Cytoarchitectonic mapping of the human claustrum

2014

In 1786, the French anatomist Felix Vicq d’Azyr published his monumental in-folio treatise on the human brain, in which the claustrum was first identified. Macroscopically, it is a rather extensive yet thin sheet-like aggregate of neurons tucked beneath the insular cortex, sandwiched between the external and extreme capsules of the mammalian brain. Two-hundred-and-nineteen years later, Francis Crick and his colleague, Christof Koch, published their seminal paper entitled “What is the function of the claustrum?” (Crick and Koch, 2005). Their paper contains an extensive review of the existing anatomical and physiological data relating to the claustrum’s reciprocal connectivity with nearly all areas of the cerebral cortex, as well as many subcortical areas. In particular, they stressed the importance of there being far fewer claustral neurons (estimated at 16 million; Braak and Braak, 1982) than the 10 billion or so occupying the cerebral cortex (Shepherd, 1998). This results in a major convergence and condensation in the corticoclaustral pathway, and a corresponding divergence in the reciprocal claustrocortical pathway. Crick and Koch concluded that the claustrum is ideally situated with regard to its connectivity with each of the primary sensory cortices to best function as a neural correlate of consciousness, thereby serving to bind the never-ending influx of sensory information and return it from whence it came for higher-level processing demands in an efficient and energy-conserving manner. They further suggested that the claustrum supports “flows of information” in which GABAergic mechanisms play a prominent role. Additionally, they posited that claustral neurons could be “especially sensitive to the timing of neurons.” However, they did not offer any precise mechanisms to perform these functions. Our intention is to provide the neuroscience audience with what will be the first book solely devoted to the claustrum. In fact, to our knowledge, there are no other published efforts (either as a journal article, book chapter or symposium) which aim to provide their audience with such an all-encompassing and leading-edge perspective on this structure. The various topics to be covered in our book - each addressed in chapters written by highly regarded neuroscientists with substantive knowledge of the claustrum and related structures - are what one would expect from such an exhaustive undertaking. As well, we will offer a venue for the development of unifying hypotheses and critical insights from a variety of experts as to the claustrum’s role in consciousness, as well as the integration of sensory information and other higher brain functions. We have noticed a steadily growing interest in the areas of cross-modal processing and multisensory integration amongst the neuroscience, neurology and neuropsychiatric community, particularly as it relates to higher-level visual and auditory processing, as well as the investigation of neural correlates of consciousness. In addition, with the explosive growth and advances in the use of fMRI and DTI, the claustrum has been clearly implicated in the development and sequelae of such debilitating disorders as autism, schizophrenia, Alzheimer's disease, and Parkinson's disease. We believe that the time has come for a book which concisely compiles and organizes all of the extant information on this enigmatic yet highly understudied brain structure, at the same time providing its audience with the first comprehensively researched hypothesis as to its function, therein providing a platform and point of reference for future investigative efforts. We envision our readership to be neuroscientists, neurologists, neuropsychiatrists, neuropsychologists and advanced students, our intention being to bring basic researchers up to speed on all things claustral in one fell swoop, while simultaneously providing our collective audience with the first comprehensively researched and evaluated hypothesis as to its function.

Cerebral Cortex Communications

The claustrum is a thin sheet of neurons enclosed by white matter and situated between the insula and the putamen. It is highly interconnected with sensory, frontal, and subcortical regions. The deep location of the claustrum, with its fine structure, has limited the degree to which it could be studied in vivo. Particularly in humans, identifying the claustrum using magnetic resonance imaging (MRI) is extremely challenging, even manually. Therefore, automatic segmentation of the claustrum is an invaluable step toward enabling extensive and reproducible research of the anatomy and function of the human claustrum. In this study, we developed an automatic algorithm for segmenting the human dorsal claustrum in vivo using high-resolution MRI. Using this algorithm, we segmented the dorsal claustrum bilaterally in 1068 subjects of the Human Connectome Project Young Adult dataset, a publicly available high-resolution MRI dataset. We found good agreement between the automatic and manual segm...

Cerebral cortex (New York, N.Y. : 1991), 2015

The claustrum is a thin layer of gray matter that is at the center of an active scientific debate. Recently, Constrained Spherical Deconvolution (CSD) tractography has proved to be an extraordinary tool allowing to track white matter fibers from cortex to cortical and subcortical targets with subvoxel resolution. The aim of this study was to evaluate claustral connectivity in the human brain. Ten normal brains were analyzed by using the High Angular Resolution Diffusion Imaging CSD-based technique. Tractography revealed 4 groups of white matter fibers connecting the claustrum with the brain cortex: Anterior, posterior, superior, and lateral. The anterior and posterior cortico-claustral tracts connected the claustrum to prefrontal cortex and visual areas. The superior tract linked the claustrum with sensory-motor areas, while the lateral pathway connected the claustrum to the auditory cortex. In addition, we demonstrated a claustral medial pathway connecting the claustrum with the ba...

2021

The claustrum is the most densely interconnected region in the human brain. Despite the accumulating data from clinical and experimental studies, the functional role(s) of the claustrum remain unknown. Here, we systematically review claustrum lesion studies and discuss their functional implications. 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. The wide range of symptoms observed following claustral lesions suggests that the claustrum may either have a number of distinct functions, or a global function that impacts many neural processes. We further discuss the implications of these lesions in the context of recent evidence linking the claustrum to sensory perception, sleep, and salience as well as highlighting an underexplored link between the claustrum and pain. We hypothesize that the claustrum is connected to multiple brain networks, both ancient a...

2019

The claustrum is an irregular and fine sheet of grey matter in the basolateral telencephalon present in almost all mammals. The claustrum has been the object of several studies using animal models and more recently in human beings using neuroimaging. Believed to be involved in cognition and disease such as fear recognition, suppression of natural urges, multisensory integration, conceptual integration, seizures, multiple sclerosis, and Parkinson’s disease. Nevertheless, the function of the claustrum still remains unclear. We present a functional connectivity study of the claustrum in order to identify its main networks. Resting state functional and anatomical MRI data from 100 healthy subjects were analyzed; taken from the Human Connectome Project (HCP, NIH Blueprint: The Human Connectome Project), with 2×2×2 mm3 voxel resolution. Positive functional connectivity was found (p<0.05, FDR corrected) between the claustrum and the insula, anterior cingulate cortex, pre-central and pos...

Frontiers in Systems Neuroscience, 2014

Cellular and Molecular Biology, 2004

The claustrum (Cl) is a subcortical structure located in the basolateral telencephalon of the mammalian brain. It has been a subject of inquiry since the mid-nineteenth century. The Cl can be identified in a number of species, and appears as a phylogenetically related nucleus in Insectivores, Prosimians and Marsupials. Ontogenetic investigations have been the subject of much debate over the years. There are three hypotheses for claustral development. To date, the "hybrid theory" has garnered the most support. Pathological conditions specifically associated with the Cl, while few in number, are of interest from a functional perspective. Several cases of claustral agenesis have been reported. The implications of these clinical reports are discussed. Claustral neuroanatomy at the lightmicroscopic and electron-microscopic level is reviewed. The morphology of the claustral neuron consists of several types, which roughly corresponds to the neuron's location within distinct claustral subdivisions. The interconnectivity of the Cl with the cerebral cortex is rather complex and reflective of complex functional interrelationships. Several researchers have investigated the angioarchitecture of the Cl. It appears that vessels permeating the insula also vascularize the Cl. Literature investigating the neurotransmitters and overall chemical neuroanatomy of the Cl is extensive. These studies clearly demonstrate that the Cl is richly innervated with a wide and diverse array of neurotransmitters and neuromodulators. Lesion, stimulation and recording experiments demonstrate that the functional and physiologic capacity of the Cl is quite robust. A recurring theme of claustral function appears to be its involvement in sensorimotor integration. This may be expected of the Cl, given the degree of heterotopic, heterosensory convergence and its interconnectivity with the key subcortical nuclei and sensory cortical areas. The Cl remains a poorly understood and under investigated nucleus. Therefore, a review of the world literature through 1986 prior to the advent of the "molecular revolution" is presented. This diverse and extensive body of knowledge is reviewed in the areas of phylogeny, ontogeny, pathology, angioarchitecture, cytochemistry, anatomy and physiology. Theories of possible claustral function are also noted. It is hoped that this work will stimulate research scientists to further investigate the functional interrelationships of the Cl as well as to aim with far greater precision and accuracy towards a deeper understanding of its raison d'etre. The recent efforts in neurosciences by Sir Francis Crick and Christof Koch implicating the Cl in visual consciousness, is an important step in understanding just what its functions could encompass. Efforts in molecular neurosciences will be indispensable for a mechanistic understanding of these functions. Currently research efforts are underway from many perspectives. In considering the past scientific literature on the Cl, it is interesting to regard that this once obscure brain structure, may serve as a model system for the study of one of the most interesting and complex brain functions -consciousness.

Microscopy and Microanalysis, 2023

With current neuroanatomical molecular techniques, further insight has developed in terms of the Cl’s functional contributions. Even so, species differences and their analysis remain important. For example, one criticism of the Cl-consciousness hypothesis is that while all mammals may have a Cl, not all are believed to experience consciousness, at least in the context of the human experience. But perhaps this criticism misses the point. The Cl may indeed be functioning in the same way but differences in overall neuroanatomy (e.g., different patterns of cortical development) will result in physiologic and cognitive processes that do not lead to consciousness, per se. The Cl functions for the species-specific needs of a given animal through alternate types of information integration.

Frontiers in Neuroanatomy, 2019

Frontiers in systems neuroscience, 2014

We examined the pattern of retrograde tracer distribution in the claustrum following intracortical injections into the frontal pole (area 10), and in dorsal (area 9), and ventral lateral (area 12) regions of the rostral prefrontal cortex in the tufted capuchin monkey (Cebus apella). The resulting pattern of labeled cells was assessed in relation to the three-dimensional geometry of the claustrum, as well as recent reports of claustrum-prefrontal connections in other primates. Claustrum-prefrontal projections were extensive, and largely concentrated in the ventral half of the claustrum, especially in the rostral 2/3 of the nucleus. Our data are consistent with a topographic arrangement of claustrum-cortical connections in which prefrontal and association cortices receive connections largely from the rostral and medial claustrum. Comparative aspects of claustrum-prefrontal topography across primate species and the implications of claustrum connectivity for understanding of cortical fu...