not in excess (zhao et al., 2016). research suggests that gpcrs (specifically the m1 achr, δ-opioid receptor, and a2a receptors) are involved in the regulation of bace1 (zhao et al., 2016). there are also a number of different proteins that are responsible for the regulation of gpcrs, and therefore may be responsible for regulating bace1 activity. it has been shown that a loss of function in these enzymes is also connected to the progression of ad in some way or another (zhao et al., 2016). for example, the upregulation of small gtpases such as rabs has been connected to cognitive impairment in ad (ginsberg et al., 2010). although there is evidence for a linkage of gpcrs to the regulation of bace1, it is not currently known exactly the mechanism through which it is done. gpcrs and the regulation of app through degradation of bace1 another possibility for a mechanism of regulation of app by gpcrs is related to the degradation of bace1. there is evidence that machr, which was previously mentioned as a possible component of bace1 downregulation, could be involved in the degradation of bace1 (jiang et al., 2012). the mechanism through which this is done is not clear to researchers and is a continuing topic of discovery. why is determining these mechanisms hard, but also so important? currently, the drugs used for the treatment of ad only scratch the surface of the problem. current treatments such as acetylcholinesterase inhibitors and memantine treat only the symptoms of ad. acetylcholinesterase inhibitors simply inhibit the breakdown of acetylcholine, which is in short supply in the brains of ad patients. similarly, memantine prevents excitotoxicity due to overstimulation (huang et al., 2017). these treatments, while helpful, leave the root of the problem unchecked. if the mechanisms behind the role of gpcrs in the processing of app are further studied, better therapies and even a possible cure for alzheimer’s may be on the horizon. the problem, however, is that there are a few difficult tasks standing in the way of our understanding of these mechanisms. first, inhibiting bace1 would not come without side effects. inhibiting bace1 may prevent unnecessary aβ production, but this does not come without consequences in application in the body. there is a strong possibility that bace1 is related to the production of many other enzymes, so inhibiting it would affect enzymes that were not meant to be affected. this could lead to unwanted effects such as impaired spatial reference and working memory, as well as problems with temporal associative memory (cole & vassar, 2007). brain matters volume v 5 figure 2. diagram of general signal transduction pathway of gpcrs (tuteja, 2005). figure 3. proposed signal transduction pathway and interaction between gpcr and bace1 (zhao et al., 2016). azam, s., haque, m. e., jakaria, m., jo, s. h., kim, i. s., & choi, d. k. (2020). g-protein-coupled receptors in cns: a potential therapeutic target for intervention in neurodegenerative disorders and associated cognitive deficits. cells, 9(2), 506. https://doi.org/10.3390/cells9020506 brooker, r. j., widmaier, e. p., graham, l. e., & stiling, p. d. (2022). cell communication. in biology (pp. 85–92). essay, mcgraw hill llc. cole, s.l., vassar, r. the alzheimer's disease βsecretase enzyme, bace1. mol neurodegeneration 2, 22 (2007). https://doi.org/10.1186/1750-1326-2-22 ginsberg, s. d., alldred, m. j., counts, s. e., cataldo, a. m., neve, r. l., jiang, y., wuu, j., chao, m. v., mufson, e. j., nixon, r. a., & che, s. (2010). microarray analysis of hippocampal ca1 neurons implicates early endosomal dysfunction during alzheimer's disease progression. biological psychiatry, 68(10), 885–893. https://doi.org/10.1016/j.biopsych.2010.05.030 gpcr | learn science at scitable. (n.d.). scitable. retrieved february 26, 2022, from https://www.nature.com/scitable/topicpage/gpcr14047471/? error=cookies_not_supported&code=4f65e9e1-a4a246fa-a388-b0b489fbf9c4 huang, y., todd, n., & thathiah, a. (2017). the role of gpcrs in neurodegenerative diseases: avenues for therapeutic intervention. current opinion in pharmacology, 32, 96–110. https://doi.org/10.1016/j.coph.2017.02.001 jiang, s., wang, y., ma, q., zhou, a., zhang, x., & zhang, y. w. (2012). m1 muscarinic acetylcholine receptor interacts with bace1 and regulates its proteosomal degradation. neuroscience letters, 515(2), 125–130. https://doi.org/10.1016/j.neulet.2012.03.026 neumann, e., khawaja, k., & müller-ladner, u. (2014). g protein-coupled receptors in rheumatology. nature reviews. rheumatology, 10(7), 429–436. https://doi.org/10.1038/nrrheum.2014.62 conclusion receptors in general are vital to the function of many bodily and brain processes. even more specifically, gpcrs are vital to our understanding of the body, as they make up a large chunk of all receptors, especially in the brain. further research into the functions of gpcrs and gpcr signal transduction pathways in relation to bace1 and other enzymes would open the door, not only to potential treatments and maybe even a cure for alzheimer’s, but also to several treatments for cns disorders such as parkinson’s and huntington’s disease. therefore, a partial, rather than full, inhibition of this enzymatic activity may be beneficial, although the percentage of bace1 inhibition required to significantly delay amyloid pathology and the associated cognitive changes, remains to be determined. references 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. tuteja n. (2009). signaling through g protein coupled receptors. plant signaling & behavior, 4(10), 942–947. https://doi.org/10.4161/psb.4.10.9530 zhao, j., deng, y., jiang, z., & qing, h. (2016). g protein-coupled receptors (gpcrs) in alzheimer's disease: a focus on bace1 related gpcrs. frontiers in aging neuroscience, 8, 58. https://doi.org/10.3389/fnagi.2016.00058 6brain matters volume vi https://doi.org/10.3390/cells9020506 https://doi.org/10.1016/j.biopsych.2010.05.030 https://www.nature.com/scitable/topicpage/gpcr-14047471/?error=cookies_not_supported&code=4f65e9e1-a4a2-46fa-a388-b0b489fbf9c4 https://doi.org/10.1016/j.coph.2017.02.001 https://doi.org/10.1016/j.neulet.2012.03.026 https://doi.org/10.1038/nrrheum.2014.62 https://doi.org/10.4161/psb.4.10.9530 https://doi.org/10.3389/fnagi.2016.00058 volume 8 (will be vol 7 on site) future research with dopamine and social contexts dopamine activity occurs during social situations, as seen in the mice in solié’s study. this brain feature may be a reason for the necessity of social environments for certain species, including humans. the involvement is complex, though, as repeated exposure to the same individual lessens dopamine activity, demonstrating habituation. future research could explore decreased dopamine levels, as seen in some neurological disorders, and their effect on social interactions. such research could provide information on whether dopamine levels are a factor causing social interactions, or whether they are an output of being social. dopamine: a social neurotransmitter vraj patel introduction humans live in a social world. we constantly exercise the social aspect of the mind in our everyday lives, face-to-face with others, in large group settings, and even online. social interactions are critical to human life; without them, we may not even be considered “human.” social interactions involve many parts of the brain, both in performing them and their outcomes. dopamine plays an interesting role in the outcomes of social interactions. it is a neurotransmitter involved in pleasure, satisfaction, motivation, and body movements (costa & schoenbaum. 2022). dopamine mainly functions in a brain pathway involved in motivation: the mesocorticolimbic pathway. originating in the ventral tegmental area (vta), dopaminergic neurons – neurons that release dopamine – project to the nucleus accumbens (nac) and the prefrontal cortex (pfc). this pathway allows for producing and maintaining feelings of motivation and desire (reynolds & flores, 2021). such feelings may arise during social situations, impacting our interactions and promoting the necessity of sociality in humans (krach et al., 2010). the focus of the discussion is on the connection between social environments and dopamine pathways. the reward system and dopamine research conducted by dr. solié clément, dr. benoit girard, and their team at the university of geneva explored the activity of the vta in mice during periods of social interaction. they found that the vta dopamine firing rate increased when the mice were in social contexts, particularly in this case, when other mice were present in their view. additionally, the physical proximity of other mice was correlated with an increase in vta activity. this means that the closer the other mouse was to the experimental mouse, the more activity was recorded. the team concluded that being around other mice activated the “reward” pathway in the brain, increasing the mouse’s desire to remain in the social setting and driving social interaction. the study also found that within the vta, a subset of neurons activate only when experiencing “novel” stimuli and decrease firing when habituated to a certain stimulus. when an experimental mouse was repeatedly placed in a context with the same mouse, the vta firing levels reduced after each subsequent round, suggesting habituation towards the social stimuli. these findings complicate the vta and reward system of the brain. figure 1. important regions regarding neurogenesis. in-depth view of where neural stem cells proliferate. (2023). neural stem cell culture protocols. https://www.sigmaaldrich.com/us/en/tec hnicaldocuments/protocol/cell-culture-an d-cell-culture-analysis/stem-cellculture/n eural-stem-cell-culture-protocols figure 2. the activity of vta da neurons when the mouse was in social settings. the black line demonstrates the firing rate during the baseline and when interacting. during each subsequent interaction, the vta firing rate decreases, as seen by the diminishing firing peaks (solié et al. 2021). brain matters・volume vii 74 references 1. batten, s. r., bang, d., kopell, b. h., davis, a. n., heflin, m., fu, q., perl, o., ziafat, k., hashemi, a., saez, i., barbosa, l. s., twomey, t., lohrenz, t., white, j. p., dayan, p., charney, a. w., figee, m., mayberg, h. s., kishida, k. t., montague, p. r. (2024). dopamine and serotonin in human substantia nigra track social context and value signals during economic exchange. nature human behaviour. https://doi.org/10.1038/s41562-024-01831-w 2. cacioppo, j. t., norris, c. j., decety, j., monteleone, g., & nusbaum, h. (2009). in the eye of the beholder: individual differences in perceived social isolation predict regional brain activation to social stimuli. journal of cognitive neuroscience, 21(1), 83-92. https://doi.org/10.1162/jocn.2009.21007 3. costa, k. m., & schoenbaum, g. (2022, august 8). dopamine. current biology, 32, 817-824. https://www.cell.com/currentbiology/pdf/s0960-9822(22)01022-3.pdf 4. krach, s., frieder, p. m., bodden, m., & kircher, t. (2010). the rewarding nature of social interactions. frontiers in behavioral neuroscience, 4(22). https://doi.org/10.3389/fnbeh.2010.00022 5. reynolds, l. m., & flores, c. (2021). mesocorticolimbic dopamine pathways across adolescence: diversity in development. frontiers in neural circuits, 15. https://doi.org/10.3389/fncir.2021.735625 6. solié, c., girard, b., righetti, b., tapparel, m., & bellone, c. (2021). vta dopamine neuron activity encodes social interaction and promotes reinforcement learning through social prediction error. nature neuroscience, 25(1), 86-97. https://doi.org/10.1038/s41593-021-00972-9 copy of volume 6 publication the neurobiology behind the making of the antisocial personality type vyapti patel the antisocial personality type is a particular type that is full of mysteries, but with the assistance of more advanced technology, and the exploration of this personality type, more knowledge upon it is slowly being gained. it is known that the diagnosis of this personality type is more common in males than it is in females, “total prevalence rate of 4.5% in community samples” (fitzgerald, 2007). there is so much more to this personality type than what the media presents, and by exploring the brain science behind the antisocial type, more equipped decisions to help these individuals can be made before unfortunate events occur. the antisocial personality type is also closely tied with the legal system, and for years has been causing turmoil upon individuals and their families; whether the individual themselves have this personality type or they themselves have been affected by someone who has this personality type. this personality type “stems from brain abnormalities” and has a lot to do with “dysfunctions in select parts of the brain” according to the research suggested in the article, the neuropsychology of antisocial personality disorder (fitzgerald, 2007). the antisocial personality type has a lot to do with the genetics and the biological aspect of oneself, but when tied with ‘nurture’, the making of a dangerous individual can be amplified. treating individuals with the antisocial personality type can be difficult as they themselves do not have the desire to change, most probably due to their lack of empathy when inflicting pain upon others. although change can be brought upon these individuals; through the exploration of the antisocial personality type in terms of the neurological as well as the psychological aspect, a more deep understanding of this personality type can be gained, which in turn can help eradicate the chaos and destruction that this personality type brings into society as well as save the lives of those experiencing this personality type. the development of the child plays a significant role in the emergence of the antisocial personality type. it is actually considered normal for children to express aggression and certain antisocial behavior when they are young, because they have yet to get a sense of the world around them, and understand what is socially appropriate and what is not. for example, a young child may take another child's toy and not give it back, but they do not know that this is not appropriate. contrary to that, this becomes a problem when aggression and antisocial behavior prospers long term. there tends to be signs at an early age with what type of turnout will come about the child; as an infant these individuals have a more ‘difficult temperament’ (rudolph, 2022). then as they progress to preschool, they may be more prone to throw tantrums, be more stubborn as well as more physically aggressive. onward to their childhoods, they may engage in fighting, bullying, while also having academic and social difficulties, but a big give away can be showing signs of animal cruelty. then as they develop into their adolescence they continue on with these behaviors on a bit of an extreme scale. finally the problem can lead to adulthood and this is when the individual becomes more involved with the legal system, while juggling a chaotic life, which may include broken relationships, psychiatric problems, unable to parent well, etc. (rudolph, 2022). these children tend to process social information differently compared to the majority of the children. according to the social information processing model carried out by psychologist ken dodge, a scenario was given to some of the children in order to determine the social processing steps the individual with a more aggressive nature went through. the scenario consisted of the child at a cafeteria, who had milk spilled over them, but prior to that when the child was waiting in line they had two children behind them, one making a goofy face and one smiling at them. when asked to explain what had happened to the child, the child with the personality disorder viewed the actions of the other children as purposefully malicious. this relates to the hostile attributional bias the tendency for the child to interpret the behaviors of others to have malintent towards them where the child is asked how they would want to react to this, and they say that they will get back at the other kid. this child is not afraid of the consequences, and they do not feel fear at the normal level that an average person would. so fulfilling a hostile goal in order to either assert dominance and/or get revenge does not require much doubt. these kids think that there will be a positive outcome to this and think they are going to be good at this. the child is not able to think of all things that could go wrong, and they are unable to see this as an accident, as they have internalized it. figure 1. brain matters volume v 7 this type of development involves not only the neurological aspect within the individual but the family/environment plays a huge role in fueling these behaviors. first of all, it can be genetically passed down from a family member which can result in a more negative temperament. adding onto that, the parenting style that these individuals have grown up with can play a big factor; there can be a ‘power assertion’ where one of the parents makes the child feel unimportant, with punishments involved. another parenting type can be the low monitoring parent, one that practically neglects the child, leading the child to be more deviant. although, parenting is not the only cause for these behaviors. a child is at school for most of their lives, so if the child experiences peer rejection either due to academics or social reasons, the child may steer from the normative group of children and become more involved in a deviant group of children, or isolate themselves. this only leads to more of a feeling of ostracism, and this coupled with early genetic deficits as well as neurological/cognitive deficits results in the child to go down a more deviant pathway. figure 2. an individual born into a low socioeconomic family can also facilitate antisocial personality traits. when exposed to neighborhood violence at a young age, the child does not know any better than from what they have seen and experienced. at a young age, they seem to understand that this is normal for them. they also become ‘desensitized to violence’ (rudolph, 2022). the parent may also not be so involved in their lives because they are busy handling multiple jobs or are not in a state to provide much for their child. all this can lead the child to partake in deviant activities with deviant peers and find a sense of belonging even though it is not safe for them. a lot of this can be avoided if the schools the children attended facilitated them into being more busy and involved within the community, but these institutions themselves are lacking in resources to provide. the schools either do not have enough funding to support the children or they do not have enough extracurriculars for the children to get involved in, which only leaves the children to pass time in their neighborhood. if these children already are biologically prone to the antisocial personality disorder, this sort of environment will only facilitate them towards the direction of atypical behavior within the community, which may result in delinquent activities. empathy and callousness play a prominent role in the development of an individual with the antisocial personality disorder. empathy relates to the ability for one to put themselves in the place of another, and callousness is the opposite where the individual is insensitive to the feelings of others. by exploring the neural and peripheral physiology of an individual with the antisocial personality disorder, more insight upon the significance that empathy and callousness holds upon these individuals will be revealed. empathy plays a significant role in promoting prosocial behavior, without it the connection between individuals is lost, causing disconnect and isolation amongst an individual, when paired with callousness and unemotional traits (cu), which are “traits related to maladaptive social information processing” (shirtcliff, 2009). the development of psychopathy emerges, which is closely affiliated with the antisocial personality type. alterations in the neural circuitry as well as the limbic system plays a huge role in relation to empathy and cu traits. the amygdala, an almond-shaped region within the brain, allows for emotions and arousal to be detected within the individual. this region is critical when it comes to responding to outside stimuli relating to arousal, and stress; low levels of it can indicate indifference to the outside environment. individuals with high levels of the cu traits ‘often show reduced amygdala activation’ which suggests amygdala hyporesponsivity; this affiliates closely with the ‘neurobiology of callousness.’ a study upon this has been conducted by marsh and colleagues according to shirtcliff as mentioned in her article. the study required the observation of youths with cu traits in comparison to youths without the cu traits. what was found through this study was that, “youth with high levels of cu traits showed similar [reduced] amygdala activation to fearful, angry or neutral faces while healthy comparison or youth with adhd displayed the typical enhancement of amygdala activation in response to fear” (shirtcliff, 2009). these findings conclude that those with amygdala hyporesponsivity to emotional stimuli are associated with the antisocial personality type. the amygdala not only is associated with emotions but stores memories acquired through emotions. the amygdala usually does not go hand in hand with memory but it does get involved when it is ‘activated by emotional arousal’. without this function, it is hard to understand how to go on about combatting a situation similar to a previous situation in the future. this is supported by an experiment performed by cahill where he performed a procedure similar to nielson and jenson: psychologists from another study, in order to determine whether the amygdala is correlated with long-term memory by showing 12 slides with narrations to human individuals being tested. at this step of the procedure he found that, “emotional arousal did not enhance long-term memory in a subject with bilateral degenerative lesions of the amygdala” (mcgaugh, 1996). this finding indicates that damage to the amygdala impairs memory dealing with certain emotional events. he then goes onto a third study using a positron-emission tomography scan in order to assess for ‘cerebral glucose metabolism in healthy volunteers’ in which one session consisted of viewing emotionally arousing film clips, while the other session consisted of the individuals watching an emotionally neutral film clip. three weeks had gone by and then memory of the clips they had seen was recalled and tested for. 8brain matters volume vi https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=shirtcliff%2c+elizabeth+a https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=shirtcliff%2c+elizabeth+a https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=shirtcliff%2c+elizabeth+a https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=shirtcliff%2c+elizabeth+a https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=shirtcliff%2c+elizabeth+a it was found that, the glucose metabolic rate of the right amygdala was “induced by viewing the emotional film clips, [it] was highly correlated (+0.93) with the number of films recalled” (mcgaugh, 1996). it is therefore concluded by this study that the amygdala is in correlation with emotional memory storage. so those that have a healthy functioning amygdala are able to understand social cues and recognize emotions in others in comparison to those that do not. supporting the idea, healthy individuals are able to reduce the distress of others by following through with actions learned in the past, but those with low activation of the amygdala are unable to reduce another's distress because they themselves are unable to feel the distress of the situation. helping another individual relates to moral decision making. when an individual has poor amygdala activation, they are also unable to make moral decisions which is associated with the impulsivity of those with the antisocial personality type. figure 3. not only does the amygdala play a key role in the empathy/callousness aspect of the antisocial personality type, but so do certain other factors such as the anterior cingulate cortex as well as the insular cortex which are considered to be a part of the paralimbic system. both of these cortices are regions of the medial pain system which play a trivial role regarding empathy (medford, 2010). the acc and insula are activated across a range of emotionrelated tasks (shirtcliff, 2009). it was found by sterzer and colleagues that there is a reduction of insular gray matter in children with low levels of empathy and high levels of aggression. this reduction indicates the inability to understand social emotions, which reduces the human-tohuman connection. a study was conducted which detected the activation of the acc and insula in fear conditioning. it was found that “control participants activated the insula and the acc as they paired neutral faces with pain, but psychopathic patients did not” (shirtcliff, 2009). this is a big indication that those with the antisocial personality type are unable to feel empathy the way others can. through the inability to feel empathy towards others and heightened callousness, a physical and emotional connection between individuals is lost. this loss of connection breeds individuals who are unable to digest the consequences they are to face when deciding to thrust themselves upon impulsive and aggressive tasks. understanding the paralimbic and limbic systems and their relation to empathy and callousness helps those wanting to make an impact understand the basis of where the antisocial personality type stems from. through digesting the main roots affiliated with this personality type, more research can be conducted upon this, and with the aid of new knowledge, more steps can be taken to prevent thesendividuals from causing chaos in our society while also helping them live a more suitable life. figure 4. the antisocial personality disorder has a lot to do with brain dysfunctions and impairments, whether it be genetic or due to a traumatic event. there are many types of psychopathic qualities that have emerged innately. the frontal lobe dysfunction theory speaks of an impairment in the executive functioning system. the damaging of the frontal lobe can lead to “distractibility, lack of guilt, periodic mood disorders, and increased sensitivity to alcohol” (fitzgerald, 2007). these are all characteristics of an individual with the antisocial personality type; they are rash and execute plans that have uncertain outcomes. the dysfunctioning of the frontal lobe is possibly innate or it can occur in individuals later in life. take the case study of phineas gage: he was known to be an energetic and a good businessman but after damaging his frontal lobe due to a railroad incident, his persona entirely shifted. he “became impulsive, irresponsible, profane, indifferent to social properties, childlike in intellectual capacity, and behaved more primitively following the accident” (fitzgerald, 2007). the hard blow that his head took completely molded his brain another way, and those regions affiliated with decision making and impulsivity changed drastically, developing in him the antisocial personality type. in this case, the brain impairments gage went through were not innate but happened due to the brain suffering from trauma. another factor that is associated with the antisocial personality type is the impairment of the amygdala. this is highly associated with the risk of aggressive behavior as ”lesions in the amygdala have 9brain matters volume vi https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=shirtcliff%2c+elizabeth+a https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=shirtcliff%2c+elizabeth+a https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=shirtcliff%2c+elizabeth+a https://onlinelibrary.wiley.com/action/dosearch?contribauthorraw=shirtcliff%2c+elizabeth+a been shown to impair the effects of aversive classical conditioning, lower automatic response to cues that predict shock, and impair passive avoidance learning’ (fitzgerald, 2007). this is very common amongst those with the antisocial personality disorder; they are not able to feel the fear and arousal of what the environment has to present, making it easier for them to act as predators because they see what they want, and go after it, and afterwards carry on to do the same without remorse. those with high or low attention tasks associate well with the risk that they take when plotting a risky venture. in the gambling task done by bechara, it was found that inmates in prison that had poor attention “performed poorly and made more risky choices more frequently,” not thinking about the consequences that they would have to face when caught (fitzgerald, 2007). the inmates were more likely to get prison time and get caught than those with high attention, who are also associated with the antisocial personality disorder but are not caught so easily. the amygdala as well as the frontal lobe play a huge role with the development of the antisocial personality disorder, and with new and improved technology, we may be able to repair some impaired portions of the brain, allowing for these innate born individuals to live a life that we all live. the antisocial personality type in itself can be dangerous, but when paired with a difficult development into adulthood, the psychopathy of the individual is heightened. it all starts when the individuals are still infants, even though the child is unable to remember their youth and the treatment they received. the neurobiology of the children captures the treatment the children received at a young age. it was found in this study reported by hane and fox that “maternal sensitivity and intrusiveness [affects] infants’ social interactions,'' so when this is lacking, the infants show “less interest'' in social interactions (frazier, 2010). this embarks their isolation and doubts upon trusting others. the children’s neurological differences are well associated with their neurobiology during a critical point in development. there seems to be a biological association with neglect in association with the neurotransmitter dopamine. according to the analysis done by pruessner et al., it was reported that there is “increased dopamine and cortisol release during stressful situations in individuals who reported low-quality relationships with caregivers in childhood” (frazier, 2010). this increase in dopamine results in an individual being more aggressive and competitive; these are traits found more intensively in individuals with antisocial personality disorder. along with that, another critical aspect of development occurs in the right hemisphere during the first 3 years of development, which is involved in emotional and social processing. furthermore, longitudinal and cross-sectional brain imaging studies chronic stress, deprivation, or maltreatment in the first 3 years of life have been shown to cause brain volume reductions and significant brain development abnormalities in affected 3-year-olds” (frazier, 2010). these developing abnormalities due to one's environment results in these children to begin adulthood not knowing what it means to be cared for, and their genetic predisposition of the development of the antisocial personality type prolongs into adulthood. shirtcliff, e. a., zahn-waxler, c., merz, j. l., gostisha, a. j., graf, a. r., & vitacco, m. j. (2009, august 20). neurobiology of empathy and callousness: implications for the ... national library of medicine. retrieved april 30, 2022, from https://onlinelibrary.wiley.com/doi/10.1002/bsl.862 fitzgerald kl, demakis gj. the neuropsychology of antisocial personality disorder. dis mon. 2007 mar;53(3):177-83. doi: 10.1016/j.disamonth.2007.04.010. pmid: 17544650. frazier, a., ferreira, p., & gonzales, j. (2019). born this way? a review of neurobiological and environmental evidence for the etiology of psychopathy. personality neuroscience, 2, e8. doi:10.1017/pen.2019.7 medford, n., & critchley, h. d. (2010). conjoint activity of anterior insular and anterior cingulate cortex: awareness and response. brain structure & function, 214(5-6), 535– 549. https://doi.org/10.1007/s00429-010-0265-x rudolph, k. (2022). aggression and antisocial behavior. [lecture powerpoint] https://learn.illinois.edu/course/view.php?id=66118 mcgaugh, j. l., cahill, l., & roozendaal, b. (1996, november 26). involvement of the amygdala in memory storage: interaction with other brain systems. proceedings of the national academy of sciences of the united states of america. retrieved june 5, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc33638/ team, h. j., & team, h. j. (2019, april 11). amygdala function, location & what happens when amygdala is damaged. health jade. retrieved april 29, 2022, from https://healthjade.net/amygdala/ blair, r. (1970, january 1). the neurobiology of psychopathic traits in youths: semantic scholar. undefined. retrieved april 29, 2022, from https://www.semanticscholar.org/paper/theneurobiology-of-psychopathic-traits-in-youthsblair/c0263a8e1fc53aa3209a3a590cd5979be0b00218 paus, r., steinhoff, m., bíró, t., & schmelz, m. (2006). frontiers in pruritus research: scratching the brain for more effective itch therapy. jci. retrieved april 29, 2022, from https://www.jci.org/articles/view/28553/figure/2 the antisocial personality type in specific is one that has many circulating questions, but through experiments, and the use of the technology we are given, the mysteries of this personality type can be gradually uncovered. this personality type has many factors that affect not only its developmental, but more so neurological and physiological impairments and also include the environment that one is born in. those with a low socioeconomic status are more likely to strengthen this personality type. through learning about this personality type, the lives of these individuals can be saved as well as the others that may be a victim to these individuals. references 1. 2. 3. 4. 5. 6. 7. 8. 9. 10brain matters volume vi https://doi.org/10.1007/s00429-010-0265-x https://learn.illinois.edu/course/view.php?id=66118 verhoef, r. e. j., dijk, a. van, & castro, b. o. (2021, april 6). a dual-mode social-information-processing model to explain individual differences in children’s aggressive behavior. research gate. retrieved may 10, 2022, from https://www.researchgate.net/publication/352204344_a_ dual-mode_social-informationprocessing_model_to_explain_individual_differences_in _children's_aggressive_behavior/fulltext/60beceb89285 1cb13d88cea8/a-dual-mode-social-informationprocessing-model-to-explain-individual-differences-inchildrens-aggressive-behavior.pdf 10. 11brain matters volume vi volume 8 (will be vol 7 on site) unraveling the links between synesthesia and autism sarah masud abstract while synesthesia and autism may not appear to be related at the surface level, they share common features such as hypersensitivity and enhanced perception, increased attention to detail, and atypical neural connectivity. synesthesia was found to be more common in autism and oddly not schizophrenia, another disorder of altered perception; however, this increased prevalence does not generalize to all forms of synesthesia and autism, and studies suggest that synesthesia is more common when autism co-occurs with savant skills. although more research needs to be conducted on whether there is a biological link, similarities between the two conditions could be explained by similar underlying neural mechanisms. as synesthesia and autism share similar theoretical models in terms of hyperexcitability and perception of the world, there may be a link between the two that makes them often co-occur. introduction do you often associate sounds with different colors? or perhaps different textures trigger different tastes? if an association is strong enough between inducing stimuli and concurrent sensations and exhibits high consistency throughout life, you may be described as a synesthete. synesthesia is a neurodevelopmental condition in which specific sensory inputs such as letters, sounds, tastes, or smells automatically and involuntarily trigger additional sensations such as texture, color, or shape (van leeuwen et al., 2020). although any combination of inducing inputs and concurrent sensations is hypothetically possible, the most common inducers are linguistic while the most common concurrents are visual, such as colors or shapes; overall, the most common type is grapheme-color synesthesia, where letters or numbers trigger color sensations (simner et al., 2006). diagnostic criterion for autism is altered sensory perception— which can be either hyposensitivity or hypersensitivity—and many autistic individuals pay increased attention to details. hypersensitivity and enhanced perception are also traits of synesthesia, and there are similarities between autism and synesthesia regarding atypical neural connectivity and preference for local (detail-oriented) over global (big picture) visual processing (van leeuwen et al., 2020). it is also hypothesized that the presence of savant skills plays an important role in determining the presence of synesthesia in autistic individuals (hughes et al., 2017). though further research needs to be conducted to confirm whether there are underlying biological mechanisms connecting synesthesia and autism, the shared features and increased co-occurrence of the two conditions indicate that there may be a link between them. this paper will discuss precisely how much overlap there is between synesthesia and autism, theories as to why this overlap occurs, and the implications of these findings. is synesthesia more prevalent in autism? as a general estimate, synesthesia occurs in 4% of the population and autism occurs in 1% of the population. if these two neurodevelopmental conditions were to be independent of each other, the chance of them co-occurring would be about 0.04% or 4 in 10,000 people. given how incredibly rare that is, it would be unlikely to ever meet someone with both synesthesia and autism. baron-cohen et al. (2013) conducted a study to investigate whether this base rate is accurate or if synesthesia is more common in autism. after exclusions, 164 adults with professionally-diagnosed autism and 97 controls completed a synesthesia questionnaire, the autism spectrum quotient (aq), and the test of genuineness-revised (tog-r), which is used to validate self-reported synesthesia. it was found that the rate of synesthesia in autistic adults is 18.9%, almost three times greater than the rate of 7.22% in the control sample. figure 1. examples of how letters, numbers, days of the week, and months may induce different color sensations in synesthetes (van leeuwen et al., 2020). although synesthesia is a relatively rare condition, research has shown that it is more prevalent in individuals with autism spectrum disorder. autism is a neurodevelopmental condition characterized by difficulties in social interaction and communication as well as patterns of restricted and repetitive behaviors, interests, or activities (van leeuwen et al., 2021). 10% of autistic individuals also have savant abilities or skills that are exceptionally above average, and 50% of those with savant skills have autism (treffert, 2009). while the relation of autism to synesthesia may not be clear at first, another the significant difference between the rate of synesthesia in autistic adults and the general population indicates that something is linking these two conditions and making them interdependent. this could perhaps be because they share underlying biological factors, such as enhanced local visual processing and hypersensitivity. there is also evidence that suggests synesthesia and autism are connected at multiple levels. a study by gregerson et al. (2013) found a significant phenotypic and genotypic overlap between synesthesia and absolute pitch, which is the ability to identify or re-create a note on demand. this trait also has a higher prevalence in people with autism, suggesting that synesthesia and autism share several characteristics that result in the two often cooccurring. however, there are issues of reliability and validity to be considered with any finding based on self-reported measures. the increased presence of synesthesia in autistic adults may be explained by individuals with autism being more likely to report abnormal sensory and perceptual experiences than those without autism. there were also three autistic participants who claimed not to have synesthesia, yet they were determined to be synesthetes based on their results on the synesthesia questionnaire; however, they were considered as non-synesthetes because they reported themselves as such. because these participants declared they did not have synesthesia because they were unsure if their experiences counted, it is possible that the resulting rate was not an over-estimate, but instead an under-estimate. this study also has several limitations, the most critical one being that researchers were unable to collect complete consistency tests to validate the results. the sample also only included high-functioning autistic adults, and it would be interesting to see if these findings generalized to autistic children and more impaired autistic individuals. comparing synesthesia in autism and schizophrenia it is also worth questioning whether this increased prevalence of synesthesia is observed in other neurodevelopmental disorders or if it is specific to autism. one way to study this is figure 2. the percentage of people with synesthesia in the autism and control groups (baron-cohen et al., 2013). by looking at relatives of synesthetes and whether certain disorders have a significantly higher chance of running in the family. nugent & ward (2022) investigated whether there is a familial aggregation between synesthesia and two disorders —autism and schizophrenia—as well as type 1 diabetes as a control predicted to have no link to synesthesia. both autism and schizophrenia were hypothesized to have a familial connection to synesthesia due to their shared features of altered sensory perception. after exclusions, 282 synesthetes and 281 non-synesthetes completed an online questionnaire, which resulted in collecting information about 1114 firstdegree relatives of synesthetes and 1130 controls. individuals were subsequently sorted into one of three groups: diagnosed autism, probable autism, and possible autism. among participants, it was found that autism was more common in synesthetes (3.93% diagnosed, 3.57% probable, 2.14% possible) than in non-synesthetes (0.38% diagnosed, 0.38% probable, 1.91% possible). among relatives, autism was also more common in first-degree relatives of synesthetes (2.98% diagnosed, 1.08% probable, 0.72% possible) than first-degree relatives of nonsynaesthetes (1.68% diagnosed, 0.18% probable, 0.71% possible). while an association between synesthesia and autism was observed, the results failed to indicate any link between synesthesia and schizophrenia at the individual or familial level. this finding was surprising considering that altered neural connectivity is also a characteristic of schizophrenia, like autism and synesthesia, and schizophrenic hallucinations and synesthetic experiences may both be explained by inflexible frameworks of sensory perception; that is, both groups are likely to distort sensory input to fit their internal models of the world even when faced with contradictory evidence. the key difference here may be that synesthetes are aware their sensory experiences are false. however, this study has certain limitations, the most significant one being that there is no way to verify the truthfulness of the responses. the inclusion of a “prefer not to respond” option may be masking positive cases as well. even assuming that all participants responded truthfully, there may still be intergroup variability in diagnosis-seeking behavior: synesthetes and their relatives may be more proactive in seeking an autism diagnosis than non-synesthetes. however, other evidence shows that high levels of autism are observed in synesthetes even without a formal autism diagnosis (van leeuwen et al., 2019). considering savant skills’ role in synesthesia one final thing to consider when measuring this cooccurrence is that it does not generalize to all types of synesthesia and autism. considering that both conditions are conceptualized to lie on a spectrum with different characteristics across individuals, there may be an increased prevalence of certain types of synesthesia among certain types of autism. a study on this investigated whether synesthesia is indeed more common in autism or only when autism co-occurs with savant skills (hughes et al., 2017). brain matters・volume vii 22 researchers tested three groups: 40 autism-savants, 34 autism-non-savants, and 29 controls without autism. participants were asked whether they had a formal diagnosis of autism and completed a questionnaire on savant skills. then, they were tested for grapheme-color synesthetes in total: one was a control, one was an autism-non-savant, and four were autism-savants. the prevalence of synesthesia in the autism-savant group (10%) was over seven times higher than the general population (1.4%) and held statistical significance, while no significant difference was observed for the control and autism-non-savant groups. figure 3. the prevalence of grapheme-color synesthesia in autism-savants, autism-non-savants, the control group, and the general population (hughes et al., 2017). a primary limitation of this study was that there is no objective test to assess for savant skills and the questionnaire involved self-reporting savant skills. it is likely that participants vary in how they perceive their own talents compared to the general population without an objective standard. factors such as overestimating and under-estimating one’s abilities as well as personality traits like modesty come into play. however, it is still worth questioning why synesthesia was more common in autism-savants and what the implications of these results are. the first possible explanation is that synesthesia leads to savant skills because synesthetes are known to have improved memory. for example, if digits are encoded as both numbers and colors, they will have richer memory representations. this improved memory could then reach savant levels. another possible explanation is that hypersystemizing and veridical mapping are common in autism. systemizing is the drive to identify patterns in rule-based information, and veridical mapping is the related ability to match two systems by their shared traits. in synesthesia and types of savant skills that require mapping two things, veridical mapping may then independently lead to both conditions, explaining why the two often co-occur with autism. shared traits between synesthesia and autism now that it is clear that synesthesia is more prevalent in autism, the next step is to ask why. what are the underlying mechanisms and shared characteristics that lead to this increased prevalence? van leeuwen et al. (2019) conducted a study to test the hypothesis that synesthesia and autism share atypical sensory sensitivity and perception. 76 synesthetes and 43 non-synesthetes completed a synesthesia screening questionnaire, the autism spectrum quotient (aq), and the glasgow sensory questionnaire (gsq), which assesses hypersensitivity and hyposensitivity across seven sensory modalities. individuals with autism typically score higher on the gsq than the general population, and it was hypothesized that synesthetes would score higher as well. participants also completed a motion coherence task to assess for global motion processing and an embedded figures task to assess for local visual processing. the hypothesis was partially confirmed. synesthetes scored higher than non-synesthetes on aqattention-to-detail, but not aq-total. synesthetes also showed gsq scores positively correlated with aq-attention-to-detail and higher scores on hypersensitivity subscales, but not hyposensitivity. lastly, synesthetes performed poorer on detecting the global motion of direction in the motion coherence task and performed better on the most difficult level of local processing in the embedded figures task. high attention to detail, hypersensitivity, and bias towards local perception are all common characteristics of autism, and these findings suggest that synesthetes share these atypicalities. these similarities between the two conditions could be explained by a shared underlying neural mechanism. there is evidence of local hyperconnectivity and reduced long-range connectivity in both synesthesia and autism, which would explain why both excel at tasks where global context, including long-range feedback, must be ignored. another similarity lies in both groups showing atypical responses in the parvocellular system, which is the system responsible for processing spatial details and colors. this would explain why synesthetes and autistic individuals both exhibit enhanced perception of details and colors at the cost of reduced global motion processing. similar theoretical models of synesthesia and autism though little research has been done to conclude whether there is a clear biological explanation, van leeuwen suggests that there are possible theoretical models of perception in synesthesia and autism that account for their similarities (van leeuwen et al., (2020)). in autism, there is an imbalance between excitation and inhibition in the brain that leads to excitation not being met with sufficient inhibition (orekhova et al., 2007). in synesthesia, the balance between excitation and inhibition has not been specifically measured, but there is evidence for hyperexcitability in the visual cortex for individuals with grapheme-color synesthesia (terhune et al., 2011). predictive processing models of perception involve comparing “priors”, or top-down knowledge based on one’s past experiences, against incoming sensory information. a prior can be any knowledge structure that influences how sensory input is perceived, such as associating red with danger. if one has an over-reliance on priors, they may wrongly interpret every red item they see as dangerous. one version of this model proposes that people with autism have weaker priors and are therefore more likely to see the world as it is. this is especially interesting because synesthesia resembles the antithesis of this. rather than the hyper-real perception of the world in autism, synesthesia appears to be an over-reliance on priors similar to hallucinations in schizophrenia. so, how is it that synesthesia and autism co-occur so commonly? there is an alternative model of perception in autism that suggests that their priors are specific, narrow, and inflexible; therefore, a lot of incoming sensory information that contradicts their worldview is treated as surprising and unpredictable. this model is potentially more compatible with synesthesia, as autism and synesthesia may be similar in demonstrating excessively strong priors that lead to altered perception. specific and inflexible priors are consistent with the imbalance between excitation and inhibition as well. if priors are too narrow to accurately predict incoming sensory signals, the brain will make more errors in predicting them. so, the different theoretical models of synesthesia and autism converge in this sense. conclusion the shared features of hypersensitivity, enhanced perception, heightened attention to detail, and atypical neural connectivity suggest a link between synesthesia and autism. while studies indicate higher rates of synesthesia in individuals with autism, there are nuanced distinctions to be made when considering different manifestations of the two conditions, one particularly being the presence of autism with savant skills. however, the absence of a similar association with schizophrenia underscores the specificity of synesthesia and autism frequently co-occurring. evidence for a definitive biological link between synesthesia and autism still remains elusive, and these preliminary findings prompt a call for more research. as the complexities of neurodiversity are further explored, unraveling the links between synesthesia and autism will hopefully allow for deeper insights into the intricacies of the human brain and the diverse ways in which it perceives and interacts with the world. references 1. baron-cohen, s., johnson, d., asher, j., wheelwright, s., fisher, s. e., gregersen, p. k., & allison, c. (2013). is synaesthesia more common in autism?. molecular autism, 4(1), 40. https://doi.org/10.1186/2040-2392-4-40 2. gregersen, p. k., kowalsky, e., lee, a., baron-cohen, s., fisher, s. e., asher, j. e., ballard, d.,freudenberg, j., & li, w. (2013). absolute pitch exhibits phenotypic and genetic overlap with synesthesia. human molecular genetics, 22(10), 2097–2104. https://doi.org/10.1093/hmg/ddt059 3. hughes, j. e. a., simner, j., baron-cohen, s., treffert, d. a., & ward, j. (2017). is synaesthesia more prevalent in autism spectrum conditions? only where there is prodigious talent. multisensory research, 30(3-5), 391–408. https://doi.org/10.1163/22134808-00002558 4. nugent, m., & ward, j. (2022). familial aggregation of synaesthesia with autism (but not schizophrenia). cognitive neuropsychiatry, 27(5), 373–391. https://doi.org/10.1080/13546805.2022.2095897 5. elam, m. (2007). excess of high frequency electroencephalogram oscillations in boys with autism. biological psychiatry, 62(9), 1022–1029. https://doi.org/10.1016/j.biopsych.2006.12.029 6. simner, j., mulvenna, c., sagiv, n., tsakanikos, e., witherby, s. a., fraser, c., scott, k., & ward, j. (2006). synaesthesia: the prevalence of atypical cross-modal experiences. perception, 35(8), 1024-1033. https://doi.org/10.1068/p5469 7. terhune, d. b., tai, s., cowey, a., popescu, t., & cohen kadosh, r. (2011). enhanced cortical excitability in grapheme-color synesthesia and its modulation. current biology : cb, 21(23), 2006–2009. https://doi.org/10.1016/j.cub.2011.10.032 8. treffert, d. a. (2009). the savant syndrome: an extraordinary condition. a synopsis: past, present, future. philosophical transactions of the royal society of london. series b, biological sciences, 364(1522), 1351–1357. https://doi.org/10.1098/rstb.2008.0326 9. van leeuwen, t. m., neufeld, j., hughes, j., & ward, j. (2020). synaesthesia and autism: different developmental outcomes from overlapping mechanisms? cognitive neuropsychology, 37(7-8), 433–449. https://doi.org/10.1080/02643294.2020.1808455 10. van leeuwen, t. m., van petersen, e., burghoorn, f., dingemanse, m., & van lier, r. (2019). autistic traits in synaesthesia: atypical sensory sensitivity and enhanced perception of details. philosophical transactions: biological sciences, 374(1787), 1–13. https://www.jstor.org/stable/26841008 brain matters・volume vii 24 https://doi.org/10.1186/2040-2392-4-40 https://doi.org/10.1163/22134808-00002558 https://doi.org/10.1016/j.biopsych.2006.12.029 https://doi.org/10.1068/p5469 https://doi.org/10.1016/j.cub.2011.10.032 https://doi.org/10.1098/rstb.2008.0326 https://psycnet.apa.org/doi/10.1080/02643294.2020.1808455 brain matters vol. 8 no. 1 written by leah rupp the difference between children's learning abilities with and without adhd introduction attention-deficit hyperactivity disorder (adhd) is one of the most common neurodevelopmental disorders found in children (cleveland clinic, 2023). it is a developmental disorder that can interfere with social and school-related activities and can be diagnosed as young as 2 years of age. low amounts of gray matter and neurotransmitter γaminobutyric acid (gaba) have all been connected to adhd symptoms. gray matter, primarily composed of neuronal cell bodies, dendrites, and unmyelinated axons, is commonly found in lower amounts in patients with adhd. another cause of adhd is lower concentrations of gaba. physicians most commonly screen for adhd by using the diagnostic and statistical manual, fifth edition (dsm-5), a test consisting of a series of yes or no questions. individuals aged 16 or younger who answer 'yes' to six or more of the questions meet the diagnostic criteria for adhd. these questions are designed to assess common behaviors associated with adhd, such as, “often does not seem to listen when spoken to directly,” “often has trouble holding attention to tasks or play activities,” and “often fidgets with or taps hands or feet” (cleveland clinic, 2023). it can be difficult to diagnose adhd because many symptoms are very similar to various anxiety and mood disorders. moreover, adhd affects young children mostly in school (cleveland clinic, 2023), where challenges sitting still for extended periods can impact their learning experience. for children six years and younger it is recommended to try behavior therapy rather than start adhd drugs (cleveland clinic, 2023). parents can try to better manage children's behavior by creating a routine, utilizing prizes when goals are achieved, and limiting choices. however, for children older than six, medical treatments are recommended (cleveland clinic, 2023). adhd medications consist of stimulants and non-stimulants, with non-stimulants being less effective. common stimulants are methylphenidate and amphetamine, which create a calming effect on children with adhd. individuals may only see results after weeks of taking the drug (cleveland clinic, 2023). gray’s matters effect on adhd dr. luke norman, a scientist at the national institute of mental health (nimh), discovered that adhd is linked to irregular connections between the brain’s frontal cortex and information processing centers. the cerebral cortex, the outermost layer of the brain, plays a critical role in processing information, supported by the dendrites that play a key role in receiving chemical messages from other nerve cells. according to the cleveland clinic, this region of the brain is also responsible for “memory, learning, and decision-making” (cleveland clinic, 2024). individuals with adhd have a smaller amount of gray matter in addition to a decreased volume of specific cortical regions, as shown in figure 1. this may help explain why individuals diagnosed with adhd 46 often exhibit a shorter attention span and may struggle to maintain focus for extended periods because of the lower amounts of dendrites that receive chemical messages. the frontal cortex of individuals with adhd tends to develop at a much slower rate than individuals with a neurotypical brain. children with neurotypical brains may have higher rates of neuroplasticity, which can increase their ability to retain information efficiently (puderbaugh, 2023). according to the national institute of health, neuroplasticity is "a process that involves adaptive structural and functional changes to the brain" (puderbaugh, 2023). children are often able to learn more quickly than adults due to greater neuroplasticity; however, this ability diminishes with age. during the early years of life, a child's brain is rapidly absorbing and processing new information like a sponge, leading to learning a language more readily than an individual in their 80s for example. studies on γ-aminobutyric acid dr. sebastian m. frank, a researcher at brown university, discovered that the increased amount of neurotransmitter γ-aminobutyric acid (gaba) in children helps them retain new information that is learned. according to the cleveland clinic, gaba is an inhibiting neurotransmitter that “creates a calming effect” as it stops chemical messages from being sent from one nerve cell to another. dr. richard a. edden, a neuroradiologist at the john hopkins university school of medicine, conducted a study connecting gaba amounts and those diagnosed with adhd. the goal of the study was to connect gaba concentration in an individual and whether or not they have adhd. patient’s brains were scanned with a 3-tesla mri scanner. children from ages 8-12 with adhd were compared with children with neurotypical brains. the findings, shown in figure 2, rreveal reveal a notable difference in gaba concentrations between children with and without adhd. children without adhd have higher levels of gaba, which may contribute to their ability to learn efficiently and maintain focus. in contrast, children with adhd tend to have lower gaba concentrations, potentially reducing the 'calming effect' that gaba provides, as described by the cleveland clinic. this difference can negatively impact their ability to stay focused in school, making it challenging to engage in prolonged learning activities. with the correlation between gaba and adhd noticed, potential gabaergic therapies could decrease symptoms of adhd seen in kids (edden, 2012). conclusion by studying gray matter and gaba, adhd medication can better target what is exactly causing adhd. qelbree and kapvay are newer drugs that target grey matter to help lower hyperactivity as seen in those diagnosed with adhd. however, so much still needs to be discovered on what is the most efficient way to reduce adhd symptoms, as many of these common drugs have drastic side effects such as nausea, headaches, and tiredness. according to the cdc, six million children between the ages of 2-17 in america have been diagnosed with adhd. the implications of this diagnosis and its treatment negatively affect them academically and socially. from the connections found between grey matter and gaba in adhd, more drugs could better target these areas to treat adhd. references 1. norman, l. (2024, march 13). nih researchers identify brain connections associated with adhd in youth. national institutes of health. https://www.nih.gov/news-events/news-releases/nihresearchers-identify-brain-connections-associated-adhdyouth (figure 1) the difference between children's learning abilities with and without adhd figure 1. smaller amounts of gray matter seen in individuals with adhd, images c and d vs those without adhd, images a and b figure 2. the bar graph displays a statistically significant difference in gaba concentration between the female and male td group (neurotypical) as compared to the female and male adhd group. 47 2. edden, r. a. e., crocetti, d., zhu, h., gilbert, d. l., & mostofsky, s. h. (2012, july). reduced gaba concentration in attention-deficit/hyperactivity disorder. archives of general psychiatry. https://pmc.ncbi.nlm.nih.gov/articles/pmc3970207/ (figure 2) 3. centers for disease control and prevention. (n.d.). treatment of adhd. centers for disease control and prevention. https://www.cdc.gov/adhd/treatment/index.html 4. adhd vs neurotypical brains: mental health academy. adhd vs neurotypical brains | mental health academy. (n.d.). https://www.mentalhealthacademy.com.au/blog/adhd-vsneurotypical-brains-implications -for-therapists 5. puderbaugh, m. (2023, may 1). neuroplasticity. statpearls [internet]. https://www.ncbi.nlm.nih.gov/books/nbk557811/ 6. professional, c. c. medical. (2024, may 1). gammaaminobutyric acid (gaba): what it is, function & benefits. cleveland clinic. https://my.clevelandclinic.org/health/articles/22857gamma-aminobutyric-acid-gaba 7. commissioner, o. of the. (n.d.). the fda has approved medications to help reduce the symptoms of adhd. u.s. food and drug administration. https://www.fda.gov/consumers/consumerupdates/treating-and-dealing-adhd 8. why do children learn more quickly than adults? new study offers clues. brown university. (2024, november 13). https://www.brown.edu/news/2022-11-15/children-learning 9. professional, c. c. medical. (2024c, september 1). cerebral cortex: what it is, function & location. cleveland clinic. https://my.clevelandclinic.org/health/articles/23073cerebral-cortex 10. attention-deficit/hyperactivity disorder (adhd). cleveland clinic. (2023, february 22). https://my.clevelandclinic.org/health/diseases/4784attention-deficithyperactivity-disorde r-adhd brain matters vol. 8 2025 about the author leah rupp is a freshman at the university of illinois in urbana-champaign studying molecular and cellular biology within the honors concentration. leah joined brain matters to get the opportunity to learn and write about new neuroscience research. leah is also a stress management peer with mckinley health center and a volunteer with the food assistance and wellbeing program. in her free time, leah enjoys running and playing the piano. her career aspiration is to become a physician. 48 49 brain matters vol. 8 no. 1 survival vs. cognition: stress mechanisms in humans vs. animals written by pravika srivastava introduction to stress mechanisms stress is defined as the physiological and psychological reaction to perceived threats or demands that activates a cascade of neurobiological processes that help maintain homeostasis (mcewen, 2007). the hypothalamic-pituitaryadrenal axis (the hpa axis) plays the primary role in regulating stress and the release of stress hormones such as cortisol and corticosterone. these hormones are used to regulate the physiological and behavioral responses in several species (sapolsky, romero, & munck, 2000). additionally, neurotransmitters play an equally important role in the regulation of stress and emotion. specifically, dopamine and norepinephrine influence stress-related cognitive and emotional regulation (joëls & baram, 2009). even with similar processes of regulating stress, animals and humans tend to respond to and process stress differently. animals are primarily concerned with acute survival-linked stressors, such as predation or resource deficiency. whereas, humans experience complex cognitive appraisal, differentiating between immediate threats and external concerns like societal or financial pressures. it is crucial to highlight and study these differences between human and animal stress responses as it allows us to improve the understanding of chronic stress disorders and coping strategies in humans while also enhancing animal stress research. fight-or-flight response in humans vs. animals animals and humans both respond differently to perceived threats; however, one mechanism that allows both to respond rapidly is the fight-or-flight response. this response is quite instinctive in animals and is triggered by the autonomic nervous system, especially in the sympathetic branch. this area is known to initiate rapid physiological changes like increased heart rate, energy mobilization and pupil dilation (cleveland clinic, 2022). in animals, these reactions and changes are crucial for survival during acute stressors. these stressors entail predator-prey encounters, where quick action is needed and can determine life or death. the hpa axis releases glucocorticoids that help maintain energy levels and modulate inflammation during high-stress periods such as these (wingfield & romero, 2001). however, in humans, physiological responses also have an added cognitive aspect. humans tend to interpret stress through fear and anxiety and this is based on whether the stress is a direct and immediate stressor or an anticipated one. since humans can overthink problems, it is common for humans to stay stressed even after the direct stressor has left. unlike animals, we continue to worry about things that have not even occurred or happened in our work and social lives. this tendency makes it more difficult for humans to recover and overtime leads to issues such as anxiety and burnout (harvard health publishing, 2018). 62 long-term stress: chronic stress in animals and humans animals in the wild are oftentimes subjected to brief, severe stressors like predators or harsh weather. these difficulties trigger quick physiological reactions, such as the release of glucocorticoids, which minimize long-term harm by rapidly returning to baseline after the threat has passed (wingfield and romero, 2001). however, some animals are kept in captivity survival-based stress response in humans vs. animals stress in animals is highly survival-driven and is elicited by immediate threats by predators, famine or weather. these acute stressors can trigger fast physiological adjustments that enable them to hide, fight or even run away. these reactions have been perfected over the course of evolution to maximize survival (wingfield & romero, 2001). as the danger leaves, the stress response switches off, and the animal can recover by returning to rest and conserving energy. figure 2 illustrates this process, showing how animals pass through an ordered cascade of physiological and behavioral responses to perceived danger, and recovery or chronic stress outcome in relation to their capacity to recover homeostasis. the way that animals are able to recover so quickly is a significant evolutionary adaptation that saves animals from experiencing effects of chronic stress. on the other hand, humans perceive stress in addition to physical danger. some examples could include public speaking, issues at work and in relationships. this difference between humans and animals is because humans have an advanced cognitive ability to imagine, evaluate and magnify risks (ohman, 2005.) due to this, humans often feel stressed in response to psychological or social problems in the absence of any real life-threatening situation. this is beneficial as humans can adapt their actions allowing them to prepare and evade threats, but it also leads to chronic disease (harvard health publishing, 2018). captivity which can lead to ongoing stress. this is due to confinement, lack of stimulation, and abnormal social structures. this is due to confinement, lack of stimulation, and abnormal social structures. according to morgan and tromborg, these disorders may cause a persistent increase in stress hormones, which can have a detrimental effect on immune system performance, reproductive success, and general animal behavior. long-term exposure to glucocorticoids in captive animals has led to chronic stress. behaviors such as disruption in circadian rhythms, and impairment of hippocampus function are just some signs (mcewen, 2007). in people, psychological and social triggers like employment obligations, interpersonal issues, and unstable finances are more frequently the cause of chronic stress. given that humans have a more developed prefrontal cortex as opposed to animals, they are able to predict, consider, and magnify stressors, triggering the hypothalamic-pituitary-adrenal (hpa) axis to continuously activate (joëls and baram, 2009). eventually, this imbalance leads to a variety of illnesses, such as diminished immune system, anxiety, depression, and cardiovascular disease (mcewen; chrousos and gold, 1998). the frequency of exposure can lead to long-term physiological damage is explained by the idea of allostatic load, which is the overall deterioration on the body brought on by chronic stress (mcewen and seeman, 1999). these consequences highlight the importance of resilience-building techniques and stressreduction tactics in human health care and lifestyle. figure 1. diagram showing the human stress response pathways. the sam pathway triggers immediate release of adrenaline and norepinephrine (fight-or-flight), while the hpa axis leads to cortisol release during prolonged stress. simply psychology, “what is the hpa axis?” figure 2. powell, roger a., et al. “diagram illustrating the stress response that follows when an animal perceives a threat to homeostasis.” researchgate, 2012 63 survival vs. cognition: stress mechanisms in humans vs. animals support systems and growth mindsets though its structure and purpose vary among different species, social support is crucial for controlling stress in both people and animals. stress levels in animal communities can be very much influenced by social hierarchies and group dynamics. for instance, constant social stress—especially in captivity—allows subordinate animals within rigid hierarchies to have higher glucocorticoid levels. on the other hand, animals that create stable social ties—such as grooming-engaging primates— often have reduced levels of stress hormones, underscoring the protective effect of positive social interactions (wingfield and romero, 2001). in humans, networks of social support—including family, friends, and community members—act as shielding buffers against ongoing psychological stress.these interactions help to downregulate the activity of the sympathetic nervous system and the hpa axis, thus reducing the physiological consequences of stress (mcewen, 2007). besides, resilience against stress depends on a person's psychological viewpoint. implications for behavioral models and future research: this paper looked into how human and animal stress mechanisms differ, emphasizing how humans frequently experience cognitively driven, chronic stress while animals depend on acute, survival-based reactions. both make use of comparable biological systems, such as the hpa axis and the sympathetic nervous system, but because of our superior cognitive abilities, humans are exposed to stress for longer periods the ability to reframe stress through a growth mindset helps humans to see obstacles as opportunities rather than hazards. this cognitive assessment modulates the stress reaction by influencing the way the brain understands threats and their consequent physiological effects (joëls and baram, 2009). using adaptive coping techniques that support emotional control and lower allostatic load—cognitive reappraisal, mindfulness, and goal-setting—helps one to reduce persistent stress (mcewen and seeman, 1999). consequently, how different animals react to and recover from stress depends much on both internal mental frameworks and outside social settings. periods of time and experience more complicated effects. important differences have been observed in the influence of social and psychological factors, long-term stress development, and fight-or-flight reactions. behavioral psychology greatly benefits from the research of stress processes in human-animal relationships. stress reactions have a direct impact on behavior, decision-making, and emotional regulation since they are based on common neurobiological systems such as the sympathetic nervous system and the hpa axis (joëls and baram, 2009). more specialized behavioral models, like those for anxiety, depression, and post-traumatic stress disorder (ptsd), can be guided by knowledge of how long-term stress changes the brain circuits involved in cognition and emotion. for instance, knowledge gained from research on animals has influenced pharmacological and exposure-based therapies to control the release of stress hormones and brain plasticity (mcewen, 2007). but the primary issue is the morality of using animals in stress studies. in order to protect animal welfare while advancing science, researchers must provide humane conditions, reduce suffering, and use alternatives when possible (morgan and tromborg, 2005). the relationship between stress resilience, neuroplasticity, and specialized treatment approaches must be further investigated in future studies. to better understand how early life stress, social context, and psychological state interact to influence long-term health outcomes, more longitudinal research in humans is needed. public health and tailored treatment can also benefit from studying how stress appears in other animals and social groups. combining psychological ideas with neurobiological facts may also improve our capacity to anticipate stress vulnerability and stop it from happening. future research can better understand stress problems and inform more efficient, moral, and focused treatments by integrating insights from animal studies into human behavioral science. references 1. af;, a. (n.d.). stress signalling pathways that impair prefrontal cortex structure and function. nature reviews. neuroscience. https://pubmed.ncbi.nlm.nih.gov/19455173/ 2. arne öhman, summary behavioral data suggest that fear stimuli automatically activate fear and capture attention. this effect is likely to be mediated by a subcortical brain network centered on the amygdala. consistent with this view, vuilleumier, p., anderson, a. k., armony, j. l., bishop, s. j., carlsson, k., cunningham, w. a., davidson, r. j., dimberg, u., globisch, j., ledoux, j. e., miltner, w. h. r., & morris, j. s. (2005a, june 16). the role of the amygdala in human fear: automatic detection of threat. psychoneuroendocrinology. https://www.sciencedirect.com/science/article/abs/pii/s030 6453005001022 3. on, p. by p. m. (2022, april 11). human steam. human steam. https://humanap.community.uaf.edu/2022/04/11/hpa-axiseffects-of-stress%ef%bf%bc/ brain matters vol. 8 2025 64 4. understanding the stress response. harvard health. (2024, april 3). https://www.health.harvard.edu/stayinghealthy/understanding-the-stress-response 5. joëls, m., & baram, t. z. (2009, april 2). the neurosymphony of stress. nature news. https://www.nature.com/articles/nrn2632 6. bs;, m. (n.d.). physiology and neurobiology of stress and adaptation: central role of the brain. physiological reviews. https://pubmed.ncbi.nlm.nih.gov/17615391/ 7. professional, c. c. medical. (2025, april 1). sympathetic nervous system (sns): what it is & function. cleveland clinic. https://my.clevelandclinic.org/health/body/23262sympathetic-nervous-system-sns-fight-or-flight 8. rosmond, r., dallman, m. f., & björntorp, p. (1998). stressrelated cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. the journal of clinical endocrinology & metabolism, 83(6), 1853-1859. 9. sapolsky, r. m., romero, l. m., & munck, a. u. (2000). how do glucocorticoids influence stress responses? integrating permissive, suppressive, stimulatory, and preparative actions. endocrine reviews, 21(1), 55-89. 10. williams, k. (2023). cat in repose. island in the net. retrieved june 2, 2025, from https://islandinthenet.com/catin-repose/ 11. 2 diagram illustrating the stress response that follows ... (n.d.-a). https://www.researchgate.net/figure/diagramillustrating-the-stress-response-that-follows-when-ananimal-perceives-a-threat_fig1_248706927 about the author pravika srivastava is a rising junior at the university of illinois urbana-champaign majoring in neuroscience with a minor in psychology on the pre-medical track. she is passionate about brain health, mental well-being, and hopes to pursue a career in psychiatry. as a writer and new social media co-chair for brain matters, she enjoys writing about neuroscience-related topics while eager in helping expand the journal’s outreach. on campus, pravika volunteers in the pediatric icu at carle foundation hospital, conducts research at the connectlab and rudolph lab, and serves on the speaker committee for alpha epsilon delta. pravika is excited to share her research and writing as part of her ongoing commitment to advancing understanding of the brain and mental health. survival vs. cognition: stress mechanisms in humans vs. animals 65 66 volume 8 (will be vol 7 on site) understanding common personality disorders: the neurological basis of ocd, npd, and bpd isabelle afshari abstract historically, the complexity of personality disorders has posed challenges to both diagnosis and treatment; however, with advances in technology, various studies have begun making new developments to elucidate the neurobiological causes of many of the most common personality disorders, such as obsessive-compulsive disorder (ocd), narcissistic personality disorder (npd), and borderline personality disorder (bpd). by understanding the neurobiological causes of these disorders, further therapeutic and pharmaceutical treatment options can be developed, and information about these disorders can become widespread. what is a personality disorder? according to the diagnostic and statistical manual of mental disorders: 5th edition (dsm-5), a personality disorder is defined by the disruption in at least two of the areas of cognition, affectivity, interpersonal control, and impulse control, with these behaviors carrying throughout a variety of situations and being tracked back to adolescence or early adulthood (5th ed.; dsm–5; american psychiatric association, 2013). the three most prevalent personality disorders in the united states include obsessive-compulsive disorder, borderline personality disorder, and narcissistic personality disorder; however, the broader diagnosis that encompasses all personality disorders is general personality disorder. general personality disorder follows a broad pattern of behaviors for a diagnosis, which as the dsm-5 defines, is “when personality traits are inflexible and maladaptive and cause significant functional impairment or subjective distress” (5th ed.; dsm–5; american psychiatric association, 2013). because of the vast range of behaviors that can be characterized as general personality disorders, symptoms are sorted into three clusters, labeled cluster a, cluster b, and cluster c. cluster a personality disorders are considered the more “severe” types of personality disorders, with symptoms including “odd beliefs, unusual perceptual experiences, odd thinking and speech, paranoid ideation, and odd or eccentric appearance or behavior” (esterberg, goulding, & walker, 2010). cluster b personality disorders are characterized as “dramatic, emotional, or erratic,” and often have connotations of a lack of empathy (kraus & reynolds, 2001). cluster c personality disorders consist of three personality disorders: avoidant personality disorder, dependent personality disorder, and obsessive-compulsive personality disorder, with all of the disorders including avoidance and control as coping strategies and an inability to form close relationships with others (bachrach & artnz, 2021). obsessive-compulsive disorder (ocd) obsessive-compulsive disorder is the most common cluster c personality disorder, as well as the most common personality disorder in the united states, with 2.3% of american individuals having diagnoses of lifetime ocd, and 1.2% of americans having diagnoses of 12-month ocd (ruscio, stein, chiu, & kessler, 2010). ocd is diagnosed based on the presence of obsessions, which are manifested by intrusive thoughts or images that increase anxiety, and by compulsions, which are performed to reduce this anxiety (stein, 2002). although the diagnosis of obsessive-compulsive disorder is made based on behaviors, research has established neurobiological and genetic factors as key underlying causes. in a cambridge university neuroimaging study, researchers found that patients with ocd tend to have hyperactivity of the ventral cognitive circuit, specifically in the basal ganglia and thalamus, which control sensory function, executive functions, and behaviors (westenberg, fineberg, & denys 2014). additionally, patients with ocd have been found to have elevated glutamate and glycine levels in their cerebrospinal fluid as compared to controls, meaning that these patients had an increase in excitatory neurotransmitters, which produce alerting signals to be transmitted throughout the nervous system. there have also been increased findings of serotonin, a modulator of glutamate, in ocd patients (bhattacharyya, khanna, chakrabarty, mahadevan, christopher, & shankar, 2009). these findings suggest that the symptoms of ocd are produced by a framework in which more excitatory neurotransmitters are released, leading to increased activity within the ventral cognitive circuit, thus contributing to the elevated feelings of anxiety and obsessions that are only subdued by engaging in compulsions. furthermore, researchers have found potential genetic ties to ocd: a study with monozygotic (identical) as compared to dizygotic (fraternal) twins found that it is more common for both the monozygotic twins, with identical dna to have an onset of ocd if at least one twin does, with a rate of 80-87% than for both the dizygotic twins, which have a 47-50% rate of both having ocd if one twin has it. the study concluded that these findings serve as evidence of a dominant or codominant mode of transmission of ocd; however, the particular allele that this would affect has not been found (jenike, 2004). brain matters・volume vii 52 though obsessive-compulsive disorder has been linked to neural activity, the most common methods of treatment are behavioral interventions. however, pharmacologic approaches–including neuroleptic augmentation of antidepressants, and neuromodulation, including deep-brain stimulation–have found positive outcomes (hirschtritt, bloch, & mathews 2017). approaches to increase the number of serotonergic neurotransmissions in narcissistic personality disorder patients (weinberg & ronningstam, 2022). borderline personality disorder (bpd) borderline personality disorder is another cluster b personality disorder, which has a prevalence of 0.5-5.9% in the general united states population (leichsenring, leibing, kruse, new, & leweke, 2011). clinical signs of borderline personality disorder include emotional dysregulation, repeated self-injury, and chronic suicidal tendencies (lieb, zanarini, schmahl, linehan, & bohus, 2004). according to the dsm-5, while the root cause of bpd is not confirmed, genetic factors and adverse events during childhood, such as abuse, contribute to the onset of the disorder. however, recent studies have begun to prove the significance of serotonin in bpd. in particular, a study conducted at the mount sinai school of medicine found that dysfunction of the serotonin (5-ht) system has been linked with borderline personality disorder (gurvits, koenigsberg, & siever, 2005). this connects to the behavioral traits of those with the disorder, as this type of dysfunction has been associated with both self-directed and non-self-directed impulse aggression. additionally, it has been found that the instability found in individuals with bpd may be affected by dysregulations in cholinergic, noradrenergic (ne) or gammaaminobutyric acid (gaba)-minergic systems. these systems regulate inhibitory pathways, which suppress signals; therefore, if these are dysfunctional, patients will be much more alert and reactive to stimuli (gurvits, koenigsberg, & siever, 2005). bpd has no effective pharmaceutical treatment to combat symptoms because there is so little known about it. however, common alternatives include psychotherapy, which includes dialectical behavioral therapy and cognitive behavioral therapy, in addition to family therapy (nimh, 2023). figure 1. signs of ocd some common characteristics of ocd include organization, perfectionism, and attention to detail (wikimedia commons, 2022). figure 2. signs of bpd some common characteristics of bpd include fear of abandonment, unstable relationships, and unstable sense of identity (wikimedia commons, 2024). narcissistic personality disorder (npd) narcissistic personality disorder is the most common cluster b personality disorder in the united states, with a lifetime prevalence rate of 6% in the general population, as found by the wave 2 national epidemiologic survey on alcohol and related conditions (ronningstam, 2010). diagnosis of narcissistic personality disorder is based on behaviors of one of two subtypes: overt or covert. the overt subtype is characterized by “grandiosity, attention seeking, entitlement, arrogance, and little observable anxiety,” whereas the covert subtype is characterized by being “inhibited, manifestly distressed… shy, outwardly self-effacing, and hypersensitive to slights” (caligor, levy, & yeomans, 2015). similar to other personality disorders, narcissistic personality disorder is diagnosed based on a pattern of behaviors, yet it does have a neurological basis. although not much research has been conducted on the effect of neurotransmitters on npd, some studies have found links of narcissism to lower levels of serotonin. in a german study conducted by paraskevi mavrogiorgou, 74 healthy control patients and 74 patients with depressive disorders completed two personality assessments and an eeg for analysis of serotonergic transmissions (mavrogiorgou, seltsam, kiefner, flashback, & juckel, 2022). the results dictated that individuals from either group that tested positive for narcissism tended to have lower serotonergic neurotransmissions. for npd, no psychotherapy nor pharmacotherapy treatments have been found to be effective, with a 63-64% drop-out rate for psychotherapy and no current approved pharmacological conclusion neurotransmitters prove to be crucial in determining the symptoms of the three most commonly diagnosed personality disorders, obsessive-compulsive disorder, narcissistic personality disorder, and borderline personality disorder. in particular, serotonin plays a significant role in determining behavioral tendencies, with higher levels leading to greater sources of anxiety, and lower levels leading to increased apathy. although the dsm-5 has yet to validate the link between neurotransmitters and these personality disorders, new studies continue to suggest that serotonin does have an impact on behaviors. if the impact of serotonin is eventually validated by the dsm-5, the detection of these disorders would become much more objective, as it would be dependent on serotonergic levels rather than a psychologist or physician’s perception of behaviors. additionally, the production of medications to alleviate the symptoms of these disorders and normalize serotonin levels could prove impactful for the large percentages of americans impacted by these disorders. affected individuals will have new means of receiving treatments and diagnostic methods for these disorders will evolve as the observed role of neurotransmitters in these disorders increases. references 1. bachrach, n., & arntz, a. (n.d.). group schema therapy for patients with cluster-c personality disorders: a case study on avoidant personality disorder. journal of clinical psychology. https://doi.org/https://doi.org/10.1002/jclp.23118 2. bhattacharyya, s., khanna, s., chakrabarty, k., mahadevan, a., christopher, r., & shankar, s. k. (2009). anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive–compulsive disorder. neuropsychopharmacology, 34(12), 2489–2496. https://doi.org/10.1038/npp.2009.77 3. caligor, e., levy, k. n., & yeomans, f. e. (2015). narcissistic personality disorder: diagnostic and clinical challenges. american journal of psychiatry, 172(5), 415–422. https://doi.org/10.1176/appi.ajp.2014.14060723 4. diagnostic and statistical manual of mental disorders: dsm-5. (2017). . american psychiatric association. 5. esterberg, m. l., goulding, s. m., & walker, e. f. (2010, may 5). cluster a personality disorders: schizotypal, schizoid and paranoid personality disorders in childhood and adolescence. 6. file:signs of bpd 1.png. (2024, july 19). wikimedia commons. retrieved 23:41, august 12, 2024 from https://commons.wikimedia.org/w/index.php? title=file:signs_of_bpd_1.png&oldid=900677099. 7. file:signs of ocpd 1.png. (2022, march 28). wikimedia commons. retrieved 23:37, august 12, 2024 from https://commons.wikimedia.org/w/index.php? title=file:signs_of_ocpd_1.png&oldid=644817909. 8. gurvits, i. g., koenigsberg, h. w., & siever, l. j. (2000). neurotransmitter dysfunction in patients with borderline personality disorder. psychiatric clinics of north america, 23(1), 27–40. https://doi.org/10.1016/s0193-953x(05)70141-6 9. hirschtritt, m. e., bloch, m. h., & mathews, c. a. (2017). obsessive-compulsive disorder. jama, 317(13), 1358. https://doi.org/10.1001/jama.2017.2200 10. jenike, m. a. (2004). obsessive–compulsive disorder. new england journal of medicine, 350(3), 259–265. https://doi.org/10.1056/nejmcp031002 11. kraus, g., & reynolds, d. j. (2001). the “a-b-c’s” of the cluster b’s: identifying, understanding, and treating cluster b personality disorders. clinical psychology review, 21(3), 345–373. https://doi.org/https://doi.org/10.1016/s02727358(99)00052-5 12. leichsenring, f., leibing, e., kruse, j., new, a. s., & leweke, f. (2011). borderline personality disorder. the lancet, 377(9759), 74–84. https://doi.org/10.1016/s01406736(10)61422-5 13. lieb, k., zanarini, m. c., schmahl, c., linehan, m. m., & bohus, m. (2004). borderline personality disorder. the lancet, 364(9432), 453–461. https://doi.org/10.1016/s01406736(04)16770-6 14. mavrogiorgou, p., seltsam, f., kiefner, d., flasbeck, v., & juckel, g. (2022). narcissism and central serotonergic neurotransmission in depression. the world journal of biological psychiatry, 24(3), 233–242. https://doi.org/10.1080/15622975.2022.2095026 15. national institute of mental health. (2023, april). borderline personality disorder. 16. pally, regina. the neurobiology of borderline personality disorder: the synergy of “nature and nurture”. journal of psychiatric practice 8(3):p 133-142, may 2002. 17. ronningstam, e. (2010). narcissistic personality disorder: a current review. current psychiatry reports, 12(1), 68–75. https://doi.org/10.1007/s11920-009-0084-z 18. ruscio, a. m., stein, d. j., chiu, w. t., & kessler, r. c. (2008). the epidemiology of obsessive-compulsive disorder in the national comorbidity survey replication. molecular psychiatry, 15. 19. stein, d. j. (2002). obsessive-compulsive disorder. the lancet, 360(9330), 397–405. https://doi.org/10.1016/s01406736(02)09620-4 20. weinberg, i., & ronningstam, e. (2022). narcissistic personality disorder: progress in understanding and treatment. focus, 20(4), 368–377. https://doi.org/10.1176/appi.focus.20220052 21. westenberg, h. g. m., fineberg, n. a., & denys, d. (2014). neurobiology of obsessive-compulsive disorder:serotonin and beyond. cns spectrums, 12(s3), 14– 27. https://doi.org/10.1017/s1092852900002479 brain matters・volume vii 54 https://commons.wikimedia.org/w/index.php?title=file:signs_of_bpd_1.png&oldid=900677099 https://commons.wikimedia.org/w/index.php?title=file:signs_of_bpd_1.png&oldid=900677099 https://commons.wikimedia.org/w/index.php?title=file:signs_of_ocpd_1.png&oldid=644817909 https://commons.wikimedia.org/w/index.php?title=file:signs_of_ocpd_1.png&oldid=644817909 volume 8 (will be vol 7 on site) brain matters writers hello! my name is celeste and i’m a december ‘23 mcb and psychology alum. my last semester as a student i had the privilege to serve on the brain matters exec board as social chair. i currently work as a mental health technician trainee at an in-patient hospital in chicago. i plan to continue working as i prepare myself to apply to medical school next year! my current hobbies include reading, spending time with my family and friends, and playing animal crossing new horizons. krisha agarwal is a sophomore in mcb honors. she is currently working in prasanth lab, which explores long non-coding rnas in terms of hypoxia in cancer. some of her interests include film, photography, and fashion. brain matters fuels her interest in writing and acts as a stepping stone for acquiring the necessary skills to publish her own research in the future, as she builds on her scientific knowledge. after her undergraduate years, she hopes to continue research in graduate school. joy akindulureni is a junior studying psychology with a concentration in cognitive neuroscience and minors in informatics and integrative biology. her research interests are in neuroimaging, neurodegenerative diseases and aging. isabelle is a freshman at the university of illinois majoring in neuroscience. isabelle became involved in brain matters to learn more about writing scientific articles and innovations in neuroscience. in addition to writing for brain matters, isabelle is involved in mckinley health stress management peers, las leaders, and women’s glee club. in the future, isabelle hopes to attend medical school and continue reading and writing about new scientific innovations! br ai n m at te rs w ri te rs erin ford is a sophomore majoring in chemical engineering with a concentration in biomolecular engineering. in her free time, she enjoys playing tennis and painting. she hopes to help others increase their knowledge about neuroscience through her writing in brain matters. harrison kennedy is a freshman studying neuroscience and spanish with a minor in legal studies on a pre-law track. he spends most of his time in the auerbach lab as an undergraduate research assistant where he investigates auditory perception in rats and the interactions between fragile x syndrome and cerebral processing of auditory stimuli. outside of lab work, he is an active member in the spikeball/roundnet club, pre-law honors society, phi alpha delta professional pre-law fraternity, and he’s in the process of registering a new rso for next semester. in his free time, he loves to hike, write, and have fun with friends. sarah masud is a sophomore studying psychology and information sciences with a minor in art & design. some of her academic interests include cognition, human-computer interaction, and treating psychiatric disorders. she enjoys drawing, finding new music, and crocheting as well! outside of brain matters, sarah is also involved in design innovation illinois, the undergraduate psychology association, and psi eta mu, a professional information sciences fraternity. she hopes to continue furthering her understanding of neuroscience and exploring topics she’s passionate about through writing for the journal. casey is a sophomore majoring in chemical and biomolecular engineering. she works in the sirk lab, conducting research on the gut microbiome. in her free time, she enjoys reading and taking her dog for hikes. after graduation, she hopes to attend medical school. brain matters・volume vii 94 vraj is a freshman at the university of illinois majoring in neuroscience. vraj joined brain matters to learn about more niche topics in neuroscience and research in the field. in addition to writing for brain matters, vraj is a course assistant for stat 100 and a volunteer at avicenna community health center. vraj hopes to explore more in the field of neuroscience from a medical perspective in the future! ananya sampathkumar is a freshman majoring in neuroscience with an interest in minoring in journalism. outside of brain matters, ananya is a part of tfn, mannmukti, a volunteer at carle hospital, and works at the office of undergraduate admissions as a tour guide and student ambassador. in her free time, ananya likes to read books, make jewelry, watch movies, and hangout with her friends! vani sharma is majoring in mcb honors on the pre-med track, with a minor in public health & neuroscience certificate. she is a writer for brain matters, which allows her the opportunity to learn about the brain & its neuroanatomy in depth along with her interest in brain disorders. on campus, she is heavily involved with medical clubs & the illini strings orchestra, serves as an undergraduate research ambassador, is a part of the madak erdogan women's health & metabolism lab, and works as a teaching assistant for chemistry. after graduating from uiuc, she hopes to attend medical school. pravika srivastava is a rising sophomore at the university of illinois urbana-champaign, majoring in neuroscience on the pre-medical track. she is an aspiring physician hoping to specialize in psychiatry. she is a writer for brain matters which gives her the opportunity to fully immerse herself in her interests regarding the nervous system and brain. in addition to writing, she pursues several other activities on campus. these include volunteering in the pediatric icu at carle foundation hospital, serving as a chair member for the american medical students association as well as being a member of the pre-health professional fraternity alpha epsilon delta. pravika is thrilled to share her first article and latest research with brain matters. through this organization and the several others, she is a part of, pravika is determined to increase awareness and understanding about the brain and field of neuroscience. br ai n m at te rs w ri te rs br ai n m at te rs w ri te rs kaitlyn is a sophomore in bioengineering on the therapeutics track with a minor in statistics. she is involved in various rsos such as the society of women engineers (swe), women in engineering (wie), and the biomedical engineering society (bmes). she is currently in two research labs the i^2 lab and gritton lab. in her free time, kaitlyn loves to bake puff pastries, go to the gym, learn new pieces on the piano, and hang out with her friends. she hopes to spark readers' interest in neurological issues and deepen her knowledge through brain matters. brain matters・volume vii 96 esther nam is a sophomore on the pre-med track majoring in psychology with a minor in public health. she is currently interested in exploring the cognitive and neurological aspects of bilingualism but is still open to other areas of research. while having started her experience in the educational psychology psycholinguistics lab with a focus on cognitive psychology, she hopes to branch out to other areas as well, including neuroscience. outside of academics, she enjoys digital drawing, watching shows, and playing video games with friends. after undergrad, she hopes to attend medical school and pursue a career in medicine. the sense of smell is powerful for its ability to evoke a response to a past experience, whether it was experienced years ago or an hour ago. this could be associated with a cooked dinner, a hike in a forest after rain, or the stench of garbage in a city alleyway. yet the association between a smell and the memory surrounding it leaves many unanswered questions about the process and the ways it is used in people. for example, one may wonder whether infants experience the same sort of memory retrieval due to olfactory stimulus that adults do, or what changes occur in the brain as a result of loss of the ability to smell. it is important to note that the reason our senses are such powerful tools lies in their connections to the brain; since our brain is perhaps the least understood organ, we already have a sense of its vast complexity and capability for what may be the unthinkable. while it may seem simple in nature that we have memories associated with smell, this trait can leave a large impact on us as we grow older. it is also this property that is exploited commercially by fragrance companies to make scents more appealing to consumers. because the brain has certain effects and capabilities in response to various stimuli, we are also able to compare these responses to other signals and how they differentiate from smell in other words what makes smell special to us. in order to better understand the process of connecting a scent with the brain, we can begin by asking: how does the brain take apart scents to process them? to answer we must look first in the nose and olfactory bulbs. the olfactory bulb is a part of the forebrain and is equipped with a set of nerves that extend past the cribriform plate – a part of the ethmoid bone that is located between the eyes – into the nasal cavity. when receptors in the nose pick up molecules from a specific scent, it is transmitted as an electrical signal to the olfactory bulb (manzini et al., 2014). in order to perceive something as a smell, the molecule must be an odorant, meaning it must meet some criteria, typically having some hydrophobicity and volatility (mayhew et al., 2022). the human nose is said to have approximately 350 different receptor types which can react to various smells through their molecular components (rinberg, 2020). olfactory receptors operate such that any combination of odor molecules can activate different sets of receptors (malnic et al., 1999). the molecules’ recognition and interaction with the receptors operates in a combinatorial way (malnic et al., 1999). this results in a system of activation allowing one to recognize what is now estimated to be up to 1 trillion different odors (bushdid et al., 2014). since the glomeruli, nerve ending bulbs found in the olfactory bulb, are unique to interactions with different smells, our perception of smell is highly dependent on how well they are activated and in what order. as a result, if we switch up the sequence in which they are activated or inactivate some of the receptors, we are likely to have a loss in ability to sense odors. one experiment testing this phenomenon of sequential activation impact on recognition was completed using a mouse model, which found that a delay or an interruption of a specific receptor receiving an orderant would decrease the system of cooperation between the receptors (nyu langone health, 2020). it was found that through the changing of the first glomeruli activated, as much as 30% of a drop could be recognized in the ability of a mouse to correctly sense the odor signal (nyu langone health, 2020). by contrast, if the last of the glomeruli was changed, only about 5% would be potentially dropped in the ability of the mouse to sense the correct odor. (nyu langone health, 2020). in order to identify what odors stand out within a mixture as well, the right sensors must be activated in the right order and time. any deviation in either of these abilities would result in the decreased ability to recognize and categorize the smell accurately. following this transmission of electrical signals to the glomeruli they will proceed to the brain’s cortex (nyu langone health, 2020). once the signal reaches the neurons of the cortex the brain takes further action. the piriform complex, a set of neurons right behind the olfactory bulb, will work in attempts to recognize the smell itself. this complex is the only known structure other than the hippocampus to have a three-layered allocortical structure, and is activated when the pyramidal cell, a type of neuron, receives information from the glomeruli and transmits it to other regions of the brain (vaughan, 2014). this also helps with responses to specific odor mixtures by aiding in the formation of a neural network that is capable of reliably transmitting these messages. the anterior piriform complex is thought to hold information of the molecular features of the odorant, whereas the posterior piriform for the quality of the odor (gottfried, 2006). the piriform complex additionally is used to help differentiate odors (howard et al., 2009) and is involved with the working memory where the odor information can be temporarily stored (zelano et al., 2009). in other words, it is of crucial importance that this complex is responsive and active in order to retain a highly functioning smell identification and memory connection system. it is from this complex that the information can then be further passed over to other areas of the brain. laura kilikevicius olfactory responses by memory 20brain matters・volume v issue ii having left off in our pathway at the piriform complex, various cells within this structure will signal and move the information to the thalamus, a complex key for translating the neural impulses that come from the receptors to the cerebral cortex. it is also important for various sensorimotor association functions, including motor activity, emotion, and memory, among others (blumenfeld, 2018). from the thalamus, the information can be passed to multiple locations, including the hippocampus. this area is a key part of the brain that stores information involved with learning and memory, and is a crucial component of the olfactory system for this connection to memory. when the neurons signal to the amygdala, the portion of the brain involved with emotion, they are able to activate it in ways that depend highly on the pleasantness of smell to the individual (zald & pardo, 1997). the location of the amygdala is what helps make the association between memory and smell so strong (walsh, 2020). the amygdala portion of this process contains a series of steps that refine the process, and since the olfactory bulb also signals directly to the limbic system, it is easy to register the emotions that are in close coordination with the smells encountered. analyzing how the sense of smell is associated with memory therefore very closely is related to the location of the centers in the brain that will respond. since the amygdala is so involved in the olfactory response, an expected response of emotional connection and memory creation/retrieval is bound to occur. just as how some people associate a certain smell with a bad memory, the brain links various memories with the senses experienced resulting in these unfortunate retrievals. in a similar manner, we can experience positive emotions with a particular smell, and both of these examples would include many different interactions of the brain to create the overall sensations that we experience. the combination of memory and smell is one that is unique in many ways for its strong connections with multiple key areas of the brain and the ability to recognize an abundance of smells. to smell an odor does much more than evoke a particular memory, despite being an important emotional contribution to the human experience. it has the capability to create connections and respond in ways in the brain that are stronger than previously thought while being a crucial contributor to our brain function. the sense of smell is powerful for its ability to evoke a response to an experience, whether it was experienced years ago or an hour ago. this could be associated with a cooked dinner, a hike in a forest after rain, or the stench of garbage in a city alleyway. however, the association between a smell and the memory surrounding it leaves many unanswered questions about the process and how it is used in people. for example, one may wonder whether infants experience the same sort of memory retrieval due to olfactory stimulus that adults do or what changes occur in the brain due to losing the ability to smell. our senses are such powerful tools because of their connections to the brain; since our brain is perhaps the least understood organ, we already have a sense of its vast complexity and capability for what may be unthinkable. while it may seem straightforward that we have memories associated with smell, this trait can significantly impact us as we grow older.this property is also exploited commercially by fragrance companies to make scents more appealing to consumers. because the brain has specific effects and capabilities in response to various stimuli, we can also compare these responses to other signals and how they differentiate from smell in other words, what makes smell unique to us. in order to better understand the process of connecting a scent with the brain, how does the brain take apart scents to process them? to answer, we must look first into the nose and olfactory bulbs. the olfactory bulb is a part of the forebrain and is equipped with a set of nerves extending past the cribriform plate – a part of the ethmoid bone located between the eyes – into the nasal cavity. when receptors in the nose pick up molecules from a specific scent, it is transmitted as an electrical signal to the olfactory bulb (manzini et al., 2014). in order to perceive something as a smell, the molecule must be an odorant, meaning it must meet some criteria, typically having some hydrophobicity and volatility (mayhew et al., 2022). the human nose is said to have approximately 350 different receptor types, which can react to various smells through their molecular components (reinberg, 2020). olfactory receptors operate such that any combination of odor molecules can activate different sets of receptors (malnic et al., 1999). the molecules' recognition and interaction with the receptors operate combinatorially (malnic et al., 1999). this results in a system of activation allowing one to recognize what is now estimated to be up to 1 trillion different odors (bush did et al., 2014). since the glomeruli, nerve-ending bulbs found in the olfactory bulb, are unique to interactions with different smells, our perception of smell depends on how well they are activated and in what order. as a result, if we switch up the sequence in which they are activated or inactivate some of the receptors, we will likely lose the ability to sense odors. one experiment testing this phenomenon of sequential activation impact on recognition was completed using a mouse model, which found that a delay or an interruption of a specific receptor receiving an orderant would decrease the system of cooperation between the receptors (nyu langone health, 2020). it was found that by changing the first glomeruli activated, as much as 30% of a drop could be recognized in the ability of a mouse to correctly sense the odor signal (nyu langone health, 2020). by contrast, if the last of the glomeruli were changed, only about 5% would be potentially dropped in the ability of the mouse to sense the correct odor. (nyu langone health, 2020). 21 in order to identify what odors stand out within a mixture as well, the right sensors must be activated in the correct order and time. any deviation in either of these abilities would result in a decreased ability to accurately recognize and categorize the smell. following this transmission of electrical signals to the glomeruli, they will proceed to the brain's cortex (nyu langone health, 2020). once the signal reaches the neurons of the cortex, the brain takes further action. the piriform complex, a set of neurons right behind the olfactory bulb, will work in attempts to recognize the smell itself. this complex is the only known structure other than the hippocampus to have a three-layered allocortical structure. it is activated when the pyramidal cell, a type of neuron, receives information from the glomeruli and transmits it to other brain regions (vaughan, 2014). this also helps with responses to specific odor mixtures by aiding in the formation of a neural network that is capable of reliably transmitting these messages. the anterior piriform complex is thought to hold information on the molecular features of the odorant, whereas the posterior piriform is for the odor's quality (gottfried, 2006). the piriform complex is additionally used to help differentiate odors (howard et al., 2009) and is involved with the working memory, where odor information can be temporarily stored (zelano et al., 2009). in other words, it is crucial that this complex is responsive and active to retain a highly functioning smell identification and memory connection system. it is from this complex that the information can then be further passed over to other areas of the brain. having left off in our pathway at the piriform complex, various cells within this structure will signal and move the information to the thalamus, a complex key for translating the neural impulses that come from the receptors to the cerebral cortex. it is also essential for various sensorimotor association functions, including motor activity, emotion, and memory (blumenfeld, 2018). from the thalamus, the information can be passed to multiple locations, including the hippocampus. this area is a vital part of the brain that stores information involved with learning and memory and is a crucial component of the olfactory system for this connection to memory. when the neurons signal to the amygdala, the portion of the brain involved with emotion, they can activate it in ways that depend highly on the pleasantness of smell to the individual (zald & pardo, 1997). the amygdala's location helps make the association between memory and smell so strong (walsh, 2020). the amygdala portion of this process contains a series of steps that refine the process. since the olfactory bulb also signals directly to the limbic system, it is easy to register emotions in close coordination with the smells encountered. therefore, analyzing how the sense of smell is associated with memory is very closely related to the location of the centers in the brain that will respond. since the amygdala is so involved in the olfactory response, an expected response of emotional connection and memory creation/retrieval is bound to occur. just as some people associate a particular smell with a bad memory, the brain links various memories with the senses experienced, resulting in these unfortunate retrievals. similarly, we can experience positive emotions with a particular smell, and both of these examples would include many different interactions of the brain to create the overall sensations we experience. the combination of memory and smell is unique in many ways for its strong connections with multiple critical areas of the brain and the ability to recognize an abundance of smells. to smell an odor does much more than evoke a particular memory, despite being an essential emotional contribution to the human experience. it can create connections and respond more substantially in the brain than previously thought while contributing to brain function. references .1. blumenfeld, h. (2018). thalamus. encyclopædia britannica. https://www.britannica.com/science/thalamus 2. bushdid, c., magnasco, m. o., vosshall, l. b., &amp; keller, a. (2014). reports humans can discriminate more than 1 trillion olfactory stimuli. https://www.rockefeller.edu/research/uploads/www.rockefelle r.edu/sites/8/2018/09/bushdidscience2014.pdf 3. gottfried, j. a., winston, j. s., & dolan, r. j. (2006). dissociable codes of odor quality and odorant structure in human piriform cortex. neuron, 49(3), 467–479. https://doi.org/10.1016/j.neuron.2006.01.007 4. harvard gazette. https://news.harvard.edu/gazette/story/2020/02/how-scentemotion-and-memory-are-intertwined-and-exploited/ 5. howard jd, plailly j, grueschow m, haynes j-d, gottfried ja. (2009). odor quality coding and categorization in human posterior piriform cortex. nat neurosci 12:932–8. doi:10.1038/nn.2324 6. malnic, b., hirono, j., sato, t., & buck, l. b. (1999). combinatorial receptor codes for odors. cell, 96(5), 713–723. https://doi.org/10.1016/s0092-8674(00)80581-4 7. manzini, i., frasnelli, j., & croy, i. (2014). wie wir riechen und was es für uns bedeutet : grundlagen des geruchssinns [how we smell and what it means to us: basic principles of the sense of smell]. hno, 62(12), 846–852. https://doi.org/10.1007/s00106-014-2925-2 8. mayhew, emily j., arayata, charles j., gerkin, richard c., lee, brian k., magill, jonathan m., snyder, lindsey l., little, kelsie a., yu, chung wen, mainland, joel d. (2022.). transport features predict if a molecule is odorous | pnas. https://www.pnas.org/doi/10.1073/pnas.2116576119 22brain matters・volume v issue ii https://www.britannica.com/science/thalamus https://www.rockefeller.edu/research/uploads/www.rockefeller.edu/sites/8/2018/09/bushdidscience2014.pdf https://doi.org/10.1016/j.neuron.2006.01.007 https://news.harvard.edu/gazette/story/2020/02/how-scent-emotion-and-memory-are-intertwined-and-exploited/ https://doi.org/10.1016/s0092-8674(00)80581-4 https://doi.org/10.1007/s00106-014-2925-2 https://www.pnas.org/doi/10.1073/pnas.2116576119 9. nyu langone health / nyu school of medicine. (2020, june 18). scientists decode how the brain senses smell. sciencedaily. www.sciencedaily.com/releases/2020/06/200618150304.htm 10. rinberg, d. (2020). scientists decode how the brain senses smell. nyu langone news. https://nyulangone.org/news/scientists-decode-how-brainsenses-smell 11. vaughan, d. n., &amp; jackson, g. d. (2014). the piriform cortex and human focal epilepsy. frontiers. https://www.frontiersin.org/articles/10.3389/fneur.2014.00259 /full 12. walsh, c. (2020, february 27). how scent, emotion, and memory are intertwined and exploited. 13. zald, d. h., & pardo, j. v. (1997). emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation. proceedings of the national academy of sciences of the united states of america, 94(8), 4119–4124. https://doi.org/10.1073/pnas.94.8.4119 14. zelano c, montag j, khan r, sobel n. (2009). a specialized odor memory buffer in primary olfactory cortex. plos one 4:e4969. doi:10.1371/journal.pone.0004965 23 http://www.sciencedaily.com/releases/2020/06/200618150304.htm https://nyulangone.org/news/scientists-decode-how-brain-senses-smell https://www.frontiersin.org/articles/10.3389/fneur.2014.00259/full https://doi.org/10.1073/pnas.94.8.4119 copy of volume 7 publication brain matters vol. 8 no. 1 effects of pregnancy on the brain and neuroplasticity written by isha kandlikar introduction to pregnancy-induced neuroplasticity the brain constantly reshapes itself and adapts throughout pregnancy, utilizing a process called neuroplasticity. in this process, the brain undergoes structural changes and reorganization in response to injury, environmental changes, learning, and a variety of other experiences. pregnancy not only transforms the body but also influences the brain's emotions, maternal instincts, cognition, and overall regulation (pawluski, lambert, & kinsley, 2016). neuroplasticity, as well as these neurological adaptations, creates long-term shifts in the brain structure and function, which allows the brain to adapt to parenthood and changes in mental state and behavior. several key neuroplastic changes occur during and after pregnancy, which have implications for maternal cognition and emotional health, highlighting the importance of such changes in maternal and child development. maintains pregnancy, also reaches peak levels before delivery and has a neuroprotective role that includes reducing stress responses and modulating the limbic system, which regulates emotions (cable, 2023). however, after the mother gives birth, progesterone levels rapidly decrease, which leads to the mother’s vulnerability towards disorders like postpartum depression. oxytocin, a hormone that plays a role in social interactions and emotional regulation, steadily increases during pregnancy, then rises dramatically during labor and breastfeeding to encourage uterine contraction and lactation. oxytocin further remodels the brain through enhancing neural plasticity in the medial preoptic area (mpoa), amygdala, and nucleus accumbens, which are key regions for maternal motivation and emotional bonding (thul, 2020). this ultimately changes the mother's brain by rewiring and strengthening motherinfant attachment, increasing her sensitivity to infant cues. not only does oxytocin affect the mother during pregnancy, but it also maintains a lasting effect through breastfeeding, as it promotes emotional resilience and reduces stress by decreasing activity in the hypothalamic-pituitary-adrenal (hpa) axis, which regulates cortisol production (blankers, 2024). the intricate interplay between oxytocin, progesterone, and estrogen leaves long-term impacts on emotional regulation, cognition, and maternal instincts during and after pregnancy. hormonal influences on maternal brain remodeling during pregnancy, there is a dramatic spike in hormones— primarily estrogen, oxytocin, and progesterone– all of which play a crucial role in shaping the mother’s brain for the longterm experiences following pregnancy. according to the nih, progesterone, which regulates the menstrual cycle and maintains 24 changes in the default mode network and empathy processing in addition to the reduction of gray matter and white matter expansion, pregnancy also alters the functional connectivity within the default mode network (dmn), the inter-regional connections that control empathy, self-reflection, and social processing structural brain changes: gray and white matter neuroimaging studies have led researchers to believe that pregnancy induces changes in the regions of the brain that regulate social cognition and emotional regulation (younis, 2025). one of the most notable findings is gray matter volume reduction in areas such as the prefrontal cortex, medial temporal lobe, and limbic system, primarily in the amygdala and hippocampus. furthermore, a reduction in gray matter likely reflects a neural pruning process, which shapes maternal instincts and caregiving behaviors. since these regions are crucial for social cognition and emotional processing, the mother’s ability to look after her child and tend to their needs is improved as maternal sensitivity is increased (snyder, 2017). processing involving the medial prefrontal cortex, posterior cingulate cortex, and inferior parietal lobule. research suggests that the reduction of gray matter, particularly in areas associated with theory of mind and social cognition, contributes to changes in dmn connectivity. these changes in the dmn activity highlight a shift in the maternal brain regarding responsiveness towards infant-related stimuli, which continues to reinforce the infant-mother bond (paternina-die, martínez-garcía, martín de blas et al., 2024). effects of pregnancy on the brain and neuroplasticity figure 2. this image shows the distribution of white matter tracts during gestation, emphasizing the enhanced neural connectivity that supports cognitive control, emotional regulation, and maternal behaviors (pritschet et. al., 2024). figure 1. this image illustrates brain regions that decrease in volume during pregnancy and increase postpartum, highlighting areas involved in emotional regulation, cognition, and maternal behavior (medical xpress, 2023) pregnancy also induces white matter expansion, which speeds up neural transmission and improves connectivity via myelin, a lipid coating of a neuron’s axon. white matter tracts facilitate communication between brain regions – this increase in white matter density occurs specifically in pathways that involve cognitive control and emotional regulation. white matter volume is increased in the prefrontal cortex, enhancing cognitive control and decision making (blankers, 2024). additionally, there is an observed increase in the cingulum bundle, a white matter tract that connects the prefrontal cortex and limbic system (including the amygdala and hippocampus), playing a role in emotional processing, stress regulation, and maternal motivation (blankers, 2024). these changes can contribute to lower cortisol levels, which helps the mother remain calm under stress. increased connectivity in reward pathways may also boost dopamine signaling, enhancing maternal motivation and infant bonding. on a much broader scale, pregnancy affects multiple brain structures, including the hippocampus (memory and learning), prefrontal cortex (decision-making and emotional regulation), and amygdala (emotion processing and threat detection). as a whole, these changes enhance maternal responsiveness, improve memory for infant cues, and reduce 25 reduce the fear response to infant stimuli. improved memory for infant cues allows mothers to better recognize responses such as their baby’s facial expression and cries, while reducing fear response to infant stimuli helps the mother stay calm in overwhelming situations. overall, during pregnancy, the size of the brain is reduced temporarily but returns to its original size 1-2 years postpartum (kohl, 2019). cognitive shifts and evolutionary adaptations pregnancy induces cognitive shifts as a result of the changes in neuroplasticity and is commonly referred to as the “mom brain” (phoenix health, 2025). this phenomenon is characterized by cognitive fog, forgetfulness, and altered attention during pregnancy and early motherhood. as the size of the brain decreases during pregnancy, it goes through a neural pruning process, which allows it to shift its focus onto infant-related stimuli. for example, mothers may experience a heightened sensitivity to infant cues such as crying, facial expressions, and touch. during pregnancy, many women struggle with focus, verbal fluency, and memory, which is due to the hormonal fluctuations but also to the physical structural changes. the changes and volume reduction of the hippocampus may explain the reduced cognitive flexibility as well as the short term forgetfulness. while these changes may seem negative, they are necessary for evolution and evolutionary mechanisms of the mother during pregnancy and its lasting effects (phoenix health, 2025). neural pruning allows the brain to be more specialized and more efficient by streamlining information deemed necessary to motherhood (kim, 2010). by restructuring the “mom brain”, these changes are optimizing maternal behavior through increases in maternal instincts, emotional regulation, and awareness of infant cues with empathy and vigilance. while pregnancy is universally known to impact neuroplasticity, affect the hormonal balance, and change the physical structure of the brain, the extent and persistence of such changes vary. some alterations to the brain and body, such as changes in gray matter volume or hormonal shifts, can persist for months or even years postpartum, influencing long-term maternal behavior and emotional regulation. mothers experience different changes in neuroplasticity based on genetics, mental health, trauma, and previous life events. genetic factors contribute to individual differences in terms of hormonal regulation, maternal behavior, brain plasticity, and more. the main variants in genes are related to the oxytocin receptor function (oxtr), dopamine signaling (drd2), and serotonin regulation (5-httlpr), all of which contribute to maternal sensitivity, stress management, and emotional bonding with the infant (duarte-guterman, leuner, & galea, 2019). women with genetic predispositions for higher oxytocin receptor sensitivity can experience stronger, more natural maternal instincts and emotional bonding. mothers with genetic vulnerabilities to dopaminergic dysfunction are more more likely to struggle with postpartum mood disorders or attachment difficulties. brain matters vol. 8 2025 mental health and its influence on postpartum brain adaptation furthermore, the mother’s mental health and past experiences before pregnancy can significantly impact how her brain adapts to pregnancy and life after. women with a history of anxiety, depression, or trauma are more likely to exhibit altered neural plasticity in response to pregnancyrelated hormonal shifts. this is highlighted in conditions such as pre-existing stress-related dysregulation in the hpa axis, which is correlated to higher susceptibility to postpartum depression (kim 2010). the persistence of neuroplasticity postpartum is largely affected by the mother’s pre-existing mental health conditions, such as anxiety, depression, or trauma. research indicates that women with a history of major depressive disorder or anxiety show altered connectivity in maternal brain regions, specifically the prefrontal cortex and amygdala, which both impact emotional responses to infants and motivation for caregiving (meireles, 2021). such disruptions can potentially lead to a shortened duration of adaptive neuroplasticity, making it more difficult for these mothers to sustain long-term changes and to support maternal responsiveness and bonding. this not only changes the way the maternal brain adapts, but also the duration of its impact (meireles, 2021). conversely, mothers with minimal mental health concerns show stronger connectivity between the amygdala and pfc, allowing for better emotional regulation and lasting positive adaptations. mothers with past experiences of positive emotional regulation are able to sustain the neuroplasticity changes in the amygdala, reinforcing maternal instincts for longer (meireles, 2021). because pregnancy is a period of significant neuroplastic adaptation, it can induce long-term neurological vulnerabilities. a representative example of this is preeclampsia, a hypertensive disorder that affects approximately 5–8% of pregnancies (karrar, 2024). preeclampsia is associated with hypertension, endothelial (relating to blood vessels) dysfunction, and systemic inflammation, which not only pose immediate perinatal risks but can also increase the mother’s long-term susceptibility to neurodegenerative diseases such as alzheimer’s disease, vascular dementia, and stroke. this increased vulnerability is hypothesized to stem from persistent endothelial dysfunction and systemic inflammation, which make up cerebrovascular integrity and neuronal function even decades after pregnancy (logue, 2016). heightened levels of pro-inflammatory cytokines, such as il-6, tnf-α, and oxidative stress markers observed in preeclamptic pregnancies can persist postpartum, leading to accelerated neurovascular aging and white matter damage (friis et al., 2024). beyond preeclampsia, there are many neurological vulnerabilities 26 vulnerabilities created from the postpartum period itself. hormonal imbalance and the sudden drop in estrogen and progesterone in the postpartum period can exacerbate neuroinflammatory pathways, increasing the risk of neuropsychiatric disorders and cognitive deficits. examples of potential neuropsychiatric disorders include postpartum depression, anxiety disorders, and even postpartum psychosis, while examples of cognitive deficits are memory impairments, brain fog, and decreased processing speed (gonzález-mesa et al., 2020). additionally, the reduction of the hippocampus postpartum can impair synaptic plasticity specifically in women with pregnancy complications, leading to longer-term cognitive impairment and dysfunction. some preventative measures to reduce neurodegenerative effects include routine neurological screenings, blood pressure management, and exercise (gonzález-mesa et al., 2020). as more than 80% of biological women become mothers by the age of 40 in the usa (pew research center, n.d.), understanding of the effects of pregnancy on neuroplasticity is crucial. pregnancy induces reshaping of the brain and hormonal changes well past childbirth. these cognitive changes are not always deficits, but adaptations that enhance maternal instincts, emotional regulation, and caregiving behaviors, strengthening the mother-infant bond. consequently, further neuroscience research is essential in order to improve maternal healthcare, mental health support for mothers, and long-term brain intervention therapies. effects of pregnancy on the brain and neuroplasticity conclusion and future directions driven by hormonal change and structural remodeling that enhance cognition, maternal behaviors, and emotional regulation, pregnancy overall triggers many neuroplastic changes in the maternal brain. these adaptations and shifts are essential in optimizing the mother’s caregiving abilities and responsiveness to the infant. however, many genetic factors, pregnancy complications, and individual mental health struggles influence and affect the persistence of these brain changes. understanding pregnancy-induced neuroplasticity and continuing research is vital for advancing maternal health care, supporting mental wellbeing, and addressing long-term neurological risks. references 1. barha, c. k., & galea, l. a. m. (2010). influence of different estrogens on neuroplasticity and cognition in the hippocampus. biochimica et biophysica acta (bba) general subjects, 1800(10), 1056–1067. https://doi.org/10.1016/j.bbagen.2010.01.006 2. blankers, s. a., go, k. a., surtees, d. c., splinter, t. f. l., & galea, l. a. m. (2024). cognition and neuroplasticity during pregnancy and postpartum. in p. j. brunton & d. r. grattan (eds.), neuroendocrine regulation of mammalian pregnancy and lactation (vol. 15). springer. https://doi.org/10.1007/9783-031-51138-7_9 3. cable, j. k., & grider, m. h. (2023, may 1). physiology, progesterone. in statpearls. statpearls publishing. https://www.ncbi.nlm.nih.gov/books/nbk558960/ 4. duarte-guterman, p., leuner, b., & galea, l. a. m. (2019). the long and short term effects of motherhood on the brain. frontiers in neuroendocrinology. https://doi.org/10.1016/j.yfrne.2019.02.004 5. friis, t., et al. (2024). gestational hypertension, preeclampsia, and eclampsia and future neurological disorders. jama neurology, 81(4), 4426. https://www.preeclampsia.org/the-news/research/doespreeclampsia-increase-your-risk-for-future-neurologicalconditions 6. gonzález-mesa, e., et al. (2020). the neuroendocrinological aspects of pregnancy and postpartum depression. journal of clinical medicine, 9(1), 241. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6992410/ 7. hoekzema, e., van steenbergen, h., straathof, m., servinbarthet, c., mutsaerts, h. j. m. m., pannekoek, j. n., ... & hommel, b. (2022). mapping the effects of pregnancy on resting state brain activity, white matter microstructure, neural metabolite concentrations and grey matter architecture. nature communications, 13, 6931. https://doi.org/10.1038/s41467-022-33884-8 8. karrar, s. a., martingano, d. j., & hong, p. l. (2024). preeclampsia. in statpearls. statpearls publishing. https://www.ncbi.nlm.nih.gov/books/nbk570611/ 9. kim, p., leckman, j. f., mayes, l. c., feldman, r., wang, x., & swain, j. e. (2010). the plasticity of human maternal brain: longitudinal changes in brain anatomy during the early postpartum period. behavioral neuroscience, 124(5), 695– 700. https://doi.org/10.1037/a0020884 10. kohl, s. k., & leuner, b. (2019). brain plasticity in pregnancy and the postpartum period: links to maternal mental health. frontiers in neuroendocrinology, 55, 100788. https://doi.org/10.1016/j.yfrne.2019.100788 11. livingston, g. (2018, january 18). they’re waiting longer, but u.s. women today more likely to have children than a decade ago. pew research center. https://www.pewresearch.org/socialtrends/2018/01/18/theyre-waiting-longer-but-u-s-womentoday-more-likely-to-have-children-than-a-decade-ago/ 12. logue, o. c., george, e. m., & bidwell, g. l. (2016). preeclampsia and the brain: neural control of cardiovascular changes during pregnancy and neurological outcomes of preeclampsia. clinical science (london, england: 1979–), 130(16), 1417–1434. https://doi.org/10.1042/cs20160108 13. medical xpress. (2023, september 19). choreography between hormones and the brain key to understanding how women adapt to motherhood. https://medicalxpress.com/news/2023-09-choreographyhormones-brain-key-women.html 27 about the author isha kandlikar is a rising junior at the uiuc majoring in molecular and cellular biology with minors in business and public health. she is an undergraduate researcher in the rudolph lab, where she studies genetic mouse models to explore treatments for psychiatric disorders. outside the lab, isha is a marketing and healthcare consultant, a member of the illini medical screening society, and involved in alpha epsilon delta, a prehealth fraternity on campus. passionate about neuroscience, she is excited to write for brain matters and dive deeper into specific topics within the field. 14. meireles, a. l. f., segabinazi, e., spindler, c., gasperini, n. f., dos santos, a. s., pochmann, d., elsner, v. r., & marcuzzo, s. (2021). maternal resistance exercise promotes changes in neuroplastic and epigenetic marks of offspring's hippocampus during adult life. physiology & behavior, 230, 113306. https://doi.org/10.1016/j.physbeh.2020.113306 15. paternina-die, m., martínez-garcía, m., martín de blas, d., & colleagues. (2024). women’s neuroplasticity during gestation, childbirth and postpartum. nature neuroscience, 27, 319–327. https://doi.org/10.1038/s41593-023-01513-2 16. pawluski, j. l., lambert, k. g., & kinsley, c. h. (2016). neuroplasticity in the maternal hippocampus: relation to cognition and effects of repeated stress. hormones and behavior, 77, 86–97. https://doi.org/10.1016/j.yhbeh.2015.05.004 17. phoenix health. (2025). pregnancy brain: the science behind it & tips to help. phoenix health. https://www.joinphoenixhealth.com/resourcecenter/pregna ncy-brain-science-and-tips/ 18. pritschet, l., taylor, c. m., cossio, d. m., santander, t., quintana, d. s., & jacobs, e. g. (2024). neuroanatomical changes observed over the course of a human pregnancy. nature neuroscience. https://doi.org/10.1038/s41593-02401741-0 19. snyder, h. r., hankin, b. l., sandman, c. a., head, k., & davis, e. p. (2017). distinct patterns of reduced prefrontal and limbic grey matter volume in childhood general and internalizing psychopathology. clinical psychological science, 5(6), 1001–1013. https://doi.org/10.1177/2167702617714563 20. thul, t. a., corwin, e. j., carlson, n. s., brennan, p. a., & young, l. j. (2020). oxytocin and postpartum depression: a systematic review. psychoneuroendocrinology, 120, 104793. https://doi.org/10.1016/j.psyneuen.2020.104793 21. younis, j., bleibel, m., el masri, j., ismail, a., & abou‑abbas, l. (2025). exploring the influence of pregnancy on cognitive function in women: a systematic review. bmc pregnancy and childbirth, 25(1), 88. https://doi.org/10.1186/s12884-025-07181-3 brain matters vol. 8 2025 28 29 volume 8 (will be vol 7 on site) revolutionizing treatment: gene therapy offers hope for hurler syndrome krisha agarwal abstract hurler syndrome, also known as mucopolysaccharidosis type i (mps i), is a rare lysosomal disorder wherein genetic mutations prevent the synthesis of enzyme idua, disrupting the breakdown of sugar molecules. this autosomal recessive condition targets newborns and causes physical and cognitive abnormalities, potentially resulting in brain damage (cleveland clinic, 2022). current treatments include bone marrow transplants, which are not only dangerous but also an unfavorable solution for progressive brain damage. recently, a new form of gene therapy, proprietary system (ps) gene editing, has shown promising results in mice as a treatment method, as concluded by researchers at the university of minnesota. using high-resolution resting-state functional mri (rs-fmri) technology, researchers could support normal neural connections using liver enzymes. this advanced approach also helps monitor brain connectivity in other lysosomal disorders affecting brain function (university of minnesota, 2023). lysosomal storage diseases lysosomes, integral to cellular function, are specialized membrane-bound organelles that house digestive enzymes. these organelles consist of luminal proteins, membraneintegral proteins, and associated proteins, which all play a crucial role in cellular processes. however, when these components are affected by congenital metabolic single-gene errors, known as lysosomal storage diseases (lsds), the intricate balance within lysosomes is disrupted. this disruption arises from mutations in lysosome-encoding genes located on a specific chromosome locus, leading to the transcription of defective lysosomes. the consequences of these disorders extend beyond the molecular level, manifesting as cell swelling and eventual organ dysfunction at the sites of substrate accumulation. this, in turn, significantly contributes to morbidity and mortality. notably, the impact is more pronounced in infants and children, as their developing brains exhibit heightened vulnerability to dysfunction (rajkumar, dumpa, 2023). hurler syndrome hurler syndrome (mps i), discovered by german pediatrician gertrud hurler in 1919, stands among the 11 disorders of mucopolysaccharidoses (mps), impacting roughly 1 in 100,000 births. this neurodegenerative condition arises from a mutation in a gene on chromosome 4, tasked with encoding the lysosomal enzyme α-l-iduronidase (idua). idua plays a pivotal role in breaking down glycosaminoglycans (gag), such as dermatan sulfate and heparin sulfate. the overaccumulation of gag leads to the enlargement and thickening of organs like the heart, spleen, and muscles, while also impairing synapses within the central nervous system. typically, symptoms of hurler syndrome manifest in the first year of a child’s life. unfortunately, the average age of mortality is five years, with the majority of patients not surviving beyond ten years. indications of the disorder progressive developmental delay, respiratory infections, and cardiac manifestations. diagnosis involves clinical examinations of urinary gag levels and dna analysis. to expand upon the latter point, gene sequencing aids in identifying inheritable mutations and facilitates improved family planning. in contrast, treatments primarily target symptoms of the disorder rather than their underlying abnormalities. options like enzyme replacement therapy (ert) through intravenous injections of recombinant idua and hematopoietic stem cell transplants (hsct) offer some relief. hsct gradually substitutes donor-derived, enzymecompetent cells for hematopoietic cells lacking enzymes (sakuru, bollu, 2023). however, it is important to note that ert cannot cross the blood-brain barrier, limiting its efficacy in curing the central nervous system, a critical concern for severe mps i patients (concolino et al., 2018). additional interventions may include surgical procedures such as cardiac valve replacement and spinal decompression to address specific symptoms (sakuru, bollu, 2023). therefore, it is imperative to seek alternative therapies that are less risky. gene therapy gene therapy is a dynamic field in biomedical science, orchestrating the modulation of gene expression to reshape the biological function of living cells. this versatile approach offers the capacity to replace defective genes with healthy counterparts, inactivate disease-causing genes, or introduce modified genes to treat specific diseases. therefore, it presents effective applications in conditions like cancer, cystic fibrosis, and diabetes. the procedural aspect involves the introduction of genes into the body via carriers known as vectors, with viruses being the primary vehicles due to their ability to recognize target cells and facilitate genetic transfer. figure 1 portrays a simplified diagram of the method. however, amidst the promises of gene therapy lie inherent risks. as the body encounters the introduced viral vectors, an undesired immune response may ensue, potentially resulting in inflammation and, in severe cases, organ failure. precision errors with the vectors may lead to unintended targeting, affecting healthy cells, or causing infections. missteps in gene insertions hold the potential for tumor formation (mayo clinic, 2017). the highly expressed endogenous albumin promoter assumes a pivotal role in governing the transgene’s expression, with its benefits harnessed through a mechanism known as cross-correction. in this process, a lysosomal enzyme produced by one cell is released and subsequently internalized by another cell. this facilitates the degradation of stored materials, culminating in metabolic correction. to prevent transgene expression in the central nervous system, the researchers strategically employed liver-specific human idua. the technique showed positive results, as evidenced by elevated idua activity and reduced gag levels in both the liver and brain. the findings suggest that maintaining a consistently elevated level of idua in the bloodstream leads to a modest yet sufficient entry of idua into the brain. notably, a particular grna,5′gtatctttgatgacaataatgggggat-3′, demonstrated the highest efficiency in driving therapeutic effects. the inherent advantage of ps gene editing lies in its potential to yield elevated enzyme levels with a single administration. this efficiency arises from the increased likelihood of successfully edited hepatocytes. consequently, the application of ps gene editing opens avenues for administering reduced doses of the adeno-associated virus (aav) vector for the treatment of lsds. this not only mitigates toxicity but also streamlines vector production, thereby reducing overall costs. the significance of this approach becomes pronounced in the context of lsd patients, particularly children, where uninterrupted cell division is essential for normal growth. traditional aav gene therapy encounters a significant hurdle in the form of vector dilution as children undergo growth and maturation. the primary merit of ps lies in its potential to confer sustained therapeutic benefits throughout an individual’s life, ensuring ongoing efficacy beyond the initial post-treatment years (ou et al., 2020). using resting state functional mri (rs-fmri) to map mps i high-resolution resting state functional mri (rs-fmri) emerges as a non-invasive and whole-brain activity imaging technique for the diagnosis and post-treatment evaluation of mps i. this tool examines the spontaneous blood oxygenation level-dependent fluctuations across various brain regions without stimulation. clinically, rs-fmri has successfully identified multiple resting state networks (rsns) in conditions such as alzheimer’s disease, major depression, and schizophrenia. these results emphasize the foundational role of neural network deficits and interconnectivity in certain neurological disorders. scientists at the university of minnesota hypothesized that the observed deficits in learning memory and spatial navigation in mps i are influenced by alterations in limbic network connectivity. hence, rs-fmri is proposed as a sensitive imaging tool to assess compromised rsns in the figure 1. diagrammatic representation of gene therapy technique (national human genome research institute, 2024) proprietary system gene editing to treat hurler syndrome researchers at the university of minnesota have pioneered a proprietary system (ps) for gene editing aimed at treating hurler syndrome in neonatal mice. this innovative technique, represented in figure 2, involves the action of cas9, which induces a double-stranded break at the intron 1 locus of liver protein albumin. simultaneously, the guide rna (grna) synthesizes therapeutic transgene promoterless idua cdna. the method employs homology-directed repair to introduce the splicing acceptor, idua cdna, and poly(a) sequence into the target, forming a cohesive genetic structure. alternatively, nonhomologous end-joining pathways come into play, incorporating the donor template at the double-stranded break. this results in the creation of a hybrid sequence of albumin exon 1 and idua sequence. therefore, ps gene editing is versatile, seamlessly functioning in both dividing and nondividing pathways. figure 2. a diagrammatic representation of the molecular mechanism of ps gene editing (ou et al. 2020) brain matters・volume vii 18 mps i brain and track their restoration following gene treatment. as seen in figure 3, in the realm of rs-fmri, the examination of wild-type mice highlighted robust functional connectivity throughout the brain. conversely, mps i mice exhibited weakened and altered connections in crucial cortical and subcortical regions associated with learning, memory, and sensorimotor behavior. notably, researchers observed a significant loss of functional connectivity in default mode networks, including the retrosplenial cortex, thalamus, and hippocampus. however, mps i mice treated with gene therapy displayed a restoration of functional connections between the anterior cingulate and motor cortex, dorsal striatum, and hippocampus. the rs-fmri findings reinforce the notion that hurler syndrome impacts synapse formation, leading to diminished neural connectivity. the observed dysfunction in hippocampal connectivity with the retrosplenial cortex holds implications for spatial navigation performance. these results bear clinical relevance for the diagnosis, monitoring, and treatment of hurler syndrome. furthermore, rs-fmri’s translational potential extends to the clinical analysis of other human neurological disorders and gene therapy outcomes (zhu et al., 2023). conclusion this comprehensive exploration provides valuable insights into hurler syndrome and underscores the promising avenues offered by gene therapy, particularly through ps gene editing. traditional treatments for hurler syndrome emphasize the necessity for more targeted interventions addressing the root cause, and gene therapy, a burgeoning field with transformative potential, emerges as a beacon of hope. ps gene editing marks a significant stride in pursuing effective and sustainable treatments for hurler syndrome. the insights gained from rs-fmri not only enhance our understanding of the neurological deficits associated with figure 3. correlation matrices and circular graphs of functional brain connections between (a) control, (b) mps i, and (c) mps i treated mice. blue-connectome with connections at anterior cingulate area, greenconnectome with connections at ammon’s horn, and yellow-connectome with connections at mediodorsal nucleus of thalamus. brain connectome is sporadic for mutant but recovers after treatment. (zhu et al., 2023) hurler syndrome but position rs-fmri as a promising diagnostic and therapeutic imaging technique. as scientists navigate this frontier of knowledge, the potential for transformative breakthroughs in treating hurler syndrome and related disorders becomes increasingly tangible. references 1. concolino, d., deodato, f., & parini, r. (2018). enzyme replacement therapy: efficacy and lmitations. italian journal of pediatrics, 44(supply, 120. https://doi.org/10.1186/s13052018-0562-1 gene therapy. genome.gov. (n.d.-a). https://www.genome.gov/geneticsglossary/gene-therapy 2. mayo foundation for medical education and research. (2017, december . gene therapy. mayo-clinic. https://www.mayoclinic.org/tests-procedures/genet herapy/about/pac20384619 3. ou, l., przybilla, m. j., ahlat, o., kim, s., overn, p., jarnes, j., o’sullivan, m. g., & whitley, c. b. (2020, june 3). a highly efficacious ps gene editing system corrects metabolic and neurological complications of mucopolysaccharidosis type i. molecular therapy : the journal of the american society of gene therapy. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7264433/ 4. rajkumar, v., & dumpa, v. (2023, july 24). lysosomal storage disease statpearls ncbi bookshelf. national library of medicinenational center for biotechnology information. https://www.ncbi.nlm.nih.gov/books/nbk563270/ 5. sakuru, r., & bollu, p. c. (2023, july 10). hurler syndrome – statpearls – ncbi bookshelf. national library of medicinenational center for biotechnology information. https://www.ncbi.nlm.nih.gov/books/nbk532261/ 6. zhu, w., ou, l., zhang, l., clark, i. h., zhang, y., zhu, x. h., whitley, c. b., hackett, p. b.,low, w. c., & chen, w. (2023). mapping brain networks in mps i mice and their restoration following gene therapy. scientific reports, 13(1), 12716. https://doi.org/10.1038/s41598-023-39939-0 brain matters・volume vii 20 brain matters vol. 8 no. 1 editors thiya ilankovan thiya is a sophomore at uiuc majoring in mcb with a minor in psychology, hoping to one day become a physician assistant. in her free time, she likes to run, crochet, and play the piano. she is currently involved in research at the liang lab for behavioral neuroscience. through her involvement with brain matters, she hopes to broaden her knowledge and gain deeper insights into the fields of neuroscience and psychology. kathryn kennedy kathryn kennedy is a freshman studying biology with minors in health technology and spanish. she joined brain matters to learn more about neuroscience, psychology, and improve her writing and editing skills. outside of the journal, she is involved in global medical training and education and training 4 health. she also dances with psa barkada, sings with the st. john's church choir, and plays guitar in her free time. her career goal is to be a pediatrician. nicholas opiola nicholas opiola is a recent ’24 mcb alumni. he is a lifelong learner and has always loved studying across all academic disciplines, especially neuroscience! nicholas joined brain matters to immerse himself in all the latest exciting work being performed in the field of neuroscience and to utilize his writing skills towards helping others produce their best work. in his free time, nicholas loves to watch fútbol, dance, sing karaoke, spend time with family and close friends, play video games, and spend time amongst nature. in the future, nicholas hopes to devote his career towards making a lasting, positive change in as many lives as possible. megan lu megan lu is a junior majoring in brain & cognitive science with a minor in health administration and business. she is involved in various rsos on campus, including fhce (future healthcare executives) and alpha epsilon delta (a pre-health fraternity). she is also currently involved in research with the illinois alternative protein project. in her free time, megan spends most of her time at the gym working out, cooking new recipes, or listening to true crime podcasts. she hopes to deepen her understanding and appreciation of the brain through writing with brain matters and will graduate this year. 85 yuliia kohut yuliia kohut is a freshman in bioengineering on a pre-medical track and a student from ukraine. apart from brain matters, on campus she is a global health executive member in the american medical student association, and she is also a student volunteer at carle hospital. yuliia is an undergraduate researcher in dr. best-popescu lab at beckman institute, working on developing imaging tools for cellular neuroscience research. in her free time yuliia enjoys cross-stitching, cooking ukrainian food, and reading sci-fi novels. she joined the editing and writing team of brain matters to share her fascination with neuroscience with uiuc! kaitlyn tuvilleja kaitlyn tuvilleja is a junior in bioengineering with a statistics minor. she is an undergraduate research assistant for bhargava lab and i^2 lab. besides brain matters, kaitlyn is involved with swe, wie, and bmes. in her spare time, she enjoys baking and running with her friends. gus dorman gus dorman is a freshman majoring in neuroscience with a minor in computer science. he joined brain matters as an editor to learn more about the field while also getting a feel for what research articles are like. if he's not studying, he's probably longboarding around campus, playing a video game, or watching shows. praise kim praise kim is the vice president of brain matters and an undergraduate researcher pursuing a bslas in brain and cognitive science. currently, as a research assistant in the gratton lab, she studies the fronto-parietal network in cognitive control tasks across different mental states. in the past, she has also presented work on the infant parasympathetic response and maternal depression with the interdisciplinary lab for social development. she is broadly interested in cognition in the brain and throughout development, also presenting work on social cognitive development at stanford university. outside of research, she lifts weights, reads fantasy novels, and spends time with her church. her future goals are to continue researching the brain—whether as a post-bacc, doctoral student, post-doc, or professor. 86 jessica chen jessica chen is a sophomore studying clinical-community psychology. with brain matters, she has been excited to integrate her interests in neuroscience, linguistics, and psychology. she has appreciated groundbreaking applications of neuroscience in skill acquisition, discrimination, addiction, and more. currently a research assistant with the health equity and action lab and the social cognition lab, jessica examines parenting and child health outcomes across cultural contexts, and neural network dissection of trends in biases. aside from academics, jessica is most likely baking a sweet treat or lounging at a matcha cafe. natalia pacheco natalia is a freshman at the university of illinois majoring in neuroscience. natalia became involved in brain matters to further her passion for the brain and to become familiar with modern topics of neuroscience. in addition to brain matters, natalia is involved in the american medical women’s association at the university of illinois. natalia hopes to continue her studies in the medical field specifically with neurology to continue learning about the brain! 87 88 volume 8 (will be vol 7 on site) table of contents astrocytes and their role in psychiatric disorders pravika srivastava...........................................................................1 fine tuning alzheimer’s disease (ad) treatment with music-based interventions (mbi): an anatomical overview celeste acosta.................................................................................9 déjà vu: what happens in the brain ananya sampathkumar....................................................................5 articles...............................................................................1 how do “walk-up” songs work: links between music and athletic performance isabelle afshari...............................................................................14 revolutionizing treatment: gene therapy offers hope for hurler syndrome krisha agarwal...............................................................................17 unraveling the links between synesthesia and autism sarah masud..................................................................................21 mesenchymal stem cell regenerative therapy in the spine recent advancements and possible applications: a review harrison kennedy...........................................................................26 inside out: a brain’s tale of introverts and extraverts krisha agarwal...............................................................................33 optical illusions: what are they, and why do they occur? ananya sampathkumar....................................................................36 the interplay of cognitive and emotional control in autism spectrum disorder kaitlyn tuvilleja .............................................................................39 brain matters・volume vii i about the writers..............................................................93 meet the board..................................................................85 understanding common personality disorders: the neurological basis of ocd, npd, and bpd isabelle afshari......................................................................52 swearing and the brain: a cultural and emotional experience vraj patel..............................................................................60 can expressing gratitude make you happier & healthier? vani sharma..........................................................................56 the use of mri for the early prevention of alzheimer’s disease joy akindulureni....................................................................63 how the brain creates predictive models of the environment glioblastoma multiforme: challenges and advancements in treatment casey meskovich....................................................................42 practical applications of the circadian rhythm erin ford..............................................................................47 brain matters・volume vii ii kaitlyn tuvilleja.....................................................................67 symphonies vs. silence: how does music affect work performance? sarah masud..........................................................................71 dopamine: a social neurotransmitter vraj patel..............................................................................74 impacts of lifelong bilingualism on neurodegenerative diseases esther nam...........................................................................77 brain matters vol. 8 no. 1 the effects of physical exercise on memory and cognitive functions written by navi singh synaptic plasticity. bdnf is important for long-term potentiation, a cellular process that is essential to help with learning and memory formation, promoting the strength of connections between neurons. exercising stimulates bdnf expression in the hippocampal pathway, which can improve memory. a recent study by sanaeifar et. al. found that individuals who regularly engage in aerobic exercise exhibited increased levels of bdnf and reduced levels of neuroinflammation, overall improving cognitive function. (sanaeifar, 2024). cognitive functions are the mental processes that allow us to think, learn, and focus. memory, in particular, involves the encoding, storage, and retrieval of information— processes that are essential for daily activities. emerging evidence in neuroscience research points to a strong relationship between physical health and cognitive performance. for instance, a study by donnelly et al. highlights a strong link between regular physical exercise and improved cognitive health (donnely, 2016). particularly, studies show that individuals who engage in physical activity demonstrate better memory, attention, and problem-solving abilities compared to those who do not exercise. these findings are particularly relevant in the context of neurodegenerative diseases such as alzheimer’s and dementia, which involve a progressive loss of brain structure and function and significantly impair cognitive abilities such as memory. examining the impact of physical activity on memory and cognition, and summarizing recent literature on its role in the development or prevention of neurodegenerative diseases, is therefore essential for guiding future neuroscience research. physical activity has been shown in several studies to reduce the risk of neurological diseases such as alzheimer’s and dementia. one of the key ways exercising benefits the brain is by enhancing brain activity through reduction of inflammation, which could impact cognitive impairment. one central mechanism involved in the regulation is brainderived neurotrophic factor (bdnf), a protein that plays a crucial role in supporting neuronal survival, growth, and syna figure 1. the impact of bdnf expression on neuronal activity in individuals who exercise and those who do not exercise (sanaeifar, 2024) 58 additionally, when individuals age, neurogenesis and synaptic plasticity naturally decline. however, studies have shown that individuals who regularly exercise maintain these essential mechanisms and preserve cognitive function at an older age. for example, a research article by isomarrku demonstrated that physically active older adults had a lower risk of developing neurodegenerative diseases such as alzheimer’s and dementia. (iso-markku, 2022; lopez-ortiz, 2023). these findings show the importance of exercising daily to preserve cognitive function and prevent early-onset neurodegenerative diseases. not only does it prevent cognitive decline, but it also reduces inflammation in the brain, increases hippocampal volume, and optimizes cognitive function at all ages (voss, 2023). in conclusion, the evidence in the current neuroscience literature strongly supports that physical exercise has been shown to enhance memory and cognitive function and also reduce the risk of neurodegenerative diseases like alzheimer’s and dementia. biological mechanisms, such as increased bdnf levels and reduced neuroinflammation, improve the memory and function of the hippocampus. additionally, regular physical activity, whether short-term or long-term, preserves cognitive ability as individuals get older and prevents the onset of alzheimer’s and dementia. any type of exercise plays a crucial role in improving memory and attention. however, there are limitations to research regarding the long-term effects of different exercise models. future studies will show what specific types of long-term exercise are crucial and bring the most cognitive benefits. understanding the importance of the impact of physical health on the brain can lead to more targeted interventions to help reduce the risk of cognitive decline and improve attention and memory. references 1. donnelly, j. e., hillman, c. h., castelli, d., etnier, j. l., lee, s., tomporowski, p., lambourne, k., & szabo-reed, a. n. (2016). physical activity, fitness, cognitive function, and academic achievement in children: a systematic review. medicine and science in sports and exercise, 48(6), 1197–1222. https://doi.org/10.1249/mss.0000000000000901 2. iso-markku, p., kujala, u. m., knittle, k., polet, j., vuoksimaa, e., & waller, k. (2022). physical activity as a protective factor for dementia and alzheimer's disease: systematic review, meta-analysis and quality assessment of cohort and case-control studies. british journal of sports medicine, 56(12), 701–709. https://doi.org/10.1136/bjsports2021-104981 3. lópez-ortiz, s., lista, s., valenzuela, p. l., pinto-fraga, j., carmona, r., caraci, f., caruso, g., toschi, n., emanuele, e., gabelle, a., nisticò, r., garaci, f., lucia, a., & santos-lozano, a. (2023). effects of physical activity and exercise interventions on alzheimer's disease: an umbrella review of existing meta-analyses. journal of neurology, 270(2), 711–725. https://doi.org/10.1007/s00415-022-11454-8 the effects of physical exercise on memory and cognitive functions figure 2. benefits of exercise in prevention of alzheimer's disease (lopez-ortiz, 2023) not only can exercise prevent neurodegenerative disease, but it also improves memory, attention, and overall cognitive activity. research has shown that both short-term and long-term exercise can lead to cognitive improvements. short-term exercises, like aerobic exercise, have been found to enhance working memory and attention by increasing the cerebral blood flow to the brain. long-term exercise, on the other hand, can cause functional changes in the brain, like increasing hippocampal volume, which is an area of the brain crucial for memory processing. (donnelly, 2016). in a review by donnelly et. al., the authors highlighted that consistent physical activity is associated with improvements in cognition, memory, and executive function. exercise interventions mentioned in donnelly’s review can lead to enhanced academic performance and cognitive development for adults and children. moreover, different types of exercise have been found to impact cognition uniquely. aerobic exercises like running have been shown to see improvements in memory and attention, whereas resistance training has been associated with better working memory and executive function. even yoga and meditation have been shown to provide cognitive benefits in reducing stress and improving attention. altogether, these findings suggest that exercise has a multitude of benefits: not 59 4. sanaeifar, f., pourranjbar, s., pourranjbar, m., ramezani, s., mehr, s. r., wadan, a. s., & khazeifard, f. (2024). beneficial effects of physical exercise on cognitivebehavioral impairments and brain-derived neurotrophic factor alteration in the limbic system induced by neurodegeneration. experimental gerontology, 195, 112539. https://doi.org/10.1016/j.exger.2024.112539 5. voss, s., cerna, j., & gothe, n. p. (2023). yoga impacts cognitive health: neurophysiological changes and stress regulation mechanisms. exercise and sport sciences reviews, 51(2), 73–81. https://doi.org/10.1249/jes.0000000000000311 about the author navi singh is a rising junior at the university of illinois urbana-champaign, majoring in neuroscience and minoring in health administration and chemistry on the pre-medical track. she is an aspiring physician hoping to specialize in neurology. she is also involved with several rso's on campus. these include serving as social chair for udaan and the undergraduate neuroscience society, being a member of a pre-health professional fraternity phi chi, mentor for illini mentor program, volunteer for global medical brigades, and research assistant at the kukekova lab. navi is excited to share her first article and research with brain matters! brain matters vol. 8 2025 60 61 brain matters vol. 8 no. 1 maternal microbiota and immune interactions in neurodevelopmental risk: a review of maternal immune activation models maternal immune activation (mia) is a model used to study the impact of maternal infection and maternal inflammatory cues on fetal brain development and vulnerability to neurodevelopmental disorders (ndds). studies using the mia model have confirmed the role of immune mediators, such as interleukin-17a (il-17a), in disrupting the cortex's structural integrity and behavior. the maternal microbiota has also been recognized as a key modulator of these immune-fetal brain interactions. microbes that inhabit the gut control th17 cell differentiation—long-term players in mia—and presence or absence can determine whether offspring become ndd-like following maternal inflammation. this association suggests the capacity of the microbiota to modulate maternal immune reactivity and thereby determine fetal neurodevelopmental processes. together, these findings position mia not as a singular immune event but as a systems-level interaction among microbes, cytokines, placental signaling, and fetal neuroimmune development. written by alexander byrne abstract introduction neurodevelopmental disorders (ndds) are some of the most notable and commonly discussed disorders in neuroscience. these disorders are dependent on prenatal environmental changes and are often studied in rodent models, though establishing one-to-one comparisons between rodents and humans remains difficult. while rodent models exhibit ndd-like symptoms, their mapping to human conditions is tentative. significant stages of development are the prenatal and early postnatal periods, which are particularly sensitive to severe viral infections and the resulting immune response (chalen, caetano-silva, et al., 2024; otero and antonson, 2022). this response can contribute to the development of ndd-like symptoms. the model used to study this interaction is known as maternal immune activation (mia), which occurs when a pregnant mother’s immune system is triggered by infection, leading to changes in fetal brain development (otero and antonson, 2022; chalen, caetano-silva, et al., 2024). the immune system plays a vital role in protecting the body from infection and disease, yet it can also have adverse effects. research indicates that certain cell populations involved in immune responses can produce unexpected neurological side effects on fetal offspring. beyond infection and immune response, other external factors, such as the maternal microbiome, have also been linked to ndds. this review aims to understand the relationship between the maternal microbiome and the phenomenon of mia. modeling mia with poly i:c the study by choi and collaborators demonstrates how gut microbes regulate maternal immune responses and influence fetal brain development (choi et al., 2016). the molecule used to study this is poly i: c, which was used to activate the immune system artificially, distinct from a live virus. this triggers the cell populations of the immune response known as t helper 17 cells (th17 cells), which are shown to be responsible for asd-like symptoms in rodent offspring. looking deeper into this, the effector cytokine interleukin-17a (il-17a) is directly related to the microbiome 6 and is necessary and sufficient to cause abnormal behaviors and brain development in the rodent model (choi et al., 2016). the maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. normally, neurons in the cerebral cortex organize into distinct layers, but mia leads to patches of disorganized neurons similar to those seen in asd postmortem brains (choi et al., 2016). while it has been shown that mia caused by infection can lead to the development of abnormal behaviors and brain development in rodent models’ offspring, it remains to be seen the degree to which other factors, such as the microbiome, play as significant a role. during th17 cell differentiation, the maternal microbiome and bacteria play an essential role. segmented filamentous bacteria (sfb) are strongly associated with th17 production and activity, and mice treated with vancomycin lack this but recover it when in contact with non-treated mice/waste (kim et al., 2017). when treated with broad-spectrum antibiotics or minimally possessing th17 cells in the small intestine, cortical patches consistent with asd-like morphology in fetal offspring decreased. therefore, maternal gut bacteria are indispensable to promote neurodevelopmental abnormalities in mouse offspring (kim et al., 2017). two genetically similar strains of mice, taconic (tac) and jackson (jax), differ in their th17 cell populations due to the presence or absence of sfb. when subjected to mia, tac offspring display ndd-like behaviors, whereas jax offspring do not. however, when jax mothers are colonized with sfb, their offspring develop asd-like behaviors, demonstrating that maternal gut bacteria influence neurodevelopment. pregnant jax mice colonized with human gut bacteria that promote th17 cells also develop asd-like offspring after mia, reinforcing the idea that human microbiota may contribute to neurodevelopmental abnormalities. building on the il-17a mechanism, shin yim and collaborators (shin yim et al., 2017) demonstrated that the neurodevelopmental outcomes of maternal immune activation (mia) are not permanent and can indeed be reversed postnatally (shin yim et al., 2017). utilizing a poly i:c model to mimic viral infection in pregnancy, offspring exhibited typical neurodevelopmental disorder (ndd)-like behaviors, such as decreased social interaction, augmented repetitive behaviors, and hyper ultrasonic vocalizations. these behaviors had already been linked to cortical disorganization in the form of loss of layer specific markers like satb2 and tbr1 (shin yim et al., 2017). notably, the study localized these defects to discrete cortical patches— primarily in the dysgranular zone of the primary somatosensory cortex (s1dz)—and linked their presence and size with the severity of behavior. in figure 1f, the s1 of mia offspring had elevated c-fos expression, indicative of elevated baseline neuronal activity, again implicating hyperexcitable cortical circuits as an etiology for the phenotypes. in a tour de force, the investigators then proceeded proceeded to employ postnatal intervention by optogenetically silencing this overactive cortical region, rescuing both behavior and cortical anatomy. importantly, the behavioral rescue was most effective when performed during the early postnatal time points, emphasizing an early window of enhanced neuroplasticity. these findings contend that while mia imposes structural and functional changes on fetal brain development, these changes are not permanent but rather are therapeutically accessible by virtue of neural activity manipulation within key cortical nodes like the s1dz (shin yim et al., 2017). maternal microbiota and immune interactions in neurodevelopmental risk: a review of maternal immune activation models modeling mia with real pathogens: the use of live viruses in research the review by otero and antonson (otero and antonson, 2022) highlights maternal immune activation (mia) as a multifaceted model for understanding how prenatal infections shape fetal neurodevelopment (otero and antonson, 2022). central to their argument is the distinction between commonly used pathogen mimetics like poly i: c and live virus models such as influenza a virus (iav) (otero and antonson, 2022). whereas poly i:c triggers a brief, acute innate immune response, iav triggers a long-term, multistage immune cascade along both innate and adaptive pathways of immunity. the paper notes that although both models activate the th17/il-17a pathway—a pathway previously demonstrated to interfere with cortical morphology and stimulate fetal microglia—iav more accurately reflects in vivo infections. importantly, they argue that poly i: c may oversimplify mia by bypassing key interactions between maternal microbes, cytokines, and fetal immune cells. the review also underscores additional mechanisms, such as placental lack of oxygen and microglial priming, which could potentially operate independently or alongside il-17a signaling. antonson and collaborators in their 2021 study provide critical insight into the threshold model of fetal vulnerability by studying the effects of moderately pathogenic iav infection during pregnancy (antonson, kenney, et al., 2021). pathogenicity is a major player in the mia model, and the degree of infection is a crucial factor to consider. according to this study, moderate infection might have muted or even negligible effects on cortical formation and fetal brain inflammation, though there is a noted impact on placental health (antonson, kenney, et al., 2021). this observation underscores the important role of the placenta as a protective barrier against maternal inflammation (antonson, kenney, et al., 2021). typical immune responses with moderate doses include systemic cytokine elevations, such as il-6, albeit to a lesser extent than those seen with high-dose infections. additionally, while cytokines in the placenta may lead to structural integrity breakdown, the absence of a fetal brain response suggests that the placenta acts as the first line of defense, a notion further supported by pathway analyses showing upregulation of inflammatory and 7 and hypoxia-related genes (antonson, kenney, et al.). in their 2024 study, otero and collaborators explored how iav infection during pregnancy affects fetal brain development in a doseand time-dependent manner (otero et al., 2024). severity has been demonstrated to be a significant factor when considering the infection type for the mia model. although the model often focuses on il-17a and th17 pathways, activation by iav does not elevate these components as one might suppose; instead, fetal microglia and border-associated macrophages emerge as the primary responders, increasing in both number and phagocytic behavior. while cytokines such as il-6 and ifn-γ consistently rise with the level of infection—a constant feature of mia— maternal il-17a and th17 cell numbers remain relatively constant. consequently, high dose iav infection results in a thinning of the cortical plate and disorganization of both deep and upper cortical layers, evidenced by altered distributions of tbr1+ and satb2+ neurons (otero et al., 2024). this disruption is absent in moderate iav infection, further reinforcing the concept of a severity threshold. high-dose infection also alters gene regulation for neuronal development, inflammation, and microglial function, indicating that severe maternal inflammation disrupts normal cortical development. the microbiome and mia other factors such as stressors, metabolites and others contribute to the complexity of the mia model and the neurological realities within. antonson and collaborators in their 2020 study investigated how prenatal stress alters both maternal immune function and gut microbiota composition (chen, antonson, et al., 2020). the study found that stress during gestation led to unique immune signatures in pregnant dams, including elevated cytokines such as il-6 and ccl2, alongside shifts in microbial diversity. these changes were linked to disrupted microbial metabolic pathways, which influence neuroactive compound production. the study underscores the importance of the microbiome as a mediator between psychological stress and systemic immune activation during pregnancy. the altered microbial and immune landscape suggests a possible route by which prenatal stress exerts long-term effects on offspring brain development. chen and collaborators in their 2020 study similarly examined prenatal stress's effects on initiating disturbances in the immune system and neurochemistry with long term behavioral impacts in offspring (chen, antonson, et al., 2020). from their findings, prenatal stress generated intrauterine inflammation characterized by increased ccl2 expression that, in turn, affected serotonin signaling pathways responsible for neurodevelopment. behavioral tests revealed that such offspring exposed to this inflammatory microenvironment had enduring impairments of anxiety-like behavior and social interaction. the altered microbial and immune landscape suggests a possible route by which prenatal stress exerts longterm effects on offspring brain development. notably, these behaviors were dependent on both microbial colonization and ccl2 signaling, indicating that stressinduced behavioral phenotypes are regulated by microbiotaimmune crosstalk. galley and collaborators in their 2021 study studied the ways in which prenatal stress regulates tryptophan metabolism, a critical connection between the gut microbiome and neurodevelopment (j. galley et al.,2021). the study demonstrated that stress during pregnancy disrupted both microbial and host tryptophan metabolic pathways, including those leading to the synthesis of serotonin and kynurenine. these were accompanied by alterations in fetal brain and placental tryptophan transporter expression, showing that maternal stress can impair neurotransmitter supply at critical developmental windows. the data suggests a mechanism where the maternal microbiome influences neurodevelopment via metabolite signaling, adding a biochemical dimension to the immune-mediated mia framework. galley and collaborators in their 2023 study examined how other stressors impact developing offspring gut microbiomes (galley et al., 2023). using human cohorts and mouse models, the study revealed that high maternal psychological distress was associated with reduced bifidobacteria abundance and decreased microbial richness in offspring. extending this work, (galley et al., 2024) studied the effectiveness of probiotic intervention by modulating bifidobacterium dentium administration during pregnancy (galley et al., 2024). the study demonstrated that prenatal exposure to this specific strain had long-term intergenerational effects, including altered immune profiles, metabolic signaling, and improved social behaviors in offspring. offspring of b. dentium-treated dams exhibited reduced pro-inflammatory cytokine expression and more balanced microbiota composition. these findings are significant in that they show intentional manipulation of maternal microbiota can have trans-generational protective effects. discussion and future directions taken together, these reports support a multi-aspect interaction among maternal stress, microbial ecology, brain matters vol. 8 2025 8 immune signaling, and neurodevelopment of the offspring. in their early phase, mia experiments focused mostly on cytokines such as il-6 and il-17a, but emerging evidence hints toward the universal involvement of maternal microbiota in eliciting immunity and programming fetal fates. pioneering experiments by (choi et al., 2016) and (kim et al., 2017) showed that gut microbiota in mothers—here specifically those triggering th17 differentiation—are required to trigger pathogenic cascades that lead to cortical defects and autism-like behaviors in offspring (choi et al, 2016.; kim et al., 2017). however, recent work by (otero et al., 2024) and (antonson, kenney, et al., 2021) has opened the paradigm using live influenza a virus (iav) models, revealing immune dynamics that encompass placental hypoxia, microglial priming, and a threshold of severity for fetal brain effects—none of which are fully captured in synthetic mimetic models like poly i:c (antonson, kenney, et al., 2021; otero et al., 2024). other recent research has tried to explore the role of il17a in the absence of microbes (chalen, wang, jung, et al. 2022; chalen, wang, florianowicz, et al., 2023). in parallel, studies by chen, galley, and antonson have extended this framework beyond infection, showing that non-infectious stressors such as psychological distress during pregnancy also disrupt maternal microbial communities and immune tone (antonson, evans, et al, 2020.; galley et al, 2024.; chen, galley, et al., 2021). these disruptions—marked by altered tryptophan metabolism, inflammatory chemokine expression, and reduced bifidobacterial abundance—contribute to long-term changes in neurodevelopmental signaling pathways and behavior. notably, (galley et al., 2024) demonstrate that probiotic interventions using b. dentium during gestation can reverse or mitigate these effects, leading to improved social behavior and reduced inflammation in offspring, even across generations (galley et al., 2024). this body of work supports a more integrative and systems-level approach to understanding mia. future studies should holistically account for the interactions among maternal microbial ecology, immune response, infection severity, psychological stress, and critical windows of neurodevelopment. covid19 in pregnant women acts as an example of mia and has already been shown to cause the development of ndd-like symptoms (duan et al., 2024). while the mechanism hasn’t been figured out, the expansive scientific literature and research on influenza will likely inform future research pathways regarding covid-mia interactions. future research will look at interactions between the microbiome and influenza infection in the mouse model and how both relate to the development of ndd. figure 1. (a) maternal respiratory infection can cause systemic inflammation and disrupt gut microbiota. (b) maternal systemic inflammation can be detrimental to fetal neurodevelopment. (source: biorender) figure 2. infected mouse and placental changes: (a) pregnant mice are innoculated with influenza on gestational day (gd) 9.5 and sacked and placentae extracted at gd 16.5. placental integrity and morphology are then measured. (source: biorender) acknowledgments: i would like to acknowledge the members of the antonson developmental neuroimmunology laboratory: izan chalen, dr adrienne antonson, rafael gonzalez-ricon, ashley otero, arnav kaushik, fernando rigal, hao-chun fan, and my family: christy beighe-janke, vincent byrne, harmony byrne, miracle byrne, cassidy byrne, and margaret byrne. 9 maternal microbiota and immune interactions in neurodevelopmental risk: a review of maternal immune activation models references 1. antonson, adrienne m., adam d. kenney, et al. “moderately pathogenic maternal influenza a virus infection disrupts placental integrity but spares the fetal brain.” brain, behavior, and immunity, vol. 96, aug. 2021, pp. 28–39, https://doi.org/10.1016/j.bbi.2021.05.004. 2. antonson, adrienne m., morgan v. evans, et al. “unique maternal immune and functional microbial profiles during prenatal stress.” scientific reports 2020 10:1, vol. 10, no. 1, nov. 2020, pp. 1–15, https://doi.org/10.1038/s41598-02077265-x. 3. chalen, izan, maria elisa caetano-silva, et al. “alterações psiconeurológicas do desenvolvimento relacionadas a infecções virais [psychoneurological alterations of development related to viral infections].” neuroinflamação: da biologia à terapia [neuroinflammation: from biology to therapy], edited by w. savino et al., 2024. 4. chalen, izan, selena wang, virginia florianowicz, et al. “measuring fetal cortical architecture in response to maternal immune activation by live influenza virus.” brain, behavior, and immunity, vol. 114, nov. 2023, p. 31, https://doi.org/10.1016/j.bbi.2024.01.098. 5. chalen, izan, selena wang, joseph jung, et al. “measuring fetal neuroarchitecture in germ-free mice in response to maternal il-17a administration.” brain, behavior, and immunity, vol. 106, nov. 2022, p. 20, https://doi.org/10.1016/j.bbi.2022.07.073. 6. chen, helen j., jeffrey d. galley, et al. “fetal ccl2 signaling mediates offspring social behavior and recapitulates effects of prenatal stress.” brain, behavior, and immunity, vol. 115, jan. 2024, pp. 308–18, https://doi.org/10.1016/j.bbi.2023.10.032. 7. chen, helen j., adrienne m. antonson, et al. “prenatal stress causes intrauterine inflammation and serotonergic dysfunction, and long-term behavioral deficits through microbeand ccl2-dependent mechanisms.” translational psychiatry 2020 10:1, vol. 10, no. 1, june 2020, pp. 1–12, https://doi.org/10.1038/s41398-020-00876-5. 8. choi, gloria b., et al. “the maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring.” science, vol. 351, no. 6276, feb. 2016, pp. 933–39, https://doi.org/10.1126/science.aad0314/suppl_file/pa pv2.pdf. 9. duan, lian, et al. “maternal covid-19 infection associated with offspring neurodevelopmental disorders.” molecular psychiatry, vol. 30, no. 5, may 2024, pp. 2108–18, https://doi.org/10.1038/s41380-024-02822z;techmeta=38,39,47;subjmeta=378,476,631,692,699;kwr d=neuroscience,ps ychiatric+disorders. 10. galley, jeffrey, et al. “prenatal stress in mice leads to dysregulation in maternal microbial tryptophan metabolism and downstream signaling in mom and fetus.” biological psychiatry, vol. 89, no. 9, may 2021, p. s286, https://doi.org/10.1016/j.biopsych.2021.02.712. 11. galley, jeffrey d, et al. “gestational administration of bifidobacterium dentium results in intergenerational modulation of inflammatory, metabolic, and social behavior.” brain, behavior, and immunity, vol. 122, nov. 2024, pp. 44–57, https://doi.org/10.1016/j.bbi.2024.08.006. 12. galley, jeffrey d., et al. “maternal anxiety, depression and stress affects offspring gut microbiome diversity and bifidobacterial abundances.” brain, behavior, and immunity, vol. 107, jan. 2023, pp. 253–64, https://doi.org/10.1016/j.bbi.2022.10.005. 13. kim, sangdoo, et al. “maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring.” nature, vol. 549, no. 7673, sept. 2017, pp. 528–32, https://doi.org/10.1038/nature23910. 14. otero, ashley m., et al. “influenza a virus during pregnancy disrupts maternal intestinal immunity and fetal cortical development in a doseand time-dependent manner.” molecular psychiatry, july 2024, https://doi.org/10.1038/s41380-024-02648-9. 15. otero, ashley m., and adrienne m. antonson. “at the crux of maternal immune activation: viruses, microglia, microbes, and il-17a.” immunological reviews, vol. 311, no. 1, oct. 2022, pp. 205–23, https://doi.org/10.1111/imr.13125. 16. shin yim, yeong, et al. reversing behavioural abnormalities in mice exposed to maternal inflammation characterization of cortical patches. 2017, https://doi.org/10.1038/nature23909. 10 brain matters vol. 8 2025 about the author alexander byrne, a native of the south side of chicago, has long fostered his fascination with science and narrative. now a student pursuing a degree in neuroscience, alexander has focused his scholarly work on the overlap of maternal immune activation, neurodevelopmental disorders, and gut-brain microbiota interactions with the aim of determining how early immune signals influence the development of the brain and long-term behavioral outcomes.in addition to this study, he is deeply engaged in molecular neuroscience investigations into the structural processes of prion protein misfolding and aggregation. after finishing his undergraduate studies, alexander plans to undertake a ph.d. in neuroscience. his desire is to be involved in translational research that converts molecular biology into clinical knowledge. 11 copy of volume 7 publication brain matters vol. 8 no. 1 noreen adoni noreen is a freshman at the university of illinois majoring in neuroscience. she joined brain matters to investigate how the brain impacts the ways in which we interact with the world around us and stay updated on current research in the field. noreen is interested in studying neurological diseases, hoping to further analyze and treat them as a physician in the future. alexander byrne alexander byrne, a native of the south side of chicago, has long fostered his fascination with science and narrative. now a student pursuing a degree in neuroscience, alexander has focused his scholarly work on the overlap of maternal immune activation, neurodevelopmental disorders, and gut-brain microbiota interactions with the aim of determining how early immune signals influence the development of the brain and long-term behavioral outcomes.in addition to this study, he is deeply engaged in molecular neuroscience investigations into the structural processes of prion protein misfolding and aggregation. after finishing his undergraduate studies, alexander plans to undertake a ph.d. in neuroscience. his desire is to be involved in translational research that converts molecular biology into clinical knowledge. anika chandola anika chandola is a freshman majoring in mcb with a minor in psychology and chemistry on the pre-med track. she is currently working in bagchi lab researching the environmental impact on reproductive health and volunteered at uchicago’s phlebotomy clinic. she is also a member of the gamma phi beta soroity working alongside girls on the run. in her freetime she enjoys fashion, swimming, pageants and playing the piano. she hopes to become more involved in the neuroscience field and learn more about this diverse community. rayyan iqbal rayyan iqbal is a sophomore at the university of illinois, majoring in chemistry. he is currently conducting research in the physical activity and neurocognitive health lab, where he studies the impact of physical behaviors—such as physical activity and sedentary time—on brain health. beyond his research, rayyan is actively involved in react, an outreach program that brings science to life for young students in the champaign-urbana area. 89 brain matters writers isha kandlikar isha kandlikar is a rising junior at the uiuc majoring in molecular and cellular biology with minors in business and public health. she is an undergraduate researcher in the rudolph lab, where she studies genetic mouse models to explore treatments for psychiatric disorders. outside the lab, isha is a marketing and healthcare consultant, a member of the illini medical screening society, and involved in alpha epsilon delta, a prehealth fraternity on campus. passionate about neuroscience, she is excited to write for brain matters and dive deeper into specific topics within the field. yuliia kohut yuliia kohut is a freshman in bioengineering on a pre-medical track and a student from ukraine. apart from brain matters, on campus she is a global health executive member in the american medical student association, and she is also a student volunteer at carle hospital. yuliia is an undergraduate researcher in dr. best-popescu lab at beckman institute, working on developing imaging tools for cellular neuroscience research. in her free time yuliia enjoys cross-stitching, cooking ukrainian food, and reading sci-fi novels. she joined the editing and writing team of brain matters to share her fascination with neuroscience with uiuc! brianna mae huner brianna mae is a junior at the university of illinois majoring in clinical/community psychology. she became involved in brain matters to gain more experience researching and writing about the current research in neuroscience. when she is not writing for brain matters, she is also involved in dr. kwapil's project on life experiences lab, and is the treasurer for the psychology research and community club (pracc). brianna mae is hoping to pursue a phd in clinical neuropsychology and conduct research about the neurological basis behind different clinical disorders. emily aldrich emily aldrich is a freshman majoring in neuroscience with minors in linguistics and psychology on the pre-med track. emily joined brain matters to gain a deeper understanding of the brain through exploring current research topics in neuroscience. in her free time, she enjoys listening to music, reading, and spending time with friends. 90 leah rupp leah rupp is a freshman at the university of illinois in urbana-champaign studying molecular and cellular biology within the honors concentration. leah joined brain matters to get the opportunity to learn and write about new neuroscience research. leah is also a stress management peer with mckinley health center and a volunteer with the food assistance and wellbeing program. in her free time, leah enjoys running and playing the piano. her career aspiration is to become a physician. ananya sampathkumar ananya sampathkumar is a sophomore, majoring in neuroscience with minors in chemistry and public health. outside of brain matters, ananya is an assistant editor-in-chief for double helix digest, a member of starcourse, a volunteer at carle hospital, and works at the office of undergraduate admissions as a tour guide and student ambassador. in her free time, ananya likes to read books, make jewelry, watch movies, and hang out with her friends. vani sharma vani sharma is pursuing a bachelor of science in molecular and cellular biology (mcb) with an honors concentration, alongside a minor in public health and a neuroscience certificate. as a writer for brain matters, she investigates the intricate interplay between the brain and diverse phenomena, including the neural foundations of gratitude, the influence of music on cognitive processes, and the complexities of neuroanatomy and neurological disorders. through her work, she blends rigorous scientific research with engaging narratives to illuminate the brain’s extraordinary intricacies while promoting scientific literacy and making complex concepts accessible to a broader audience. navi singh navi singh is a rising junior at the university of illinois urbana-champaign, majoring in neuroscience and minoring in health administration and chemistry on the pre-medical track. she is an aspiring physician hoping to specialize in neurology. she is also involved with several rso's on campus. these include serving as social chair for udaan and the undergraduate neuroscience society, being a member of a pre-health professional fraternity phi chi, mentor for illini mentor program, volunteer for global medical brigades, and research assistant at the kukekova lab. navi is excited to share her first article and research with brain matters! 91 pravika srivastava pravika srivastava is a rising junior at the university of illinois urbana-champaign majoring in neuroscience with a minor in psychology on the pre-medical track. she is passionate about brain health, mental well-being, and hopes to pursue a career in psychiatry. as a writer and new social media co-chair for brain matters, she enjoys writing about neuroscience-related topics while eager in helping expand the journal’s outreach. on campus, pravika volunteers in the pediatric icu at carle foundation hospital, conducts research at the connectlab and rudolph lab, and serves on the speaker committee for alpha epsilon delta. pravika is excited to share her research and writing as part of her ongoing commitment to advancing understanding of the brain and mental health. micah wang micah is a freshman at uiuc majoring in neuroscience. he became involved in brain matters to gain experience writing research articles. outside of academics, you can find him staying active in the arc by working out or playing volleyball. in the future, micah hopes to make it to medical school one day. may yang may is a freshman at the university of illinois majoring in brain & cognitive science. she joined brain matters to learn more about the brain, develop her research skills, and connect with people who share similar interests. in addition to writing for brain matters, may is also involved in dr. hotaling’s cognitive decision making lab. in the future, she hopes to pursue a phd in a related field. 92 93 brain matters vol. 8 no. 1 table of contents the impact of glp-1 receptor agonists on the brain’s addiction and satiety networks noreen adoni.....................................................................................1 impact of meditation on brain function anika chandola.................................................................................12 maternal microbiota and immune interactions in neurodevelopmental risk: a review of maternal immune activation models alexander byrne.................................................................................6 articles................................................................................ the potential of hybrid models in alzheimer's diagnosis: combining neural networks and svms for enhanced accuracy rayyan iqbal.....................................................................................18 effects of pregnancy on the brain and neuroplasticity isha kandlikar..................................................................................24 adaptive plasticity of the colorblind brain: a model for sensory compensation yuliia kohut.....................................................................................30 interview with two professors brianna mae huner...........................................................................36 amusia: the science behind tone deafness emily aldrich...................................................................................42 the difference between children's learning abilities with and without adhd leah rupp........................................................................................46 how do we measure intelligence? ananya sampathkumar .....................................................................50 i about the writers...............................................................89 meet the board...................................................................77 neural mechanisms of smartphone use, adhd, and dopamine dysregulation: implications for cognitive function and attention vani sharma....................................................................................54 survival vs. cognition: stress mechanisms in humans vs. animals pravika srivastava.............................................................................62 the effects of physical exercise on memory and cognitive functions navi singh.......................................................................................58 fear on repeat: examining the impact of ptsd on the amygdala micah wang.....................................................................................67 the cognitive neuroscience of moral decision-making in extreme situations: high-stress or life-threatening scenarios may yang.........................................................................................72 ii volume 8 (will be vol 7 on site) a lack of properly functioning circadian rhythm can lead to various sleeping disorders, as well as issues related to the absence of zeitgebers—environmental signals like light, temperature, or food that cue the body to adapt its processes accordingly (chaix, 2016). for example, “while blind individuals do have a pathway in the brain that functions as their body clock, roughly half of blind individuals experience non-24-hour sleep-wake rhythm disorder, during which their sleep cycles get later every night, jumps around, or results in waking up later in the day” (reddy, 2023). this process is just one of many that is controlled by the circadian rhythm, stressing its importance. the circadian rhythm is able to function because of the influence of zeitgebers. because of the many bodily processes influenced by the circadian rhythm, the manipulation of zeitgebers and timing of treatments along with them is being researched as a method of treatment for various illnesses and infections via the immune system. additionally, lifestyle changes that utilize the timing of the circadian rhythm can lead to better overall health; the circadian rhythm is even being taken into consideration for cancer treatment in a practice called “circadian medicine or chronotherapy” (dose, 2023). the importance of the circadian rhythm and its ability to be manipulated through zeitgebers has led discoveries about its influence over immune response efficiency. practical applications of the circadian rhythm erin ford abstract the circadian rhythm is a cycle within the body that controls multiple biological processes such as the sleep-wake cycle, body temperature, hormone releasing, and digestive system. the circadian rhythm is widely theorized and understood to be developed because of the daily cycle of light and dark. this can be attributed to sunlight serving as the primary source of food for photosynthetic organisms, causing a cycle within the organism that causes food to be processed during the hours of daylight and a period of fasting during the night. recent research has suggested that disruptions in this rhythm can lead to various issues within the body. however, there have been advancements in the applications of the circadian rhythm in the areas of the immune system and infection; exercise and sleep; digestion and food-processing; and cancer and treatments. this paper explores the fundamental mechanisms of the circadian rhythm and the impact on human health in various areas, advocating for practical applications of this profound biological cycle. introduction to the circadian rhythm and its importance the circadian rhythm can be defined as the internal clock that controls feelings of awakeness and sleepiness in response to the 24 hour cycles of light and dark from the environment. the importance of the circadian rhythm cannot be understated, as the proper functioning of this cycle is crucial for everything from memory consolidation, eating habits, and digestion to body healing, temperature, and hormone release (reddy, 2023). these processes ensure that your body is able to function normally. an example emphasizing the importance of the circadian rhythm is the release of melatonin and cortisol, a process necessary for the proper functioning of the sleep wake cycle and even further, the proper functioning of the brain. melatonin is a hormone that is released from the pineal gland to induce sleepiness in response to a lack of light while cortisol is a hormone that promotes alertness in response to the presence of light (reddy, 2023). this occurs because of the suprachiasmatic nucleus (scn) of the hypothalamus, the region of your brain that controls homeostasis. in the presence of light, the retinal cells within the eyes will perceive this light and transmit this information via the optic nerve. the optic nerve then activates the scn, producing a signaling molecule called gaba (gamma-amino-butyric acid), inhibiting the release of melatonin. in essence, the light perceived by the optic nerve causes the body to send out signals through the scn, preventing the release of melatonin so that the feeling of sleepiness goes away during the day. the opposite occurs when there is no longer light: the retinal cells recognize the lack of light and inhibit the scn, preventing the release of gaba and initiating the production of melatonin and inducing sleepiness (reddy, 2023).the proper functioning of the circadian rhythm for this process is essential because a lack of/excess melatonin could cause the body to not be able to sleep at night or a feeling of tiredness during the day. lack of sleep can even affect mood, learning ability, and social cognisance (sleep deprivation, 2022). timing and the immune system one of the systems the circadian rhythm can be used to control and improve is the immune system. the circadian rhythm is responsible for the timing of expression of many proteins; some of these are important for the initial response for the immune system. one such protein is rev-erbα: this protein is a key part of the immune system because it “regulates transcription of inflammatory genes in macrophages” (ruan, 2021). these macrophages are the lymphocytes that are responsible for removing unfamiliar and potentially harmful entities in the body. another example is nuclear receptor rorγt which is “a master regulator for the development of il-17-producing t helper cells (th17 cells), an important immune cell type for autoimmunity” (ruan, 2021). t helper cells are essential for activating other cells within the immune system, such as those required to eliminate infected cells and foreign bodies. additionally, the circadian rhythm controls the acquisition of lymphocytes. for example, the amount of b and t lymphocytes in circulation oscillates along with the rest and activity cycle, with increased numbers in the rest phase. the more lymphocytes in circulation, the more effective the immune response will be and the faster the recovery. the control the circadian rhythm has over these processes make the manipulation of zeitgebers a viable option for the treatment of infections. for example, light and dark cycles are used to increase t and b cells within a patient because of their peak during the rest phase. the lack of light acts as a zeitgeber to initiate the rest phase, leading to the increase in production of these cells. this leads to an increased immune response from the patient and a better chance of recovery from the infection (ruan, 2021). by placing the patient in a room with low light and initiating this rest phase of the circadian rhythm, more white blood cells can be produced. this timing along with the circadian rhythm can contribute to the immune system’s ability to fight off an infection. exercise and the circadian rhythm the timing of daily activities such as eating and exercise along with the circadian rhythm can result in more efficient bodily processes such as exercise and digestion. as light and dark cycles are important in the moderation of lymphocytes, the timing of daily activities--like eating or exercising--can improve the effectiveness of various bodily processes. research has demonstrated that blood pressure, body temperature, hormone levels, and heart rate variability are all controlled by circadian variation (dose, 2023). with these physiological features being integral to sport performance, timing exercise with the optimal levels of these factors can increase effectiveness of exercise and peak performance during periods of exercise. conversely, misalignment can be detrimental to effectiveness of sleep cycles: “night exercise causes a phase delay of the onset of dim-light melatonin” (wang, 2022). as a result, exercise before bed is not recommended because it can block the production of the hormone that induces the feeling of tiredness and it is advised that physical activity take place slightly earlier in the day. therefore, a better sleep schedule can be obtained based on the timing of exercise with consideration of the circadian rhythm. this better sleep schedule leads to all of the benefits associated with more sleep, such as improved immune response to possible pathogens (ruan 2021). this indicates that consideration of the circadian rhythm in the timing of exercise can not only improve the quality of the exercise but also improve other necessary functions such as sleep and digestion. effective digestion and the circadian rhythm similar to the timing of exercise, the timing of meals with consideration of the circadian rhythm can also result in a healthier lifestyle. for example, “insulin mediates the phase adjustment of the circadian rhythm of the tissues related to food in mice” (wang, 2022). this process is important for tissue function which, in turn, assists in digestion and absorption of nutrients and aligning the stomach’s circadian rhythm with meal times. hence, the timing of meals with respect to the circadian rhythm can affect the efficiency of meal processing. recent research supports this idea: in a study describing how the circadian rhythm controls pathways related to metabolic processing, researchers found that these pathways begin to increase when eating is anticipated. this is a temporary effect that declines after a few hours (chaix. a, 2019). these results indicate that having a scheduled eating time every day can assist in the absorption of nutrients because the body will always be prepared to process food during that time. furthermore, deviating from this schedule would mean consuming a large amount of nutrients when the body is not prepared to process it, and, as a result, leads to a less efficient digestive process. this supports the argument that “the consumption of a larger portion of caloric intake during the first half of wakeful hours may be preferred for better blood glucose regulation and weight control“ (dose, 2023). essentially, after a large period of fasting, or sleep, the body has had a long period of time to prepare for the next meal and because of this, the circadian rhythm has ensured that the proper pathways are prepared. cumulatively, the timing of meals alongside the circadian rhythm results in more efficient digestion and leads to better absorption of the nutrients necessary for other processes within the body. figure 1. a diagram explaining the processes controlled by the circadian rhythm as well as the factors controlling it. cycle zoomed in on previous page. obtained from an overview article by ana amiama-roig and others. brain matters・volume vii 48 chronotherapy and cancer treatment the circadian rhythm’s applications are not only exclusive to day to day life but also have significance within the medical field. the timing of the circadian rhythm can be used to increase effectiveness of cancer treatments and the overall quality of life in cancer patients. the time of day when cancer treatments are administered can affect how much of the dose can be tolerated and the side effects experienced by the patient. an example of this was a study done with mice that found “the same dose of an anticancer drug became lethally toxic only when administered at certain times of day, whereas at other times of day, a 10-fold increase in dose was tolerated”(ancoli-israel, 2005). these results seem logical when considering the amount of processes that are controlled by the timing of the circadian rhythm. certain proteins being made at specific times may help the body process the drugs or could cause unpleasant interactions leading to side effects of the drug. if the circadian rhythm dependent proteins that cause unpleasant interactions are made mostly within the first hours of waking, then the majority of this interaction can be avoided by taking the drug treating the cancer later in the day. other research focusing on cancer patients has shown that the quality of life of the patient increases significantly when chronotherapy is used. administration of the drug during the morning was compared with administration during the evening and it was found that during the morning hours patients experienced “milder nausea, and less vomiting in those receiving the chemotherapy in the evening” (ancoli-israel, 2005). the reduction of these unpleasant side effects leads to the patient feeling better physically, which in turn leads to “better psychosocial adaptation (including better social relations, less feeling of loss of independence, less anxiety, less depression, and less somatic discomfort) than patients receiving traditional therapy” (ancoli-israel, 2005). it is then likely that chronotherapy plays a part in the patient having fewer side effects and better quality of life during treatment. chronotherapy is an effective treatment method because of the difference between the circadian rhythms followed by cancerous and noncancerous cells. according to benjamin dose “chronotherapy aims to exploit these differences in circadian rhythms by administering treatments at times when cancer cells are most vulnerable, and healthy cells are least vulnerable, thereby reducing toxicity and enhancing efficacy” (dose, 2023). this strategy ensures that the cancer treatment can be administered at a time when it will be the most effective and when the healthy cells will be least affected which is what causes the minimized side effects. this kind of thinking may extend beyond cancer treatment and to other more common medications with adverse side effects. if other medications can be found to be more effective or have reduced side effects at certain periods of the circadian rhythm, then the same benefits as those from chronotherapy can be obtained. conclusion to summarize, the circadian rhythm is a very powerful process in the human body that has a great deal of control over the different processes in the body; therefore, it is important to consider the circadian rhythm when carrying out certain processes, such as fighting off an infection. for example, more lymphocytes are produced during the rest phase which is initiated by a lack of light. the use of light and dark cycles can then be used to increase the amount of lymphocytes in circulation, which could increase the immune response to an infection. it is also important to consider the circadian rhythm in everyday habits such as when to eat or exercise. exercising before bed can delay the release of melatonin and can lead to a worse night of sleep. additionally, eating at the same time everyday can help the body process the caloric intake better because the circadian rhythm causes the proper digestive proteins to be produced at that same time each day. furthermore, because the circadian rhythms of cancerous and noncancerous cells differ, the timing of cancer treatments to when cancerous cells are most vulnerable and noncancerous cells will be least affected by the treatment. this can lead to a decrease in unpleasant side effects, increase in effectiveness and overall better treatment experience for the patient. these applications emphasize how important the circadian rhythm truly is and further research may reveal even more applications of this complex system leading to new treatments and even more ways to live a healthier lifestyle. re ferences 1. amiama-roig, a., verdugo-sivianes, e. m., carnero, a., & blanco, j. r. (2022). chronotherapy: circadian rhythms and their influence in cancer therapy. cancers, 14(20), 5071. https://doi.org/10.3390/cancers14205071 2. chaix, a., manoogian, e., melkani, g., ,and satchidananda p(2019). time-restricted eating to prevent and manage chronic metabolic diseases. annual reviews. https://www.annualreviews.org/doi/10.1146/annurev-nutr082018-124320 3. chaix, a., zarrinpar, a., & panda, s. (2016). the circadian coordination of cell biology. the journal of cell biology, 215(1), 15–25. https://doi.org/10.1083/jcb.201603076 4. dose, benjamin, et al. timeteller for timing health: the potential of circadian medicine to improve performance, prevent disease and optimize treatment. frontiers, 27 mar. 2023, www.frontiersin.org/journals/digitalhealth/articles/10.3389/fdgth.2023.1157654/full. 5. reddy s, reddy v, sharma s. physiology, circadian rhythm. [updated 2023 may 1]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2023 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk519507/ 6. ruan, w., yuan, x. & eltzschig, h.k. circadian rhythm as a therapeutic target. nat rev drug discov 20, 287–307 (2021). https://doi.org/10.1038/s41573-020-00109-w 7. sonia ancoli-israel, chapter 103 sleep and fatigue in cancer patients, editor(s): meir h. kryger, thomas roth, william c. dement, principles and practice of sleep medicine (fourth edition), w.b. saunders, 2005, pages 1218-1224, isbn 9780721607979, https://doi.org/10.1016/b0-72-160797-7/50110-5. (https://www.sciencedirect.com/science/article/pii/b07216079 77501105) 8. wang, j., shen, l., zhang, y., shen, b. (2022). circadian rhythm and personalized exercise. in: shen, b. (eds) translational informatics . springer, singapore. https://doi.org/10.1007/978-981-16-9162-1_6 9. “what are sleep deprivation and deficiency?” national heart lung and blood institute, u.s. department of health and human services, 24 mar. 2022, www.nhlbi.nih.gov/health/sleepdeprivation#:~:text=sleep%20 deficiency%20is%20linked%20to,adults%2c%20teens%2c %20and%20children. accessed 17 nov. 2023. brain matters・volume vii 50 brain matters vol. 8 no. 2 graphic processing units (gpus) are a major component of artificial intelligence (ai) processing power. as ai becomes more sophisticated and more processing power is needed to run these intellectual models, a growing concern of energy demand and extensive ai training becomes an increasing concern. to create more sophisticated machine learning algorithms, scientists in the field of neuromorphic computing studied the brain for its ability to efficiently process and store information. finding a way to incorporate the brain directly into computing may create novel algorithms to meet the increasing demands of information processing. written by edward lin abstract biological neural networks as the forefront of ai processing introduction graphic processing units (gpus) are chips within a computer that process data simultaneously, performing parallel computations. making approximately 36,500 calculations per second, gpus consist of three major components that use basic arithmetic operations for neural network processing. the gpu’s tensor core is the forefront of critical ai operations and ai learning, which uses geometric transformations and large matrix computations for ai neural network optimization. as science further progresses, we obtain more data about the world, which requires more processing power. this exponential growth in data requires increasingly more powerful processing capabilities to interpret this data. however, the current processing power of modern-day computational systems are inefficient and expensive, as they have a high energy and resource demand for running the gpus and regulating their temperature as shown in figure 1. since the late 1980s, scientists and engineers have been studying the structural organization within the brain to help them optimize information processing, giving rise to the field of neuromorphic computing. the processing speed of the brain is similar to that of a supercomputer, and outperforms a supercomputer in terms of energy efficiency, spatial optimization, memory, and storage. rather than mimicking and studying how brain structures optimize information processing, it may be effective to explore the direct integration of these systems, also known as “reverse figure 1. comparison between supercomputer and human brain 1 neuromorphic computing”. implementing the biological neuronal networks within the brain directly into a computer’s processing units can maximize efficiency, leading to greater information processing and more sophisticated machine learning algorithms (kagan et. al, 2023). as the brain receives new information, it reorganizes itself and forms new connections. the incorporation of selfrestructuring capabilities to ai opens more dynamic approaches to ai training. in addition, the incorporation of neuroplasticity functions in gpus may allow neural networks to adjust how they process inputs without rigorous retraining. such approaches give engineers the freedom to develop more powerful algorithms with deeper, more advanced neural networks. the implementation of neuroplasticity would enable ai models to process complex, continuous flows of data more effectively, allowing the energy-efficient and adaptable data processing of the brain to be manifested in gpus. the implementation of neuroplasticity would enable ai models to process complex, continuous flows of data more effectively, allowing the energy-efficient and adaptable data processing of the brain to be manifested in gpus. biological neural networks (bnns) biological neural networks bnns, or biological neural networks, are clusters of neurons connected to each other through axons and dendrites (in a sense, they can be described as miniature brains with the most basic complexity). through these axonal and dendritic connections, bnns are able to demonstrate characteristics that mirror those of artificial intelligence: computational performance and network plasticity (the ability of neurons to arrange themselves based on the stimulation received). the vast quantity of connections within a bnn enables the biological structure to undergo parallel processing across multiple neuronal signaling pathways and allows stimuli to be distributed vastly. when integrated within computing systems, bnns have the ability to not only process the information and exhibit a response, but also rearrange themselves according to the stimulus, displaying plasticity and small amounts of memory (dranias et. al, 2014). memory consolidation in bnns can be categorized into two types of memory processes, fading memory and hidden memory. fading memory relies on the firing activity in response to a brain matters vol. 8 2025 2 stimulus, lasting only for a brief moment, while hidden memory depends on synaptic plasticity to strengthen the connections between neurons. hidden memory allows the bnn to retain information for prolonged periods. however, the retention of this information is disrupted or restructured when the bnn receives a high-intensity electrical input (stimuli). multielectrode arrays meas, or multielectrode arrays, help researchers integrate neurons within computational devices. structurally, they are a flat surface with multiple microelectrodes embedded in an array placed underneath a bnn that is in a petri dish. each electrode independently records extracellular activity. the recorded signals are then digitized and processed by a computer to interpret neural activity. the computer then generates an electrical stimulus that is sent as a response to the neurons to evoke another response, generating a realtime feedback loop. figure 2. multielectrode array structure (left to right) schematic, 60 electrode array, cultured neurons ping-pong experiment through an experiment revolving around ping-pong, researchers connected a bnn to an mea that provided input of the game’s environment, allowing the bnn to control a ping-pong paddle in real-time. the neurons received structured feedback through successful (positive reinforcement) and missed hits (negative reinforcement), allowing the bnn to self-correct from an optimal to a more accurate dynamic state. through this, the bnn could retain task-specific information for brief intervals, displaying a positive correlation between branching ratio (neuroplasticity) and task performance. this enhanced bnn performance for that one specific task. when researchers no longer provided feedback to the bnn, its “hit-to-miss ratio” decreased (habibollahi and kagan, 2023). once connected to a computing system through a multielectrode array, bnns rearranged themselves until they reached an optimal dynamic state to efficiently process the structured stimuli. despite reaching an optimal state, bnns displayed low accuracy but a high level of computing, thus requiring feedback. feedback was only in regards to one specific task, allowing bnns to process information efficiently and with high accuracy for one task, making bnns optimal for computing one task over and over again. however, if required to switch tasks, bnns needed to rearrange themselves and be given the correct feedback to perform a task swiftly (habibollahi and kagan, 2023). neuronal capabilities of matrix processing the ping-pong experiment's success with parallel processing and real-time adaptation points to the potential of larger neural systems. in the brain, neural processing in the cerebral cortex occurs at intervals of a few milliseconds. despite being slower than a computer, the cortex is able to compensate for this difference through its ability to process vast amounts of information in parallel (ballard, 1986). resembling gpus, this parallel processing in the brain is how the brain receives sensory information and executes motor skills (sigman and dehaene, 2008). in addition, hierarchical (information flowing through successive layers of processing) and modular organization (each cortex is divided into specialized regions for particular tasks) of the brain is essential for matrix computations. present artificial intelligence neural networks follow a similar information flow, but creating a processing system consisting of specialized bnns can structure information for maximal efficiency and scalability. this hypothetical computational system, much like the brain, will have areas of the computer’s processing unit distinguished by function. each area will have their own specialization of information processing. as information is received, the information will be decomposed and sent to the right processing subregions, taking into advantage a bnn’s fading memory. information processing can then be split into smaller, manageable bits of information that each subregion of bnns can process, allowing for scalability and efficiency. ethics despite using only bnns, which in comparison to a human brain is minuscule in proportion, it is possible to create a sentient life force when such an organization is scaled to an extent. eventually, if such biotechnological methods are implemented, one will create structures that contain a neuron count that mirrors certain large mammalian organisms. in the ping-pong game, researchers were able to notice a certain degree of self awareness within the bnn, despite being comparatively small to that of a simple organism’s (kagan et. al, 2022). however, if neurons were integrated into technology, will such a system eventually have a form of consciousness? due to exponential growth of technology, the size of bnn integrated systems will also have to increase to address this demand. but once a certain number of neurons are integrated and interacting, it can eventually have its own life force. it is essential to bring up such topics when discussing the potential future direction advancement of biocomputational devices to prevent the unethical exploitation of sentient beings as inanimate objects. furthermore, ethical considerations regarding the creation of such conscious systems must be explored, drawing a line as to when a system has developed consciousness. conclusion although the idea of integrating neurons into the processing biological neural networks as the forefront of ai processing system of computers seems efficient and beneficial to the further advancement of ai, it is still fairly new and many caveats have yet to be considered. for example, how would bnns be integrated at a scale into computers/super computers that will provide enough processing power to match that of the computer? how much energy and resources would it take to maintain the functionality of a bnn once integrated into the computer’s processing? such topics are hard to answer and current research on the topic is in its infancy. in addition, with the global emergence of ai made public in only the past few years. but the benefits of such computational systems are apparent and mitigate the flaws of current information processing systems in computers.the ability of the brain to process information in a hierarchical and modular manner, as well as bnn’s plasticity and hidden memory, can allow information processing systems to be optimally efficient. without the rigid structure of ai neural networks, such a system allows for fluidity of adaptability, while taking on an energyefficient approach. references 1. smirnova, l., caffo, b. s., gracias, d. h., huang, q., pantoja, i. e. m., tang, b., zack, d. j., berlinicke, c. a., boyd, j. l., harris, t. d., johnson, e. c., kagan, b. j., kahn, j., muotri, a. r., paulhamus, b. l., schwamborn, j. c., plotkin, j., szalay, a. s., vogelstein, j. t., . . . hartung, t. (2023). organoid intelligence (oi): the new frontier in biocomputing and intelligence-in-a-dish. frontiers in science, 1. https://doi.org/10.3389/fsci.2023.1017235 2. roberts, t. p., kern, f. b., fernando, c., szathmáry, e., husbands, p., philippides, a. o., & staras, k. (2019). encoding temporal regularities and information copying in hippocampal circuits. scientific reports, 9(1), 19036. https://doi.org/10.1038/s41598-019-55395-1 3. kagan, b. j., gyngell, c., lysaght, t., cole, v. m., sawai, t., & savulescu, j. (2023). the technology, opportunities, and challenges of synthetic biological intelligence. biotechnology advances, 68, 108233. https://doi.org/10.1016/j.biotechadv.2023.108233 4. dranias, m. r., westover, m. b., cash, s., & vandongen, a. m. (2015). stimulus information stored in lasting active and hidden network states is destroyed by network bursts. frontiers in integrative neuroscience, 9, 14. https://doi.org/10.3389/fnint.2015.00014 5. sigman, m., & dehaene, s. (2008). brain mechanisms of serial and parallel processing during dual-task performance. the journal of neuroscience : the official journal of the society for neuroscience, 28(30), 7585–7598. https://doi.org/10.1523/jneurosci.0948-08.2008 6. nelson, m. e., & bower, j. m. (1990). brain maps and parallel computers. trends in neurosciences, 13(10), 403– 408. https://doi.org/10.1016/0166-2236(90)90119-u 7. ballard, d. h. (1986). cortical connections and parallel processing: structure and function. behavioral and brain sciences, 9(1), 67–90. https://doi.org/10.1017/s0140525x00021555 3 8. kagan, b. j., kitchen, a. c., tran, n. t., habibollahi, f., khajehnejad, m., parker, b. j., bhat, a., rollo, b., razi, a., & friston, k. j. (2022). in vitro neurons learn and exhibit sentience when embodied in a simulated game-world. neuron, 110(23), 3952–3969.e8. https://doi.org/10.1016/j.neuron.2022.09.001 brain matters vol. 8 2025 about the author edward is a sophomore at the university of illinois majoring in neural engineering. through his studies, he aspires to implement biological mechanisms/systems into computers and explore aineural network connections. some of his interests include playing volleyball, filming, and going on road trips. after graduation, he hopes to attend graduate school. 4 5 brain matters vol. 8 no. 1 written by noreen adoni abstract glucagon-like peptide-1 receptor agonists (glp-1 ras), with one of the most recognized being ozempic, have increased in popularity for their abilities to help individuals with obesity or type 2 diabetes experience weight loss results. these medications mimic the glp-1 hormone secreted by intestinal l-cells in response to the ingestion of a meal to slow gastric emptying, help regulate blood glucose levels, and promote feelings of fullness. a large aspect of their success in stimulating weight loss comes from their ability to bind to glp1 receptors in the hypothalamus, which stimulates satiety by activating neurons that produce satiety signals while inhibiting neurons that promote hunger, lowering overall food consumption and reducing appetite as a result. the impact that altering feeding networks in the brain can have on weight management illustrates the strong correlation between levels of food consumption and psychological aspects of hunger and fullness. while glp-1 ras are effective in providing weight loss results, they often come with adverse effects, such as nausea and headaches. therefore, understanding the mechanisms behind glp-1 ras in the brain altering feeding behavior may help to develop future treatments that have a similar function in stimulating weight-loss but do not result in harmful side effects. the impact of glp-1 receptor agonists on the brain’s addiction and satiety networks in the past decade, many individuals have turned to glp-1 ras desperate for a solution to their struggle with weight. use of these drugs has increased by 40-fold between 2017 and 2021, and six million americans are now on either ozempic or mounjaro, which is another class of glp-1 medication. from 2018 to 2023, 1,063,200 patients were prescribed a glp-1 drug (gratzl et. al, n.d.). an estimated nine million prescriptions were written in 2022, and roughly 2-3% of the united states population may now be taking one of these drugs (logan, 2024). these statistics illuminate the increased prevalence of and dependency on glp-1 ras in recent years to combat weight issues. although glp-1 ras are commonly used for and understood as effective in stimulating weight-loss, there is a risk of experiencing side-effects when administered these medications. several case reports have linked the use of these drugs with the occurrences of acute kidney injury, nausea, injection site reactions, headache, and nasopharyngitis (filippatos et. al., 2014). therefore, it is crucial to assess how glp-1 ras function in the brain to alter feeding behavior to eventually develop similar treatments that can suppress hunger and relay satiety signals to stimulate weight-loss without causing these harmful effects. increased prevalence of glp-1 ras ozempic, one of the most well-known glucagon-like peptide-1 receptor agonist (glp-1 ra) drugs on the market, has been referred to in the media as a “miracle drug” due to its ability to help individuals who have struggled with their weight for the majority of their lives finally achieve weight loss results. obesity, defined as a bmi greater than or equal to 30, is a crucial issue in the united states. in 2017-2018, the age-adjusted prevalence of obesity in adults was 42.4%, increasing by 12% since 2000 (hales et al., 2020). according to the national institute of diabetes and digestive and kidney diseases, nearly one in three adults are overweight, and more than two in five adults are obese (niddk, n.d.). obesity can have a serious impact on health, leading to heart disease, stroke, type two diabetes, musculoskeletal disorders, and certain cancers, which all contribute to premature death and substantial disability (world health organization, 2024). therefore, obesity is a long-standing problem that severely endangers the health of a large portion of society. glp-1 ras, such as ozempic, have been found to help individuals with obesity experience weight loss results, and a crucial reason for their success can be credited towards their ability to impact the appetite and satiety networks in the brain, altering feeding behavior. 1 glp-1 ra mechanisms glp-1 ras alleviate obesity by mimicking the action of glucagon-like peptide, a hormone secreted by the small intestine. glucagon-like peptide triggers insulin, which is an essential hormone released from the pancreas that allows the body to use food for energy by lowering the amount of glucose in the blood (cleveland clinic, 2023). this extra insulin stimulated by a glp-1 ra helps lower blood sugar levels, which is helpful for controlling type 2 diabetes and obesity. glp-1 ras also curb hunger by slowing the movement of food from the stomach into the small intestine, resulting in the body releasing less glucose from food into the bloodstream and allowing the individual to feel full faster and for longer. it is currently not completely understood why obese patients secrete less glp-1 (castro, 2022). while these effects of glp-1 ra drugs are crucial to their success in causing weight loss, the ability of glp-1 ras to influence the central nervous system’s regulation of appetite and satiety is a major reason for their effectiveness. glp-1 drugs exert their effects on glucose homeostasis and feeding behavior via indirect and direct pathways that the central nervous system mediates (bloemendaal et. al., 2014). hunger can be viewed as an addiction, as it is a learned behavior that eating is initially reinforcing by reversing an unpleasant bodily signal, such as changes in nutrient levels in the blood, changes in hunger hormones, and stomach contractions (dagher, 2009). altering and observing the brain’s addiction and satiety networks can help an individual with a hunger or food addiction control their feeding behaviors. therefore, a large reason for the effectiveness of glp-1 drugs for weight loss is their ability to address the psychological factors that lead to obesity, impacting the brain’s addiction and satiety networks in order to alter feeding behavior. uch these results can also be observed when glp-1 receptor agonists (glp-1 ras) are made to bind to glp-1 receptors, mimicking the effects of glp-1. glp-1 ras are administered subcutaneously, ensuring rapid absorption and peak concentration within hours. post absorption, glp-1 ras exhibit a low volume of distribution and primarily remain in the bloodstream. these agents then selectively target glp-1 receptors in various tissues involved in glucose regulation, with specific affinities for pancreatic cells and other metabolic control sites (collins and costello, 2024). in particular, by binding to glp-1 receptors in the hypothalamus, glp-1 ras adapt the ability of glp-1 to help control food intake and satiety. impact of glp-1 ras on feeding behavior demonstrated the effectiveness of glp-1ras on feeding behavior has been hunger and satiety. additional signals released from the gut,such as short-acting cholecystokinin and long-acting incretin, work to inhibit appetite in order to regulate energy homeostasis (yeung and tadi, 2023). in particular, glp-1 drugs specifically mimic the long acting incretin-glp signal to inhibit appetite. glucagon-like peptide-1 (glp-1) belongs to a family of hormones called incretins, which enhance the secretion of insulin. glp-1 is synthesized and secreted by lcells of the small intestine in response to food intake. it is also synthesized by a small population of neurons in the hunger center nucleus of the solitary tract (nts) in the caudal brainstem, with the nts projecting to areas in the hypothalamus and hindbrain, such as the arcuate nucleus, that express glp-1 receptors (barakat et al., 2024). when food is ingested, the vagus nerve relays satiety signals from glp-1s that are secreted by l-cells to the glp-1 receptors in the hypothalamus, with the purpose of controlling food intake. glp-1 receptors in the hypothalamus stimulate fullness by activating neurons that produce satiety signals, such as pro-opiomelanocortin and cocaine and amphetamine-regulated transcript, while reducing food intake by inhibiting neurons that promote hunger, such as neuropeptide y and agouti-related peptide (baggio and drucker, 2014). brain matters vol. 8 2025 figure 1. this model represents the interaction between glp-1 sent from the nts to glp-1 receptors in the paraventricular nucleus within the hypothalamus, resulting in feeding suppression (katsurada & yada, 2016). regulation of appetite and satiety multiple parts of the hypothalamus, including the ventromedial nuclei, lateral hypothalamic area, and arcuate nucleus, work together to regulate appetite and satiety. feelings of hunger and fullness involve complex interactions between hormones from the gastrointestinal tract to the hypothalamus. ghrelin and leptin are two hormones that frequently signal to the hypothalamus to regulate sensations of hunger and satiety and to maintain energy homeostasis by balancing energy intake and expenditure. first, ghrelin, known as the hunger hormone, is produced by the gut and acts on the lateral hypothalamus. ghrelin interacts with the growth hormone secretagogue receptor to promote feelings of hunger and food anticipation. conversely, leptin, which is produced from adipose tissue, is the body’s satiety signal and acts upon the arcuate nucleus, ventromedial nucleus, and lateral hypothalamus to promote stimulatory effects of satiety and inhibitory effects of hunger to coordinate the body’s energy homeostasis. together, ghrelin and leptin signals regulate sensations of hunger2 demonstrated in multiple studies. for example, a study performed by friedrichsen and colleagues in 2021 demonstrated the influence of glp-1 ras, specifically semaglutide, on feeding habits and hunger levels. a group of seventy two adults with obesity were randomized with either taking a once-weekly semaglutide of 2.4 milligrams or a placebo for twenty weeks. gastric emptying was assessed following a standardized breakfast, in addition to energy intake during lunch being examined. researchers also assessed participants’ appetite ratings and responses from a “control of eating” questionnaire, which prompted participants to note their eating behaviors and feelings around food during the study. results demonstrated that participants who took semaglutide experienced reduced hunger and food consumption and increased fullness and satiety compared to the placebo group. their responses to the “control of eating” questionnaire indicated better selfcontrol regarding eating and fewer and weaker food cravings compared to the placebo group responses. body weight was reduced by 9.9% with semaglutide use and 0.4% with the placebo (friedrichsen et al., 2021). therefore, friedrichsen and colleagues concluded that a once-weekly administration of semaglutide suppressed appetite, improved self-control regarding eating, and reduced food cravings, illustrating the effect of glp-1 ras on feeding behavior. since glp-1 ras are effective in altering feeding behavior and decreasing appetite, individuals who stop taking glp-1 medications typically re-gain a majority of the weight they lost while taking the drug. this result is due to the secretion of glp-1 and its binding to glp-1 receptors both returning to pre-treatment levels once glp-1 ras are no longer administered, resulting in greater feelings of hunger and less satiety (wilding et. al., 2022). this re-gaining of weight when administration of a glp-1 ra is terminated demonstrates the ability of these medications to significantly alter feeding behavior and the regulation of satiety and hunger. conclusion the abilities of glp-1 receptor agonists to mimic glp-1 in individuals with less endogenous glp-1 secretion, bind to glp-1 receptors, and relay satiety signals to the hypothalamus to control feeding behavior, are what make these medications highly sought after by individuals seeking weight loss results. the impact of glp-1 medications on the brain to alter feeding behaviors demonstrates that levels of food consumption is highly contingent on the ability of satiety signals to reach the brain. therefore, glp-1 ras do not just work by slowing down gastric emptying to stimulate a feeling of fullness, but also directly impact the appetite centers in the brain by binding to glp-1 receptors and relaying satiety signals. the direct impact of glp-1 ras on the brain by altering feeding behavior may be overlooked, but is demonstrated through the weight gain effects following termination of administration of the glp1ras and subsequent increased appetite. given that glp-1 levels are lower in obese patients, future endeavors may seek to investigate the reasons for and mechanisms behind reduced secretion of glp-1 in obese individuals. if the mechanisms behind the reduced glp-1 secretion in obese patients are more fully understood, then treatments that target appetite centers and the reception of satiety signals in the brain may be developed that reduce the adverse withdrawal and weight-gain effects experienced when coming off glp-1 ra medications. trials on medications similar to glp-1 ras or that similarly target the appetite centers of the brain may also be conducted. regardless, future research regarding medications that affect the appetite centers of the brain such as glp-1ras are limited to the difficulties of studying the in-vivo brain. by first fully understanding the complex mechanisms regarding satiety and feeding behavior in live individuals without invasive procedures, safer and more effective medications may be developed that permanently improve the quality of life for all. figure 2. results from the study performed by blundell and colleagues, which randomized thirty subjects to a onceweekly dosage of semaglutide or placebo. results show that overall appetite is lower and that satiety is higher in subjects who took the semaglutide (blundell et. al., 2017). references 1. baggio, l. l., & drucker, d.j. (2014). “glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight.” journal of clinical investigation, 124(10), 42234226. https://doi.org/10.1172/jci78371 2. barakat gm, ramadan w, assi g, khoury nbe. satiety: “a gut-brain-relationship.” j physiol sci. 2024 feb 17;74(1):11. doi: 10.1186/s12576-024-00904-9. pmid: 38368346; pmcid: pmc10874559. 3. blundell, j., finlayson, g., axelsen, m., flint, a., gibbons, c., kvist, t., & hjerpsted, j. b. (2017b). “effects of once‐weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity.” diabetes, obesity and metabolism, 19(9), 1242–1251. https://doi.org/10.1111/dom.12932 4. cleveland clinic medical. (2024, october 11). “glp-1 agonists.” cleveland clinic. https://my.clevelandclinic.org/health/treatments/13901-glp1-agonists the impact of glp-1 receptor agonists on the brain’s addiction and satiety networks 3 5. collins, l. (2024, february 29). “glucagon-like peptide-1 receptor agonists.” national library of medicine. https://www.ncbi.nlm.nih.gov/books/nbk551568/ 6. dagher, a. “the neurobiology of appetite: hunger as addiction.” int j obes 33 (suppl 2), s30–s33 (2009). https://doi.org/10.1038/ijo.2009.69 7. fillippatos, t. d., panagiotopoulou, t. v., & elisaf, m. s. (2015). “adverse effects of glp-1 receptor agonists.” https://doi.org/10.1900/rds.2014.11.202. 8. friedrichsen, m., breitschaft, a., tadayon, s., wizert, a., & skovgaard, d. (2021). “the effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity.” diabetes, obesity and metabolism, 23(3), 754–762. https://doi.org/10.1111/dom.14280 9. gratzl, s., rodriguez, p. j., cartwright, b. m., baker, c., & stucky, n. l. (2024a). “monitoring report: glp-1 ra prescribing trends september 2024 data.” https://doi.org/10.1101/2024.01.18.24301500 10. hales, c. m., carroll, m. d., fryar, c. d., & ogden, c. l. (2020, february 27). “prevalence of obesity and severe obesity among adults: united states, 2017-2018.” february 2020. centers for disease control and prevention. https://www.cdc.gov/nchs/products/databriefs/db360.htm 11. katsurada, k., & yada, t. (2016). “neural effects of gut‐ and brain‐derived glucagon‐like peptide-1 and its receptor agonist.” journal of diabetes investigation, 7(s1), 64-69. https://doi.org/10.1111/jdi.12464 brain matters vol. 8 2025 4 about the author noreen is a freshman at the university of illinois majoring in neuroscience. she joined brain matters to investigate how the brain impacts the ways in which we interact with the world around us and stay updated on current research in the field. noreen is interested in studying neurological diseases, hoping to further analyze and treat them as a physician in the future. 12. national institute of diabetes and digestive and kidney diseases. (n.d.-a). “overweight & obesity statistics.” niddk. https://www.niddk.nih.gov/health-information/healthstatistics/overweight-obesity 13. pierce, l. (2024, june 27). “on the increase in use of glp1s.” https://medicine.iu.edu/blogs/bioethics/on-theincrease-in-use-of-glp-1s 14. van bloemendaal, l., ten kulve, j. s., la fleur, s. e., ijzerman, r. g., & diamant, m. (2013b). “effects of glucagonlike peptide 1 on appetite and body weight: focus on the cns.” journal of endocrinology, 221(1). https://doi.org/10.1530/joe-13-0414 15. wilding, j. p., batterham, r. l., davies, m., van gaal, l. f., kandler, k., konakli, k., lingvay, i., mcgowan, b. m., oral, t. k., rosenstock, j., wadden, t. a., wharton, s., yokote, k., & kushner, r. f. (2022). “weight regain and cardiometabolic effects after withdrawal of semaglutide: the step 1 trial extension.” diabetes, obesity and metabolism, 24(8), 1553– 1564. https://doi.org/10.1111/dom.14725 16. yeung, a. y. (2023, january 3). “physiology, obesity, neurohormonal appetite and satiety control.” national library of medicine. https://www.ncbi.nlm.nih.gov/books/nbk555906/ 5 volume 8 (will be vol 7 on site) déjà vu: what happens in the brain ananya sampathkumar abstract déjà vu is a common phenomenon that most healthy people experience. despite its commonness, it is difficult to stimulate in a lab situation, making information on this experience scarce. in order to combat this, researchers have come up with multiple theories on where déjà vu takes place, what occurs, and why it actually happens. researchers have also begun to study mental disorders that involve déjà vu in order to possibly learn more about the elusive experience. understanding déjà vu is crucial to gaining a fuller understanding of memory, and how the brain reacts when memories are altered or off kilter; as further technology is developed, scientists will be able to test out all theories surrounding déjà vu and narrow down the true cause. introduction despite the common manifestation of déjà vu in mental illness, 97% of healthy individuals experience it (khomutov et al., 2023). déjà vu is the french word for “seen before” and refers to when an individual feels they are feeling an experience identical to that they have lived before (texas a&m, 2016). oftentimes, this feeling can be described as unnerving, leading some researchers to incorporate déjà vu with what is known as the “dreamy state.” the dreamy state is a term that refers to the many symptoms (which can often be difficult to distinguish between) that lead to the conscious being distorted (gillinder et al., 2022). despite the commonality of these emotions, there is very little known about déjà vu and the other processes in the “dreamy state.” the main reason for this is simple: these internal processes are very difficult to study. according to dr. michelle hook of texas a&m, there is “no clear, identifiable stimulus that elicits a déjà vu experience (it is a retrospective report from an individual); moreover, it is very difficult to study déjà vu in a laboratory” (texas a&m, 2016). as a result, there is very little that we know about déjà vu as a phenomenon; however, there are many different theories being explored surrounding the feeling. where déjà vu takes place when it comes to discussions of where déjà vu takes place, a common theory is the optical system. for many, déjà vu is triggered by seeing a specific object, place, person in their visual system. from there, it is thought that these signals were compared to current memories, thus causing déjà vu. however, researchers have found proof of otherwise. in their 2006 study, researchers akira o'connor and chris moulin at university of leeds studied a blind participant who claimed to experience déjà vu. being blind, the participant’s déjà vu was caused by familiar sounds and smells that brought up memories and part experiences such as a particular piece of music playing as he unzipped a jacket (university of leeds, 2006). this was the first time this particular situation was reported, opening much discussion on the possible location of déjà vu in the brain. while the hypothalamus was not thought to directly play a role in déjà vu, research has found that a stimulated hypothalamus can also lead to the feeling of déjà vu. andres lozano, professor of neurosurgery and canada research chair in neuroscience, led the effort to experimentally treat a man with morbid obesity through a dbs surgery. dbs stands for deep brain stimulation, and this surgery often is used on patients with movement disorders such as parkinson’s disease. lozano and his team were attempting to identify possible appetite suppressants in the patient’s hypothalamus, and found that activating the electrodes caused the patient to experience déjà vu. the patient reported a memory of being with his friends in a park when he was 20, and as the strength of the stimulation was increased, the description of the memory got more detailed. this experiment was repeated again in a double-blind situation, and the results also stated that the participants experienced déjà vu. researchers said that the feeling of déjà vu increased as the part of the hypothalamus closest to the fornix was stimulated. the fornix is a group of fibers that carry signals within the limbic system that is located close to the hypothalamus in the brain. despite this seeming to point to the fornix and hypothalamus’s participation in the process of déjà vu, there is little research surrounding their involvement in the processes behind other “dreamy state” emotions (wiley-blackwell, 2008). additionally, there are several theories surrounding which parts of the brain react to déjà vu stimuli. the main theory is that it takes place in the corticolimbic network. the corticolimbic network’s main functions are motor programming and control, decision making, mnemonic function and emotional regulation. the main parts of the brain assumed to participate in the emotion of déjà vu are hippocampus, rhinal cortices, parahippocampal gyri, and the amygdala. the hippocampus is a part of the limbic system that deals with episodic memory and spatial reasoning and the rhinal cortices also generally work with memory and object recognition. specifically with déjà vu, the feeling that you have experienced something before, the hippocampus and rhinal cortices seem to be crucial. furthermore, the amygdala works with emotions and aggression and the parahippocampal gyri works with memory retrieval and encoding (gillinder et al., 2022). even though it is difficult to place the exact places déjà vu takes place in the brain, these parts of the brain are associated with the “dreamy state” and déjà vu as a result. possible reasons for déjà vu when it comes to déjà vu, scientists have a multitude of theories as to why déjà vu occurs in the brain. one of these theories is the electrical malfunction theory. this theory proposes that déjà vu is a result of mismatched synaptic transmissions. seizures are often caused by many abnormal electrical signals that interrupt the regular transmission of typical electrical signals. however, any differences in connections between nerve cells can cause a seizure in the brain (john hopkins, 2019). patients with epileptic seizures have said that they often experience déjà vu before a seizure; seizures are often caused by dysfunctional neuron activity in the brain. as a result, scientists theorize that déjà vu could be caused by lesser malfunctions in neuronal activity (texas a&m, 2016). a second theory surrounding the occurrence of déjà vu is the neural pathway mismatch. brains are equipped to process a certain amount of sensory information, but there is a lot of information in the world. due to sensory information being classified as short term memory, scientists believe that long term memory is engaged instead, causing the brain to pull information from past memories and experiences (texas a&m, 2016). in the visual cortex, several pieces of information travel through the neuronal pathways, with all of them reaching the destination at the same time. due to the visual cortex processing the current information while the sensory cortex processes past information, there is a “mismatch” in the information between the two cortices, causing the brain to believe that this situation is familiar despite it being new. the third theory is called the “glitch” theory. scientists believe that déjà vu could be caused by the neurons in the brain mistakenly recognizing a stimulus and firing. this causes the brain to confuse the past and present, and for the body to feel déjà vu. this “glitch” is often compared to a hypnagogic jerk (texas a&m, 2016). hypnagogic jerks happen when someone is sleeping and their body involuntary jerks. these two processes are similar in the way that the body is experiencing one thing and the neurons fire for something else (either a different experience or for wakefulness.) the fourth theory is known as the split perception theory. the idea is that the person perceives the same stimulus twice, but in different states of true perception. the first stimulus is perceived when distracted, quickly or in a period of delusion of some sort, and as a result, the input is weaker than most regular stimuli. this stimulus is then perceived again; this time, the stimulus is grasped fully. this second viewing of the stimulus causes our minds to believe that this stimulus is strangely familiar in some way, but not being able to place why as a result of the unregistered original stimulus. this theory helps to explain why our brains would be unable to place why we feel this moment has occurred before (brown & marsh, 2010). however, when it comes to theories of déjà vu, it is incredibly difficult to study and prove any of these methods with our current technology due to the inability to replicate such emotions in a clinical setting. as a result, scientists have turned to other methods in order to gather information on the elusive experience. mental disorders related to déjà vu since déjà vu is challenging to replicate, scientists have turned to other subjects to learn more about the phenomena such as mental disorders. one mental disorder that has been linked to déjà vu is anxiety. in a case study from 2014, a man diagnosed with anxiety and depersonalization who experiences extreme déjà vu was compared. in comparison to other patients who experience déjà vu such as dementia patients, this man was completely aware of his déjà vu happening. figure 1. brain visualization of several different systems in the brain. dorsal stream connects the parietal areas with parahippocampal cortex. the rhinal cortices attaches to anterior hippocampus, and the parahippocampal cortex attaches to posterior hippocampus. coloured dots represent neuronal activity areas in the occipital and parieto-occipital cortex (gillinder et al., 2022). figure 2. the neuron sets off an electrical impulse in order to communicate with one another. seizures are caused by abnormal electrical activity (john hopkins, 2019). brain matters・volume vii 6 he claims he was constantly living in a loop due to his extreme déjà vu, and lived in constant anxiety. while this case study does draw a possible link between déjà vu and anxiety, the only evidence scientists currently have is regarding the location of the neural signals. both anxiety and déjà vu take place in the hippocampal formation, which could show a possible connection via location of signals (wells et al., 2014). however, there has not been enough research for this possible connection to be confirmed. on the other hand, scientists have conducted a test on patients with temporal lobe epilepsy and déjà vu. scientists tested 16 patients with temporal lobe epilepsy and tried to evoke the “dreamy state” by stimulating the hippocampus and amygdala. they did this in different ways: six patients had a collective nine dreamy states as a result of seizures, 14 patients had a collective 43 dreamy states due to electrical stimulation, and three patients had a collective five dreamy states as a result of chemical stimulation. furthermore, the study shows that the amygdala was involved in 73% of stimulation cases, the anterior hippocampus in 83% and the temporal neocortex in 88% (bancaud, brunet-bourgin, chauvel & halgreen, 1994). mental disorders that involve déjà vu as a symptom are incredibly helpful in the study of déjà vu due to the difficulty of stimulating déjà vu, and will continue to aid in the research on déjà vu. summary while déjà vu is generally just described as a feeling of having experienced something before, it is far more than an emotion. déjà vu is a complicated process that scientists do not fully understand the purpose and reason for. along with déjà vu, there are several other similar emotions that are often associated with déjà vu known as the “dreamy state.” while we do not know much about the location of déjà vu, scientists believe that this process takes place in the hippocampus, rhinal cortices, parahippocampal gyri, and the amygdala. there are four major theories as to how déjà vu occurs in the brain: the electrical malfunction theory, the neural pathway mismatch theory, and the “glitch” theory. despite all these theories, it is incredibly difficult to study déjà vu due to the difficulty of stimulating the experience in a lab situation. as science improves, we will get closer and closer to understanding the mechanisms and purpose of déjà vu. references 1. a&m, t. (2016, april 13). what causes déjà vu?. sciencedaily. https://www.sciencedaily.com/releases/2016/04/1604131135 30.htm 2. bancaud, j., halgren, e., chauvel, p., & brunet-bourgin, f. (1994). anatomical origin of déjà vu and vivid “memories” in human temporal lobe epilepsy. national center for biotechnology information. https://pubmed.ncbi.nlm.nih.gov/8149215/ 3. gillinder, l., chauvel, p., & liegeois-chauvel, c. (2022, january 29). what déjà vu and the “dreamy state” tell us about episodic memory networks. sciencedirect. https://www.sciencedirect.com/science/article/abs/pii/s13882 45722001444 4. john hopkins. (2019, november 19). evaluation of a first-time seizure. johns hopkins medicine. https://www.hopkinsmedicine.org/health/conditions-anddiseases/epilepsy/evaluation-of-a-firsttime-seizure 5. khomutov, kolesnikova, mingazova, & bespyatykh. (2023). [personalized approach in the diagnostics and treatment of symptomatic epilepsy with déjà vu seizures]. stork. https://www.storkapp.me/pubpaper/37742269 6. marsh, e. j., & brown, a. s. (2010, may 19). digging into déjà vu: recent research on possible mechanisms. psychology of learning and motivation. https://www.sciencedirect.com/science/article/abs/pii/s00797 42110530020 7. university of leeds. (2006, november 29). a stunning new look at déjà vu. sciencedaily. https://www.sciencedaily.com/releases/2006/11/0611281405 52.htm 8. wells, c. e., moulin, c. j., ethridge, p., illman, n. a., davies, e., &amp; zeman, a. (2014, december 8). persistent psychogenic déjà vu: a case report journal of medical case reports. biomed central. https://jmedicalcasereports.biomedcentral.com/articles/10.11 86/1752-1947-8-414 9. wiley-blackwell. (2008, january 30). deep brain stimulation in hypothalamus triggers “déjà vu” memory recall in patient. sciencedaily. https://www.sciencedaily.com/releases/2008/01/0801300921 02.htm brain matters vol. 8 no. 2 andrew hamilton andrew hamilton is a junior with a major in neuroscience and minors in spanish and chemistry. one thing he enjoys about editing is that he gets to read so many interesting articles about science-related discoveries every day! outside of the club, he pursues research regarding optimization with on-tissue chemical derivatization. michelle bishka michelle bishka is a senior majoring in specialized chemistry and minoring in computer science. outside of brain matters, she is an undergraduate researcher in the silverman lab and a member of american chemical society. she later hopes to pursue graduate studies in chemistry. president brain matters board chief editor vice president 73 praise kim praise kim is the vice president of brain matters and an undergraduate researcher pursuing a bslas in brain and cognitive science. currently, as a research assistant in the gratton lab, she studies the fronto-parietal network in cognitive control tasks across different mental states. in the past, she has also presented work on the infant parasympathetic response and maternal depression with the interdisciplinary lab for social development. she is broadly interested in cognition in the brain and throughout development, also presenting work on social cognitive development at stanford university. outside of research, she lifts weights, reads fantasy novels, and spends time with her church. her future goals are to continue researching the brain—whether as a post-bacc, doctoral student, post-doc, or professor. krisha agarwal krisha agarwal is a junior in mcb honors with a minor in informatics. she is the editor-in-chief of brain matters and a member of american medical women’s association. she is also an undergraduate researcher at the kv prasanth lab in cell and developmental biology. in the future, she hopes to attend graduate school and work in the biotechnology industry. in her free time, krisha enjoys crocheting, reading, sketching, and spending time with friends. macy hoeveler macy hoeveler is a sophomore in the brain & cognitive science program at uiuc. she is pursuing a double minor in integrative biology and music. aside from being the editor-in-chief of brain matters, she is a writing consultant with the writer’s workshop. in addition, she is a beckman fellow with the auditory cognitive neuroscience lab and a lab assistant at the dolezal bee research lab. in her free time, macy is a violinist in the philharmonia orchestra and enjoys reading, listening to music, and collecting bugs. she hopes to continue pursuing biology in graduate school, studying behavioral genetics and neurobiology. vraj patel vraj patel is a sophomore majoring in neuroscience with minors in chemistry and psychology. vraj joined brain matters to learn about more niche topics in neuroscience and research in the field. in addition to being treasurer for brain matters, vraj is an undergraduate researcher in the sweeney lab, which studies neuroscience in the context of feeding and related behaviors. he is also a volunteer for avicenna community health center, a course assistant for stat 200, and a peer mentor for first-year students in the neuroscience major. vraj hopes to explore more in the field of neuroscience from a medical perspective in the future! assistant chief editor assistant chief editor treasurer 74 erin ford erin ford is a junior majoring in chemical engineering with a concentration in biomolecular engineering. in her free time, she enjoys playing tennis and painting. she hopes to help others increase their knowledge about neuroscience through her writing in brain matters. isabelle afshari isabelle is a sophomore at the university of illinois majoring in neuroscience. isabelle became involved in brain matters to learn more about writing scientific articles and innovations in neuroscience. in addition to writing for brain matters, isabelle is involved in mckinley health stress management peers, las leaders, and women’s glee club. in the future, isabelle hopes to attend medical school and continue reading and writing about new scientific innovations! social media chair social media chair social chair vani sharma vani sharma is pursuing a bachelor of science in molecular and cellular biology (mcb) with an honors concentration, alongside a minor in public health and a neuroscience certificate. as a writer for brain matters, she investigates the intricate interplay between the brain and diverse phenomena, including the neural foundations of gratitude, the influence of music on cognitive processes, and the complexities of neuroanatomy and neurological disorders. through her work, she blends rigorous scientific research with engaging narratives to illuminate the brain’s extraordinary intricacies while promoting scientific literacy and making complex concepts accessible to a broader audience. 75 sarah masud sarah is a junior studying psychology and information sciences with a minor in art & design. some of her academic interests include cognition, human-computer interaction, and treating psychiatric disorders. she enjoys drawing, finding new music, and crocheting as well! outside of brain matters, sarah is also involved in design innovation illinois and psi eta mu, a professional information sciences fraternity. she hopes to continue furthering her understanding of neuroscience and exploring topics she’s passionate about through the journal. social chair design head kaitlyn tuvilleja kaitlyn tuvilleja is a junior in bioengineering with a statistics minor. she is an undergraduate research assistant for bhargava lab and i^2 lab. besides brain matters, kaitlyn is involved with swe, wie, and bmes. in her spare time, she enjoys baking and running with her friends. 76 77 copy of volume 6 publication laura is a junior majoring in molecular and cellular biology and is pursuing a minor in food science. she is very excited to showcase the new volume and hopes to expand the journal to new horizons. aside from working on the journal, she is an assistant researcher in the robinson lab, is an mcb leader, an orientation leader, a member of bioscience journal club, and an executive board member of the undergraduate neuroscience society. fiza is a junior majoring in molecular and cellular biology on the pre-med track. in addition to her involvement in the neuroscience journal committee, she has communicated her illinois experience by being a former uiuc admissions blogger and enjoys science through volunteering at a local free clinic and doing research at vet med. she is thrilled to promote a neuroscience dialogue on campus! chief editor assistant chief editor julia gainski is a junior majoring in integrative biology with a minor in german. she is the public relations chair and a writer for brain matters. she is a research assistant at the control & network connectivity team (connectlab) at the beckman institute of advanced science and technology, where she assists with an eeg procedure in a concurrent eeg-fmri study. additionally, she is a personal assistant for students with physical disabilities at beckwith residential support services at nugent hall on campus, the secretary and a mentor of the pre-physician assistant club, and a member of the illini club tennis team. public relations chair brain matters board 43 br ai n m at te rs b oa rd brain matters volume vi br ai n m at te rs b oa rd carolyn is a junior majoring in molecular and cellular biology and is currently conducting research in neurochemistry in dr. jonathan v. sweedler’s lab. outside of academics, she is passionate about illinithon, the university of illinois’ dance marathon program that fundraises for st. john’s children’s hospital in springfield, il. she is excited to collaborate with the other students behind “brain matters” and promote brain awareness on campus. editors rajvi javeri is a junior pursuing a major in psychology with a concentration in behavioral neuroscience and a minor in music. apart from being a part of the undergraduate neuroscience society, she helps out as a research assistant at the cognitive neuroimaging laboratory at the beckman institute. in her free time. she likes to practice guitar and sing. she also loves drinking infused teas and reading books whenever she can. she loves going on treks and any outdoor activities in general and is also a part of the uiuc archery club! 44 hi! my name is sneha mittal and i am the treasurer and an editor for brain matters. i am currently a sophomore majoring in biochemistry on the pre-med track. outside of brain matters, i work as an emt and serve as the advocacy chair for the unicef branch on campus. when i am not working i enjoy spending time with my friends and exploring new things (i plan on going skydiving in a couple of weeks). my name is reilly ruzella and i was an editor on brain matters. i graduated from university of illinois urbana champaign in may 2022 with a double major in molecular & cellular biology and brain & cognitive science, and a certificate in health technology. i am currently pursuing a master's degree in kinesiology, which i will complete in may 2023. in fall 2023, i plan to attend suny college of optometry in new york. brain matters volume vi sarah is a junior majoring in biochemistry and intradisciplinary psychology. in addition to editing for brain matters, sarah works in dr. auinash kalsotra’s biochemistry lab as a research assistant and in dr. kara federmeier’s cognitive neuroscience lab. in the future, sarah hopes to pursue an md-phd in biochemistry to study the mechanisms of neurodegenerative disorders. in her free time, sarah loves to play soccer, go hiking, watch television, and spend time with friends. design board* manan is a junior majoring in brain and cognitive sciences and is pursuing a minor in chemistry. apart from being a pre-dental student, manan has previously been an orientation leader at uiuc. last summer, manan worked with people of determination and designed thinking modules for underprivileged students in india. outside of class, manan is deeply interested in reading books that pertain to cognitive psychology and productivity, engaging in insightful scientific dialogue and community service. he looks forward to making brain matters an inclusive and engaging scientific committee on campus katy simmons is an mcb major pursuing a certificate in neuroscience! her interests include cellular neuroscience and neuroimmunology. she is involved in brain matters as a design team member, editor, and writer. her favorite thing about being a part of the journal is meeting and engaging with others that are passionate about neuroscience. apart from her role in brain matters, she is a research assistant in the evolution of intelligent systems lab, as well as the evolutionary immunology and genomics laboratory. after undergrad, she plans to attend grad school to conduct her own research in cellular neuroscience! *due to publishing delays, volume vii was designed by the design board from the 2022-2023 academic year michelle is a sophomore pursuing a major in chemistry and a minor in computer science. aside from being a part of the journal, michelle is currently working in the silverman lab as an undergraduate researcher. she is excited to explore the field of neuroscience by writing for brain matters. 45 br ai n m at te rs b oa rd brain matters volume vi volume 8 (will be vol 7 on site) mesenchymal stem cell regenerative therapy in the spine recent advancements and possible applications: a review harrison kennedy abstract a spinal cord injury (sci) is an injury which damages the central nervous system, particularly the neurons and structures located in the spine. treatment options involving mesenchymal stem cells (mscs) have recently been recognized as possible repair solutions to an sci. mscs have multifaceted functionality which allows for a wide range of applications; and, specifically for usage in the spine, mscs do not contain immunogenic response agents, which makes them suitable for treatment involving the central nervous system. clinical usage of mscs has been proven successful in other facets of medicine, but the exact mechanisms by which they repair scis is not fully understood (xia et al., 2023). recent research, however, suggests msc involvement in reducing neuronal inflammation, regenerating axons, and repairing spinal blood vessels (staff, 2022). these new findings anticipate future advancements in the usage of mscs conjunctively with neurorehabilitation therapies (xia et al., 2023). further speculations could even involve treatment for reversing paralysis, inhibiting glial scarring, and reducing neurological symptoms of scis all within the spine. introduction as strides in medical advancements occur across the frontier between health and illness, one area continues to elude reliable treatment: the nervous system. particularly concerning substantial injuries to the spinal cord, modes by which to reverse and heal damage are currently underdeveloped. one possible solution to this “last frontier” of medicine is regenerative spinal cord injury (sci) therapy using mesenchymal stem cells (mscs). this novel development is currently the focus of a multitude of reviews, trials, and examinations; its efficacy in treatment is being revealed as having great promise. this is a relevant issue considering that treating the nervous system is considered to be one of the final areas of medicine for humans to conquer. additionally, scis are life-altering injuries, often disabling those who sustain them. in the united states alone, “there were 17,810 new sci cases reported in 2020, with a total of 294,000 americans living with sci,” a number that could significantly decrease with msc therapy (ma et al., 2022). mscs have shown efficacy in aiding in the regeneration of neuronal tissue in many clinical trials and have evidence backing their properties that allow for them to be a prime candidate for sci treatment. such properties include “neuroprotection, immunomodulation, axon sprouting and/or regeneration, neuronal relay formation, and myelin regeneration, among other mechanisms,” which reinforce the assertion that msc therapy is among the best approaches for treating the complex pathophysiology of scis (shang et al., 2022). furthermore, the use of msc therapy in conjunction with other neurodegenerative-focused therapies is being explored due to the multimodal facets of an sci and their complex pathological conditions. timing and the im mune system mesenchymal stem cells (mscs) are cells harvested from various tissues and contain the ability to proliferate into different types of specialized cells, including neurons. in the realm of the nervous tissue within the spine, mscs have the distinct ability of aiding in overall regeneration thanks to their high proliferation abilities. this is fostered by their ability to release chemical factors that can influence cell interactions within the spinal cord, which is a useful tool in treating scis. among cytokines and exosomes with antiinflammatory abilities, mscs also release “vascular endothelial growth factor (vegf), nerve growth factor (ngf), glia-derived neurotrophic factor (gdnf), and brain-derived neurotrophic factor (bdnf)”, which not only allow for expedited nerve cell regeneration but also work to eliminate the effects of glial scarring, a major motor-inhibiting issue following sci which can result in inflammation that stifles neuronal repairing and formation (xia et al., 2023). additionally, in major scis, the upregulation of endogenous neurotrophic factors often is not significant enough to produce meaningful regeneration or recovery in the traumaaffected areas. the need for an exogenous neurotrophic factor explains the effectiveness of gdnf and bdnf administered externally through msc therapy. another important factor, vegf, works in a different way to repair neuronal tissue through its vascularity; as an angiogenic factor, it promotes pericyte recruitment, which allows vascular tissues to mature and regenerate. within the central nervous system (cns), neurons and blood vessels work in units considered neurovascular units. these units allow vegf to promote neuronal regeneration by enhancing the nutrient flow (pan et al., 2013). furthermore, vegf mediates “vascular endothelial cell proliferation and migration, angiogenesis, and vascular permeability and leakage,” enhancing the function of neuronal vascularity while appropriating the beneficial capacities of vascular components (pan et al., 2013). within the nervous system, vascular health is crucial due to the importance of blood supply for neuronal function and repairing sequences. other growth factors such as ngf aid in the survival retention of neurons by enabling increased axonic regeneration. brain matters・volume vii 26 ngf overproduction has been shown to improve functional recovery in a mouse model when administered following a sci (wang et al., 2021). after chemically modifying neural stem cells (nscs) to overproduce ngf following a sci, researchers found the motor functions of the affected limbs were generally improved, and, at the site of the trauma, the affected cells did not retain extreme pathological states over a prolonged timeline. this can be observed in figure 1, which displays data showing the regenerative properties of ngfmodified nscs. the introduction of ngfs appears to have shrunk the affected area of an sci lesion and improved the motor function of the hindlimbs. this reinforces the assertion that ngf can regulate the neuronal environment and increase endogenous responses from certain neurons such as nscs (wang et al., 2021). exogenous factors of the same chemical makeup have similar effects in regulating microenvironments and increasing regenerative ability. gdnf and bdnf are often linked with “β iii tubulin, enolase 2, and microtubule associated protein 1b” (xia et al., 2023). these neuromarkers have been shown to encourage microtubule health, axon regeneration, appropriate neuronal aging, and overall maintenance of synaptic areas. high level dosages of bdnf may also improve motor function, help maintain the recovering blood spinal cord barrier after scis, and improve neuronal regeneration (muheremu et al., 2021). sequentially, when gdnf is introduced to the sci site, nerve cell density and motor function can increase. these neurotrophic factors, when paired with “recombinant proteins such as osmotic pumps, nanoparticles, viral vectors, as well as polymer scaffolds,” can encourage the regeneration of the sci-affected area of the spine by providing it with ample neurotrophic support (muheremu et al., 2021). these various factors secreted by mscs within the microenvironments of the neural tissue in the spinal cord chemically support regenerative capabilities and are therapeutic in the case of scis. each factor in combination can change the effects of a sci and be applied to regenerative therapies in humans. and, when paired with other therapeutic methods of interneural intervention, their positive effects can be amplified. clinical applications and recent advancements when an sci occurs, endogenous repair is induced and cells, such as schwann, myelinating, and regenerative cells, migrate to the trauma site to repair damaged tissue. there are positive benefits to this process, but the main problem stemming from endogenous repair is that axon growth is inhibited, and glial scarring often occurs due to oligodendrocyte myelin debris from the trauma (nandoe tewarie et al., 2009). logistically, the introduction of mscs to treat scis and combat the negative endogenous effects appears legitimate, but the methodology behind achieving similar results to the expected outcome in clinical trials is actually much more complicated. there are multiple factors to address regarding the introduction and transplantation of mscs to an area of trauma including “mode of transplantation, dose and frequency of mscs, timing of sci, and type of sci,” which complicate the process of clinical research and require further studies to apply mscs to sci treatment effectively(xia et al., 2023). this is due to the diversity in proliferation and differentiation that mscs contain, as illustrated by figure 2. with the exponential number of possibilities that mscs contain, the implicating factors, such as the mode and timing of transplantation, complicate this even further. the standard mode of transplantation is a local injection within the site of a sci, but msc transplant injections into the subarachnoid space and intravenously are also common in clinical trials (xia et al., 2023). figure 1. ngf-modified nscs figures a-c highlight the benefits of ngf-modified neural stem cells (nscs) on “functional recovery of hindlimbs and alleviated histopathological damage after sci” by analyzing the angular and quantitative improvements. figure d shows the area of injured tissue 4 weeks after initial injury, circled by red dotted lines. this shows the minimized histopathological damage contained within the epicenter of the lesion when utilizing ngf-nscs. after transplantation, rats with significant scis regained improved function of hindlimbs once they received treatment from ngfnscs. figure 2. properties of mscs a figure illustrating the multifaceted properties of mscs, showing their ability to target various pathological conditions within a sci (ma et al., 2022). this emphasizes the proliferation abilities of mscs to differentiate and offer support to various aspects of the neuronal and spinal tissues. each image stemming off the initial stem cell source represents a unique use that they can serve within the human body. clinically these assertions have shown merit as well. in a clinical trial involving patients with advanced scis, yannan zhao et al. found that biomaterial scaffolding paired with mscs regenerated motor function of spinal cord transmission through the peripheral nervous system (pns) (blando et al., 2022). one patient, with a major thoracic sci eventually regained the ability to walk after experiencing msc scaffolding therapy, and another regained lower body control after losing it to a major cervical sci. by using electrophysiology, researchers were able to determine that following treatment, the patients were able to conduct electrical transmission through the spinal cord more effectively than when paralysis was sustained. another mode by which to influence the effectiveness of mscs in treating scis is through pre-injection gene modification. after genetically modifying rat mscs to express mnts1, “a multineurotrophin that binds trka, trkb and trkc, and p75(ntr) receptors or msc-mnts1/p75(-) that binds mainly to the trk receptors,” gentaro kumagai et al. injected the genetically modified mscs to the central affected area of a contusive sci (kumagai et al., 2013). this resulted in promotion of angiogenesis, enhanced axonal growth, reduced inflammation and glial scarring, and various other positive factors after regenerative sci therapy (kumagai et al., 2013). additionally, mscs genetically modified to release growth-factor-1, an insulin-like factor, exhibit better survival and capacity to improve myelination (xia et al., 2023). as found by yuan-haun ma et al., the use of genetic modifications and tissue engineering like biomaterial scaffolding, produced greater functionality and motor rehabilitation in animal spine models (xia et al., 2023). additionally, related to the secretions of mscs that give them regenerative properties, three-dimensional scaffolding and tissue engineering can increase the expression of specialized neurotrophic factors like bdnf and gdnf, which expedite the idea of enhancing mscs through additive therapy and procedures is also being explored clinically. methods such as pre-conditioning, three-dimensional cultures, genetic modifications, and pairing with neurorehabilitation show promise in enhancing capabilities of mscs (ma et al., 2022). one example of pre-conditioning, ifn-γ pretreatment, has been observed to aid in the release of chemical factors that give mscs their immunosuppressive and immunomodulatory abilities (ma et al., 2022). this is an important aspect within the spinal cord due to immunogenic complications common in the neural system, like glial scarring and microglia activity, as immunogens retroactively damage the neural tissue following an sci. alterations with oxygen levels of mscs, such as hypoxic treatment followed by reoxygenation, seem to improve proliferative abilities and migratory actions of mscs, allowing them to regenerate numbers and relocate to affected areas. additionally, similar preliminary oxygen treatments have proved to enhance survival rates of mscs, a common downfall when examining prolonged timelines and chronic scis. it is believed that within the spine, these benefits are due to an “up-regulation of cytokines,” like vegf, which promote neuronal regeneration among other therapeutic effects (ma et al., 2022). similarly, using certain types of tissue engineering, the proliferation and survival of mscs can be altered; one mode by which to achieve this is biomaterialistic scaffolding. biomaterials within scaffolding can aid in cell survival, intercellular interactions, proliferation, and protection (blando et al., 2022). by using certain gels, as well as synthetic and biological materials, the microenvironments in which mscs are comfortable reproducing and releasing chemical factors in can be replicated (xia et al., 2023). these “neurotrophic factor codelivery” assisters can increase production of cytokines, promoting the regeneration of targeted areas of the spinal cord (xia et al., 2023). biomaterial scaffolds, such as “block copolymer of plga and poly-l-lysine (pll) with a highly interconnected porous structure (approximately 250–500-μmdiameter pores),” when paired with msc therapy, have clinically been proven to regenerate nerve tissue in rat models with scis as well as restore motor function (ashammakhi et al., 2019). additionally, figure 3 shows the wide range of scaffolding methods available, and what benefits might come with each. the combinations of what materials to use and how to assemble them are numerous. this offers a view on how beneficial this method could be and how adaptable the possibilities are to address many distinct types of scis and lesions. a large factor in the dangers of spinal cord lesions and trauma is the loss of cells in the affected area and the following necrosis of tissue. this environment makes it hard to encourage cell-proliferation, and neuronal microenvironments of cell necrosis-affected tissues do not make suitable areas to introduce new cells. so, scaffolding mscs with biomaterial can promote proliferation and tissue regeneration whilst inhibiting glial scarring and inflammation (blando et al., 2022). the creation of a habitable extracellular matrix (ecm) can support “regenerative environment, differentiation, and trophic support” in the form of releasing factors that can regenerate tissues (blando et al., 2022). figure 3. msc scaffolding a figure displaying the ways by which scaffolds could be used to enhance the functionality of mscs and allow for positive implications (ashammakhi et al., 2019). additionally, it illustrates the ways other therapy options like gene or controlled drug delivery can be utilized to enhance these effects. the three images following the arrows below the scaffolds figure in the middle represent implementations of scaffolding. the two images above the middle image represent the materials (both synthetic and natural) used in scaffolding. brain matters・volume vii 28 additionally, zhinzhong et al. found that side effects such as “neuropathic pain, abnormal feeling, muscle spasms, vomiting, and urinary tract infection were (the most) common, with an incidence of > 20%.” the likelihood and inexplicable nature of these side effects are most concerning (shang et al., 2022). this demonstrates the premature excitement regarding msc transplantation therapy, as there is still so much more to address and understand, especially regarding the effectiveness and risks. currently, the main problem in analyzing contemporary data is its scarcity. this highlights the importance of promoting research; with time, sufficient data will become available to make accurate conclusions without doubts. overall, these current clinical applications make integration of mscs in the cases of scis, more realistic and feasible when regenerating tissue and restoring function. however, the exact mechanisms are not fully understood. additionally, while the clinical data sounds promising, it is still debatable whether certain data is conclusive due to controversial methods or studies that take novel approaches. furthermore, certain risks should not be ignored concerning msc therapy. serious effects have been observed in patients, like a “large tumor-like mass inside the spinal cord after 8 years of olfactory mucosa cell transplantation,” due to the msc therapy the patient was receiving (lukomska et al., 2019). moreover, in neurological applications of mscs, there have been even further negative side-effects observed. after injection, unintended symptoms consisting of fevers, headaches, and pain were common, while definitive positive results were quite rare (lukomska et al., 2019). adversities and current limiting factors while the attractiveness of mesenchymal stem cell therapy, specifically in neural systems, has led to many valuable studies, there seems to be an overstatement regarding the actual applicability and current understanding of msc therapy. as a novel topic, there has been a recent influx in interest regarding msc therapy in combating scis, but the conclusions made are not in support with each other. there also seems to be a degree of confirmation bias in the current state of public opinion. with the recent increase of interest in stem cell therapies, many phase i studies, reports, and reviews have been published; however, significant clinical data is yet to be attained. a large-scale meta-analysis focused on adverse events (aes) or negative side effects of a msc treatment of a sci. zhizhong shang et al. discovered that clinical trials and research have produced approximately 28 possible aes (shang et al., 2022). additionally, it was also found that the development of viable sci treatment using stem cells is still in the early, infantile, stages. not only do the ideal parameters for injection and treatment need to be established, but the exogenous effects of msc introduction to a site of trauma also need to be better understood. better clinical trials, research on large mammals, and early-stage human trials need to be further studied for the advancement of the stem cell field. currently, knowledge is limited on both the interactions between neuronal tissue and mscs as well as the optimal operations on a sci trauma site. nerve cell axonal regeneration and minimize the effects of glial scarring. furthermore, neurorehabilitation can be paired with these modes by which to transplant mscs to enhance their regenerative capabilities. studies have shown that physical and mental activities such as “treadmill training, electrical stimulation, electroacupuncture, transcranial magnetic stimulation (tms), ultrashort wave therapy, and swimming training,” enhance the effects of msc transplant therapy after a sci (xia et al., 2023). the hypothesis that cns controls aspects of the pns can promote rehabilitation within the neural tissue of the spine that controls muscle motor activity. another important aspect of understanding the importance of the mode by which to transplant mscs is the form of injection. the most used is intravenous (iv), intrathecal (it), and intralesional (il) injections, each with their own benefits and drawbacks (xia et al., 2023). while il injections have been observed to be effective in locating mscs to the site of the initial sci trauma, it is normally an intricate procedure with a lot of room for error, especially when dealing with already damaged cell tissue. the risks of further damage or contamination of spinal tissue outweigh the efficacy of an il injection of mscs, pushing for the exploration of other injection modes. it and iv injections are not only less invasive but also easier operations to perform. furthermore, it injections are generally more effective “in terms of cell engraftment and safety” (17). additionally, it has been established that it injections can be a noninvasive and safe therapy when trying to improve neuronal functioning and motor capabilities in humans, including the general rehabilitation of spinal cord tissue (bydon et al., 2019). according to mohamad bydon et al., it injections improved both objective and subjective measures of recovery in patients, as established in a human clinical trial involving 14 patients suffering from scis (bydon et al., 2019). with each msc transplantation method having different benefits and drawbacks, there is no end-all, best method. each method can be utilized in many ways, and through clinical research, the consensus is in favor of the idea that in cases of scis, it is more advantageous to utilize multiple different injection methods to transplant mscs. clinical applications and recent advancements while there are plentiful examples of clinical studies, not many are standardized or contain large enough sample sizes to draw supported conclusions. one study, however, unified a large quantity of results regarding msc therapy in scis into a single meta-analysis using data from 62 clinical trials. to address “how much scientific evidence there is to support the sufficiency of stem cell therapy in preclinical and clinical studies of scis”, zhinzhong shang et al. analyzed 62 clinical trials involving 2,439 patients (shang et al., 2022). after extracting data, it was observed that in 48.9% of patients receiving msc therapy, their american spinal injury association (asia) impairment scale score, a neurological assessment that takes sensory and motor ability of the spinal cord into account, improved by at least one grade. there are mechanisms by which mscs work that are not understood due to the discrepancy between expected success and actual success of the treatment. https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02482-2#auth-zhizhong-shang-aff1 surrounding msc therapy and applications within the nervous system of the spine. while there are obviously possibilities in the future, at the current state of research and clinical trials, the effectiveness of msc therapy is questionable at best. there are still many factors that need to be addressed as progress is made, such as standardizing methods, developing lower-risk results, and exploring the mechanism of msc therapy. with a better understanding of these intricate modes by which mscs work to regenerate neurons and enhance the microenvironments within tissues following a sci, future trials in humans could be seen as safer and more realistic. references 1. ashammakhi, n., kim, h.-j., ehsanipour, a., bierman, r., kaarela, o., & xue, c. (2019, december 16). regenerative therapies for spinal cord injury. https://www.liebertpub.com/doi/10.1089/ten.teb.2019.0182 2. blando, s., anchesi, i., mazzon, e., & gugliandolo, a. (2022, july 7). can a scaffold enriched with mesenchymal stem cells be a good treatment for spinal cord injury? ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9319719/ 3. bydon, m., dietz, a., goncalves, s., terzic, a., windebank, a., & qu, w. (2019, november 27). celltop clinical trial: first report from a phase 1 trial of autologous adipose tissue–derived mesenchymal stem cells in the treatment of paralysis due to traumatic spinal cord injury. mayo clinic. https://www.mayoclinicproceedings.org/article/s00256196(19)30871-7/fulltext 4. kumagai, g., tsoulfas, p., toh, s., mcniece, i., bramlett, h., & dietrich, d. (2013, july 22). genetically modified mesenchymal stem cells (mscs) promote axonal regeneration and prevent hypersensitivity after spinal cord injury. experimental neurology. https://pubmed.ncbi.nlm.nih.gov/23856436/ 5. lukomska, b., stanaszek, l., zuba-surma, e., legosz, p., sarzynska, s., & drela, k. (2019, april 9). challenges and controversies in human mesenchymal stem cell therapy. stem cells international. https://www.hindawi.com/journals/sci/2019/9628536/ 6. ma, y.-h., liang, q.-y., ding, y., han, i., & zeng, x. (2022, september 30). multimodal repair of spinal cord injury with mesenchymal stem cells. neurospine. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9537826/#:~:t ext=mscs%20can%20also%20secrete%20laminin,therapeu tic%20efficacy%20by%20secreting%20exosomes 7. mansoori, n., bansil, r., & sinha, s. (2016, february 24). current status of spinal cord regenerative therapies: a review. indian journal of neurosurgery. https://www.thiemeconnect.de/products/ejournals/abstract/10.1055/s-00361572379 8. muheremu, a., shu, l., aili, a., & jiang, k. (2021, january 1). sustained delivery of neurotrophic factors to treat spinal cord injury. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8633588/ in addition, clinical trials are not closely regulated. therefore, more research on mscs and their functions is needed for the current interest and excitement surrounding this topic to be justifiable and within reason. ethical concerns of stem cell therapy while the ethics of using mscs, cells often derived from tissues like adipose, bone marrow, or other general tissue groups, is not disputed, there have been concerns raised in the scientific community surrounding stem cell research and its morality. this conversation is often centered around the idea of scientific misuse of stem cells, immoral genetic manipulation, and human cloning. an example of scientific misuse of stem cells can be seen with rishi s. nandoe tewarie et al.’s research done in the field of human asexual or same-sex reproduction through the use of oocytes proliferated from male stem cells, which can enable one male or two males to produce a human embryo (nandoe tewarie et al., 2009). while this is entirely possible and within the realms of scientific reason, it has been debated whether this would be an ethical action. there is no way of knowing the detrimental effects this could have on a child due to the pairing of strictly male dna. this leap, while scientifically relevant, would be concerning ethically and could eventually lead to the degradation of human moral laws. additionally, cloning human cells follows the same line of reasoning: while scientifically possible, it is still ethically questionable. many believe that there needs to be a line drawn in how deeply science interferes with natural human development and evolution over time. the implications of cloning open doors that generate additional issues. another ethical concern regarding stem cell research is genetic modification and human germline engineering. by utilizing stem cells to produce artificial gametes, the expression of certain genes can possibly be altered, thus allowing human intervention within the genomic sequence of embryos (nandoe tewarie et al., 2009). this is ethically concerning because it would essentially enable humans to design the type of child they wish to bear, eliminate all genetically expressed diseases, and change the physical appearance of their future child. this is concerning on various levels and would lead to the dissolution of countless social, economic, and cultural values. conclusion as a novel method of approaching sci regenerative therapy, msc transplantation is a promising and exciting solution. not only are the factors secreted by mscs beneficial for neuronal repair and regrowth, but their effectiveness is amplified when paired with other enhancing. multiple studies and clinical trials have shown that the factors secreted by mscs can enable tissue repair and neuronal regeneration in the spine. however, msc therapy can also come with concerning side effects. the promise of msc therapy is offset by its inconsistency, risks, and ineffectiveness in current clinical trials. it is hard to find substantial and valid research supporting large-scale msc transplantation in the human spine that does not include many failures and low successrates. this puts into check the current excitement brain matters・volume vii 30 https://pubmed.ncbi.nlm.nih.gov/?term=tewarie%20rs%5bauthor%5d https://pubmed.ncbi.nlm.nih.gov/?term=tewarie%20rs%5bauthor%5d 9. nandoe tewarie, r. s., hurtado, a., bartels, r. h., grotenhuis, a., & oudega, m. (2009, april). stem cell-based therapies for spinal cord injury. the journal of spinal cord medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2678281/ 10. newson, a. j., & smajdor, a. c. (2005, march). artificial gametes: new paths to parenthood?. journal of medical ethics. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc1734101/ 11. pan, z., fukuoka, s., karagianni, n., guaiquil, v. h., & rosenblatt, m. i. (2013, july). vascular endothelial growth factor promotes anatomical and functional recovery of injured peripheral nerves in the avascular cornea. faseb journal : official publication of the federation of american societies for experimental biology. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3688738/#:~:t ext=thus%2c%20vegf%20can%20mediate%20peripheral, may%20modulate%20physiological%20nerve%20repair 12. shang, z., wang, m., zhang, b., wang, x., & wanyan, p. (2022, september 5). clinical translation of stem cell therapy for spinal cord injury still premature: results from a singlearm meta-analysis based on 62 clinical trials bmc medicine. biomed central. https://bmcmedicine.biomedcentral.com/articles/10.1186/s12 916-022-024822#:~:text=studies%20have%20shown%20that%20stem,mec hanisms%20%5b4%2c%207%5d 13. soufi, k., castillo, j., rodriguez, f., demesa, c., & ebinu, j. (2023, may 17). potential role for stem cell regenerative therapy as a treatment for degenerative disc disease and low back pain: a systematic review. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10219191/ staff, m. c. (2022, march 19). answers to your questions about stem cell research. mayo clinic. https://www.mayoclinic.org/tests-procedures/bone-marrowtransplant/in-depth/stem-cells/art-20048117 14. takami, t., shimokawa, n., parthiban, j., zileli, m., & ali, s. (2020, december). pharmacologic and regenerative cell therapy for spinal cord injury: wfns spine committee recommendations. neurospine. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7788403/ 15. wang, l., gu, s., gan, j., tian, y., zhang, f., zhao, h., & lei, d. (2021, november 15). neural stem cells overexpressing nerve growth factor improve functional recovery in rats following spinal cord injury via modulating microenvironment and enhancing endogenous neurogenesis. frontiers. https://www.frontiersin.org/articles/10.3389/fncel.2021.77337 5/full 16. xia, y., zhu, j., yang, r., wang, h., & fu, c. (2023, february 13). mesenchymal stem cells in the treatment of spinal cord injury: mechanisms, current advances and future challenges. frontiers. https://www.frontiersin.org/articles/10.3389/fimmu.2023.1141 601/full volume 8 (will be vol 7 on site) with regulating emotions, extensive connections exist between the amygdala and the prefrontal cortex (pfc), the brain region that regulates executive functions such as planning, judgment, and behaviors. the amygdala sends emotional information to the pfc to process the information and respond accordingly. the medial prefrontal cortex (mpfc) in particular plays a role in emotion regulation, including swearing. it focuses on judging appropriate social behavior, including inhibiting the use of obscene language. however, in the case of automatic swearing, the mpfc does not perform at its highest capabilities, and “the performance of the inhibitory guards deteriorates and the automatic swearing wins over” (finkelstein, 2018). thus, while the prefrontal cortex typically regulates speech for an appropriate response, this control is lessened in instances of automatic swearing, and our deep, emotional responses manifest verbally. the right hemisphere and swearing broca’s area, the region of the frontal cortex focused on language production, exists in the left hemisphere of the brain for most individuals. however, cases have occurred where damage to the left hemisphere leads to the inability to talk, but the ability to swear remains intact. these situations lead to the idea that the right hemisphere plays a prominent role in the production of automatic speech, including swearing. the differences in the right and left hemispheres extend to the basal ganglia, where its right portion enables swearing. studies where the right basal ganglia was removed demonstrated the absence of automatic speech (finkelstein, 2018). the right hemisphere has been studied as a path for unconscious emotional processing. behavioral studies, brain imaging, and studies focused on brain pathologies have found that the right hemisphere activates during situations involving automatic emotional responses, specifically subcortical regions such as the right amygdala and thalamus, and visual areas such as the superior colliculus and pulvinar swearing and the brain: a cultural and emotional experience vraj patel abstract swearing stems from functions involved in the brain, specifically automatic and emotional swearing. the process excludes regions involved in conscious thought, like the prefrontal cortex and language processing centers, typically active in deliberate speech. it is important to note that this exclusion does not imply that these language areas are completely uninvolved; rather, automatic swearing relies more heavily on emotional circuitry such as the amygdala and basal ganglia. research has focused on exploring the right hemisphere and its involvement with the automatic processing of emotional information, which is crucial in spontaneous swearing. evidence and imaging tests from cases including damage to the left hemisphere point to significant activity in the right hemisphere during instances of automatic swearing. additionally, the concept of swearing also involves the idea of “taboo,” and the brain responds to expletives in a manner similar to when responding to threats to safety, indicating a deep-rooted emotional and survival mechanism at play. introduction swears are everywhere. expletive words are prominent in everyday discussions and environments, including family gatherings, schools, campuses, workplaces, and social settings. given this extensive exposure, an intriguing question arises: how do these spontaneous expressions relate to the brain’s wiring? according to stapleton, a prominent researcher at ulster university, “swearing” refers to the act of using words and phrases that stem from a negative emotional reaction and can produce an equivalent reaction in the listeners. swear words are also categorized within a language as “taboo” words, leading the listener to experience increased physical and emotional reactivity towards them when used (byrne, 2019; stapleton et al., 2022). due to the prevalence of expletives in language, the act of swearing can result from two different origins: a consciously decided path and an automatic, involuntary path (stapleton et al., 2022). these separate pathways suggest that intentional or spontaneous swearing engages complex brain networks, contributing to a multifaceted output. adding to the complexity, the use of swear words then incorporates a neural process from multiple pathways, including language and speech production, somatosensory processes, and the limbic system for emotional responses (finkelstein, 2018). the emotional pathways related to automatic swearing are the focus of this discussion. the emotional pathway of swearing though swearing leaves the mouth in the form of speech and language, the neural process of swearing is highly connected to emotional pathways. swearing activates parts of the limbic system such as the basal ganglia and amygdala, which respectively process memory and emotions. based on studies done with individuals with aphasia – disorders concerning limited capabilities of language processes – their ability to swear does not lessen, suggesting that reflexive and spontaneous swearing originates from regions in the brain unrelated to the language processing centers (stapleton et al., 2022). brain matters・volume vii 60 (gainotti, 2012). automatic swearing as a response to stimuli is an example of such an unconscious emotional response, following the same right hemispheric activation as explored by gainotti. the taboo of swearing the brain activates not only when one swears, but also when one hears swearing. the “taboo” aspect of swearing is connected to the limbic system. jeffrey bowers and christopher pleydell-pearce explored the link in their experiment which studied the idea that “the phonological form of a word can directly evoke a negative emotional response” (bowers and pleydell-pearce, 2011). the researchers conducted an experiment where participants were exposed to swear words and “neutral” words, and their physical responses were recorded. neutral words included terms not categorized as “taboo” in a language, such as “glue” and “drum.” the participants read aloud words that appeared on a screen, including swear words, euphemisms referring to certain swears (i.e. “f-word”), and neutral words. the researchers recorded the participants’ skin conductance levels while they read out the words, a measure of activation of the sympathetic nervous system. the results showed a drastic increase in skin conductance when swear words appeared on the screen compared to euphemisms and neutral words. the researchers concluded that “people find it more stressful to say aloud a swear word than its corresponding euphemism” (bowers and pleydell-pearce, 2011). the physical responses when hearing expletives are similar to when a threat is perceived, activating the sympathetic nervous system – “increased heart rate, sweating, faster breathing” (stapleton et al., 2022) – and reinforcing the taboo aspect of swearing. conclusion the brain’s functions involved with swearing highlight the complexity of its abilities. whether the expletives originate internally or externally, the brain activates the emotional pathways when responding, limiting conscious speech typically in control via the medial prefrontal cortex. the right hemisphere of the brain in particular demonstrates high activity during emotional responses and continues the production of swears independent from the left hemisphere. this lateralization reveals the necessity of both hemispheres to allow for proper human behavior in response to one’s environment. future research may explore specific features of the right hemisphere that connect it to automatic emotional responses and details on why the right and left hemispheres are lateralized in terms of conscious versus emotional response. references 1. bowers, j.s., & pleydell-pearce, c.w. (2011). swearing, euphemisms, and linguistic relativity. plos one, 6(7), e22341. https://doi.org/10.1371/journal.pone.0022341 byrne, e. (2019). swearing is good for you: the amazing science of bad language. w.w. norton. 2. finkelstein, s.r. (2018). swearing and the brain. in k. allan (ed.), the oxford handbook of taboo words and language (pp. 108-139). oxford university press. https://doi.org/10.1093/oxfordhb/9780198808190.013.7 3. gainotti, g. (2012). unconscious processing of emotions and the right hemisphere. neuropsychologia, 50(2), 205-218. https://doi.org/10.1016/j.neuropsychologia.2011.12.005 4. mackay, d.g., shafto, m., taylor, j.k., marian, d.e., abrams, l., & dyer, j.r. (2004). relations between emotion, memory, and attention: evidence from taboo stroop, lexical decision, and immediate memory tasks. memory & cognition, 32, 474-488. https://doi.org/10.3758/bf03195840 5. smithsonian magazine. (2018, january 30). the science of swearing. smithsonian magazine. https://www.smithsonianmag.com/science-nature/scienceswearing-180967874/ 6. stapleton, k., fägersten, k.b., stephens, r., loveday, c. (2022). the power of swearing: what we know and what we don’t. lingua, 277, 103406. https://doi.org/10.1016/j.lingua.2022.103406 7. stephens, r., & umland, c. (2011). swearing as a response to pain-effect of daily swearing frequency. journal of pain, 12(12), 1274–1281. https://doiorg.proxy2.library.illinois.edu/10.1016/j.jpain.2011.09.004 8. wood, c. (2019, july 10). your cursing cortex. brainfacts. https://www.brainfacts.org/thinking-sensing-andbehaving/language/2019/your-cursing-cortex-071019 fig. 1. skin conductance (μs) as a variable of time (seconds) following stimulus onset. stimuli: swear words, neutral words, swear word euphemism, neutral word euphemism (bowers and pleydellpearce, 2011). volume 8 (will be vol 7 on site) what is gbm? gbm is a type of glioma. gliomas originate from genetic mutations in glial cells, which provide physical and chemical support for neurons (nord, n.d.). according to the world health organization, gliomas are divided into grades i-iv, depending on the degree of malignancy. grade i gliomas are typically benign and slow-growing, often associated with mutations in the neurofibromin i (nf i) gene, responsible for growth regulation (roswell park comprehensive cancer center, n.d.). grade ii and grade iii gliomas, characterized by rapid growth, most often arise from mutations in the tp53 gene. this gene is responsible for the production of a tumor suppressor protein. grades ii and iii are rare in children, but commonly manifest in young adults. grade iv gliomas are gbm, and are the most common and malignant (roswell park comprehensive cancer center, n.d.). gbm is commonly seen in patients over 50 years of age. however, there is growing evidence that gbm can also develop in children, adolescents, and young adults. tumors found in younger individuals, though, are genetically unique from those found in older adults (mdpi, n.d.). gbm, in particular, develops from astrocytes (fig. 1). glioblastoma multiforme: challenges and advancements in treatment casey meskovich abstract glioblastoma multiforme (gbm) is a tumor that is initiated in glial cells, usually astrocytes. gbm presents difficulties in treatment due to the delocalization of tumor cells, inherent resistance to most cancer drugs, and the limited capacity of the brain to repair itself. although most cancers have demonstrated an increase in treatment efficacy associated with recent technologies, the recovery rate of gbm has remained stagnant over the years. recent research, focusing on the immune response of the brain, has sparked hope for better treatments. this paper discusses why previous treatments have been ineffective and describes the recent advancements in treatment. introduction one afternoon in september of 2018, henry leonard’s office hummed with the clacking of computer keys and quiet chatter between coworkers–and, henry’s snoring. he had been asleep at his desk for approximately fifteen minutes before a concerned colleague shook him awake. taking a sip of his coffee, henry dismissed his lethargy as a symptom of aging; he had always been healthy and didn’t see any other explanation. he squinted at his computer, unsure of what he’d been working on before falling asleep, and sighed. it was open to an extensively chaotic weekly calendar. typically, henry took pride in being well-organized, but had recently found himself struggling to keep track of projects. a dull ache throbbed in his temples as henry considered the work he had to finish that day. preferring to avoid medication when possible, henry ignored the pain. as the day progressed, his headache developed into nauseating pain. for the first time in fifteen years, henry swallowed an aspirin tablet. the day trudged on, and henry was happy to go home. later that night, he called a close friend to discuss his overtiredness, but was met with anger rather than sympathy. henry was shocked to learn that he had spoken to his friend the day before, and had been aggressive and barely lucid. he had no recollection of this conversation, and apologized profusely. later that month, henry was diagnosed with glioblastoma multiforme, an advanced form of brain cancer. in hindsight, these were his first symptoms–disorganization, headaches, memory loss, and inexplicable aggression. it was a bleak prognosis for henry; very little is known about the causes of the disease, and it is highly incurable. despite being the most common type of brain tumor, treatments for gbm have shown minimal advancements compared to treatments for other types of brain cancer. gbm carries an average fiveyear survival rate of 7.2%, significantly lower than the overall five-year survival rate for all types of brain cancer, which stands at 13% (nuffield trust, 2023). figure 1. an astrocyte (ferri, 2023). brain matters・volume vii 42 external conditions (like, the presence of a new drug in the system). the plasticity (ability of tumors to change and adapt) of gbm, combined with the recurring nature of the tumors, presents a difficulty in treatment. gbm is most commonly treated with surgery, followed by chemotherapy. radiation therapy is also used, often after a surgery to destroy inaccessible cancerous cells. each of these treatments are uniquely unsuccessful. in surgery, for example, the delocalization of the tumor presents a problem– gbm diffusely invades the brain, unlike tumors in other parts of the body. as a result, it’s difficult to remove the entire tumor with surgery (ncbi, 2020). the presence of barriers presents a challenge for chemotherapy. both the blood-brain barrier (bbb) (fig. 2) and the blood-tumor barrier (btb) are in effect when treating gbm. the blood vessels that vascularize in the cns are highly selective, and function to regulate the movement of molecules between the blood and the brain, resulting in a membrane known as the blood-brain barrier (bbb) (ncbi, 2020). tumors are known to compromise the bbb, resulting in vasculature called the btb. the btb is characterized by a non-uniform permeability, resulting from high heterogeneity (ncbi, 2019), and forms during the development of metastasis. as the tumor progresses, vasculature becomes increasingly heterogeneous. normal vasculature is neatly arranged in a hierarchy of evenly spaced and welldifferentiated arteries, capillaries, venules, and veins. vessels supplying tumors (those that compromise the btb) are increasingly chaotic, often following an irregular serpentine path (ncbi, 2010). selectively permeable barriers have been shown to reduce the effectiveness of cancer therapies for gbm. current therapeutics have similar sizes to molecules that will not cross the bbb, such as recombinant proteins and peptides, antibodies, and viral vectors. this makes it difficult, if not impossible, to find therapeutics that cross into the brain. astrocytes have a multitude of functions within the brain, ranging from clearing excess neurotransmitters, to stabilizing and regulating the blood-brain barrier (bbb) (ncbi, 2023). astrocytes make up the majority of cells in the central nervous system; this is unsurprising, considering their versatility. astrocytes also have a wide variety of locations within the central nervous system; as a result, gbm can start anywhere in the brain. however, it most commonly forms in the frontal and temporal lobes, which play roles in speech, movement, behavior, and memory. resulting symptoms, then, coincide with these functions; headaches, drowsiness, personality changes, and memory loss are among the most common (moffitt cancer center, n.d.). the intensity of these symptoms is influenced by genetic, epigenetic, and microenvironmental factors. uniquely, family history is not a factor; the majority of patients have no family history of cancerous brain tumors. there is, however, a correlation between gbm patients and the diagnosis of close family members–individuals with immediate relatives afflicted with gbm are twice as likely to develop the disease. the disease is linked to age, with a median age of 64, and is slightly more common in men. the only controllable risk factor for gbm is exposure to ionizing radiation therapy, as this can contribute to genetic mutations (moffitt cancer center, n.d.). in most cases, the exact cause of gbm is unknown. however, there are a few similarities between characteristics of patients; many harbor mutations in the idhi, egfr, pten, tp53, pi3k, and tert genes, which are coincidentally among the most commonly mutated genes in human beings (ncbi, 2023). although functions of these genes are generally different, they all play a role in cellular pathway signaling. in rare cases, gbm can be linked to certain genetic syndromes, such as turcot syndrome and neurofibrosis type 1 (ncbi, 2023). current therapies and their success rates for gbm patients, options are extremely limited, as gbm presents distinct challenges. localization of brain tumors, the presence of the bbb, and the limited capacity of the brain to repair itself are among these challenges. arguably the most, however, is the inherent resistance to conventional treatments (american association of neurological surgeons, n.d.). gbm cells have stem cell properties. they’re able to selfrenew and differentiate into different cell types. this means that tumors are often made of a number of different types of cells, a phenomenon referred to as heterogeneity (mdpi, n.d.). additionally, cells are able to take on different functions or roles within any one tumor, and change these roles as needed. cells in a tumor are able to interact dynamically, forming a flexible tumor environment (mdpi, n.d.). as a result, gbm is able to adapt quickly and effectively to figure 2. diagram of the blood brain barrier (parashar, 2012) aimed to specifically examine the effect of immune checkpoint inhibitors to explain the higher response of tumors originating outside of the brain to immunotherapy. it was found that t cells in tumors that did not originate in the brain had characteristics that implied tumors were blocked from entering the brain (heady & sun, 2023). immunotherapy led to a significant increase in t cell lymphocytes in brain metastases, but this increase was much smaller in patients with gbm (heady & sun, 2023). this data suggests that the priming circuit is not as effective in gbm, as t cells are best primed in draining lymph nodes outside of the brain–a process that is not possible for tumors originating inside of the brain. in the context of tumors, draining lymph nodes refer to lymph nodes that receive lymphatic drainage from the area surrounding a tumor. tumors often stimulate the growth of new blood vessels and lymphatic vessels to support their growth and spread. as a result, tumor cells and antigens can enter the lymphatic system and be transported to nearby lymph nodes (koukourakis & giatromanolaki, 2022). from these findings, researchers have suggested that dendritic cells are a potential therapeutic strategy. dendritic cells are able to reach t cells in the brain, which lymph nodes cannot do. this process would include generating dendritic cells from patients in the lab, pulsing them with tumor-specific proteins, and then re-injecting them back into the same patient (heady & sun, 2023). by recreating the priming process in dendritic cells, the effects of lymph node activation can be re-created as well. this poses exciting possibilities for the field of neurooncology. currently, the ucla researchers are attempting which immune cells are changing in the more responsive tumors to help better explain the higher response rate to the treatment. no study has comprehensively examined the differential effect of immune checkpoint blockade treatment on these two types of brain tumors (those that originate in the brain, and those that metastasize to it) before. in future studies, the researchers plan to analyze data from a larger, more uniform group of people who were diagnosed with melanoma that had spread to the brain (branca, 2023). conclusion glioblastoma arises due to genetic mutations in these cells, causing uncontrolled growth. unlike many brain tumors, treating glioblastoma presents specific hurdles. challenges include the brain tumor's location, the bbb, and the brain's limited self-repair capacity. however, the most significant challenge is its inherent resistance to standard treatments. while gbm has been generally difficult to treat, immunotherapy (which activates t-cells to target cancer cells) has proven to be particularly unhelpful. new studies show that this could potentially be due to a t-cell priming step that occurs outside of the brain, whereas gbm originates in the brain. ongoing research into t-cell activation by dendritic cells offers hope for patients like henry leonard. additionally, endothelial cells of vessels limit intercellular support of large hydrophilic drugs, a category many cancer drugs fall into (ncbi, 2023). these factors make many therapeutics ineffective in treating gbm. gbm also exhibits interesting resistance patterns that make it difficult to treat. resistance is most commonly acquired through the mechanism of dna enzyme repair. some cancer drugs (most notably temozolomide) create methyl adducts, which inhibit normal functions, on dna. this modification is toxic to the cell's dna and can trigger cell death. however, the repair enzyme o6-methylguanine-dna methyltransferase (mgmt) is capable of reversing this methyl adduct, effectively repairing the damaged dna before it leads to cell death (ncbi, 2020). this repair process prevents cell death and allows cancer cells to survive the chemotherapy's intended effects (ncbi, 2020). immunotherapies in treating cancer while there are a few options available for gbm patients, immunotherapy is not one of them. immunotherapy has been proven to be effective for various other cancers, including some that frequently metastasize to the brain. melanoma, kidney cancer, and breast cancer are among these. however, as gbm does originate in the brain, immunotherapy has not been seen to be effective. in tumors that don’t originate in the brain (but may potentially metastasize to the brain), drugs called immune checkpoint inhibitors are used. human immune systems have several checkpoints to regulate immune responses and prevent the immune system from attacking healthy cells. however, cancer cells can often take advantage of these checkpoints to avoid being attacked by the immune system. immune checkpoint inhibitors are drugs that block these checkpoints, allowing it to recognize and attack cancer cells more effectively. these drugs have been found to elicit a significant increase in both active and exhausted t cells—signs that the t cells have been triggered to fight the cancer (heady & sun, 2023). when the checkpoints are blocked, the immune system's killer t-cells become more active and capable of recognizing cancer cells as threats. t-cells are activated in lymph nodes. during this process, antigen presenting cells are recruited to the tumor, where they phagocytose dead or dying tumor cells (heady & sun, 2023). receptors on the dead cells activate the antigen-presenting cells and these cells then migrate to the nearest lymph node and prime naïve t cells moving through there, allowing the immune system to continue to target the tumor (branca, 2023). in gbm, and other tumors originating in the brain, however, this t cell priming process isn’t effective–leading to the lack of response to immunotherapy treatments. researchers have found a significant difference in the way the two types of tumors (those that originate in the brain, and those that don’t) respond to immunotherapy. in a study by ucla, researchers brain matters・volume vii 44 14. molecular mechanisms of treatment resistance in glioblastoma. (2020, december 31). ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7794986/ 15. recurrent glioblastoma: a review of the treatment options. (2023, august 26). ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10487236/ moving forward, many scientists suggest a holistic approach that combines innovative therapies, personalized medicine, and current chemotherapies. this collective momentum in research not only aims to improve survival rates but also prioritizes enhancing the quality of life for individuals facing this challenging diagnosis. references 1. arvanitis, c. d., ferraro, g. b., & jain, r. k. (2020). the blood-brain barrier and blood-tumour barrier in brain tumours and metastases. nature reviews. cancer, 20(1), 26–41. https://doi.org/10.1038/s41568-019-0205-x 2. branca, m. (2023, september 6). why glioblastoma does not respond to immunotherapy, but other brain cancers do. inside precision medicine. https://www.insideprecisionmedicine.com/topics/oncology/wh y-glioblastoma-does-not-respond-to-immunotherapy-butother-brain-cancers-do/ 3. cancer survival rates. (2023, june 27). nuffield trust. https://www.nuffieldtrust.org.uk/resource/cancersurvival-rates 4. expanding the disease network of glioblastoma multiforme via topological analysis. (2023, february 4). ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9965660/ 5. glioblastoma causes & risk factors | moffitt. (n.d.). moffitt cancer center. https://www.moffitt.org/cancers/glioblastoma/diagnosis/cause s/ 6. glioblastoma multiforme – symptoms, diagnosis and treatment options. (n.d.). american association of neurological surgeons. https://www.aans.org/en/patients/neurosurgical-conditionsand-treatments/glioblastoma-multiforme. 7. glioma symptoms, causes, treatment | nord. (n.d.). national organization for rare disorders. https://rarediseases.org/rare-diseases/glioma/ 8. glioma vs. glioblastoma: what's the difference? (2021, may 28). roswell park comprehensive cancer center. https://www.roswellpark.org/cancertalk/202105/glioma-vsglioblastoma-whats-difference 9. heady, d., & sun, l. (2023, september 1). study could help explain why certain brain tumors don't respond well to immunotherapy. ucla health. https://www.uclahealth.org/news/why-certain-brain-tumorsdont-respond-to-immunotherapy 10. heterogeneity of the tumor vasculature pmc. (2010, may 20). ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3278036/ 11. histology, astrocytes statpearls. (2023, may 1). ncbi. https://www.ncbi.nlm.nih.gov/books/nbk545142/ 12. koukourakis, m. i., & giatromanolaki, a. (2022, may). tumor draining lymph nodes, immune response, and radiotherapy: towards a revisal of therapeutic principles. ncbi. https://pubmed.ncbi.nlm.nih.gov/35227831/ 13. mechanisms of resistance and current treatment options for glioblastoma multiforme (gbm). (n.d.). mdpi. https://www.mdpi.com/2072-6694/15/7/2116 https://www.insideprecisionmedicine.com/topics/oncology/why-glioblastoma-does-not-respond-to-immunotherapy-but-other-brain-cancers-do/ https://www.nuffieldtrust.org.uk/resource/cancer-survival-rates https://www.moffitt.org/cancers/glioblastoma/diagnosis/causes/ https://www.uclahealth.org/news/why-certain-brain-tumors-dont-respond-to-immunotherapy https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3278036/ https://pubmed.ncbi.nlm.nih.gov/35227831/ brain matters vol. 8 no. 1 meditation can be defined as a collection of mental training techniques aimed at regulating cognition, emotions, and the self. rooted in spirituality, these practices take many forms in a variety of religions for some, or music and connection with nature for others. western medical communities have begun to take a deeper look at this ancient phenomenon and have found it has several benefits, including the improvement of neuroplasticity, mental health, multifactorial diseases, and even age-related neurodegeneration. specifically, magnetic resonance imaging (mri) has shown positive physical changes and introduced the idea of the brain theory of meditation (btm). this theory suggests that, through meditation, individuals can surpass previously assumed limitations of the human brain, increasing a multitude of cognitive functions. this change in physiology introduces a new field of discovery that calls for a reexamination of the inner workings of spirituality and health and what the potential for the human mind truly is. written by anika chandola abstract impact of meditation on brain function figure 1. eeg spectral modulations associated with meditation in meditators and control groups (rodriguez-larios et al., 2021) introduction meditation has become a modern focus in research after discovering the many benefits of this ancient practice, especially associated with the brain. through the use of neuroimaging techniques, specifically eeg, researcher julio rodriguez-larios has found that repetitive meditation practice can lead to increased activation of productive brain sites, strong neural pathways, and reconstruction of the brain over time (rodriguez-larios et al., 2021). through mri experiments, more evidence suggests that over time meditation results in the activation of emotional and cognitive centers of the brain, specifically the prefrontal cortex, amygdala, and hippocampus, potentially lowering the risk for age-related neurodegenerative diseases and increasing cognition in young and middle-aged individuals (davidson & mcewen, 2012) & (newberg, 2001). such drastic changes from a mental exercise suggest that thoughts affect our biology as seen in a slow down of telomerase shortening which increases the longevity of cells by preserving chromosomes throughout the aging process and implying an antiaging effect of meditation. (epel, e. s., et al. 2009). gray matter– which plays a critical role in processing information and regulating thoughts, memories, emotions, sensory input, and muscle movements–consists of high concentrations of neuronal bodies, axon terminals, and dendrites. more recent evidence shows that activities like meditation can boost the production of gray matter cells, challenging previous assumptions that brain cells stop developing after childhood. studies have found that the brain's neuroplasticity continues into adulthood, meaning that the brain can grow and adapt, particularly through practices that stimulate cognitive and sensory engagement, such as mindfulness and other forms of meditation (lazar et al., 2005; hölzel et al., 2011). these findings highlight the brain's capacity for ongoing development and regeneration, even in later stages of life. 12 new studies indicate that meditation may also promote the growth of new neurons in areas of the brain associated with memory, emotion, and stress regulation, suggesting substantial advantages for both mental and physical health (chaix, r., et al. 2017). although the field is in its infancy, these discoveries offer promising opportunities for employing meditation not only as a means for mental clarity and relaxation but also as a technique that could enhance brain health at a cellular level. as researchers continue to explore these effects, meditation remains a promising and accessible practice with potential benefits that may surpass our existing understanding. in this paper, we will analyze the physiological effects of meditation on the brain, its longterm effects throughout the aging process, and how assorted meditations manifest in different effects in the brain. physiological effect in regards to studies conducted determining hot spots during meditation, neuroimaging studies have implied a few candidate regions that are most activated in continuous practice. an 8-week study using structural magnetic resonance imaging (mri) on long-term mindfulness meditators revealed physical changes in brain structure (hölzel et al. 2011). notable findings included increased gray matter density and greater cortical thickness in brain regions associated with cognition, particularly in the posterior areas of the dorsal attention network (dan). other commonly activated regions include the precuneus, a region dedicated to visuospatial processing, episodic memory retrieval, self-relevant processing, consciousness, and prefrontal regions of the default mode network (dmn), a notoriously large brain network most commonly active when the brain is at rest or not actively focused on the outside world. more longitudinal studies (yang 2019), argue that the effects are more prevalent in longer-practicing meditators (people who meditate) and find more drastic physiological effects, in addition to a reduction in perceived stress and gray matter pathway strength, alluding to a correlation between improvement in mental emotional health and neuroplastic efficiency. meditation starts a chain of intricate neurobiological mechanisms that spread its advantages from the mind to the body. research, exemplified by a study conducted by hölzel et al. (2011), suggests that meditation can alter the structure and function of brain regions associated with stress, pain, and emotional control. specifically, mri scans revealed that engaging in mindfulness meditation can increase the thickness of the prefrontal cortex, a brain region involved in emotional control and decision-making. improved function in the prefrontal cortex could potentially help the brain handle stress more effectively, leading to lower activation of the sympathetic nervous system, resulting in decreased blood pressure and reduced inflammation in the body. during pain management, meditation influences the somatosensory cortex and insula, which are important in processing pain. zeidan et al. (2011) showed that meditation decreased pain perception by influencing these brain regions, leading to less activity in the somatosensory cortex (related to feeling physical pain) and more activity in the anterior insula (connected to thinking about pain). this change assists the brain in reinterpreting pain signals, resulting in decreased pain perception and modifying chronic pain responses by reducing the brain's usual response to pain stimuli. moreover, meditation influences the brain's limbic system, particularly the amygdala, to help regulate the body's response to stress. research conducted by taren et al. (2013) discovered that participating in mindfulness training resulted in a decrease in the volume of the amygdala and a decrease in its activity when faced with stress. this change assists in controlling the release of cortisol from the hypothalamic-pituitary-adrenal (hpa) axis, which plays a crucial role in the body's response to stress. decreased cortisol levels aid in cardiovascular health, enhance immune function, and decrease inflammation (thau et al, 2023), demonstrating how meditation's impact on the brain's structure and function results in tangible physical health advantages in various bodily systems. meditation and aging meditation’s most notable benefits are its prevention and improvement of alzheimer’s, dementia, and other neurodegenerative diseases. increasing life expectancy across the globe leads to increased cases of these neurocognitive diseases. the alzheimer's disease international association estimates 36 million people worldwide currently suffer from dementia with this number expected to double every 20 years. with meditation research in its infancy, many medical professionals project this technique to be used as a counter mechanism to fight dementia after its onset as well as as a preventative measure for those who are at risk. a study was conducted at the university of pennsylvania, of 50 subjects ranging from 52 and 72 who have a history of memory complications or a diagnosis of cognitive impairment (newberg, a. b., et al. 2006). one group was instructed to practice a 12-minute guided meditation every day for eight weeks while the others were said to have been placed on a waiting list. after examination of cognitive tests and a single photon emission computed tomography (spect) scan, measuring cerebral blood flow through brain imaging, it was found that those who practiced meditation showed significantly higher activity in the posterior cingulate gyrus region, associated with learning and memory, and the first area of the brain to decline in function in the onset of alzheimer's disease. all participants who underwent the meditation regimen saw at least some statistically significant improvement in cognitive ability– impact of meditation on brain function 13 more specifically improvements in verbal memory, executive function, and attention. principle investigator andrew newberg m.d., assistant professor of radiology at the university of pennsylvania school of medicine, added not confirm the absence of a difference and may require further investigation with larger samples. researchers noted that the average cortical thickness in meditation practitioners aged 40-50 was comparable to that of individuals aged 20-30, including both meditators and controls. this suggests that meditation may help preserve cortical integrity and mitigate age-related neural degeneration and that practicing meditation regularly can slow the rate of natural neurodegeneration at risk locusts and preserve these areas for longer periods of time. damage to these areas creates at-risk individuals for other neurocognitive diseases that commonly come with age such as alzheimer's disease and dementia (lazar et al, 2005). assorted meditations, with assorted effects being an ancient technique, meditation has evolved into hundreds of practices worldwide today, some being connected to religion while others being used as relaxation methods in schools. as a result, each form of meditation serves a different purpose and many times a different outcome and physiological change in the body, with some being more effective than others. the most common forms of meditation include zen, which focuses on seated meditation and breath awareness; vipassana, a practice rooted in observing sensations and thoughts to develop insight; mindfulness, where attention is brought to the present moment without judgment; loving-kindness, which involves cultivating compassion and positive feelings toward oneself and others; and transcendental meditation, a technique using a mantra to reach a deep state of relaxation and awareness. as a result, no definition of meditation is truly all-encompassing. the scientific community began to study the differences to help categorize but their findings have revealed the benefits of each. a study published in the journal of personality and social psychology, aimed to find if there was a difference in effectiveness between the three in terms of retaining cognitive ability, the findings were aimed to determine which would be most beneficial to those suffering with neurocognitive diseases.the study involved 73 seniors with an average age of 81, who were randomly divided into four groups. three groups practiced different meditation techniques for 12 weeks while the fourth group served as the control group. the techniques included transcendental meditation, mindfulness meditation, and a breath work relaxation program which were to be practiced twice a day for 20 minutes for 12 weeks. the study included a variety of tests to get a cohesive idea of the specific effects each meditation technique was offering, including the stroops test for cognitive flexibility, associate learning subtest for memory, and word fluency scale/overlearned verbal task for verbal fluency of elderly. the tests were administered before and after the meditation regimen, after 18 months, and after 3 years. the results suggest a strong improvement in measured variables in the group of subjects using brain matters vol. 8 2025 figure 2. side by side mri comparison of brain during meditation with attentional area on the frontal lobe (newberg et al., 2006) in 2005, dr. lazar conducted a study with 35 participants: 15 control subjects representing the average person and 20 practitioners of vipassana, a form of mindfulness meditation typically taught over 10 days with 10 hours of daily practice and minimal resources.. the objective was to compare the speed of neurodegeneration between the control and meditation practitioners through observation of cortical thickness in 2 of the commonly at-risk areas of the brain–the right insula and right frontal cortex. cortical thickness was measured at thousands of points in the vicinity of the area, between inner white and gray matter as well as outer gray and cerebrospinal fluid boundaries. analysis revealed a significant interaction between group type and age in the right frontal brain region. while participants in the control group demonstrated marked agerelated cortical thinning (r = −0.76; p = 0.001), the study did not find evidence of significant differences in cortical thickness between older and younger meditation practitioners (r = −0.05; p = 0.83). however, this result does more evidence suggests that meditation can even be used as a preventative mechanism before neurodegeneration. for the first time, we are seeing scientific evidence that meditation enables the brain to actually strengthen itself, and battle the processes working to weaken it. 14 transcendental meditation, followed by mindfulness. worse results on memory tests were shown in the control group and in the group with the relaxation program. in addition, testing after 3 years revealed 100% maintained effects of enhanced cognitive ability in persons using transcendental meditation and 87.5% in those within the mindfulness program. other groups had lower scores (65 and 75%) (alexander et al 1989). conclusion meditation is emerging as a promising tool with profound effects on the brain and body. research has shown its ability to enhance neuroplasticity, reduce chronic stress, and improve cognitive functioning, all of which are critical in preventing or slowing neurodegenerative diseases such as alzheimer’s and parkinson’s (lavretsky et al., 2015). by decreasing brain inflammation, promoting healthy neural connections, and reducing oxidative stress, meditation may serve as a non-invasive, cost-effective preventive strategy for these and other age-related conditions (creswell et al., 2012). ongoing studies are focusing on how meditation can influence specific biomarkers associated with neurodegeneration, such as amyloid-beta plaques in alzheimer’s or alpha-synuclein in parkinson’s. other research is delving into the role of meditation in enhancing mitochondrial health (epel et al., 2009) and reducing systemic inflammation—factors linked to many chronic diseases, including cardiovascular issues, diabetes, and autoimmune conditions. advances in neuroimaging and biomarker analysis are helping researchers identify the precise neural pathways and physiological changes meditation induces, offering insights into personalized prevention strategies. as this field expands, meditation may become an integral part of preventive healthcare. it holds promise not only for delaying the onset of neurodegenerative diseases but also for improving overall health, reducing the prevalence of chronic conditions, and fostering resilience against the challenges of aging. by combining ancient wisdom with modern science, meditation could redefine our approach to health and disease prevention. references 1. alexander, c. n., robinson, p., & rainforth, m. v. (1989). a model for maintaining cognitive ability in elderly individuals through meditation. journal of personality and social psychology, 56(4), 581-590. 2. chaix, r., gassama, m., messaoudi, m., & brigitte, h. (2017). meditation induces structural changes in the brain: a study of its role in neurogenesis and its potential implications. frontiers in psychology, 8, 430. 3. creswell, j. d., pacilio, l. e., doll, r., & saron, c. d. (2012). mindfulness meditation and reduction of psychological distress in cancer patients: a meta-analysis. journal of psychosocial oncology, 30(3), 256-276. 4. davidson, r. j., & mcewen, b. s. (2012). social influences on neuroplasticity: stress and interventions to promote well-being. nature neuroscience, 15(5), 689-695. 5. epel, e. s., blackburn, e. h., lin, j., dhabhar, f. s., adler, n. e., morrow, j. d., & cawthon, r. m. (2004). accelerated telomere shortening in response to life stress. proceedings of the national academy of sciences, 101(49), 17312-17315. 6. hölzel, b. k., carmody, j., vangel, m., congleton, c., yerramsetti, s. m., & gard, t. (2011). mindfulness practice leads to increases in regional brain gray matter density. psychiatry research: neuroimaging, 191(1), 36-43. 7. lazar, s. w., hölzel, b. k., & houghton, d. (2005). meditation experience is associated with increased cortical thickness. neuroreport, 16(17), 1893-1897. 8. lavretsky, h., o'hara, r., & epel, e. (2015). meditation, aging, and neurodegenerative disease. journal of clinical psychology, 71(10), 943-953. 9. newberg, a., alavi, a., baime, m., pourdehnad, m., santanna, j., & d'aquili, e. (2001). the measurement of regional cerebral blood flow during the complex cognitive task of meditation. psychiatry research: neuroimaging, 106(2), 113-122. 10. newberg, a. b., iversen, j. p., & jones, j. (2006). meditation and neuroimaging: a study on brain function in long-term practitioners. journal of cognitive enhancement, 9(4), 373-388. 11. rodriguez-larios, j., bracho montes de oca, e. a., & alaerts, k. (2021). the eeg spectral properties of meditation and mind wandering differ between experienced meditators and novices. neuroimage, 245. https://doi.org/10.1016/j.neuroimage.2021.118669 12. sharma, v. k., & sood, n. (2015). neuroplasticity and meditation: a review of the literature. annals of the new york academy of sciences, 1369, 145-156. https://doi.org/10.1111/nyas.12217 13. taren, a. a., creswell, j. d., & matthis, m. (2013). mindfulness meditation training and the amygdala: effects on emotion regulation and stress resilience. social cognitive and affective neuroscience, 8(2), 80-88. 14. thau l, gandhi j, sharma s. physiology, cortisol. [updated 2023 aug 28]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2025 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk538239/ 15. yang, j. l. (2019). long-term meditation practice leads to neuroplasticity in regions associated with attention and emotion regulation. frontiers in psychology, 10, 1930. 16. zeidan, f., johnson, s. k., diamond, b. j., & david, z. (2011). mindfulness meditation improves cognition: evidence of brief mental training. consciousness and cognition, 19(2), 201-212. impact of meditation on brain function 15 about the author anika chandola is a freshman majoring in mcb with a minor in psychology and chemistry on the pre-med track. she is currently working in bagchi lab researching the environmental impact on reproductive health and volunteered at uchicago’s phlebotomy clinic. she is also a member of the gamma phi beta soroity working alongside girls on the run. in her freetime she enjoys fashion, swimming, pageants and playing the piano. she hopes to become more involved in the neuroscience field and learn more about this diverse community. brain matters vol. 8 2025 16 17 volume 8 (will be vol 7 on site) design board sarah masud is a sophomore studying psychology and information sciences with a minor in art & design. some of her academic interests include cognition, human-computer interaction, and treating psychiatric disorders. she enjoys drawing, finding new music, and crocheting as well! outside of brain matters, sarah is also involved in design innovation illinois, the undergraduate psychology association, and psi eta mu, a professional information sciences fraternity. she hopes to continue furthering her understanding of neuroscience and exploring topics she’s passionate about through writing for the journal. edward lin is a freshman majoring in neural engineering. he spends much of his time exploring the intricate connections between artificial intelligence and neural networks, with a focus on developing advanced neural interfaces. in his free time, edward enjoys playing volleyball, starting up business ventures, and editing videos. brain matters・volume vii 88 madelyn feliciano is sophomore majoring in neuroscience and psychology. she is passionate about biopsychological research, with a particular focus on neurodevelopmental disorders and supporting individuals with intellectual disabilities. hi! my name is jessica george and i’m a junior majoring in molecular and cellular biology and brain and cognitive science. outside of school, i volunteer at a nursing home in the activities department, where i work closely with residents who have dementia. in my free time i love dancing, listening to music, and trying new restaurants! br ai n m at te rs b oa rd volume 8 (will be vol 7 on site) inside out: a brain’s tale of introverts and extraverts krisha agarwal introduction what makes us who we are? according to the american psychological association, personality is the ‘the enduring configuration of characteristics and behavior that comprises an individual’s unique adjustment to life, including major traits, interests, drives, values, self-concept, abilities, and emotional patterns.’ (detloff, 1972) two primary types of human personality are introversion and extraversion. psychologist carl gustav jung differentiated introversion and extraversion based on the “direction of flow of psychic energy”. an extravert places importance on an external object (another person, place, or thing) based on his qualities (detloff, 1972). on the other hand, introverts are loyal to an inner point of reference that takes precedence over the external object (detloff, 1972). the object becomes important if it aligns with the inner self. therefore, the differential feature between introverts and extraverts is how the person arrives at this perspective rather than the actual relationship between the object and subject (detloff, 1972). physical structure psychologist hans eysenck suggests that the behavioral differences in extraverts are due to an inherent drive to compensate for underactive reticulo-thalamo-cortical pathways. as a result, extraverts have lower activity in their behavioral inhibition system, a functional loop including the ascending reticular activating system, the frontal lobes, septal regions, and hippocampus. a positive correlation has also been found between extraversion and gray matter concentration in the left amygdala (omura et al., 2005). the thinner cortical gray matter ribbon in the dorsolateral prefrontal cortex (dlpfc) emphasizes its importance in extraversion (wright et al., 2006). the dlpfc strategically controls an individual’s thoughts and actions based on goaloriented behavior and positive affective states (macdonald et al., 2000). its dysfunction has been associated with depression and anxiety, which may also explain why low levels of extraversion lead to increased vulnerability (grimm et al., 2011). neurotransmitters in some people’s brains, enhanced release of neurotransmitter dopamine, part of the brain’s reward system, leads to greater excitement and engagement with the world (watson, 2021). this release is linked to the sympathetic nervous system, responsible for the ‘fight, flight, or freeze’ response, which makes the brain alert and hyper-focused on its environment (granneman, 2016). a study by researchers at cornell university observed that rewards like food, sex, and money trigger dopamine release, producing positive emotions and increased drive for these goals (depue & fu, 2013). in the study, it was noted that extraverts have a more robust dopamine response system, making them experience strong positive emotions more frequently. moreover, with time, extraverts develop a more extensive network of rewardcontext memories to activate the brain’s reward system, further increasing the feeling of positivity and excitement. on the other hand, it was noted that acetylcholine, which is linked to introspection, was more prevalent in introverts. this neurotransmitter is integral in the ability to think deeply and to concentrate. this idea is reinforced by the fact that acetylcholine is associated with the parasympathetic nervous system, responsible for the ‘rest and digest’ response, due to its features of energy conservation, muscle relaxation, and decreased blood pressure–necessary for periods of intense study (granneman, 2016). figure 1. personality differences between introverts and extraverts (the minds journal, 2022) figure 2. neurotransmitter pathways between introverts and extraverts (medium, 2016) environmental influences introversion and extraversion hold a genetic component, but environmental factors also play a role. results from identical twin studies suggest that one’s surroundings greatly influence personality, with a 40% genetic and 60% environmental variance (loehlin & nichols, 2012). in another study, professor brian little developed the free trait theory, which states, “...introverts may temporarily act as extraverts in order to advance projects requiring expressions of enthusiastic assertiveness.” (little, 2008). in conclusion, introversion and extraversion are flexible, complex blends of genetic components and environmental factors. these personality types of extraversion and intraversion arise from neurological and biochemical processes, influencing our behavioral and emotional responses. understanding this dynamic can provide valuable insights into human behavior. references 1. detloff, w. (1972). psychological types: fifty years after. psychological perspectives, 3(1), 62–73. https://doi.org/10.1080/00332richey927208408804 2. depue, r. a., & fu, y. (2013). on the nature of extraversion: variation in conditioned contextual activation of dopamine-facilitated affective, cognitive, and motor processes. frontiers in human neuroscience, 7, 288. https://doi.org/10.3389/fnhum.2013.00288 3. granneman, j. (n.d.). why introverts and extraverts are different: the science. quiet schools network. https://www.quietrev.com/wp-content/uploads/2016/05/whyintroverts-and-extraverts-are-different-the-science-byjennifer-grannerman.pdf 4. grimm, s., schubert, f., jaedke, m., gallinat, j., & bajbouj, m. (2012). prefrontal cortex glutamate and extraversion. social cognitive and affective neuroscience, 7(7), 811–818. https://doi.org/10.1093/scan/nsr056 5. how introvert and extravert brains differ: 6 differences according to science. the minds journal. (2022, june 23). https://themindsjournal.com/introvert-and-extravert-braindifferences/ 6. johnson dl, wiebe js, gold sm, et al. cerebral blood flow and personality: a positron emission tomography study, american journal of psychiatry, 1999, vol. 156 (pg. 252-7) 7. little, b. r. (2008) ‘personal projects and free traits: personality and motivation reconsidered’, social and personality psychology compass, 2(3), pp. 1235–1254. doi: https://doi.org/10.1111/j.1751-9004.2008.00106.x. 8. loehlin, j. c. and nichols, r. c. (2012) heredity, environment, and personality: a study of 850 sets of twins. university of texas press. 9. macdonald aw, cohen jd, stenger va, carter cs. dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control, science, 2000, vol. 288 (pg. 1835-8) 10. omura k, todd constable r, canli t. amygdala gray matter concentration is associated with extraversion and neuroticism, neuroreport, 2005, vol. 16 (pg. 1905-8) 11. watson, s. (2021, july 20). dopamine: the pathway to pleasure. harvard health. https://www.health.harvard.edu/mind-and-mood/dopaminethe-pathway-to-pleasure 12. wright ci, williams d, feczko e, et al. neuroanatomical correlates of extraversion and neuroticism, cerebral cortex, 2006, vol. 16 (pg. 1809-19) brain matters・volume vii 34 https://doi.org/10.1111/j.1751-9004.2008.00106.x volume 8 (will be vol 7 on site) there are many studies and scenarios that can be examined to see this in action. one study from the national library of medicine demonstrated that those who showed gratitude as opposed to resentment had lower heart rates, as shown in figure 2 (kyeong et al., 2017). this response is due to the parasympathetic and sympathetic systems respectively. previous studies have shown that heart rate is decreased among those with high self-esteem and increased in those with high stress and anxiety. the results of this study suggest that gratitude changes heart rhythms in a way that enhances mental health as well as self-confidence. another study published in the brain, behavior, and immunity journal looked at gratitude among women in an online six-week program. they were instructed to do a gratitude writing intervention with a control group present to see if there were effects on neural activity (hazlett et al., 2021). it was observed at the end that gratitude reduces inflammatory responses and increases support-giving. with that being said, gratitude is not just a social-moral emotion but is a neural correlate with cognitive implications. can expressing gratitude make you happier & healthier? vani sharma abstract the human brain consistently receives stimuli and adjusts accordingly. from social cues and emotions to memory consolidation for your studies, the brain is a moving part that is shaped by the environment and its inputs. one of these inputs is gratitude which can lead to changes in the brain’s molecular and chemical structure leading to outcomes such as increased confidence, less anxiety and depression, increased resilience, motivation, and productivity. this paper focuses on the power of gratitude and positive self-talk and how that can be harnessed in applications in the real world and to improve overall mental health. introduction gratitude: the quality of being thankful and showing appreciation. from learning as little children to practicing saying “thank you,” to the popular holiday celebration, thanksgiving, to the high sale of gratitude journals, there is no doubt that showing appreciation for what we have is a cornerstone ideal of society. showing gratitude in society is considered a marker of social and emotional intelligence, but what if it also impacts our neural plasticity? expressing gratitude could help us boost our brain health, motivation pathways, productivity, happiness levels, resilience, and more. the objective of this paper is to delve deeper into the neurochemical and structural changes our brain undergoes when we express gratitude and how humans can harness this to improve mental health. power of gratitude gratitude not only impacts central nervous system functioning but also changes the brain's molecular structure. firstly, according to ucla’s mindfulness awareness research center, gratitude keeps the gray matter functioning, making us healthier and happier (moran, 2013). gray matter plays a large role in emotional functioning in addition to memory as well as movement. with that being said, even just a few minutes of daily recognition of gratitude can create an environment of positivity and boost your mental state. on a more rudimentary neuroscience level, when we express gratitude or receive it, the brain releases dopamine and serotonin (chowdhury, 2019). both are considered ‘feel good’ neurotransmitters that play key roles in our emotions, mood enhancement, and extending happiness as shown in figure 1. when gratitude is practiced consistently and daily, these neural pathways that release these neurotransmitters can be strengthened to create a stable sense of positivity within us. fig 1. serotonin & dopamine chemical structures (guy-evans, 2023) fig 2. heart rate fluctuations (kyeong et al., 2017) brain matters・volume vii 56 positive self-talk & cognition language can impact how we think, feel, and behave under social stress. it can also improve cognition performance (kim et al., 2021). prior research has confirmed that self-talk has positive effects on attention, emotional regulation, performance enhancement in sports, academic engagement, and regulating anxiety and depression. when we engage in positive self-talk, it promotes positive psychological states, and the reverse is true with negative self-talk. furthermore, neuroscience studies have found that positive self-talk promotes functional connectivity in the reward-motivation network (“clinical depression, n.d.”). the reward motivation network is responsible for pleasure, motivation, and learning. the basis of the reward pathway is that neurons release dopamine to allow you to feel pleasure. the brain makes associations between the source of pleasure and the pleasurable feeling. then, the brain continues to make this connection stronger over time and encourages the repetition of behaviors that bring pleasure.the pathway is outlined in figure 3. positive selftalk increases motivation, cognitive fatigue-related inattention, and self-respect. additionally, it can help individuals cope with difficult situations. a real-life example of this is people who use self-talk before a presentation are less anxious than those who say negative words to themselves. it can also help athletes as they compete. real-world applications & improved mental health benefits there are many practical applications of the aforementioned teachings and ways we can harness gratitude, positivity, and positive self-talk to increase neural plasticity as well as improve our mental health and productivity. firstly, we can use these principles to help neutralize self-talk, which has poor effects on cognition, self-esteem, and goals (raina, 2021). when we self-criticize and engage in negative selftalk, this has a high correlation with stress and anxiety as well as subsequent clinical diagnoses such as depression. when our brains criticize, emotional systems related to punishment and behavioral inhibition are activated. the brain sees this as a threat and creates a hyperfocus to not let something repeat. this leads to physical and mental stress and leads to mental exhaustion from overthinking. some strategies we can take to mitigate this based on the practice of gratitude are to notice negative self-talk, reassure ourselves, and show compassion. by practicing self-kindness, normalizing the experience, and being mindful, we can motivate ourselves to improve and do better while being cognizant of our well-being and happiness. in the same way, positive self-talk can also make you feel better and raise your productivity levels (“how positive”). experts at mayo clinic, ranked as one of the top hospitals in the country, say to harness these effects we must not say anything to ourselves that we wouldn’t say to someone else. mayo clinic further states that redirecting negative thoughts to a positive manner may lead to increased life span, lower depression rates, lower levels of distress, better psychological and physical well-being, better cardiovascular health and reduced cardiovascular disease, and better coping skills during hardship and stressful times. one technique that can be tried is changing the self-talk point of view. a harvard business review recently shared that referring to yourself in the second or third person can make a grand difference and lead to being calmer and more confident as opposed to using ‘i’ or ‘me.’ limitations & future directions it is important to note that research in this field is quite new, and there is much that is left to be further known, especially in conducting studies and looking at the nervous system response. there is no doubt that bigger studies can be funded with a greater sample size and looking at diverse patient populations. there are so many limitations as it is difficult to just pinpoint gratitude as the sole source for some of these changes. the brain is stimulated by a multitude of factors and many things can cause the release of “feel-good” neurotransmitters. with that being said, some future directions for this area of study would be to do larger-scale studies that are able to limit confounding factors to study the effects of gratitude and positive self-talk. concluding statements gratitude is not only a social and emotional component of our lives but remains integrated with our neural systems. over time, practicing gratitude can alter the circuitry of our brain to become more resilient, and productive, and dampen demotivating negative sentiments. humans can harness the powerful effects of gratitude such as neurotransmitter release and the calming effects of positive self-talk to live happier and healthier lives. even just small acts of gratitude a day can tremendously improve brain health. fig. 3. dopamine reward pathway (guy-evans. 2023) references 1. chowdhury, m. (2023, october 3). the neuroscience of gratitude and effects on the brain. https://positivepsychology.com/neuroscience-ofgratitude/#:~:text=when%20we%20express%20gratitude%2 0and,feel%20happy%20from%20the%20inside 2. guy-evans, o. (2023a, september 14). brain reward system. simply psychology. https://www.simplypsychology.org/brainreward-system.html 3. guy-evans, o. (2023b, september 18). serotonin vs. dopamine: what are the differences?. simply psychology. https://www.simplypsychology.org/serotonin-vsdopamine.html 4. hazlett, l., moieni, m., irwin, m., haltom, k., jevtic, i., meyer, m., breen, e., cole, s., & eisenberger, n. (2021, april 28). exploring neural mechanisms of the health benefits of gratitude in women: a randomized controlled trial. science direct. https://www.sciencedirect.com/science/article/pii/s088915912 100177x 5. how positive self talk can make you feel better and bemore productive. walden university. (n.d.). https://www.waldenu.edu/onlinebachelors-programs/bs-in-psychology/resource/how-positiveself-talk-can-make-you-feel-better-and-be-more-productive 6. kim, j., kwon, j. h., kim, j., kim, e. j., kim, h. e., kyeong, s., & kim, j.-j. (2021, july 21). the effects of positive or negative self-talk on the alteration of brain functional connectivity by performing cognitive tasks. nature news. https://www.nature.com/articles/s41598-021-94328-9 7. kyeong, s., kim, j., kim, d. j., kim, h. e., & kim, j. j. (2017). effects of gratitude meditation on neural network functional connectivity and brain-heart coupling. scientific reports, 7(1), 5058. https://doi.org/10.1038/s41598-01705520-9 8. moran, j. (2014, march 24). pause, reflect and give thanks: the power of gratitude during the holidays. ucla. https://newsroom.ucla.edu/stories/gratitude-249167 9. raina, s. (2021, may 6). four brain science habits to help neutralize negative self-talk. forbes. https://www.forbes.com/sites/forbescoachescouncil/2021/05/ 06/four-brain-science-habits-to-help-neutralize-negative-selftalk/?sh=42a56ff34f3c brain matters・volume vii 58 brain matters vol. 8 no. 2 the influence of maternal stress on a child's development in the womb and the long-term effects on the child's neurodevelopment and mental health  written by alexa divito introduction stress during pregnancy is common amongst both new and experienced mothers. (dunkel schetter and tanner, 2012) many can attest to the fact that a stressed mother can impact her children at any age, whether it be requiring them to do extra chores or causing anxiety. however, what many people may not realize is the immense impact stress during pregnancy has on children. maternal stress does not only affect the mother but the fetus as well, especially during their development and later life. research shows that when pregnant women experience various stressors (such as grief, daily challenges, or natural disasters), it can lead to significant changes in their children’s neurodevelopment. these changes can include a higher likelihood of autism, emotional disorders, and diminished cognitive abilities. the fetal programming hypothesis ‘the fetal programming hypothesis’ states that during critical and sensitive periods of development, a disturbance in environmental factors has an organizational effect on biological systems (seckl and holmes, 2007). these systems include the central nervous system (the brain and spinal cord), autonomic nervous system (regulates involuntary physiological process such as heart rate and respiration), neuroendocrine (comprised of the hypothalamic-pituitaryadrenal axis), cardiovascular, and immune systems. (bale, 2015). disturbances can also negatively affect intrinsic plasticity, which is the nervous system’s ability to change its activity activity in response to stimuli. this can be done by reorganizing its structure, fruition, or connections, to react and adapt to environmental influences. this hypothesis states that fetal conditions can have major impacts later in life. these impacts can be presented in many ways, depending on which part of the brain is affected. how the fetal brain is physically affected certain parts of a fetus’s brain can be affected by maternal stress, hindering proper fetal brain development. for example,in animal models, acute periods of prenatal or postnatal stress have profound effects on hpa function and behavior in adult offspring. this means that maternal stress during prenatal development can affect how the fetus’s brain and associated parts of the body will respond to stress later in life. these effects can be different based on sex. chronic maternal stress increases locomotor activity, which can cause higher sensitivity to change or trouble focusing in adult male offspring; on the other hand, it decreases sensorimotor gating (regulation of sensory information) in adult female offspring. (emack and matthew, 2011). naturalistic studies with humans find similar effects on motor behavior (huizink et al. 2004). studies of prenatal maternal anxiety (o’connor et al. 2002), prenatal exposure to stressful life events (stott 1973), and even prenatal exposure to dexamethasone (a synthetic glucocorticoid that is an antiinflammatory and immunosuppressive steroid) (trautman et al. 1995) are associated with children who are more withdrawn, anxious and depressed. 36 the influence of maternal stress on a child's development in the womb and the long-term effects on the child's neurodevelopment and mental health how the brain is cognitively affected various research shows that prenatal exposure to maternal stress increases the risk of behavioral and mental health problems later in life (van den bergh et al. 2020). a classic study by hutten and niskanen (1978) examined rates of mental illness in samples of children from finland whose fathers had died either during pregnancy or within their first year of life. significantly greater rates of schizophrenia and other mental illness were found in the prenatal stress exposure group. van os and selton (1998) also found a significant increase in rates of schizophrenia in holland as a function of the german invasion during world war ii. these studies show specific effects of the timing of the stressor during pregnancy, with the most noxious effects being associated with exposure during the second trimester. because of this, it has been hypothesized that the timing of the disruption in fetal neural development, rather than the type of disruption, may be even more critical in determining the risk for negative outcomes and which developmental processes are likely to be affected (mednick et al. 1998). these findings alter the impact of prenatal stress timing on development, a concept further explored by researchers in project ice storm, which examined the effects of a largescale natural disaster on pregnant women and their children. project ice storm through january 5th and 9th of 1998, a series of freezing rain storms hit southern quebec, canada. there was widespread flooding and ice accumulation causing around 1.3 million power outages,which led to water filtration plants being shut down, leaving many people to seek new shelter. while the meteorological event itself occurred over a period of four days, the recovery process lasted even longer, with longterm impacts lingering for months afterwards (senesac, 2019). shortly after, project ice storm was initiated. the objective of this project was to determine the nature and duration of the effects of an independent stressor during pregnancy on the unborn child by using a prospective design with a large sample of families. by conducting repeated assessments of affected women and their children over several years, the impact of objective stress exposure and subjective stress reaction on perinatal outcomes, maternal postpartum depression, and the behavioral, physical, and cognitive development of the children was found. the test group, storm32, split mothers into three groups depending on the stress levels demonstrated (low, moderate, and high stress), and contrasted the low stress group with the combined moderate-high stress group. they found that moderate to high objective prenatal maternal stress is associated with poorer intellectual and language functioning at the age of two when scientists examined interactions between trimester of exposure and severity of ice storm stress. this is demonstrated by graph 1.1. figure 1. toddlers’ mean (+/standard error) bayley mental developmental index (mdi) scores at 2 years of age, as a function of objective prenatal maternal stress levels (low, high) and trimester of exposure (1 , 2 , or 3rd).st nd these findings were reinforced by the results of their analyses of the children’s play behaviors (laplante et al.2004). for intellectual abilities, children whose mothers were exposed to the ice storm during their 1st or 2nd trimester of pregnancy and who experienced moderate or high objective stress had significantly lower bayley mdi scores (a neural development assessment). this is demonstrated by graph 1.2. figure 2. toddlers’ mean (+/standard error) macarthur communicative development index (mcdi) scores for productive and receptive language abilities at 2 years of age, as a function objective prenatal maternal stress levels (low, high) and trimester of exposure (1 , 2 , or 3rd).st nd the findings from project ice storm strongly suggest that major stressful events, independent of maternal personality factors, can have a negative impact on cognitive and language development of the unborn child.  37 brain matters vol. 8 2025 references 1. almond, d., & currie, j. (2011). killing me softly: the fetal origins hypothesis. the journal of economic perspectives : a journal of the american economic association, 25(3), 153–172. https://doi.org/10.1257/jep.25.3.153  2. dunkel schetter, c., & tanner, l. (2012). anxiety, depression and stress in pregnancy: implications for mothers, children, research, and practice. current opinion in psychiatry, 25(2), 141–148. https://doi.org/10.1097/yco.0b013e3283503680 conclusion maternal stress during pregnancy has far-reaching effects that go beyond the immediate challenges of pregnancy. the evidence shows that stress during this crucial period can leave lasting marks on a child’s neural development and mental health, with impacts that may only surface after birth. whether it’s everyday stress or more severe circumstances, the timing and intensity of stress exposure during pregnancy can influence the child’s risk for cognitive and emotional difficulties. supporting mothers during pregnancy isn't just about the mother’s well-being at the moment– it’s also about safeguarding the long-term health and development of their children. addressing maternal stress will help ensure healthier outcomes for future generations. 38 about the author alexa divito is a freshman at the university of illinois. she is currently an undeclared major on the pre-nursing track and plans to declare as a psychology major next year. alexa became part of brain matters to develop her knowledge of the brain and share her new knowledge with others. apart from writing for brain matters, alexa is involved in greek life, rso’s, and is working on getting her cna license. 3. emack, j., & matthews, s. g. (2011). effects of chronic maternal stress on hypothalamo–pituitary–adrenal (hpa) function and behavior: no reversal by environmental enrichment. hormones and behavior, 60(5), 589–598.  https://doi.org/10.1016/j.yhbeh.2011.08.008  4. king, s., & laplante, d. p. (2005). the effects of prenatal maternal stress on children's cognitive development: project ice storm. stress, 8(1), 35–45.  https://doi.org/10.1080/10253890500108391  5. kinsella, m. t., & monk, c. (2009). impact of maternal stress, depression and anxiety on fetal neurobehavioral development. clinical obstetrics and gynecology, 52(3), 425– 440. https://doi.org/10.1097/grf.0b013e3181b52df1  6. van den bergh, b. r. h., van den heuvel, m. i., lahti, m., braeken, m., de rooij, s. r., entringer, s., hoyer, d., roseboom, t., räikkönen, k., king, s., & schwab, m. (2020). prenatal developmental origins of behavior and mental health: the influence of maternal stress in pregnancy. neuroscience & biobehavioral reviews, 117, 26-64.  https://doi.org/10.1016/j.neubiorev.2017.07.003 39 brain matters vol. 8 no. 2 the development of psychogenic pain written by lily kushnick introduction pain is a complex experience, but it can be better understood when divided into three broad categories: nociceptive pain, caused by tissue damage, neuropathic pain, resulting from nerve damage, and the newly recognized psychogenic pain (also known as nociplastic pain). nociplastic pain refers to physical pain caused or increased by psychological, emotional, or social factors rather than physical or neurological damage. nociceptors (i.e. pain receptors) release neurotransmitters to the thalamus and other parts of the brain through the nervous system. pain manifests as a physical and subjective experience. despite the lack of a clear physical cause, and though some dismiss it as entirely psychological, psychogenic pain remains a genuine condition as it is both physical and psychological. while there is no clear underlying physical cause, and although some people may discount it being all in a person's head, psychogenic pain is still real. the development of pain there are four major processes in the development of pain. it starts with transduction, which refers to the activation of pain receptors in response to stimuli—either mechanical (i.e. pressure), heat, or chemical. next, transmission involves the nociceptive message being sent from the peripheral nervous system (pns) to the central nervous system (cns). these nociceptive messages are encoded in the patterns and frequency of impulses from the nociceptor. along this pathway, modulation occurs, altering the pain signals as they travel. modulation is one of the reasons people experience pain in different severities, even with similar stimuli (kirkpatrick et al., 2015). for example, the activation of nociceptors may not always lead to a sensation of stronger pain due to modulation. finally, perception occurs and is the cumulative subjective experience resulting from an array of sensory signals. this step includes the attention, expectation, and interpretation of the pain messages and cannot be objectively measured unlike the other neural processes. for instance, when you stub your toe, nociceptors are activated in response to a mechanical stimulus. the message would travel through the anterolateral system (a sensory pathway that carries information about stimuli such as temperature and touch) in the spinal cord and then to the brain (specifically, the thalamus then to various areas of the figure 1. pathway of pain signaling and processing (nih, 2022). 54 the detection of pain nociception—the process by which the nervous system detects painful stimuli—is crucial to understanding psychogenic pain and the mechanisms behind pain in general. nociceptive pain refers to the activation of nociceptors in response to actual or threatened tissue damage. on the other hand, nociplastic (psychogenic) pain arises from the activation of nociceptors without the presence or clear threat of physical damage (milner & doherty, 2015). in this case, the excitation of nociceptors is mediated by retrograde activation by messages from the sympathetic nervous system (sns). this means that the postsynaptic neuron, the cell receiving a signal, sends information back to the presynaptic neuron, the cell sending a signal. nociceptors detect harmful stimuli and signal the cns which causes the sensation of pain. so, retrograde activation in this context would involve the injured areas sending signals back to the nociceptors (tao & poo, 2001). another way nociceptors could be activated is by reflex muscle tension. prolonged muscle tension is often accompanied by increased sensitization of nociceptor terminals in muscles (isagulyan & kashcheev, 2022). muscle tension is a reflexive response to stress and can significantly decrease the mechanical threshold for nociceptor activation in muscles (chen et al., 2011). essentially, elevated and extended periods of stress heighten muscle tension which generally lowers pain tolerance or increases sensitivity to stimuli. unction the development of psychogenic pain cerebral cortex) as an electrical impulse, which is interpreted and experienced as pain (institute of medicine (us) committee on pain, disability, and chronic illness behavior et al., 1987)estrogend figure 2. the major neural structures relevant to pain and pathway/development of pain from nociceptive transduction of stimulus from tissue. in psychogenic (nociplastic) pain, there is no physical stimulus (institute of medicine (us) committee on pain, disability, and chronic illness behavior et al., 1987). figure 3. areas of the brain involved with pain processing (gore, 2022). factors effecting the development of psychogenic pain there are a few proposed mechanisms for the development of psychogenic pain. pathophysiologically, one mechanism pointed to is hyperresponsiveness to pain stimuli. nociceptors may become more sensitive to stimuli and lower the threshold for activation, causing even seemingly nonpainful stimuli to produce pain (bułdys ́et al., 2023). the extent of nociceptor activation determines the input the cns receives which determines the severity of pain experienced. nociceptors sensitize, meaning their excitability can increase. as a result, there is a reduction of the threshold and an increase in magnitude of response to a stimulus (gold & gebhart, 2010). another potential influence could be hyperactivity and connectivity between regions of the brain responsible for perceiving pain, such as the medial prefrontal cortex (mpfc), anterior cingulate cortex (acc), thalamus, and somatosensory cortex, which would also cause an amplified response to pain signals. decreased activity and connectivity in the regions of the brain such as the rostral ventromedial medulla (rvm) and periaqueductal gray (pag) can impact the development of psychogenic pain as well (bułdys ́ et al., 2023). the pag activates a pain inhibitory system and influences pain modulation by its connections with the rvm, which can both facilitate and inhibit nociceptive inputs (ossipov et al., 2014). additionally, psychogenic pain may be caused by the nervous system’s recognition of pain that has already healed, supporting the idea that confused signaling may be a part of the cause (moini et al., 2023). pain plasticity—the adaptive processes of the nervous system in response to pain stimulus—may lead to changes in nociceptors, causing them to activate atypically. because of this plasticity 55 brain matters vol. 8 2025 conclusion psychogenic pain most commonly manifests as headaches, stomach aches, and back pain, and is overall commonly associated with mental disorders like depression and anxiety (galli, 2023). however, psychogenic pain is very complex and still not fully understood, so there is not a standard diagnosis or treatment of the condition yet. due to its novelty, misunderstanding, and the general dismissive attitude towards it up until only recently, many patients suffering from psychogenic pain have not received the attention they deserve. with many technological advancements and development of new research, new techniques for diagnosis, treatment and prevention of psychogenic pain are not far out of reach. in the meantime, a greater emphasis on recognizing and accepting this condition and approaching it with compassion and an open mind is crucial to ensuring patients receive the appropriate care. plasticity, signaling is amplified and a “pain memory” is formed (price & inyang, 2015). it is most likely a combination of these factors as many regions of the brain (acc, mpfc, thalamus, somatosensory cortex, rvm, and pag) work together to create the experience of pain. other important factors are cognitive and psychological. psychogenic pain is commonly associated with psychosocial and emotional conflicts, as the brain can interpret mental distress as physical pain (moini et al., 2023). chronic stress can trigger or exacerbate pain because it can contribute to the sensitization of nociceptors, causing the brain to become hypersensitive to pain signaling (hannibal & bishop, 2014). in addition, problems with emotional regulation may lead to somatization—the expression of emotional/psychological conflicts as physical (somatic) symptoms (lumley & schubiner, 2019). generally, positive emotions inhibit pain while negative emotions facilitate it. issues with regulating negative emotions can heighten the amplification of pain signaling (toledo et al., 2024). the idea of “catastrophizing” can also be associated with the development of psychogenic pain. people who tend to catastrophize (i.e. exaggerating negative mentality) are more likely to experience more intense pain and have more difficulty managing it. this is linked to activation of pfc, acc, and amygdala, which is involved in perception of pain and emotional regulation (sullivan et al., 2000). 2. the “anatomy of pain pathways.” (n.d.). https://www.ucl.ac.uk/anaesthesia/sites/anaesthesia/files/p erioperative-msc-programme the-anatomy-of-painpathways.pdf 3. bułdys,́ k., górnicki, t., kałka, d., szuster, e., biernikiewicz, m., markuszewski, l., & sobieszczańska, m. (2023, june 17). what do we know about nociplastic pain?. healthcare (basel, switzerland). https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10298569/ 4. chen, x., green, p. g., & levine, j. d. (2011, june 30). stress enhances muscle nociceptor activity in the rat. neuroscience. https://pmc.ncbi.nlm.nih.gov/articles/pmc3101313/ 5. galli, f. (2023, february 10). understanding nociplastic pain: building a bridge between clinical psychology and medicine. journal of personalized medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9968114/ 6. gold, m. s., & gebhart, g. f. (2010, november). nociceptor sensitization in pain pathogenesis. nature medicine. https://pmc.ncbi.nlm.nih.gov/articles/pmc5022111/ 7. gore, d. g. (2022, may 23). the anatomy of pain. anaesthesia & intensive care medicine. https://www.sciencedirect.com/science/article/pii/s1472029 922000820 8. hannibal, k. e., & bishop, m. d. (2014, december 1). chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation. oup academic. https://academic.oup.com/ptj/article/94/12/1816/2741907? login=true 9. institute of medicine (us) committee on pain, disability, and chronic illness behavior. (1987, january 1). the anatomy and physiology of pain. pain and disability: clinical, behavioral, and public policy perspectives. https://www.ncbi.nlm.nih.gov/books/nbk219252/ 10. isagulyan, e. d., & kashcheev, a. a. (2022). psychogenic pain. psychogenic pain an overview. https://www.sciencedirect.com/topics/neuroscience/psych ogenic-pain 11. kirkpatrick, d. r., mcentire, d. m., hambsch, z. j., kerfeld, m. j., smith, t. a., reisbig, m. d., youngblood, c. f., & agrawal, d. k. (2015, december). therapeutic basis of clinical pain modulation. clinical and translational science. https://pmc.ncbi.nlm.nih.gov/articles/pmc4641846/ 12. lumley, m. a., & schubiner, h. (2019). emotional awareness and expression therapy for chronic pain: rationale, principles and techniques, evidence, and critical review. current rheumatology reports. https://socialwork.buffalo.edu/content/dam/socialwork/con tinuingeducation/documents/lumley%20&%20schubiner% 20(2019).%20eaet%20for%20chronic%20pain.%20rationale ,%20principles%20and%20techniques,%20evidence,%20an d%20review%20(1).pdf 56 references 1. abdallah, c. g., & geha, p. (2017, february). chronic pain and chronic stress: two sides of the same coin?. chronic stress (thousand oaks, calif.). https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5546756/ the development of psychogenic pain 13. milner, r., & doherty, c. (2015). pathophysiology of pain in the peripheral nervous system. science direct. https://www.sciencedirect.com/topics/neuroscience/nocice ption#:~:text=nociception%20is%20the%20detection%20of, the%20body%20of%20potential%20dangers. 14. moini, j., gutierrez, a., & avgeropoulos, n. (2023, may 19). pain. clinical neuroepidemiology of acute and chronic disorders. https://www.sciencedirect.com/science/article/pii/b9780323 959018000055 15. nih pain consortium. (2022). https://coepes.nih.gov/module/joyce-osteoarthritis-kneeand-risk substance-use-disorder/additional-material 16. ossipov, m. h., morimura, k., & porreca, f. (2014, june). descending pain modulation and chronification of pain. current opinion in supportive and palliative care. https://pmc.ncbi.nlm.nih.gov/articles/pmc4301419/ 17. price, t. j., & inyang, k. e. (2015a). commonalities between pain and memory mechanisms and their meaning for understanding chronic pain. progress in molecular biology and translational science. https://pmc.ncbi.nlm.nih.gov/articles/pmc4664460/ 18. sullivan, m. j. l., thorn, b., haythornthwaite, j. a., keefe, f., martin, m., bradley, l. a., & lefebvre, j. c. (2000). theoretical perspectives on the relation between... : the clinical journal of pain. the clinical journal of pain. https://journals.lww.com/clinicalpain/fulltext/2001/03000/t heoretical_perspectives_on_the _relation_between.8.aspx 19. tao, h. w., & poo, m.-m. (2001, september 25). retrograde signaling at central synapses. proceedings of the national academy of sciences of the united states of america. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc58675/ 20. toledo, t. a., rhudy, j. l., huber, f. a., & vore, c. n. (2024, june). the effect of emotion regulation on the emotional modulation of pain and nociceptive flexion reflex. pain. https://pubmed.ncbi.nlm.nih.gov/38227556/ 21. yang, s., & chang, m. c. (2019, june 26). chronic pain: structural and functional changes in brain structures and associated negative affective states. international journal of molecular sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6650904/ 57 about the author lily kushnick is a freshman at the university of illinois majoring in neuroscience. lily became involved in brain matters to learn more about the process of writing scientific articles and about current neuroscience research and innovations. in addition to writing for brain matters, she is a member of healthcare book club and volunteers at carle hospital. 58 brain matters vol. 8 no. 2 written by ananya sampathkumar isolation how it affects fear responses and anxiety introduction loneliness is commonly referred to as the feeling of social isolation. while this can be a familiar feeling for many people, loneliness is not ingrained into human nature (finley, schaefer, 2022). humans are inherently social creatures: communication is so crucial for people that the usage of isolation as a torture tactic leads to drastic responses such as psychological disintegration or even death (umberson, montez, 2011). like many other animals, complex social behavior and interactions are essential to proper health and survival (young, 2008). since socialization is consequential for proper health and development, the lack thereof can lead to several issues. isolation is associated with higher rates of dementia and cardiovascular disease and an increased risk of mortality (finley, schaefer, 2022). when it comes to neurological symptoms, extended isolation can cause issues such as cognitive decline and lack of social understanding (offord, 2020). these effects can be seen in the amygdala and the processes that it controls. figure 1. in the brain, the amygdala affects emotions, specifically fear and anger, which are heavily influenced by a lack of social interaction. our current understanding of the amygdala suggests that increased levels of anxiety and further fear responses are mediated by the amygdala. (istock.com, jambojam) how social isolation changes the amygdala: social isolation can cause the brain to undergo neural plasticity, or the changing and adaptation of the brain. several circuit changes in the amygdala are associated with the effects of social isolation. to properly study this, arry harlow performed many well-known experiences with rhesus monkeys in 1944 (offman, 2020). harlow separated baby monkeys from their mothers and raised them in clinical settings. it was noticed that these monkeys showed strange behavior such as circling their cage mindlessly and self-mutilating (aps, 2018). specifically, harlow demonstrated that baby monkeys born and raised in social isolation were naturally more aggressive and struggled with maintaining social interactions with other monkeys in 1944. these experiments started many conversations regarding how social isolation can affect interactions between different lobes of the brain. one longitudinal study by the bucharest early intervention project followed 136 adopted children (mean age of 55.56 months) who were exposed to social isolation in institutions such as orphanages as young isolation is a common state for many people to feel. despite this, isolation can have detrimental effects on people’s emotions and brain. in particular, isolation affects the amygdala, specifically when it comes to anxiety and fear responses. researchers have recently become further interested in the effects of isolation on the brain, especially following the covid-19 quarantine. understanding social isolation and its effects on the brain is crucial to learning more about the sociability of human beings, as well as how social anxiety can be caused or affected by interactions with others. abstract 26 children. this study utilized magnetic resonance imaging (mri) in order to study the brain’s structure and neural connections. in children raised in institutions, the connectivity between the pfc and amygdala was immature in comparison to a traditional upbringing: this link is crucial in regulating emotions and influencing fear learning. this could lead to a possible lack of rational decision-making, as if the amygdala is unable to communicate with the prefrontal cortex, then learning aversive stimuli would be strained. interestingly, children who grew up socially isolated were found to have increased activity between the pfc and hippocampus regions associated with aversive learning through the same study. although these findings seem to be contradictory, each brain connection is responsible for regulating and expressing specific emotions, reactions, or other important mechanisms; no one connection is responsible for the entirety of one large-scale interaction. the relationship between the pfc and the hippocampus being increased could be causing increased memory storage. by remembering more, the brain is able to make more educated decisions about more things, and this overthinking is often associated with higher levels of anxiety. the majority of other neural pathways affected by the increased social isolation in children who grew up in institutions are between the pfc, amygdala, hippocampus and striatum, all of which are associated with fear, anxiety, and rewards (xiong, et al. 2023). ...each brain connection is responsible for regulating and expressing specific emotions, reactions, or other important mechanisms... brain has been heavily associated with an increase of depression and anxiety, which can all be tied back to the social isolation’s effects on the blood barrier of the amygdala (wu, et al. 2022). researchers at peking university health science center utilized male and female mice in a study to test childhood isolation’s effects on the brain. three-weekold mice were either caged alone or with four to six other mice for eight weeks. the results showed that female mice were incredibly affected by this isolation. interestingly, there were minimal changes observed in male mice in comparison. when the female mice caged in isolation were examined, their brains showed signs of inflammation. chronic stress can affect the blood barrier of the amygdala, and oftentimes, can lead to inflammation of the brain, and is likely a result of the social isolation that these mice underwent over the eight-week period (wu, et al. 2022). isolation how it affects fear responses and anxiety figure 2. (zeanah et al., 2009) moreover, the size of the brain can be affected by these changes as well. researchers have found that the size of your amygdala is inversely proportional to the size of your social circle; generally, smaller amygdalas are associated with fewer angry emotions and increased socialization (offman, 2020). these changes are fascinating and important to consider when it comes to the importance of social interaction in the brain. finally, chronic stress caused by solitude during childhood has been shown to alter the blood-brain barrier of the amygdala. inflammation in the long and short-term effects of social isolation: there are many long-term and short-term effects seen by individuals who have experienced social isolation of any kind. one of the major symptoms seen as a result of social isolation is the increase of chronic stress or anxiety. these disorders can be debilitating, and cause many issues and difficulties for many people who struggle with them. furthermore, social isolation may lead to an increase in the likelihood of developing alzheimer’s. in 2018, researchers at he tsinghua-peking center for life sciences studied how mice’s ability to recognize one another was affected by social isolation. this was assessed by recording how long the mice spend interacted with one another. the mice were kept in isolation for either one day or seven days, and then given either 150 minutes or 15 minutes to explore a new environment with new mice. interestingly, when mice were returned to their original enclosures afterward, they were able to interact with and recognize their colony mates again. this effect was also seen when researchers inhibited the rac1 protein. rac1 is a small signaling protein that is commonly linked to alzheimer’s and other memory loss issues (offord, 2020). the inhibition of this protein means that signals are not being expressed as well as necessary for proper function, and specifically can affect the cell cycle and cellular plasticity. this can lead to many detrimental effects 27 such as memory loss (tangella, et al. 2020). the expression of this protein during social isolation may contribute to the lack of recognition shown by the isolated mice, and seems to point towards a possible association between alzheimer’s and social isolation (offord, 2020). these physical changes can cause many differing effects on the behavior of the individual experiencing social isolation such as heightened anxiety and depression. still, there is still a large possibility that many of these effects are reversible. when it comes to the covid-19 pandemic, there were many changes witnessed in the amygdala, such as a shrinkage in size. fortunately, researchers have noted that after the social isolation period of the pandemic passed, the changes in the amygdala have returned to regular size and function, showing the plasticity of the brain (xiong, et al. 2023). a case study covid’s effects on the brain in late 2019, the world witnessed the most recent pandemic caused by sars-cov-2. this infectious disease spread throughout the world, forcing everyone into isolation in order to protect themselves and their loved ones from getting sick. as a result, the covid pandemic stands as a great case study for the effects of social isolation on people for a long period of time. for many teenagers, this social isolation caused many mental health issues and neural changes. adolescence is a major time for brain development, and the social isolation forced onto teenagers all over the world led to notable changes in their brain. a study performed on 16-year-olds reported that teenage brains had substantial physical changes from before and after the pandemic (corrigan, et al. 2024). following the pandemic, teenagers had lower average brain cortical thickness and larger bilateral hippocampal and amygdala volumes. these changes seem to indicate that the brains of these teenagers are maturing at a faster rate than they were prior to the pandemic. this can lead to issues such as early cognitive decline. this trend can be seen in children as well. interestingly, this trend is more prominent in females than males. in order to track these changes, researchers utilized was 1.4 years, meaning that post pandemic male’s brains were 1.4 years older than they should have been. the difference between female brains prior to and after the pandemic is more drastic. the average difference in ages between pre-pandemic female 16-year-old brains and post pandemic 16-year-old brains is about 4.2 years. this means that female brains have aged at a much faster rate than male brains during the pandemic (corrigan, et al. 2024). while researchers are unsure as to exactly why male and female brains have aged, aging in the brain is often associated with increased rates of anxiety and depression. the faster your brain ages, the more likely anxiety and depression are to be risk factors for you (han, et al. 2021). conclusion social isolation is the state of having very little social interaction or contact with other people. human society is built upon complex interactions with one another due to our social nature, and a lack of social interaction can lead to many issues. whether those issues are neurological such as increased anxiety or more physical such as increased likelihood to develop cardiovascular disease, social isolation can be detrimental to the health of people. this is seen specifically in the amygdala, where we see increased levels of anxiety and fear response as a result of the neural circuits and structure being adapted by prolonged isolation. these long term and short term effects can be extremely difficult to adapt to, and this is clearly shown in experiments discussing the covid-19 pandemic. now that the peak of the pandemic was about three years ago, researchers have finally begun to start understanding the mental health effects of the quarantine on differing groups. we have finally started getting results about the neural implications of the pandemic, but there is still a lot of room to learn and understand more about the effects of social isolation on the brain and the lives of the people around us. references 1. aps. (2018, june 20). harlow’s classic studies revealed the importance of maternal contact. association for psychological science aps. https://www.psychologicalscience.org/publications/observe r/obsonline/harlows-classic-studies-revealed-theimportance-of-maternalcontact.html#:~:text=infant%20rhesus%20monkeys%20wer e%20taken,and%20engaging%20in%20self%2dmutilation 2. catherine offered. (2020, july 13). how social isolation affects the brain. department of psychiatry and behavioral neuroscience | the university of chicago. https://psychiatry.uchicago.edu/news/how-social-isolationaffects-brain 3. corrigan, n. m., rokem, a., & kuhl, p. k. (2024, september). covid-19 lockdown effects on adolescent brain structure ... pnas. https://www.pnas.org/doi/full/10.1073/pnas.2403200121 4. finley, a. j., & schaefer, s. m. (2022). affective neuroscience of loneliness: potential mechanisms underlying the association between perceived social isolation, health, and well-being. journal of psychiatry and brain science. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9910279/ 5. han, l. k. m., schnack, h. g., brouwer, r. m., veltman, d. j., van der wee, n. j. a., van tol, m.-j., aghajani, m., & penninx, b. w. j. h. (2021, july 21). contributing factors to advanced brain aging in depression and anxiety disorders. translational psychiatry. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8295382/ 6. tangella, l., clark, m. e., & gray, e. s. (2020, september 18). resistance mechanisms to targeted therapy in brafmutant melanoma a mini review. biochimica et biophysica acta (bba) general subjects. https://www.sciencedirect.com/science/article/pii/s0304416 520302488 brain matters vol. 8 2025 28 7. umberson, d., & montez, j. k. (2010). social relationships and health: a flashpoint for health policy. journal of health and social behavior. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3150158/ 8. wu, x., ding, z., fan, t., wang, k., li, s., zhao, j., & zhu, w. (2022, august 16). childhood social isolation causes anxietylike behaviors via the damage of blood-brain barrier in amygdala in female mice. frontiers in cell and developmental biology. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9424755/ 9. xiong, y., hong, h., liu, c., & zhang, y. q. (2023, january). social isolation and the brain: effects and mechanisms. molecular psychiatry. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9702717/ 10. young, s. n. (2008, september). the neurobiology of human social behaviour: an important but neglected topic. journal of psychiatry & neuroscience : jpn. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2527715/ 11. zeanah, c. h., egger, h. l., smyke, a. t., nelson, c. a., fox, n. a., marshall, p. j., & guthrie, d. (1970, july 1). institutional rearing and psychiatric disorders in romanian preschool children. american journal of psychiatry. https://psychiatryonline.org/doi/10.1176/appi.ajp.2009.0809 1438 isolation how it affects fear responses and anxiety about the author ananya sampathkumar is a sophomore, majoring in neuroscience with minors in chemistry and public health. outside of brain matters, ananya is an assistant editor-in-chief for double helix digest, a member of starcourse, a volunteer at carle hospital, and works at the office of undergraduate admissions as a tour guide and student ambassador. in her free time, ananya likes to read books, make jewelry, watch movies, and hang out with her friends. 29 30 brain matters vol. 8 no. 1 written by micah wang fear on repeat: examining the impact of ptsd on the amygdala what is ptsd? post-traumatic stress disorder (ptsd) is a psychiatric disorder inflicted by experiencing or witnessing a traumatic event, triggering a variety of symptoms. individuals with ptsd can experience symptoms such as nightmares, flashbacks, and detached behavior, leading to the inability to function normally, particularly in social or family life (iribarren et al., 2005). these symptoms can affect a person for a lifetime, emphasizing the importance of this disorder. what is the amygdala? the amygdala is one of the main brain regions that is affected by ptsd. the amygdala is a cluster of nuclei that lies in front of the hippocampus and near the temporal lobe (johns, 2016). the amygdala is divided into many different sections of nuclei, but the three main groups are the basolateral, corticomedial, and the central nucleus (johns, 2016). the basolateral group receives visual and auditory projections from the temporal lobe, and the corticomedial group receives input from the olfactory bulb, which processes smell information. therefore, the corticomedial group is more important in animals with a keen sense of smell. the central nucleus elicits emotional responses and projects them to the hypothalamus and autonomic region of the brain stem (johns, 2016). in a study where lesions of the central nucleus were found, fear conditioned responses were eliminated, which suggests its involvement in experiencing fear (ressler, 2010). 67 the amygdala processes external stimuli as well as regulatory stimuli that come from connections with areas of the brain that modulate the amygdala (ressler, 2010). areas such as the prefrontal cortex and the sensory cortical and thalamic areas mediate subregions in the amygdala and are involved in inhibiting its ability to elicit fear responses (ressler, 2010). figure 1. a) diagram of the amygdala and its subregions. b) central nucleus is involved in sending response output via the stria terminalis, which is a major output pathway for the amygdala. the cortical nucleus receives olfactory stimuli while the basal nucleus receives non-olfactory stimuli. brain matters vol. 8 2025 how does ptsd affect the amygdala? the amygdala is one of the most strongly involved brain structures in the pathophysiology of ptsd (morey et al., 2012). however, studies that have shown differences in amygdala volume in those with ptsd fail to draw a conclusive correlation between amygdala volume and the onset of ptsd (pieper et al., 2020; ousdal et al., 2020). inconsistent results of these studies could come from varying demographics in the studies (sex, race, type of trauma) and measuring the amygdala as a homogeneous rather than heterogeneous structure (haris et al., 2023). the amygdala can be seen as both one whole nucleus as well as a structure consisting of multiple subnuclei, thus making it hard to determine whether it should be measured as one whole or multiple subparts. however, the many symptoms of ptsd corresponding with fear suggest it is critically involved in ptsd (morey et al., 2012). figure 2. abnormal amygdala volumes in adolescent ptsd patients. bar graphs display smaller mean gray matter in both the basolateral amygdala and corticomedial amygdala for the right hemisphere in the ptsd patients. left hemisphere displayed a smaller mean gray matter of the corticomedial amygdala in the ptsd patients. 68 treatments for ptsd psychotherapy and pharmacology are both effective treatments for depressive disorders (kamenov et al., 2017). there are also numerous studies done that have proven that healthy habits and practices such as exercise and diet greatly contribute to reducing ptsd symptoms as well (schry et al., 2015; van den berk-clark et al., 2018; correll et al., 2023). for example, van der kolk et al. published findings that yoga can greatly reduce ptsd symptomology and can help patients with ptsd control negative physical sensory experiences and overall functioning (2013). treatments directly affecting the amygdala are limited, but one modern neurological technique called laser interstitial thermal therapy (litt) or laser ablation has been shown to be effective (patel & kim, 2020). the surgical process of laser interstitial thermal therapy is outlined by patel & kim. the surgical procedure begins with an mri or ct scan prior to surgery. then, the optimal trajectory for the laser is planned using a computerbased navigation system. once the patient is in the operating room, they are positioned properly to align with the laser probe, and a small stab incision is made at the planned entry site, followed by drilling a burr hole in the skull at the incision site. the laser probe is then inserted through the burr hole based on the pre-planned trajectory, and the patient is placed in an mri scanner to verify probe position. when the probe is in position and secured, ablation can initiate, and periodic mri images are taken. during the ablation, the laser emits photons, which are then absorbed by tumor chromophores (molecules in tumor cells that absorb light at specific wavelengths), releasing thermal energy. once an ideal, elevated temperature is reached, proteins denature, cellular necrosis occurs, and tissue coagulates. after the ablation is completed and no other trajectories are planned, the patient is removed from the mri scanner, the probe is removed, and the incision site is irrigated and closed. in a case study done in 2020 by jon willie et al., two patients with chronic ptsd underwent an amygdalohippocampectomy, a technique in which a neurosurgeon surgically removes the amygdala and/or hippocampus. the procedure targeted the amygdala in the right hemisphere and resulted in a reduced amount of seizures and a significant decrease in ptsd symptoms (willie, 2020). the overall conclusion of this case series was that amygdalohippocampectomy can provide therapeutic healing for patients with ptsd, although it is a risky procedure. fear on repeat: examining the impact of ptsd on the amygdala figure 3. laser interstitial thermal therapy uses a laser, shown by the white arrow, to ablate destructive or harmful regions of the brain such as tumors. this method is still being developed and enhanced, such as innovations in laser probe design, probe cooling, and tissue temperature measuring technology (patel & kim, 2020). these developments continually make this procedure a more practical surgical technique and show promising indications to grow in the surgical field. conclusion ptsd is a mental disorder that affects the amygdala, a fearprocessing center and regulator for emotional responses. there are implications suggesting that ptsd affects amygdala physiology and volume, as it is often hyperactive in ptsd subjects. litt is a promising treatment to treat patients with ptsd, and has potential to be more widely used as more research on its development continues. references 1. correll, t., gentile, j., & correll, a. (2023). healthy lifestyle interventions augmenting psychotherapy in anxiety and ptsd. innovations in clinical neuroscience, 20(7-9), 18. https://pmc.ncbi.nlm.nih.gov/articles/pmc10561983/ 2. haris, e. m., bryant, r. a., williamson, t. h., & korgaonkar, m. s. (2023). functional connectivity of amygdala subnuclei in ptsd: a narrative review. molecular psychiatry. https://doi.org/10.1038/s41380-023-02291-w 3. iribarren, j., prolo, p., neagos, n., & chiappelli, f. (2005). post-traumatic stress disorder: evidence-based research for the third millennium. evidence-based complementary and alternative medicine, 2(4), 503–512. https://doi.org/10.1093/ecam/neh127 4. johns, p. (2016, october 14). functional neuroanatomy. clinical neuroscience. https://www.sciencedirect.com/science/article/pii/b97804431 03216000035#s0140 5. kamenov, k., twomey, c., cabello, m., prina, a. m., & ayuso-mateos, j. l. (2017). the efficacy of psychotherapy, pharmacotherapy and their combination on functioning and quality of life in depression: a meta-analysis. psychological medicine, 47(3), 414–425. https://doi.org/10.1017/s0033291716002774 6. morey, r. a., gold, a. l., labar, k. s., beall, s. k., brown, v. m., haswell, c. c., nasser, j. d., wagner, h. r., & mccarthy, g. (2012a, november). amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group amygdala volume changes with post traumatic stress disorder in a large case-controlled veteran group. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3647246/ 7. ousdal, o. t., milde, a. m., hafstad, g. s., hodneland, e., dyb, g., craven, a. r., melinder, a., endestad, t., & hugdahl, k. (2020). the association of ptsd symptom severity with amygdala nuclei volumes in traumatized youths. translational psychiatry, 10(1). https://doi.org/10.1038/s41398-020-00974-4 8. patel, b., & kim, a. h. (2020). laser interstitial thermal therapy. missouri medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7023945/ 9. pieper, j., chang, d. g., mahasin, s. z., swan, a. r., quinto, a. a., nichols, s. l., diwakar, m., huang, c., swan, j., lee, r. r., baker, d. g., & huang, m. (2020). brain amygdala volume increases in veterans and active-duty military personnel with combat-related posttraumatic stress disorder and mild traumatic brain injury. journal of head trauma rehabilitation, 35(1), e1–e9. https://doi.org/10.1097/htr.0000000000000492 10. ressler, k. j. (2010). amygdala activity, fear, and anxiety: modulation by stress. biological psychiatry, 67(12), 1117–1119. https://doi.org/10.1016/j.biopsych.2010.04.027 11. van den berk-clark, c., secrest, s., walls, j., hallberg, e., lustman, p. j., schneider, f. d., & scherrer, j. f. (2018). association between posttraumatic stress disorder and lack of exercise, poor diet, obesity, and co-occuring smoking: a systematic review and meta-analysis. health psychology, 37(5), 407–416. https://doi.org/10.1037/hea0000593 12. schry, a. r., rissling, m. b., gentes, e. l., beckham, j. c., kudler, h. s., straits-tröster, k., & calhoun, p. s. (2015). the relationship between posttraumatic stress symptoms and physical health in a survey of u.s. veterans of the iraq and afghanistan era. psychosomatics, 56(6), 674–684. https://doi.org/10.1016/j.psym.2015.07.010 13. van der kolk, b. a., stone, l., west, j., rhodes, a., emerson, d., suvak, m., & spinazzola, j. (2013, november 14). yoga as an adjunctive treatment for posttraumatic stress disorder: a randomized control trial. trauma research foundation. https://traumaresearchfoundation.org/wpcontent/uploads/2021/05/yoga-f-j-clin-psychiat-1.pdf 14. willie, c. j. t. (2020, october). case series: unilateral amygdala ablation ameliorates...: neurosurgery. cns neurosurgery. https://journals.lww.com/neurosurgery/fulltext/2020/10000 /case_series__unilateral_amygdala_ablation.23.aspx 69 brain matters vol. 8 2025 70 about the author micah is a freshman at uiuc majoring in neuroscience. he became involved in brain matters to gain experience writing research articles. outside of academics, you can find him staying active in the arc by working out or playing volleyball. in the future, micah hopes to make it to medical school one day. 71 volume 8 (will be vol 7 on site) president brain matters board katy is a graduating senior in mcb with a certificate in neuroscience. her favorite thing about being the president of brain matters has been meeting new people each semester and sharing her passion for neuroscience. her research interests center around the interactions between the peripheral immune system and the brain, with a particular focus on the modulation of microglia by peripheral infection. after graduation, she plans to attend ohio state university to pursue a phd in neuroscience. co-chief editor andrew is a sophomore with a major in neuroscience and minors in spanish and chemistry. one favorite thing about being editor in chief for brainmatters is that he gets to read so many interesting articles about neuroscience-related discoveries everyday! outside of the club, he pursues research regarding optimization with on-tissue chemical derivatization and proteomics projects. c0-chief editor vice president manan is a senior majoring in brain and cognitive sciences and is pursuing a minor in chemistry. apart from being a pre-dental student, manan has previously been an orientation leader at uiuc. last summer, manan worked with people of determination and designed thinking modules for underprivileged students in india. outside of class, manan is deeply interested in reading books that pertain to cognitive psychology and productivity, engaging in insightful scientific dialogue and community service. he looks forward to making brain matters an inclusive and engaging scientific committee on campus shireen aydogan is a senior majoring in molecular and cellular biology on a premed track and exploring the possibility of an arabic and communications minor. she devotes time to teach english to refugees and volunteer at the free health clinic in the community throughout the school year as well. in her free time she enjoys playing the guitar, and spending time with her family. she also likes to stay active by playing basketball and snowboarding. she hopes to increase awareness in neuroscience through her writing and as social/advertising chair for brain matters. social events chair social media chair hello! my name is celeste and i’m a december ‘23 mcb and psychology alum. my last semester as a student i had the privilege to serve on the brain matters exec board as social chair. i currently work as a mental health technician trainee at an in-patient hospital in chicago. i plan to continue working as i prepare myself to apply to medical school next year! my current hobbies include reading, spending time with my family and friends, and playing animal crossing new horizons. vani sharma is majoring in mcb honors on the pre-med track, with a minor in public health & neuroscience certificate. she is a writer for brain matters, which allows her the opportunity to learn about the brain & its neuroanatomy in depth along with her interest in brain disorders. on campus, she is heavily involved with medical clubs & the illini strings orchestra, serves as an undergraduate research ambassador, is a part of the madak erdogan women's health & metabolism lab, and works as a teaching assistant for chemistry. after graduating from uiuc, she hopes to attend medical school. design head michelle bishka is a junior majoring in specialized chemistry and minoring in computer science. outside of brain matters, she is an undergraduate researcher in the silverman lab and a member of american chemical society. she later hopes to pursue graduate studies in chemistry. br ai n m at te rs b oa rd brain matters・volume vii 86 treasurer kamile aleksaite is a senior in bioengineering with a minor in health administration. she is the treasurer, co-social chair, and editor for the brain matters journal. her hobbies include playing volleyball and tennis, and she works as a lab technician at the evolutionary immunology and genomics laboratory. she plans to continue her studies at uiuc through the master’s program in bioengineering. brain matters vol. 8 no. 2 written by brianna mae huner investigations came to the forefront. it was initially projected that the data collected from the hgp would revolutionize the screening, diagnosis, and treatment of mental illnesses. however, 20 years after this prediction was made, the etiology of these conditions remains unclear, as the nature of these illnesses has been found to be difficult to discern through genetic studies. schizophrenia spectrum disorder (also known as schizophrenia) is characterized by symptoms of three types: positive, negative, and disorganized symptoms, with a poor prognosis and heavy cost toward the individual, their family, and society. positive symptoms are referred to as such because their symptoms add characteristics that are not already present in normal functioning, such as hallucinations or delusions. negative symptoms are the opposite, “taking away” from normative functioning, such as avolition (lack of motivation) and diminished emotional expression. disorganized symptoms refer to a lack of order and form in terms of thinking or activity, such as disorganized speech and motor behavior (american psychological association, 2022). schizophrenia exists on a spectrum of disorders and is believed to be at least partially caused by genetics. the risk of developing schizophrenia is linked to the degree of relation to a family member with schizophrenia. as seen in figure 1, a first degree relative to a patient with schizophrenia would have a 3.0% hospitalization rate for psychosis, and a second degree relative would have a 2.2% hospitalization rate, both compared genetic research and its revolutionary? contributions to schizophrenia prevention introduction for over a century, physicians, neurologists, psychiatrists, biologists, and eventually geneticists have been working hard to answer the question: what causes schizophrenia and its related disorders? in earlier days of research, much of the focus was placed on the treatment of such conditions, and scientists have made great advancements in this area. for example, in the early 19th century, it was typical to see patients with schizophrenia exhibit catatonia, which is a symptom characterized by a decrease in reactivity to environmental stimuli. these patients were stuck within these states for days or weeks. now, catatonia is treated with benzodiazepines, and patients can return to noncatatonic functioning over a much shorter period of time. sienart et al., 2014). this pharmacological discovery has improved the lives of schizophrenia patients dramatically and has shifted the typical symptomology observed in this disorder. yet, the question remains: what causes this disorder, and can we use that knowledge to prevent its development in the first place? investigations into the etiology (or causes) of schizophrenia have proven to be less fruitful than their treatment-based counterparts. the knowledge that schizophrenia is at least partially genetic motivated a surge of investigations into the human genome. this research began with studies using molecular genetics, a method proven to be incredibly effective in discoveries into etiology of other genetic diseases. with the completion of the human genome project (hgp), genome-wide investigations 59 compared to the general population hospitalization rate of 0.9% (karlsson, 1971). this disorder can be debilitating, often requiring full-time hospitalization and lifetime treatment. many patients never return to normal functioning, even between episodes. there is also a higher risk of suicide and early death associated with this disorder (jobe & harrow, 2005). the severity of such a disease, combined with its proven genetic component, has driven large-scale research into the etiology of schizophrenia at the order of the genes, producing a myriad of results. table 1. rates of hospitalization with functional psychosis in relatives of psychotic index cases in iceland. segregation such as dominant, recessive, and x-linked (chial, 2008). one can follow along using genetic information to make reasonable predictions about the phenotype, such as hair or eye color, of an organism by simply examining their pedigree. the diseases with causes found through molecular genetics followed mendelian patterns of inheritance, such as huntington’s disease, whose pattern of inheritance can be observed in figure 2. by comparing the genes of people who both do and do not have a familial disorder, target genes can be identified. additionally, disorders such as hd and als are caused by a single defective gene that can be isolated and identified relatively easily. on the contrary, mental illnesses do not follow mendelian patterns of inheritance. they are likely polygenic (caused by multiple genes) and multifactorial (caused by genetic and environmental factors, as well as interactions between genes and environment). by using these methods of searching and comparing target areas of the genome, there were genes identified as possibly being involved in mental illnesses, but the results weren’t as clear-cut as finding one gene that causes a certain disorder. brain matters vol. 8 2025 60 research method #1: molecular genetics biologists have been using the varying tools at their disposal over time to investigate the etiology of genetic diseases, with one of these methods being molecular genetics. this research revealed key insights into the fields of biology, neurology, and genetics, though it was not as comparatively impactful in psychiatry. molecular genetics, a field of research that studies genes on a molecular level, focuses on variations in dna. studies using this framework have shed light on the genetic mutations behind a number of neurological disorders, such as huntington’s disease (hd), fragile x syndrome (fxs), and amyotrophic lateral sclerosis (als) (cowan et al., 2002). these discoveries allowed for improved screening and early identification of these conditions. however, studies using molecular genetics to find the causes of mental illnesses gave mixed results of small effect sizes. this difference can be explained through the nature of these conditions, particularly within the inheritance patterns of the disorder whose causes were found. many americans are made aware of mendelian patterns of inheritance, though they may not know it by that name, while taking high school biology, through lessons about yellow and green peas and punnett squares. classic mendelian patterns of inheritance involve patterns of segregation while investigating the human genome to find associations between certain genes and specific psychiatric disorders, a number of loci were identified. linkage analysis was often used in these studies prior to the completion of the human genome project, which uses genetic markers to find areas on the genome that are close to genes thought to cause certain conditions (pulst, 1999). some well-known findings from analyses looking into schizophrenia identified chromosomal regions associated with the serotonin 5ht2a receptor gene (13q14.1-32), as well as chromosomal regions related to synapse-related genes (22q11-12) (cowan et al., 2002). these findings garnered interest, considering the importance of synapses in neuronal function and serotonin’s role in mood regulation and homeostatic roles (mohammad-zadeh & bryant, 2008). with the advent of new techniques figure 1. correa & guimaraes (2006). pedigree showcasing the inheritance of huntington's disease (hd). research method #2: data analysis from the human genome project the human genome project (hgp) was a moon-shot project, with the goal of sequencing the entire human genome, and its completion created a new wave of data and discoveries into the field of genetic biology. launching in 1990 and concluding in 2003, the hgp cost $3 billion (gannett, 2023). the ability to map the entire human genome created a vast bank of data that could be utilized when researching, for example, cancer and its treatment (rood & regev, 2021). it was predicted that the discoveries resulting from the hgp data would allow for gene-based treatments for critical disease such as diabetes and hypertension, as well as change the game for the treatment of mental illnesses. some scientists went so far as to say that the impact the hgp would have on the field of medicine would be comparable to the discovery of antibiotics (torrey, 2024). genome wide association studies (gwas) were conducted using the new data, and nearly 300 single nucleotide polymorphism (snp) genetic loci were linked to an increased risk of the development of schizophrenia. such findings seemed to signal that major breakthroughs were on the way. unfortunately, much of the evidence uncovered through gwas did not hold up under scrutiny. through comparisons between studies, about half of the genomic loci associated with schizophrenia was discovered to also be associated with other disorders believed to be partially genetic, such as bipolar disorder and autism (torrey, 2024). therefore, an argument can be made that these loci are associated with psychiatric disorders as a whole, rather than schizophrenia specifically. additionally, many of the snps identified were found to have a very small effect size, and while they could be linked to schizophrenia, they could not be linked to a cause of schizophrenia. this bears resemblance to how a reduction in size of the frontal lobe is associated with depression, but it is not known if this reduction causes depression, or is caused by depression (joseph et al., 2025). despite these discouraging findings, there may be one with promise. a change in the region of the genome known as the major histocompatibility complex presents strong evidence of an association with schizophrenia, potentially revealing a link between the disorder and the immune system. the major histocompatibility complex (mhc), located on chromosome 6, is associated with the regulation of immune functions, as well as many infectious diseases and autoimmune disorders (abualros et al., 2021). a gwas revealed an association between a small alteration in this area and the development of schizophrenia (caseras et al., 2024). while this finding may initially seem confusing, it does connect some previous findings and hypotheses about schizophrenia. the presence of some infectious diseases during pregnancy, such as influenza, though new evidence reveals that more research is needed in this area (fung et al., 2022), and toxoplasma gondii (yang et al., 2024), are known to slightly increase the risk of the child developing schizophrenia. the mhc’s association to autoimmune disorders could also shed light onto the hypothesis that differences in the functions of microglia (the “brain’s immune system”) could explain some of the symptoms of schizophrenia, as it is hypothesized that essential synapses could be erroneously tagged for consumption by microglia as a part of the brain’s synaptic pruning process used to clear unused and unneeded synapses (li et al., 2023). this incorrect deletion of synapses could explain the cognitive and disorganized issues often associated with schizophrenia, as vital neuronal pathways could be disrupted. unfortunately, this finding only had a polygenic risk score, which gives an estimate of an individual’s genetic risk for developing a specific trait, to explain less than 10% of the variation in liability for the disease (andreassen et al., 2023). while these findings are promising, they are far from the revolution that was predicted. genetic research and its revolutionary? contributions to schizophrenia prevention one can follow along using genetic information to make reasonable predictions about the phenotype, such as hair or eye color, of an organism by simply examining their pedigree. 61 techniques and technology, it was believed that we would be able to find clearer answers in these areas and their connection to schizophrenia. future directions despite the lack of definitive findings through genetic studies, there may still be something to be gleaned from this data. the results of the hgp still have hopes of finding significant results, as researchers hope to use newly introduced machine learning functions to aid in their search. they are also making efforts to factor in potential epigenetic changes caused by environmental factors and gene x environment interactions, or perhaps the solution lies in something that hasn’t been considered yet. it is possible that the flaw in this system is the question itself. it is widely accepted that there is no single or primary cause of many mental disorders, and it is possible that these disorders are the result of multiple different pathways. to explain this, we may look toward an example in the medical world: obesity, and its association with leptin and leptin genes. leptin is a hormone that signals satiety, telling the body when it should stop eating. leptin receptor deficiency is a rare genetic disorder which causes a mutation in the leptin gene that results in an inability for the body to produce leptin. without a satiety signal, the body’s ability to regulate eating is compromised, and the subject becomes obese obese. however, when this subject is treated with leptin supplements, their food intake regulation ability is restored, and they return to a normal weight. in this case, this mutation causes obesity. but not all cases can be explained this way. leptin treatment only works on obese patients who have this mutation, and if they do not, the treatment produces little effect (milan et al., 2021). obesity has multiple causes, and treatment must be derived based on the specific cause. could a similar approach be applied to schizophrenia, where different treatments could be used for different causes? could we pinpoint these different causes? one of the most important traits needed in research is curiosity. while many may be discouraged by the lack of major breakthroughs in the genetic research of schizophrenia and other psychiatric disorders, others may see this as eye-opening, and an invitation to think nontraditionally about these findings. while it was originally believed that genetic research such as molecular genetics, linkage analysis, genome wide association studies, and more would be the key to understanding the etiology of schizophrenia, this was found to be inaccurate, but that doesn’t mean that all hope is lost. all that is needed is a new question to be asked. about the author brianna mae is a junior at the university of illinois majoring in clinical/community psychology. she became involved in brain matters to gain more experience researching and writing about the current research in neuroscience. when she is not writing for brain matters, she is also involved in dr. kwapil's project on life experiences lab, and is the treasurer for the psychology research and community club (pracc). brianna mae is hoping to pursue a phd in clinical neuropsychology and conduct research about the neurological basis behind different clinical disorders. 6. corrêa, b.b., xavier, m. & guimarães, (2006). j. association of huntington's disease and schizophrenia-like psychosis in a huntington's disease pedigree. clin pract epidemiol ment health 2(1). https://doi.org/10.1186/1745-0179-2-1 7. cowan, w. m. et al. (2002). the human genome project and its impact on psychiatry. annual review of neuroscience, 25. doi: 10.1146/annurev.neuro.25.112701.142853 8. fung et al. (2022). neuropsychiatric outcomes in offspring after fetal exposure to maternal influenza infection during pregnancy: a systematic review. reproductive toxicology. 113. https://doi.org/10.1016/j.reprotox.2022.09.002 9. gannet, l. (2023). the human genome project. the stanford encyclopedia of philosophy. metaphysics research lab, standford university. 10. gottesman, i. i. (1991). schizophrenia genesis: the origins of madness. w h freeman/times books/ henry holt & co. 10. jobe, t. h., & harrow, m. (2005). long-term outcome of patients with schizophrenia: a review. the canadian journal of psychiatry. 50(14). https://doi.org/10.1177/070674370505001403 11. joseph et al. (2025). structural brain changes and neuroticism in late-life depression: a neural basis for depression subtypes. international psychogeriatrics. 33(5). https://doi.org/10.1017/s1041610221000284 12. karlsson, j. l. (1971). rates of the schizophrenic genotype in relatives of psychotic persons. hereditas. 69(2). https://doi.org/10.1111/j.1601-5223.1971.tb02437.x 13. li, j. et al. (2023). new insight in the cross-talk between microglia and schizophrenia: from the perspective of neurodevelopment. frontiers in psychiatry. 14. doi=10.3389/fpsyt.2023.1126632 14. milan et al. (2021). leptin and obesity: role and clinical implication. frontiers in endocrinology. 12. doi=10.3389/fendo.2021.585887 15. pulst, s. m. (1999). genetic linkage analysis. arch neurol. 56(6) doi:10.1001/archneur.56.6.667 16. sienart et al. (2014). a clinical review of the treatment of catatonia. frontiers in psychiatry. 5. doi.org/10.3389/fpsyt.2014.00181 17. torrey, e. f. (2024). did the human genome project affect research on schizophrenia?, psychiatry research, 333. https://doi.org/10.1016/j.psychres.2023.115691. 18. yang et al. (2024). toxoplasma gondii infection positively associated with schizophrenia: evidences from uk biobank cohort and case-controlled studies. journal of psychiatric research. 175. https://doi.org/10.1016/j.jpsychires.2024.05.025 brain matters vol. 8 2025 62 references 1. abualrous et al. (2021). major histocompatibility complex (mhc) class i and class ii proteins: impact of polymorphism on antigen presentation. current opinion in immunology. 70. https://doi.org/10.1016/j.coi.2021.04.009 2. american psychological association, (2022). schizophrenia spectrum and other psychotic disorders. diagnostic and statistical manual of mental disorders. https://doi.org/10.1176/appi.books.9780890425787.x02_schizop hrenia_spectrum 3. andreassen et al. (2023). new insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications. world psychiatry. 22(1). https://doi.org/10.1002/wps.21034 4. caseras et al. (2024). common risk alleles for schizophrenia within the major histocompatibility complex predict white matter microstructure. translational psychiatry. 14(194). https://doi.org/10.1038/s41398-024-02910-2 5. chial, h. (2008). mendelian genetics: patterns of inheritance and single-gene disorders. nature education 1(1) https://doi.org/10.1186/1745-0179-2-1 https://doi.org/10.1016/j.reprotox.2022.09.002 https://doi.org/10.1177/070674370505001403 https://doi.org/10.1017/s1041610221000284 https://doi.org/10.1111/j.1601-5223.1971.tb02437.x https://doi.org/10.1016/j.psychres.2023.115691 https://doi.org/10.1016/j.jpsychires.2024.05.025 https://doi.org/10.1016/j.coi.2021.04.009 https://doi.org/10.1176/appi.books.9780890425787.x02_schizophrenia_spectrum https://doi.org/10.1176/appi.books.9780890425787.x02_schizophrenia_spectrum https://doi.org/10.1002/wps.21034 https://doi.org/10.1038/s41398-024-02910-2 63 volume 8 (will be vol 7 on site) the use of mri for the early prevention of alzheimer’s disease joy akindulureni abstract alzheimer’s disease (ad) is a neurodegenerative disorder that affects the cells in the brain which results in dementia. ad is caused by the accumulation of amyloid beta (a𝛽)peptides made from protein forms an accumulation in the brain that leads to plaques and tangles that affects the medial temporal lobes and neocortical structures. early detection of ad is very important for intervention and early treatment to prevent the further progression of the disease in individuals. magnetic resonance imaging (mri) is a neuroimaging tool that can be used to help study brain changes. mri can help to detect biomarkers that are associated with ad which could be white matter hyperintensities, hippocampal volume loss, and tau phosphorylation. tau phosphorylation is due to cerebral atrophy which leads to neurodegeneration. the application of mri in the early detection of ad could help in the progressive treatment and preventative methods for individuals who have ad or are at risk of developing the disease. this paper will discuss the use of neuroimaging, specifically mri on the early detection of alzheimer's in people which can be used in clinical settings and lead to better prevention methods. introduction alzheimer’s disease (ad) is characterized by decline in cognition, memory loss which in turn alters behavior and interferes with activities of daily living (breijyeh& karaman., 2020). it is more defined as an interaction of amyloid 𝛽eta protein with glial cells and neurons, which results in neuritic plaques and neurofibrillary tangles in the cerebral cortex mostly in the medial temporal lobes and neocortical structures (srivastava & ahmad, 2021). ad is shown by cognitive decline, language capabilities, and loss of memory all of which can later affect behavior of the individual. some structural symptoms would be progressive loss of neurons, neuronal network destruction and atrophy of the hippocampus (blennow, 2006). ad symptoms are categorized based on early, moderate or late stages. ad is a very complicated disease that could be caused by very different factors and there is no precise cause of the disease. for the early stage, the symptoms like misplacement of items, mood changes and memory loss are easily dismissed . the moderate stage is when the symptoms become more severe with difficulty in communication and spatial navigation which can interfere with personal life. in the late stage, symptoms are more severe with no remedy like inability to recognize familiar faces, physical capabilities (khan et al., 2020) previous studies have also shown that atrophy and volume loss in the hippocampus are an early characteristics of ad as they can be associated with cognitive and memory decline (eskildsen et al., 2015).therefore, ad is the leading cause of dementia in the world; its prevalence continues to increase with the numbers doubling every 20 years. ad constitutes challenges for the healthcare system and signifies the need for strategies that could lead to early detection. early detection of ad is very important for the development of preventive measures and progressive treatment methods for individuals at risk. with neuroimaging tools today, mri and pet are the most common for their ability to detect brain abnormalities that could lead to a risk in developing ad (mosconi et al., 2007). witb these neuroimaging tools, we can be able to further prevent the development of ad in individuals. alzheimer’s disea se ad is a neurodegenerative disorder and a common cause of dem entia that is caused by cell death due to neuritic plaques and neurofibrillary tangles in the cerebral cortex. it is the sixth most leading cause of death in the united states and is caused by neuronal cell death which starts in the entorhinal cortex of the hippocampus. ad’s etiology involves the combination of genetic predisposition, environmental factors and lifestyle choices. even though ad is known to affect people who are older, it is necessary to know that the symptoms do not progress with age (zvěřová, m., 2019). many studies have shown that aging is associated with ad as they have been with approximately 90% of the cases. ad usually affects people from ages 65 and older but it is also possible that the disorder could show up earlier due to other factors like genetic mutations or even underlying health risks like heart diseases or stroke (blennow., 2006). ad prevalence has been known to be increasing for each year and could keep increasing with the amount of cases each year. the biomarkers for ad are mostly with blood and the structural brain changes due to the neuroimaging tool that is being used like mri as it is more accessible and can be better used for diagnosis of the disease.(altuna-azkargorta & mendioroz-iriarte, 2021). biomarkers are very essential for the diagnosis of the disease and also help with the use in treatment methods as well. pathology of ad stems from the plaques and tangles in the brain due to tau phosphorylation. another biomarker for diagnosing ad could be due to the lessening of hippocampal volume and hyperintensities of white matter in the brain (schapiro et al., 2009). early detection of ad would lead to better preventative methods that can be used in clinical settings for individuals. the role of mri in the detection of alzheimer’s disease mri, an innovative and non-invasive tool plays an important role in identifying brain changes earlier that are associated with ad leading to progressive interventions. with mri, neurodegeneration which is present in cerebral atrophy can be captured by mri imaging. while not being specific to cerebral atrophy, this biomarker of neurodegeneration along with neuronal injury serves as an important biomarker in the diagnosis of ad. are also another type of biomarkers that can be used in the diagnosis of ad. cerebral atrophy is caused by neurodegeneration which can be captured by mri. optimization of mri to diagnose ad can be very valuable in the early detection of the disease. progression of the atrophy is also later seen in the medial temporal lobe (mtl) and entorhinal cortex which later results in deficits in executive functioning and memory loss for ad patients. mri can also be used to detect white matter hyperintensities which show demyelination and axonal loss. with the use of mri, it can play a huge role in the early detection of the disease which could lead to better treatment methods for individuals at risk before it progresses further. the focus of the use of mri can help in detecting the biomarkers associated with ad. the biomarkers associated with ad that could be detected would be cerebral atrophy, which is the loss of neurons and synapses that leads to brain shrinkage from neurodegeneration. atrophy and volume loss of the hippocampus also show the characteristic of ad that is associated with cognitive decline. this could spread to other regions which leads to worse progression of the disease. when the atrophy spreads to the cortical regions like frontal, parietal and temporal brain regions, the disease worsens which can be captured with mri (chandra et al., 2018).white matter hyperintensities is another biomarker that could be detected by mri as they show the demyelination and loss of axons in the brain. the application of mri in early detection of ad could make for better treatment methods that can help individuals with the disease or who could be at risk (chandra et al., 2018). challenges and directions while mri can be used in the detection of ad, it also faces limitations due to sensitivity of being able to differentiate ad from either normal aging or other neurological diseases. this limitation showcases the importance for research and refinement. another limitation would be that there could be an overlap of the imaging characteristics with other disorders that could make the results more complex. another limitation would be the accessibility and cost that comes with using the mri due to the equipment, which could limit its use and availability in certain settings. mri in the early detection of ad can be useful for the progression of treatment methods of the disease. mri can be used to capture the alterations in brain structure like the hippocampal volume, white matter loss, and atrophy, which can give a quick insight on the development and progression of the disease before it worsens. mri can also help clinicians and researchers be able to understand better about the brain structures affected and how they impact function so that there could be more methods for treatment which might eventually lead to a decrease in the prevalence. conclusion ad is a neurodegenerative disorder that affects millions of people worldwide and is known for being associated with aging as it mostly affects the elderly. it is caused by tangles and plaques due to tau phosphorylation which leads to neuronal cell death that affects the cerebral cortex. it is characterized by memory loss, brain structure atrophy, language capabilities and behavioral alterations. although there is no known cause, there could also be a lot of factors that contribute to the disease which could be genetic or environmental. there are no preventive measures but there are protective measures like maintaining a healthy lifestyle and being physically active which could help. mri being a non-invasive tool in neuroimaging could play an important role in the detection of ad that could potentially lead to the further progress of treatment methods. there are some limitations and challenges which could come with the use of the neuroimaging tool like the cost, complexity of the detecting for the disease, and the overlap in imaging features although it can still be an innovative tool to be able to detect for the disease earlier that could lead to better methods for treatment. figure 1. a) structure of the brain when a healthy with the neurons and hippocampus with b) alzheimer’s showing the plaques in neurons and shrinkage of hippocampus (breijyeh& karaman., 2020) figure 2. increased white matter hyperintensities in an alzheimer’s patient compared to a healthy normal control and a patient with mild cognitive impairment (mci) (chandra et al., 2018). brain matters・volume vii 64 references 1. altuna-azkargorta, m., & mendioroz-iriarte, m. (2021). blood biomarkers in alzheimer's disease. neurología (english edition), 36(9), 704–710. https://doi.org/10.1016/j.nrleng.2018.03.006 2. battineni, g., hossain, m. a., chintalapudi, n., traini, e., dhulipalla, v. r., ramasamy, m., & amenta, f. (2021). improved alzheimer's disease detection by mri using multimodal machine learning algorithms. diagnostics (basel, switzerland), 11(11), 2103. https://doi.org/10.3390/diagnostics11112103 3. blennow, k., de leon, m. j., & zetterberg, h. (2006). alzheimer's disease. the lancet, 368(9533), 387-403. breijyeh, z., & karaman, r. (2020). comprehensive review on alzheimer's disease: causes and treatment. molecules, 25(24), 5789. https://doi.org/10.3390/molecules25245789 4. chandra, a., dervenoulas, g., & politis, m. (2018). magnetic resonance imaging in alzheimer's disease and mild cognitive impairment. journal of neurology, 266(6), 1293–1302. https://doi.org/10.1007/s00415-018-9016-3 5. craig-schapiro, r., fagan, a. m., & holtzman, d. m. (2009). biomarkers of alzheimer's disease. neurobiology of disease, 35(2), 128-140. 6. eskildsen, s. f., coupé, p., fonov, v. s., pruessner, j. c., collins, d. l., & alzheimer's disease neuroimaging initiative. (2015). structural imaging biomarkers of alzheimer's disease: predicting disease progression. neurobiology of aging, 36, s23-s31. 7. khan, s., barve, k. h., & kumar, m. s. (2020). recent advancements in pathogenesis, diagnostics and treatment of alzheimer's disease. current neuropharmacology, 18(11), 1106–1125. https://doi.org/10.2174/1570159x18666200528142429 8. mosconi, l., brys, m., glodzik-sobanska, l., de santi, s., rusinek, h., & de leon, m. j. (2007). early detection of alzheimer’s disease using neuroimaging. experimental gerontology, 42(1-2), 129-138. 9. srivastava, s., ahmad, r., & khare, s. k. (2021). alzheimer’s disease and its treatment by different approaches: a review. european journal of medicinal chemistry, 216, 113320. 10. zvěřová, m. (2019). clinical aspects of alzheimer's disease. clinical biochemistry, 72, 3-6 brain matters vol. 8 no. 1 interview with two professors written by brianna mae huner introduction while psychology and neuroscience have a long history, this knowledge is not set in stone, nor is it all-encompassing. new findings are always being presented, sometimes disproving generally accepted principles. the scientific method allows scientists to constantly be testing and retesting hypotheses, and if these hypotheses are wrong, then sometimes the solution is questioning the foundation on which these hypotheses are built upon. asking questions is the entire foundation of science. the scientific model requires questioning what is known. the importance of asking these questions cannot be overstated, as investigation into these hypotheses can benefit the field and humanity at large. at the university level, professors have the opportunity to choose what they teach, including their own hypotheses. at the psychology department at the university of illinois, a variety of perspectives and hypotheses can be observed, coloring the general understanding of the topic of psychology and its concentrations, such as neuroscience and clinical psychology. professor justin rhodes professor justin rhodes is a professor at the beckman institute for advanced science and technology and an affiliate at the carl r. woese institute for genomic biology. he earned his bachelor's degree in biology from stanford and his phd in zoology from the university of wisconsinmadison. madison. professor rhodes has a research focus in cognitiveneuroscience and is researching how genes and the environment can affect behavior. his current lab research investigates how exercise can affect neurogenesis (the creation of new neurons) in the hippocampus. rhodes frequently discusses these concepts in the classes he teaches, which are psyc/neur 302 (applied neuroscience) and psyc/neur/phil 433 (evolutionary neuroscience), which is also cross coded as ib 436. prof. rhodes often collaborates with colleagues and wrote a chapter in the book of his doctoral advisor, dr. theodore garland jr., on behavior and neurobiology. rhodes described the importance of splitting duties based on expertise when collaborating on academic writing, writing sections of papers dedicated to concepts he has the most experience in, and leaving space for collaborators with more experience in other topics. recently, he wrote a paper with dr. ki yun lee and dr. taher saif about the involvement of astrocytes in the muscle fiber contraction-hippocampal development network, which showed that astrocytes may mediate this relationship. prof. rhodes expressed his interest in the unknown roles of glia in the brain, highlighting how microglia are seen to have specific responses to different levels of an organism engaging in physical activity. cumulatively, the function of microglia is altered by the effect of an organism running. he would like to see an investigation into the role of signaling in the blood in this effect. rhodes has conducted an abundance of research on 36 interview with two professors the hippocampus and has some of his own propositions to its functions. during intense physical activity, it has been observed that the hippocampus, typically associated with learning and memory, becomes activated. the level of activation in the hippocampus appears to have a positive relationship with the level of intensity of the activity, further indicating that these two are related. this phenomenon is a subject of curiosity and debate among neuroscientists, as the current understanding of the hippocampus and intense physical activity seem to be independent processes. there is evidence to show that physical activity could encourage neurogenesis in the hippocampus. but this evidence is not sufficient to explain how the level of intensity seems to correlate with the level of activation in the hippocampus. the classic interpretation behind this activation is that the hippocampus is acting as a part of the sensory system. this hypothesis assumes that the hippocampus activates in response to speed, because if the animal is moving through space faster, they will need to sample their environment faster to keep their spatial map up to date. the spatial map is the brain’s representation of the spatial environment surrounding it, which is used to support functioning in the environment and relating to the space one is in. the mechanism used to explain this activation is that during hippocampal activation, the hippocampus creates waves of activity, with the most salient, or powerful and effective, learning occurring at the peaks and troughs of these waves. this supposes that to increase the rate of learning, the hippocampus would need to increase the frequency of these waves to maximize learning potential. prof. rhodes believes that the hippocampus is serving a different purpose in this intense activity system, acting as a motivator of this system, instead of serving as a reactionary sensory organ. he hypothesizes that the hippocampus acts as an intensity generator, allowing the animal to move at intense speeds by motivating the body to move. it should be noted that this form of motivation is not of the higher order of consciousness, where people choose to move intensely because of their understanding of the health benefits of such activity or because they want to escape something. instead, prof. rhodes and his colleagues believe that the hippocampus is the organ needed to allow the body to move at such intense speeds when necessary. there have been several studies conducted testing this hypothesis, and a wealth of evidence collected to support it. recordings taken in the entorhinal cortex reveal that hippocampal activity precedes intense movement. this evidence could not be explained by the popular hypothesis of the hippocampus acting as a reaction to the activity, as this movement could not cause neural activity that precedes it. the sensory hypothesis also does not explain why this hippocampal activation does not occur when a subject is being moved through an environment at high speeds whenthey are not running. in a study where test mice were placed in transportation carts (analogous to a car for a human) and moved at a rapid rate, the level of activation seen in intense activity is not observed in the hippocampus, despite the need to rapidly update the spatial map still being present. however, this is a potential side effect of human evolution adjusting far slower than human technological development. this lack of activation when moving quickly through technological means could be explained by human evolution not progressing past the stage where the only way to get around quickly was through intense activity such as running. these recordings of neural activity support the hypothesis that prof. rhodes believes. stimulating these areas, instead of simply observing them, could also generate evidence to support this theory. figure 1. positive correlation of gcamp5 fluorescence slope and velocity. prof. rhodes cited a study conducted with dr. stefan remy, a professor at the university of bonn in germany. this study was conducted in mice using optogenetics, a revolutionary new technique that allows for the stimulation of specific cells using light. the study used optogenetics to stimulate the hippocampus of mice while on a treadmill. when the hippocampus was stimulated, the mice began to move around and run at an intensity that matched the level of activation in the hippocampus. this evidence supports the idea that the hippocampus supports motivation and ability to move quickly. this theory has its detractors, however, who call on the current understanding of the motor system and clinical history. the hippocampus is not traditionally connected to the movement system in the field of neuroscience. patient h.m., a famous patient in the history of psychology, was known for having large portions of his temporal lobe removed from his brain, including his hippocampus. while patient h.m. is widely known to have lost many of the abilities traditionally associated with the hippocampus, such as the ability to form new memories, he was able to move quickly or engage in intense movement after his operation. 37 brain matters vol. 8 2025 though, this possibility was not officially studied with hm. the hypothesis believed by prof. rhodes of hippocampal involvement provides evidence for why this may have been. this data has also been seen in studies, as the loss of the ability for intense movement when the hippocampus is lesioned has also been observed in experiments where rats have their hippocampus suppressed via anesthetics. the combination of evidence discussed, through studies of recording and stimulation in the hippocampus as well as lesion studies, supports rhodes’s motivator hypothesis. if hippocampal activation precedes intense movement, then it cannot be caused by intense movement, nor can it explain why similar hippocampal activation in response to nonneural-motor forms of rapid movement is not seen. in addition, his idea supports why directly stimulating the hippocampus induces intense motor activity. finally, while removal of the hippocampus does not have all-encompassing effects on the motor system, it seems to remove the organism’s ability to engage in intense movement. the commonly held sensory hypothesis of the relationship between hippocampal activation and intense physical activity does not explain this evidence. discussions such as these encourage neuroscientists to look deeper into the validity of these hypotheses. prof. rhodes’s research and hypotheses of the hippocampus can aid in growing the scientific understanding of the brain region associated with some of the most damaging effects of aging. the hippocampus is the first part of the brain to begin deteriorating as humans age, losing about 1% of it every year after the age of 20. the hippocampus is the brain region most associated with dementia, but it is also one of only two brain regions that is able to create new neurons throughout the human lifetime. studies have shown that hippocampal exercise may be beneficial for retaining hippocampal mass as humans age as regular strenuous exercise can promote neurogenesis in the hippocampus. evaluating the current knowledge of the hippocampus, especially in relation to exercise, could grant a revolutionary tool in the treatment of neurodegenerative diseases, as well as the regular struggles of aging and memory impairment. professor thomas kwapli professor thomas kwapil is the director of clinical training and an associate head of the psychology department at the university of illinois. he describes his role as being responsible for ensuring that the clinical-community program runs smoothly, as well as acting as a liaison with the department head. the clinical-community program comes with extra responsibilities, as it requires accreditation, which requires reporting to outside agencies. he received his bachelor's degree in psychology from louisiana state university, and his m.s. in psychology and phd in clinical psychology from the university of wisconsinmadison. prof. kwapil is the current supervising professor for psyc 238 (psychopathology and problems in living) and psyc 239 (community psych). this is a role that rotates among different professors in the department. instead of being the instructor for the course, the supervising professor supports and supervises the graduate students who teach the course. professor kwapil also regularly teaches a psyc 496 (adv current topics in psych) course on schizophrenia-spectrum disorders, which is his area of interest. schizophrenia-spectrum disorders include schizophrenia and other psychotic disorders, including schizophreniform disorder and brief psychotic disorder, as well as schizotypal personality disorder. it is seen through abnormalities in “positive” symptoms (including delusions and hallucinations), disorganized symptoms (such as disorganized thinking, speech, and behavior), and “negative” symptoms (such as avolition and diminished emotional expression). an estimated 3-4% of the population suffers from schizophrenia spectrum disorders. many psychologists, especially those whose perceptions are colored by the categorical nature of the diagnostic and statistical manual of mental disorders (dsm), would see these as categorical disorders, following a yes/no binary. prof. kwapil disagrees with this notion. figure 2. seq figure \* arabic 2. schizophrenia spectrum disorders. giovanni, v. (2015). it is widely believed that other disorders, such as depression and anxiety, exist on a spectrum of intensity and subclinical presentations, yet this line of thinking is not often extended to schizophrenia-spectrum disorders. many people report experiencing anxiety or depression. with some, a more clinical expression is seen. with others, these symptoms are less intense, do not last as long, and/or cause less impairment. all are experiencing these symptoms; some are simply experiencing them on a subclinical level. the same can be true for schizophrenia-spectrum psychopathology. even when it comes to clinical schizophrenia-spectrum disorder presentations, categorical measures fall short to dimensional measures. those with schizophrenia may experience psychotic episodes, which remit and return, similar to depressive episodes seen in major depressive disorder. an all-or-none categorical form of thinking, in which a subject is either in or out of an episode, may be easier to conceptualize, but is not entirely accurate to describe this phenomenon. often when people remit from episodes, their expression of symptoms doesn’t go from disordered to regularly functioning, but rather a less intense symptomology or degree of impairment. where the categorical model fails to encapsulate these observations, prof. kwapil has a more fitting explanation. 38 interview with two professors prof. kwapil and his colleagues support a dimensional model, in which schizophrenia-spectrum disorders and subclinical presentations of schizophrenia exist on a continuum, called schizotypy. prof. kwapil and his colleagues are pursuing an effort to reconceptualize schizophrenia and related disorders as not simply extreme and rare disorders, but also milder presentations. often conceptualized as extreme manifestations in clinical cases, milder forms of positive, disorganized, and negative symptoms can also be seen. these subclinical symptoms can develop and change in a variety of ways, if at all. some of these milder symptoms go on to develop into a clinical, disordered presentation. some continue to have these symptoms, but they do not get worse or interfere with functioning. others will have these symptoms come and go, sometimes never appearing again. a key difference between milder symptoms and clinical symptoms when it comes to, for example, delusional thinking, is in conviction. someone with a clinical expression of delusional thinking may be convinced that someone is stealing their thoughts or threatening them, whereas someone with a subclinical expression of delusional thinking may wonder or suspect if it may be possible but are unsure. prof. kwapil’s method for studying the dimensional model involves a complex process that he has implemented into his research. first, development of a conceptual model for understanding the dimensions of schizotypy is needed. models have been developed to measure the dimensions of positive, disorganized, and negative schizotypy in order to identify people who exist on this scale and how their symptoms should present. when observed in subclinical expressions, which do not cause impairment, those being studied are not seen as patients, but rather personality traits. people can be elevated on one, two, or all three dimensions. for example, someone who may be high in the positive dimension, experiencing magical beliefs or strange perceptual experiences, may be low in negative and disorganized dimensions, such that they would not be experiencing the symptoms such as flattened affect, anhedonia, or difficulty organizing and executing thoughts and emotions. participants for a study of subclinical presentations of schizotypy are typically found through extensive interview studies or questionnaire studies focusing on schizotypal traits, personality, and emotion. one of the testing methods favored by prof. kwapil is experience sampling methodology, or esm. esm is a measurement that uses a system of daily surveys sent out multiple times each day that assesses the dynamic system of emotional and psychological phenomena throughout the day. this is a more effective measurement system for seeing a larger picture of a participant’s life by measuring them over a larger period of time than a single lab interview session, making it a fitting choice for studying subclinical presentations of psychological disorders. schizotypy, like many dimensional models of clinical disorders, offers a useful conceptual model of schizophrenia spectrum disorders that has advantages over traditional categorical models. human behavior and emotions have a complexity and nuance that cannot be entirely captured through a yes/no binary. similar to anxiety and depression, which are generally accepted to be experienced both clinically and subclinically, symptoms of schizophrenia spectrum disorder can be observed on a lower impairment level among those who do not fit the criteria for schizophrenia spectrum disorders. prof. kwapil has been studying schizotypy for years and has developed an effective model of study of the dimensions of schizotypy. with models such as these, the scientific community can move on to a better understanding of the truly dimensional model of psychological disorders and their subclinical presentations. prof. kwapil’s proposed model of schizotypy can advance the understanding of schizotypy, allowing for an improved early detection system and potentially negating some of the stigma associated with these disorders. an estimated 10% of people experience subclinical expressions of schizotypy, which is a large portion of the population and merits investigating the presentation and mechanism behind these symptoms. identifying these individuals could be instrumental in instituting early intervention services for those who will eventually develop a clinical presentation of schizotypy. however, those with schizophrenia spectrum disorders have a heavy stigma against them among the general public, and it is important to acknowledge this during research. when trying to identify potential prodromal symptoms, which can help with preventing these symptoms from developing to a clinical level, those identified with subclinical symptoms could put at risk of losing social support systems, losing their jobs, and potentially being prevented from being covered by insurance because of the association with these disorders. being identified as being at risk of developing heavily stigmatized disorders such as schizophrenia or its related disorders carries a much difference social weight than those identified as being at risk for the development of less stigmatized illnesses, such as breast cancer. as those with schizophrenia are often mischaracterized as dangerous or violent. however, as the understanding of schizotypy grows through research, it is possible for education about schizotypy to be spread outside of the scientific community, placing logic and understanding in place of fear. 39 brain matters vol. 8 2025 40 about the author brianna mae is a junior at the university of illinois majoring in clinical/community psychology. she became involved in brain matters to gain more experience researching and writing about the current research in neuroscience. when she is not writing for brain matters, she is also involved in dr. kwapil's project on life experiences lab, and is the treasurer for the psychology research and community club (pracc). brianna mae is hoping to pursue a phd in clinical neuropsychology and conduct research about the neurological basis behind different clinical disorders. 41 brain matters vol. 8 no. 2 thank you! to the brain matters writers, editors, & executive board members, as well as the university of illinois university library & merinda kaye hensley for all of your hard work in making this journal possible. about brain matters brain matters discusses all things neuroscience, psychology, and biology written by uiuc’s very own. the journal welcomes all authors no matter their area of study or year, therefore, authors come from diverse backgrounds, from molecular and cellular biology & psychology, to computer science & engineering. this diversity allows volumes to have a wide range of articles. the journal is mainly written for the college community yet is accessible to anyone as brain matters is published in an open access format by the university library at the university of illinois urbanachampaign. brain matters vol. 8 no. 1 neural mechanisms of smartphone use, adhd, and dopamine dysregulation: implications for cognitive function and attention written by vani sharma figure 1. dopaminergic pathways & crude neuroanatomy (wikimedia commons) introduction the pervasiveness of smartphones in contemporary society has redefined human cognition, affecting attention, memory, and choice. at the core of this interaction is the brain's dopaminergic system, which underlies reward processing and reinforcement learning. dopamine release, triggered by random digital stimuli in the form of notifications and social media feedback, creates a cycle of compulsive phone use, akin to behavioral reinforcement processes in addictive disorders foreshadowing an extreme impact on the dopaminergic system of the brain.. meanwhile, adhd is characterized by dysregulated dopamine signaling in key neural circuits, including the prefrontal cortex (pfc), striatum, and midbrain structures. the neurobiological convergence of adhd and problematic smartphone use indicates that attention-deficit individuals might be especially susceptible to technology overuse. this article discusses the interaction between dopamine dysregulation caused by smartphone use and neural mechanisms of adhd, with special reference to cognitive functioning and attentional control. elucidating these interactions can provide insight into the impact of contemporary technology on cognitive functioning and guide interventions to prevent its possible negative effects. dopamine, reward circuitry, and smartphone use dopamine plays a fundamental role in the brain reward system system, where it primarily controls neuronal activity in the mesocorticolimbic pathway, which includes the ventral tegmental area (vta), nucleus accumbens (nac), and pfc (volkow et al., 2018). the system is responsible for reinforcing behavior that has pleasurable effects, driving motivated and habitual behavior. smartphone usage, particularly that based on social media and notifications, activates this pathway by offering intermittent rewards and fueling habitual checking behaviors (montag et al., 2019). similar 54 and adhd, ongoing research is critical to define chronic digital consumption effects on the brain over the long term. however, precautions can be taken beforehand to mitigate these effects and preserve attentional integrity in an increasingly digital world. cognitive training through attentional control exercises, meditation, or working memory training can also improve executive function and digital distraction resistance. behavioral therapies, including screen-time monitoring apps, dopamine fasting, and replacing digital activity with offline hobbies, offer other means of controlling excessive phone usage. environmental adjustments, such as establishing tech-free zones, keeping phones out of the workplace, and using physical alarm clocks instead of smartphones, can also facilitate improved habits. by combining these strategies, individuals can offset the neural effects of long-term smartphone use, decreasing the likelihood of attentional deficits and promoting higher cognitive control in a world where digital stimuli prevail. strategies such as mindful use of technology —taking scheduled phone breaks, disabling notifications, or employing grayscale mode to reduce visual salience—can alleviate compulsive engagement. similar to substance use disorders, excessive phone use can lead to the downregulation of dopamine receptors, decreasing the brain's sensitivity to natural rewards and reinforcing compulsive use behaviors (kühn & gallinat, 2015). the repeated overstimulation of these circuits can regulate synaptic plasticity, which is expressed as attentional impairment as well as cognitive impulsivity in individuals susceptible to adhd. neural mechanisms of smartphone use, adhd, and dopamine dysregulation: implications for cognitive function and attention neuroanatomical foundations of attention dysregulation adhd and chronic smartphone use have been correlated with structural as well as functional changes within brain regions crucial for attentional control. neuroimaging studies show reduced gray matter volume in the pfc and acc in adhd individuals, interrupting executive function and impulse regulation (shaw et al., 2007). excessive screen time exerts a similar effect on these regions, with prolonged digital exposure linked to reduced functional connectivity between the pfc and striatum, the hallmark of impaired top-down cognitive control (firth et al., 2019). the interference of dopamine signaling within the frontostriatal circuits, which is shared by both adhd and addictive phone use, therefore reflects a shared neural process that may additionally strengthen attentional difficulties along with cognitive instability in the individuals concerned. behavioral and neurological implications of dopamine overload the chronic hyperstimulation of the brain's reward system through smartphone usage may lead to fundamental alterations in attentional processing as well as selfregulation. research indicates that individuals with high smartphone dependency have reduced attentional blink capacity and working memory impairment, due to overstimulation of dopaminergic activation and neural fatigue in attention networks (loh & kanai, 2016). additionally, compulsive reinforcement of online behavior has the potential to interfere with the brain's ability to sustain focus on tasks requiring deep cognitive processing, a particularly troublesome situation for those with adhd (wilmer et al., 2017). promising treatments include behavioral modification in the form of digital detoxification practices and enforced screen time limitations, intending to restore dopamine homeostasis and re-establishing attentional control. conclusion this intersection of smartphone behavior, dopamine dysregulation, and adhd constitutes a central axis of concern within modern cognitive neurosciences. the addictive power of digital messaging, driven by intermittent reward and dopamine release, demonstrates the attention disorder neurobiology. with associated structural and functional brain changes present in both heavy phone use and references 1. file: ventral tegmental area.svg. (2022, august 2). wikimedia commons. retrieved 17:36, april 2, 2025 from https://commons.wikimedia.org/w/index.php? title=file:ventral_tegmental_area.svg&oldid=679710867. 2. firth, j., torous, j., stubbs, b., firth, j. a., steiner, g. z., smith, l., & sarris, j. (2019). the neural basis of digital distraction and its cognitive consequences: a systematic review and meta-analysis. neuroscience & biobehavioral reviews, 105, 12-21. 3. individual care of texas. (2024). digital detox for mental clarity: a guide to reclaim focus. google image result for https://individualcareoftx.com/wpcontent/uploads/2024/01/blog-highlands-jan-1.jpg. https://images.app.goo.gl/iakp7d3sg24l8ywh8 4. kühn, s., & gallinat, j. (2015). brains online: structural and functional correlates of habitual internet use. addiction biology, 20(2), 415-422. 55 5. loh, k. k., & kanai, r. (2016). how has the internet reshaped human cognition? neuroscientist, 22(5), 506-520. 6. montag, c., lachmann, b., herrlich, m., & zweig, k. (2019). addictive features of social media/messenger platforms and freemium games against the background of psychological and economic theories. international journal of environmental research and public health, 16(14), 2612. 7. shaw, p., eckstrand, k., sharp, w., blumenthal, j., lerch, j. p., greenstein, d., clasen, l., evans, a., giedd, j., & rapoport, j. (2007). attention-deficit/hyperactivity disorder is marked by slowing of cortical maturation. proceedings of the national academy of sciences, 104(49), 19649-19654. 8. volkow, n. d., wang, g. j., tomasi, d., & baler, r. d. (2018). the neuroscience of addiction: implications for clinical practice. nature reviews neuroscience, 19(4), 224-236. about the author vani sharma is pursuing a bachelor of science in molecular and cellular biology (mcb) with an honors concentration, alongside a minor in public health and a neuroscience certificate. as a writer for brain matters, she investigates the intricate interplay between the brain and diverse phenomena, including the neural foundations of gratitude, the influence of music on cognitive processes, and the complexities of neuroanatomy and neurological disorders. through her work, she blends rigorous scientific research with engaging narratives to illuminate the brain’s extraordinary intricacies while promoting scientific literacy and making complex concepts accessible to a broader audience. brain matters vol. 8 2025 56 57 brain matters vol. 8 no. 2 curcumin and glioblastoma: how turmeric can be a dietary supplement against brain cancer written by kathryn kennedy figure 1. 2d structure of curcumin. national center for biotechnology information. introduction imagine a brain tumor so aggressive that it can resist both chemotherapy and surgery, causing an alarming survival expectancy of only 12 to 18 months after diagnosis. this intimidating and complex disease is glioblastoma (gbm), the most common and deadliest brain tumor in adults (yalamarty, et al., 2023). researchers are urgently exploring new methods to prevent this serious disease. one particular intriguing dietary supplement researchers have studied as a means to reduce gbm tumor cell development is increased curcumin intake. understanding how curcumin affects gbm cell mechanisms and how to incorporate turmeric into a diet are key components to taking advantage of this fascinating scientific breakthrough. a promising supplement curcumin is a compound found within turmeric, a relatively accessible root vegetable native to india and southeast asia. curcumin has been known to possess antioxidant, antiinflammatory, neuroprotective, and antiproliferative properties, leading researchers to explore curcumin’s potential anticancer mechanisms. system in a recent meta-analysis of studies involving curcumin’s specific role in preventing and mitigating the danger of gbm cells, dr. ângelo luís et al. identified that a compelling attribute of curcumin is that it can target signaling pathways properties and can modulate pathways involved in gbm cell growth. notably, curcumin impacts gbm cell proliferation, cell death, and tumor cell mobility, among other functions (luís, et al., 2024). to come to this conclusion, dr. luís et al. analyzed the efficacy of curcumin on the tumor volume in animal subjects before and after curcumin consumption across 24 studies. another study conducted by researchers zexia wang et al. at the hubei 45 brain matters vol. 8 2025 curcumin has been found to have pleiotropic effects, meaning it can modulate a number of signaling pathways, specifically major gbm pathways. it hinders cell growth and proliferation by inhibiting tumor-promoting pathways such as nuclear factor κb (nf-kb) and phosphoinositide 3kinases/akt/mammalian target of rapamycin (pi3k/akt/mtor). the nf-kb pathway also plays a role in enhancing proinflammatory genes, so curcumin’s ability to inhibit this pathway contributes to its anti-inflammatory properties. as an antioxidant, curcumin protects cells from damage caused by free radicals, a major source of oxidative stress, which is known to activate the pi3k pathway. by reducing oxidative stress, curcumin is able to inhibit the pl3k pathway, and therefore suppress tumor cell proliferation. the compound has also been shown to influence pathways involving cell cycle arrest, chemosensitizing effects, and cell migration and invasion (ryskalin et al., 2020), though further research is needed to determine the specific quantity of curcumin necessary to maximize these effects. university of science and technology found that after comparing gbm tumor volume in mice before and after curcumin consumption, curcumin was effective at reducing the volume of the tumors. these results suggest that curcumin can be a useful supplement in preventing cancer cell growth, specifically for gbm (wang et al., 2020). to better understand how curcumin has these effects, it is important to explore its molecular mechanisms. effect on specific gbm pathways incorporating curcumin in a diet knowing how to effectively incorporate curcumin into a diet is crucial for maximizing its vast health benefits. mary-eve brown, an oncology clinical dietitian at johns hopkins medicine, provides recommendations on how to safely increase curcumin intake through turmeric. she notes that consuming too much curcumin can be risky, so it is wise to avoid turmeric supplements and instead boost curcumin intake by including turmeric into meals. she recommends adding turmeric to stews, chilis, chicken soup, and making tea with turmeric root. she also encourages frequently finding and cooking healthy recipes online that contain turmeric as an ingredient (brown, 2024). gbm currently remains a dangerous and complex disease, and its resistance to current treatment stresses the urgent need for further gbm research and new prevention methods. the intriguing and relatively recent finding of curcumin’s anticancer properties may be a promising step forward as a supplement to aid the prognosis of gbm. however, it is crucial to note that curcumin is not a figure 2. effects of curcumin on gbm cancer stem cells (gscs). molecules. phytochemical properties curcumin is also known to be a type of phytochemical, which are “plant-based bioactive compounds produced by plants for their protection… [that] can be derived from various sources such as whole grains, fruits, vegetables, nuts, and herbs” (kumar, et al., 2023). as a phytochemical, curcumin has been widely studied for its potential properties associated with other phytochemicals, such as its benefits to counteract stress, mitochondrial damage, synaptic dysfunction, and neuro-inflammation. phytochemicals also play a role in protecting against major diseases such as diabetes, obesity, cancer, cardiovascular diseases, and lung and prostate cancers. the vast health benefits of phytochemicals, and therefore curcumin, are fascinating, and stress the importance and reward of knowing how to effectively increase curcumin intake. figure 3. ground turmeric. marco verch. 46 treatment for gbm – it cannot replace chemotherapy and surgery. instead, it may complement these treatments as a dietary supplement. further research in how this compound can target gbm signaling pathways can determine how to maximize its effect in humans. though curcumin’s full anticancer potential is unknown, taking advantage of its known properties can support health benefits. references 1. brown, m.-e. (2024, june 20). turmeric benefits. johns hopkins medicine. https://www.hopkinsmedicine.org/health/wellness-andprevention/turmeric-benefits 2. kumar, a., p, n., kumar, m., jose, a., tomer, v., oz, e., proestos, c., zeng, m., elobeid, t., k, s., & oz, f. (2023). major phytochemicals: recent advances in health benefits and extraction method. molecules (basel, switzerland), 28(2), 887. https://doi.org/10.3390/molecules28020887 3. luís, â., amaral, l., domingues, f., pereira, l., & cascalheira, j. f. (2024). action of curcumin on glioblastoma growth: a systematic review with meta-analysis of animal model studies. biomedicines, 12(2), 268. https://doi.org/10.3390/biomedicines12020268 curcumin and glioblastoma: how turmeric can be a dietary supplement against brain cancer 47 4. national center for biotechnology information (2025). pubchem compound summary for cid 969516, curcumin. 5. nci dictionary of cancer terms. (n.d.). retrieved from https://www.cancer.gov/publications/dictionaries/cancerterms/def/antioxidant 6. ryskalin, l., biagioni, f., busceti, c. l., lazzeri, g., frati, a., & fornai, f. (2020). the multi-faceted effect of curcumin in glioblastoma from rescuing cell clearance to autophagyindependent effects. molecules (basel, switzerland), 25(20), 4839. https://doi.org/10.3390/molecules25204839 7. verch, m. (2018). ground turmeric in a wooden spoon [photograph]. ccnull. https://ccnull.de/foto/groundturmeric-in-a-wooden-spoon/1008418 8. wang, z., liu, f., liao, w., yu, l., hu, z., li, m., & xia, h. (2020). curcumin suppresses glioblastoma cell proliferation by p-akt/mtor pathway and increases the pten expression. archives of biochemistry and biophysics, 689. doi:10.1016/j.abb.2020.108412 9. yalamarty, s. s. k., filipczak, n., li, x., subhan, m. a., parveen, f., ataide, j. a., rajmalani, b. a., & torchilin, v. p. (2023). mechanisms of resistance and current treatment options for glioblastoma multiforme (gbm). cancers, 15(7), 2116. https://doi.org/10.3390/cancers15072116 about the author kathryn kennedy is a freshman studying biology with minors in health technology and spanish. she joined brain matters to learn more about neuroscience, psychology, and improve her writing and editing skills. outside of the journal, she is involved in global medical training and education and training 4 health. she also dances with psa barkada, sings with the st. john's church choir, and plays guitar in her free time. her career goal is to be a pediatrician. 48 brain matters vol. 8 no. 1 abstract color vision deficiency (cvd) or color blindness results from x-linked recessive genetic mutation that decreases or impairs the expression of cone cell photoreceptors essential for normal color perception. as a result, individuals with color blindness are unable to distinguish certain colors or hues in the same way as individuals with typical color vision. on a molecular level, the most common forms of cvd arise from the absence or malfunction of one type of cone cell in the retina, which reduces sensitivity to specific wavelengths of light. this disruption in normal color processing leads to altered color perception, often making daily visual tasks more challenging. however, the colorblind brain can adapt to these perceptual differences through neural plasticity. recent neuroscience research indicates that visual cortical areas v2 and v3 are particularly involved in cortical reorganization in individuals with cvd. additionally, at the cellular level, structures such as rods, intrinsically photosensitive retinal ganglion cells (iprgcs), and neurons in the lateral geniculate nucleus (lgn) may contribute to compensatory neuroplastic responses to altered visual input. by using current research on the adaptive plasticity of the brain in color blind people, scientists can further the potential of neural training for rehabilitation and therapeutic strategies targeted to treat brain trauma, injuries, or other visual impairments. adaptive plasticity of the colorblind brain: a model for sensory compensation 2023). unlike sudden sensory loss, congenital color blindness is a lifelong deficiency, allowing researchers to explore how the brain adapts to deficiency from an early age (isherwood, 2020). as a result, studying these adaptations may offer valuable clues for developing therapies to restore vision or improve recovery after brain injury. this review will discuss neural plasticity associated with colorblindness and how current literature suggests these insights can be used to inform broader neuroscience research on therapies for sensory deprivation and sensory repair. introduction around 1 in 12 men and 1 in 200 women are colorblind (fareed, 2015), yet we rarely consider how they perceive the world around us. colorblindness is often dismissed as a minor inconvenience, but it could offer a unique opportunity to study how the brain adapts to sensory deficits. color blindness, or color vision deficiency (cvd), is a condition characterized by a decreased ability to perceive color differences under normal light conditions and can be genetic or acquired due to trauma. in cvd, cone cells in the eye retina fail to process color information correctly due to malfunctioning or missing opsin proteins (simunovic, 2009). depending on the mutation, colorblind individuals may experience anomalous trichromacy (opsins are present but less sensitive), dichromacy (one of the cone types is missing), or monochromacy (all cones are missing or nonfunctioning). the most common forms, protanomaly (redweak) and deuteranomaly (green-weak), result in a shifted perception of color, altering how individuals interact with their environment. current research suggests that the altered photoreceptor function in individuals with color vision deficiency may influence neural processing at the cortical level (rina, 2024), introducing changes in brain function, especially its plasticity—the brain’s ability to ‘rewire’ itself due to injury or experience (puderbaugh, 2023). mechanisms of color vision the physiology of color vision is thought to be the same across all species, yet scientists still have much to uncover. at its core, color vision relies on our brain's ability to analyze the energy and frequency of light scattered by an object, using opsins—light-activated protein receptors— embedded in cell membranes of photoreceptor cells. so, color processing in humans involves two organs: the retina and the brain, specifically the visual cortex in the occipital lobe. photoreceptor cells, or photoreceptors, are specialized neurons in the eye retina that detect light. there are two major types of photoreceptors in humans: rods that are used for vision in the dark and cones that are used to detect color via opsin proteins, which are, therefore, crucial for understanding color vision deficiency. written by yuliia kohut 30 the mechanism of color vision discussed so far is known as trichromatic color theory, which states that our perception of color relies on detecting signal intensities from three types of cones—s, m, and l cones—that correspond to blue, green, and red light. psychology research also suggests other color vision models, like opponent processing theory, that act in tandem with trichromatic theory to allow us to perceive colors differently (lee, 2011). further color encoding (e.g. detecting color hues) depends on neural activity in the visual cortex to compare if a given wavelength, for example, excites m or l cone receptors more (isherwood, 2020). figure 3 from a 2020 review by isherwood illustrates differences in s, m, and l cone sensitivities in normal color vision as compared to trichromat deuteranomalus or trichromat protanomalus vision. in deuteranomalus vision, the green spectrum(i.e. range of absorbed wavelengths that result in green color) overlaps more with the red spectrum, resulting in green-color weakness. similarly, the red spectrum shifts closer to the green spectrum sensitivity in protanomalous vision, resulting in a red-color weakness. there are also cvds where one type of cone is completely missing or non-functioning, resulting in a more drastic change of color vision. when m cones are missing, an individual experiences deuteranopia, leading to the inability to detect green light. missing l cones leads to protanopia— the inability to detect red light. humans have opsin proteins sensitive to short (s; maximally sensitive to blue wavelength light), medium (m; maximally sensitive to green wavelength light), and long (l; maximally sensitive to red wavelength light) wavelengths, resulting in routine trichromatic vision (isherwood, 2020; pasmanter). to understand how opsins can detect specific colors of light and transmit signals to the brain, we need to explore the physics of light and the molecular structure of opsin proteins. according to the electromagnetic spectrum theory in physics, all electromagnetic radiation, which includes light, can be characterized by its wavelength and energy. the visible portion of the electromagnetic spectrum, which we perceive as colors, has wavelengths ranging roughly from 400 to 700 nanometers. within this spectrum, different wavelengths correspond to different colors; for example, as shown in figure 1, longer wavelengths appear red, while shorter wavelengths appear violet or blue (ailioaie, 2020). when referring to s, m, or l cones (or also s, m, or l opsins in other literature), we mean that each type is activated by a specific range of wavelengths with a corresponding energy. this activation induces a conformational change in the opsin protein, triggering a cascade of biochemical reactions that transmit a signal to the brain. as illustrated in figure 2, opsins act as g-protein coupled receptors. in their signalling conformation opsins can bind to and activate the g protein by catalysing the exchange of gdp (guanosine diphosphate) to gtp (guanosine triphosphate). the gtp-bound gα subunit dissociates from the gβγ subunit exposing its active site and binding to its effector, phosphodiesterase. phosphodiesterase then starts a cascade of reactions that eventually create a hyperpolarization response in the cones. this membrane hyperpolarization in cones modulates the release of neurotransmitters to ganglion cells which form the optic nerve, finally projecting the signal to the brain (shichida, 2009). adaptive plasticity of the colorblind brain: a model for sensory compensation figure 1. the visible spectrum of light inside the electromagnetic radiation spectrum (ailioaie, 2020) figure 3. overlapping sensitivities for different color vision deficiencies (isherwood, 2020). figure 2. a schematic showing the molecular and physiological mechanism of phototransduction from the retina in mammalian eyes. this schematic uses bovine rhodopsin as an example of opsin protein and its function (shichida, 2009) 31 scientists can use computational tools to visualize how individuals with these conditions experience color, see figure 4 (wong, 2011). figure 3 displays a simulation of dichromat percept with decreased l-m light spectrum comparison, assuming this image is a close representation of how protanopes and deuteranopes perceive color. brain matters vol. 8 2025 although color blindness might result from a brain injury or eye disease (cowey, 1997), it is most commonly diagnosed as a congenital condition. the genes that code for opsins are located on the x chromosome. this explains why men are more likely to be color blind than women because mutation on the x chromosome is guaranteed to be expressed in the male population with only one x chromosome copy and not two copies like in females. the genetic designations for the l and m opsin genes are opn1lw and opn1mw, respectively. mutations in these genes, therefore, lead to color vision deficiencies, such as protanopia or deuteranopia, when affecting either opn1lw or opn1mw. on a physiological level, mutation in these genes leads to decreased or absent expression of opsin receptors, affecting visual perception of contrast sensitivity, color discrimination, and object recognition. as a result of these genetic changes, colorblind individuals often rely on several post-receptoral adaptations (isherwood, 2020)—processes in the neural activity of the colorblind brain that help individuals with cvd compensate for receptoral malfunction. such adaptations are of great interest in neuroscience because they pose questions about mechanisms of neuroplasticity and how the brain adjusts to cvd on the level beyond the eye retina. neural plasticity in color vision deficiencies color blindness is a unique “natural experiment" (isherwood, 2020) to study neural plasticity due to two main reasons. firstly, cvds arise from a discrete change on the first step of color vision, which allows us to study brain reorganization as a result of a constant and simple change in informational input like the altered light detection (isherwood, 2020). secondly, because each color blind individual spends a lifetime experiencing a defective color vision, which serves as a valuable opportunity to study brain plasticity on timescales much larger than scientists can afford in the lab (isherwood, 2020). it is obvious that cvd causes perceptual changes at the retinal level of color vision, but neuroscientists are also interested in studying how deficient light input changes cortical function. some studies hypothesize that neuroplasticity adapts to cvd through cortical reorganization, where the brain assigns a function to a cortical area that it does not normally have due to altered sensory input. there is evidence of strong compensation for color losses in anomalous trichromacy via amplification of cortical responses to chromatic contrast in the v1 (primary visual cortex), v2 (secondary visual cortex), and v3 (v1 and v2 signal processing; motion processing) areas of the visual cortex (tregillus 2021; huff; arcaro, 2015). interestingly, in an fmri study examining brain activity in colorblind and healthy subjects performing tasks requiring attention fixation on image contrast sensitivity, researchers found that v1 activity was decreased in colorblind individuals, while v2 and v3 activity remained unchanged, meaning that these parts of the visual cortex might play a role in color processing and associations in color blind individuals, see figure 4 (tregillus 2021). 32 figure 5: simulated dichromat percept of color (isherwood, 2020) figure 4. immunofluorescence image in original color (red and green) and simulated images as seen by protanopes and deuteranopes (wong, 2011) figure 6. fmri data on v1, v2, and v3 cortical activity during attention heavy experiments. a. cvd brain activity is on the right of a being compared to normal brain function on the left of a. retinotopic polar‐angle and eccentricity maps (0– 9.5°) overlaid on an inflated left hemisphere for v1, v2v, and v3v. the central 0–0.95° (fixation zone) was excluded. b. elucidation of the results in a heat maps with plots of fmri signal change. mean % signal change in v1, v2v, and v3v for one subject, averaged over 6 runs (12 repeats per condition). each block had 14 s of stimulus followed by an 8 s gray‐ screen rest. (tregillus, 2021). additional research supports the idea that chromatic adaptation occurs at the retinal level and within central visual pathways. studies on the mccollough effect (a visual illusion that causes color aftereffects) suggest that some chromatic adaptation mechanisms operate at an early monocular stage (stromeyer, 1978). however, further experiments indicate that normalization mechanisms extend beyond the retina. electroretinography (erg) recordings showed no significant differences in spectral sensitivity before, during, or after chromatic alteration, suggesting that these effects are mediated at a postreceptoral level (neitz, 2002). furthermore, monocular chromatic alteration experiments demonstrated interocular transfer of color perception shifts, supporting that chromatic adaptation occurs within central visual pathways at a postsynaptic locus where chromatic information from both eyes has already been integrated (neitz, 2002). other studies also suggest that the cortex shows much more plasticity related to color-contrast adaptation compared to the lateral geniculate nucleus (lgn), which is a part of the thalamus that relays information from the retina to the visual cortex or retinal cells (isherwood, 2020). these findings further raise the significance of cortical plasticity as the cortex seems more adaptive to changes in light input and not anatomical areas that come first in relaying visual information. on a cellular level, current research suggests that intrinsically photosensitive retinal ganglion cells (iprgcs) mediate color processing (raja, 2023), and can be considered a part of adaptive neuroplasticity in color blindness. while traditionally associated with non-image-forming functions such as circadian regulation, sleep, mood, and cognition, iprgcs also receive input from cones and rods, and project to visual pathways, influencing both brightness and color percepts (isherwood, 2020). this raises intriguing possibilities for their role in color vision deficiencies, particularly in dichromats lacking one cone type. despite the absence of a full trichromatic signal, dichromats can still reliably categorize colors in ways that align with trichromats, a phenomenon attributed to sensory mechanisms and learned associations. some studies suggest that dichromats can achieve a form of functional trichromacy over large visual fields by utilizing variations in spectral sensitivity across the retina or by incorporating rod-based signals (isherwood, 2020). although rods are generally considered "color blind," they have been shown to contribute to color perception under certain conditions. given that iprgcs integrate inputs from cones and rods, they may play an unrecognized role in color perception, particularly in individuals with color vision deficiencies who rely more heavily on alternative visual pathways (isherwood, 2020). while the specific contributions of iprgcs to color processing in dichromats remain unexplored, their distinct signaling properties may offer a valuable test case for investigating alternative mechanisms of color coding in the visual system. adaptive plasticity of the colorblind brain: a model for sensory compensation rehabilitation and assistive technologies given recent advancements in neuroscientific research on brain plasticity in colorblind individuals, this knowledge can be applied to developing rehabilitation and assistive technologies for optic injuries. understanding neuroplasticity mechanisms in the visual cortex allows for creating personalized treatment approaches based on an individual's plasticity pattern. one common approach to aiding color blindness is using color-correcting glasses tailored to a person's specific receptor sensitivity. however, some researchers are also exploring gene therapy as a potential method to alleviate or even cure color blindness (dougherty, 2024). more importantly, insights into brain plasticity extend beyond color blindness and can aid in treating brain injuries. recent studies suggest that doctors can use neural training techniques, such as virtual reality therapy and constraint-induced movement therapy, to help the brain recover from damage (zotey, 2023). a deeper understanding of neuroplasticity could make neural training a key component of non-invasive rehabilitation therapies. additionally, research on the plasticity of the visual cortex may provide valuable insights into treating vision-related injuries (barton, 2020) and conditions such as myopia (tan, 2008). conclusion in conclusion, color blindness offers a unique perspective on adaptive neuroplasticity, especially in the brain's visual cortex. interestingly, the brains of individuals with different types of color blindness are more likely to experience structural and functional changes in the cortex and not in the retina. hence, studying color blindness brings more attention to cortical neuroplasticity because these areas seem to play a more significant role in adaptation to vision impairment when compared to neurons and receptors involved in the first steps of color vision. brain areas most involved in color vision adaptation are v1, v2, and v3 areas of the visual cortex, and research shows that v2 and v3 play a role in cortical reorganization of colorblind individuals. however, some studies also explore the extent to which cellular retinal structures like rods, iprgcs, or neurons in lgn contribute to adaptive neuroplasticity as a response to altered light input. by using the knowledge about the adaptive neuroplasticity of the colorblind brain, scientists are looking to study neural training for rehabilitation and therapeutic technologies to treat brain injuries or visual impairments. references 1. ailioaie, laura & litscher, gerhard. (2020). molecular and cellular mechanisms of arthritis in children and adults: new perspectives on applied photobiomodulation. international journal of molecular sciences. 21. 10.3390/ijms21186565. 33 2. andriani, r. (2024). investigating neural processing of color in normal and impaired vision. medrxiv. https://doi.org/10.1101/2024.12.22.24319498 3. arcaro, m j, and s kastner. “topographic organization of areas v3 and v4 and its relation to supra-areal organization of the primate visual system.” visual neuroscience vol. 32 (2015): e014. doi:10.1017/s0952523815000115 4. barton, j. j. s., & ranalli, p. j. (2020). vision therapy: ocular motor training in mild traumatic brain injury. annals of neurology, 88(3), 453–461. https://doi.org/10.1002/ana.25820 5. dougherty, e. (2024). color therapy. harvard medical school magazine. retrieved from https://magazine.hms.harvard.edu/articles/color-therapy 6. fareed, m., anwar, m. a., & afzal, m. (2015). prevalence and gene frequency of color vision impairments among children of six populations from north indian region. genes & diseases, 2(2), 211–218. https://doi.org/10.1016/j.gendis.2015.02.006 7. huff t, mahabadi n, tadi p. neuroanatomy, visual cortex. [updated 2023 aug 14]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2025 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk482504/ 8. isherwood, z. j., joyce, d. s., parthasarathy, m. k., & webster, m. a. (2020). plasticity in perception: insights from color vision deficiencies. faculty reviews, 9, 8. https://doi.org/10.12703/b/9-8 9. lee, b. b. (2008). the evolution of concepts of color vision. neurociencias, 4(4), 209–224. 10. neitz, j., carroll, j., yamauchi, y., neitz, m., & williams, d. r. (2002). color perception is mediated by a plastic neural mechanism that is adjustable in adults. neuron, 35(4), 783– 792. https://doi.org/10.1016/s0896-6273(02)00818-8 11. pasmanter n, munakomi s. physiology, color perception. [updated 2022 sep 12]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2025 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk544355/ 12. puderbaugh m, emmady pd. neuroplasticity. [updated 2023 may 1]. in: statpearls [internet]. treasure island (fl): statpearls publishing; 2025 jan-. available from: https://www.ncbi.nlm.nih.gov/books/nbk557811/ 13. raja, s., milosavljevic, n., allen, a. e., & cameron, m. a. (2023). burning the candle at both ends: intraretinal signaling of intrinsically photosensitive retinal ganglion cells. frontiers in cellular neuroscience, 16. https://doi.org/10.3389/fncel.2022.1095787 14. shichida, yoshinori, and take matsuyama. “evolution of opsins and phototransduction.” philosophical transactions of the royal society of london. series b, biological sciences vol. 364,1531 (2009): 2881-95. doi:10.1098/rstb.2009.0051 15. simunovic, m. (2010). colour vision deficiency. eye, 24, 747–755. https://doi.org/10.1038/eye.2009.251 16. tan, d. t., & fong, a. (2008). efficacy of neural vision therapy to enhance contrast sensitivity function and visual acuity in low myopia. journal of cataract and refractive surgery, 34(4), 570–577. https://doi.org/10.1016/j.jcrs.2007.11.052 17. tregillus, k. e. m., isherwood, z. j., vanston, j. e., engel, s. a., macleod, d. i. a., kuriki, i., & webster, m. a. (2021). color compensation in anomalous trichromats assessed with fmri. current biology, 31(5), 936–942.e4. https://doi.org/10.1016/j.cub.2020.11.039 18. zotey, v., andhale, a., shegekar, t., & juganavar, a. (2023). adaptive neuroplasticity in brain injury recovery: strategies and insights. cureus, 15(9), e45873. https://doi.org/10.7759/cureus.45873 about the author yuliia kohut is a freshman in bioengineering on a pre-medical track and a student from ukraine. apart from brain matters, on campus she is a global health executive member in the american medical student association, and she is also a student volunteer at carle hospital. yuliia is an undergraduate researcher in dr. best-popescu lab at beckman institute, working on developing imaging tools for cellular neuroscience research. in her free time yuliia enjoys cross-stitching, cooking ukrainian food, and reading sci-fi novels. she joined the editing and writing team of brain matters to share her fascination with neuroscience with uiuc! 34 brain matters vol. 8 2025 35 brain matters vol. 8 no. 1 jessica george hi! my name is jessica george and i’m a junior majoring in molecular and cellular biology and brain and cognitive science. outside of school, i volunteer at a nursing home in the activities department, where i work closely with residents who have dementia. in my free time i love dancing, listening to music, and trying new restaurants! jeslyn chen i’m a rising sophomore majoring in psychology and minoring in chemistry. i joined brain matters to combine my interests of neuroscience, psychology, and journalism. outside of this magazine, i plan to become a student emt at uiuc and enjoy drawing, going to concerts, and thrifting. design board esther nam esther nam is a junior on the pre-medical track majoring in psychology with a minor in public health. she is interested in exploring the cognitive and neurological impacts of bilingualism, and is currently a research assistant in the educational psychology psycholinguistics lab with a focus on cognitive psych. in her free time, she loves to draw, play games, and spend time with friends. after undergrad, esther hopes to attend medical school to become a physician. ruth anderson ruth anderson is a rising sophomore at the university of illinois majoring in neuroscience and minoring in psychology. she joined brain matters to get involved with the neuroscience community on campus and learn more about the field. ruth currently is hoping to pursue a career in research. she is passionate about womens health and child development. outside of school ruth enjoys hanging out with her friends, crocheting, and reading. 82 lisa patel lisa patel is a rising junior and an integrative biology major on the pre-medical track with minors in chemistry and nutrition at uiuc. passionate about medicine and community outreach, she co-founded and serves as president of the illini sheltering hands society, where she teaches basic life-support skills and organizes volunteering initiatives. as public relations coordinator for react, lisa coordinates hands-on chemistry demonstrations at local elementary and middle schools. she’s volunteered over 300 hours at ui health hospital while assisting across emergency, diagnostics, radiology, university health services, and surgical departments. she also directs community health initiatives as director of medicine for uiuc’s medlife chapter. her end goal is to become a physician and she is dedicated to expanding her knowledge to better serve her community. sania shah sania shah is a sophomore majoring in brain and cognitive science with a minor in data science. she works as an undergraduate research assistant in the cognitive decision-making lab and dances competitively with the illini raas team. outside of brain matters, sania enjoys playing badminton with friends and curling up with a good book and an iced coffee. 83 84 brain matters vol. 8 no. 2 written by emily aldrich the detrimental effects of aberrant regulation on the hedgehog signaling pathway ...the dysregulation of the hh signaling pathway may lead to a variety of diseases and disorders, including tumorigenesis of medulloblastoma, the most common malignant brain tumor. what is sonic hedgehog? the hedgehog (hh) signaling pathway is a conserved neural pathway that plays an important role in the embryonic development of both invertebrates and vertebrates. this pathway was originally discovered in the species drosophila melanogaster, the common fruit fly, and is found among a variety of species. the signal transmission from cell membranes are regulated by the hh signaling pathway and dictate embryonic development. there are three main hedgehog ligand proteins that regulate the transcription of target genes for this pathway. the three types of hedgehog 31 in the mammalian body are sonic hedgehog (shh), important in the specification of cells in the nervous system, desert hedgehog (dhh) which is seen in the hormoneproducing gonad glands involved in reproduction, and indian hedgehog (ihh) which plays a role in skeletal development (carballo et al., 2018). all of the components in the hh pathway are found in the primary cilium, which is an immobile organelle that juts out from the side of a cell and can sense the surrounding environment (gigante & caspary, 2020). when the pathway is regulated, typical development can occur. however, the dysregulation of the hh signaling pathway may lead to a variety of diseases and disorders, including tumorigenesis of medulloblastoma, the most common malignant brain tumor. the signal transduction pathway of sonic hedgehog the shh pathway is most commonly activated by canonical signaling, in which there are ligand-dependent interactions or receptor-induced signalings. without the glycoprotein shh, this signaling pathway does not occur. smoothened (smo) is a gpcr-like transmembrane protein that is usually inhibited by another transmembrane protein called patched (ptch 1) when the glycoprotein shh is absent. gli transcription factors are present in the cilia in a complex with kif7, an ift-kinesin that moves necessary materials toward the cilium during cellular signaling. additionally, the repressor factor sufu promotes the truncation of gli proteins, in which gli proteins are shortened and turned into the glir repressor form. this inhibits the transcription of shh target genes (traiffort et al., 2012). during shh canonical signaling, the glycoprotein shh binds to and inactivates ptch 1, which, in turn, activates smo. when this protein is activated, it accumulates at the primary cilium. this accumulation relieves the inhibition that sufu exerts on gli proteins, which allows them to turn into the glia activated form, and move into the nucleus to activate the transcription of shh target genes. each target gene has a specific function. for example, gli1 and ptch1 are involved in pathway feedback, cyclin-d1 and myc promote cell proliferation, and ccnd2 and ccne1 regulate the cell cycle. in addition, bcl2 regulates apoptosis, agn1/2 are involved in angiogenesis, snail is involved with epithelial-tomesenchymal transitions, and nanog and sox2 regulate the self-renewal of stem cells. brain matters vol. 8 2025 32 dysregulation of hh signaling pathway when the hh signaling pathway is not carefully controlled, the effects on the development of cells and tissues can be very harmful. the aberrant activation of the hh signaling pathway is caused either by mutations in pathway-related genes or by the excessive expression of hh signaling molecules. this uncontrolled activation is what leads to tumorigenesis. the shh pathway plays a particularly important role in regulating neural development in the cerebellum, a part of the brain linked to motor learning and coordination. aberrant activation of this pathway is linked to pathway-activating mutations in ptc (a protein found in drosophila, the common fruit fly, that is similar to ptch in humans), sufu, or smo, which all have key roles in the figure 1. canonical activation of the sonic hedgehog (shh) signaling pathway occurring at the primary cilium (adapted from robbins et al., 2012). regulation of the hh signaling pathway. it has been seen in mice medulloblastoma brain tumor stem cells that there is markedly higher gli1 expression than in the normal stem cells. these cells do not undergo apoptosis (programmed cell death). instead, they continue to proliferate when they are not supposed to. this suggests that there is a lack of protective mechanisms in place for these malignant stem cells, whereas non-malignant stem cells are able to control excessive proliferation in response to signals that promote mitosis. interestingly, only 25% of medulloblastomas displaying abnormally high hh signaling pathway activation have been found with mutations in ptc, sufu, or smo (traiffort et al., 2012). this means that there are other genetic pathways associated with hh signaling that play a role in the development of cancer cells. tumor suppressors are genes that regulate cell growth in order to prevent the development of cancer. without them, cells will not perform apoptosis and instead continuously divide uncontrollably. tumor suppressors such as ren(kctd11), numb, and p53 have suppressive effects on gli-dependent activation of hh target genes. the activity of these tumor suppressors may decrease and lead to unregulated glli protein activation, contributing to cancer development. figure 2. medulloblastoma subgroups and the histological characteristics (cotter & hawkins, 2021). research for improvement and treatments the findings of how the hh signaling pathway works and its involvement in tumorigenesis have opened up the possibilities of developing methods of molecular targeting and tumor prevention associated with the pathway. several studies support the hypothesis that malignant tumors are initiated and maintained by cancer stem cells (tan et al., 2006; xie et al., 2022). specific neuronal cancer stem cells can be found in a niche, where neurons and glial cells are generated from stem cells or progenitor cells. the niche provides signals that regulate whether the stem cells should differentiate, remain dormant, or actively divide. shh is very important for determining cell fate and patterning during embryo development. it was discovered that the level of shh signaling pathway activation in adulthood played an important role in regulating the balance between dormant and activated neuron stem cells (carballo et al., 2018). currently, the standard treatment for most brain tumors is the removal of the majority of the tumor, followed by chemotherapy and radiotherapy. researchers are currently trying to determine alternative treatments involving the inhibition of the shh pathway activation in cancer stem cells. there is great interest in targeted hh signaling pathway inhibition (hpi) as a type of treatment for aggressive cancer cells when radiotherapy and surgery are not effective (skoda et al., 2018). there have been multiple hpi molecules identified that act at different levels of the hh pathway. one group is hh ligand inhibitors, hpis that inhibit the binding of the hh protein to ptch receptors, keeping smo inhibited and therefore the rest of the pathway blocked from activating target genes. this includes cyclopamine, vismodegib, and sonidegib. another group is smo antagonists which bind to a specific site on the smo receptor that prevents the downstream activation of the hh signaling cascade. however, clinical studies have shown that the use of smo inhibitors can induce development of mutations that lead to treatment resistance. moreover, shh medulloblastomas are highly mutated tumors, and it is not uncommon for these tumors to develop a resistance to smo inhibition, as they present alterations in downstream shh pathway genes such as sufu and gli2. this turned researchers to gli-based inhibitors, which is an alternative group of shh antagonists that act directly in gli to block transcription factors. this includes nvplde-225 and bms833923, which are currently being tested in brain tumors (carballo et al., 2018). while most of the hpis that have entered clinical trials mainly target smo, the resistance to these inhibitors have lead to the discovery of new hpis that may be essential to bypass these resistance mechanisms and control the tumorigenesis of medulloblastoma. a gateway into the future the hh signaling pathway plays a critical role in healthy embryonic development, putting into action a multitude of target genes that are needed for the initial stages of development. there are many steps in the transduction pathway leading to expression of target genes. mutations that form can cause this highly regulated pathway to either activate uncontrollably or become inhibited at the wrong times. when this occurs, continuous and inappropriate cell the detrimental effects of aberrant regulation on the hedgehog signaling pathway division can lead to the rapid growth of tumors in the body. with the knowledge that scientists have today about the hh signaling pathway, there is great potential for certain treatments and therapies that can inhibit the aberrant regulation of the hh pathway, either from ligand-dependent or ligand-independent signaling inhibition. further research into which pathway mechanisms are most likely to elicit a strong response to inhibition can provide a greater understanding of the hh pathway, and can be used to create better, more effective, and safer anti-cancer therapies. references 1. carballo, g. b., honorato, j. r., de lopes, g. p., & spohr, t. c. (2018). a highlight on sonic hedgehog pathway. cell communication and signaling, 16(1). 2. cotter, j. a., & hawkins, c. (2022). medulloblastoma: who 2021 and beyond. pediatric and developmental pathology, 25(1), 23–33. 3. gigante, e. d., & caspary, t. (2020). signaling in the primary cilium through the lens of the hedgehog pathway. wires developmental biology, 9(6). 4. sasai, n., & briscoe, j. (2012). primary cilia and graded sonic hedgehog signaling. wires developmental biology, 1(5), 753–772. https://doi.org/10.1002/wdev.43 5. skoda, a. m., simovic, d., karin, v., kardum, v., vranic, s., & serman, l. (2018). the role of the hedgehog signaling pathway in cancer: a comprehensive review. bosnian journal of basic medical sciences, 18(1), 8–20. 6. tan, b. t., park, c. y., ailles, l. e., & weissman, i. l. (2006). the cancer stem cell hypothesis: a work in progress. laboratory investigation, 86(12), 1203–1207. 7. traiffort, e., angot, e., & ruat, m. (2010). sonic hedgehog signaling in the mammalian brain. journal of neurochemistry, 113(3), 576–590. 8. xie, x. p., laks, d. r., sun, d., ganbold, m., wang, z., pedraza, a. m., bale, t., tabar, v., brennan, c., zhou, x., & parada, l. f. (2022). quiescent human glioblastoma cancer stem cells drive tumor initiation, expansion, and recurrence following chemotherapy. developmental cell, 57(1). 33 brain matters vol. 8 2025 34 about the author emily aldrich is a freshman majoring in neuroscience with minors in linguistics and psychology on the pre-med track. emily joined brain matters to gain a deeper understanding of the brain through exploring current research topics in neuroscience. in her free time, she enjoys listening to music, reading, and spending time with friends. 35 brain matters vol. 8 no. 1 andrew hamilton andrew hamilton is a junior with a major in neuroscience and minors in spanish and chemistry. one thing he enjoys about editing is that he gets to read so many interesting articles about science-related discoveries every day! outside of the club, he pursues research regarding optimization with on-tissue chemical derivatization. michelle bishka michelle bishka is a senior majoring in specialized chemistry and minoring in computer science. outside of brain matters, she is an undergraduate researcher in the silverman lab and a member of american chemical society. she later hopes to pursue graduate studies in chemistry. president brain matters board chief editor vice president 77 praise kim praise kim is the vice president of brain matters and an undergraduate researcher pursuing a bslas in brain and cognitive science. currently, as a research assistant in the gratton lab, she studies the fronto-parietal network in cognitive control tasks across different mental states. in the past, she has also presented work on the infant parasympathetic response and maternal depression with the interdisciplinary lab for social development. she is broadly interested in cognition in the brain and throughout development, also presenting work on social cognitive development at stanford university. outside of research, she lifts weights, reads fantasy novels, and spends time with her church. her future goals are to continue researching the brain—whether as a post-bacc, doctoral student, post-doc, or professor. krisha agarwal krisha agarwal is a junior in mcb honors with a minor in informatics. she is the editor-in-chief of brain matters and a member of american medical women’s association. she is also an undergraduate researcher at the kv prasanth lab in cell and developmental biology. in the future, she hopes to attend graduate school and work in the biotechnology industry. in her free time, krisha enjoys crocheting, reading, sketching, and spending time with friends. macy hoeveler macy hoeveler is a sophomore in the brain & cognitive science program at uiuc. she is pursuing a double minor in integrative biology and music. aside from being the editor-in-chief of brain matters, she is a writing consultant with the writer’s workshop. in addition, she is a beckman fellow with the auditory cognitive neuroscience lab and a lab assistant at the dolezal bee research lab. in her free time, macy is a violinist in the philharmonia orchestra and enjoys reading, listening to music, and collecting bugs. she hopes to continue pursuing biology in graduate school, studying behavioral genetics and neurobiology. vraj patel vraj patel is a sophomore majoring in neuroscience with minors in chemistry and psychology. vraj joined brain matters to learn about more niche topics in neuroscience and research in the field. in addition to being treasurer for brain matters, vraj is an undergraduate researcher in the sweeney lab, which studies neuroscience in the context of feeding and related behaviors. he is also a volunteer for avicenna community health center, a course assistant for stat 200, and a peer mentor for first-year students in the neuroscience major. vraj hopes to explore more in the field of neuroscience from a medical perspective in the future! assistant chief editor assistant chief editor treasurer 78 erin ford erin ford is a junior majoring in chemical engineering with a concentration in biomolecular engineering. in her free time, she enjoys playing tennis and painting. she hopes to help others increase their knowledge about neuroscience through her writing in brain matters. isabelle afshari isabelle is a sophomore at the university of illinois majoring in neuroscience. isabelle became involved in brain matters to learn more about writing scientific articles and innovations in neuroscience. in addition to writing for brain matters, isabelle is involved in mckinley health stress management peers, las leaders, and women’s glee club. in the future, isabelle hopes to attend medical school and continue reading and writing about new scientific innovations! social media chair social media chair social chair vani sharma vani sharma is pursuing a bachelor of science in molecular and cellular biology (mcb) with an honors concentration, alongside a minor in public health and a neuroscience certificate. as a writer for brain matters, she investigates the intricate interplay between the brain and diverse phenomena, including the neural foundations of gratitude, the influence of music on cognitive processes, and the complexities of neuroanatomy and neurological disorders. through her work, she blends rigorous scientific research with engaging narratives to illuminate the brain’s extraordinary intricacies while promoting scientific literacy and making complex concepts accessible to a broader audience. 79 sarah masud sarah is a junior studying psychology and information sciences with a minor in art & design. some of her academic interests include cognition, human-computer interaction, and treating psychiatric disorders. she enjoys drawing, finding new music, and crocheting as well! outside of brain matters, sarah is also involved in design innovation illinois and psi eta mu, a professional information sciences fraternity. she hopes to continue furthering her understanding of neuroscience and exploring topics she’s passionate about through the journal. social chair design head kaitlyn tuvilleja kaitlyn tuvilleja is a junior in bioengineering with a statistics minor. she is an undergraduate research assistant for bhargava lab and i^2 lab. besides brain matters, kaitlyn is involved with swe, wie, and bmes. in her spare time, she enjoys baking and running with her friends. 80 81 brain matters vol. 8 no. 2 understanding the genetics of adhd written by meredith kremitzki attention deficit hyperactivity disorder (adhd) is one of the most common childhood disorders. recently, it has been a source of debate and criticism in the media due to the increase in diagnoses. despite the controversies surrounding overdiagnosis, treatment, and the disorder itself, one clear thing is that there is a genetic component to adhd. in understanding adhd as a whole, the discussion must start with the history and symptoms of the disorder, then focus on heritability, searching for a causal gene, and finally, analyzing possible genes of interest.  abstract introduction attention deficit hyperactivity disorder (adhd) has been described for centuries and is now the most common childhood disorder, affecting around 10% of the us population. adhd has three core symptoms, which include inattention, hyperactivity, and impulsiveness that generally disrupt functioning (mahone, 2017). the impairment must also be present in multiple environments (holland, 2019). this disorder was initially named hyperactive/hyperkinetic syndrome in the 1980s, and the use of stimulants as treatment led people to believe that the root cause was some sort of brain damage. then, as research into this disorder continued, the name evolved to attention deficit disorder (add). with the publication of the dsm-iii, it was finally renamed adhd, which included the inattentive, hyperactive/impulsive, and combined subtypes with the dsm-iv. the dsm-v diagnostic guidelines include the age of onset being 12 years of age, with symptoms of inattention and/or impulsivity/hyperactivity being present. it also added an addendum where those over 17 could be diagnosed if they had five symptoms of inattention and/or impulsivity/hyperactivity (mahone, 2017). like many mental disorders, the definition of adhd has changed over time, adjusting for new knowledge and research. heritability of adhd research involving twin studies has found that the heritability is between 70-80%, and if a person has a firstdegree degree relative with adhd, they will have 5-105-10 times the risk of also developing adhd (mahone, 2017). in their paper, faraone and larsson review the data on twin, family, and adoption studies, as well as discuss genome-wide association studies, when discussing the heritability of adhd (faraone, 2019). one of the studies faraone and larsson reviewed encompassed a study of 894 people with adhd who had siblings between the ages of 5-17. this study found that their rate of adhd was 9 times higher than in those who did not have siblings with adhd (faraone, 2019). additionally, adoption studies suggest that genetic factors could be more impactful than environmental factors. then, when working with twin studies, researchers take advantage of the differences between monozygotic and dizygotic twins (faraone, 2019). monozygotic twins are commonly called identical twins, and they share 100% of their genetic makeup. on the other hand, dizygotic twins only share 50% of their dna and are no more related to each other than a non-twin sibling would be. overall, studies with both types of twins are very important in determining the heritability of a gene/disorder. specifically, monozygotic twins help to compare the effects of the environment on the development of a disorder. in these twin studies, they estimated that the mean heritability of adhd was 74% (faraone, 2019). faraone conducted a meta-analysis that included a swedish study composed of 16,366 twins that found a strong connection between the extreme and subthreshold criteria of adhd. the findings of faraone 2019 49 brain matters vol. 8 2025 are significant to the discussion surrounding heritability due to the amount of data they compiled into their metaanalysis. faraone and team compiled data around the heritability of adhd from many different studies in figure 1 of their paper. these studies had publication years from 1971 to 2017. these comparisons are significant as they show that the heritability of adhd has been in scientific discussion for the past 50 years. additionally, this comparison shows that all mentioned studies, with one exception, had a heritability of 0.6 or greater, indicating the heritability of adhd to be greater than 50% at a minimum. this measure means that the differences seen are due to genetic factors rather than other factors. additionally, this comparison strengthens the argument that adhd has a strong genetic component. figure 1. bar chart showing the heritability of adhd across multiple studies. while the heritability of adhd is well supported, it is also worth noting that a reporter effect has been seen in selfreporting. in this case, the incidence of self-rating of adhd symptoms with different teachers of a twin pair showed lower heritability, around 30-40%, than with the same teachers of a twin pair showed a heritability around 70-80%. of course, this difference could be because of different raters for each twin, which could have introduced effects where the rater experiences different adhd symptoms (faraone, 2019).  the search for the adhd gene after the positive results of the heritability of adhd, the search for a gene began. this started with genetic linkage studies, which found linkage on chromosome 16. then, using linkage across multigenerational populations, evidence was found indicating chromosomes chromosomes 4, 5, 8, 11, and 17 (faraone, 2019). then, a candidate gene association study (cgas) was done to try and find a specific gene. cgas are studies that use knowledge about biology or biological function to target specific genes they hypothesize might be of interest. after doing a cgas, there were 6 genes found: serotonin transporter 5htt, dopamine transporter dat1, dopamine receptor drd4, dopamine receptor drd5, serotonin 1b htr1b, and a synaptic vesicle regulating protein snap25 (faraone, 2019). what can be seen from these studies is that it is not known what exact gene causes adhd, nor where this gene is located. however, the cgas did give researchers some possible genes to start with for in their adhd research. genome-wide association studies (gwas) are similar to cgas except that they look across the entire genome and see if there are genetic variations that are found in those with adhd versus those without adhd. a meta-analysis with 2455 controls, 896 people with adhd, and 2064 trios of two parents and an adhd child found no significant genes. overall, gwas shows that a significant portion of the heritability of adhd was due to the influence of multiple genes that all have a small effect. a specific single-nucleotide polymorphism was found to have a heritability of 22%, making up a third of the heritability found in twin studies. this multi-gene theory was confirmed by using a polygenic risk score that predicted adhd. in even more support for the multi-gene theory, it discusses how certain polymorphisms are located in places in the genome that are important for brain function (faraone, 2019). the difficulty of a disorder like adhd is that while multiple genes are likely to be involved, genetic studies are still unable to determine which genes are involved and to what extent. promising adhd genes despite the lack of specific data on the genetic cause of adhd, there has been a lot of research investigating certain genes and pathways that could be involved. bidwell et al. discuss three specific genes of interest: the dopamine receptor gene (drd4), the dopamine transporter gene (dat1), and the serotonin transporter (5htt). bidwell et al. first start with the dopamine receptor gene, drd4. the drd4 gene is located on chromosome 11 and is interesting because drd4 receptors are expressed in regions associated with attention and inhibition. many studies have specifically looked into a 48-base-pair variable repeat polymorphism in a specific exon that codes for a loop around the receptor. generally, the 4-repeat polymorphism is most common in the population, but the 7-repeat allele has been associated with adhd. in response to this change, research has been focused on testing whether this difference in repeats has made a difference in the efficacy of drugs, but there have not been consistent 50 understanding the genetics of adhd results in this kind of testing (bidwell, 2011). another reason that dopamine is of interest to those studying adhd is because of how many brain functions dopamine signaling is involved in. another gene of interest is the dopamine transporter gene, which is located on chromosome 5. this gene is of specific interest because it is heavily expressed in the striatum, a region of the brain associated with attention, working memory, reward, and decision-making, where its main function is to reuptake dopamine. additionally, this gene is interesting because dopamine transporters are the primary site that stimulants used to treat adhd target. the most popular polymorphism is a variable repeat that is found in the untranslated region of the dat1 gene. untranslated regions are part of the genome that are not translated into protein, so these untranslated regions do not affect the protein of the dopamine transporter. however, the significance of this sequence is that it is believed to affect the expression of the dopamine transporter (bidwell, 2011). overall, this gene is significant because it can affect the dopamine levels in the brain regions associated with attention, memory, etc, which could cause some of the symptoms commonly seen in adhd. another gene that bidwell et al. focus on is the serotonin transporter gene (5htt). unlike the dopamine-associated genes, the role of serotonin has been less studied. where this 5htt has been promising is in animal studies that show serotonin having a key role in regulating things like attention. additionally, when this transporter has been disrupted, there has been an increase in hyperactivity in mice. this is interesting, as one of the hallmarks of adhd is hyperactivity. similar to the dat1 gene, the polymorphism of interest is associated with changes in transcription and activity of the transporter. specifically, this polymorphism is a 44-base pair deletion in the promoter region of the gene. the function of promoter regions is to regulate the transcription of specific genes. with this specific change, researchers see less transcription and a reduced amount of the transporter itself (bidwell, 2011). given the data on the three genes, bidwell et al. performed a family-based association test (fbat) on the polymorphism surrounding the drd4, 5htt, and dopamine transporter genes. they then performed testing to determine how often that variance was associated with either overall adhd or a certain symptom, like inattention or hyperactivity/impulsivity. this data can be seen in table 4 from their paper. what they found was that the drd4 gene was statistically significant for all types of adhd compared to. additionally, they found statistically significant results with the dopamine transporter gene when comparing against total adhd and the inattentive phenotype. however, this result was not seen in the hyperactive/inattentive phenotype (bidwell, 2011). these results from bidwell et al. are are significant as they could give further insight into a specific polymorphism in a particular gene that is associated with adhd. it also provides a guide for further studies to repeat this analysis and to compare with different polymorphisms. figure 2. table with fbat results for each polymorphism and related adhd phenotype with significance value. despite any controversies surrounding adhd, the research has shown that this is a multifaceted disorder. unlike many other disorders or illnesses, no one gene can explain the cause of adhd. however, whatever factors influence this disorder have a strong genetic component that can be observed in heritability studies. the many different hypotheses of the root cause of adhd include problems with dopamine and serotonin. further research could test combinations of genes and adhd. these studies could investigate whether a change in activity in both the dopamine and serotonin genes is correlated with increased adhd symptoms. this could help understand the likely polygenic aspect of adhd.  references 1. mahone, e. m., & denckla, m. b. (2017). attentiondeficit/hyperactivity disorder: a historical neuropsychological perspective. journal of the international neuropsychological society : jins, 23(9-10), 916–929. https://doi.org/10.1017/s1355617717000807 title=file:ventral_tegmental_area.svg&oldid=679710867. 2. bidwell, l. c., willcutt, e. g., mcqueen, m. b., defries, j. c., olson, r. k., smith, s. d., & pennington, b. f. (2011). a family based association study of drd4, dat1, and 5htt and continuous traits of attention-deficit hyperactivity disorder. behavior genetics, 41(1), 165–174. https://doi.org/10.1007/s10519-010-9437-y 3. faraone, s.v., larsson, h. genetics of attention deficit hyperactivity disorder. mol psychiatry 24, 562–575 (2019). https://doi.org/10.1038/s41380-018-0070-0 4. holland, j., sayal, k. relative age and adhd symptoms, diagnosis and medication: a systematic review. eur child adolesc psychiatry 28, 1417–1429 (2019). https://doi.org/10.1007/s00787-018-1229-6 51 https://doi.org/10.1017/s1355617717000807 https://doi.org/10.1007/s10519-010-9437-y https://doi.org/10.1038/s41380-018-0070-0 https://doi.org/10.1007/s00787-018-1229-6 brain matters vol. 8 2025 about the author meredith kremitzki is a junior at the university of illinois, majoring in psychology with a concentration in cognitive neuroscience and a minor in integrative biology. she became involved with brain matters to learn more about the different topics in neuroscience. along with writing for brain matters, meredith is a laboratory teaching assistant for the chemistry department. she hopes to become a doctor and continue learning about the brain and body. 52 53 brain matters vol. 8 no. 2 table of contents biological neural networks as the forefront of ai processing edward lin........................................................................................1 the critical window for estrogen replacement therapy in menopausal women: exploring the neuroprotective effects of estrogen in reducing dementia risk sylvia merz.......................................................................................11 the role of human leukocyte antigens in multiple sclerosis and brain atrophy tanisha mandal..................................................................................6 articles................................................................................ the consequential effects of sleep quality on the academic performance of university students siwon park......................................................................................16 understanding the different types of cerebral palsy and treatment options leah rupp........................................................................................22 isolation how it affects fear responses and anxiety ananya sampathkumar......................................................................26 the detrimental effects of aberrant regulation on the hedgehog signaling pathway emily aldrich....................................................................................31 the influence of maternal stress on a child's development in the womb and the long-term effects on the child's neurodevelopment and mental health alexa divito.....................................................................................36 can we train our brains to break social media addiction? meha goswami.................................................................................40 i about the writers...............................................................85 meet the board...................................................................73 curcumin and glioblastoma: how turmeric can be a dietary supplement against brain cancer kathryn kennedy..............................................................................45 the development of psychogenic pain lily kushnick....................................................................................54 understanding the genetics of adhd meredith kremitzki...........................................................................49 genetic research and its revolutionary? contributions to schizophrenia prevention brianna mae huner...........................................................................59 pathophysiology of postpartum depression: etiology and interplay of structural and functional brain changes sylvia merz......................................................................................64 ii the ethics of brain-computer interfaces (bcis) ruchi prakash..................................................................................69 brain matters vol. 8 no. 2 cerebral palsy is caused by damage to the brain during or right after birth. the damage– caused by infections or reduced oxygen supply–may affect certain areas of the brain such as white matter or the motor cortex. these injuries to the brain may lead to abnormal muscle stiffness or strokes, which are major symptoms of cerebral palsy. the three fundamental types of cerebral palsy are spastic, dyskinetic, and mixed. each have individual classifications of muscle stiffness. physicians may prescribe anticonvulsants to combat seizures and benzodiazepines to reduce muscle spasms. recently, new technological advancements have improved the lives of those with cerebral palsy such as voicett, a talking device. written by leah rupp abstract understanding the different types of cerebral palsy and treatment options introduction in the united states, between 5,500 and 13,100 children are born with cerebral palsy each year (cleveland clinic, 2023). cerebral palsy is a neurological disease that affects muscle movement. since there is no test to diagnose someone with cerebral palsy, physicians have to use a combination of magnetic resonance imaging (mri) and computed tomography (ct) scans, as well as neurological tests to determine if an individual has cerebral palsy. many of the symptoms first appear in early childhood, such as having an abnormal gait, which is when individuals struggle with balance and coordination while walking. these motor impairments are mostly caused by damage to the brain. further symptoms can arise such as seizure disorders, delayed growth and development, and impaired speech, vision, and hearing. causes of this disease there are many different causes of cerebral palsy. birth complications and infections during pregnancy can be risk factors and causes of cerebral palsy. a child born prematurely, specifically before the 37th week of pregnancy, has a higher rate of developing cerebral palsy. additionally, a baby with a low birthweight, less than 5 pounds and 8 ounces, has a higher rating of developing cerebral palsy (centers for disease control and prevention, 2025). various infections during pregnancy can increase the chance of developing cerebral palsy. for example, recent studies have connected cerebral palsy to chickenpox, rubella, rubella, and cytomegalovirus (cleveland clinic, 2023). these bacterial infections can infect the placenta causing the baby to be infected. other infections can lead to a high amount of proteins, such as interleukin cytokines. a recent study conducted by madison paton, a researcher at cerebral palsy alliance research institute, proved a link between specific cytokines such as il-6 and il-10, and cerebral palsy. these proteins are seen in high amounts for those with cerebral palsy. in a similar discovery, dr. mark r schleiss, a pediatrician and researcher at the university of minnesota, conducted a study finding the correlation between cerebral palsy and cytokines. dr. schleiss studied how interleukin cytokines are involved in neuroinflammation. they promote inflammation when the brain is injured through trauma or infections. inflammation can lead to neuronal damage, causing motor development impairment, as seen in those with cerebral palsy (national library of medicine, 2021). brain damage many different changes to the brain can cause cerebral palsy such as damage to white matter, cerebral dysgenesis, and intracranial hemorrhage (national institute of neurological disorders and stroke, 2025). white matter is a tissue in the brain full of a large network of axons, which aid in communicating to the rest of the body. it does this by passing down nerve impulses to neurons. figure 1 shows six different newborns with acute to severe white matter injury. patients d and f have low white matter, making them more likely to develop cerebral palsy. white matter can become injured by poor blood flow and nutrients, causing22 causing ineffective communication throughout the body leading to abnormal motor development. understanding the different types of cerebral palsy and treatment options cerebral dysgenesis is the abnormal development of the brain. these abnormalities can be caused by trauma, mutations, and infections. intracranial hemorrhage is bleeding in the brain, commonly caused by a fetal stroke. babies in the womb can experience a stroke when a blood clot occurs in the placenta. damage to white matter, cerebral dysgenesis, and intracranial hemorrhage can all lead to abnormal motor development. this happens when areas of the brain that control motor function are affected. different types of cerebral palsy it is important to note that different types of brain damage can lead to various kinds of cerebral palsy. the three fundamental classifications of cerebral palsy are spastic, dyskinetic, and mixed (national institutes of health, 2021). many medical professionals have discovered subclasses to spastic cerebral palsy, including diplegic and quadriplegic. spastic cerebal palsy is the most common type, and it is classified by extremely stiff muscles. muscles can become abnormally stiff when damage is done to the motor cortex in the brain. the motor cortex controls muscles and movement, it can become injured by poor oxygen flow during or after pregnancy (cleveland clinic, 2025). one of the main subclasses of spastic cerebral palsy is diplegic. individuals with diplegic cerebral palsy have stiffness only in the legs, as the arm and neck muscles are unaffected. intellectual abilities are neurotypical, as well as speech abilities for diplegic cerebral palsy. quadriplegic cerebral palsy is the second subclass of spastic cerebral palsy and it is the most severe. it is when the legs and arms are stiff, but neck muscles are extremely weak. for those with quadriplegic quadriplegic cerebral palsy speech is most likely impaired. individuals may need assistance when eating and walking (cleveland clinic, 2023). dyskinetic cerebral palsy is a second type of cerebral palsy. it is the uncontrollable jerking movements of arms and legs. this is caused by damage to the basal ganglia in the neocortex, which is heavily involved in motor control (national library of medicine, 2023). for those with dyskinetic cerebral palsy, balance and motor skills may be abnormal. facial muscles may also be affected, causing drooling. the last type of cerebral palsy is mixed. mixed cerebral palsy is rare, and it is is a combination of spastic and dyskinetic. treatment options there are many great drug options for those diagnosed with cerebral palsy. anticonvulsants are mainly to combat seizures and benzodiazepines are to reduce muscle spasms. anticonvulsants work by decreasing the excessive electrical activity in the brain. this is done by altering the electrical activity of neurons. neurons work by transmitting electrical and chemical signals to each other. when an individual has a seizure, neurons uncontrollably relay these signals. anticonvulsants can inhibit certain ion channels, including sodium, potassium, chloride ion channels (cleveland clinic, 2023). some of the more common anticonvulsants include topiramate, valproic acid, and phenobarbital. benzodiazepines are some of the oldest medical treatments to treat spasticity as seen in those with cerebral palsy. benzodiazepines notify the brian to release more of a neurotransmitter called gamma-aminobutyric acid (gaba). gaba slows the nervous system down, creating a sedative effect on the body (cleveland clinic, 2023). in addition to medications, many new technological advancements have improved the lives of those with cerebral palsy. voicett is an ai speech device for those with extreme speech impediments. the machine essentially “talks” for the patient with a click of a few buttons. another great piece of technology is stasism. statism is a fun interactive way for children to complete physical therapy. the program utilizes games, sound effects, and colorful graphics. conclusion cerebral palsy can be caused from pregnancy implications or from brain injuries after birth. damage to areas of the brain that control motor skills, vision, and speech can cause impairment. multiple studies have been conducted on the correlation between interleukin cytokines and cerebral palsy (national library of medicine, 2021). dr. paton and dr. schleiss have conducted separate research on the correlation between interleukin cytokines and cerebral palsy. cytokines are involved in neuroinflammation, where excessive inflammation can lead to neuronal damage, causing motor development impairment. amount of white matter figure 1. patients a, b, c have relatively high amounts of white matter. patients d, e, f have relatively low amounts of white matter, so they have a higher chance to develop cerebral palsy (nature, 2009). 23 6. u.s. department of health and human services. (n.d.). cerebral palsy. national institute of neurological disorders and stroke. https://www.ninds.nih.gov/healthinformation/disorders/cerebral-palsy 7. medications for cerebral palsy helping manage symptoms. cerebral palsy guide. (2024, july 9). https://www.cerebralpalsyguide.com/treatment/medication s/ 8. elsevier. (2016, may 29). automated, quantitative measures of grey and white matter lesion burden correlates with motor and cognitive function in children with unilateral cerebral palsy. neuroimage: clinical. https://www.sciencedirect.com/science/article/pii/s2213158 216300948 9. u.s. department of health and human services. (n.d.). what are the types of cerebral palsy?. eunice kennedy shriver national institute of child health and human development. https://www.nichd.nih.gov/health/topics/cerebralpalsy/conditioninfo/types 10. antiseizure medication. cleveland clinic. (2025a, march 19). https://my.clevelandclinic.org/health/treatments/24781antiseizure-medications-anticonvulsants 11. benzodiazepines: what they are, uses, side effects & risks. cleveland clinic. (2025b, march 19). https://my.clevelandclinic.org/health/treatments/24570benzodiazepines-benzos 12. schleiss, m. r. (2021, april). altered cytokine responses in children with cerebral palsy: pathogenesis and novel therapies. developmental medicine and child neurology. https://pmc.ncbi.nlm.nih.gov/articles/pmc8173757/ brain matters vol. 8 2025 matter is also a factor in developing cerebral palsy. white matter can be damaged through poor blood flow, inhibiting communication to the rest of the body. however, there are many different types of cerebral palsy, caused by different levels of brain damage. spastic, dyskinetic, and mixed are the main types each effecting different parts of the body. medical professionals have been utilizing anticonvulsants and benzodiazepines to treat seizures and spacity, respectively. many more pieces of technology and medications are yet to be invented to better improve the lives of those with cerebral palsy. references: 1. figure 1 li, a. m. (n.d.). white matter injury in term newborns with neonatal encephalopathy. nature. https://www.nature.com/articles/pr200915 2. risk factors for cerebral palsy. center for disease control . (2025, february 24). https://www.cdc.gov/cerebralpalsy/risk-factors/index.html 3. mayo foundation for medical education and research. (2023, september 28). cerebral palsy. mayo clinic. https://www.mayoclinic.org/diseases-conditions/cerebralpalsy/diagnosis-treatment/drc-20354005 4. cerebral palsy: a variety of causes, effects and treatments. cleveland clinic. (2025, march 19). https://my.clevelandclinic.org/health/diseases/8717cerebral-palsy 5. 3 new technologies to assist people with cerebral palsy. focus care. (n.d.). https://focuscare.com.au/blog/3-newtechnologies-to-assist-people-with-cerebralpalsy#:~:text=voiceitt%20is%20an%20innovative%20speec h,impairments%20to%20communicate%20more%20effectiv ely. about the author leah rupp is a freshman at the university of illinois in urbana-champaign studying molecular and cellular biology within the honors concentration. leah joined brain matters to get the opportunity to learn and write about new neuroscience research. leah is also a stress management peer with mckinley health center and a volunteer with the food assistance and wellbeing program. in her free time, leah enjoys running and playing the piano. her career aspiration is to become a physician. 24 25 brain matters vol. 8 no. 2 editors thiya ilankovan thiya is a sophomore at uiuc majoring in mcb with a minor in psychology, hoping to one day become a physician assistant. in her free time, she likes to run, crochet, and play the piano. she is currently involved in research at the liang lab for behavioral neuroscience. through her involvement with brain matters, she hopes to broaden her knowledge and gain deeper insights into the fields of neuroscience and psychology. kathryn kennedy kathryn kennedy is a freshman studying biology with minors in health technology and spanish. she joined brain matters to learn more about neuroscience, psychology, and improve her writing and editing skills. outside of the journal, she is involved in global medical training and education and training 4 health. she also dances with psa barkada, sings with the st. john's church choir, and plays guitar in her free time. her career goal is to be a pediatrician. nicholas opiola nicholas opiola is a recent ’24 mcb alumni. he is a lifelong learner and has always loved studying across all academic disciplines, especially neuroscience! nicholas joined brain matters to immerse himself in all the latest exciting work being performed in the field of neuroscience and to utilize his writing skills towards helping others produce their best work. in his free time, nicholas loves to watch fútbol, dance, sing karaoke, spend time with family and close friends, play video games, and spend time amongst nature. in the future, nicholas hopes to devote his career towards making a lasting, positive change in as many lives as possible. megan lu megan lu is a junior majoring in brain & cognitive science with a minor in health administration and business. she is involved in various rsos on campus, including fhce (future healthcare executives) and alpha epsilon delta (a pre-health fraternity). she is also currently involved in research with the illinois alternative protein project. in her free time, megan spends most of her time at the gym working out, cooking new recipes, or listening to true crime podcasts. she hopes to deepen her understanding and appreciation of the brain through writing with brain matters and will graduate this year. 81 yuliia kohut yuliia kohut is a freshman in bioengineering on a pre-medical track and a student from ukraine. apart from brain matters, on campus she is a global health executive member in the american medical student association, and she is also a student volunteer at carle hospital. yuliia is an undergraduate researcher in dr. best-popescu lab at beckman institute, working on developing imaging tools for cellular neuroscience research. in her free time yuliia enjoys cross-stitching, cooking ukrainian food, and reading sci-fi novels. she joined the editing and writing team of brain matters to share her fascination with neuroscience with uiuc! kaitlyn tuvilleja kaitlyn tuvilleja is a junior in bioengineering with a statistics minor. she is an undergraduate research assistant for bhargava lab and i^2 lab. besides brain matters, kaitlyn is involved with swe, wie, and bmes. in her spare time, she enjoys baking and running with her friends. gus dorman gus dorman is a freshman majoring in neuroscience with a minor in computer science. he joined brain matters as an editor to learn more about the field while also getting a feel for what research articles are like. if he's not studying, he's probably longboarding around campus, playing a video game, or watching shows. praise kim praise kim is the vice president of brain matters and an undergraduate researcher pursuing a bslas in brain and cognitive science. currently, as a research assistant in the gratton lab, she studies the fronto-parietal network in cognitive control tasks across different mental states. in the past, she has also presented work on the infant parasympathetic response and maternal depression with the interdisciplinary lab for social development. she is broadly interested in cognition in the brain and throughout development, also presenting work on social cognitive development at stanford university. outside of research, she lifts weights, reads fantasy novels, and spends time with her church. her future goals are to continue researching the brain—whether as a post-bacc, doctoral student, post-doc, or professor. 82 jessica chen jessica chen is a sophomore studying clinical-community psychology. with brain matters, she has been excited to integrate her interests in neuroscience, linguistics, and psychology. she has appreciated groundbreaking applications of neuroscience in skill acquisition, discrimination, addiction, and more. currently a research assistant with the health equity and action lab and the social cognition lab, jessica examines parenting and child health outcomes across cultural contexts, and neural network dissection of trends in biases. aside from academics, jessica is most likely baking a sweet treat or lounging at a matcha cafe. natalia pacheco natalia is a freshman at the university of illinois majoring in neuroscience. natalia became involved in brain matters to further her passion for the brain and to become familiar with modern topics of neuroscience. in addition to brain matters, natalia is involved in the american medical women’s association at the university of illinois. natalia hopes to continue her studies in the medical field specifically with neurology to continue learning about the brain! 83 84 brain matters vol. 8 no. 2 the consequential effects of sleep quality on the academic performance of university students sleep is a vital biological process essential for proper physiological and cognitive functioning. while its true purpose remains largely theoretical, sleep deprivation has been proven to impair numerous brain functions, particularly in college students who are increasingly susceptible to irregular sleep patterns. drawing on evolutionary and neurological theories, such as the restorative, synaptic homeostasis, and brain plasticity theories, the article examines the impact of sleep deprivation on cognitive processes, memory retention, attention span, and overall brain connectivity. through recent studies utilizing tools such as mri and attention network tests, a consistent decline in brain activity and memory function was observed in sleep-deprived individuals. these effects are especially prevalent in university settings, where academic pressures, lifestyle changes, and increased substance intake contribute to deteriorating sleep quality. the findings highlight that inadequate sleep not only diminishes students’ ability to retain and process information but also places them at higher risk for academic failure and long-term health consequences. ultimately, the article emphasizes that sleep is not only necessary for survival but also fundamental to academic success and cognitive resilience. abstract written by siwon park the detrimental effects of sleep deprivation are evident. sleep quality is subjective for every person; varying durations of overall sleep, along with duration within each stage of the sleep cycle, can differ. however, a general deviation from quality sleep has demonstrated harmful effects. while the issue of sleep deprivation has been on the rise introduction while sleep is understood as a state of unconsciousness for rest and several dynamic neuroligical processes, the purpose behind its true nature has not been fully discovered. many correlative theories and evolutionary explanations exist to uncover the true purpose of sleep. scientifically reasonable theories include inactivity, energy conservation, restoration, synaptic homeostasis, and brain plasticity theory (division of sleep medicine at harvard medical school, 2021). the inactivity theory–also described as the evolutionary or adaptive theory–suggests that sleep was an evolutionarily advantageous quality, particularly for survival. the energy conservation theory theorizes another evolutionary explanation for sleep: when sources of food were scarce, conserving energy by sleeping would be an efficient method to maximize the utility of energy. more recent research has led to the other three theories: restorative, synaptic homeostasis, and brain plasticity, all of which refer to the function of the brain and its necessity to reset in terms of necessary chemicals, neural connections, and memory along with developmental aspects. much like the human body–which cannot sustain exertive physical activity and requires recovery through sustenance, reconnection of muscle fibers, and rest–the brain can function ordinarily through mandatory rest. regardless of the true physiological objective of sleep, sleep is an essential, life-sustaining activity necessary for function. figure 1. research has indicated multiple phases in one sleep cycle, each with varying characteristics and roles. the main phases include n1, n2, n3, and rem, which describe the physical stages of sleep one experiences throughout their sleep (suni, 2025). 16 compromise of cognitive activity a study explored the characteristics of sleep deprivation imposed on eight healthy male and female subjects, with normal sleep conditions as the control. within the study, the brain activity of subjects who received normal sleep and 24 hours of sleep deprivation was monitored. although “normal sleep” was not specified to an exact time of unconsciousness, “good” or “normal” sleep was accepted as being subjective. thus, the researchers utilized measurements of fitness, usage of certain substances, presence of sleep disorders, and a pittsburgh sleep quality index ( <5) to filter participants and maintain their norm throughout the study. (l wang, y chen, y yao, y pan, y sun, 2016). with every participant having a fitbit monitoring their sleep status, subjects were randomly assigned to sessions of an attention network test, followed by an mri test that measured the amplitude of low-frequency fluctuations (alff). the data gathered described higher alff areas in the right cuneus and lower alff areas in the right lentiform nucleus, right claustrum, left middle frontal gyrus, left dorsolateral prefrontal cortex, and left inferior parietal cortex within the sleep-deprived subjects. the research team associated the lower alff in the left dorsolateral prefrontal cortex with a reduction in gray matter rise for the general american population, the greatest contributors to this statistic are college students. as the number of sleep-deprived college students rises, the importance of exploring possible causes of sleep deprivation grows. many students find college to be their first experience away from home, which can be an unfamiliar and uncomfortable environment. aspects of this new environment, such as dining hall food and roommates, can negatively affect sleep quality. in addition, the potential increase in workload for students can affect the quality and duration of sleep due to factors such as lack of sufficient time and stress. college also presents easier access to alcohol and other substances, which may cause passing out, and although the duration of unconsciousness may be long, the quality of sleep is poor (gaultney 2010). furthermore, unregulated intake of caffeine severely affects sleep as the substance indirectly inhibits melatonin synthesis and secretion by preventing the binding of adenosine triphosphate to the active site of the receptor, leading to prolonged time without sleep. with these facets for decreased sleep quality, the potential development of sleep and mental health disorders increases, which can further affect a student’s sleep. with the specific analysis of university students and their decreased sleep quality, the correlation between sleep deprivation and academic performance can be explored. this article argues that sleep deprivation significantly impairs the academic performance of university students by reducing cognitive function as well as diminishing memory retention and attention span, ultimately hindering their ability to succeed academically and maintain overall well-being. an essential tissue in the brain and spinal cord for many cognitive and motor-control functions, as well as a reduction in regional homogeneity (wang, chen, yao, pan, sun, 2016). with the brain scans that demonstrated lower alff levels, the cognitive function and the connectivity between the inferior parietal cortex and the medial prefrontal cortex were compromised, thus, detrimentally affecting memory recall, consolidation, and retrieval along with crucial cognitive functions. the left inferior parietal cortex is involved in memory recall, consolidation, and retrieval, as well as cognitive functions like bodily awareness, responsibility, and moral decisionmaking (l wang, y chen, y yao, y pan, y sun, 2016). one particular finding demonstrated that “sleep deprivation reduced the left inferior prefrontal cortex deactivation during a visual short-term memory task” (a. krause, e. simon, b. mander, s. greer, j. saletin, a. goldstein-piekarski, m. walker, 2017). with crucial cognitive functions within the responsibilities of the left inferior prefrontal cortex and the left inferior parietal cortex, sleep deprivation that contributes to the declining function of both leaves an overall underperforming brain. this research demonstrates the significant effect that sleep deprivation contributes to the rapid degeneration of several crucial areas of the brain and their respective functions. within the brain, two primary networks—the default mode network (dmn) and its anticorrelated network (acn)—exist to establish connections between neural networks to fulfill applicative tasks. typically, the acn corresponds to the frontoparietal network (fpn), which shows a negative correlation with dmn activity (l wang, y chen, y yao, y pan, y sun, 2016). “in the sleep-deprived state, there is unstable reciprocal inhibition between task-related fpn activity and dmn activity, and erratic ascending arousal activity influencing thalamic activity” (krause, simon, mander, greer, saletin, goldstein-piekarski, walker, 2017). the lower alff in these regions describes a weakening of the neurological connections within the brain, ultimately demonstrating detrimental effects on attention, working memory, and overall cognitive function. the consequence of sleep deprivation and the associated reduced function of areas within the brain stimulated compensatory activity from non-orthodox regions such as the lentiform nucleus and claustrum. although the compensatory activity of these regions of the brain allows for extended cognitive function, the quality of such functions is compromised, with results demonstrating inconsistent cognitive abilities. the consequential effects of sleep quality on the academic performance of university students diminishing memory retention and attention span memory is one of the main functions of the brain, and sleep deprivation has significant effects on memory. the tired hippocampus: the molecular impact of sleep deprivation on hippocampal function, published by curr opin neurobiol, states that “sleep deprivation has the biggest impact on hippocampal memory consolidation in the first few hours following 17 following training when it overlaps with the second wave of camp signaling, transcription, and protein synthesis critical for increasing synaptic efficacy and memory storage.” sleep deprivation results in the attenuation of camp-pkalimk pathways (chua, e. c., fang, e., & gooley, j. j., 2017), which is the direct cause of the detrimental effects on hippocampal function. furthermore, this study discovered that sleep deprivation also reduces the translational and transcriptional processes through the inhibition of the mtorc1 pathway. in their study effects of total sleep deprivation on divided attention performance, chua, fang, and gooley (2017) reported that “divided attention performance was impaired during exposure to total sleep deprivation, as demonstrated by a significant interaction between task load (single, dual, and triple tasks) and time since wake on agng response times and errors.” the auditory go/no-go (agng) task, which measures attention and response control, was used to assess participants’ performance under varying cognitive loads. results showed that participants performed worse on the agng task when required to divide attention across multiple tasks, compared to when completing the agng task alone. this decline in performance was further exacerbated by sleep deprivation, highlighting its significant negative impact on multitasking and overall cognitive functioning. in addition to impaired memory, distractibility, which is the difficulty in maintaining performance and effort, is increased (chua, e. c., fang, e., & gooley, j. j., 2017). just like food and water, sleep is a necessity for life, and the homeostatic pressure of sleep and the given task conflict, ultimately resulting in the reduction of attention span and an increase in distractibility. general academic detriments the possible theories of sleep describe reasons for the necessity of sleep. the restorative, synaptic homeostasis, and brain plasticity theory all propose that the necessity of sleep is correlated with the functional reset of the brain and explains a process of recovery and restoration during sleep. deviations from quality sleep and resetting of the brain can cause insufficient recovery of the brain. consequently, the homeostasis of the brain can be offset, and susceptibility to sleep and mental disorders can be escalated. the poor physiological conditions, along with the deteriorating cognitive functions described previously, are direct results of sleep deprivation, demonstrating the negative consequences of sleep deprivation on academic performance. academic performance is critical, as college and university education are crucial steps toward future careers and further education. however, the process of learning is not so simple as going to a lecture and taking notes. the complex pathway to academic success involves a variety of aspects, one of the most important being sleep. with sleep, sufficient information encoding can take place while allowing for brain space to absorb more information. on the contrary, students brain matters vol. 8 2025 figure 2. the barplot graph describes a negatively correlated relationship between the average hours of sleep a student gets on weeknights with how much they felt their sleep interfered with their academic performance (mcgowan, coughlin, 2017). “students reported insufficient sleep and a discrepancy between weekday and weekend amount of sleep. students at risk for sleep disorders were overrepresented among students in academic jeopardy (gpa < 2.0),” said jane f gaultney, professor of psychology at north carolina, charlotte (nih). without such a crucial aspect of academics, simply thinking, remembering, and paying attention becomes more difficult. the beneficial aspects of quality sleep, along with the detrimental consequences of sleep deprivation, contribute directly and indirectly to the academic success of an individual, clearly demonstrating the absolute necessity of sleep, not just out of physiological necessity, but for academic success. extensive neurological and behavioral research demonstrates that sleep is not merely a passive state but a fundamental biological process crucial to cognitive functioning and academic performance. with evidence indicating the individual decline of each cognitive function in their effectiveness and efficiency, sleep deprivation has been demonstrated to be a significant detriment. with sleep being an absolute physiological need for humans, sleep deprivation not only harms cognitive function but also the person. with sleep deprivation demonstrating to be an incredible barrier to academic success and damaging to health, the emphasis on quality sleep is truly an imperative message to university students. references 1. brain fog: solutions to help you improve concentration | bangkok international hospital. (n.d.). www.bangkokinternationalhospital.com. https://www.bangkokinternationalhospital.com/healtharticles/disease-treatment/brain-fog-syndrome 2. brain fog: why your mind feels like it’s buffering. (2024, may 14). cleveland clinic. https://my.clevelandclinic.org/health/symptoms/brain-fog 18 3. brinkman, j. e., sharma, s., & reddy, v. (2023, april 3). physiology of sleep. pubmed; statpearls publishing. https://www.ncbi.nlm.nih.gov/books/nbk482512/ 4. chua, e. c.-p., fang, e., & gooley, j. j. (2017). effects of total sleep deprivation on divided attention performance. plos one, 12(11), e0187098. https://doi.org/10.1371/journal.pone.0187098 5. duplessis, k. (2024, april 2). research finds college students should get more sleep. georgia state news hub. https://news.gsu.edu/2024/04/02/research-finds-collegestudents-should-get-more-sleep/ 6. emerson, j. (2024, november 22). the importance of sleep for college students. admissions.usf.edu. https://admissions.usf.edu/blog/the-importance-of-sleepfor-college-students 7. figure 1 in vivo brain imaging shows that one night of total sleep... (2021). researchgate. https://www.researchgate.net/figure/n-vivo-brain-imagingshows-that-one-night-of-total-sleep-deprivation-reducesmolecular_fig1_350749209 8. gaultney, j. f. (2010). the prevalence of sleep disorders in college students: impact on academic performance. journal of american college health, 59(2), 91–97. https://doi.org/10.1080/07448481.2010.483708 9. guo, c., shang guo piao, wang, c., yu, l., wang, k., qu, q., zhang, c., & yu, x. (2023). the prevalence and associated factors of sleep deprivation among healthy college students in china: a cross-sectional survey. peerj, 11, e16009–e16009. https://doi.org/10.7717/peerj.16009 10. harvard medical school. (2021, october 1). why sleep matters: benefits of sleep. sleep.hms.harvard.edu. https://sleep.hms.harvard.edu/education-training/publiceducation/sleep-and-health-education-program/sleephealth-education-41 11. havekes, r., & abel, t. (2017). the tired hippocampus: the molecular impact of sleep deprivation on hippocampal function. current opinion in neurobiology, 44, 13–19. https://doi.org/10.1016/j.conb.2017.02.005 12. honma, a., revell, v. l., gunn, p. j., davies, s. k., middleton, b., raynaud, f. i., & skene, d. j. (2019). effect of acute total sleep deprivation on plasma melatonin, cortisol and metabolite rhythms in females. european journal of neuroscience, 51(1), 366–378. https://doi.org/10.1111/ejn.14411 3. krause, a. j., simon, e. b., mander, b. a., greer, s. m., saletin, j. m., goldstein-piekarski, a. n., & walker, m. p. (2017). the sleep-deprived human brain. nature reviews neuroscience, 18(7), 404–418. https://doi.org/10.1038/nrn.2017.55 14. krishnan, d. (2021). orchestration of dreams: a possible tool for enhancement of mental productivity and efficiency. sleep and biological rhythms. https://doi.org/10.1007/s41105-021-00313-0 15. mayo clinic staff. (2021, march 3). melatonin. mayo clinic. https://www.mayoclinic.org/drugs-supplementsmelatonin/art-20363071 16. mcgowan, a., & coughlin, k. (2017, march 26). study examines impact of sleep on student performance. the brown and white. https://thebrownandwhite.com/2017/03/26/lehigh-sleepstudy/ 17. national heart, lung, and blood institute. (2022, march 24). how sleep works why is sleep important? national heart, lung, and blood institute. https://www.nhlbi.nih.gov/health/sleep/why-sleepimportant 18. patel, a. k., & araujo, j. f. (2024, january 26). physiology, sleep stages. national library of medicine; statpearls publishing. https://www.ncbi.nlm.nih.gov/books/nbk526132/ 19. schlarb, a., friedrich, a., & claßen, m. (2017). sleep problems in university students – an intervention. neuropsychiatric disease and treatment, 13(13), 1989–2001. 20. sleep irregularity and academic performance | the journal of optometric education. (n.d.). https://journal.opted.org/article/sleep-irregularity-andacademic-performance/ 21. sun, y., wang, l., chen, y., yao, y., & pan, y. (2016). sleep deprivation disturbed regional brain activity in healthy subjects: evidence from a functional magnetic resonanceimaging study. neuropsychiatric disease and treatment, 801. https://doi.org/10.2147/ndt.s99644 22. suni, e., & singh, a. (2023, december 8). stages of sleep: what happens in a sleep cycle. sleep foundation; sleep foundation. https://www.sleepfoundation.org/stages-ofsleep 23. trucchia, s. m., lucchese, m. s., enders, j. e., & fernández, a. r. (2013). relationship between academic performance, psychological well-being, and coping strategies in medical students. revista de la facultad de ciencias medicas (cordoba, argentina), 70(3), 144–152. https://pubmed.ncbi.nlm.nih.gov/24646930/ 24. wein, h. (2021, april). good sleep for good health. nih news in health; national institutes of health. https://newsinhealth.nih.gov/2021/04/good-sleep-goodhealth the consequential effects of sleep quality on the academic performance of university students 19 brain matters vol. 8 2025 about the author siwon is a pre-medical student majoring in biochemistry at the university of illinois urbana-champaign, with a strong interest in the intersection of research and clinical medicine. passionate about understanding the molecular basis of disease and pharmacology. at uiuc, siwon is engaged in research involving cell culture and cellular differentiation, with a focus on inducing stem cells to become muscle and neuron-like cells. additionally, siwon has contributed to research at the feinberg school of medicine, studying corneal damage and repair mechanism. siwon plans to pursue a career in medicine that integrates both clinical practice and biomedical research. through this dual path, he aims to help bridge laboratory discoveries with therapeutic advances that improve lives. 20 21 brain matters vol. 8 no. 1 written by ananya sampathkumar how do we measure intelligence? introduction intelligence is something that scientists have studied for centuries. from a neuropsychological standpoint, intelligence can be defined as one's abilities to adapt and change according to different environments and learn from one's experiences (sternberg, 2012). this somewhat vague definition has led to multiple ways to measure it over the years, with each one prioritizing and measuring different aspects of cognitive function. alfred binet was the father of the iq test, working with theodore simon to create the binet-simon iq test in 1905. this test consisted of 30 questions and had many issues as it did not consider the complexities of iq and intelligence and therefore, could not provide a holistic result (sternberg & jarvin, 2015). however, this iq test stands as the first prolific intelligence measurement exam. consequently, it has acted as a basis for almost every iq exam that has followed. some examples of iq tests that have been derived from the binet-simon test are the stanford-binet test in 1916 (sternberg & jarvin, 2015) and the army alpha/army beta exams used by military generals during world war i (warne et al. 2019). the stanford-binet iq test would provide a single number, an iq quotient, that represented an individual’s place on the scale. the army alpha test was written, while the beta version was pictures, for soldiers who could not read. they were used in determining what soldiers were suited for—which positions and leadership roles. however, the most prominent and used example is the wechsler intelligence scale (wais), developed by david wechsler (niileksela & reynolds, 2019), and has many uses. iq: an introduction due to the complexity of intelligence, research on the neurobiological aspect of intelligence is reliant on two main forms of information gathering: brain imaging and genetic studies. these studies are thought to be able to help researchers learn more about higher-level cognitive processing. several brain scans have shown that iq scores were correlated with intracranial, cerebral, temporal lobe, hippocampal, and cerebellar volumes, which essentially makes up the entirety of the brain (goriounova & mansvelder, 2019). however, voxel-based morphometry (vbm), a neuroimaging technique that allows scientists to make estimations about the spacing and distribution of differences between important or central brain regions, has been used to study iq in the brain as well. goriounova and mansvelder (2019) found positive correlations between intelligence (found using the wais) and cortical thickness were seen in several different regions of the temporal and frontal lobes. studies like these show the many different parts of the brain 50 that are affected by and interact with one another. as a result of the complex interplay between a multitude of brain regions, it is essential to utilize a complex and comprehensive iq examination in order to best measure the trait of intelligence (colom et al. 2010). these intricacies need to be reflected in the iq and intelligence examinations that psychologists and neuroscientists use to study higherorder cognition. the current most popular iq test in usage is the wais-v, which david wechsler developed to study the cognitive abilities of adults (sternberg & jarvin, 2015). this test provides a comprehensive measure of one’s cognitive functioning in both verbal and performance situations. this scale assesses several unique types of intelligence through five main areas: fluid reasoning, processing speed, verbal comprehension, visual-spatial ability, and working memory. each of these sections contains several different tests within them. along with these, two broader areas are scored: full-scale iq, which is based on the total combined performance of the past five categories and general ability index (gai), which is only based on the perceptual reasoning index and verbal comprehension index. together, all of this is expected to provide a holistic view of one’s iq (niileksela & reynolds, 2019). these scores are calculated through a complex process. on the wais, the scores of the test-taker are compared to the scores of others within their general age group. from there, the average score is set around 100, and having a score of 90 to 110 is considered average intelligence (loring & bauer, 2010). ... useful for determining one’s intellectual abilities, identifying learning disabilities, and has been utilized to guide education and learning... in addition, the wais has good test-retest reliability (watkins & smith, 2013). this ensures that the results that scientists are getting through these tests are accurate and consistent between each person. this consistency is incredibly important, especially when it comes to situations where an individual’s data will be compared against that of the “entire population.” on the other hand, the wais does not cover every form of intelligence believed to exist. for example, creativity is not tested on the exam (niileksela & reynolds, 2019) but is considered to be a crucial type of intelligence (dechaume et al. 2024). this exclusion of important intelligence factors may lead to several people high in related types of intelligence doing poorly on the wais. additionally, there are many concerns that factors such as race, gender, or nationality could play a role in testing and lead to unfair results. these exams are administered by psychologists, and their inherent biases could lead to results being different than the expected or accurate results from the person. this is seen most prominently regarding the black and hispanic american communities, which often face external stereotyping and discrimination. this bias can be seen through the cultural test bias hypothesis (ctbh), the idea that any gender, ethnic, or other minority groups that perform differently on the mental examinations are due to flawed methodology that was used to make and administer the exam (reynolds et al, 2021). finally, the reliability of iq exams has been brought into question. while all iq exams have the same structure and format for the questions and sections, there are many external factors that could play a role in test results. one pilot study of the wais-ii, one of the older versions, showed that testing reliability changed depending on the testing conditions. elements such as which psychologist is proctoring the exam or what room the examination is being taken in can greatly affect one's score and results (worhach et al., 2021). how do we measure intelligence? figure 1. (sfu, 2005) benefits and downsides the wais is incredibly useful for determining one’s intellectual abilities, identifying learning disabilities, and has been utilized to guide education and learning throughout the many years of its use (koriakin et al. 2014). this test can also be used to diagnose and assess traumatic brain injuries, and is used in clinical trials and studies to learn about the effects of tbis (lida et al, 2021). 51 conclusion intelligence has been studied by scientists for centuries, and the complex interplay between brain regions is still not understood today. despite testing flaws, scientists continue to use iq testing to learn more about intelligence levels because they are a useful tool to reflect what is understood about the trait of higher-order cognitive functioning. in the future, scientists will use tools such as functional brain imaging in order to learn more about intelligence’s changes to the brain. for example, a recent study that used lesionmapping technology and wais-iii index scores showed scientists that higher scores were correlated with more localized regions for the verbal comprehension index (vci), and working memory index (wmi) than for other regions of the brain (coalson et al., 2010). while not perfect, researchers continue to work on reducing the flaws and mistakes that these examinations make so that iq testing can continue to act as a dependable tool for intelligence testing and research. references 1. coalson, d. l., raiford, s. e., saklofske, d. h., & weiss, l. g. (2010). wais-iv. wais-iv clinical use and interpretation, 3– 23. https://doi.org/10.1016/b978-0-12-375035-8.10001-1 2. colom, r., karama, s., jung, r. e., & haier, r. j. (2010). human intelligence and brain networks. dialogues in clinical neuroscience, 12(4), 489–501. https://doi.org/10.31887/dcns.2010.12.4/rcolom 3. dechaume, m., mercier, m., feybesse, c., lubart, t., chouvelon, g., kermarrec, s., & tordjman, s. (2024). is intelligence necessary and sufficient for creativity? an analysis of convergent and divergent thinking. learning and individual differences, 116, 102575. https://doi.org/10.1016/j.lindif.2024.102575 4. goriounova, n. a., & mansvelder, h. d. (2019, february 15). genes, cells and brain areas of intelligence. frontiers in human neuroscience. https://pmc.ncbi.nlm.nih.gov/articles/pmc6384251/ 5. koriakin, t. a., mccurdy, m. d., papazoglou, a., pritchard, a. e., zabel, t. a., mahone, e. m., & jacobson, l. a. (2013). classification of intellectual disability using the wechsler intelligence scale for children: full scale iq or general abilities abilities index? developmental medicine &amp; child neurology, 55(9), 840–845. https://doi.org/10.1111/dmcn.12206. iida, y., chiba, h., ikeda, s., tohyama, h., & ikoma, k. (2021). association between the wechsler adult intelligence scale iii and early return to work after traumatic brain injury. work, 68(4), 1101–1111. https://doi.org/10.3233/wor-213440 7. loring dw, bauer rm. testing the limits: cautions and concerns regarding the new wechsler iq and memory scales. neurology. 2010;74(8):685–690. doi:10.1212/wnl.0b013e3181d0cd12 8. niileksela, c. r., & reynolds, m. r. (2019). enduring the tests of age and time: wechsler constructs across versions and revisions. intelligence, 77, 101403. https://doi.org/10.1016/j.intell.2019.101403 9. reynolds, c. r., altmann, r. a., & allen, d. n. (2021). the problem of bias in psychological assessment. mastering modern psychological testing, 573–613. https://doi.org/10.1007/978-3-030-59455-8_15 10. sfu. (2005). intelligence theories. learner differences. https://www.sfu.ca/~jcnesbit/educ220/week4/week4.html 11. sternberg, r. j. (2012). intelligence. dialogues in clinical neuroscience, 14(1), 19–27. https://doi.org/10.31887/dcns.2012.14.1/rsternberg 12. sternberg, r. j., & jarvin, l. (2015). binet, alfred (1857– 1911). international encyclopedia of the social &amp; behavioral sciences, 596–599. https://doi.org/10.1016/b9780-08-097086-8.61008-5 13. warne, r. t., burton, j. z., gibbons, a., & melendez, d. a. (2019). stephen jay gould’s analysis of the army beta test in the mismeasure of man: distortions and misconceptions regarding a pioneering mental test. journal of intelligence, 7(1), 6. https://doi.org/10.3390/jintelligence7010006 14. watkins, m. w., & smith, l. g. (2013). long-term stability of the wechsler intelligence scale for children—fourth edition. psychological assessment, 25(2), 477–483. https://doi.org/10.1037/a0031653 15. worhach, j., boduch, m., zhang, b., & maski, k. (2021). remote assessment of pediatric patients with daytime sleepiness and healthy controls: a pilot study of feasibility and reliability. child neurology open, 8. https://doi.org/10.1177/2329048x211048064 brain matters vol. 8 2025 52 about the author ananya sampathkumar is a sophomore, majoring in neuroscience with minors in chemistry and public health. outside of brain matters, ananya is an assistant editor-in-chief for double helix digest, a member of starcourse, a volunteer at carle hospital, and works at the office of undergraduate admissions as a tour guide and student ambassador. in her free time, ananya likes to read books, make jewelry, watch movies, and hang out with her friends. 53 brain matters vol. 8 no. 1 abstract scientists have researched the intricacies of cognitive neuroscience in an attempt to explain how extreme stress changes moral decision-making in critical life-or-death situations. by examining the complicated interactions among key brain regions–the amygdala, ventromedial prefrontal cortex (vmpfc), dorsolateral prefrontal cortex (dlpfc), and anterior cingulate cortex (acc)–we uncover how increases in cortisol and adrenaline modulate the shift from ethical reasoning to base instinctual reactions. compelling research and neuroimaging results have revealed how high-stress situations amplify emotional reactions while impairing rational thinking, leading to impulsive decisions that favor self-preservation over morality. such findings are in direct opposition to leading views regarding moral reasoning and make a strong case for the urgent need for strategies to improve ethical decision-making in high-pressure situations–especially among individuals standing at the forefront when crises occur. the cognitive neuroscience of moral decision-making in extreme situations: high-stress or life-threatening scenarios written by may yang i. introduction imagine a moment when your entire being jolts to attention–your blood surges through your veins, every cell in your body tingles. suddenly, you're moving, acting, driven by some primal force beyond your conscious control. afterward, you're dazed, trying to recall the hazy sequence. you question your actions. this is the instinct in control– decision-making under extreme situations. decision making, defined by the american psychological association (apa), refers to the cognitive process of choosing between two or more alternatives (apa, 2018). but when we assume that every decision made could mean life or death, the situation becomes less simple. in the blink of an eye, a firefighter must choose: rush into a collapsing building to save lives, or stay back and live another day. this splitsecond moral dilemma under extreme pressure shatters the comfortable paradigms of kahneman's dual-process theory. while we leisurely ponder between a sandwich or burger, tapping into our system 1 or system 2 thinking, these heroes face a crucible where morale and morality collide (apa, 2018). this raises the central question of this article: how does extreme stress influence the brain's moral decisionmaking? ii. neurobiological foundations the brain is like a puzzle. each piece contains its own unique details and meaning, but it's only when these pieces are put together that they provide a full picture. the key components involved in moral decision-making are: the amygdala, ventromedial prefrontal cortex (vmpfc), dorsolateral prefrontal cortex (dlpfc), temporoparietal junction (tpj), anterior cingulate cortex (acc), and posterior cingulate cortex (pcc). beginning with the amygdala–a small almond-shaped structure located in the medial temporal lobe (salzman, 2024). the amygdala is the fastest brain component to react to stress when anything may potentially threaten one’s life. it is connected to the thalamus, so input from sensory systems will relay to the amygdala which can trigger a response ready for danger, signaling the body to initiate a fight-or-flight response. it works as a counterforce to rational thinking and decisionmaking, allowing individuals to prioritize their own survival (mendez, 2009). if we primarily relied on the amygdala’s reaction, it would mean we could never make moral decisions in life-threatening situations, but that is not the case. this is where the vmpfc comes into play. the vmpfc helps balance emotions and rationality. it anticipates potential outcomes, then decides whether to prioritize personal safety or saving others (yoder and decety, 2018; mendez, 2009). 72 the dorsolateral prefrontal cortex (dlpfc) also plays a crucial role by helping evaluate the long-term consequences of decisions, ensuring that the individual isn’t driven purely by short-term emotional reactions (baumgartner et al., 2013). meanwhile, the anterior cingulate cortex (acc) mediates conflicts between emotion and logic, helping to reconcile the often-competing interests of the amygdala and the prefrontal cortex (mendez, 2009). together, these regions create a dynamic network where rationality, emotion, and survival instincts are constantly negotiating the best course of action, particularly under stress. this seamless interaction explains how humans can make complex moral decisions even when faced with imminent danger. iii. impact of extreme stress on the brain stress institutes a cascade of physiological reactions that cause the brain to function differently during moral decision-making. during extreme levels of stress, the brain releases the prefrontal cortex, which is responsible for rational thinking and long-term decision-making, is significantly compromised in the event of high levels of stress. for instance, cortisol has been found to diminish the functioning of the pfc, which makes it rather difficult to deliberate a complex decision or to weigh consideration against long-term consequences (arnsten, 2009). at the same time, there is an increase in the activity level of the amygdala, hence giving rise to increased emotional response as well as giving way to immediate reactions based on survival instincts rather than ethical ones (ochsner et al., 2009). the resulting imbalance between the pfc and amygdala tips the brain toward emotionally-laden instinctive action, bypassing careful deliberation that is necessary for moral judgments. further, the acc overworks itself trying to moderate the conflict between these parts of the brain. stressed-induced disturbances in the brain make it more arduous for the acc to promote clear decision-making, thus pushing the person toward faster and often emotionally rationalized choices. in extreme stress, moral decision-making is heavily biased toward emotional reactions rather than reason-based judgment, which underlines the fragility of our ethical reasoning under pressure. the cognitive neuroscience of moral decision-making in extreme situations: high-stress or life-threatening scenarios 73 figure 1: the amygdala and vmpfc brain regions (walls et al., 2011) figure 2: acc and dlpfc brain regions (torres-quesada, 2013) figure 3: cortisol's flow and impact (russell & lightman, 2019) releases large amounts of cortisol and adrenaline, two stress hormones designed to prepare the body for a rapid response. these surges of hormones, however, strongly influence the different brain regions' operation. iv. empirical evidence: studies on stress and moral choices several laboratory experiments have revealed decisive evidence of how moral decision-making is distorted by stress. in these controlled experiments, participants are exposed to simulated conditions of stress such as public speaking or physical discomfort, in which circumstances subjects are more likely to favor immediate and emotionally driven responses when faced with dilemmas. for example, studies that put their participants in high levels of stress showed that participants are more likely to depend on intuition when solving complex moral dilemmas rather than ethical reasoning for human survival or their safety (starcke et al., 2008). neuroimaging allows a glimpse of the activity of the brain involved in such decisions. fmri scans revealed that during stressful conditions, decisions resulted in decreased activity of the prefrontal cortex along with increased amygdala activation. such findings support the hypothesis that the cognitive load created by stress impairs the brain's ability to sustain or otherwise continue its state of rational ethical thinking. instead, the hypertrophied activity of the amygdala enhances emotional responses and motivates individuals toward behaviors that fulfill the immediate need for survival or emotional gratification (shin et al., 2005). one of the clear findings that come out of these studies is that under intense stress, moral calculus, as it normally runs in the brain, tends to get disrupted. people are more likely to make decisions that have to do with self-preservation rather than broader ethical concerns – a powerful illustration of how deeply stress embeds its influence on shaping moral behavior. the cognitive clarity to navigate these moral dilemmas effectively. organizations could also implement ethical policies or procedures that consider how much stress modifies decision-making, such as reviewing decisions made under extreme tension orembedding procedures that may mitigate the effects of stress on moral judgment. furthermore, this knowledge can enhance technology, particularly ai systems. by embedding models that describe how human decision-making changes under stress, ai algorithms–such as those used in autonomous driving systems–could be configured in a way that takes into consideration subtle, stress-driven behavior of human operators. v. real-world applications the implications of cognitive neuroscience’s impact on moral-decision making are great for professions that face high levels of stress: healthcare workers, soldiers, firefighters, and law enforcement officers. these professionals make sound ethical decisions during life-anddeath situations. training programs inculcating stress management techniques would help professionals maintain the under intense stress, moral calculus, as it normally runs in the brain, tends to get disrupted. vi. conclusion extreme stress causes a critical disruption of the balance between emotion and reason within the brain during moral decision-making. it is this delicate balance in the interplay between the amygdala, prefrontal cortex, and anterior cingulate cortex that becomes imbalanced, resulting in decisions driven by survival and emotion rather than reasoned ethical judgment. awareness of these neural mechanisms in high-stress settings may inform strategies for supporting better moral decision-making by individuals and organizations. this implication requires further research about stress and the brain, so that the systems and structures we rely on during crises are equipped to make morally sound decisions when overwhelming stress occurs. references 1. american psychological association. (2018). moral decision making. apa dictionary of psychology. https://dictionary.apa.org/moral-decision-making 2. apa. (2024). apa dictionary of psychology. apa.org. https://dictionary.apa.org/decision-making 3. apa. (2024). apa dictionary of psychology. apa.org. https://dictionary.apa.org/dual-process-theory 4. arnsten, a. f. (2009). stress signaling pathways that impair prefrontal cortex structure and function. nature reviews neuroscience,10(6), 410-422. https://doi.org/10.1038/nrn2648 5. baumgartner, t., knoch, d., hotz, p., eisenegger, c., & fehr, e. (2013). dorsolateral and ventromedial prefrontal cortex orchestrate normative choice. nature neuroscience, 16(9), 1251-1253. https://doi.org/10.1038/nn.3445 6. greene, j. d., nystrom, l. e., engell, a. d., darley, j. m., & cohen, j. d. (2004). the neural bases of cognitive conflict and control in moral judgment. neuron, 44(2), 389-400. https://doi.org/10.1016/j.neuron.2004.09.027 7. mcewen, b. s. (2012). brain on stress: how the social environment gets under the skin. proceedings of the national academy of sciences, 109(supplement_2), 1718017185. https://doi.org/10.1073/pnas.1121254109 brain matters vol. 8 2025 74 8. mendez, m. f. (2009). the neurobiology of moral behavior: review and neuropsychiatric implications. cns spectrums, 14(11), 608-620. https://doi.org/10.1017/s10928529000237769. ochsner, k. n., & gross, j. j. (2009). the neural architecture of emotion regulation. handbook of emotion regulation, 38, 87-106. https://doi.org/10.1093/acprof:oso/9780195311353.003.0004 10. russell, g., & lightman, s. (2019). the human stress response. nature reviews endocrinology, 15(9), 525–534. https://doi.org/10.1038/s41574-019-0228-0 11. salzman, c. daniel (2024). amygdala. encyclopedia britannica. https://www.britannica.com/science/amygdala 12. shin, l. m., wright, c. i., cannistraro, p. a., wedig, m. m., mcmullin, k., martis, b., macklin, m. l., lasko, n. b., cavanagh, s. r., krangel, t. s., orr, s. p., pitman, r. k., whalen, p. j., & rauch, s. l. (2005). a functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. archives of general psychiatry,62(3), 273–281. https://doi.org/10.1001/archpsyc.62.3.273 13. starcke, k., & brand, m. (2012). decision making under stress: a selective review. neuroscience & biobehavioral reviews, 36(4), 1228-1248. https://doi.org/10.1016/j.neubiorev.2012.02.003 14. torres-quesada, maryem. (2013). reactive and proactive modulation in cognitive and emotional control. walls, andrew, okumus, fevzi, & wang, youcheng. (2011). cognition and affect interplay: a framework for the tourist vacation decision-making process. journal of travel & tourism marketing, 28, 567-582. https://doi.org/10.1080/10548408.2011.588121 15. yoder, k. j., & decety, j. (2018). the neuroscience of morality and social decision-making. annual review of psychology, 69, 101-127. https://doi.org/10.1146/annurevpsych-122216-011403 75 the cognitive neuroscience of moral decision-making in extreme situations: high-stress or life-threatening scenarios may yang may is a freshman at the university of illinois majoring in brain & cognitive science. she joined brain matters to learn more about the brain, develop her research skills, and connect with people who share similar interests. in addition to writing for brain matters, may is also involved in dr. hotaling’s cognitive decision making lab. in the future, she hopes to pursue a phd in a related field. 76 brain matters vol. 8 no. 2 jessica george hi! my name is jessica george and i’m a junior majoring in molecular and cellular biology and brain and cognitive science. outside of school, i volunteer at a nursing home in the activities department, where i work closely with residents who have dementia. in my free time i love dancing, listening to music, and trying new restaurants! jeslyn chen i’m a rising sophomore majoring in psychology and minoring in chemistry. i joined brain matters to combine my interests of neuroscience, psychology, and journalism. outside of this magazine, i plan to become a student emt at uiuc and enjoy drawing, going to concerts, and thrifting. design board 78 esther nam esther nam is a junior on the pre-medical track majoring in psychology with a minor in public health. she is interested in exploring the cognitive and neurological impacts of bilingualism, and is currently a research assistant in the educational psychology psycholinguistics lab with a focus on cognitive psych. in her free time, she loves to draw, play games, and spend time with friends. after undergrad, esther hopes to attend medical school to become a physician. ruth anderson ruth anderson is a rising sophomore at the university of illinois majoring in neuroscience and minoring in psychology. she joined brain matters to get involved with the neuroscience community on campus and learn more about the field. ruth currently is hoping to pursue a career in research. she is passionate about womens health and child development. outside of school ruth enjoys hanging out with her friends, crocheting, and reading. 79 lisa patel lisa patel is a rising junior and an integrative biology major on the pre-medical track with minors in chemistry and nutrition at uiuc. passionate about medicine and community outreach, she co-founded and serves as president of the illini sheltering hands society, where she teaches basic life-support skills and organizes volunteering initiatives. as public relations coordinator for react, lisa coordinates hands-on chemistry demonstrations at local elementary and middle schools. she’s volunteered over 300 hours at ui health hospital while assisting across emergency, diagnostics, radiology, university health services, and surgical departments. she also directs community health initiatives as director of medicine for uiuc’s medlife chapter. her end goal is to become a physician and she is dedicated to expanding her knowledge to better serve her community. sania shah sania shah is a sophomore majoring in brain and cognitive science with a minor in data science. she works as an undergraduate research assistant in the cognitive decision-making lab and dances competitively with the illini raas team. outside of brain matters, sania enjoys playing badminton with friends and curling up with a good book and an iced coffee. 80 brain matters vol. 8 no. 2 abstract human leukocyte antigens (hla) are significant components of the human immune system responsible for autoimmunity. these genes are located on chromosome 6 and encode for proteins that assist the body in fighting against foreign invaders. however, hla may have the potential to induce varying degrees of brain atrophy (ba) and multiple sclerosis (ms), both of which are neurodegenerative disorders. examining the protective and aggravating effects of hla on these neurological disorders, as well as potential preventive measures that could be implemented through hla, may prove to have significant effects on the approach to ba and ms. the role of human leukocyte antigens in multiple sclerosis and brain atrophy written by tanisha mandal when the loss of connection is so great that it can be considered abnormal. due to the fact that ms is an autoimmune disorder, it can be linked to human leukocyte antigens. human leukocyte antigens, or hla for short, are found on chromosome 6 and encode for proteins that present as antigenic peptides on t cells. this means that ms is a t-cell-mediated autoimmune disorder. hla -dr antigens specifically are membrane heterodimeric glycoproteins, which means that they consist of proteins that are found in cell membranes, and often play a role in communication and signaling (scholz, e. m, marcilla, m, daura, x, et al., 2017). in the case of hla specifically, they play an important role in the autoimmune response system of the human body. as a result, many autoimmune disorders are caused by defects in the hla gene. after extensive research, the allele responsible for this development has been narrowed down to class ii hladrb1*1501 (lorefice l, fenu g, sardu c, et al., 2019). more research has uncovered that hla can also provide protective effects against the demyelination caused by ba and ms. this is due to another class ii allele, specifically drb1*1302, which works in the cns and has been shown to prevent the rapid degeneration of neurons associated with ba. class ii hla has complex effects on the cns, thus contributing to the development of brain atrophy and multiple sclerosis, with different alleles of the same gene providing vastly different outcomes. introduction brain atrophy (ba) is a progressive neurodegenerative disorder that leads to neuronal loss and connectivity. as a result, brain volume decreases and symptoms such as memory loss, seizures, and aphasia occur. while it is not uncommon to lose neurons as one gets older, ba refers to when an individual has more abnormal brain changes than what is expected for their age. in its most severe forms, ba can become fatal (harris tc, de rooij r, kuhl e., 2019). there are two types of ba, focal and generalized. focal refers to atrophy in a specific part of the brain, and generalized refers to atrophy spread throughout the brain. another chronic neurological disorder is multiple sclerosis (ms) which is caused by the autoimmune system, inducing the body to attack the central nervous system (cns). common symptoms include muscle weakness, coordination issues, cognitive difficulties such as memory problems, and slowed processing speed. the exact causes of ms remain unclear, but several factors contribute, particularly genetic predisposition. in an individual with ms, the autoimmune system attacks the myelin sheath surrounding the body’s neurons, which disrupts communication between neurons (national institute of neurological disorders and stroke, 2024). the loss of neuronal connections caused by the presence of ms, is also an aforementioned key symptom of ba. thus, ms can significantly worsen the damage done by atrophy. in addition, ms can also be the primary cause of ba, when 6 description of hla class ii alleles structure and function as seen in figure 1, the primary structural difference between two types of human leukocyte antigens is that class 1 hla molecules have 1 polypeptide chain, combined with a beta-2 microglobulin subunit while class ii molecules contain 2 polypeptide chains. this results in the distinct roles that the molecules play in the human body. for populations that express a high frequency of drb1*1302, neurodegeneration can be slowed by around 45.2%. scientists hypothesize that its protective effect could be due to the removal of antigens that persist in causing gradual brain atrophy. these beneficial effects have also been attributed to drb1*13:02’s binding to cathepsin s, a known harmful substance in brain aging (james, l. m., & georgopoulos, a. p., 2019). this is best demonstrated in the research done on drb1*1302’s effect on dementia and gulf war illness, which are both caused by some levels of neurodegeneration. thus, it is reasonable to assume that drb1*1302 demonstrates preventative effects against general atrophy of the brain. class i molecules are responsible for facilitating cell destruction, whereas class ii molecules are responsible for recognizing invaders and producing the appropriate antibodies (james, l. m., & georgopoulos, a. p., 2019). however, since class ii hla binds to antigen-presenting cells (apc) and is ultimately responsible for determining what the body considers a harmful microorganism, a miscoding in certain alleles can cause the body to attack itself, known as an autoimmune disorder. as previously stated, ms is classified as an autoimmune disorder, meaning that the introduction of ms in the body is almost entirely due to class ii hla molecules. this is why class ii hla molecules are the primary focus concerning ba and ms. the role of human leukocyte antigens in multiple sclerosis and brain atrophy the protective effects of drb1*1302 on demyelination and atrophy studies have discovered that the frequency of class ii hladrb1*1302 has an inverse association with dementia, which is caused by the loss of synaptic connections, in 14 western european countries (james, l. m., & georgopoulos, a. p., 2019). as displayed in figure 2, this is suspected to be due to the fact that the hla drb1*1302 allele helps encode for antibodies that specifically protect against pathogens that cause neurodegeneration. dementia is linked to ba through the most prominent symptoms of neurodegeneration, loss of memory. since the frequency of the drb1*1302 allele has an inverse association with the loss of synaptic connections, it is suspected that the allele protects against pathogens that cause this neurological degeneration, which in turn causes ba. therefore, it is reasonable to assert that the presence of the drb1*1302 allele has an inverse effect on the onset of dementia, and thus the onset of ba. the harmful effects of drb1*1501 on ms and brain atrophy hla-drb1*1501 is an hla haplotype, a group of closely linked alleles that are frequently inherited together and has been linked to a significantly higher risk of ms, and consequently, also to ba (scholz, e. m, marcilla, m, daura, x, et al., 2017). in fact, drb1*1501 is the single strongest genetic factor in the development of ms. while t-cells aren’t typically considered apc, they do express major histocompatibility complex (mhc is known as hla in humans) class ii antigens, which are precisely what class ii hla control (pichler, w. j & wyss-coray, t, 1994). figure 1: structure of class i and class ii hla molecules (grubic, 2017). 7 figure 2: flowchart demonstrating link between decreased hla and dementia (james, l. m., & georgopoulos, a. p., 2019) research suggests that pathogens involved with demyelination may appear to be similar to the actual myelin itself. as a result, drb1*1501 could be especially susceptible to being “tricked” by this mimicry and produce agents that begin attacking myelin instead of the pathogens (sospedra, m., & martin, r., 2005). in addition, research shows that drb1*1501 is suspected to interact with specific cytokines that are responsible for signaling immune responses in the brain, causing inflammation and degeneration of cells in the cns. they essentially secrete proinflammatory cytokines that predispose the body to autoimmune diseases such as ms. when reviewing patients who expressed a high frequency of drb1*1501, scientists found that “carriage of hla-drb1*15 was associated with increases in the development of brain grey and white matter pathology, as reflected by reduced [magnetization transfer ratio] (mtr), a trend toward increased t2 lesion load over 5 years, and greater t2 lesion volumes at each time point over the follow-up” (tur, c., ramagopalan, s., altmann, d. r., et al., 2014). thus, it was concluded that individuals showed a significant amount of brain atrophy when contrasted with the healthy control group. this shows a strong positive correlation between the presence of the drb1*1501 allele and abnormal amounts of atrophy in the brain. brain matters vol. 8 2025 effects of hla on the pathways of ms and ba in nearly every case of ms, the early stages of pathology result from abnormal amounts of inflammation in the brain (kiss, m. & mcalpine, c.s., 2023). neuroinflammation is caused by the increased presence of t-cells in response to supposed invaders, which in cases of ms are the body’s own cells, and the regulation of these t-cells is linked back to hla. individuals carrying the drb1*1501 allele, have an increased susceptibility to ms and more severe disease progression, which can lead to greater demyelination. this is due to the role of these alleles in promoting an autoimmune response against myelin proteins. similarly, the onset of ba is caused by abnormal amounts of demyelination in the brain. one of the most common causes of demyelination is inflammation, linking the root cause of ba to the root cause of ms. thus, ba is similarly influenced by the hla alleles. conclusion although the significance of hla on the pathways of ba and ms has not been widely explored, the link between the two is most certainly present. due to both neurodegenerative diseases being directly linked to the loss of synapses onset by autoimmune responses in the brain, and hla being responsible for the immune system, hla is a clear factor in the development of ba and ms. the two alleles most closely related to the onset of the diseases, drb1*1501 and drb1*1302, are haploids of hla, so genomic editing and therapy may provide the first preventative cure for ba and ms. proposed preventative gene therapy: brain atrophy and multiple sclerosis have long been thought to be incurable, with treatment mainly consisting of just improving the quality of life of people afflicted with these diseases. since different alleles of hla can produce different effects on ba and ms, a potential goal for gene therapy could be to activate drb1*1302 more often and suppress the expression of drb1*1501 in hla. as a result, preventative effects would be much higher, and the rate of ba and ms in individuals would likely decrease significantly. one form of gene therapy could focus on monoallelic expression, as demonstrated in figure 4, which is when one allele of a gene is expressed, and another allele of that same gene is silenced. techniques such as crispr have been used to selectively silence one allele while leaving the other intact, which seems to be exactly what individuals at risk for atrophy need (hsu, p. d., lander, e. s., & zhang, f., 2014). overall, a preventative cure for atrophy may be just around the corner, providing a means to protect against one of the most complicated and unstoppable neurodegenerative effects. 8 figure 3: binding motif of hla drb1*1501 (hla protein, 2024). figure 4: diagram of monoallelic gene therapy (eckersley-maslin, m. a.,& spector, d. l., 2014) 9. pichler, w. j., & wyss-coray, t. (1994). t cells as antigenpresenting cells. immunology today, 15(7), 312–315. https://doi.org/10.1016/0167-5699(94)90078-7 10. alcina, a., abad-grau, m., fedetz, m., et al. (2012). multiple sclerosis risk variant hla-drb1*1501 associates with high expression of drb1 gene in different human populations. plos one, 7(1), e29819. https://doi.org/10.1371/journal.pone.0029819 11. james, l. m., & georgopoulos, a. p. (2019). dementias caused by persistent pathogens and the protective role of hla against them. journal of neurology & neuromedicine, 5(1). https://www.jneurology.com/articles/dementiascaused-by-persistent-pathogens-and-the-protective-roleof-hla-against-them.html 12. sospedra, m., & martin, r. (2005). immune reactions in multiple sclerosis. the lancet neurology, 4(3), 168-180. https://doi.org/10.1016/s1474-4422(05)70020-5 13. tur, c., ramagopalan, s., altmann, d. r., et al. (2014). hla-drb1*15 influences the development of brain tissue damage in early ppms. neurology, 83(19), 1712–1718. https://doi.org/10.1212/wnl.0000000000000959 14. hsu, p. d., lander, e. s., & zhang, f. (2014). targeted gene editing using crispr/cas9: a review of its applications in human diseases. nature reviews genetics, 15(5), 321-334. https://doi.org/10.1038/nrg.2014.36 15. kiss, m. & mcalpine, c.s. (2023). a key biological pathway for multiple sclerosis is uncovered by mount sinai researchers. mount sinai health system. references 1. harris, t. c., de rooij, r., & kuhl, e. (2019). the shrinking brain: cerebral atrophy following traumatic brain injury. annals of biomedical engineering, 47(9),1941–1959. https://doi.org/10.1007/s10439-018-02148-2 2. cruz-tapias, p. (2013). major histocompatibility complex: antigen processing and presentation. https://www.ncbi.nlm.nih.gov/books/nbk459467/#:~:text=h la%20class%20i%20antigens%20are,endothelial%20cells%2 c%20and%20thymic%20epithelial 3. lorefice l, fenu g, sardu c, et al. (2019). multiple sclerosis and hla genotypes: a possible influence on brain atrophy. multiple sclerosis journal, 25(1), 23-30. https://doi.org/10.1177/1352458517739989 4. national institute of neurological disorders and stroke. (2024, july 19). multiple sclerosis. www.ninds.nih.gov. https://www.ninds.nih.gov/healthinformation/disorders/multiple-sclerosis 5. hla protein. (2024). hlaprotein.com. https://www.hlaprotein.com/hladrb11501-drb11501 6. grubic, zorana. (2017). human leukocyte antigen polymorphism in search for a matched unrelated donor in haematopoietic stem cell transplantation. 4-12. 7. scholz, e. m, marcilla, m, daura, x, et al. (2017). human leukocyte antigen (hla)-drb1*15:01 and hla-drb5*01:01 present complementary peptide repertoires. 8. eckersley-maslin, m. a., & spector, d. l. (2014). random monoallelic expression: regulating gene expression one allele at a time. trends in genetics, 30(6), 237–244. https://doi.org/10.1016/j.tig.2014.03.003 9 the role of human leukocyte antigensin multiple sclerosis and brain atrophy tanisha mandal tanisha mandal is a freshman at the university of illinois, studying neural engineering with a minor in computer science. her interests in neuroscience include computational neuroscience, specifically its applications in treating neurodegenerative diseases, and internal causes of severe brain lesions, such as brain cancer. she also enjoys going skiing, playing cards, and listening to music. tanisha was interested in being a writer for brain matters to have the opportunity to practice writing her own research papers in the future and explore new neuroscience topics in depth. outside of brain matters, tanisha is involved in research programs such as neurotech’s cortex codex and ur2phd, and fun rsos such as the cooking collective and uiuc’s book club! 10 brain matters vol. 8 no. 1 written by emily aldrich amusia: the science behind tone deafness what is tone deafness? for most, the ability to distinguish basic pitch, rhythm, and melody of music is something that comes naturally. the brain is attuned to hearing certain sounds and perceiving them as music, allowing for listeners to enjoy what they are listening to as well as imitate what they hear. this seemingly simple, unconscious knowledge of music for individuals is something that about 2.5% of the population lacks (lehmann et al., 2015). congenital amusia, often referred to as “tone deafness”, is a disorder present at birth that is characterized by the impairment of musical perception. although amusic individuals know that the sound they are hearing is supposed to be a song, the concept of music as a whole is lost on them. those with congenital amusia have an inability to perceive music as a coherent network of melodic elements (szyfter & wigowska, 2021). instead, they recognize it only as disorganized noise in the environment, and can have deficits in perception of tune, melody, and rhythm – all factors that make up music. audition process auditory processing occurs during any moment where sound is made and can be perceived, triggering the activation of neural pathways in the brain. sounds start as air pressure waves that go through the ear canal, which is then detected by hair-like projections called stereocilia, located on the basilar membrane of the cochlea (kulsoom & karim, 2021). at this point in processing, these vibrations are transformed into electrical signals that are then sent to neurons neurons in the spiral ganglion, whose axons form the auditory nerve (kulsoom & karim, 2021). the auditory nerve then sends the signal to the brainstem’s auditory nuclei, a relay station for these signals to then be sent out to numerous different areas of the brain for further processing. although these signals extend far out into different parts of the brain, this auditory process occurs all in the span of milliseconds. figure 1. audition process where sound waves become nerve impulses (gollisch & herz, 2005). physiological aspects biological differences between those with amusia and the general population have been studied to better understand how tone deafness manifests in both the nervous system and the genetics of the affected group. one area that has been shown to have ties with amusia and general musical ability is the brainstem (lehmann et al., 2015), a structure that sits just below the brain and connects to the spinal cord.42 cord. the brainstem mediates many pathways of neuronal activity, allowing for the coordination of different brain functions. researchers used complex auditory brain responses (cabrs) to measure the subcortical processing of complex sounds like tones, speech, and in this case, music (anderson & kraus, 2013). for amusic individuals who process music irregularly, their cabrs have shown decreased spectral amplitude meaning frequencies were weaker in magnitude, and slower onset responses; the stronger the disability in musical processing, the stronger these differences show up as cabrs (lehmann et al., 2015). these areas of deviation from the norm show that there are specific locations and pathways where music is processed. when these pathways are not processed correctly, this may elicit a misunderstanding of sound in a way that amusics perceive as disorganized and not melodious. this information indicates that the physiological differences between amusics and non-amusics affect how their perceptions of complex sounds like music. genetic components there is likely a genetic component regarding congenital amusia, as many people who have this disorder are shown to have other family members with similar musical deficits. to learn more about the genetic underpinnings of congenital amusia, researchers began to study self-identified amusic individuals who also did poorly on the montreal battery of evaluation of amusia (mbea), a test to determine the level of musical capability one has by assessing scale, contour, interval, rhythm, metric, and music memory–all components of music processing (nunes-silva & haase, 2012). they had both amusic and non-amusic control groups encourage family members to take an assessment similar to mbea that tested the same musical skills to determine whether or not these family members would have a comparable score to their relative. this study deduced that 39% of first degree relatives of people with amusia also have the same disorder, while only 3% of relatives have amusia in the control group (peretz et al., 2007). the heritability of amusia is very evident, meaning genetics plays an important role in the phenotype of congenital amusia. sociocultural impacts of amusia a highlighting feature of amusia is the consistent inability to recognize musical tunes, which also extends to music memory. it is strongly connected to deficits in recognizing small pitch changes. a noteworthy feature from amusia studies is that although difficulties in musical perception does not extend to the language realm for non-tonal languages like english, amusical people who use tonal languages like mandarin or vietnamese do slightly struggle in speech perception. in tonal languages, the pitch or tone of a syllable itself can change the meaning of words. in mandarin, for example, the syllable /ma/ can mean either “mother”, “horse”, “hemp”, or “to scold” depending on which tone is used, as shown in figure 2 (li et al., 2021). amusics who do speak tonal languages are able to produce the the correct tones when creating speech, but have greater difficulty in accurately imitating pitches for tones they hear (liu et al., 2013). although they are still able to produce language at a proficient level, there is still some overlap between the presence of amusia and speech imitation in tonal languages because they are so reliant on the ability to use the correct pitches and match them accordingly. further look into amusia the progression of our understanding of congenital amusia has gone very far in just the past few decades. there have been many groundbreaking studies that further explain both the origins and long-term effects of this cognitive deficit. it is essential that we learn more about this lifelong disorder. from the progression in research that we have seen so much of, there are even more thoughts and questions that are important to answer. we now know there is a strong genetic component of this disorder. future research can help identify amusia-related genes in individuals to learn more about how it is inherited, as well as finding treatments to target amusia. additionally, it would be interesting to dig deeper in the social impact amusia has on its individual–particularly how the emotions that are elicited when listening to a certain song compares to controls, as well as its possible impact on individuals who speak pitch-accent languages. through further research, we could potentially gain greater understanding of how amusics perceive and experience the world around them. references 1. anderson s, kraus n. the potential role of the cabr in assessment and management of hearing impairment. int j otolaryngol. 2013;2013:604729. doi: 10.1155/2013/604729. epub 2013 jan 30. pmid: 23431313; pmcid: pmc3572655. 2. gollisch, t., & herz, a. (2005, january). file:processing-ofsound.svg. wikimedia commons. https://commons.wikimedia.org/wiki/file:processing-ofsound.svg amusia: the science behind tone deafness figure 2. standard chinese tone contours (wikimedia foundation, 2021). 43 3. kawamura m, miller mw. history of amusia. front neurol neurosci. 2019;44:83-88. doi: 10.1159/000494955. epub 2019 apr 30. pmid: 31220839. 4. kulsoom b, karim n. sound: production, perception, hearing loss and treatment options. j pak med assoc. 2022 apr;72(4):725-732. doi: 10.47391/jpma.4051. pmid: 35614609. 5. lehmann a, skoe e, moreau p, peretz i, kraus n. impairments in musical abilities reflected in the auditory brainstem: evidence from congenital amusia. eur j neurosci. 2015 jul;42(1):1644-50. doi: 10.1111/ejn.12931. epub 2015 jun 18. pmid: 25900043. 6. li y, tang c, lu j, wu j, chang ef. human cortical encoding of pitch in tonal and non-tonal languages. nat commun. 2021 feb 19;12(1):1161. doi: 10.1038/s41467-02121430-x. pmid: 33608548; pmcid: pmc7896081. 7. liu f, jiang c, pfordresher pq, mantell jt, xu y, yang y, stewart l. individuals with congenital amusia imitate pitches more accurately in singing than in speaking: implications for music and language processing. atten percept psychophys. 2013 nov;75(8):1783-98. doi: 10.3758/s13414-013-0506-1. pmid: 23877539.\ brain matters vol. 8 2025 8. nunes-silva m, haase vg. montreal battery of evaluation of amusia: validity evidence and norms for adolescents in belo horizonte, minas gerais, brazil. dement neuropsychol. 2012 oct-dec;6(4):244-252. doi: 10.1590/s198057642012dn06040008. pmid: 29213804; pmcid: pmc5619336. 9. peretz i, cummings s, dubé mp. the genetics of congenital amusia (tone deafness): a family-aggregation study. am j hum genet. 2007 sep;81(3):582-8. doi: 10.1086/521337. epub 2007 jul 20. pmid: 17701903; pmcid: pmc1950825. 10. szyfter k, wigowska-sowińska j. congenital amusiapathology of musical disorder. j appl genet. 2022 feb;63(1):127-131. doi: 10.1007/s13353-021-00662-z. epub 2021 sep 21. pmid: 34545551; pmcid: pmc8755656. 11. vuust p, heggli oa, friston kj, kringelbach ml. music in the brain. nat rev neurosci. 2022 may;23(5):287-305. doi: 10.1038/s41583-022-00578-5. epub 2022 mar 29. pmid: 35352057. 12. wikimedia foundation. (2021, december). file:mandarin tone contours (beijing standard).svg. wikipedia. https://en.m.wikipedia.org/wiki/file:mandarin_tone_conto urs_(beijing_standard).svg about the author emily aldrich is a freshman majoring in neuroscience with minors in linguistics and psychology on the pre-med track. emily joined brain matters to gain a deeper understanding of the brain through exploring current research topics in neuroscience. in her free time, she enjoys listening to music, reading, and spending time with friends. 44 45 volume 8 (will be vol 7 on site) how the brain creates predictive models of the environment kaitlyn tuvilleja abstract researchers, utilizing technologies like fnirs (functional near-infrared spectroscopy) on 6-month-olds and eeg (electroencephalography) on infants viewing image sequences, can uncover how young brains craft and apply predictive models to react to events. adult brain learning is also examined through two types: model-free learning (trial and error) and model-based learning (implementing predictive models). by analyzing data from various age groups, researchers can examine how brains craft predictive models of the environment and leverage those findings for future implications. dissecting the way the brain constructs predictive models of the environment at distinct ages is crucial for developing enhanced educational practices: this paper examines the development of predictive cognitive models from infancy through adulthood using neurological studies, highlighting their implications for enhancing educational strategies and adaptive behaviors. introduction the way that we react or the choices we make in certain situations is hypothesized to be guided by internal models. this can trigger the body’s flight-or-fight response, curiosity, and even hunger. for example, when going to the doctor, the doctor will hit an individual’s knee to check their reflexes. what may seem like a knee-jerk reaction is a realization of the brain’s predictions about immediate danger, analogous to how a pianist’s fingers can predict where the next note is through repetitive practice and auditory exposure to their piece. the brain actively constructs a "call for action" that drives us to continuously shape the brain’s internal models (kayhan et al., 2019). this way, the internal map that the brain has created can guide future actions and decisions. the brain’s activation process for predictive models can even be thought of as a construction zone: a place where it actively repairs and reshapes the mental map in response to unexpected changes. to support this theory, o’reilly’s team from oxford university selected a handful of adults and presented a target object that would change positions. the positions included both predictable locations, learned through repeated exposure and unexpected ones. the study revealed that “activation in the parietal cortex when an immediate motor response was programmed as participants had to update their internal models to accommodate the change of target locations” (o'reilly, 2013). when the change was predictable, the parietal cortex, a region of the brain responsible for processing sensory information and coordinating motor responses, quickly adjusted the planned motor commands. however, a surprise triggers the brain’s anterior cingulate cortex–an area responsible for updating internal models based on error detection–to activate. essentially, when unexpected movements occur, they trigger specific brain regions in charge of movement planning and adaptation, evidence to the hypothesis of the brain creating internal models. this factors into the ability to create internal predictive models, and how individuals learn and react to the world through these models, starting from infancy. predictive model creation in infants current research explores how infants develop the capacity to construct mental maps. as of 2015, a functional nearinfrared spectroscopy (fnirs) study was conducted on infants (gallagher, 2023). an additional study conducted by e. kayhan at the university of potsdam demonstrated that at 6 months old human brains already create a predictive model of the environment. more specifically, “after a learning period, when images were unexpectedly omitted, infants showed activation in the occipital cortex, as if an image was presented, suggesting that they generated predictions about the visual input”(kayhan et al., 2019). researchers were interested in how babies process and adapt to change when prompted by unfamiliar environments. to explore this, they conducted a study with sixty 9-monthold infants. dr. kayhan and his team had predicted that “if participants formed predictions based on the repeated observations of the predictable stimuli, they would show a prediction error response when their predictions were violated by the unexpected appearance of the cues” (kayhan et al., 2019). the study involved showing pictures to the babies and would utilize a system that combined sound and brainwave monitoring (audio-visual eeg). the pictures featured a bee, but the sequence changed to test the babies' predictions. first, the babies were shown repetitive images of a bee (expected sequence). this established a control data set for the scientists. next, the babies were then shown a predictable surprise which included a bee image followed by an image that could be associated with the bee (i.e. a flower). finally, the babies were shown an unexpected sequence where the bee image was followed by an image that wouldn’t make sense (i.e. a truck). scientists expected that babies' brains would be more surprised if a pattern was not followed, inducing a stronger electrical response called an nc wave. the first session involved participants to observe predetermined choices without rewards. from this, researchers were able to measure state prediction errors (spes) – the difference between predicted and actual outcomes – and reward prediction errors (rpes) – surprises associated with unexpected rewards. by examining the errors, researchers were able to gauge the participant's initial understanding of the system. the second session gave participants the liberty to implement their own choices with the potential of a reward. this tested whether patients could utilize the knowledge in the previous session. researchers revealed that 13 out of the 18 participants were successfully able to employ modelbased learning to execute optimal choices. suggesting a clear preference for constructing predictive models over trial and error approaches. participants acquired optimal decisionmaking through model-based learning which is illustrated through their ability to adapt to the system's modifying tasks, even when rewards were provided. this would demonstrate the idea that “participants would acquire knowledge about the transition probabilities during session 1, despite the absence of any rewarding outcomes. this state knowledge can therefore be only acquired through model-based learning, potentially updated via an spe” (gläscher, 2023). future implications for learning like infants, these findings can be used to configure educational plans for students. as children grow older, their brain develops. to aid these developments, it should be important to continue implementing lessons that can be designed to build upon and challenge these predictive abilities. brains do not inactively experience the world but actively work to construct models to predict what will happen next. before the experiment, researchers had predicted that babies would portray a weaker nc wave (less electrical activity) by seeing the repeated bee images. nc waves detected whether attention was suppressed during the trials (if infants didn’t pay attention during trials). interestingly enough, there was not a significant difference in nc wave strength between the update and no-update trials within the enclosed section (fig. 1). this shows that infants might be processing given information more deeply than expected, almost challenging previous knowledge on how infants create predictive models of the environment. these results can potentially be incorporated in lower education fields, potentially setting a foundation for surprisebased learning. teachers can implement some surprise or novelty in learning experiences that could benefit children's learning. for example, allowing for more open-ended questions can encourage students to explore different approaches to problem-solving scenarios, sparking curiosity toward unexpected results. by honing in on a child’s ability to create predictive models, educators can create more effective and engaging learning practices that foster critical thinking and problem-solving skills. predictive modeling in adults however, before revamping academic frameworks based on children’s predictive models of the environment, understanding the brain’s decision-making is essential. in part, adult brains can learn from reinforcement learning: model-free and model-based (otto et al., 2015). model-free rl directly uses past experiences to figure out what actions are rewarding, while model-based rl builds a mental map of how the world works and uses this map to decide what action to take. to further explore this phenomenon, scientist gläscher strived to find how predictions are created through “trial-by-trial neural signals that reflect the dynamics of this learning” (gläscher, 2023). the study consisted of 18 caltech adult students with normal vision) and no neurological or psychiatric conditions (20/20 and not colorblind). within two sessions, researchers examined how participants developed optional decisions in a reward-based environment. figure 1. shows the brain signal from the vertex of the head for the different trial types. the update line shows the highest amplitude meaning the brain produced a stronger nc wave with the update trial than no-update and expected (kayhan et al., 2019). figure 2. illustration of the decision-making process of scientist gläscher and his research team at caltech’s study on model-free reward learning and model-based reward learning (gläscher) brain matters・volume vii 68 this “auto-pilot” function, through its remarkable plasticity, continues to refine its predictive models. research on infants illustrates the ability to effectively detect unexpected events and update models accordingly. meanwhile, in part, adults utilize model-free and model-based learning for decisionmaking. with knowledge of children and adult brain plasticity, educators can leverage these traits to create more engaging learning environments and foster groundwork for adult learning styles. these findings in plasticity hold the potential for unlocking new opportunities for personalized cognitive training programs for children. for example, educational practices can be designed to refine and challenge a student’s predictive models. these implications can be extended to older individuals, as well. with this new profound knowledge of brain plasticity, the possibilities are truly invigorating. references 1. arsten, a., et al. (2012, april). neural circuits responsible for conscious self-control are highly vulnerable to even mild stress. when they shut down, primal impulses go unchecked and mental paralysis sets in. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4774859/#fngroup-a.f.atitle 2. gallagher, a. (2023, march 3). functional near-infrared spectroscopy in pediatric clinical research: different pathophysiologies and promising clinical applications. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9982436/ 3. gläscher, j. (2023, june 16). states versus rewards: dissociable neural prediction error signals underlying modelbased and model-free reinforcement learning. neuron. https://www.cell.com/fulltext/s0896-6273(10)002874#secd29307264e631 kayhan, e., et al. (2019, july 10). nine-month-old infants update their predictive models of a changing environment. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6969335/ 4. moran, r. j. (2014, january 23). the brain ages optimally to model its environment: evidence from sensory learning over the adult lifespan. plos. https://journals.plos.org/ploscompbiol/article? id=10.1371/journal.pcbi.1003422 5. o'reilly, j. x. (2013, june 14). making predictions in a changing world—inference, uncertainty, and learning. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3682109/ 6. otto, a. r., et al. (2015, may 1). cognitive control predicts use of model-based reinforcement-learning. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4387848/ 7. roozendaal, b., & mcgaugh, j. l. (2011, december). memory modulation pmc. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3236701/ 8. šimić, g., et al. (2021, may 31). understanding emotions: origins and roles of the amygdala. ncbi. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8228195/ brain matters vol. 8 no. 2 can we train our brains to break social media addiction? written by meha goswami introduction social media has revolutionized communication, allowing people to stay connected with family and friends, and build relationships across the globe. while these benefits enhance social and psychological well-being, excessive use of social media can have detrimental effects on mental and physical health (cheng et al., 2022). many individuals turn to social media as an escape from reality, using it to avoid problems rather than address them. cheng et al., (2022) found that when social media consumption becomes compulsive and interferes with daily life, it can develop into social media addiction—a behavioral addiction characterized by excessive use that disrupts crucial aspects of well-being, such as physical health, productivity, and interpersonal relationships. similar to substance use disorders, social media addiction is driven by neurobiological mechanisms that reinforce compulsive behavior. at the core of this addiction lies the brain’s dopamine reward system, which is exploited by social media platforms through unpredictable rewards such as likes, comments, and shares that trigger dopamine release and reinforce habitual use (cheng et al., 2022). understanding how social media manipulates these neural pathways is essential for developing effective strategies to reduce dependence and restore healthy digital habits. the neuroscience of social media addiction to fully grasp the addictive nature of social media, it is important to explore the underlying neural mechanisms that sustain compulsive digital behaviors. this section delves into the neuroscience behind social media addiction, examining the brain’s reward pathways, structural differences, and cognitive impacts. dopamine reward system social media platforms exploit the brain’s reward system, specially the mesolimbic pathway, by triggering dopamine release in response to engagement on accounts. dopaminedriven reinforcement contributes to problematic behaviors including excessive social media use (de et al., 2025). variable reward systems activate the brain’s mesolimbic dopamine system, the same pathway involved in drug addiction. this system gauges the reward value of these social experiences and reinforces behavior that would lead to more pleasurable outcomes; this creates a cycle of reinforcement where users continue checking social media in hopes of receiving pleasurable stimuli. moreover, the anticipation of these rewards can be more impactful than the rewards themselves. over time, this pattern of expectation strengthens neural circuits associated with craving and compulsive behaviors (de et al., 2025). highly active neural circuits reinforce the habitual use of social media and makes it even tougher to resist overuse. 40 al., 2009). prolonged social media use has been associated with reduced efficiency in attentional networks, leading to difficulties in filtering distractions and maintaining sustained focus on cognitively demanding tasks. together, these effects illustrate how habitual digital multitasking can compromise core cognitive functions, ultimately diminishing our ability to concentrate and perform effectively in everyday life. fmri studies reveal increased activity in the ventral striatum, a key reward-processing center, when individuals engage with social media, further reinforcing addictive tendencies (de et al., 2025). can we train our brains to break social media addiction? impulse control and gray matter differences in the brain gray matter is a crucial component of the brain that contains most of the neuronal cell bodies and plays a vital role in processing information, decision-making, and impulse control. solly et al., (2022) found that chronic social media use may alter brain structures responsible for decision-making and self-control. for example, excessive social media engagement is linked to reduced gray matter volume in areas such as the left anterior cingulate cortex (acc), supplementary motor area (sma), and left dorsolateral prefrontal cortex (dlpfc). these regions play a crucial role in inhibitory control and impulse regulation. these alterations contribute to reduced inhibitory control, making it more difficult for individuals to regulate their social media consumption (solly et al., 2022). additionally, solly et al. (2022) highlights that compulsive digital engagement leads to neuroplastic changes that reinforce habitual behaviors, further impairing self-regulation. overall, chronic social media use can significantly impact brain structures involved in self-control, potentially creating a cycle of compulsive behavior and diminished ability to regulate usage. cognitive overload and impact on attention the constant multitasking required by social media— switching between apps, notifications, and conversations— overloads cognitive resources and weakens the brain’s ability to sustain attention on a single task (ophir et al., 2009). over time, multitasking leads to decreased working memory capacity, making it harder to focus and engage deeply in offline activities. neuroscientific research suggests that excessive digital multitasking affects the prefrontal cortex (i.e., the brain region responsible for executive function), attention control, and working memory (ophir et al strategies to break social media addiction given the profound neurological and cognitive impact of excessive social media use, it is vital to explore evidencebased strategies for intervention. the following sections outline psychological and neurobiological approaches that have shown promise in reducing social media dependence and restoring healthy digital habits. cognitive behavioral therapy (cbt) cbt is a well-established method for treating behavioral addictions, including social media dependence. cbt focuses on developing alternative coping mechanisms, delaying gratification, and utilizing self-monitoring tools to track and reduce usage (dong et al., 2025). by identifying triggers and restructuring thought patterns, cbt helps individuals regain control over their digital habits and has been shown to be effective in addressing problematic internet use and social media addiction. 41 brain matters vol. 8 2025 individuals undergoing cbt interventions showed significant reductions in compulsive digital engagement and improvements in impulse control (dong et al., 2025). these findings suggest that targeted behavioral strategies can help retrain the brain’s response to social media stimuli and reduce dependence over time. cbt promotes healthier coping strategies, self-monitoring, and delayed gratification to manage digital habits—tools that directly counter the instant-reward mechanisms of social media platforms. by encouraging individuals to recognize and interrupt automatic thought patterns and behaviors associated with compulsive use, cbt helps break the cycle of addiction. selfmonitoring increases awareness of usage patterns, while learning to delay gratification reduces reliance on the immediate dopamine-driven rewards of likes, notifications, or scrolling. together, these techniques support lasting behavioral change and greater psychological resilience in the face of digital temptations. neurofeedback training neurofeedback training is a promising therapeutic approach for addressing social media addiction. by providing realtime feedback on brain activity, neurofeedback enables individuals to learn how to regulate neural responses to addictive stimuli, such as social media engagement (marzbani et al., 2016). neurofeedback training can enhance self-regulation and reduce compulsive behaviors, which are key factors in addiction. marzbani et al. (2016) found that neurofeedback training significantly improved impulse control and reduced cravings in individuals with addictive behaviors, suggesting its potential applicability in treating social media addiction. neurofeedback could help users break the cycle of compulsive social media checking by promoting healthier brain responses and greater control over digital impulses. cognitive overload and impact on attention a digital detox involves consciously limiting social media use to prevent excessive dopamine release (anandpara et al., 2024). specific strategies—such as turning off notifications, using digital wellbeing apps to monitor and limit screen use, and implementing tech-free hours—have been shown to improve sleep, reduce anxiety, and enhance emotional regulation (hoeppner, 2024). research highlights the effectiveness of digital detox strategies in improving mental well-being and reducing screen dependency. for example, limiting screen time through controlled interventions, such as setting time limits and engaging in offline activities, led to better emotional regulation and reduced reliance on digital devices (anandpara et al., 2024). these findings suggest that digital detox strategies can help individuals break free from compulsive social media use, ultimately promoting healthier behavioral patterns and improving overall mental health. conclusion social media addiction alters key neural pathways related to reward, impulse control, and attention, making it difficult for individuals to break free from compulsive use. central to this addiction is the brain's dopamine system, which is triggered by unpredictable rewards from social media engagement, reinforcing habitual use. however, emerging neuroscience-based strategies—such as cognitive behavioral therapy, neurofeedback training, and digital detox—offer promising solutions for retraining the brain and fostering healthier digital habits. by implementing these strategies, individuals can regain control over their online behaviors, reduce dependence on social media, and promote long-term well-being. despite these advancements, current research on social media addiction has notable limitations. many studies rely heavily on self-reported data, which can be biased or inaccurate, and often lack longitudinal designs that are necessary to determine long-term neural and behavioral changes. additionally, much of the existing research has focused on adolescents and young adults, leaving gaps in understanding how social media affects other age groups. the neurobiological mechanisms underlying digital addiction are still not fully understood, and interventions often lack standardization, making it difficult to assess their efficacy across diverse populations. future research should aim to address these shortcomings by incorporating more objective neuroimaging data, expanding demographic diversity, and developing standardized protocols for intervention to better support sustainable behavioral change. references 1. cheng, c., ebrahimi, o. v., & luk, j. w. (2022). heterogeneity of prevalence of social media addiction across multiple classification schemes: latent profile analysis. journal of medical internet research. https://doi.org/10.2196/27000 2. de, d., el jamal, m., aydemir, e., & khera, a. (2025). social media algorithms and teen addiction: neurophysiological impact and ethical considerations. cureus. https://doi.org/10.7759/cureus.77145 3. solly, j. e., hook, r. w., grant, j. e., cortese, s., & chamberlain, s. r. (2022). structural gray matter differences in problematic usage of the internet: a systematic review and meta-analysis. molecular psychiatry. https://doi.org/10.1038/s41380-021-01315-7 4. ophir, e., nass, c., & wagner, a. d. (2009). cognitive control in media multitaskers. proceedings of the national academy of sciences of the united states of america. https://doi.org/10.1073/pnas.0903620106 42 5. dong, g. h., kim, s. m., king, d. l., li, h. h., lin, c. y., meng, s. q., mestre-bach, g., park, s.y., alavi, s. s., andré, f., borenstein, m., burkauskas, j., cheng, y. s., conn, v. s., darvesh, n., du, y. s., george, s., ghali, s., & gonzálezbueso, v. (2025). effects of cognitive behavioral therapy (cbt) on addictive symptoms in individuals with internet gaming disorders: a systematic review and meta-analysis. psychiatry research. https://doi.org/10.1016/j.psychres.2025.116425 6. marzbani, h., marateb, h. r., & mansourian, m. (2016). neurofeedback: a comprehensive review on system design, methodology and clinical applications. basic and clinical neuroscience. https://doi.org/10.15412/j.bcn.03070208 7. anandpara, g., kharadi, a., vidja, p., chauhan, y., mahajan, s., & patel, j. (2024). a comprehensive review on digital detox: a newer health and wellness trend in the current era. cureus. https://doi.org/10.7759/cureus.58719 8. hoeppner , b. b., simpson, h. v., weerts, c., riggs, m. j., williamson, a. c., finley-abboud, d., hoffman, l. a., rutherford, p. x., mccarthy, p., & ojed, j. (2024). a nationwide survey study of recovery community centers supporting people in recovery from substance use disorder. journal of addiction medicine. https://doi.org/10.1097/adm.0000000000001285 can we train our brains to break social media addiction? 43 about the author meha goswami is a sophomore majoring in psychology, with an interest in double majoring in molecular and cellular biology, and is on the pre-med track. outside of brain matters, she is involved with phi chi, delta kappa delta, and illini sheltering hands society, and she works as a research assistant in the vision lab. in her free time, meha enjoys painting, listening to music, and spending time with her friends! 44 brain matters vol. 8 no. 1 written by rayyan iqbal the potential of hybrid models in alzheimer's diagnosis: combining neural networks and svms for enhanced accuracy introduction alzheimer’s disease (ad) affects over 55 million people worldwide, posing a major challenge for healthcare systems as populations continue to age. as a progressive neurodegenerative disorder, ad leads to severe cognitive decline, memory loss, and a profound reduction in quality of life, ultimately resulting in death. the mortality rate for ad approaches 100%, with patients typically living only 3 to 11 years after diagnosis, underscoring the critical importance of early detection (alzheimer’s stages: how the disease progresses, n.d.). despite extensive research, early diagnosis of ad remains difficult. the need for early detection is clear when observing cognitive tests like clock-drawing exercises. the differences between healthy individuals and those in late-stage ad are striking; however, distinguishing early-stage ad from normal aging is much harder, as seen in the clock drawings, in which there isn’t as profound of a difference in the quality of the clock drawn between normal and early ad individuals (mattson 2014). additionally, brain degeneration progresses significantly as ad advances, as shown in the brain degeneration image (maha 2023). while late-stage ad presents notable structural changes, the brain deterioration in early stages is minimal, making it challenging to identify ad before symptoms become severe. traditional diagnostic methods—including clinical assessments, cognitive tests, and neuroimaging—often struggle to detect ad at these early stages, delaying the possibility of effective interventions. recent advancements in machine learning offer new hope. neural networks (nns), particularly convolutional neural networks (cnns), excel at extracting complex patterns from large datasets, such as mri or pet scans, allowing for a more nuanced analysis of brain images (taherdoost 2023). support vector machines (svms), powerful classification tools, complement this process by distinguishing between healthy individuals and those with various degrees of cognitive impairment (ahmadi et al., 2024). while each model has shown promise independently, hybrid models that combine the strengths of cnns and svms could further improve diagnostic accuracy. hybrid models leverage cnns’ ability to identify intricate patterns and svms’ adeptness at classification, potentially making early detection achievable (li 2023). however, research in this area is still limited, with few large-scale studies validating these methods. before these hybrid models can be integrated into clinical practice, more robust data and validation are necessary to ensure their reliability. while the potential of these hybrid models is promising, caution is urged in their application until further research solidifies their effectiveness. 18 neural networks: identifying early-stage alzheimer’s in neuroimaging neural networks, especially convolutional neural networks (cnns), have proven highly effective at analyzing neuroimaging data like mri or pet scans, which is essential for diagnosing alzheimer’s disease in its early stages. neural networks are inspired by the human brain’s structure, consisting of interconnected layers of “neurons” that learn from data by recognizing patterns and relationships. when given input data (such as numbers, images, or text), the network adjusts the connections between these neurons to improve its understanding. this allows neural networks to perform tasks such as predicting outcomes, classifying objects, and identifying trends (taherdoost 2023). cnns are a specialized type of neural network designed specifically for image data. they use a process called “convolution,” where small filters scan sections of an image to identify important features like edges, shapes, or textures. rather than analyzing the entire image at once, cnns focus on small regions at a time, making them exceptionally good at interpreting visual information. in simple terms, while a standard neural network might act as a general “decision-maker,” cnns operate more like a team of “spotters,” with each focusing on a different part of the image to capture crucial details (e.g., one “spotter” might identify the nose, another the eyes). this approach allows cnns to excel at tasks such as recognizing objects in photos or detecting abnormalities in medical images. cnns can achieve remarkable accuracy in identifying early signs of alzheimer’s. in one study using a dataset of healthy individuals, those with early alzheimer’s, and those with late-stage alzheimer’s, a cnn model called resnet-18 achieved an impressive 96.85% accuracy in distinguishing between different stages of the disease based on mri and pet scans (odusami et al., 2021). this performance far exceeds conventional diagnostic methods, such as physician evaluations of pet scans, which typically achieve about 85% accuracy, according to the texas department of state health services (texas dshs, 2021). however, cnns have limitations. one major drawback is their “black-box” nature, meaning they generate results without revealing how they reached those conclusions. this lack of transparency can be problematic in clinical settings, where doctors need to understand the reasoning behind a diagnosis to justify treatment decisions. without insight into how cnns make their determinations, it becomes challenging for physicians to fully trust and adopt these models in practice, despite their accuracy (patil et al., 2022). svms: precise classification but limited in complex data while cnns are excellent for identifying features in images, support vector machines (svms) are highly effective for classifying data once those features are identified. the image above illustrates how an svm functions: two sets of data points, shown as green and red dots, represent two different classes the svm aims to separate. the axes, labeled x1 and x2, represent a two-dimensional feature space where the data points are plotted. the blue line running diagonally across the plot is the decision boundary, which separates the two classes. this boundary isn’t just any line—it is chosen to maximize the distance between itself and the nearest data points from each class, a concept known as the “margin.” one of the points closest to the boundary, called a “support vector” (represented by the purple dot), plays a crucial role in defining this margin (tan 2020). the potential of hybrid models in alzheimer's diagnosis: combining neural networks and svms for enhanced accuracy figure 1. clock drawings showing cognitive decline: normal (accurate), early ad (slightly distorted), late ad (severely disorganized). (linus health) figure 2. brain atrophy progression: healthy, early alzheimer's (mild shrinkage), severe alzheimer's (significant shrinkage). (first choice neurology 2019). 19 svms have demonstrated reliable performance in classifying patients by analyzing mri data, with their highest accuracy reaching 89%. they excel in identifying key features like gray matter volume and brain asymmetry to distinguish between control groups, early mild cognitive impairment (emci), late mild cognitive impairment (lmci), and alzheimer’s disease stages. in one approach, researchers used hippocampal volume—a primary indicator of alzheimer’s—as the main feature, which contributed to the high accuracy achieved in their study (ahmadi et al., 2024). despite their strengths, svms face challenges, particularly with high-dimensional data, where each data point has numerous characteristics or “dimensions.” in such cases, it becomes harder for svms to identify clear patterns or find a meaningful decision boundary. without careful feature selection and model tuning, svms may struggle to classify complex data accurately, leading to overfitting. overfitting occurs when a model performs well on training data but poorly on new, unseen data, reducing its real-world effectiveness (ameen et al., 2024). hybrid models: combining neural networks and svms for enhanced accuracy in recent years, hybrid models that combine convolutional neural networks (cnns) and support vector machines (svms) have gained attention in alzheimer’s disease diagnosis, offering a more comprehensive approach to early detection and classification (li 2023). by integrating cnns and svms, these models provide a robust framework to handle the complexity of high-dimensional neuroimaging data, which is essential for identifying subtle early-stage markers of alzheimer’s. hybrid models leverage the unique strengths of cnns and svms. cnns are particularly skilled at extracting features brain matters vol. 8 2025 figure 3. support vector machine (svm) diagram showing a decision boundary separating two classes. (tan 2020). from complex neuroimaging data, such as magnetic resonance imaging (mri) and positron emission tomography (pet) scans. these models can detect early neurodegenerative changes, including hippocampal atrophy, cortical thinning, and ventricular enlargement— key biomarkers for diagnosing alzheimer’s at its early stages (oostven 2021). however, while cnns excel at identifying these features, they often lack the precision needed for effective classification. this is where svms become valuable, as they create precise boundaries that distinguish different cognitive states, such as healthy controls, patients with mild cognitive impairment (mci), and those with alzheimer’s disease (ahmadi et al., 2024). a study by al subaie et al. demonstrated the effectiveness of a cnn-svm hybrid model applied to neuroimaging data, showing the model’s ability to distinguish between mci patients likely to progress to alzheimer’s and those who are not. this research highlighted the advantage of combining cnns’ feature extraction capabilities with svms’ classification strength. the hybrid model achieved a higher accuracy of 98.20%, compared to 91.70% for models relying solely on cnns or svms. the model was particularly successful in detecting subtle brain changes indicative of mci conversion, which is essential for timely intervention (al subaie et al., 2024). basheera et al. explored hybrid deep learning models using multimodal neuroimaging data, combining mri and pet scans (basheera et al., 2019). in this approach, the cnn component analyzed the raw imaging data to extract patterns of brain degeneration, which the svm then classified into diagnostic categories like non-demented, mci, and ad. this hybrid method demonstrated superior diagnostic accuracy, especially in differentiating between early mci and advanced cognitive decline stages. the results showed that the cnn-svm model outperformed traditional diagnostic methods and standalone machine-learning models in terms of accuracy, sensitivity, and specificity, achieving 90.47% accuracy, 86.66% recall, and 92.59% precision (basheera et al., 2019). both studies emphasize the potential of hybrid models to bridge the gap between feature extraction and classification, especially when dealing with high-dimensional neuroimaging data. by allowing cnns to identify complex biomarkers and enabling svms to classify these features accurately, hybrid models offer a more nuanced approach to diagnosing alzheimer’s disease. this combination captures subtle brain patterns that conventional methods might miss, which is crucial for early detection. with earlier intervention, hybrid models could lead to more accurate diagnoses and better treatment options, potentially improving patient outcomes. 20 considerations and future directions: evaluating the potential of hybrid models for clinical adoption while hybrid models combining neural networks (nns) and support vector machines (svms) show significant potential in improving the accuracy of alzheimer’s diagnosis, several challenges currently limit their adoption in clinical practice. one major challenge is the complexity and quality of data required for these models to perform effectively. cnns, a critical component of hybrid models, rely heavily on neuroimaging data, which is often difficult and costly to obtain at the scale needed for robust machine learning. studies, including those focusing on multimodal approaches, have highlighted that even well-curated datasets like the alzheimer’s disease neuroimaging initiative (adni) are often insufficiently large or diverse to ensure the generalizability of cnns across various populations. additionally, collecting such data is complicated by privacy concerns, which can further limit the availability of comprehensive datasets (ismail et al., 2022). another significant challenge is the interpretability of hybrid models. neural networks, especially cnns, often function as “black boxes,” producing diagnostic results without revealing how they arrived at those conclusions. this lack of transparency makes it difficult for healthcare professionals to understand and trust the model’s rationale, particularly when making critical patient care decisions. while efforts like explainable ai have aimed to make machine learning models more interpretable, the need for transparent decision-making remains a major barrier to adoption in clinical settings (prijs et al., 2022). in addition, hybrid models are prone to overfitting—a problem where the model performs well on training data but poorly on new, unseen data. this is especially relevant for models that incorporate both svms and cnns, as svms can struggle with high-dimensional data without careful feature selection, and cnns require extensive computational resources and large datasets to avoid overfitting. if not properly managed, overfitting can undermine the model’s real-world effectiveness and limit its reliability in clinical settings (ying 2019). overall, while hybrid models hold great promise, they are not yet ready for widespread clinical adoption. more research is needed to validate their performance across larger, more diverse datasets and to address issues related to interpretability and scalability. addressing these challenges will be essential for realizing the full potential of hybrid models in alzheimer’s diagnosis and ensuring they can be safely and effectively integrated into everyday clinical practice (wang et al., 2024). conclusion the integration of neural networks and support vector machines represents a promising approach to improving early alzheimer’s diagnosis. neural networks, particularly convolutional neural networks (cnns), excel at identifying subtle patterns in neuroimaging data, while svms provide precise classification capabilities. by combining these techniques in hybrid models, diagnostic accuracy can be significantly enhanced, potentially enabling earlier intervention and improved patient outcomes (oostven et. al., 2021). however, despite these advancements, the field remains under-researched. the studies conducted so far, while encouraging, are not yet sufficient to support the widespread adoption of hybrid models in clinical practice. more research is necessary to validate these models on larger and more diverse datasets and to address their limitations, particularly in terms of neural network interpretability and the extensive feature selection required for svms. as machine learning continues to evolve, hybrid models combining neural networks and svms may ultimately transform alzheimer’s diagnosis, enabling more accurate and timely detection. for now, however, these methods should be approached with caution, as further rigorous and repetitive studies are needed to confirm their reliability in clinical settings. with continued research, these models could one day offer a breakthrough in diagnosing and managing alzheimer’s disease. references 1. ahmadi, m., javaheri, d., khajavi, m., danesh, k., & hur, j. (2024). a deeply supervised adaptable neural network for diagnosis and classification of alzheimer’s severity using multitask feature extraction. plos one, 19(3), e0297996. https://doi.org/10.1371/journal.pone.0297996 2. ameen, t. b., kashif, s. n., abbas, s. m. i., babar, k., ali, s. m. s., & raheem, a. (2024). unraveling alzheimer’s: the promise of aducanumab, lecanemab, and donanemab. the egyptian journal of neurology psychiatry and neurosurgery, 60(1). https://doi.org/10.1186/s41983-02400845-5 3. alsubaie, m. g., luo, s., & shaukat, k. (2024). alzheimer’s disease detection using deep learning on neuroimaging: a systematic review. machine learning and knowledge extraction, 6(1), 464–505. https://doi.org/10.3390/make6010024 4. basheera, s., & ram, m. s. s. (2019). convolution neural network–based alzheimer’s disease classification using hybrid enhanced independent component analysis based segmented gray matter of t2 weighted magnetic resonance imaging with clinical valuation. alzheimer’s & dementia: translational research & clinical interventions, 5(1), 974– 986. https://doi.org/10.1016/j.trci.2019.10.001 21 the potential of hybrid models in alzheimer's diagnosis: combining neural networks and svms for enhanced accuracy 5. ismail, w. n., pp, f. r., & ali, m. a. s. (2022). multforad: multimodal mri neuroimaging for alzheimer’s disease detection based on a 3d convolution model. electronics, 11(23), 3893. https://doi.org/10.3390/electronics11233893 6. li, m., jiang, y., zhang, y., & zhu, h. (2023). medical image analysis using deep learning algorithms. frontiers in public health, 11, 1273253. https://doi.org/10.3389/fpubh.2023.1273253 7. odusami, m., maskeliūnas, r., damaševičius, r., & krilavičius, t. (2021). analysis of features of alzheimer’s disease: detection of early stage from functional brain changes in magnetic resonance images using a finetuned resnet18 network. diagnostics, 11(6), 1071. https://doi.org/10.3390/diagnostics11061071 8. patil, v., madgi, m., & kiran, a. (2022). early prediction of alzheimer’s disease using convolutional neural network: a review. the egyptian journal of neurology psychiatry and neurosurgery, 58(1). https://doi.org/10.1186/s41983-02200571-w 9. taherdoost, h. (2023). deep learning and neural networks: decision-making implications. symmetry, 15(9), 1723. https://doi.org/10.3390/sym15091723 10. van oostveen, w. m., & de lange, e. c. m. (2021). imaging techniques in alzheimer’s disease: a review of applications in early diagnosis and longitudinal monitoring. international journal of molecular sciences, 22(4), 2110. https://doi.org/10.3390/ijms22042110 11. wang, y., gao, r., wei, t., johnston, l., yuan, x., zhang, y., & yu, z. (2024). predicting long-term progression of alzheimer’s disease using a multimodal deep learning model incorporating interaction effects. journal of translational medicine, 22(1). https://doi.org/10.1186/s12967-024-05025-w 12. ying, x. (2019). an overview of overfitting and its solutions. journal of physics: conference series, 1168, 022022. https://doi.org/10.1088/1742-6596/1168/2/022022 brain matters vol. 8 2025 images: 1. first choice neurology. (2019). june is alzheimer’s and brain awareness month. first choice neurology. retrieved february 18, 2025, from https://www.fcneurology.net/june-is-alzheimers-andbrain-awareness-month/ 2. linus health. (n.d.). history of the clock drawing test and the linus health platform. linus health. retrieved february 18, 2025, from https://linushealth.com/history-of-clockdrawing-test-and-dctclock 3. tan, a. (2020). support vector machine. anthony’s blogs. retrieved february 18, 2025, from https://anthonytan.com/discriminant-functions-and-decision-boundary/ 22 about the author rayyan iqbal is a sophomore at the university of illinois, majoring in chemistry. he is currently conducting research in the physical activity and neurocognitive health lab, where he studies the impact of physical behaviors—such as physical activity and sedentary time—on brain health. beyond his research, rayyan is actively involved in react, an outreach program that brings science to life for young students in the champaign-urbana area. 23 brain matters vol. 8 no. 2 the ethics of brain-computer interfaces (bcis) written by ruchi prakash such as robotic arms, wheelchairs, and speech neuroprosthetics. speech neuroprosthetics, a specialized type of bci, translate brain activity into text or synthesized speech. this technology enables users to bypass the peripheral nervous system and muscles entirely, restoring their ability to communicate and interact with their environment. beyond simply replacing lost motor function, bcis can also serve as rehabilitation tools. feedback from bci systems can help rewire or strengthen brain circuits, promoting the restoration of native motor functions over time (daly & wolpaw, 2008). although originally limited to restoring motor functions, the scope of bcis is expanding into exciting new frontiers. today, bcis can be used for everything from controlling smart devices to cognitive enhancement and interacting with virtual worlds. leading companies in the field like neuralink and synchron are developing bcis that could allow people to interact with technology in ways that were previously only seen in science fiction. with the immense potential of this technology comes important ethical questions: who owns and controls the data from our minds? could cognitive enhancement through bcis deepen social divides? how do we protect our privacy and autonomy over which thoughts are converted into digital signals? as bcis become more integrated into daily life, addressing these ethical concerns will be essential in shaping the future of human agency. 69 fifteen years after a stroke left cathy hutchinson paralyzed, she discovered a surprising path to independence. using nothing but her thoughts, she can now control a robotic arm to feed herself and perform everyday tasks, something that was once thought impossible (image 1). this life-changing feat is made possible by brain-computer interfaces (bcis), an upcoming technology that establishes a direct link between the brain and an external device (orenstein, 2012). image 1. cathy controls a robotic arm with her thoughts, despite being paralyzed. bcis capture and translate brain signals into computer commands, which are then interpreted by external devices such privacy and data security as bcis become more widespread, concerns over privacy and data security are growing. bcis generate highly sensitive neural data that could reveal a person’s thoughts, intentions, and emotions. without proper safeguards, this information could be hacked, misused, or even sold without consent. martinovic first introduced the term “brain spyware” to describe identity and agency bcis raise important concerns regarding identity and agency. many of these technologies are considered invasive because they require electrodes to be implanted directly onto or into brain tissue to record and stimulate neural activity with high precision. unlike electroencephalography (eeg), which uses electrodes placed on the scalp to passively measure general brain activity, invasive bcis bypass the skull to achieve greater accuracy and control. this procedure, however, carries several risks, including infection, tissue damage, and gradual electrode degradation (burwell et al., 2017). while many bcis used in clinical and research settings today are non-invasive and rely on eeg, they offer lower resolution compared to invasive systems that require surgical implantation. these medical risks are compounded by ethical dilemmas, particularly when bcis are used by patients with motor disabilities or neurodegenerative disorders. one major issue is the difficulty in ensuring ongoing informed consent, especially in patients with cognitive impairment. conditions like alzheimer’s and parkinson’s can impair decision-making, making it difficult for patients to understand and assess the risks involved. similarly, individuals with conditions like amyotrophic lateral sclerosis (als), which affect speech and communication, may struggle to provide clear and consistent consent (klein & ojemann, 2016). on the other hand, using this technology may empower individuals and provide a sense of autonomy not previously possible as seen in the case of cathy hutchinson. mood disorders, such as depression, further complicate the consent process. research has shown that depression can impair decision-making, potentially influencing a patient's willingness to continue participation in bci studies or treatment (dunn et al., 2011). these factors highlight the importance of continuously assessing a patient’s capacity to consent to ensure their autonomy is respected. alongside these concerns, bcis raise questions about control. a common fear is that these devices are capable of “mind reading” and can extract any information from the user's brain. as such, many worry that this technology could alter an individual’s sense of self and free will. it is crucial to understand that bcis do not operate autonomously but instead work together with the user to initiate actions (shih et al., 2012). this joint action ensures that the user’s agency and intentionality are not compromised. describe the security risks involved with collecting eeg data through bcis. using a low-cost gaming headset, martinovic and his team created an application capable of secretly collecting brain data while showing the user different images. for example, to infer a bank pin, the system would flash digits on the screen while monitoring brain signals. when a familiar number appeared, the user’s brain would produce a p300 brain wave, revealing recognition without any conscious input (martinovic et al., 2012). future experiments concluded that it took less than 13.3 milliseconds of presenting specific visual stimuli to extract this sensitive information (takabi et al., 2016). this research highlights the ease with which bcis can be misused. with the growing commercialization of bcis and their integration into games and mobile apps (image 2.), the threat of data breaches is increasing. brain matters vol. 8 2025 70 image 2. new generation of bcis are being used to improve the gaming experience. currently, there is no unified framework for regulating the ownership of neural data, creating uncertainty about whether the neural data belongs to the user, the company, or healthcare provider? as bcis continue to collect personal information, experts argue for stronger collaboration between manufacturers and governments to address these privacy issues. xia et al. (2023) recommend enhancing encryption, adding noise to the data, and separating relevant from irrelevant data to better protect user privacy. while these solutions are a step in the right direction, much more work remains to be done. equity and cognitive enhancement given the novelty of this technology, bcis are currently expensive and not widely available. this limited affordability of bcis can enlarge social inequities as only privileged hospitals or institutions with access to such technology would be able to offer these treatments to patients. moreover, some bcis aim to enhance cognitive and physical abilities in healthy individuals, a concept known as neuroenhancement. 71 neuroenhancement. while some fear that advancing this technology could deepen social divides and disrupt human nature, others view it as a potential way to integrate man and machine and enhance human capabilities. through this, they believe humankind can move closer to perfection and improve moral judgement, emotional perception, and reasoning (khan & aziz, 2019). regardless of the rationale, this debate emphasizes the need for better regulations to ensure equitable access to this life-changing technology. while brain-computer interfaces offer remarkable potential to transform healthcare, enhance cognitive abilities, and the quality of life, they also raise significant ethical and privacy concerns. as the technology continues to evolve, ethical guidelines and safeguards must be established to protect individual autonomy, safety, and access. by addressing these challenges thoughtfully, we can harness the full potential of bcis while minimizing risks and inequalities. references 1. burwell, s., sample, m., & racine, e. (2017). ethical aspects of brain computer interfaces: a scoping review. bmc medical ethics, 18, 1-11. https://doi.org/10.1186/s12910-017-0220-y 2. daly, j. j., & wolpaw, j. r. (2008). brain-computer interfaces in neurological rehabilitation. the lancet. neurology, 7(11), 1032–1043. https://doi.org/10.1016/s14744422(08)70223-0 3. dunn, l. b., holtzheimer, p. e., hoop, j. g., mayberg, h. s., roberts, l. w., & appelbaum, p. s. (2011). ethical issues in deep brain stimulation research for treatment-resistant depression: focus on risk and consent. ajob neuroscience, 2(1), 29–36. https://doi.org/10.1080/21507740.2010.533638 4. klein, e., & ojemann, j. (2016). informed consent in implantable bci research: identification of research risks and recommendations for development of best practices. journal of neural engineering, 13(4), 043001. https://doi.org/10.1088/1741-2560/13/4/043001 5. khan, s., & aziz, t. (2019). transcending the brain: is there a cost to hacking the nervous system?. brain communications, 1(1), fcz015. https://doi.org/10.1093/braincomms/fcz015 the ethics of brain-computer interfaces (bcis) 6. martinovic, i., davies, d., frank, m., perito, d., ros, t., & song, d. (2012). on the feasibility of side-channel attacks with brain-computer interfaces. proceedings of the 21st usenix conference on security symposium, 34. presented at the bellevue, wa. usa: usenix association. 7. orenstein, d. (2012, may 16). people with paralysis control robotic arms using brain-computer interface. brown university. https://news.brown.edu/articles/2012/05/braingate2 8. shih, j. j., krusienski, d. j., & wolpaw, j. r. (2012). braincomputer interfaces in medicine. mayo clinic proceedings, 87(3), 268–279. https://doi.org/10.1016/j.mayocp.2011.12.008 9. takabi, h., bhalotiya, a., & alohaly, m. (2016). brain computer interface (bci) applications: privacy threats and countermeasures. 2016 ieee 2nd international conference on collaboration and internet computing (cic), 102-111. 10. xia, k., duch, w., sun, y., xu, k., fang, w., luo, h., zhang, y., sang, d., xu, x., wang, f., & wu, d. (2023). privacypreserving brain–computer interfaces: a systematic review. ieee transactions on computational social systems, 10, 2312-2324. about the author ruchi is a junior at the university of illinois at urbana-champaign majoring in neuroscience and psychology. she joined brain matters to explore her passion for the brain and stay connected to cuttingedge research in the field. in addition to writing for brain matters, ruchi serves as the vice president of neurotech@uiuc, a projectbased organization focused on the intersection of neuroscience and technology. she looks forward to pursuing graduate studies and expanding her experience in research and innovation. https://doi.org/10.1186/s12910-017-0220-y https://doi.org/10.1016/s1474-4422(08)70223-0 https://doi.org/10.1016/s1474-4422(08)70223-0 https://doi.org/10.1080/21507740.2010.533638 https://doi.org/10.1088/1741-2560/13/4/043001 https://doi.org/10.1093/braincomms/fcz015 https://news.brown.edu/articles/2012/05/braingate2 https://doi.org/10.1016/j.mayocp.2011.12.008 72 volume 8 (will be vol 7 on site) impacts of lifelong bilingualism on neurodegenerative diseases esther nam abstract lifelong bilingualism is the regular use of two languages throughout one’s daily life. constantly switching between languages requires more control over word selection and the ability to resolve interference from the language not in use (abutalebi & green, 2016). because bilinguals face these conflicts on a regular basis more often than monolinguals, there has been evidence of structural changes and increased connectivity from overuse of certain areas and networks of the brain associated with carrying out these executive control tasks. this article aims to provide insight into how bilingualism and reserve works together, and how that relationship can manifest improvement in cognitive functioning in individuals with neurodegenerative diseases. introduction according to the 2021 census, 22% of the u.s. population who are older than 5 years speak another language other than english (u.s. census bureau, n.d.). researchers have found that alzheimer’s disease (ad) is delayed by 4-5 years in lifelong bilinguals when compared to their monolingual counterparts (bialystok et al., 2007; craik et al., 2010). the exact mechanisms underlying this phenomenon are not quite known, but many interpretations of various observational results have indicated that because the bilingual experience involves constant cognitive conflict between two languages, there is a strengthening in associated networks as well as structural changes in the brain that ultimately contribute to cognitive and brain reserve. since bilinguals face these conflicts much more often than monolinguals do, they consequently have larger reserves that serve as a neuroprotective factor against neurodegeneration or even the normal course of cognitive decline that comes with aging. reserve is a hypothetical construct used to explain how some individuals who have suffered brain damage maintain similar cognitive and functional ability to those with healthy undamaged brains. the amount of reserve an individual has determines the amount of damage the brain can tolerate without deterioration in functioning. increased brain reserve allows for ‘damage’ to accumulate without significantly affecting cognitive ability, which may explain why bilingual individuals show less cognitive decline than monolinguals, even when their brains exhibit greater levels of deterioration (gold, 2015; bialystok et al., 2007; sala et al., 2021). this then leads to the question of whether bilingualism may also help protect against expression of clinical symptoms in other neurodegenerative disorders such as parkinson’s disease (pd) and multiple sclerosis (ms). according to one literature review, this is possible as there is insufficient evidence to conclude otherwise (voits et al., 2020). the incidence of alzheimer’s disease in the u.s. in 2050 is projected to double, according to alzheimer’s association (alzheimer’s association, 2023). therefore, it is vital to thoroughly investigate the link between neurodegeneration and the bilingual experience, which may reduce neurodegenerative disease prevalence (bialystok et al., 2007) and improve overall quality of life. but to understand how bilingualism can delay clinical expression of neurodegenerative diseases, we must first understand the concept of reserve and the protective role it plays. reserve reserve explains how some people with brain damage demonstrate a similar level of cognitive ability to people with non-damaged brains. one case showing this is a study done by katzman et al. where 10 patients with ad performed as well as matched controls did on cognitive tests. they also found that these patients had larger brain weights and more neurons than the controls to maintain cognitive and functional ability through mechanisms of reserve (katzman et al., 1988). there are two types of reserve models: active and passive. these models differ in the way they are defined and may lead to different interpretations of results, but in the case of bilingualism, both are applicable. active model cognitive reserve and compensation the active model currently involves two subtypes of reserve: cognitive reserve and compensation. cognitive reserve (cr) refers to the way an individual approaches a task in terms of the networks and resources the brain uses in the moment, hence “active.” it is also active in the sense that it depends on neural activity, experiences, and exposures that the person experiences in their lifetime (barulli & stern, 2013). therefore, people with higher cognitive reserve can carry out cognitive tasks in a more efficient manner (stern, 2002). the main proxies that have been the most studied are education, occupation complexity, iq, and, a more recently introduced yet prevalent one, bilingualism. in terms of these proxies, if a person suffers through an insult to the brain, the functional impairment is expressed in the amount of damage that has exceeded the amount of brc. in other words, there is a “threshold” that must be surpassed for brain damage to express its effect on cognitive function (barulli & stern, 2013; stern, 2002). this is not to say that brc is predetermined at birth. it is based on brain structure at the time insult was received, which can account for any accumulated structural changes. lifelong bilingualism and reserve bilingualism can be defined as a gradient in terms of the proficiency of the second language (l2), from elementary to near-native. in this paper, bilingualism is defined as having near-native proficiency of l2 from a young age, unless specified otherwise. bilingualism as a proxy for cognitive reserve has more recently gained prevalence in the last couple decades compared to other proxies such as occupation (bialystok et al., 2007, gold, 2015; subramaniapillai et al., 2021 (review)). this includes selecting the target language according to context, selecting vocabulary consistent with the target language, inhibiting words from the language not in use, monitoring speech for intrusions from the other language, and disengaging and engaging in language when switching back and forth (abutalebi & green, 2016). these processes all contribute to increasing cr because they are cognitively demanding tasks that are completed regularly, depending on the context of the language use. in terms of differential functionality, a study by mouthon et al. (2019) demonstrates how the use of a second language increases efficiency of network use in university student translators who were moderately (lp) or highly proficient (hp) in their l2.e participant name the object in the given picture in their first language (l1) and/or l2 depending on the task conditions. the authors found that the hp group exhibited activation in the general control network whereas the lp group exhibited activation in the language control networks. the language control network is larger and responsible for linguistic-related cognitive processes while the general control network is responsible for more general processes such as planning. the findings suggest that with higher l2 proficiency, there is less reliance on the language control network as controlling the two languages can be done with the same resources as any other general cognitive task. this corresponds to what stern wrote about efficient network use where the more difficult the task, individuals with higher reserve tended to show less activation in task-related areas (less activation in language networks for language-related tasks) compared to those with less reserve recruiting more of the task-related areas (stern 2002). the language control network consists of several key brain regions. these include the dacc/pre-sma complex, left prefrontal cortex, right inferior frontal cortex, inferior parietal lobules, cerebellum, and subcortical structures like the thalamus, left caudate, and left putamen (abutalebi & green, 2016). higher education levels, cognitive demand by an occupation, and iq are associated with greater levels of cognitive reserve. an example of cognitive reserve coming into play includes a study done by poletti et al. where they found more educated patients with parkinson’s disease (mild cognitive impairment (pd-mci)) had a slower progression towards parkinson’s disease dementia (pdd) than those who were less educated (poletti et al., 2011). a different study by thorvaldsson et al. investigated effects of iq in terminal decline (td) on motor speed, perceptual speed, spatial ability, and verbal ability in the elderly population of gothenburg, sweden. td is the acceleration of cognitive decline a person experiences in their final years before death. they first measured the iq of the participants using a simplified version of the raven standard progressive matrix called the raven coloured progressive matrix, which was more suitable for older participants. results show that those with higher iq tended to express later onset of cognitive declines in the variables of interest than those with lower iq, which is in line with the cognitive reserve hypothesis (thorvaldsson et al., 2017). stern describes cognitive reserve as arising from two ways of using brain networks: increased efficiency in using a network of interest and the ability to recruit alternative networks to carry out increasingly demanding tasks (stern, 2002). according to referenced studies, the normal response to a more difficult task is to use the current brain network more actively and/or to recruit additional networks to help (stern, 2002). between two individuals with different levels of cognitive reserve, the person with a higher amount will recruit the same amount of neuronal activity on a difficult task as the individual with a lesser amount on an easier task. for the ability to recruit alternative networks, stern writes that having a higher cognitive reserve enables an individual to recruit a larger array of networks to carry out a difficult task (stern, 2002). compensation is very similar to cognitive reserve, but it is referred to as such in the context of brain injury or brain damage (barulli & stern, 2013; stern, 2002). when someone suffers brain damage that affects the normal brain network they use for a certain task, they are forced to use an alternative method to complete the same type of task. their brain must “compensate” for the impaired or lost network. one of the proposed neurological bases for cognitive reserve is known as neural reserve, which encompasses the networks that are used during task processing (barulli & stern, 2013). passive model brain reserve (threshold model) the passive model, or threshold model, is solely based on the brain’s anatomical structure. this would include brain size or weight, the number of neurons it has, the number of synapses, gray matter volume, and so on. compared to cognitive reserve, this model is much more objective as it relies on a strict structural component that determines what is called brain reserve capacity (brc). the theory is that every person has a certain predetermined level of brc based on their brain structure, hence why this model is “passive.” brain matters・volume vii 78 bilingualism may also affect networks involved in executive function. in a literature review comparing the effects of bilingualism on memory systems and executive functioning systems, it seems that the effects of bilingualism act via the protection of executive functioning networks rather than the protection of memory circuits (gold, 2015), which dementia mainly impacts. continuous language switching requires a great deal of control, which with overuse, indirectly strengthens general executive control systems through old age (gold et al., 2013; gold, 2015). it has been hypothesized in one study that increased activity in frontoparietal and frontostriatal networks that are associated with the bilingual experience can lead to neuroprotection against the decline in the executive control circuits (which involve frontostriatal and frontoparietal networks) (gold et al., 2013). this is supported by that study’s findings comparing older adults’ performance in a task-switching paradigm involving switching between colors and shapes. older bilinguals outperformed older monolinguals with less effort, indicated by requiring less activation, suggesting that switching in language also improved the ability to switch in general areas outside of language (gold et al., 2013). the protective effect of bilingualism against the expression of ad symptoms has been evidenced, as well as its protective effects against age-related decline. bilingualism and alzheimer’s disease alzheimer’s disease (ad) has been consistently listed as one of the top causes of death among older adults. the main etiologic theory of ad is the amyloid cascade hypothesis: the accumulation of amyloid-β peptide in the brain is a significant cause for the development of ad (karran et al., 2011), of which the main components are amyloid plaques, neuritic plaques, and neurofibrillary tangles (nfts) (thal et al., 2013). dementia is sometimes a symptom resulting from this disease, and progression to this stage can often be predicted with the presence of mild cognitive impairment (mci). mci is characterized by cognitive impairment that cannot be considered normal healthy cognition but is also insufficient to be diagnosed with ad (voits et al., 2020). with respect to reserve and the expression of ad symptoms including mci, previous research provides evidence for brain reserve or cognitive reserve to be responsible for the delay in onset of dementia symptoms (voits et al., 2020). to summarize, patients diagnosed with alzheimer’s who are bilingual can demonstrate similar cognition functioning to their monolingual counterparts with greater brain atrophy, or a decrease in brain tissue. it is also suggested that bilinguals are able to maintain normal cognitive processing by making up for brain atrophy by using alternative networks that do not use the atrophied brain regions. this aligns with the study by sala et al. (2021), where despite exhibiting similar levels of cognitive impairment, bilinguals with ad showed greater levels of cerebral hypometabolism than monolinguals. cerebral hypometabolism is when the brain is consuming less glucose than normal, and can be indicative of damage. some of these structures experience an anatomical change from continued use by bilinguals. one such case mentioned by abutalebi and green is the dorsal acc (dacc) and presupplementary motor area (pre-sma), which are involved with conflict resolution, language selection, and language switching. studies reviewed by these authors have found increased gray matter density, often measured as the mass of neuronal cell bodies in grams per cubic cm, of the dacc in bilinguals (abutalebi & green, 2016). borsa et al. (2018) conducted a study with older bilingual and monolingual adults that investigated the cognitive and neural hypotheses at the same time. gray matter volume (gmv) of the acc, one of the region of interests that were selected, showed to be a strong predictor of interference and conflict effects in the cognitive control test attentional network task (ant) in older bilingual adults, which was not the case for the monolingual group. gray matter volume (gmv) of the acc, one of the region of interests that were selected, showed to be a strong predictor of interference and conflict effects in the cognitive control test attentional network task (ant) in older bilingual adults, which was not the case for the monolingual group. an interesting finding from this study was that the mean gmv between the monolingual and bilingual groups had no significant difference, which contrasts with previous studies that did find a difference (abutalebi et al., 2015). one possible explanation could be the proficiency level of the l2. it is hard to tell if proficiency levels in the l2 were close to proficiency in l1 in borsa et al.’s study as a result. another difference is the age of acquisition (aoa) of the l2, where in borsa et al., 2015, the mean aoa was 6.20 years compared to 12.68 years in abutalebi et al. (2015). in addition to gray matter, white matter, and the amount of myelinated neuronal axons per unit volume may also be affected by a bilingual experience. in a study by luk et al., white matter integrity was found to be higher in older bilingual people, and they also displayed stronger white matter connectivity between anterior-posterior regions of the brain. these results have been interpreted as possible explanations for previous research showing older bilinguals to have higher levels of cognitive control than their monolingual counterparts (luk et al., 2011). olsen et al. have also found an increase in overall brain volume, including both gray and white matter, in the frontal and temporal lobes compared to monolinguals. these differences are interpreted to enable bilingual individuals to access a larger network of brain regions and stronger connectivity (olsen et al., 2015). bilingualism, as mentioned earlier, is a continuum of l2 proficiency. higher proficiency level is associated with increasing gray matter volume (abutalebi & green, 2016) and the evolution of the mechanisms of language control (gradually shifting resourcing from language-specific networks to general cognitive networks) (mouthon et al., 2019). to put it another way, the benefits of bilingualism are given in a “dose-dependent manner” (sala et al., 2021), which emphasizes the bilingual continuum. thalamus, caudate nucleus, putamen, hippocampus, amygdala, and nucleus accumbens. there have been findings that these regions are associated with deterioration in attention, executive functioning, and cognitive decline (aarsland et al., 2017). there is widespread thinning of cortical gray matter that is associated with increased cognitive decline. before gray matter deterioration, however, white matter is impaired first and has been found to predict the course of cognitive decline in pd patients towards pdmci (voits et al., 2020). in terms of the relationship between pd symptoms and cr, one of the most commonly studied proxies seems to be education. like bilingualism, education can also impact the amount of cr an individual has because it can require more controlled processes and conceptualization abilities (le carret et al., 2010). in a systematic review of cognitive reserve and pd, hindle et al. only found studies that used education as a proxy in their search that included education, occupation, and leisure activity (hindle et al., 2014). their review shows that while there was a significant association between higher education level and better performance on cognitive tests, there is insufficient evidence to make the conclusion that cognitive reserve has enough of an impact to delay the onset of pd-related cognitive decline or dementia. another review that looked at pd-mci and cognitive reserve also found education to exert a protective effect against cognitive decline (poletti et al., 2011), and that having more education can decrease the risk of progressing from healthy cognition to pd-mci (gu & xu, 2022). however, further research would be required to investigate the underpinnings of this relationship, along with investigation of how other proxies of cognitive reserve may affect mci differently. ciccarelli et al. tries to diverge from using solely education to measure reserve by including other factors like intelligence, occupation, and leisure activities (ciccarelli et al., 2022). through this new operationalization, they found that cognitive reserve is also associated with creative and cognitive leisure activities, such as playing music, along with education for both pd patients and healthy controls. this gives potential for bilingualism to have an impact on the progression of cognitive impairment in pd-diagnosed individuals. in contrast to education and intelligence, bilingualism and its relation to pd is severely under-researched. there are only two studies to date (hindle et al., 2015; fishman et al., 2021) that investigate the two, specifically testing whether the cognitive reserve model holds in the face of cognitive impairment (stern, 2002). hindle et al. conducted a study that evaluated executive functioning performance in monolingual and bilingual pd patients with tasks that assess mental generativity and speed, working memory, inhibitions, response conflict monitoring, set shifting and switching, and attention. results showed there was no significant difference between the two groups, suggesting that the cognitive reserve model does not apply. similar findings were found by fishman et al. where there were no significant differences found between bilingual and monolingual pd patient performance in executive functioning, memory, and it has also been found that bilingual patients rely on alternative network use than normal ones that may have been affected by ad pathology. this is indicative of compensation due to the context of a brain injury, in this case damages caused by ad. a common conclusion in the study of bilingualism as a lifestyle is that it can delay the onset of alzheimer’s disease symptoms by around 4-5 years (bialystok et al., 2007; craik et al., 2010). studies reviewed by gold also find delays of 3 years for multilinguals, 4.5 years for native-born bilinguals, and 6 years for illiterate bilinguals (gold, 2015). while some argue that reserve slows the decline rate, others argue that both monolinguals and bilinguals experience decline at the same rate. however, bilinguals still maintain functioning for several years before they begin to experience cognitive impairment. bialystok et al. supports the latter theory, with their study–of bilingual and monolingual patients meeting criteria for ad with dementia or other dementiarelated neurodegenerative disorders–showing both groups display similar rates of cognitive descent, but bilinguals have better cognition than monolinguals despite that because they have more cr to compensate for degeneration (bialystok et al., 2007). this is also in agreement with the study by sala et al. (2021) regarding cerebral hypometabolism described earlier. the neural explanation of this effect is in its initial stages of study but is suggested to be that bilingualism mitigates atrophy not through memory systems but through executive function systems. gold’s hypothesis states that an increase in activity in the frontoparietal and frontostriatal networks, both of which are part of executive function systems, due to inhibiting and switching caused by bilingualism may protect against decline in executive control circuits. neural mechanisms that arise from this include increased neuronal activity, enhanced glucose/oxygen delivery, myelination, myelin protection, and others (gold, 2015). in other words, the usage of two languages may accumulate more reserve via adaptations in neural mechanisms within the executive functioning/control networks. bilingualism and parkinson’s disease parkinson’s disease (pd) is a disease that affects the nervous system, causing motor symptoms including tremors and/or stiffness (mayo clinic, 2023). in addition to motor symptoms, people with pd may also exhibit a range of cognitive impairment: healthy, mild cognitive impairment (pdmci), and dementia (pdd). pd has a range of etiology, including both genetic and environmental factors that make it a heterogenous disease (voits et al., 2020). pathology is largely characterized by loss of dopaminergic neurons in the nigrostriatal pathway of the brain, which can cause the motor symptoms that are often associated with parkinson’s (poletti et al., 2011). neurologically, parkinson’s affects both gray and white matter structure and integrity. notable regions of gray matter affected that may explain mci are the basal ganglia, brain matters・volume vii 80 functioning in the face of increasing difficulty (task difficulty or difficulty due to damage) because they have learned to use networks more efficiently or recruit more networks. there has also been literature by overlapping authors that delve further into cognitive reserve and ms specifically. sumowski and leavitt authored a review of literature that investigated the types of contributors to cognitive reserve and how they could reduce or delay cognitive decline (sumowski & leavitt, 2013). they described two major categories: larger maximal lifetime brain growth (mlbg), which is heritable, and lifetime intellectual enrichment, which is obtained from environmental factors. essentially, ms patients with larger mlbg are able to withstand more severe brain atrophy while still being able to maintain cognitive functioning. in terms of intellectual enrichment, ms patients who had more intellectual enrichment (i.e. level of education, vocabulary knowledge) could perform better cognitively and, like those with higher mlbg, withstand greater atrophy while maintaining cognitive functioning. this establishes a trend in bilingualism and a delay in cognitive decline in ms patients. sumowski and others follow up on the ideas of mlbg and intellectual enrichment by conducting a longitudinal investigation, which is a study design that collects data from the same people over a period of time. results indicated that increased mlbg and increased lifetime intellectual enrichment have led to a delay in the decline of cognitive functioning by 4.5 years, further supporting the cognitive reserve model (sumowski et al., 2014). bilingualism as a cognitive reserve proxy against ms has not been yet thoroughly studied, but there may be some preliminary conclusions that can be made about this relationship. in a study comprising of patients diagnosed with rrms, aveledo et al. examined for differences between the performances of bilingual and monolingual patients on the flanker task, assessing monitoring load and cost (monitoring mechanism) and conflict effect, or the time it takes to resolve a conflict like those presented in the flanker task (inhibitory control) (aveledo et al., 2021). a flanker task is a test displaying a series of five arrows from which the participant has to determine if the arrows are congruent or not based on the target arrow (middle arrow), and which direction the target arrow is facing as fast as possible. in this study in particular, the arrows are replaced by five fish, and monitoring load and costs were measured by performance accuracy, and the difference in performance between the high-monitoring (equal number of incongruent and congruent trials) and lowmonitoring (greater number of congruent trials) conditions, respectively. the bilingual group did as well or better than healthy controls in monitoring, but performed no differently than monolinguals in inhibitory control. on the other hand, in a study of patients diagnosed with rrms that compared the executive functioning tasks of bilinguals and monolinguals showed the bilingual group only outperformed the monolingual group with significance in non-verbal tasks involving both attention and inhibitory control (soltani et al., 2018). as of now, there are not any conclusive theories that can be made about how the bilingual experience could and visuospatial domain assessing neuropsychological tests. bilinguals also performed worse than their monolingual counterparts in both language-related tasks (boston naming task, test of adult/adolescent word finding: verb naming, boston diagnostic aphasia examination: semantic probe, vocabulary) and attention/working-memory-related tasks (forward and backward digit span test). however, a major limitation of this study in particular is the ratio of bilingual to monolingual patients in the sample, with only 15% being bilingual. one plausible explanation for these results may be that the bilinguals have accumulated more severe atrophy than the monolinguals and are performing with similar cognitive ability, which cannot be known without establishing the amount of pathology each group experienced (voits et al., 2020). another explanation voits et al. raises is the age of onset of pd, which is usually during old adulthood. because of this, it may take much longer for clear differences to rise. in other words, cognitive impairment was too minimal for a difference to be observed. bilingualism and multiple sclerosis multiple sclerosis (ms) is a disease where the immune system attacks myelin in the central nervous system (“multiple sclerosis,” 2023). it affects both gray and white matter, with common pathology including demyelination, axonal destruction, and loss of oligodendrocytes (lassmann, 2018). ms differs from other neurodegenerative diseases in that the age of onset is much earlier (early adulthood between 20 to 40 years), and it presents itself differently person-to-person depending on the damage done (voits et al., 2020; nih). there are four subtypes of ms: relapsing remitting ms (rrms), primary progressive ms (ppms), secondary progressive ms (spms), and progressiverelapsing ms (prms). the progressive subtypes are continuous, consequently having more severe cognitive outcomes. because ms presentation consists of a variety of symptom presentations with different etiology, it is considered a heterogeneous disease (voits et al., 2020). this variability results from the widespread development of lesions that can lead to independent cognitive, neuropsychiatric, and motor symptoms (chiaravalloti & deluca, 2008). while the trend between ms and reserve has not been thoroughly studied as much as that between ad and reserve, there is some evidence supporting the theory that increased cognitive reserve can delay the onset of cognitive decline that comes with the disease. in an investigation to see how cognitive reserve could affect cognitive functioning in ms patients, it was found that ms patients who had higher cognitive reserve performed as well as the healthy controls in tasks that tested processing speed (symbol digit modalities test – oral version), working memory (paced auditory serial addition test), and verbal learning and verbal memory (logical memory subtests i and ii). healthy controls also outperformed ms patients with lower cognitive reserve (sumowski et al., 2009). this supports stern’s cognitive reserve model (stern, 2002) that having higher amounts of reserve can enable an individual to maintain their cognitive 5. aarsland, d., creese, b., politis, m., chaudhuri, k.r., ffytche, d.h., weintraub, d., & ballard, c. (2017). cognitive decline in parkinson disease. nature reviews neurology, 13, 217–231. https://doi.org/10.1038/nrneurol.2017.27 6. aveledo, f., higueras, y., marinis, t., bose, a., pliatsikas, c., meldaña-rivera, a., martínez-ginés, m. l., garcíadomínguez, j. m., lozano-ros, a., cuello, j. p., & goicochea-briceño, h. (2021). multiple sclerosis and bilingualism: some initial findings. linguistic approaches to bilingualism, 11(4), 551-577. https://doi.org/10.1075/lab.18037.ave 7. barulli, d., & stern, y. (2013). efficiency, capacity, compensation, maintenance, plasticity: emerging concepts in cognitive reserve. trends in cognitive sciences, 17(10), 502509. https://doi.org/10.1016/j.tics.2013.08.012 8. bialystok, e., craik, f. i. m., freedman, m. (2007). bilingualism as a protection against the onset of symptoms of dementia. neuropsychologia, 45(2), 459-464. https://doi.org/10.1016/j.neuropsychologia.2006.10.009 9. borsa, v. m., perani, d., della rosa, p. a., videsott, g., guidi, l., weekes, b. s., franceschini, r., & abutalebi, j. (2018). bilingualism and healthy aging: aging effects and neural maintenance. neuropsychologia, 111, 51-61. https://doi.org/10.1016/j.neuropsychologia.2018.01.012 10. chiaravalloti, n. d, & deluca, j. (2008). cognitive impairment in multiple sclerosis. lancet neurology, 7 (12), 1139-1151. 11. ciccarelli, n., colombo, b., pepe, f., magni, e., antonietti, a., & silveri, c. (2022). cognitive reserve: a multidimensional protective factor in parkinson’s disease related cognitive impairment. aging, neuropsychology, and cognition: a journal on normal and dysfunctional development, 29(4), 687-702. https://doi.org/10.1080/13825585.2021.1892026 12. craik, f. i. m., bialystok, e., & freedman, m. (2010). delaying the onset of alzheimer disease: bilingualism as a form of cognitive reserve. neurology, 75(19), 1726-1729. https://doi.org/10.1212/wnl.0b013e3181fc2a1c 13. thal, d. r., von arnim, c., griffin, w. s. t., yamaguchi, h., mrak, r. e., attems, j., & upadhaya, a. r. (2013). pathology of clinical and preclinical alzheimer’s disease. european archives of psychiatry and clinical neuroscience, 263, 137-145. https://doi.org/10.1007/s00406-013-0449-5 14. fishman, k. n., roberts, a. c., orange, j. b., sunderland, k. m., marras, c., tan, b., steeves, t., kwan, d., lang, a. e., grimes, d., levine, b., masellis, m., binns, m. a., jog, m., strother, s. c., investigators, o., mclaughlin, p. m., & troyer, a. k. (2021). bilingualism in parkinson’s disease: relationship to cognition and quality of life. journal of clinical and experimental neuropsychology, 43(2), 199212. https://doi.org/10.1080/13803395.2021.1902946 15. gold, b. t., kim, c., johnson, n. f., kryscio, r. j., & smith, c. d. (2013). lifelong bilingualism maintains neural efficiency for cognitive control in aging. the journal of neuroscience, 33(2), 387-396. https://doi.org/10.1523/jneurosci.3837-12.2013 impact ms symptoms with regards to inhibition and attention. it is especially difficult to identify differences that occur potentially because of bilingualism because the advantages that are seen with bilingualism are more prominent in older populations (aveledo et al., 2021; gold et al., 2013). there is also the need to address the heterogeneity of ms presentation which could also be a confounding source to some of these results. because participants were diagnosed with rrms, the subtype of ms least subject to cognitive decline, they may not have experienced sufficient impairment to demonstrate a significant difference between monolinguals and bilinguals in executive functioning performance (aveledo et al., 2021; voits et al., 2020). while there is still more research that would need to be done, there is potential for bilingualism to have a positive impact on people diagnosed with ms in maintaining some of their executive functioning. conclusion bilingualism and ad has been much more thoroughly studied than with pd, ms, or other neurodegenerative diseases. however, given the findings of previous research, it is becoming important to investigate these other probable links especially with bilingualism becoming a recurring cognitive reserve proxy in reserve studies. bilingualism, specifically for those who have been bilingual since a young age, is classified as having the potential to increase both brain and cognitive reserve because the control of languages in use lead to anatomical structural adaptations and functional activity. in the case of alzheimer’s disease, there have been repeated findings of delay in onset of ad symptoms and diagnosis in bilinguals. while pd and ms have not been studied as much, there is potential to find more direct reserve effects because of bilingualism based on the reserve effects by levels of intelligence and education. while not a cure for these diseases, being able to ground a relationship between neurodegenerative cognitive impairment could provide methods for improving the quality of life for more years in the older adult population. references 1. abutalebi, j., cappa, s. f., & perani, d. (2001). the bilingual brain as revealed by functional neuroimaging. bilingualism: language and cognition, 4(2), 179-190. https://doi.org/10.1017/s136672890100027x 2. abutalebi, j., guidi, l., borsa, v., canini, m., della rosa, p. a., parris, b. a., & weekes, b. s. (2015). bilingualism provides a neural reserve for aging populations. neuropsychologia, 69, 201-210. https://doi.org/10.1016/j.neuropsychologia.2015.01.040 3. abutalebi, j., & green, d. w. (2016). neuroimaging of language control in bilinguals: neural adaptation and reserve. bilingualism: language and cognition, 19(4), 689-696. https://doi.org/10.1017/s1366728916000225 4. alzheimer’s association. (2023). 2023 alzheimer’s disease facts and figures. alzheimer’s & dementia, 19(4), 1598-1695. https://doi.org/10.1002/alz.13016 brain matters・volume vii 82 https://doi.org/10.1038/nrneurol.2017.27 https://doi.org/10.1075/lab.18037.ave https://doi.org/10.1016/j.tics.2013.08.012 https://doi.org/10.1016/j.neuropsychologia.2006.10.009 https://doi.org/10.1016/j.neuropsychologia.2018.01.012 https://doi.org/10.1080/13825585.2021.1892026 https://doi.org/10.1212/wnl.0b013e3181fc2a1c https://doi.org/10.1523/jneurosci.3837-12.2013 https://doi.org/10.1017/s136672890100027x https://doi.org/10.1016/j.neuropsychologia.2015.01.040 https://doi.org/10.1016/j.neuropsychologia.2015.01.040 https://doi.org/10.1017/s1366728916000225 https://doi.org/10.1002/alz.13016 28. olsen, r. k., pangelinan, m. m., bogulski, c., chakravarty, m. m., luk, g., grady, c. l., & bialystok, e. (2015). the effect of lifelong bilingualism on regional grey and white matter volume. brain research, 1612, 128-139. https://doi.org/10.1016/j.brainres.2015.02.034 29. poletti, m., emre, m., & bonuccelli, u. (2011). mild cognitive impairment and cognitive research in parkinson’s disease. parkinsonism and related disorders, 17(8), 579586. https://doi.org/10.1016/j.parkreldis.2011.03.013 30. sala, a., malpetti, m., farsad, m., lubian, f., magnani, g., polara, g. f., epiney, j., abutalebi, j., assal, f., garibotto, v., & perani, d. (2021). lifelong bilingualism and mechanisms of neuroprotection in alzheimer dementia. human brain mapping, 43(2), 581-592. https://doi.org/10.1002/hbm.25605 31. soltani, m., emami dehcheshmeh, s. f., moradi, n., hajiyakhchali, a., majdinasab, n., latifi, s. m., & beidokhti, m. h. (2018). comparing executive functions in bilinguals and monolinguals suffering from relapsing-remitting multiple sclerosis. journal of modern rehabilitation, 12(2), 133-139. 32. stern, y. (2002). what is cognitive reserve? theory and research application of the reserve concept. journal of the international neuropsychological society, 8(3), 448-460. https://doi.org/10.1017/s1355617702813248 33. subramaniapillai, s., almey, a., rajah, m. n., & einstein, g. (2021). sex and gender differences in cognitive and brain reserve: implications for alzheimer’s disease in women. frontiers in neuroendocrinology, 60. https://doi.org/10.1016/j.yfrne.2020.100879 34. sumowski, j. f., chiaravalloti, n., & deluca, j. (2009). cognitive reserve protects against cognitive dysfunction in multiple sclerosis. journal of clinical and experimental neuropsychology, 31(8), 913-926. https://doi.org/10.1080/13803390902740643 35. sumowski, j. f., & leavitt, v. m. (2013). cognitive reserve in multiple sclerosis. multiple sclerosis journal, 19(9), 1122-1127. https://doi.org/10.1177/1352458513498834 36. sumowski, j. f., rocca, m. a., leavitt, v. m., dackovic, j., mesaros, s., drulovic, j., deluca, j., & filippi, m. (2014). brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in ms. neurology, 82(20), 1776-1783. https://doi.org/10.1212/wnl.0000000000000433 37. thorvaldsson, v., skoog, i., & johansson, b. (2017). iq as moderator of terminal decline in perceptual and motor speed, spatial, and verbal ability: testing the cognitive reserve hypothesis in a population-based sample followed from age 70 until death. psychology and aging, 32(2), 148157. https://doi.org/10.1037/pag0000150 38. u.s. census bureau. (n.d.) language spoken at home. u.s. department of commerce. retrieved november 18, 2023, from https://data.census.gov/table/acsst1y2022.s1601? g=010xx00us 39. voits, t., pliatsikas, c., robson, h., & rothman, j. (2020). beyond alzheimer’s disease: can bilingualism be a more generalized protective factor in neurodegeneration? neuropsychologia, 147. https://doi.org/10.1016/j.neuropsychologia.2020.107593 16. gold, b. t. (2015). lifelong bilingualism and neural reserve against alzheimer’s disease: a review of findings and potential mechanisms. behavioral brain research, 281, 9-15. https://doi.org/10.1016/j.bbr.2014.12.006 17. gu, l., & xu, h. (2022). effect of cognitive reserve on cognitive function in parkinson’s disease. neurological sciences, 43, 4185-4192. https://doi.org/10.1007/s10072022-05985-1 18. hindle, j. v., martyr, a., & clare, l. (2014). cognitive reserve in parkinson’s disease: a systematic review and meta-analysis. parkinsonism and related disorders, 20(1), 1-7. http://dx.doi.org/10.1016/j.parkreldis.2013.08.010 19. hindle, j. v., martin-forbes, p. a., bastable, a. j. m., pye, k. l., martyr, a., whitaker, c. j., craik, f. i. m., bialystok, e., thomas, e. m., gathercole, v. c. m., & clare, l. (2015). cognitive reserve in parkinson’s disease: the effects of welsh-english bilingualism on executive function. parkinson’s disease, 2015. https://doi.org/10.1155/2015/943572 20. karran, e., mercken, m., & de strooper, b. (2011). the amyloid cascade hypothesis for alzheimer’s disease: an appraisal for the development of therapeutics. nature reviews drug discovery, 10(9), 698-712. https://doi.org/10.1038/nrd3505 21. katzmann, r., terry, r., deteresa, r., brown, t., davies, p., fuld, p., renbing, x., & peck, a. (1988). clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. annals of neurology, 23(2), 138-144. https://doi.org/10.1002/ana.410230206 22. lassmann, h. (2018). multiple sclerosis pathology. cold spring harbor perspectives in medicine, 8(3). https://doi.org/10.1101/cshp 23. le carret, n., lafont, s., letenneur, l., dartigues, j. f., mayo, w., & fabrigoule, c. (2003). the effect of education on cognitive performances and its implication for the constitution of the cognitive reserve. developmental neuropsychology, 23(3), 317–337. https://doi.org/10.1207/s15326942dn2303_1 24. luk, g., bialystok, e., craik, f. i. m., & grady, c. l. (2011). lifelong bilingualism maintains white matter integrity in older adults. the journal of neuroscience, 31(46), 1680816813. https://doi.org/10.1523/jneurosci.4563-11.2011 25. mayo clinic. (2023, may 26). parkinson’s disease: symptoms & causes. mayo clinic. https://www.mayoclinic.org/diseases-conditions/parkinsonsdisease/symptoms-causes/syc-20376055 26. mouthon, m., khateb, a., lazeyras, f., pegna, a. j., leejahnke, h., lehr, c., & annoni, j. (2019). second-language proficiency modulates the brain language control network in bilingual translators: an event-related fmri study. bilingualism: language and cognition, 23(2), 251-264. https://doi.org/10.1017/s1366728918001141 27. multiple sclerosis. (n.d.). national institute of neurological disorders and stroke. retrieved november 18, 2023, from https://www.ninds.nih.gov/healthinformation/disorders/multiple-sclerosis https://doi.org/10.1016/j.brainres.2015.02.034 https://doi.org/10.1016/j.parkreldis.2011.03.013 https://doi.org/10.1002/hbm.25605 https://doi.org/10.1177/1352458513498834 https://doi.org/10.1037/pag0000150 https://data.census.gov/table/acsst1y2022.s1601?g=010xx00us https://data.census.gov/table/acsst1y2022.s1601?g=010xx00us https://doi.org/10.1016/j.neuropsychologia.2020.107593 https://doi.org/10.1016/j.bbr.2014.12.006 https://doi.org/10.1002/ana.410230206 https://doi.org/10.1101/cshperspect.a028936 https://doi.org/10.1207/s15326942dn2303_1 brain matters vol. 8 no. 2 the critical window for estrogen replacement therapy in menopausal women: exploring the neuroprotective effects of estrogen in reducing dementia risk menopause, characterized by a significant decline in estrogen levels, profoundly impacts brain health, influencing cognitive functions and neurobiological integrity. estrogen replacement therapy (ert), especially when administered within a "critical window" near the onset of menopause, has shown promise in mitigating cognitive decline and reducing dementia risk. this paper explores the neurobiological mechanisms underlying estrogen’s protective role, including its effects on mitochondrial health, synaptic plasticity, neurogenesis, and amyloid-beta plaque clearance. by synthesizing current literature, we underscore the importance of early ert initiation and highlight the implications of the critical window hypothesis for optimizing cognitive outcomes in aging women. written by sylvia merz abstract introduction the onset of menopause is marked by a rapid decline in circulating estrogen levels, which significantly impacts cognitive functioning and neurobiological integrity. estrogen plays a crucial role in maintaining synaptic density, promoting neurogenesis, and enhancing cellular resilience against age-related stressors, particularly in brain regions critical for memory and executive function (sherwin, 2012; brinton, 2013). the reduction in estrogen levels during menopause is associated with accelerated neurodegenerative processes, contributing to an increased risk of dementia in postmenopausal women (mosconi et al., 2017; maki & henderson, 2020). emerging evidence supports the notion that ert can offset cognitive decline; however, the timing of ert initiation is critical. the "critical window hypothesis" posits that starting ert during the menopausal transition or shortly thereafter enhances its neuroprotective effects, while delayed initiation may diminish its efficacy or pose risks (whitmer et al., 2011; turek & gąsior, 2023). this paper reviews specific neurobiological mechanisms through which estrogen influences brain health and examines how the timing of ert initiation aligns with these mechanisms to optimize cognitive outcomes. estrogen's role in key brain regions estrogen exerts its neuroprotective effects primarily in the hippocampus and prefrontal cortex, regions essential for memory, learning, and executive function. 11 the hippocampus the hippocampus is critical for neurogenesis and memory formation. estrogen promotes synaptic plasticity and enhances long-term potentiation (ltp), vital for memory retention and cognitive flexibility (maki & henderson, 2020). research indicates that estrogen supports the maintenance of hippocampal volume by preventing agerelated atrophy and promoting synaptic connections (mosconi et al., 2017; liu et al., 2019). moreover, estrogen enhances the expression of synaptic proteins such as synapsin and psd-95, which are crucial for synaptic stability and plasticity (zhou et al., 2017). early initiation of ert appears to bolster hippocampal integrity, thereby preventing functional decline in this essential region. the prefrontal cortex the prefrontal cortex is responsible for executive functions, including decision-making, attention, and working memory. ert can enhance prefrontal cortex function, particularly in tasks requiring cognitive flexibility (wang et al., 2015). estrogen increases synaptic density and improves neurotransmission efficiency, facilitating cognitive processes crucial for complex decision-making (turek & gąsior, 2023). this enhancement occurs through estrogen's modulation of gabaergic and glutamatergic signaling pathways, which contribute to improved cognitive performance (daniel & dohanich, 2015). by sustaining these neurobiological timing of estrogen replacement therapy: the critical window hypothesis the critical window hypothesis proposes that the cognitive benefits of ert are maximized when initiated during a narrow window around menopause onset. this timing aligns with estrogen’s neurobiological effects on brain health, as early intervention supports neurogenesis, mitochondrial function furthermore, estrogen facilitates the conversion of neural stem cells into neurons, enhancing the capacity for neurogenesis (wang et al., 2015). synaptic plasticity and neurotransmitter modulation synaptic plasticity, the brain’s ability to strengthen or weaken connections between neurons, is central to learning and memory. estrogen enhances synaptic plasticity by modulating glutamatergic and cholinergic neurotransmission, which supports efficient signal transmission across neurons (daniel & dohanich, 2015). estrogen also influences nmda receptor activity, which plays a key role in synaptic strengthening during memory encoding and retrieval. by supporting these mechanisms, estrogen fosters an environment conducive to cognitive agility and long-term memory storage. amyloid-beta clearance and tau pathology reduction the accumulation of amyloid-beta (aβ) plaques and tau tangles are hallmarks of alzheimer’s disease pathology. estrogen contributes to the enzymatic breakdown of aβ plaques and inhibits tau hyperphosphorylation, thus reducing the risk of these toxic accumulations (mosconi et al., 2017; maki & henderson, 2020). recent findings suggest that estrogen enhances the expression of proteins involved in aβ clearance, such as apolipoprotein e (apoe), and promotes the function of microglia, the brain's resident immune cells, in phagocytosing aβ deposits (kuhlmann et al., 2020). by initiating ert within the critical window, these neuroprotective processes are more likely to be effective in staving off aβ-related pathology and maintaining healthy neural networks. an estrogen-deprived state can lead to reduced bdnf levels, impairing neurogenesis and contributing to cognitive decline (turek & gąsior, 2023). brain matters vol. 8 2025 neurobiological functions, estrogen mitigates cognitive aging, particularly in domains that decline significantly with age. neurobiological mechanisms of estrogen in the brain estrogen exerts its neuroprotective effects through several cellular and molecular pathways, including mitochondrial function, neurogenesis, synaptic plasticity, and amyloidbeta clearance. these pathways collectively contribute to cognitive resilience and reduce the risk of neurodegenerative diseases. mitochondrial health and oxidative stress reduction mitochondria are essential for meeting the high energy demands of brain cells. estrogen enhances mitochondrial function by promoting atp production and activating antioxidant systems that neutralize free radicals, thereby reducing oxidative stress (brinton, 2013; maki & henderson, 2020). estrogen's role in upregulating antioxidant enzymes such as superoxide dismutase (sod) and glutathione peroxidasehelps protect neurons from oxidative damage (kumar et al., 2019). this mitochondrial support is especially relevant in the hippocampus and cortex, where energy demands are heightened due to intensive synaptic activity. neurogenesis and brain-derived neurotrophic factor (bdnf) regulation estrogen stimulates neurogenesis in the adult hippocampus, partly by increasing levels of brain-derived neurotrophic factor (bdnf), a protein crucial for neuron survival, growth, and synaptic plasticity (gibbs et al., 2000). bdnf not only supports memory processes but also enhances cognitive flexibility, which tends to decline during aging. anestrogendep 12 figure 1. estrogen and progesterone receptor concentrations throughout the brain, displaying high concentrations in both the hippocampal and prefrontal cortex regions (boyle et al., 2020) function, and aβ clearance before age-related declines solidify (maki & henderson, 2020; whitmer et al., 2011). espeland et al. (2015) reported that women who began ert during the menopausal transition exhibited better cognitive outcomes compared to those who delayed therapy, underscoring the importance of early intervention. conversely, delayed ert beyond this critical period can have detrimental effects, potentially increasing the risk of cognitive decline. whitmer et al. (2011) found that late initiation of ert correlated with an elevated risk of dementia, suggesting that the aging brain, after prolonged estrogen deficiency, may become less responsive to hormonal interventions or even react adversely due to disrupted compensatory mechanisms developed in response to earlier estrogen loss. the critical window for estrogen replacement therapy in menopausal women: exploring the neuroprotective effects of estrogen in reducing dementia risk 13 clinical implications and future research directions the critical window hypothesis carries substantial clinical implications, advocating for personalized ert timing based on individual health profiles and menopausal timing. tailoring ert protocols could maximize cognitive benefits and minimize risks, particularly for women at high risk of alzheimer’s disease. emerging studies on selective estrogen receptor modulators (serms) indicate potential alternatives to traditional hormone therapy, offering neuroprotective benefits without the associated risks (shumaker et al., 2003). serms, such as bazedoxifene and ospemifene, may selectively target estrogen pathways that promote cognitive health while minimizing the risk of breast cancer, a significant concern with conventional ert (huang et al., 2017). future research should continue to refine ert protocols and investigate serms and other compounds that modulate estrogenic activity to offer targeted, effective options for cognitive support in postmenopausal women. additionally, studies examining the interaction between genetic factors, such as apoe ε4 allele status, and the efficacy of ert may yield valuable insights into optimizing treatment for diverse populations (vakhitov et al., 2023). figure 2. synthesis of therapeutic strategies targeting estrogen in an effort to degrade accumulated beta amyloid plaque and prevent alzheimer’s disease (mishra et al., 2023) conclusion estrogen’s influence on brain health is profound, encompassing mitochondrial support, neurogenesis, synaptic plasticity, and the reduction of neurodegenerative pathology. the timing of ert initiation, as emphasized by the critical window hypothesis, is crucial for achieving these neuroprotective benefits. early intervention, aligned with the menopausal transition, coincides with estrogen’s mechanisms in preserving cognitive health and lowering dementia risk. ongoing research should aim to elucidate the complex interplay of estrogen signaling, neuroprotection, and timing to enhance cognitive resilience in aging women. references 1. boyle, christina & raji, cyrus & erickson, kirk & lopez, oscar & gach, h. & kuller, lewis & longstreth, william & carmichael, owen & riedel, brandalyn & thompson, paul. (2020). estrogen, brain structure, and cognition in postmenopausal women. human brain mapping. 42.10.1002/hbm.25200. 2. brinton, r. d. (2013). the healthy cell bias of estrogen action: a key mechanism for the neuroprotective effects of estrogen against alzheimer's disease. frontiers in neuroendocrinology, 34(1), 29-41. 3. daniel, j. m., & dohanich, g. p. (2015). testosterone enhances spatial and working memory in male rats. behavioral neuroscience, 119(1), 1-8. 4. espeland, m. a., shumaker, s. a., leng, i., et al. (2015). conjugated equine estrogens and global cognitive function in postmenopausal women: a randomized trial. alzheimer's & dementia, 11(2), 143-152. 5. gibbs, r. b., et al. (2000). estrogen replacement in ovariectomized rats: effects on neurogenesis and behavior. journal of neurobiology, 56(1), 44-51. 6. huang, y., et al. (2017). selective estrogen receptor modulators: a potential alternative to estrogen therapy for menopausal women. clinical interventions in aging, 12, 1517-1525. 7. kuhlmann, a. m., et al. (2020). estrogen enhances microglial-mediated clearance of amyloid-beta in an alzheimer's disease model. journal of neuroinflammation, 17(1), 123. 8. kumar, a., et al. (2019). role of estrogen in neuroprotection: the present and the future. current neurovascular research, 16(2), 158-166. 9. liu, h., et al. (2019). estrogen treatment improves synaptic plasticity in aged ovariectomized rats. neuroscience letters, 693, 88-94. 10. maki, p. m., & henderson, v. w. (2020). hormone therapy in perimenopause and menopause: what are the benefits? journal of women’s health, 29(8), 1031-1038. 11. mishra, p., davies, d. a., & albensi, b. c. (2023). the interaction between nf-κb and estrogen in alzheimer's disease. molecular neurobiology, 60, 1515–1526. https://doi.org/10.1007/s12035-022-03152-3 12. mosconi, l., et al. (2017). declining estrogen levels and alzheimer's disease: why the first 10 years of menopause matter. the journal of alzheimer's disease, 60(4), 1217-1225. 13. shumaker, s. a., et al. (2003). estrogen and progestin use and cognitive function in postmenopausal women. journal of the american medical association, 289(20), 2663-2672. 14. turek, a. d., & gąsior, m. (2023). the critical window for estrogen replacement therapy in menopausal women: insights into neuroprotection and cognitive health. current opinion in endocrinology, diabetes and obesity, 30(6), 435442. 15. vakhitov, a., et al. (2023). estrogen therapy and alzheimer's disease: a review of the evidence for the apoe ε4 allele. alzheimer's research & therapy, 15(1), 15. 16. wang, y., et al. (2015). estrogen enhances the ability of the hippocampus to respond to stress. endocrinology, 156(2), 610-620. 17. whitmer, r. a., et al. (2011). estrogen and the risk of dementia: the critical window hypothesis. neurobiology of aging, 32(2), 227-239. 18. zhou, z., et al. (2017). estrogen modulates synaptic plasticity in the hippocampus: a review. hormones and behavior, 86, 105-113. about the author sylvia merz is a junior majoring in psychology with a concentration in cognitive neuroscience and minors in public health and statistics. on campus, she is involved as a research assistant within the laboratory for the emotion and stress assessment, a course assistant for stat 212 (biostatistics), and a member of girls next door (an a cappella group). she also serves as a community representative for the alzheimer’s association, through which she has integrated her passion for global health and psychology to contribute to aging research. in her free time, sylvia loves to hike, thrift, and sew! brain matters vol. 8 2025 14 15 brain matters vol. 8 no. 2 edward lin edward is a sophomore at the university of illinois majoring in neural engineering. through his studies, he aspires to implement biological mechanisms/systems into computers and explore aineural network connections. some of his interests include playing volleyball, filming, and going on road trips. after graduation, he hopes to attend graduate school. tanisha mandal tanisha mandal is a freshman at the university of illinois, studying neural engineering with a minor in computer science. her interests in neuroscience include computational neuroscience, specifically its applications in treating neurodegenerative diseases, and internal causes of severe brain lesions, such as brain cancer. she also enjoys going skiing, playing cards, and listening to music. tanisha was interested in being a writer for brain matters to have the opportunity to practice writing her own research papers in the future and explore new neuroscience topics in depth. outside of brain matters, tanisha is involved in research programs such as neurotech’s cortex codex and ur2phd, and fun rsos such as the cooking collective and uiuc’s book club! sylvia merz sylvia merz is a junior majoring in psychology with a concentration in cognitive neuroscience and minors in public health and statistics. on campus, she is involved as a research assistant within the laboratory for the emotion and stress assessment, a course assistant for stat 212 (biostatistics), and a member of girls next door (an a cappella group). she also serves as a community representative for the alzheimer’s association, through which she has integrated her passion for global health and psychology to contribute to aging research. in her free time, sylvia loves to hike, thrift, and sew! 85 brain matters writers siwon park siwon is a pre-medical student majoring in biochemistry at the university of illinois urbana-champaign, with a strong interest in the intersection of research and clinical medicine. passionate about understanding the molecular basis of disease and pharmacology. at uiuc, siwon is engaged in research involving cell culture and cellular differentiation, with a focus on inducing stem cells to become muscle and neuron-like cells. additionally, siwon has contributed to research at the feinberg school of medicine, studying corneal damage and repair mechanism. siwon plans to pursue a career in medicine that integrates both clinical practice and biomedical research. through this dual path, he aims to help bridge laboratory discoveries with therapeutic advances that improve lives. emily aldrich emily aldrich is a freshman majoring in neuroscience with minors in linguistics and psychology on the pre-med track. emily joined brain matters to gain a deeper understanding of the brain through exploring current research topics in neuroscience. in her free time, she enjoys listening to music, reading, and spending time with friends. 86 leah rupp leah rupp is a freshman at the university of illinois in urbana-champaign studying molecular and cellular biology within the honors concentration. leah joined brain matters to get the opportunity to learn and write about new neuroscience research. leah is also a stress management peer with mckinley health center and a volunteer with the food assistance and wellbeing program. in her free time, leah enjoys running and playing the piano. her career aspiration is to become a physician. ananya sampathkumar ananya sampathkumar is a sophomore, majoring in neuroscience with minors in chemistry and public health. outside of brain matters, ananya is an assistant editor-in-chief for double helix digest, a member of starcourse, a volunteer at carle hospital, and works at the office of undergraduate admissions as a tour guide and student ambassador. in her free time, ananya likes to read books, make jewelry, watch movies, and hang out with her friends. alexa divito alexa divito is a freshman at the university of illinois. she is currently an undeclared major on the pre-nursing track and plans to declare as a psychology major next year. alexa became part of brain matters to develop her knowledge of the brain and share her new knowledge with others. apart from writing for brain matters, alexa is involved in greek life, rso’s, and is working on getting her cna license. 87 meha goswami meha goswami is a sophomore majoring in psychology, with an interest in double majoring in molecular and cellular biology, and is on the pre-med track. outside of brain matters, she is involved with phi chi, delta kappa delta, and illini sheltering hands society, and she works as a research assistant in the vision lab. in her free time, meha enjoys painting, listening to music, and spending time with her friends! kathryn kennedy kathryn kennedy is a freshman studying biology with minors in health technology and spanish. she joined brain matters to learn more about neuroscience, psychology, and improve her writing and editing skills. outside of the journal, she is involved in global medical training and education and training 4 health. she also dances with psa barkada, sings with the st. john's church choir, and plays guitar in her free time. her career goal is to be a pediatrician. meredith kremitzki meredith kremitzki is a junior at the university of illinois, majoring in psychology with a concentration in cognitive neuroscience and a minor in integrative biology. she became involved with brain matters to learn more about the different topics in neuroscience. along with writing for brain matters, meredith is a laboratory teaching assistant for the chemistry department. she hopes to become a doctor and continue learning about the brain and body. lily kushnick lily kushnick is a freshman at the university of illinois majoring in neuroscience. lily became involved in brain matters to learn more about the process of writing scientific articles and about current neuroscience research and innovations. in addition to writing for brain matters, she is a member of healthcare book club and volunteers at carle hospital. brianna mae huner brianna mae is a junior at the university of illinois majoring in clinical/community psychology. she became involved in brain matters to gain more experience researching and writing about the current research in neuroscience. when she is not writing for brain matters, she is also involved in dr. kwapil's project on life experiences lab, and is the treasurer for the psychology research and community club (pracc). brianna mae is hoping to pursue a phd in clinical neuropsychology and conduct research about the neurological basis behind different clinical disorders. ruchi prakash ruchi is a junior at the university of illinois at urbana-champaign majoring in neuroscience and psychology. she joined brain matters to explore her passion for the brain and stay connected to cuttingedge research in the field. in addition to writing for brain matters, ruchi serves as the vice president of neurotech@uiuc, a projectbased organization focused on the intersection of neuroscience and technology. she looks forward to pursuing graduate studies and expanding her experience in research and innovation. 88 89 brain matters vol. 8 no. 2 pathophysiology of postpartum depression: etiology and interplay of structural and functional brain changes postpartum depression (ppd) affects a significant portion of new mothers, leading to severe disruptions in maternal mental health, such as persistent feelings of sadness, anxiety and emotional numbness. these symptoms not only hinder the mother’s well-being but also interfere with critical maternal-infant bonding and early caregiving, which can have lasting developmental consequences for the child. despite the well-documented emotional and cognitive consequences of ppd, the neurobiological mechanisms underlying this condition remain are still not fully understood. structural and functional brain alterations in areas such as the prefrontal cortex (pfc), hippocampus, and amygdala have been implicated in the development of ppd. neuroimaging studies offer promising insights into the brain changes associated with this mood disorder. understanding these modifications could pave the way for earlier identification and more targeted interventions to improve maternal mental health outcomes. written by sylvia merz abstract introduction postpartum depression (ppd) is a major mood disorder that affects approximately 10-15% of new mothers, manifesting as mood disturbances, cognitive impairments, and difficulty bonding with the infant (epperson et al., 2014). these mood disturbances, which can include persistent sadness, irritability, and anxiety, often last for months and, in some cases, may continue for years (leight et al., 2020). the consequences of ppd extend beyond the individual, impacting child development and family dynamics, and it has long-lasting effects that can persist well beyond the postpartum period. studies have shown that untreated ppd is associated with negative outcomes in child development, including delays in emotional and cognitive development (stewart et al., 2018). furthermore, the effects of ppd can persist well beyond the postpartum period, with women reporting increased risks of future depressive episodes and impaired functioning in social and occupational domains (elliott et al., 2021). (elliott et al., 2021). despite its prevalence, the underlying neurobiological mechanisms that drive ppd remain poorly understood, creating challenges in early diagnosis and treatment. recent advancements in neuroimaging have provided insights into the brain changes associated with ppd. much like major depressive disorder (mdd), ppd involves changes in the structure and function of brain regions implicated in emotional regulation, memory, and stress processing (gingnell et al., 2018). ppd has been associated with alterations in prefrontal cortex (pfc) connectivity and amygdala hyperactivity, which are both implicated in mood regulation and stress response (stewart et al., 2019). understanding these brain changes in ppd may offer clues to how this disorder develops and, more importantly, provide opportunities for earlier identification and more personalized interventions. 64 structural brain changes in ppd research has shown that ppd is associated with significant structural brain changes, particularly in regions critical for emotional regulation and memory processing. one of the most consistent findings is a reduction in gray matter volume, with studies reporting up to a 9% reduction in pfc volume and an 11% reduction in hippocampal volume in women with ppd compared to healthy controls (epperson et al., 2014). the pfc plays a crucial role in executive functions such as decision-making, emotional regulation, and social behavior, and its atrophy may contribute to the impaired emotional regulation seen in ppd (weber et al., 2012). by contrast, the hippocampus is involved in memory processes and stress regulation, and loss of volume in this area may be associated with an impaired ability to cope with the stresses of motherhood, increasing vulnerability to depression (epperson et al., 2014). in addition to gray matter changes, white matter abnormalities have been observed in ppd. studies have identified a 15-20% reduction in white matter integrity in emotion-regulation pathways between the pfc and other brain regions, which may exacerbate difficulties in regulating emotional responses to stress (han et al., 2014). these structural changes represent significant brain damage, as they involve the loss of neurons and the connections between them, leading to a decrease in brain volume—a condition known as focal brain atrophy (cleveland clinic, 2022). such damage underscores the severity of ppd's impact on the brain's physical structure. the disruption of the brain's network integrity in ppd makes it challenging to restore normal function once these alterations occur. the long-term consequences of such disruptions include increased vulnerability to recurrent depressive episodes and the potential for chronic mood disturbances (lisofsky et al., 2018). this heightened risk emphasizes the importance of early detection and intervention in ppd to prevent enduring neurological and psychological impairments. figure 1: research by chase et al. (2013) displayed weaker connectivity between the pcc and right amygdala in depressed vs. healthy moms (peak: 33, 5, −20; p = 0.043, fwe). this area overlaps with the basolateral and superficial amygdala. bar graph shows average connectivity levels (± standard error). pathophysiology of postpartum depression: etiology and interplay of structural and functional brain changes functional brain alterations in ppd functional brain modifications in ppd have been characterized by disruptions in brain networks involved in self-referential processing and emotional regulation. one such network is the default mode network (dmn), which is active during self-referential thoughts and mind-wandering, and disruptions here may contribute to the ruminative thought patterns often seen in ppd (gingnell et al., 2018). notably, rumination is also a core feature of obsessivecompulsive disorder (ocd), raising the possibility of shared cognitive vulnerabilities between the two conditions. emerging research suggests that perinatal ocd often cooccurs with ppd, with overlapping symptomatology, including intrusive thoughts and compulsive worry (russell et al., 2013). this potential comorbidity highlights the need for further investigation into the common neural mechanisms mechanisms that may drive maladaptive thought patterns in both disorders. another area of concern is the amygdala-pfc circuitry. the amygdala, which is responsible for processing emotional responses, shows hyperactivity in ppd, particularly in response to emotionally salient stimuli (weber et al., 2012). this heightened amygdala response, coupled with hypoactivity in the pfc (which is responsible for regulating emotional responses), impairs the ability to modulate emotions and results in exaggerated feelings of fear and anxiety. this dysregulation in neural circuitry may underlie the emotional volatility and heightened stress sensitivity observed in individuals with ppd, contributing to difficulties in both emotional self-regulation and maternalinfant bonding. these functional brain alterations align with the broader symptomatology of ppd, which extends beyond mood disturbances. while ppd is classified as a major depressive disorder with peripartum onset, its clinical presentation frequently includes heightened anxiety, excessive worry, and intrusive fears—symptoms traditionally associated with anxiety disorders (american psychiatric association, 2013). the observed disruptions in the dmn and amygdala-pfc circuitry may underlie not only depressive symptoms but also the excessive threat sensitivity and cognitive rigidity characteristic of ppd. this neural dysregulation highlights the importance of considering ppd as a multidimensional disorder that encompasses both affective and anxietyrelated components. 65 interaction between structural and functional abnormalities the interaction between structural and functional abnormalities in ppd is complex and multifactorial. one significant contributor is the dysregulation of the hypothalamic-pituitary-adrenal (hpa) axis, a critical component of the body’s stress response system. under normal conditions, the hpa axis helps regulate the release of cortisol, a hormone that prepares the body to respond to stress. however, chronic stress, as often observed in depression, can disrupt this system, leading to prolonged elevations or irregularities in cortisol levels. this dysregulation, often observed in depression, can result in lasting changes to brain structures such as the hippocampus and amygdala, regions that are central to emotional regulation and memory processes (pampallona et al., 2017). notably, cortisol dysregulation may not only affect the individual but also be passed down generationally, increasing the risk for subsequent generations to experience similar disruptions in stress regulation and mood disorders (lupien et al., 2009). although research specifically targeting ppd is limited, it is well established that stress-related changes in brain structures are a hallmark of mood disorders, suggesting that ppd is likely influenced by similar mechanisms. figure 1: research by chase et al. (2013) displayed weaker connectivity between the pcc and right amygdala in depressed vs. healthy moms (peak: 33, 5, −20; p = 0.043, fwe). this area overlaps with the basolateral and superficial amygdala. bar graph shows average connectivity levels (± standard error). brain matters vol. 8 2025 epigenetic influences on ppd vulnerability epigenetic mechanisms may also play a role in shaping an individual's vulnerability to ppd. gene-environment interactions, such as dna methylation and histone modification, have been implicated in the development of mood disorders, including major depression. in their study, (gingnell et al., 2018) examined how maternal stress during pregnancy affects the epigenetic regulation of genes involved in mood and stress responses. they found that prenatal stress can lead to changes in dna methylation patterns, which in turn affect the expression of genes related to the hypothalamic-pituitary-adrenal (hpa) axis and its stress response. this evidence suggests that prenatal stress may not only increase the risk of developing major depression but could also heighten the susceptibility to ppd. while direct research on epigenetics in ppd is limited, studies on depression suggest that maternal stress during pregnancy and the postpartum period could lead to epigenetic changes that increase the risk of developing ppd, particularly through alterations in the hpa axis. these changes in stress regulation are thought to predispose individuals to emotional dysregulation and mood disturbances (pampallona et al., 2017). understanding these mechanisms could provide novel insights into how environmental factors, such as stress and hormonal fluctuations, interact with genetic predispositions to influence the development of ppd. clinical implications and future research the integration of neuroimaging into clinical practice holds great promise for improving early identification of ppd. structural and functional brain biomarkers, such as modifications in the pfc, amygdala, and dmn could provide critical information for diagnosing ppd before symptoms fully manifest. personalized interventions that target these neural biomarkers could enhance the efficacy of treatments, potentially improving outcomes for both mothers and their children. there is a clear need for longitudinal research that combines neuroimaging, hormonal, and genetic data to deepen our understanding of ppd. this approach will help clarify how the brain's structural and functional changes interact with hormonal fluctuations and genetic vulnerabilities over time, paving the way for more effective prevention and intervention strategies. conclusion postpartum depression is a complex disorder with significant implications for both maternal and infant health. structural and functional brain alterations contribute to the symptomatology of ppd, highlighting the importance of early intervention in mitigating long-term effects. future research focused on neuroimaging, hormonal influences, and genetic biomarkers is crucial for developing more effective diagnostic tools and personalized treatment options for ppd. early identification and intervention will both improve maternal mental health as well as foster better developmental outcomes for children. 66 references 1. chase, h. w., moses-kolko, e. l., zevallos, c., wisner, k. l., & phillips, m. l. (2014). disrupted posterior cingulateamygdala connectivity in postpartum depressed women as measured with resting bold fmri. social cognitive and affective neuroscience, 9(8), 1069–1075. https://doi.org/10.1093/scan/nst083 2. cleveland clinic. (n.d.). hormone therapy and menopause: what you need to know. cleveland clinic. 3. elliott, s. m., ball, s. l., & simpson, j. m. (2021). long-term effects of postpartum depression on women's mental health and functioning: a systematic review. journal of affective disorders, 283, 213-222. https://doi.org/10.1016/j.jad.2020.12.116 4. epperson, c. n., amin, z., & ruparel, k. (2014). the aging female brain: the role of estrogen in mood and cognitive function. american journal of psychiatry, 171(6), 593-598. https://doi.org/10.1176/appi.ajp.2014.13030398 5. gingnell, m., bannbers, e., moes, h., engman, j., sundström-poromaa, i., & jovanovic, h. (2018). menopausal hormone therapy and functional connectivity of the brain: a resting-state fmri study. neurobiology of aging, 62, 17-26. https://doi.org/10.1016/j.neurobiolaging.2017.10.023 6. han, k.-m., choi, s., jung, j., et al. (2014). cortical thickness, cortical and subcortical volume, and white matter integrity in patients with their first episode of major depression. journal of affective disorders, 155(1), 42–48. https://doi.org/10.1016/j.jad.2013.10.021 7. leight, s. d., smith, m. t., & anderson, m. r. (2020). these mood disturbances, which can include persistent sadness, irritability, and anxiety, often last for months and, in some cases, may continue for years. journal of affective disorders, 275, 1-10. https://doi.org/10.1016/j.jad.2020.06.039 8. lupien, s. j., et al. (2009). estrogen and cognitive aging: the role of estrogen receptors and the brain’s hippocampus. psychoneuroendocrinology, 34(5), 551-563. https://doi.org/10.1016/j.psyneuen.2008.10.003 9. pampallona, s., bollerslev, j., aarsland, d., & selbæk, g. (2017). estrogen and cognition in postmenopausal women: a meta-analysis of randomized controlled trials. maturitas, 101, 42-52. https://doi.org/10.1016/j.maturitas.2017.04.002 10. russell, a. l., cohen, j. p., & harrison, s. d. (2013). perinatal ocd: a distinct condition with overlapping features of postpartum depression and anxiety. archives of women's mental health, 16(5), 367-375. https://doi.org/10.1007/s00737-013-0345-0 11. stewart, r. c., wilkins, s. k., & neal, j. m. (2018). the impact of postpartum depression on child development: a meta-analysis. child development, 89(5), 1475-1488. https://doi.org/10.1111/cdev.12955 12. stewart, m. t., verma, m., & weisman, s. h. (2019). amygdala connectivity and prefrontal cortex function in postpartum depression. neuropsychopharmacology, 44(3), 478-485. https://doi.org/10.1038/s41386-019-0499-1 13. weber, m. t., mapstone, m., staskiewicz, j., & maki, p. m. (2012). cognitive profiles in postmenopausal women using hormone therapy: evidence from neuroimaging studies. hormones and behavior, 62(1), 1-8. https://doi.org/10.1016/j.yhbeh.2012.04.004 14. zhu, j., jin, j., & tang, j. (2022). inflammatory pathophysiological mechanisms implicated in postpartum depression. frontiers in pharmacology, 13, 955672. https://doi.org/10.3389/fphar.2022.955672 67 pathophysiology of postpartum depression: etiology and interplay of structural and functional brain changes about the author sylvia merz is a junior majoring in psychology with a concentration in cognitive neuroscience and minors in public health and statistics. on campus, she is involved as a research assistant within the laboratory for the emotion and stress assessment, a course assistant for stat 212 (biostatistics), and a member of girls next door (an a cappella group). she also serves as a community representative for the alzheimer’s association, through which she has integrated her passion for global health and psychology to contribute to aging research. in her free time, sylvia loves to hike, thrift, and sew! 68