Human lesions and animal studies link the claustrum to perception, salience, sleep and pain
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Table of Contents
Annotations for: Human lesions and animal studies link the claustrum to perception, salience, sleep and pain
✅ Key Points
The claustrum is the most densely interconnected region in the human brain. [@atilganHumanLesionsAnimal2022, p. 1610]
Despite the accumulating data from clinical and experimental studies, the functional role of the claustrum remains unknown [@atilganHumanLesionsAnimal2022, p. 1610]
Conversely, the lesions studies support the hypothesis that the claustrum regulates cortical excitability. We argue that the claustrum is connected to, or part of, multiple brain networks that perform both fundamental and higher cognitive functions. [@atilganHumanLesionsAnimal2022, p. 1610]
The claustrum is a sheet-like bilateral brain region tucked beneath the insular cortex [@atilganHumanLesionsAnimal2022, p. 1610]
Unfortunately, lesions to the human claustrum are rarely specific due to its anatomy and bilateral location. [@atilganHumanLesionsAnimal2022, p. 1618]
Background
Claustral lesions are associated with an array of signs and symptoms, including changes in cognitive, perceptual and motor abilities; electrical activity; mental state; and sleep. [@atilganHumanLesionsAnimal2022, p. 1610]
The claustrum is a sheet-like bilateral brain region tucked beneath the insular cortex [@atilganHumanLesionsAnimal2022, p. 1610]
Strong reciprocal connectivity with most neocortical areas is perhaps the most noteworthy feature of the claustrum [@atilganHumanLesionsAnimal2022, p. 1610]
Understanding the anatomy and connectivity of a brain region can provide important insights into its function. [@atilganHumanLesionsAnimal2022, p. 1611]
The claustrum has been implicated in processes including the amplification of cortical oscillations,28,29 attentional allocation,2,4,26,30 consciousness,16,31 cognition,6 spatial navigation,32 the transfer of information across sensory modalities,33 sexual function,34 and aesthetic judgement.35 [@atilganHumanLesionsAnimal2022, p. 1611]
Hypothesis
review claustrum lesion studies and discuss their functional implications. [@atilganHumanLesionsAnimal2022, p. 1610]
To our knowledge no review has comprehensively assessed clinical studies of human claustrum lesions. [@atilganHumanLesionsAnimal2022, p. 1611]
we present a meta-analysis of all studies to date that describe cases of claustrum lesions in human patients. [@atilganHumanLesionsAnimal2022, p. 1611]
Methods
To tackle this, we examined claustrum lesion cases by searching the following terms on PubMed and Scopus: ‘claustrum AND (lesion OR contusion OR injury OR trauma)’ (n = 103). Studies were then screened for cases in which reported lesions included the claustrum according to neuroimaging. Thirty-eight individual cases (Supplementary Tables 1 and 2) and 14 cohort studies (Supplementary Table 3) were included in this review. [@atilganHumanLesionsAnimal2022, p. 1611]
Results
Claustrum lesions resulted in numerous symptoms including disturbances in cognitive function, perceptual and motor abilities, mental state, electrical activity, sleep, and pain. [@atilganHumanLesionsAnimal2022, p. 1618]
At first, it seems difficult to reconcile these diverse findings and potential functions. [@atilganHumanLesionsAnimal2022, p. 1618]
Rather than performing a single function, the claustrum may instead play multiple intersecting roles that underlie the diverse range of disruptions observed following claustrum lesions. [@atilganHumanLesionsAnimal2022, p. 1618]
Among the diverse consequences of claustrum lesions, we observed a strikingly high incidence of seizures. [@atilganHumanLesionsAnimal2022, p. 1618]
Conclusions
Conversely, the lesions studies support the hypothesis that the claustrum regulates cortical excitability. [@atilganHumanLesionsAnimal2022, p. 1610]
We argue that the claustrum is connected to, or part of, multiple brain networks that perform both fundamental and higher cognitive functions. [@atilganHumanLesionsAnimal2022, p. 1610]
claustrum lesions lead to a wide range of signs and symptoms. [@atilganHumanLesionsAnimal2022, p. 1611]
Most commonly, patients experienced impairments in different levels of cognitive, perceptual, and motor abilities, as well as seizures and disturbances to mental state and sleep. [@atilganHumanLesionsAnimal2022, p. 1611]
we consolidate evidence concerning the claustrum’s role in sensory perception, sleep, pain, and salience, and facilitate a critical re-evaluation of existing hypotheses of the claustrum’s function. [@atilganHumanLesionsAnimal2022, p. 1611]
Our results do not support prominent hypothesized functions such as multisensory integration and salience processing, [@atilganHumanLesionsAnimal2022, p. 1611]
Further research will be required to understand if this increased risk of seizures is specific to the claustrum, or whether similar results would be obtained from any such large disruption of brain connectivity. [@atilganHumanLesionsAnimal2022, p. 1618]
These diverse findings suggest a far-reaching function for the claustrum [@atilganHumanLesionsAnimal2022, p. 1618]
The lesion studies described above do not lend conclusive support to any one theory of the claustrum’s function [@atilganHumanLesionsAnimal2022, p. 1618]
In neuroscience, we are often tempted to conclude that a brain region or cell type is responsible for a specific function, but this does not always generate understanding. The claustrum is a brain structure where this strategy is particularly unhelpful, urging us to rethink our approach both methodologically and conceptually. [@atilganHumanLesionsAnimal2022, p. 1618]
Implications
We hypothesize that the claustrum is connected to, or is a part of, many different networks, and propose that the brain-wide connectivity of the claustrum may have provided a useful scaffold onto which many functional roles could subsequently be built. [@atilganHumanLesionsAnimal2022, p. 1611]
It remains possible that the claustrum underlies many discrete functions and/or possesses a, so far, unidentified global function that ties together these disparate findings [@atilganHumanLesionsAnimal2022, p. 1618]
Further Reading
One possibility is to continue work on the claustrum across species, which has already usefully spanned reptiles, rodents, rabbits, cats, monkeys, and humans [@atilganHumanLesionsAnimal2022, p. 1618]
Annotations
(04/10/2023, 07:38:35 )
CLA excitatory regulation is a main hypothesis here
“regulating cortical excitability” (Atilgan et al., 2022, p. 1618)
“In neuroscience, we are often tempted to conclude that a brain region or cell type is responsible for a specific function, but this does not always generate understanding” (Atilgan et al., 2022, p. 1618)
“The CLA connections is the most densely interconnected region in the human brain”
(Atilgan et al., 2022, p. 1610)
CLA lesion associated with an array of signs and symptoms, including changes in cognitive, perceptual and Motor abilities; electrical activity; mental state; and sleep.”
(Atilgan et al., 2022, p. 1610)
The extensive symptoms after lesions do not seem to support important theories as CLA sensory integration or the CLA salience computation
“The wide range of symptoms observed following claustral lesions do not provide compelling evidence to support prominent current theories of claustrum function such as multisensory integration or salience computation” (Atilgan et al., 2022, p. 1610)
lesion studies “do not provide strong evidence for prominent theories such as multisensory integration and salience processing while lending support to other theories such as the regulation of cortical excitability” (Atilgan et al., 2022, p. 1618)
CLA excitatory regulation: CLA lesion “support the hypothesis that the claustrum regulates cortical excitability” (Atilgan et al., 2022, p. 1610)
CLA connections: Connecting or part of various brain networks, involved in fundamental and higher cognitive functions
“we argue that the claustrum is connected to, or part of, multiple brain networks that perform both fundamental and higher cognitive functions” (Atilgan et al., 2022, p. 1610)
!500
CLA lesion studies show various symptoms such as “disturbances in cognitive function, perceptual and motor abilities, mental state, electrical activity, sleep, and pain”
“lesions resulted in numerous symptoms including disturbances in cognitive function, perceptual and motor abilities, mental state, electrical activity, sleep, and pain” (Atilgan et al., 2022, p. 1618)
“Rather than performing a single function, the claustrum may instead play multiple intersecting roles that underlie the diverse range of disruptions observed following” CLA lesion
(Atilgan et al., 2022, p. 1618) -> difficulty to differentiale from other brain areas
Claim that high CLA connections might serve fundamental reasons (CLA evolution)
“widespread connectivity substrate provided by the claustrum may have initially developed for evolutionarily ancient and fundamental functions” (Atilgan et al., 2022, p. 1618)
- Yes, but what should have been the role?
“Putative claustra have been described in all extant mammals, but the claustrum is likely far older.” (Atilgan et al., 2022, p. 1618)
Sleep linked to claustrum in separated species (CLA sleep)
“Sleep, one of the most ancient neural processes, has been linked to the claustrum in species separated by hundreds of millions of years of evolution” (Atilgan et al., 2022, p. 1618) -> What Sleep phases
CLA sleep: “Jansen et al.77 linked the claustrum to insomnia in humans”
(Atilgan et al., 2022, p. 1618)
CLA sleep: “it is clear that the early claustrum was involved in some facet of sleep”
(Atilgan et al., 2022, p. 1618)
Apparently increased risk of seizure
“Further research will be required to understand if this increased risk of seizures is specific to the claustrum, or whether similar results would be obtained from any such large disruption of brain connectivity.” (Atilgan et al., 2022, p. 1618)
“lesions to the human claustrum are rarely specific due to its anat- omy and bilateral location”
(Atilgan et al., 2022, p. 1618)
CLA lesion “lesions inevitably impact neighboring areas”
(Atilgan et al., 2022, p. 1618)
Argument for claustrum not being involved in low-level sensory processing
“While recent anatomical findings exclude the claustrum from some functions such as low-level sensory processing (given the lack of inputs from sensory thalamic nuclei and sparse inputs from primary sensory cortices) and direct generation and/or modi- fication of motor output (given lack of connectivity with striatum), research has not yet yielded a conclusive function for the claustrum” (Atilgan et al., 2022, p. 1618)