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 Music-
Based 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.1749-
6632.2000.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 Music-
Based 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/s1053-
8119(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/s1474-
4422(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

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