Table Of ContentTHE
CLAUSTRUM
Structural, Functional, and
Clinical Neuroscience
Edited by
John R. Smythies
Lawrence R. Edelstein
Vilayanur S. Ramachandran
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14 15 16 17 10 9 8 7 6 5 4 3 2 1
List of Contributors
Joan Susan Baizer Department of Physiology and Biophysics, University of
Buffalo, NY, USA
W. Ted Brown Department of Human Genetics, NYS Institute for Basic
Research in Developmental Disabilities, Staten Island, NY, USA
Nicola G. Cascella Neuropsychiatry Program, Sheppard Pratt Hospital,
Baltimore, MD, USA
Michael E. Corcoran Department of Anatomy, and Cell Biology, University of
Saskatchewan, Saskatoon, Canada
Rastislav Druga Institute of Anatomy, 2nd Medical Faculty, Charles University,
Prague, Czech Republic
Lawrence R. Edelstein Medimark Corporation, Del Mar, CA, USA
Brian A. Fenske Department of Radiology, Division of Human Anatomy,
Michigan State University, East Lansing, MI, USA
Juan C. Fernandez-Miranda Department of Neurological Surgery, University
of Pittsburgh Medical Center, Pittsburgh, PA, USA
Michael Flory Department of Infant Development, NYS Institute for Basic
Research in Developmental Disabilities, Staten Island, NY, USA
Alex O. Holcombe School of Psychology, University of Sydney, NSW, Australia
Humi Imaki Department of Developmental Neurobiology, NYS Institute for
Basic Research in Developmental Disabilities, Staten Island, NY, USA
John Irwin Johnson Department of Radiology, Division of Human Anatomy,
Michigan State University, East Lansing, MI, USA
Michail E. Kalaitzakis Neuropathology Unit, Division of Brain Sciences,
Department of Medicine, Imperial College London, UK
Przemysław Kowiański Department of Anatomy and Neurobiology, Medical
University of Gdansk, Poland
Izabela Kuchna Department of Developmental Neurobiology, NYS Institute for
Basic Research in Developmental Disabilities, Staten Island, NY, USA
Shuang Yong Ma Department of Developmental Neurobiology, NYS Institute
for Basic Research in Developmental Disabilities, Staten Island, NY, USA
Janusz Moryś Department of Anatomy and Neurobiology, Medical University
of Gdansk, Poland
Denis Noble Department of Physiology, Anatomy and Genetics, University of
Oxford, Oxford, UK
Raymond Noble Institute for Women’s Health, University College London,
London, UK
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List of Contributors
Krzysztof Nowicki Department of Developmental Neurobiology, NYS Institute
for Basic Research in Developmental Disabilities, Staten Island, NY, USA
Hiroyuki Okuno Medical Innovation Center, Kyoto University Graduate
School of Medicine, Tokyo, Japan
Sudhir Pathak Department of Psychology, Learning Research and
Development Center, University of Pittsburgh, PA, USA
Luis Puelles Department of Human Anatomy and Psychobiology, School of
Medicine, University of Murcia, Spain
Vilayanur S. Ramachandran Center for Brain and Cognition, Department of
Psychology, UC San Diego, La Jolla, CA, USA
Akira Sawa Department of Psychiatry and Behavioral Sciences, Johns Hopkins
University School of Medicine, Baltimore, MD, USA
James Schwaber Department of Pathology, Anatomy and Cell Biology, Thomas
Jefferson University, Philadelphia, PA, USA
Michael Shanks Academic Unit of Psychiatry, University of Sheffield, UK
Helen Sherk Department of Biological Structure, University of Washington,
Seattle, WA, USA
John R. Smythies Center for Brain and Cognition, Department of Psychology,
UC San Diego, La Jolla, CA, USA
Klaus M. Stiefel University of Western Sydney, MARCS Institute,
Bioelectronics and Neuroscience, University of Western Sydney, NSW, Australia
Annalena Venneri Department of Neuroscience, University of Sheffield, UK
Jarek Wegiel Department of Developmental Neurobiology, NYS Institute for
Basic Research in Developmental Disabilities, Staten Island, NY, USA
Jerzy Wegiel Department of Developmental Neurobiology, NYS Institute for
Basic Research in Developmental Disabilities, Staten Island, NY, USA
Thomas Wisniewski Department of Psychiatry, New York University School of
Medicine, New York, NY, USA
Acknowledgments
As with most any book, especially one of a technical nature, there exist
motivational and experiential forces beyond the ken of the author or edi-
tor; this book is no exception. In this regard, we wish to express our sin-
cere thanks to several individuals who truly helped us to make it so.
Were it not for the steadfast focus and requisite prodding of Elsevier’s
able-bodied acquisition editors, Mica Haley and April Graham, our jour-
ney from concept to publication would have undoubtedly taken a lon-
ger and less predictable route. We are most grateful to Professor Doctor
Stan Gielen, Dean of the Faculty of Science at Radboud University
in Nijmegen, for his cogent insights with respect to the intricacies of
spike timing and oscillations. Walter Freeman, Professor Emeritus
at UC Berkeley, was most kind to have reviewed an early draft of our
Hypotheses chapter, thus affording us a modicum of comfort in knowing
that we were heading in the right direction. Last and foremost, we are
beholden to Francis Crick and Christof Koch for illuminating the path
while throwing down the mother of all gauntlets (wink and all).
ix
Introduction
The editors of this volume, who also wrote the chapter on hypothe-
ses relating to the function of the claustrum, came from different back-
grounds in neuroscience. This facilitated the multidisciplinary approach
so necessary for such an enterprise. In their own words, they tell the
story of their collaboration that developed.
Lawrence (‘Larry’) Edelstein
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 fol-
lowed shortly thereafter, co-authored with my long-time friend and fel-
low claustrophile, Professor Frank Denaro. For some time prior to his
xi
xii
IntroductIon
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?”
Vilayanur (‘Rama’) Ramachandran
It is my belief that the same strategy used to crack the genetic code
might prove successful in cracking the “neural code” of consciousness
and self. It’s a long shot, but worth considering. The basis of this strategy
is the ability to grasp analogies, seeing the difference between deep and
superficial ones. Crick and Watson’s own solution to the riddle of hered-
ity ranks with natural selection as biology’s most elegant discovery. Will
a solution of similar elegance emerge for the problem of consciousness?
In biology, knowledge of structure often leads to knowledge of
function – one need look no further than the whole of medical his-
tory. Inspired by Griffith and Avery, Crick and Watson realized that
the answer to the problem of heredity lay in the structure of DNA.
Localization was critical, as indeed it may prove to be for brain function.
I believe there are similar correlations between brain structure and mind
function, between neurons and consciousness.
After his triumph with heredity, Crick turned to what he called the
“second great riddle” in biology – consciousness. Crick did not, in my
opinion, succeed in solving consciousness (whatever that might mean).
Nonetheless, I believe he was headed in the right direction. He had been
richly rewarded earlier in his career for grasping the analogy between
biological complementarities, the notion that the structural logic of the
molecule dictates the functional logic of heredity. Given his phenomenal
success using the strategy of structure–function analogy, it is hardly
surprising that he imported the same style of thinking to study con-
sciousness. He and his colleague Christof Koch did so by focusing on a
relatively obscure structure called the claustrum.
The claustrum is a thin sheet of cells underlying the insular cortex
of the brain, one on each hemisphere. It is histologically more homo-
geneous than most brain structures, and intriguingly, unlike most brain
structures (which send and receive signals to and from a small subset
of other structures), the claustrum is reciprocally connected with almost
every cortical region. The structural and functional streamlining might
xiii
IntroductIon
ensure that, when waves of information come through the claustrum, its
neurons will be exquisitely sensitive to the timing of the inputs.
What does this have to do with consciousness? Instead of focusing
on pedantic philosophical issues, Crick and Koch began with their naive
intuitions. “Consciousness” has many attributes – continuity in time, a
sense of agency or free will, recursiveness or “self-awareness,” etc. But
one attribute that stands out is subjective unity: you experience all your
diverse sense impressions, thoughts, willed actions and memories as
being a unity – not jittery or fragmented. This attribute of consciousness,
with the accompanying sense of the immediate “present” or “here and
now,” is so obvious that we don’t usually think about it; we regard it as
axiomatic.
So a central feature of consciousness is its unity – and here is a brain
structure that sends and receives signals to and from practically all other
brain structures, including the right parietal (involved in polysensory
convergence and embodiment) and anterior cingulate (involved in the
experience of “free will”). Thus the claustrum seems to unify everything
anatomically, and consciousness does so mentally. Crick and Koch rec-
ognized that this may not be a coincidence: the claustrum may be central
to consciousness. It is this kind of childlike reasoning that often leads to
great discoveries. Obviously, such analogies don’t replace rigorous science,
but they’re a good place to start. I think Crick and Koch may be right or
wrong, but their idea is elegant. If they’re right, they’ve paved the way to
solving one of the great mysteries of biology. Even if they are wrong, stu-
dents entering the field would do well to emulate their style, as we have
attempted to do ourselves. Crick has been right too often to ignore.
I visited Francis at his home in La Jolla in July of 2004. He saw me to
the door as I was leaving and as we parted, gave me a sly, conspiratorial
wink: “I think it’s the claustrum, Rama; it’s where the secret is.” A week
later he passed away.
John Smythies
My background is in neuroanatomy, neuropsychiatry and neurophi-
losophy. Latterly I had been working in Rama’s lab on problems related
to de- and re-afferentation plasticity, when one afternoon in late August
2011, I received an email from Rama, just then departing on a visit to
India. It said something like this “John – you should really have a look
at the claustrum – you know Francis’s idea that it plays a key role in con-
sciousness. The fact that it is connected with every other part of the brain
must mean something. Get together with Larry on this. See you when I
get back” – Larry being Lawrence Edelstein, a leading authority on the
claustrum, who was working down the road from the UCSD campus.
His daughter also happened to be a graduate student in Rama’s lab.
xiv
IntroductIon
At first I was puzzled. At that time the claustrum was of not much
interest to anyone, except a few devoted claustrophiles, of which Larry
was one. In 2004 Francis Crick and Christof Koch had taken up its cause
and claimed that its interesting connections made it an excellent candi-
date to be the “conductor” of the consciousness “orchestra.” The general
response from the neuroscience community had been somewhat lacking
in enthusiasm. Most neuroscientists tend to shy like startled horses at the
very mention of the word “consciousness.” This did not deter Francis
one iota and he continued to work on the claustrum until the day he
died.
So I fished the paper by Crick and Koch out of the archives and re-
read it. I soon became intrigued with its contents. I had read it when it
came out, but had put it on one side like almost every one else had done.
So I read it this time more attentively. I was soon struck by the cogency
of their arguments. When Rama got back from India we got together
with Larry and decided to work together to try and take up the problem
of what the claustrum is doing from where Crick and Koch had left it six
years before. The general results of this enterprise led to this volume: the
specific result was the hypothesis presented in our chapter.
Cover Image
High-definition fiber tractography (HDFT) reconstruction of the right
claustrocortical projection fibers in a 35-year-old healthy male volun-
teer. Such reconstructions have shown accurate fiber tracking in crossing
regions and robust end-point connectivity between cortical and subcorti-
cal regions (Fernandez-Miranda et al. (2012) Neurosurgery, 71, 430–453).
Freesurfer-based segmented cortical regions of interest were used to
subsegment claustrum connections and DSI-Studio was used to calcu-
late the volume of fibers terminating at each cortical region: superior
frontal gyrus (cyan) 21.3 ml; rostral middle frontal gyrus (purple) 4.1 ml;
precentral gyrus (red) 5.6 ml; postcentral gyrus (yellow) 7.3 ml; superior
parietal lobule (blue) 5.9 ml. The cover image was provided courtesy of
Juan Fernandez-Miranda, M.D., Department of Neurological Surgery,
University of Pittsburgh Medical Center.
C H A P T E R
1
History of the Study and
Nomenclature of the Claustrum
John Irwin Johnson and Brian A. Fenske
Department of Radiology, Division of Human Anatomy,
Michigan State University, East Lansing, MI, USA
THE FIRST ERA: 1780–1820
Something New in the Brain: A Product of Revolutions in
Science and Society
The history of the study and nomenclature of the claustrum of the
mammalian brain begins with the remarkable and revolutionary career
of the Frenchman Félix Vicq d’Azyr (see Parent, 2007, for a fascinating
account of this spectacular, tragically brief career, and its lasting imprint on
biological science and medical education).
Americans will note with interest that this entry into the scientific lit-
erature was published in 1786, three years following the recognition of
the United States as an independent nation, and three years before the
adoption of the equally revolutionary Constitution of the United States of
America, distinctively French in its design and principles.
By 1789 the fame of Vicq d’Azyr, through his work in the founda-
tion of comparative biology as a field of study and his applications of
this approach to solve important matters of public health, had led to his
appointment as physician to Queen Marie Antoinette. Three years later,
both he and the queen were dead, but his influence was profound and lives
on in many ways, including in our continued attention to the structure we
now know as the claustrum.
This young and superbly talented medical student was one of the
early enthusiasts who pursued the anatomical study of animals as well
as humans, attending lectures on the anatomy of both. He won fame by
a series of lectures, on the same topics, which he initiated when he was
J. Smythies, L. Edelstein and V. Ramachandran (Eds): DOI: http://dx.doi.org/10.1016/B978-0-12-404566-8.00001-5
1
The Claustrum. © 22001144 Elsevier Inc. All rights reserved.
