The Claustrum: Structural, Functional, and Clinical Neuroscience

The present day is witnessing an explosion of our understanding of how the brain works at all levels, in which complexity is piled on complexity, and mechanisms of astonishing elegance are being continually discovered. This process is most developed in the major areas of the brain, such as the cortex, thalamus, and striatum. The Claustrum instead focuses on a small, remote, and, until recently, relatively unknown area of the brain. In recent years, researchers have come to believe that the claustrum is concerned with consciousness, a bold hypothesis supported by the claustrum’s two-way connections with nearly every other region of the brain and its seeming involvement with multisensory integrations―the hallmark of consciousness. The claustrum, previously in a humble position at the back of the stage, might in fact be the conductor of the brain’s orchestra.

The Claustrum brings together leading experts on the claustrum from the varied disciplines of neuroscience, providing a state-of-the-art presentation of what is currently known about the claustrum, promising lines of current research (including epigenetics), and projections of new lines of investigation on the horizon.

• Develops a unifying hypothesis about the claustrum’s role in consciousness, as well as the integration of sensory information and other higher brain functions
• Discusses the involvement of the claustrum with autism, schizophrenia, epilepsy, Alzheimer’s disease, and Parkinson’s disease
• Coverage of all aspects of the claustrum, from its evolution and development to promising new lines of research, including epigenetics, provides a platform and point of reference for future investigative efforts

John Smythies is a neuropsychiatrist and neuroscientist and has made significant contributions to both these disciplines. Together with Humphrey Osmond he developed the first biochemical theory of schizophrenia―the transmethylation hypothesis. This has recently come back into focus following the finding that DNA methylation is abnormal in schizophrenia. He has made extensive contributions to knowledge in a number of fields including the neuropharmacology of psychedelic drugs; the functional neuroanatomy of synapses with particular regard to the role of synaptic plasticity, endocytosis and redox factors ; the role in the brain of orthoquinone metabolites of catecholamines; and, in particular, theories of brain-consciousness relations. More recently he has worked on epigenetic processes in information processing in the brain, and the functional neuroanatomy of the claustrum. Smythies has served as President of the International Society of Psychoneuroendocrinology from 1970-1974, Consultant to the World Health Organization from 1963-1968, and Editor of the International Review of Neurobiology from 1958-1991. He was elected a member of the Athenaeum in 1968. He has published over 240 scientific papers and sixteen books. Smythies has held positions as the Charles Byron Ireland Professor of Psychiatric Research at the University of Alabama Medical Center at Birmingham, Visiting Scholar at the Center for Brain and Cognition, University of California San Diego, and Senior Research Fellow at the Institute of Neurology, University College London.

Spring semester 1974, State University of New York at Stony Brook, “Introduction to Physiological Psychology,” Professor John Stamm (mentor and frontal lobe physiologist par excellence). “Essentials of Physiological Psychology,” by Sebastian P. Grossman. As a significant percentage of our final grade, we were tasked with submitting a term paper on the brain structure of our choosing, to be selected from those mentioned in our textbook. Owing to an already burdensome semester with numerous finals in the air, I immediately went to work looking for that part of the brain to which was paid the least attention, in essence, the Rodney Dangerfield of the CNS. Hippocampus? Fuhgeddaboudit. Amygdala? Fight or flight; I chose the latter. Claustrum – function unknown; barely made the index. Clearly, it got no respect. The seed was planted, eventually sprouting into a doctoral thesis: “The anatomy of the claustrum: A light and electron-microscopic analysis in rat and monkey incorporating the technique of HRP cytochemistry.”

I moved to San Diego in late 2001, the claustrum something I once dabbled with in the distant past. Cut to September 27, 2004 and the live-streamed public memorial held at The Salk Institute for Francis Crick. Although I was long into a new career and deskbound at the time, I felt the need to somehow be a part of this event, if only as a virtual observer. Thick with notables, Nobelists (and those to be) and molecular biology, I watched and listened with rapt attention as V.S. Ramachandran took the podium and proceeded to eloquently honor a close friend and esteemed colleague. Somewhere in the middle of his tribute I learned of Francis’ interest in the claustrum, at which point my jaw dropped rather precipitously, and a few choice unmentionables were uttered upon return to its normal position. A comprehensive review paper followed shortly thereafter, co-authored with my long-time friend and fellow claustrophile, Professor Frank Denaro. For some time prior to his passing, Francis Crick, along with his brilliant Caltech colleague-in-arms, Christof Koch, had honed in on the very same slab of grey matter as I did thirty years prior, and found it to be as salient a stimulus, with mysteries yet to be revealed.

Nearly forty years on, I’m still working on that term paper. However, thanks to Francis, Christof, my fortuitously catching that live-stream, and subsequently befriending my esteemed UCSD colleagues John Smythies and Rama, I can safely say that I chose wisely. And the title of what was fated to be Francis’ final publication? “What is the function of the claustrum?”

Dr. Edelstein is the Editor-in-Chief of Claustrum, a peer-reviewed, open access journal, conceived as a nexus for all things pertaining to the claustrum. For more info, visit www.claustrumresearch.net.

V. S. Ramachandran is Director of the Center for Brain and Cognition and Distinguished Professor with the Psychology Department and Neurosciences Program at the University of California, San Diego, and Adjunct Professor of Biology at the Salk Institute. Ramachandran initially trained as a doctor and subsequently obtained a Ph.D. from Trinity College at the University of Cambridge. Ramachandran's early work was on visual perception but he is best known for his experiments in behavioral neurology which, despite their apparent simplicity, have had a profound impact on the way we think about the brain. He has been called "The Marco Polo of neuroscience" by Richard Dawkins and "The modern Paul Broca" by Eric Kandel.

In 2005 he was awarded the Henry Dale Medal and elected to an honorary life membership by the Royal Institution of Great Britain, where he also gave a Friday evening discourse (joining the ranks of Michael Faraday, Thomas Huxley, Humphry Davy, and dozens of Nobel Laureates). His other honors and awards include fellowships from All Souls College, Oxford, and from Stanford University (Hilgard Visiting Professor); the Presidential Lecture Award from the American Academy of Neurology, two honorary doctorates, the annual Ramon Y Cajal award from the International Neuropsychiatry Society, and the Ariens-Kappers medal from the Royal Netherlands Academy of Sciences. In 2003 he gave the annual BBC Reith lectures and was the first physician/psychologist to give the lectures since they were begun by Bertrand Russel in 1949. In 1995 he gave the Decade of the Brain lecture at the 25th annual (Silver Jubilee) meeting of the Society for Neuroscience. In 2010 he delivered the annual Jawaharlal Nehru memorial lecture in New Delhi, India. Most recently the President of India conferred on him the second highest civilian award and honorific title in India, the Padma Bhushan. And TIME magazine named him on their list of the 100 most influential people in the world in 2011.

Ramachandran has published over 180 papers in scientific journals (including five invited review articles in the Scientific American). He is author of the acclaimed book "Phantoms in the Brain" that has been translated into nine languages and formed the basis for a two part series on Channel Four TV (UK) and a 1 hour PBS special in USA. NEWSWEEK magazine has named him a member of "The Century Club" one of the "hundred most prominent people to watch in the next century." He has been profiled in the New Yorker Magazine and appeared on the Charlie Rose Show. His book, "The Tell Tale Brain" is a New York Times best-seller.