Claustrum: Difference between revisions

Claustrum
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.
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MeSH	D000079482
NeuroNames	252
NeuroLex ID	birnlex_1522
TA98	A14.1.09.421
TA2	5535
FMA	67440
	Anatomical terms of neuroanatomy [edit on Wikidata]

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Claustrum

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 are 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].

Structure

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 19^th 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].

General Connectivity of the Claustrum

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.

Internal Organization of the Claustrum

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 Within the Claustrum

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

The claustrum has been shown to have widespread activity to numerous cortical components, all of which that 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 being 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” notion can also be supported through connections between 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; through divisive normalization the claustrum may implement resistance to certain input modalities to prevent “distraction”.

Potential Function of the Claustrum

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). Using fMRI looks at oxygenated blood levels in the brain as a way of observing the activity of specific cortical areas. Observed dampened effects with fMRI when anesthetized versus awake in rats, specifically claustrum connections to the medial prefrontal cortex (mPFC) and the mediodorsol thalamus (MD thalamus). As well it has been found that the claustrum anatomically is connected with the contralateral hemispheres claustrum and has strong 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 additionally supports the notion of an integration center from 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

The claustrum has the differential ability to select between task relevant information and task irrelevant information to provide directed attention. Per-unit volume in the cortex, it contains the highest density of connecting white matter tracts. This supports the notion of networking and coordination among different regions of the brain^[8]. As well, the claustrum has regional specificity to it, information coming in from visual centers project to specific areas of the grey matter neurons in the structure. The same is said of the auditory cortex^[1]. This is supported by unexpected stimuli inducing activation of the claustrum, suggesting an immediate focusing or allocation of function. In lower mammals (such as rats), claustral regions receive input from somatosensory modalities – this also supports as input from a “whisker” 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 object and feature. 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 induce the prevention 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. Projections to motor and occulomotor areas for example 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 awareness³. Drug application (salvinorin A) will work on its respective Salvinorium A receptors to induce synesthesia, where different sensory modalities are interpreted by different sensory cortex’s – auditory sensation is smelt. This acts to support the idea of intrathalamic segregation and conduction (attention). The claustrum is saturated with Salvinorium A receptors, to which this chemical is capable of binding and eliciting this effect ^[3]^[9].

Empirical Evidence

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, suggesting some functional role relevant to consciousness^[25]. In humans this same effect can be observed. It has been reported that stimulation of the left claustrum in humans produced volitional behaviour, unresponsiveness and amnesia; also suggesting role involved 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 has has been found to be associated with Focal dyscognitive seizures; a seizure that does not involve convulsions yet elicits impairment of awareness or consciousness. The individual becomes unaware of his or her environment, and the seizure will manifest as blank or empty stare for a window of time. These show a role in consciousness and sustained attention by the claustrum.

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 – suggesting and supporting a functional role in sustained attention^[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

Functionally, the claustrum will integrate various cortical inputs through its connections, into one experience; 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].

Animal Models

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.

Cats

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 areas¹. 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 info 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].

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Rodents

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

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 claustrum¹. 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].

Pathology

Schizophrenia

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

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 KA seizures (Kainic-Acid induced seizures)^[2].

Conciousness

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].

References

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^ Meletti, Stefano; Slonkova, Jana; Mareckova, Iva; Monti, Giulia; Specchio, Nicola; Hon, Petr; Giovannini, Giada; Marcian, Vaclav; Chiari, Annalisa (2015-10-06). "Claustrum damage and refractory status epilepticus following febrile illness". Neurology. 85 (14): 1224–1232. doi:10.1212/WNL.0000000000001996. ISSN 1526-632X. PMC 4607596. PMID 26341869.{{cite journal}}: CS1 maint: PMC format (link)
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External links

[:0-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r Crick, Francis C.; Koch, Christof (2005-06-29). "What is the function of the claustrum?". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 360 (1458): 1271–1279. doi:10.1098/rstb.2005.1661. ISSN 0962-8436. PMC 1569501. PMID 16147522.{{cite journal}}: CS1 maint: PMC format (link)

[:1-2] ^ ^a ^b ^c ^d ^e ^f ^g Bayat, Arezou; Joshi, Sweta; Jahan, Sahar; Connell, Phillip; Tsuchiya, Komei; Chau, David; Syed, Tanvir; Forcelli, Patrick; Koubeissi, Mohamad Z. (02 2018). "A pilot study of the role of the claustrum in attention and seizures in rats". Epilepsy Research. 140: 97–104. doi:10.1016/j.eplepsyres.2018.01.006. ISSN 1872-6844. PMID 29324357. {{cite journal}}: Check date values in: |date= (help)

[:2-3] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Chau, Aileen; Salazar, Andres M.; Krueger, Frank; Cristofori, Irene; Grafman, Jordan (2015-11). "The effect of claustrum lesions on human consciousness and recovery of function". Consciousness and Cognition. 36: 256–264. doi:10.1016/j.concog.2015.06.017. ISSN 1090-2376. PMID 26186439. {{cite journal}}: Check date values in: |date= (help)

[:3-4] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k Brown, Solange P.; Mathur, Brian N.; Olsen, Shawn R.; Luppi, Pierre-Hervé; Bickford, Martha E.; Citri, Ami (2017-11-08). "New Breakthroughs in Understanding the Role of Functional Interactions between the Neocortex and the Claustrum". The Journal of Neuroscience: The Official Journal of the Society for Neuroscience. 37 (45): 10877–10881. doi:10.1523/JNEUROSCI.1837-17.2017. ISSN 1529-2401. PMC 5678020. PMID 29118217.{{cite journal}}: CS1 maint: PMC format (link)

[:4-5] Braak, H.; Braak, E. (1982). "Neuronal types in the claustrum of man". Anatomy and Embryology. 163 (4): 447–460. ISSN 0340-2061. PMID 7091711.

[:5-6] Smith, Jared B.; Liang, Zhifeng; Watson, Glenn D. R.; Alloway, Kevin D.; Zhang, Nanyin (2017-7). "Interhemispheric resting-state functional connectivity of the claustrum in the awake and anesthetized states". Brain Structure & Function. 222 (5): 2041–2058. doi:10.1007/s00429-016-1323-9. ISSN 1863-2661. PMC 5382132. PMID 27714529. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)

[7] Stevens, Charles F. (2005-06). "Consciousness: Crick and the claustrum". Nature. 435 (7045): 1040–1041. doi:10.1038/4351040a. ISSN 1476-4687. {{cite journal}}: Check date values in: |date= (help)

[:6-8] Torgerson, Carinna M.; Irimia, Andrei; Goh, S. Y. Matthew; Van Horn, John Darrell (2015-3). "The DTI connectivity of the human claustrum". Human Brain Mapping. 36 (3): 827–838. doi:10.1002/hbm.22667. ISSN 1097-0193. PMC 4324054. PMID 25339630. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)

[:7-9] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Goll, Yael; Atlan, Gal; Citri, Ami (2015-8). "Attention: the claustrum". Trends in Neurosciences. 38 (8): 486–495. doi:10.1016/j.tins.2015.05.006. ISSN 1878-108X. PMID 26116988. {{cite journal}}: Check date values in: |date= (help)

[:8-10] Koubeissi, Mohamad Z.; Bartolomei, Fabrice; Beltagy, Abdelrahman; Picard, Fabienne (2014-8). "Electrical stimulation of a small brain area reversibly disrupts consciousness". Epilepsy & Behavior: E&B. 37: 32–35. doi:10.1016/j.yebeh.2014.05.027. ISSN 1525-5069. PMID 24967698. {{cite journal}}: Check date values in: |date= (help)

[11] "Development of the endopiriform nucleus and the claustrum in the rat brain". Neuroscience. 45 (2): 391–412. 1991-01-01. doi:10.1016/0306-4522(91)90236-H. ISSN 0306-4522.

[12] Baizer, Joan S.; Sherwood, Chet C.; Noonan, Michael; Hof, Patrick R. (2014). "Comparative organization of the claustrum: what does structure tell us about function?". Frontiers in Systems Neuroscience. 8: 117. doi:10.3389/fnsys.2014.00117. ISSN 1662-5137. PMC 4079070. PMID 25071474.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)

[13] Mathur, Brian N. (2014). "The claustrum in review". Frontiers in Systems Neuroscience. 8: 48. doi:10.3389/fnsys.2014.00048. ISSN 1662-5137. PMC 3983483. PMID 24772070.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)

[:9-14] Edelstein, L. R.; Denaro, F. J. (2004-9). "The claustrum: a historical review of its anatomy, physiology, cytochemistry and functional significance". Cellular and Molecular Biology (Noisy-Le-Grand, France). 50 (6): 675–702. ISSN 0145-5680. PMID 15643691. {{cite journal}}: Check date values in: |date= (help)

[15] Buchanan, Kenneth J.; Johnson, John Irwin (2011-5). "Diversity of spatial relationships of the claustrum and insula in branches of the mammalian radiation". Annals of the New York Academy of Sciences. 1225 Suppl 1: E30–63. doi:10.1111/j.1749-6632.2011.06022.x. ISSN 1749-6632. PMID 21599698. {{cite journal}}: Check date values in: |date= (help)

[16] Grasby, Katrina; Talk, Andrew (2013-03-07). "The anterior claustrum and spatial reversal learning in rats". Brain Research. 1499: 43–52. doi:10.1016/j.brainres.2013.01.014. ISSN 1872-6240. PMID 23318254.

[17] "Physiology of the Claustrum". The Claustrum: 177–191. 2014-01-01. doi:10.1016/B978-0-12-404566-8.00005-2.

[18] S., Smythies, John R. (John Raymond), 1922- Edelstein, Lawrence R. Ramachandran, V. (2014). The claustrum : structural, functional, and clinical neuroscience. Academic Press. ISBN 9780124045668. OCLC 861211388.{{cite book}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)

[19] Fernandez-Miranda, Juan C.; Pathak, Sudhir; Engh, Johnathan; Jarbo, Kevin; Verstynen, Timothy; Yeh, Fang-Cheng; Wang, Yibao; Mintz, Arlan; Boada, Fernando (2012-8). "High-definition fiber tractography of the human brain: neuroanatomical validation and neurosurgical applications". Neurosurgery. 71 (2): 430–453. doi:10.1227/NEU.0b013e3182592faa. ISSN 1524-4040. PMID 22513841. {{cite journal}}: Check date values in: |date= (help)

[20] LeVay, S. (1986-12-01). "Synaptic organization of claustral and geniculate afferents to the visual cortex of the cat". Journal of Neuroscience. 6 (12): 3564–3575. doi:10.1523/JNEUROSCI.06-12-03564.1986. ISSN 1529-2401. PMID 2432202.

[21] Zingg, Brian; Hintiryan, Houri; Gou, Lin; Song, Monica Y.; Bay, Maxwell; Bienkowski, Michael S.; Foster, Nicholas N.; Yamashita, Seita; Bowman, Ian (2014-02-27). "Neural networks of the mouse neocortex". Cell. 156 (5): 1096–1111. doi:10.1016/j.cell.2014.02.023. ISSN 1097-4172. PMC 4169118. PMID 24581503.{{cite journal}}: CS1 maint: PMC format (link)

[22] Markowitsch, H. J.; Irle, E.; Bang-Olsen, R.; Flindt-Egebak, P. (1984-6). "Claustral efferents to the cat's limbic cortex studied with retrograde and anterograde tracing techniques". Neuroscience. 12 (2): 409–425. ISSN 0306-4522. PMID 6462456. {{cite journal}}: Check date values in: |date= (help)

[23] Smith, Jared B.; Alloway, Kevin D. (2010-12-15). "Functional specificity of claustrum connections in the rat: interhemispheric communication between specific parts of motor cortex". The Journal of Neuroscience: The Official Journal of the Society for Neuroscience. 30 (50): 16832–16844. doi:10.1523/JNEUROSCI.4438-10.2010. ISSN 1529-2401. PMC 3010244. PMID 21159954.{{cite journal}}: CS1 maint: PMC format (link)

[24] Smith, Jared B.; Alloway, Kevin D. (2014). "Interhemispheric claustral circuits coordinate sensory and motor cortical areas that regulate exploratory behaviors". Frontiers in Systems Neuroscience. 8: 93. doi:10.3389/fnsys.2014.00093. ISSN 1662-5137. PMC 4032913. PMID 24904315.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)

[25] "Alterations of behavior following stimulation of the claustrum of the cat". Electroencephalography and Clinical Neurophysiology. 17 (5): 513–519. 1964-11-01. doi:10.1016/0013-4694(64)90181-6. ISSN 0013-4694.

[26] Silva, Guilherme; Jacob, Sylvia; Melo, Cláudia; Alves, Dílio; Costa, Dias (2018-6). "Claustrum sign in a child with refractory status epilepticus after febrile illness: why does it happen?". Acta Neurologica Belgica. 118 (2): 303–305. doi:10.1007/s13760-017-0820-9. ISSN 2240-2993. PMID 28741106. {{cite journal}}: Check date values in: |date= (help)

[27] Meletti, Stefano; Slonkova, Jana; Mareckova, Iva; Monti, Giulia; Specchio, Nicola; Hon, Petr; Giovannini, Giada; Marcian, Vaclav; Chiari, Annalisa (2015-10-06). "Claustrum damage and refractory status epilepticus following febrile illness". Neurology. 85 (14): 1224–1232. doi:10.1212/WNL.0000000000001996. ISSN 1526-632X. PMC 4607596. PMID 26341869.{{cite journal}}: CS1 maint: PMC format (link)

[28] Shapleske, Jane; Rossell, Susan L.; Chitnis, Xavier A.; Suckling, John; Simmons, Andrew; Bullmore, Edward T.; Woodruff, Peter W. R.; David, Anthony S. (2002-12). "A computational morphometric MRI study of schizophrenia: effects of hallucinations". Cerebral Cortex (New York, N.Y.: 1991). 12 (12): 1331–1341. ISSN 1047-3211. PMID 12427683. {{cite journal}}: Check date values in: |date= (help)

[:10-29] "The insula–claustrum region and delusions in schizophrenia". Schizophrenia Research. 133 (1–3): 77–81. 2011-12-01. doi:10.1016/j.schres.2011.08.004. ISSN 0920-9964.

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@@ Line 1: / Line 1: @@
 {{Distinguish|Colostrum}}
+== Claustrum ==
 {{Infobox Brain
 |  Name            = Claustrum
@@ Line 12: / Line 14: @@
 |  Vein            =
 }}
+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<ref name=":0">{{Cite journal|last=Crick|first=Francis C.|last2=Koch|first2=Christof|date=2005-06-29|title=What is the function of the claustrum?|url=https://www.ncbi.nlm.nih.gov/pubmed/16147522|journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|volume=360|issue=1458|pages=1271–1279|doi=10.1098/rstb.2005.1661|issn=0962-8436|pmc=PMC1569501|pmid=16147522}}</ref><ref name=":1">{{Cite journal|last=Bayat|first=Arezou|last2=Joshi|first2=Sweta|last3=Jahan|first3=Sahar|last4=Connell|first4=Phillip|last5=Tsuchiya|first5=Komei|last6=Chau|first6=David|last7=Syed|first7=Tanvir|last8=Forcelli|first8=Patrick|last9=Koubeissi|first9=Mohamad Z.|date=02 2018|title=A pilot study of the role of the claustrum in attention and seizures in rats|url=https://www.ncbi.nlm.nih.gov/pubmed/29324357|journal=Epilepsy Research|volume=140|pages=97–104|doi=10.1016/j.eplepsyres.2018.01.006|issn=1872-6844|pmid=29324357}}</ref>. It is located between the [[Insular cortex|insula]] laterally and the [[putamen]] medially, separated by the extreme and external capsules respectively<ref name=":0" /><ref name=":2">{{Cite journal|last=Chau|first=Aileen|last2=Salazar|first2=Andres M.|last3=Krueger|first3=Frank|last4=Cristofori|first4=Irene|last5=Grafman|first5=Jordan|date=2015-11|title=The effect of claustrum lesions on human consciousness and recovery of function|url=https://www.ncbi.nlm.nih.gov/pubmed/26186439|journal=Consciousness and Cognition|volume=36|pages=256–264|doi=10.1016/j.concog.2015.06.017|issn=1090-2376|pmid=26186439}}</ref>. The blood supply to the claustrum is fulfilled via the [[middle cerebral artery]]<ref name=":0" />. 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<ref name=":2" /><ref name=":3">{{Cite journal|last=Brown|first=Solange P.|last2=Mathur|first2=Brian N.|last3=Olsen|first3=Shawn R.|last4=Luppi|first4=Pierre-Hervé|last5=Bickford|first5=Martha E.|last6=Citri|first6=Ami|date=2017-11-08|title=New Breakthroughs in Understanding the Role of Functional Interactions between the Neocortex and the Claustrum|url=https://www.ncbi.nlm.nih.gov/pubmed/29118217|journal=The Journal of Neuroscience: The Official Journal of the Society for Neuroscience|volume=37|issue=45|pages=10877–10881|doi=10.1523/JNEUROSCI.1837-17.2017|issn=1529-2401|pmc=PMC5678020|pmid=29118217}}</ref>. The claustrum is difficult to study given the limited number of individuals with claustral lesions and the poor resolution of [[neuroimaging]]<ref name=":2" />.
-The '''claustrum''' is a thin, irregular sheet of [[neuron]]s that is attached to the underside of the [[neocortex]] in the center of the [[brain]]. It is suspected to be present in the brains of all [[mammals]].
+The claustrum is made up of various cell types differing in size, shape and neurochemical composition<ref name=":2" />. Five cell types exist and a majority of these cells are resemble pyramidal neurons found in the cortex<ref name=":4">{{Cite journal|last=Braak|first=H.|last2=Braak|first2=E.|date=1982|title=Neuronal types in the claustrum of man|url=https://www.ncbi.nlm.nih.gov/pubmed/7091711|journal=Anatomy and Embryology|volume=163|issue=4|pages=447–460|issn=0340-2061|pmid=7091711}}</ref>. 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<ref name=":0" />. The principal cell type found in the claustrum is Type 1 cells, which are large cells covered in spiny dendrites.
-The claustrum in the [[human brain]] is a fraction of a millimetre to a few millimetres thick and is a vertical curved sheet of [[cerebral cortex|subcortical]] [[gray matter]] oriented [[Sagittal plane|sagittally]] between the [[white matter]] [[Nerve tract|tracts]] of the [[external capsule]] and [[extreme capsule]]. The claustrum is lateral to the [[putamen]] and medial to the [[insular cortex]] and is considered by some sources to be part of the [[basal ganglia]].  There are lateral and medial tracts connecting the claustrum to many parts of the cortex and perhaps to the [[hippocampus]], the [[amygdala]], and the [[caudate nucleus]] (connections with subcortical centers are a matter of debate).
+The claustrum usually connects to the cortex in an [[Anatomical terms of location|ipsilateral]] manner; however, the few that travel contralaterally are considerably weaker than the former<ref name=":0" />. The claustrum acts as a conductor for inputs from the cortical regions so these respective areas do not become unsynchronized<ref name=":0" /><ref name=":1" /><ref name=":5">{{Cite journal|last=Smith|first=Jared B.|last2=Liang|first2=Zhifeng|last3=Watson|first3=Glenn D. R.|last4=Alloway|first4=Kevin D.|last5=Zhang|first5=Nanyin|date=2017-7|title=Interhemispheric resting-state functional connectivity of the claustrum in the awake and anesthetized states|url=https://www.ncbi.nlm.nih.gov/pubmed/27714529|journal=Brain Structure & Function|volume=222|issue=5|pages=2041–2058|doi=10.1007/s00429-016-1323-9|issn=1863-2661|pmc=PMC5382132|pmid=27714529}}</ref><ref>{{Cite journal|last=Stevens|first=Charles F.|date=2005-06|title=Consciousness: Crick and the claustrum|url=https://www.nature.com/articles/4351040a|journal=Nature|language=en|volume=435|issue=7045|pages=1040–1041|doi=10.1038/4351040a|issn=1476-4687}}</ref>. Without the claustrum, one could respond to stimuli that are familiar to the individual but not to complex events<ref name=":0" />. Additionally, the claustrum is essential in combining [[Sensory nervous system|sensory]] and motor modalities so that various anatomical patterns are present<ref name=":5" /><ref name=":6">{{Cite journal|last=Torgerson|first=Carinna M.|last2=Irimia|first2=Andrei|last3=Goh|first3=S. Y. Matthew|last4=Van Horn|first4=John Darrell|date=2015-3|title=The DTI connectivity of the human claustrum|url=https://www.ncbi.nlm.nih.gov/pubmed/25339630|journal=Human Brain Mapping|volume=36|issue=3|pages=827–838|doi=10.1002/hbm.22667|issn=1097-0193|pmc=PMC4324054|pmid=25339630}}</ref>.One of the proposed functions of the claustrum is to differentiate between relevant and irrelevant information so that the latter can be ignored<ref name=":3" /><ref name=":6" /><ref name=":7">{{Cite journal|last=Goll|first=Yael|last2=Atlan|first2=Gal|last3=Citri|first3=Ami|date=2015-8|title=Attention: the claustrum|url=https://www.ncbi.nlm.nih.gov/pubmed/26116988|journal=Trends in Neurosciences|volume=38|issue=8|pages=486–495|doi=10.1016/j.tins.2015.05.006|issn=1878-108X|pmid=26116988}}</ref>. 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]]<ref name=":1" />. 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<ref name=":8">{{Cite journal|last=Koubeissi|first=Mohamad Z.|last2=Bartolomei|first2=Fabrice|last3=Beltagy|first3=Abdelrahman|last4=Picard|first4=Fabienne|date=2014-8|title=Electrical stimulation of a small brain area reversibly disrupts consciousness|url=https://www.ncbi.nlm.nih.gov/pubmed/24967698|journal=Epilepsy & Behavior: E&B|volume=37|pages=32–35|doi=10.1016/j.yebeh.2014.05.027|issn=1525-5069|pmid=24967698}}</ref>.
-The claustrum has a uniformity in its types of cells, indicating a uniform type of processing by all claustral neurons. Though organized into modality specific regions, the claustrum contains a great deal of longitudinal connections between its neurons that could serve to synchronize the entire anterior-posterior extent of the claustrum.<ref name="Alloway KD 2010">{{cite journal |doi=10.1523/JNEUROSCI.4438-10.2010 |title=Functional Specificity of Claustrum Connections in the Rat: Interhemispheric Communication between Specific Parts of Motor Cortex |year=2010 |last1=Smith |first1=J. B. |last2=Alloway |first2=K. D. |journal=Journal of Neuroscience |volume=30 |issue=50 |pages=16832–44 |pmid=21159954 |pmc=3010244}}</ref> [[Francis Crick]] and [[Christof Koch]] have compared the claustrum to the conductor of an orchestra, referring to its regulatory role in consciousness and cognition.<ref name="Crick">{{cite journal |last1=Crick |first1=FC |last2=Koch |first2=C |title=What is the function of the claustrum? |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |date=29 June 2005 |volume=360 |issue=1458 |pages=1271–9 |doi=10.1098/rstb.2005.1661 |pmid=16147522|pmc=1569501 }}</ref><ref>{{cite journal  |doi=10.1016/j.yebeh.2014.05.027 |title=Electrical stimulation of a small brain area reversibly disrupts consciousness |year=2014 |last1=Koubeissi |first1=M. Z. |last2=Bartolomei |first2=F. |journal=Epilepsy & Behavior |volume=37 |pages=32–35 |pmid=24967698 }}</ref> The different parts of the cortex must play in harmony or else the result is a cacophony of sounds.<ref name="Crick"/> The claustrum may be involved in widespread coordination of the cerebral cortex, using synchronization to achieve a seamless timescale between both the two cortical hemispheres and between cortical regions within the same hemisphere, resulting in the seamless quality of [[consciousness|conscious experience]].
+{{tocleft}}
 ==Structure==
+The claustrum is a small bilateral [[Grey matter|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 19<sup>th</sup> century<ref name=":0" /><ref>{{Cite journal|date=1991-01-01|title=Development of the endopiriform nucleus and the claustrum in the rat brain|url=https://www.sciencedirect.com/science/article/abs/pii/030645229190236H|journal=Neuroscience|language=en|volume=45|issue=2|pages=391–412|doi=10.1016/0306-4522(91)90236-H|issn=0306-4522}}</ref>. 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<ref name=":7" /><ref>{{Cite journal|last=Baizer|first=Joan S.|last2=Sherwood|first2=Chet C.|last3=Noonan|first3=Michael|last4=Hof|first4=Patrick R.|date=2014|title=Comparative organization of the claustrum: what does structure tell us about function?|url=https://www.ncbi.nlm.nih.gov/pubmed/25071474|journal=Frontiers in Systems Neuroscience|volume=8|pages=117|doi=10.3389/fnsys.2014.00117|issn=1662-5137|pmc=PMC4079070|pmid=25071474}}</ref><ref>{{Cite journal|last=Mathur|first=Brian N.|date=2014|title=The claustrum in review|url=https://www.ncbi.nlm.nih.gov/pubmed/24772070|journal=Frontiers in Systems Neuroscience|volume=8|pages=48|doi=10.3389/fnsys.2014.00048|issn=1662-5137|pmc=PMC3983483|pmid=24772070}}</ref>.
-<gallery>
-File:Slide5kk.JPG|Claustrum
+===General Connectivity of the Claustrum===
+Despite this long history of reports on the claustrum, descriptions of its overall connectivity have been sparse<ref name=":9">{{Cite journal|last=Edelstein|first=L. R.|last2=Denaro|first2=F. J.|date=2004-9|title=The claustrum: a historical review of its anatomy, physiology, cytochemistry and functional significance|url=https://www.ncbi.nlm.nih.gov/pubmed/15643691|journal=Cellular and Molecular Biology (Noisy-Le-Grand, France)|volume=50|issue=6|pages=675–702|issn=0145-5680|pmid=15643691}}</ref>. However, recent work has suggested that this mysterious structure is present in all mammals, with extensive connections to cortical and subcortical regions<ref>{{Cite journal|last=Buchanan|first=Kenneth J.|last2=Johnson|first2=John Irwin|date=2011-5|title=Diversity of spatial relationships of the claustrum and insula in branches of the mammalian radiation|url=https://www.ncbi.nlm.nih.gov/pubmed/21599698|journal=Annals of the New York Academy of Sciences|volume=1225 Suppl 1|pages=E30–63|doi=10.1111/j.1749-6632.2011.06022.x|issn=1749-6632|pmid=21599698}}</ref><ref>{{Cite journal|last=Grasby|first=Katrina|last2=Talk|first2=Andrew|date=2013-03-07|title=The anterior claustrum and spatial reversal learning in rats|url=https://www.ncbi.nlm.nih.gov/pubmed/23318254|journal=Brain Research|volume=1499|pages=43–52|doi=10.1016/j.brainres.2013.01.014|issn=1872-6240|pmid=23318254}}</ref>. More specifically, [[Electrophysiology|electrophysiological]] studies show extensive connections to [[List of thalamic nuclei|thalamic nuclei]] and the [[basal ganglia]], while isotopological reports have linked the claustrum with the prefrontal, frontal, parietal, temporal and occipital cortices<ref>{{Cite journal|date=2014-01-01|title=Physiology of the Claustrum|url=https://www.sciencedirect.com/science/article/pii/B9780124045668000052|journal=The Claustrum|language=en|pages=177–191|doi=10.1016/B978-0-12-404566-8.00005-2}}</ref><ref>{{Cite book|url=http://worldcat.org/oclc/861211388|title=The claustrum : structural, functional, and clinical neuroscience|last=S.|first=Smythies, John R. (John Raymond), 1922- Edelstein, Lawrence R. Ramachandran, V.|date=2014|publisher=Academic Press|isbn=9780124045668|oclc=861211388}}</ref>. 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<ref>{{Cite journal|last=Fernandez-Miranda|first=Juan C.|last2=Pathak|first2=Sudhir|last3=Engh|first3=Johnathan|last4=Jarbo|first4=Kevin|last5=Verstynen|first5=Timothy|last6=Yeh|first6=Fang-Cheng|last7=Wang|first7=Yibao|last8=Mintz|first8=Arlan|last9=Boada|first9=Fernando|date=2012-8|title=High-definition fiber tractography of the human brain:  neuroanatomical validation and neurosurgical applications|url=https://www.ncbi.nlm.nih.gov/pubmed/22513841|journal=Neurosurgery|volume=71|issue=2|pages=430–453|doi=10.1227/NEU.0b013e3182592faa|issn=1524-4040|pmid=22513841}}</ref>. Reciprocal connections also exist with motor, [[Somatosensory system|somatosensory]], [[auditory]] and visual cortical regions<ref name=":7" />. 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<ref>{{Cite journal|last=LeVay|first=S.|date=1986-12-01|title=Synaptic organization of claustral and geniculate afferents to the visual cortex of the cat|url=http://www.jneurosci.org/content/6/12/3564|journal=Journal of Neuroscience|language=en|volume=6|issue=12|pages=3564–3575|doi=10.1523/JNEUROSCI.06-12-03564.1986|issn=1529-2401|pmid=2432202}}</ref><ref>{{Cite journal|last=Zingg|first=Brian|last2=Hintiryan|first2=Houri|last3=Gou|first3=Lin|last4=Song|first4=Monica Y.|last5=Bay|first5=Maxwell|last6=Bienkowski|first6=Michael S.|last7=Foster|first7=Nicholas N.|last8=Yamashita|first8=Seita|last9=Bowman|first9=Ian|date=2014-02-27|title=Neural networks of the mouse neocortex|url=https://www.ncbi.nlm.nih.gov/pubmed/24581503|journal=Cell|volume=156|issue=5|pages=1096–1111|doi=10.1016/j.cell.2014.02.023|issn=1097-4172|pmc=PMC4169118|pmid=24581503}}</ref>.  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<ref name=":7" /><ref name=":9" /><ref>{{Cite journal|last=Markowitsch|first=H. J.|last2=Irle|first2=E.|last3=Bang-Olsen|first3=R.|last4=Flindt-Egebak|first4=P.|date=1984-6|title=Claustral efferents to the cat's limbic cortex studied with retrograde and anterograde tracing techniques|url=https://www.ncbi.nlm.nih.gov/pubmed/6462456|journal=Neuroscience|volume=12|issue=2|pages=409–425|issn=0306-4522|pmid=6462456}}</ref>.<sup> </sup> 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.
+===Internal Organization of the Claustrum===
+Inputs to the claustrum are organized by modality, which include visual, auditory and [[Somatomotor system|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<ref>{{Cite journal|last=Smith|first=Jared B.|last2=Alloway|first2=Kevin D.|date=2010-12-15|title=Functional specificity of claustrum connections in the rat: interhemispheric communication between specific parts of motor cortex|url=https://www.ncbi.nlm.nih.gov/pubmed/21159954|journal=The Journal of Neuroscience: The Official Journal of the Society for Neuroscience|volume=30|issue=50|pages=16832–16844|doi=10.1523/JNEUROSCI.4438-10.2010|issn=1529-2401|pmc=PMC3010244|pmid=21159954}}</ref><ref>{{Cite journal|last=Smith|first=Jared B.|last2=Alloway|first2=Kevin D.|date=2014|title=Interhemispheric claustral circuits coordinate sensory and motor cortical areas that regulate exploratory behaviors|url=https://www.ncbi.nlm.nih.gov/pubmed/24904315|journal=Frontiers in Systems Neuroscience|volume=8|pages=93|doi=10.3389/fnsys.2014.00093|issn=1662-5137|pmc=PMC4032913|pmid=24904315}}</ref>. 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 [[Topology|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<ref name=":7" />.
+===Neurons Within the Claustrum===
+The claustrum is made up of various cell types that differ in size, shape and neurochemical composition<ref name=":2" />. Five types of cells exist and the majority of these cells are structurally similar to [[Pyramidal cell|pyramidal neurons]] found in the cortex<ref name=":4" />. Within the claustrum, the somas of the cells can be found with a pyramidal, fusiform or circular shape<ref name=":0" />. 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<ref name=":0" />. 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<ref name=":3" />.
+== Function ==
+The claustrum has been shown to have widespread activity to numerous cortical components, all of which that 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 being 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=":0" />. This “conductor” notion can also be supported through connections between 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; through divisive normalization the claustrum may implement resistance to certain input modalities to prevent “distraction”.
+===Potential Function of the Claustrum===
+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). Using fMRI looks at oxygenated blood levels in the brain as a way of observing the activity of specific cortical areas. Observed dampened effects with fMRI when anesthetized versus awake in rats, specifically claustrum connections to the medial prefrontal cortex (mPFC) and the mediodorsol thalamus (MD thalamus). As well it has been found that the claustrum anatomically is connected with the contralateral hemispheres claustrum and has strong functional connections. Connections with MD thalamaus, mPFC, and surrounding and distant cortical areas also exist<ref name=":5" />.
+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 additionally supports the notion of an integration center from 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<ref name=":0" />.
+===Attention===
+The claustrum has the differential ability to select between task relevant information and task irrelevant information to provide directed attention. Per-unit volume in the cortex, it contains the highest density of connecting white matter tracts. This supports the notion of networking and coordination among different regions of the brain<ref name=":6" />. As well, the claustrum has regional specificity to it, information coming in from visual centers project to specific areas of the grey matter neurons in the structure. The same is said of the auditory cortex<ref name=":0" />. This is supported by unexpected stimuli inducing activation of the claustrum, suggesting an immediate focusing or allocation of function. In lower mammals (such as rats), claustral regions receive input from somatosensory modalities – this also supports as input from a “whisker” motor control perspective because of its sensory and discriminatory use in these mammals<ref name=":7" />.
+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 object and feature. 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 induce the prevention 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. Projections to motor and occulomotor areas for example would assist with gaze movement, to direct attention to new stimuli by increasing the firing frequency of claustral neurons<ref name=":7" />.
+Salvia divinorum is a derivative from a psychoactive plant that is capable of inducing loss of awareness<sup>3</sup>. Drug application (salvinorin A) will work on its respective Salvinorium A receptors to induce synesthesia, where different sensory modalities are interpreted by different sensory cortex’s – auditory sensation is smelt. This acts to support the idea of intrathalamic segregation and conduction (attention). The claustrum is saturated with Salvinorium A receptors, to which this chemical is capable of binding and eliciting this effect <ref name=":2" /><ref name=":7" />.
-</gallery>
+===Empirical Evidence===
-The claustrum is a subcortical structure.  It is a thin sheet of grey matter underneath the inner part of the [[neocortex]].  It is on both sides of the brain, and can be found between the insular cortex, which is deep to the temporal and parietal lobes at the deepest point of the [[lateral sulcus]], and the [[striatum]], which is a component of the [[basal ganglia]].<ref>{{cite journal|last1=Goll|first1=Y|last2=Atlan|first2=G|last3=Citri|first3=A|title=Attention: the claustrum.|journal=Trends in Neurosciences|date=August 2015|volume=38|issue=8|pages=486–95|pmid=26116988|doi=10.1016/j.tins.2015.05.006}}</ref> The sheet is approximately one to several millimeters thick, and can cover up to a couple centimeters in length, depending on the animal.
+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, suggesting some functional role relevant to consciousness<ref>{{Cite journal|date=1964-11-01|title=Alterations of behavior following stimulation of the claustrum of the cat|url=https://www.sciencedirect.com/science/article/abs/pii/0013469464901816|journal=Electroencephalography and Clinical Neurophysiology|language=en|volume=17|issue=5|pages=513–519|doi=10.1016/0013-4694(64)90181-6|issn=0013-4694}}</ref>. In humans this same effect can be observed. It has been reported that stimulation of the left claustrum in humans produced volitional behaviour, unresponsiveness and amnesia; also suggesting role involved in consciousness<ref name=":8" />. 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<ref>{{Cite journal|last=Silva|first=Guilherme|last2=Jacob|first2=Sylvia|last3=Melo|first3=Cláudia|last4=Alves|first4=Dílio|last5=Costa|first5=Dias|date=2018-6|title=Claustrum sign in a child with refractory status epilepticus after febrile illness: why does it happen?|url=https://www.ncbi.nlm.nih.gov/pubmed/28741106|journal=Acta Neurologica Belgica|volume=118|issue=2|pages=303–305|doi=10.1007/s13760-017-0820-9|issn=2240-2993|pmid=28741106}}</ref><ref>{{Cite journal|last=Meletti|first=Stefano|last2=Slonkova|first2=Jana|last3=Mareckova|first3=Iva|last4=Monti|first4=Giulia|last5=Specchio|first5=Nicola|last6=Hon|first6=Petr|last7=Giovannini|first7=Giada|last8=Marcian|first8=Vaclav|last9=Chiari|first9=Annalisa|date=2015-10-06|title=Claustrum damage and refractory status epilepticus following febrile illness|url=https://www.ncbi.nlm.nih.gov/pubmed/26341869|journal=Neurology|volume=85|issue=14|pages=1224–1232|doi=10.1212/WNL.0000000000001996|issn=1526-632X|pmc=PMC4607596|pmid=26341869}}</ref>. As well, increased signal intensity has has been found to be associated with Focal dyscognitive seizures; a seizure that does not involve convulsions yet elicits impairment of awareness or consciousness. The individual becomes unaware of his or her environment, and the seizure will manifest as blank or empty stare for a window of time. These show a role in consciousness and sustained attention by the claustrum.
+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 – suggesting and supporting a functional role in sustained attention<ref name=":1" />. 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=":3" />.
-In most parts of the brain, especially in the cortical regions, there is a considerable differentiation of cell types, giving way to a number of functions.  However, in the claustrum, as Dr. Crick and others pointed out, there are three main types of cells.<ref>{{cite journal |doi=10.1016/j.brainres.2007.05.011 |title=Neurochemically defined cell types in the claustrum of the cat |year=2007 |last1=Rahman |first1=Fahad E. |last2=Baizer |first2=Joan S. |journal=Brain Research |volume=1159 |pages=94–111 |pmid=17582386}}</ref>  The first, which is deemed Type 1, is large and covered with  [[dendritic spine]]s. These cells receive input as well as project back toward various regions, both laterally and medially.  The other two types of cells do not have spines, but can be told apart based on the cell body size.  However, both are restricted to the claustrum and, thus, are labeled [[interneurons]].
+===Lesions and Consciousness===
-It is clear that the claustrum projects to, and receives projections from, a number of cortices, including the primary motor, [[premotor]], [[prefrontal cortex|prefrontal]], [[Auditory system|auditory]], and [[visual]], among others.  In one study conducted in France by Judith Tanne-Gariepy et al. (9), these projections were traced back to segregated areas, including differentiated areas along the [[dorsoventral]] axis for the pre-supplementary motor area and supplementary motor area proper.  Projections from the claustrum to various sub-regions of the motor cortex were shown to overlap somewhat, but did show a degree of local segregation.<ref name="TanneGariepy" /><ref name="FernandexMiranda" />  The truly interesting thing about the claustrum, however, is how it can take in multiple information [[Modality (semiotics)|modalities]], including motor, visual, and auditory.  It has even been shown that the same cells can process information across all these types, even though there is some semblance of segregation across a single type of information.
+Functionally, the claustrum will integrate various cortical inputs through its connections, into one experience; 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<ref name=":2" />.
+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<ref name=":8" />. 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|last=Shapleske|first=Jane|last2=Rossell|first2=Susan L.|last3=Chitnis|first3=Xavier A.|last4=Suckling|first4=John|last5=Simmons|first5=Andrew|last6=Bullmore|first6=Edward T.|last7=Woodruff|first7=Peter W. R.|last8=David|first8=Anthony S.|date=2002-12|title=A computational morphometric MRI study of schizophrenia: effects of hallucinations|url=https://www.ncbi.nlm.nih.gov/pubmed/12427683|journal=Cerebral Cortex (New York, N.Y.: 1991)|volume=12|issue=12|pages=1331–1341|issn=1047-3211|pmid=12427683}}</ref>. Negative correlations between grey matter volume, and severity of hallucinations in the context of auditory hallucinations of schizophrenia has been supported<ref name=":10">{{Cite journal|date=2011-12-01|title=The insula–claustrum region and delusions in schizophrenia|url=https://www.sciencedirect.com/science/article/pii/S092099641100435X|journal=Schizophrenia Research|language=en|volume=133|issue=1-3|pages=77–81|doi=10.1016/j.schres.2011.08.004|issn=0920-9964}}</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=":0" />'''.'''
-There have also been a number of interesting studies looking at the proteins inside the
-claustrum.  In one experiment performed at the University of South Carolina by J.R. Augustine et al.,<ref>Augistine JR.  [[Calbindin|Calcium-binding proteins]] in the claustrum of the rhesus monkey. 2008.  Society for Neuroscience.  Program#/Poster#: 79.9/OO31</ref> researchers looked at [[Calbindin|calcium-binding proteins]] in the [[rhesus monkey]] claustrum, including [[Calbindin|calbindin D28K]], parvalbumin, and calretinin.  After removing the brains and properly preserving them, the group used various [[antibodies]] and [[antiserum]]s to detect the presence of the proteins.  The [[calbindin]] proteins were shown as likely elements in the inhibitory circuitry of the claustrum, while the calretinin most likely served as calcium buffer to maintain homeostasis. Another study looked at the serotonergic innervation in the claustrum.<ref>{{cite journal |doi=10.1016/S0361-9230(01)00535-4 |title=Serotonergic innervation of the primate claustrum |year=2001 |last1=Baizer |first1=J.S |journal=Brain Research Bulletin |volume=55 |issue=3 |pages=431–4 |pmid=11489351}}</ref>  The clear conclusion here was that, in the ventral claustrum where the visual projections are, the stained axons were short and arranged randomly.  However, in the dorsal, non-visual section of the claustrum, the fibers ran consistently in long lengths along the dorsal-ventral direction.  Like many of the other studies, this is a good first step toward determining the true functions of the claustrum, although there is still much room for work.
-==Function==
+== Animal Models ==
+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<ref name=":1" />. A variety of animal models have been used such as cats, rodents and monkeys.
-Very little is known about the actual function of the claustrum.  Anatomical hindrances combined with a lack of case studies have left many holes in the research on the claustrum. For these reasons, systematic studies of the claustrum have been sparse.{{citation needed|date=July 2014}}
+[[File:Anatomy of the cat (1991) (18167720666).jpg|thumb|229.965x229.965px|Anatomy of a [[Cat]] [[Brain]]]]
+===Cats===
-Although the exact function of the claustrum remains to be verified, connectivity studies have shown that the claustrum plays a strong role in communication between the two hemispheres of the brain, specifically between cortical regions controlling attention.<ref name="Alloway KD 2010"/>
+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"<ref name=":1" />. Recordings, primarily in cats and primates, show that claustral neurons respond to sensory stimuli and during voluntary movements<ref name=":3" />. Mapping from visual cortex to claustrum includes just a single map, which includes V1 and three other visual areas<sup>1</sup>. 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<ref name=":0" />.
+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<ref name=":7" />. 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 info based on motion in the visual field’s periphery and has no real selectivity<ref name=":7" />. 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<ref name=":7" />.
-Clinical evidence has suggested that the claustrum plays an important role in maintaining consciousness, potentially being usable as an "on-off switch". In 2014, a case was reported of one woman who became unresponsive when her claustrum was electrically stimulated, regaining responsiveness as soon as the stimulation stopped. The woman had no memory of the period during which she was unresponsive.<ref>{{cite web|url=https://www.newscientist.com/article/mg22329762.700#.U7dJq_ldWiV|title=Consciousness on-off switch discovered deep in brain|author=Helen Thomson|publisher=New Scientist|date=2 July 2014|accessdate=2014-07-04}}</ref><ref>{{cite journal|last1=Koubeissi|first1=Mohamad Z.|last2=Bartolomei|first2=Fabrice|last3=Beltagy|first3=Abdelrahman|last4=Picard|first4=Fabienne|title=Electrical stimulation of a small brain area reversibly disrupts consciousness|journal=Epilepsy & Behavior|volume=37|pages=32–35|doi=10.1016/j.yebeh.2014.05.027|pmid=24967698|date=Aug 2014}}</ref>
+[[File:Dynamics-of-place-boundary-and-object-encoding-in-rat-anterior-claustrum-Video 1.ogv|left|thumb|Dynamics of place boundary and object encoding in [[rat]] anterior claustrum. |alt=|251.997x251.997px]]
+===Rodents===
-Further evidence for a role of the claustrum in supporting consciousness comes from a recent [[resting state fMRI]]  study in awake versus anesthetized rodents.<ref>{{Cite journal|last=Smith|first=Jared B.|last2=Liang|first2=Zhifeng|last3=Watson|first3=Glenn D. R.|last4=Alloway|first4=Kevin D.|last5=Zhang|first5=Nanyin|date=July 2017|title=Interhemispheric resting-state functional connectivity of the claustrum in the awake and anesthetized states|journal=Brain Structure & Function|volume=222|issue=5|pages=2041–2058|doi=10.1007/s00429-016-1323-9|issn=1863-2661|pmc=5382132|pmid=27714529}}</ref> This study revealed strong interhemispheric functional connectivity from the claustrum with medial prefrontal cortex and mediodorsal thalamus in the awake state that are lost in the anesthetized state. This is the first study to identify the specific neural substrates by which the claustrum might promote consciousness.
+In rats, motor whisker areas receive input from the ipsilateral claustrum but will then project to the contralateral claustrum<ref name=":3" />. 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<ref name=":3" />.
+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<ref name=":3" />. 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<ref name=":3" />.
-===Integration of modalities===
-A number of different studies, summed up succinctly by [[Francis Crick|Crick]] and [[Christof Koch|Koch]], have suggested that the claustrum is essential in [[multisensory integration]].  Objects in real life have many different characteristics, such as sound, shape, color, speed, and smell. For example, the subject might both see a bird and hear it chirping, where the combination of visual and auditory stimuli will be perceived as being from the same source. We need to take in all of this information and integrate it correctly to perceive a single object.  "Binding" of various sensory modalities is essential to merge all the information of a single stimulus into a single [[percept]]. Crick and Koch suggest the claustrum might be involved in neural processes sub-serving perceptual binding.<ref name="Crick"/>
+Recent experiments in mice monitoring claustrocortical axonal activity to changing visual stimuli suggest the claustrum signals stimulus changes<ref name=":3" />. 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<ref name=":3" />
-Despite this hypothesis by Crick and Koch, a November 2010 study in primates reported that claustrum does not seem to be integrating information from multiple sensory modalities, but instead contains separated unimodal processing regions.<ref>{{cite journal |doi=10.1523/JNEUROSCI.2937-10.2010 |title=Unimodal Responses Prevail within the Multisensory Claustrum |year=2010 |last1=Remedios |first1=R. |last2=Logothetis |first2=N. K. |last3=Kayser |first3=C. |journal=Journal of Neuroscience |volume=30 |issue=39 |pages=12902–7 |pmid=20881109}}</ref> Furthermore, neuroanatomical tracing studies in rodents have shown the claustrum, though not involved in sensorimotor integration, is involved in sensorimotor coordination that is driven by dense inputs from the motor cortex.<ref>{{cite journal |doi=10.1523/JNEUROSCI.1524-12.2012 |title=Rat Claustrum Coordinates but Does Not Integrate Somatosensory and Motor Cortical Information |year=2012 |last1=Smith |first1=J. B. |last2=Radhakrishnan |first2=H. |last3=Alloway |first3=K. D. |journal=Journal of Neuroscience |volume=32 |issue=25 |pages=8583–8 |pmid=22723699 |pmc=3390683}}</ref><ref>{{Cite journal|last=Smith|first=Jared B.|last2=Alloway|first2=Kevin D.|date=2014|title=Interhemispheric claustral circuits coordinate sensory and motor cortical areas that regulate exploratory behaviors|journal=Frontiers in Systems Neuroscience|volume=8|pages=93|doi=10.3389/fnsys.2014.00093|issn=1662-5137|pmc=4032913|pmid=24904315}}</ref>
+===Monkeys===
+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<ref name=":0" />. 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<sup>1</sup>. Additionally, large or small types of aspiny are reported in the monkey brain, which are classified as “local circuit neurons"<ref name=":4" />.
+The dorsal claustrum has bi-directional connections with motor structures in the cortex<ref name=":0" />. 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<ref name=":0" />.
-A talk<ref>{{cite journal|last1=Torgerson|first1=Carinna M.|last2=Goh|first2=S. Y. Matthew|last3=Can Horn|first3=John Darrell|title=The DTI connectivity of the human claustrum|journal=Human Brain Mapping|volume=36|issue=3|pages=827–838|doi=10.1002/hbm.22667|pmid=25339630|language=English|pmc=4324054|year=2014}}</ref> presented 15 February 2017, at a [[BRAIN Initiative]] meeting in Bethesda, Maryland, described neurons in the mouse brain, which originate in the claustrum and "send out shoots that connect with other neurons throughout the organ. A new digital reconstruction method shows three neurons, termed "giant neurons", that branch extensively throughout the brain, including one that wraps around its entire outer layer.  The finding may help to explain how the brain creates consciousness."<ref>{{cite journal|last1=Reardon|first1=Sara|title=A giant neuron found wrapped around entire mouse brain|journal=Nature|date=March 2, 2017|volume=543|issue=7643|pages=14–15|doi=10.1038/nature.2017.21539|pmid=28252090|url=https://www.nature.com/news/a-giant-neuron-found-wrapped-around-entire-mouse-brain-1.21539|accessdate=7 March 2017|bibcode=2017Natur.543...14R}}</ref>
-==History==
+== Pathology ==
-The claustrum has been studied for nearly two centuries.<ref>{{cite journal |author=Edelstein LR, Denaro FJ |title=The claustrum: a historical review of its anatomy, physiology, cytochemistry and functional significance |journal=Cell. Mol. Biol. (Noisy-le-grand) |volume=50 |issue=6 |pages=675–702 |date=September 2004 |pmid=15643691}}</ref>  Historically, many researchers have viewed it as an interesting structure that could hold the key to a number of neuroscientific questions. The claustrum has a phylogenetic background appearing predominantly in [[insectivore]]s, [[Strepsirrhini|strepsirrhine]] primates, and [[marsupial]]s. It is difficult to trace where the evolution of the structure originated.{{Citation needed|date=December 2014}}
+===Schizophrenia===
-One big point of discussion with regard to the claustrum has been on the [[ontogeny]]. One side, which Dr. Edelstein deems the pallial group, believes the claustrum is a derivative of the insular cortex. While some designated this as a certain distinguished area not to be confused with the rest of the cortex, they still ascertained that the ontogeny was based on the development of the cortex. The other side states that the claustrum is derived from basal ganglia. Ramon y Cajal supported this latter theory, as did many other researchers.<ref>Mathur BN. A comparative analysis of claustrum anatomy. 2008. Society for Neuroscience.  Program#/Poster#: 79.11/OO33</ref>  Based on more recent methods of looking at the development of both the human and animal mind, including [[fMRI]] among others, there has been increasing evidence against the claustrum being a part of the cortex. They seem to have distinct developmental periods and are, therefore, deemed separate structures. The third theory, which is supported by the majority at present, says that the claustrum is neither distinctly part of the cortex nor from the [[basal ganglia]] complex. Based on a number of studies, including those that show projections on both sides of the claustrum, many believe the claustrum should be considered a seventh layer of the cortex, in the insular region.<ref name="TanneGariepy">{{cite journal |doi=10.1002/cne.10425 |title=Projections of the claustrum to the primary motor, premotor, and prefrontal cortices in the macaque monkey |year=2002 |last1=Tanné-Gariépy |first1=Judith |last2=Boussaoud |first2=Driss |last3=Rouiller |first3=Eric M. |journal=The Journal of Comparative Neurology |volume=454 |issue=2 |pages=140–57 |pmid=12412139}}</ref>  This hypothesis, which is growing support, including the aforementioned Dr. Larry Edelstein, is labeled as Filiminoff's hypothesis since he was estimated to be the first to come to this conclusion.<ref name="FernandexMiranda">{{cite journal |doi=10.3171/JNS/2008/108/4/0764 |title=The claustrum and its projection system in the human brain: A microsurgical and tractographic anatomical study |year=2008 |last1=Fernández-Miranda |first1=Juan C. |last2=Rhoton |first2=Albert L. |last3=Kakizawa |first3=Yukinari |last4=Choi |first4=Chanyoung |last5=Álvarez-Linera |first5=Juan |journal=Journal of Neurosurgery |volume=108 |issue=4 |pages=764–74 |pmid=18377257}}</ref> A fourth theory, known as the "claustroamygdalar DVR hypothesis" suggests that the reptilian dorsal ventricular ridge (DVR) is homologous to the claustrum and basolateral amygdala, suggesting a closer relationship of the claustrum to the amygdala rather than insular cortex or basal ganglia.<ref>{{Cite book|title=Principles of Brain Evolution|last=Striedter|first=Georg|publisher=Sinauer Associates, Inc|year=2005|isbn=978-0-87893-820-9|location=|pages=274–283}}</ref>
+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<ref name=":10" />.
+[[File:New-Onset-Refractory-Status-Epilepticus-with-Claustrum-Damage-Definition-of-the-Clinical-and-Video 1.ogv|thumb|225x225px|New Onset Refractory Status [[Epileptic seizure|Epilepticus]] with Claustrum Damage|alt=]]
+===Epilepsy===
-There are few historical cases that shed light on the anatomy and function of the claustrum.  There was one documented case on an enlarged claustrum in a patient with epilepsy, as well as another case in which the insula was malformed but the claustrum remained.  These cases have not lent very much toward the pursuit of truth regarding the claustrum.  At this point in time, pathology involved with the claustrum remains unknown.  Also, due to the location and complex integration of the claustrum with other parts of the brain, it is difficult to do lesion studies without affecting other regions.  Likewise, ablation is not an effective option, either.  Most studies involve either the removal and preservation of the brain or [[in vivo]] scanning of the area of interest during different studies.  This could involve [[fMRI]], the newer [[Tractography]] technology, or others.
+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 KA seizures (Kainic-Acid induced seizures)<ref name=":1" />.
-===Etymology===
+===Conciousness===
+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<ref name=":2" /><ref name=":8" />. 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<ref name=":2" />. 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<ref name=":7" />.
-The name "claustrum" comes from Latin [ME. cloistre, a. OF. cloistre, earlier clostre:—L. claustr-um, clōstr-um, ‘a bar, bolt, lock’, later ‘a shut up place, a cloister’, f. claud-, claus- to shut + -trum instrumental suffix. Before the adoption of the French form, OE. had already clauster and clústor from Latin, and ME. had also closter, and clowster.] .<ref>{{cite web|url=http://www.oed.com|publisher=OUP |date= |accessdate=2015-01-29|title=OED}}</ref>
 ==References==