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.

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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 higher-
order 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. 

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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 ‘first-
order’ 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

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