Claustrum

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Not to be confused with Colostrum.

Claustrum

Coronal section of human cerebrum. The claustrum is indicated by the

arrow.

Transverse section of human cerebrum. The claustrum is indicated by

the arrow.

Details
 Part of Human brain

Artery Middle cerebral artery

Identifiers

NeuroNames 252

NeuroLex ID birnlex_1522

TA A14.1.09.421

FMA 67440

Anatomical terms of neuroanatomy

[edit on Wikidata]

The claustrum (Latin for: to close or shut) is a thin, bilateral structure which connects

to cortical (ex. pre-frontal cortex) and subcortical regions (ex. thalamus) of the brain. [1][2] It is
located between the insula laterally and the putamen medially, separated by the extreme and
external capsules respectively.[1][3] The blood supply to the claustrum is fulfilled via the middle
cerebral artery.[1] It is considered to be the most densely connected structure in the brain allowing
for integration of various cortical inputs (ex. colour, sound and touch) into one experience rather
than singular events.[3][4] The claustrum is difficult to study given the limited number of individuals
with claustral lesions and the poor resolution of neuroimaging.[3]
The claustrum is made up of various cell types differing in size, shape and neurochemical
composition.[3] Five cell types exist and a majority of these cells resemble pyramidal neurons
found in the cortex[5] Within the claustrum, there is no organization of cell types compared to the
cortex and the somas of the cells can be a pyramidal, fusiform or circular shape. [1] The principal
cell type found in the claustrum is Type 1 cells, which are large cells covered in spiny dendrites.
The claustrum usually connects to the cortex in an ipsilateral manner; however, the few that
travel contralaterally are considerably weaker than the former. [1] The claustrum acts as a
conductor for inputs from the cortical regions so these respective areas do not become
unsynchronized.[1][2][6][7] Without the claustrum, one could respond to stimuli that are familiar to the
individual but not to complex events.[1] Additionally, the claustrum is essential in
combining sensory and motor modalities so that various anatomical patterns are present. [6][8] One
of the proposed functions of the claustrum is to differentiate between relevant and irrelevant
information so that the latter can be ignored.[4][8][9] Cortical components of consciousness include
the fronto-parietal cortex, cingulate and precuneus. Due to the claustrum's widespread
connectivity to these areas, it is suggested that it may play a role in
both attention and consciousness.[2] The neural networks that mediate sustained attention and
consciousness implicate numerous cortical areas, many of which overlap in connectivity with the
claustrum. Previous clinical reports suggest that conscious processes are lateralized to the left
hemisphere in humans.[10]

Contents
 1Structure
o 1.1Connections
o 1.2Microanatomy
o 1.3Neurons
 2Function
o 2.1Potential function
o 2.2Attention
o 2.3Empirical evidence
o 2.4Lesions and consciousness
 3Clinical significance
o 3.1Schizophrenia
o 3.2Epilepsy
o 3.3Consciousness
o 3.4Parkinsonism
 4Other animals
o 4.1Cats
o 4.2Rodents
o 4.3Monkeys
 5References
 6External links

Structure[edit]
The claustrum is a small bilateral gray matter structure (comprising roughly 0.25% of the cerebral
cortex) located deep to the insular cortex and extreme capsule, and superficial to the external
capsule and basal ganglia. As mentioned, its name means “hidden or shut away” and was first
identified in 1672, with more detailed descriptions coming later on during the 19th century. [1]
[11]
 Although the regional neuroanatomical boundaries of the claustrum have been defined, there
remains a lack of consensus in the literature when defining its precise margins. [9][12][13]
Connections[edit]
Despite this long history of reports on the claustrum, descriptions of its overall connectivity have
been sparse.[14] However, recent work has suggested that this mysterious structure is present in
all mammals, with extensive connections to cortical and subcortical regions. [15][16] More
specifically, electrophysiological studies show extensive connections to thalamic nuclei and
the basal ganglia, while isotopological reports have linked the claustrum with the prefrontal,
frontal, parietal, temporal and occipital cortices.[17][18] Additional studies have also looked at the
relationship of the claustrum to well-described subcortical white matter tracts. Structures such as
the corona radiata, occipital-frontal fasciculus and uncinate fasciculus project to the claustrum
from frontal, pericentral, parietal and occipital regions. [19] Reciprocal connections also exist with
motor, somatosensory, auditory and visual cortical regions.[9] Altogether, these findings leave the
claustrum as the most highly connected structure per regional volume in the brain and suggest
that it may serve as a hub to coordinate activity of cerebral circuits. [20][21] Interestingly, even with
this extensive connectivity, most projections to and from the claustrum are ipsilateral (although
there are still contralateral projections), and little evidence exists to describe its afferent or
efferent connections with the brainstem and spinal cord.[9][14][22] In summary, the cortical and
subcortical connectivity of the claustrum implies that it is most involved with processing sensory
information, as well as the physical and emotional state of an animal.
Microanatomy[edit]
Inputs to the claustrum are organized by modality, which include visual, auditory
and somatomotor processing areas. In the same way that the morphology of neurons in
the spinal cord is indicative of function (i.e. rexed laminae), the visual, auditory and somatomotor
regions within the claustrum share similar neurons with specific functional characteristics. For
example, the portion of the claustrum that processes visual information (primarily synthesizing
afferent fibers concerned with our peripheral visual field) is comprised by a majority of binocular
cells that have “elongated receptive fields and no orientation selectivity. [23][24] This focus on
peripheral sensory system is not an isolated occurrence, as most sensory afferents entering the
claustrum bring peripheral sensory information. Moreover, the claustrum possesses a
distinct topological organization for each sensory modality. For example, there is a retinotopic
organization within the visual processing area of the claustrum that mirrors that of visual
association cortices and V1, in a similar (yet less complicated) manner to the retinotopic
conservation within the lateral geniculate nucleus. [9]
Neurons[edit]
The claustrum is made up of various cell types that differ in size, shape and neurochemical
composition.[3] Five types of cells exist and the majority of these cells are structurally similar
to pyramidal neurons found in the cortex.[5] Within the claustrum, the somas of the cells can be
found with a pyramidal, fusiform or circular shape. [1] The principal cell type found in the claustrum
is Type 1 cells, which are large neurons covered in spiny dendrites. These cells receive inputs
from the cortex, and their axons will then leave in a medial or lateral fashion and send reciprocal
projections back to the cortex.[1] GABAergic interneurons represent only 10%-15% of the neurons
within the claustrum. Finally, many studies show that the claustrum is best distinguished
structurally by its prominent plexus of parvalbumin-positive fibers formed by local interneurons. [4]

Function[edit]
The claustrum has been shown to have widespread activity to numerous cortical components, all
of which have been associated with having components of consciousness and sustained
attention. This is because of widespread connectivity to fronto-parietal areas, cingulate cortex,
and thalami. Sustained attention is from the connections to the cingulate cortex, temporal cortex,
and thalamus.
Crick and Koch suggest that the claustrum has a role similar to that of a conductor within an
orchestra as it attempts to co-ordinate the function of all connections. [1] This “conductor” analogy
can also be supported through connections between the claustral, sensory, and frontal regions.
The claustrum has been confirmed to be reciprocally connected to the prefrontal cortex, visual,
auditory, sensory, and motor regions respectively. Connections to these modalities provide
insight into the functionality of the claustrum. Here it is proposed that the claustrum functions in
the gating of selective attention. Through this gating process the claustrum can selectively
control input from these modalities to facilitate the process of “focusing”. It has also been
suggested that it operates in the opposite context; that through divisive normalization the
claustrum may implement resistance to certain input modalities to prevent “distraction”.
Potential function[edit]
The claustrum, in order to facilitate consciousness, would need to integrate various sensory and
motor modalities from various parts of the cortex. The anatomical connections of the claustrum
have been observed using DTI (diffusion tensor imaging). An fMRI scan looks at oxygenated
blood levels in the brain as a way of observing the activity of specific cortical areas. fMRI scans
show dampened activity when anesthetized versus awake in rats, specifically claustrum
connections to the medial prefrontal cortex (mPFC) and the mediodorsol thalamus (MD
thalamus). The claustrum is connected with the contralateral hemispheres claustrum with strong
and functional connections. Connections with MD thalamaus, mPFC, and surrounding and
distant cortical areas also exist.[6]
Electrical stimulation in the dorsal claustrum of cats elicits excitatory responses within the visual
cortex. The claustrum is situated anatomically at the confluence of a large number of white-
matter tracts used to connected different parts of the cortex. This further suggests an integration
center role for these different modalities, such as sensory and motor. Gap junctions have been
shown to exist between aspiny interneurons of the claustrum – suggesting a role in its ability to
synchronize these modalities as input is received.[1]
Attention[edit]
The claustrum has the differential ability to select between task relevant information and task
irrelevant information to provide directed attention. It contains the highest density of connecting
white matter tracts in the cortex. This supports the notion of networking and coordination among
different regions of the brain.[8] The claustrum has regional specificity to it; information coming in
from visual centers project to specific areas of grey matter neurons in the structure and the
auditory cortex.[1] Unexpected stimuli also activate the claustrum, effecting an immediate focusing
or allocation of function. In lower mammals (e.g. rats), claustral regions receive input from
somatosensory modalities, such as whiskers' motor control perspective because of its sensory
and discriminatory use in these mammals. [9]
Functionally, it is proposed that it segregates attention between these modalities. Attention itself
has been considered as top-down processing or bottom-up processing; both fit contextually with
what is observed in the claustrum structurally and functionally, supporting the notion that
interactions occur with high-order sensory areas involved in encoding objects and features. Input
from the prefrontal cortex, for example, will define attention based upon higher-cognitive task
driven behaviour. Moreover, induction of electrical stimulation to the claustrum has been shown
to cause inhibition reading, a blank stare, and unresponsiveness. It has been reported that the
claustrum has a basal frequency firing that is modulated to increase or decrease with directed
attention. For example, projections to motor and occulomotor areas would assist with gaze
movement to direct attention to new stimuli by increasing the firing frequency of claustral
neurons.[9]
Salvia divinorum is a derivative from a psychoactive plant that is capable of inducing loss of
awareness. Consumption of salvinorin A will work on its respective salvinorium A receptors to
induce synesthesia, in which different sensory modalities are interpreted by different sensory
cortices. This supports the idea of intrathalamic segregation and conduction (attention). The
claustrum has Salvinorium A receptors, to which this chemical is capable of binding and eliciting
this effect.[3][9]
Empirical evidence[edit]
High frequency stimulation (HFS) in cat claustrum(s) has the capability to induce autonomic
changes and induce “inactivation syndrome”. This syndrome is described as a decrease in
awareness, indicating the relationship between the claustrum and consciousness. [25] In humans
this same effect can be observed. Stimulation of the left claustrum in humans has produced
volitional behaviour, unresponsiveness, and amnesia, suggesting the involvement in
consciousness.[10] Furthermore, MRI studies have shown that increased signal intensity with the
claustrum has been associated with status epilepticus – a condition in which epileptic seizures
follow one another without recovery of consciousness in-between events. [26][27] As well, increased
signal intensity is associated with Focal dyscognitive seizures, which are seizures that elicit
impairment of awareness or consciousness without convulsions. The individual becomes
unaware of his or her environment, and the seizure will manifest as a blank or empty stare for a
window of time.
Using an operant conditioning task combined with HFS of the claustrum resulted in significant
behavioural changes of rats; this included modulated motor responses, inactivity and decreased
responsiveness. [2] Beyond this, studies have also shown that the claustrum is active during REM
sleep, alongside other structures such as the dentate gyrus. These have associative roles in
spatial memory, suggesting that some form of memory consolidation takes place in these areas. [4]
Lesions and consciousness[edit]
Functionally, the claustrum will integrate various cortical inputs through its connections into
consciousness. Based upon its structure and connectivity, its function is suggested to do with
coordination of different brain function; i.e. the conductor analogy. Consciousness functionally
can be divided into two components: (i) wakefulness, which is arousal and alertness; (ii) content
of consciousness, which is the processing of content. A study of traumatic brain injuries in war
veterans was undertaken to better understand the functional role of the claustrum. Damage to
the claustrum was associated with duration of loss of consciousness, but not frequency. Lesion
size was correlated with greater duration of LOC events. Interestingly, no consequences were
shown to attenuate cognitive processing. [3]
In a single case-study, consciousness was shown to be disrupted when there was stimulation to
the extreme capsule of the brain – is in close proximity to the claustrum – such that upon
termination of stimulation, consciousness was regained. [10] Another study looking at the
symptomology of schizophrenia established that the severity of delusions was associated with
decreased grey matter volume of the left claustrum; postulating that correlations exist between
the structure and positive symptoms seen in this psychiatric disorder. Further supporting this
correlation between schizophrenia and the claustrum is that there is an increase in white matter
volume entering the claustrum.[28] Negative correlations between grey matter volume, and severity
of hallucinations in the context of auditory hallucinations of schizophrenia has been supported.
[29]
 As well, to see the total loss of function of the claustrum, lesions to both claustrums on each
hemisphere would need to occur.[1]

Clinical significance[edit]
Schizophrenia[edit]
Damage to the claustrum can lead to various common diseases or mental disorders; delayed
development of the structure leads to autism. The claustrum may be involved in schizophrenia as
findings show an increase in positive symptoms, such as delusions, when the grey matter
volume of the left claustrum and right insula is decreased. [29]

New Onset Refractory Status Epilepticus with Claustrum Damage

Epilepsy[edit]
The claustrum is also seen to play a role in epilepsy; MRIs have found increased claustral signal
intensity in those that have been diagnosed with epilepsy. In certain cases, seizures tend to
appear to originate from the claustrum when they are involved in early kainic acid induced
seizures.[2]
Consciousness[edit]
A single case-study showed that consciousness was disrupted when the area between the insula
and claustrum was electrically stimulated; consciousness was regained when stimulation
stopped.[3][10] Patients that had a lesion in their left claustrum were more likely to experience a loss
of consciousness compared to those that presented with lesions outside of the claustrum. [3] For
example, a patient that was subjected to electrode stimulation at the claustrum stopped reading,
stared blankly and was unresponsive. Once the electrode was removed, the patient resumed
reading and could not remember the events of being dazed. [9]
Parkinsonism[edit]
A team of investigators led by neuroscientists at Beth Israel Deaconess Medical Center has
identified the claustrum as the likely origin of parkinsonism across different conditions. The team
used a novel methodology called lesion network mapping to discover the origins of parkinsonism
in 29 patients whose symptoms were not the result of Parkinson’s disease but rather attributed to
a brain lesion – an abnormality or injury to the brain visible on brain imaging. The mapping of the
29 lesions – which were located in different regions of the brain – revealed that connectivity to
the claustrum was the single most sensitive and specific marker of lesion-induced
parkinsonism. [30]

Other animals[edit]
In animals, through tract tracing, findings have shown that the claustrum has extensive
connections throughout the cortex with sensory and motor regions along with the hippocampus.
[2]
 A variety of animal models have been used such as cats, rodents and monkeys.
Anatomy of a Cat Brain

Cats[edit]
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In cats, high-frequency stimulation (HFS) of the claustrum can alter motor activity,

induce autonomic changes, and precipitate an “inactivation syndrome” described as “decreased
awareness".[2] Recordings, primarily in cats and primates, show that claustral neurons respond to
sensory stimuli and during voluntary movements.[4] Mapping from visual cortex to claustrum
includes just a single map, which includes V1 and three other visual areas. Cells in the V1 are
part of layer 6, which different from cells that go to the lateral geniculate nucleus; these cells
use glutamate as their neurotransmitter. The cat claustrum has 3 defined zones: (1) the anterior
dorsal zone, which connects to the motor and somatosensory cortex, (2) the posterior dorsal
zone that has connections to the visual cortex and (3) a third zone that is ventral to visual one
and connects to the auditory areas.[1]
Sensory input is segregated based on modalities and there is a high preference for peripheral
sensory information. In the cat, input is received from various visual cortical areas and projects
back to the area.[9] These loops are retinotopical, meaning that regions getting visual input are
responsible for the same region in the visual field as the area of the cortex that projects to the
claustrum. The visual claustrum is a single map of contralateral visual hemifield, receiving
information based on motion in the visual field's periphery and has no real selectivity. [9] In terms
of somatosensation, claustral neurons will receive whisker motor innervations. They then project
back to the whisker motor and somatosensory cortex. This cortical-claustral-cortical circuit plays
a role in whisker movements for orientation and palpation. [9]

Dynamics of place boundary and object encoding in rat anterior claustrum.

Rodents[edit]
In rats, motor whisker areas receive input from the ipsilateral claustrum but will then project to the
contralateral claustrum.[4] The sensory barrel cortex and primary visual cortex also receive input
from the ipsilateral claustrum but send very few projection back to the claustrum. Studies
therefore indicate distinct patterning of connectivity of claustrum with different cortical areas.
These suggest, rather than a diffuse role, they play specialized roles in cortical processing. [4]
In mice, parvalbumin fibres are highly interconnected by chemical and electrical synapses. They
are additionally also highly interconnected with claustrocortical neurons – suggesting that these
inhibitory interneurons strongly modulate their activity. [4] These local networks suggest to
synchronize activity of claustrocortical projections to therefore influence brain rhythms and co-
ordinated activity of different cortical brain regions. There are additional classes of inhibitory
interneurons with local connections within the claustrocortical neurons. [4]
Recent experiments in mice monitoring claustrocortical axonal activity to changing visual stimuli
suggest the claustrum signals stimulus changes. [4] Interestingly although claustrocortical input to
visual cortical areas were engaged, the strongest responses measured were in higher-order
regions of the cortex, this included the anterior cingulate cortex which is densely innervated by
claustral projection.[4]
Monkeys[edit]
In the monkey, there are widespread connections of the claustrum with allocortical and
neocortical regions. These connections project towards the frontal lobe, visual cortical regions,
temporal cortex, parieto-occipital cortex and somatosensory areas amongst others. [1] The
subcortical areas receiving projections are the amygdala, caudate nucleus and hippocampus. It
is unknown if there are cortical regions that do not receive input from the claustrum. Additionally,
large or small types of aspiny are reported in the monkey brain, which are classified as “local
circuit neurons".[5]
The dorsal claustrum has bi-directional connections with motor structures in the cortex. [1] The
relationship between animal's movement and how neurons in the dorsocaudal claustrum
behaves are as follows: 70% of movement neurons are non-selective and can fire to do any
push, pulls or turn movements in the forelimb, the rest were more discerning and did only one of
the three movements listed above. [1]