Editing Claustrum (section)

== Function ==
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.<ref name="Crick2005" /> 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 ===
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 [[diffusion tensor imaging]] (DTI). A [[functional magnetic resonance imaging]] (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 [[Medial dorsal nucleus|mediodorsal thalamus]] (MD thalamus). The claustrum is connected with the contralateral hemisphere's claustrum with strong, functional connections. Connections with MD thalamus, mPFC, and surrounding and distant cortical areas also exist.<ref name="Smith2017" />

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.<ref name="Crick2005" />

Additional studies point to involvement in [[Spatial memory|spatial navigation]]<ref>{{cite journal | vauthors = Grasby K, Talk A | title = The anterior claustrum and spatial reversal learning in rats | journal = Brain Research | volume = 1499 | pages = 43–52 | date = March 2013 | pmid = 23318254 | doi = 10.1016/j.brainres.2013.01.014 | s2cid = 19605350 }}</ref> and [[slow-wave sleep]].<ref name="Norimoto2020">{{cite journal | vauthors = Norimoto et al. | title = A claustrum in reptiles and its role in slow-wave sleep | journal = Nature | volume = 578 | pages = 413–418 | date = 2020 | issue = 7795 | pmid = 32051589 | doi = 10.1038/s41586-020-1993-6 | bibcode = 2020Natur.578..413N | s2cid = 256820426 | url = http://id.nii.ac.jp/1394/00001182/ | hdl = 21.11116/0000-0008-09DB-8 | hdl-access = free }}</ref><ref name="Narikiyo2020">{{cite journal | vauthors = Narikiyo et al. | title = The claustrum coordinates cortical slow-wave activity | journal = Nature Neuroscience | volume = 23 | pages = 741–753 | date = 2020 | issue = 6 | pmid = 32393895| doi = 10.1038/s41593-020-0625-7 | s2cid = 256840965 }}</ref>

===Attention===
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.<ref name="Torgerson2015" /> 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.<ref name="Crick2005" /> 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.<ref name="Goll2015" />

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.<ref name="Goll2015" />

[[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 [[Κ-opioid receptor|kappa opioid receptors]] to which Salvinorin A binds, eliciting this effect.<ref name="Chau2015" /><ref name="Goll2015" />

=== Empirical evidence ===
[[Tetanic stimulation|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.<ref>{{cite journal |last1=Gabor |first1=Andrew J. |last2=Peele |first2=Talmage L. |title=Alterations of behavior following stimulation of the claustrum of the cat |journal=Electroencephalography and Clinical Neurophysiology |date=November 1964 |volume=17 |issue=5 |pages=513–519 |doi=10.1016/0013-4694(64)90181-6 |pmid=14229851 }}</ref> In humans this same effect can be observed. Stimulation of the left claustrum in humans has produced "a complete arrest of volitional behavior, unresponsiveness, and amnesia without negative motor symptoms, or mere aphasia" suggesting the involvement in consciousness.<ref name="Koubeissi-2014" /> Furthermore, MRI studies have shown that increased signal intensity within the claustrum has been associated with status epilepticus – a condition in which epileptic seizures follow one another without recovery of consciousness between events.<ref>{{cite journal | vauthors = Silva G, Jacob S, Melo C, Alves D, Costa D | title = Claustrum sign in a child with refractory status epilepticus after febrile illness: why does it happen? | journal = Acta Neurologica Belgica | volume = 118 | issue = 2 | pages = 303–305 | date = June 2018 | pmid = 28741106 | doi = 10.1007/s13760-017-0820-9 | s2cid = 32771124 }}</ref><ref>{{cite journal | vauthors = Meletti S, Slonkova J, Mareckova I, Monti G, Specchio N, Hon P, Giovannini G, Marcian V, Chiari A, Krupa P, Pietrafusa N, Berankova D, Bar M | title = Claustrum damage and refractory status epilepticus following febrile illness | journal = Neurology | volume = 85 | issue = 14 | pages = 1224–32 | date = October 2015 | pmid = 26341869 | pmc = 4607596 | doi = 10.1212/WNL.0000000000001996 }}</ref> 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.<ref name="Koubeissi-2014"/> 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.<ref name="Brown" />

=== Lesions and consciousness ===
Functionally, the claustrum will integrate various cortical inputs through its connections into consciousness. Based upon its structure and connectivity, its function is suggested to be related to coordination of different brain functions; 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 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.<ref name="Chau2015" />

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.<ref name="Koubeissi-2014" /> 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.<ref>{{cite journal | vauthors = Shapleske J, Rossell SL, Chitnis XA, Suckling J, Simmons A, Bullmore ET, Woodruff PW, David AS | s2cid = 33360335 | title = A computational morphometric MRI study of schizophrenia: effects of hallucinations | journal = Cerebral Cortex | volume = 12 | issue = 12 | pages = 1331–41 | date = December 2002 | pmid = 12427683 | doi = 10.1093/cercor/12.12.1331 | doi-access = free }}</ref> Inverse correlations between grey matter volume and severity of hallucinations in the context of auditory hallucinations of schizophrenia has been supported.<ref name="Cascella2011">{{cite journal | vauthors = Cascella NG, Gerner GJ, Fieldstone SC, Sawa A, Schretlen DJ | title = The insula-claustrum region and delusions in schizophrenia | journal = Schizophrenia Research | volume = 133 | issue = 1–3 | pages = 77–81 | date = December 2011 | pmid = 21875780 | doi = 10.1016/j.schres.2011.08.004 | s2cid = 45564142 }}</ref> As well, to see the total loss of function of the claustrum, lesions to both claustrums on each hemisphere would need to occur.<ref name="Crick2005" />

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.<ref name="Bickel2019"/>