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The claustrum (Latin, meaning "to close" or "to shut") is a thin sheet of and supporting glial cells in the brain, that connects to the cerebral cortex and subcortical regions including the amygdala, hippocampus and thalamus. It is located between the insular cortex laterally and the putamen medially, encased by the Extreme capsule and respectively. Blood to the claustrum is supplied by the middle cerebral artery. It is considered to be the most densely connected structure in the brain, and thus hypothesized to allow for the integration of various cortical inputs such as vision, sound and touch, into one experience. Other hypotheses suggest that the claustrum plays a role in Salience network, to direct attention towards the most behaviorally relevant stimuli amongst the background noise. The claustrum is difficult to study given the limited number of individuals with claustral lesions and the poor resolution of neuroimaging.
The claustrum is made up of various cell types differing in size, shape and neurochemical composition. Five cell types exist, and a majority of these cells resemble pyramidal neurons found in the cortex. Within the claustrum, there is no laminar organization of cell types as in the cortical layers, and the cell bodies can be a pyramidal, fusiform or circular. The principal cell type found in the claustrum is the Golgi type I neuron, which is a large cell with covered in dendritic spine.
Through interhemispheric connections, the claustrum is believed to play a role in synchronizing activity in widely separated, but functionally related, parts of the brain such as between frontal eye fields and the visual cortex. As such, the claustrum is thought to play a role in combining different information modalities, potentially to support consciousness itself. Another proposed function of the claustrum is to differentiate between relevant and irrelevant information so that the latter can be ignored.
Cortical components of consciousness include the fronto-parietal cortex, Cingulate cortex 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. The neural networks that mediate sustained attention and consciousness send inputs to the claustrum, and one case report in humans suggests that electrical stimulation near the claustrum reversibly disrupted the patient's conscious state.
Its name means "hidden away", and was first identified in 1672, with more detailed descriptions coming later on during the 19th century. 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, though a meeting in 2019 of experts has posited a framework by which to refer to the structures across species.
This focus on the 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 Topology organization for each sensory modality as well as the dense connectivity it shares with frontal cortices. 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.
Within the claustrum, local connectivity is dominated by feed-forward disynaptic inhibition wherein parvalbumin-expressing interneurons suppress the activity of nearby projection neurons. Local interneurons themselves are connected through both Synapse and Gap junction, allowing for widespread and synchronous inhibition of local claustrum circuitry. In recent studies of the claustrum in mice and , cortically-projecting excitatory claustrum neurons were found to form synapses across the anteroposterior axis and were biased toward neurons that do not share projection targets, with the possible function of joining the activity of different afferent modules. Combined, these two circuits suggest that the claustrum is capable of performing local transformations of diverse input information from across the brain.
Several approaches in mice have been used to assess claustrum cell types, including electrophysiological, morphological, genetic, and connectomic approaches. While no clear consensus has yet been reached regarding the exact number of excitatory cell types, recent studies have suggested that cortically- and subcortically-projecting claustrum neurons are likely distinct and vary along several metrics, such as their intrinsic electrophysiological profiles, afferent projections, and neuromodulatory profiles.
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. 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".
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 connect 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 (lacking dendrite projections) interneurons of the claustrum – suggesting a role in its ability to synchronize these modalities as input is received.
Additional studies point to involvement in Spatial memory and slow-wave sleep.
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 of 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 oculomotor areas would assist with gaze movement to direct attention to new stimuli by increasing the firing frequency of claustral neurons.
Salvinorin A, the active hallucinogenic compound found in Salvia divinorum, is capable of inducing loss of awareness. Consumption of salvinorin A can induce synesthesia, in which different sensory modalities are interpreted by different sensory cortices. (For example: seeing sounds, tasting colours.) This supports the idea of intrathalamic segregation and conduction (attention). The claustrum has kappa opioid receptors to which Salvinorin A binds, eliciting this effect.
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. 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.
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 the duration of one's loss of consciousness, but not its frequency. Lesion size was correlated with a longer duration of LOC events. No consequences were shown to attenuate cognitive processing.
In a single-case study, consciousness was shown to be disrupted when there was stimulation to the extreme capsule of the brain – which is in close proximity to the claustrum – such that upon termination of stimulation, consciousness was regained. 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. Inverse correlations between grey matter volume and severity of hallucinations in the context of auditory hallucinations of schizophrenia has been supported. As well, to see the total loss of function of the claustrum, lesions to both claustrums on each hemisphere would need to occur.
However, a study in 2019, consisting of electrical stimulation of the claustrum, found no disruption of consciousness in any of the five patients that were subjected to the analysis. The tested patients reported subjective experiences in various sensory domains and exhibited reflexive movement, but none of them displayed loss of consciousness, thus questioning the claustrum's ability to disrupt consciousness when stimulated electrically.
A 2019 study consisting of electrical stimulation of the claustrum found no disruption of consciousness in any of the five patients that were subjected to the analysis. The tested patients reported subjective experiences in various sensory domains and exhibited reflexive movement, but none of them displayed loss of consciousness, thus questioning the claustrum's ability to disrupt consciousness when stimulated electrically.
A 2020 study involving artificial activation of the claustrum by optogenetic light stimulation silenced brain activity across the cortex, a phenomenon known as a "Down state," which can be seen when mice are sleeping or resting awake (quiet wakefulness). The authors state that 'The claustrum is a coordinator of global slow-wave activity, and it is so exciting that we are getting closer to linking specific brain connections and actions with the ultimate puzzle of consciousness.'
However, cognitive scientist Stevan Harnad does not consider the claustrum to be a "switch" for consciousness, but merely for wakefulness. He claims that if the claustrum were truly a switch for consciousness, artificial activation of the claustrum would not result in the patient passing out, but instead the patient would continue behaving normally, and later report that they experienced no sensations during the period of time when their claustrum was being stimulated.
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 the visual one and connects to the auditory areas.
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. 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 the contralateral visual hemifield, receiving information based on motion in the visual field's periphery and has no real selectivity.
In terms of somatosensation, cat claustrum receives dense inputs from primary somatosensory cortex (S1), but weaker inputs from secondary somatosensory cortex (S2). The inputs from S1 overlap with inputs from primary motor cortex (at least those from the forepaw representations of both). Rodent claustrum does not receive input from S1 or S2, and is primarily driven by motor cortex.
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. 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.
Experiments in mice monitoring claustrocortical axonal activity to changing visual stimuli suggest the claustrum signals stimulus changes. 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.
The dorsal claustrum has bi-directional connections with motor structures in the cortex. The relationship between the animal's movement and how neurons in the dorsocaudal claustrum behave are as follows: 70% of movement neurons are non-selective and can fire to do any push, pull or turn movements in the forelimb; the rest were more discerning and did only one of the three movements listed above.
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