Table Of Content© 2019 Massachusetts Institute of Technology and
the Frankfurt Institute for Advanced Studies
Series Editor: J. R. Lupp
Editorial Assistance: M. Turner, A. Ducey-Gessner, C. Stephen
Photographs: N. Miguletz
Lektorat: BerlinScienceWorks
All rights reserved. No part of this book may be reproduced in any form
by electronic or mechanical means (including photocopying, recording,
or information storage and retrieval) without permission in writing from
the publisher.
The book was set in TimesNewRoman and Arial.
Printed and bound in the United States of America.
Library of Congress Cataloging-in-Publication Data
Names: Singer, W. (Wolf), editor.
Title: The neocortex / edited by Wolf Singer, Terrence J. Sejnowski, and
Pasko Rakic.
Description: Cambridge, MA : The MIT Press, [2019] | Series: Strüngmann
forum reports | Includes bibliographical references and index.
Identifi ers: LCCN 2019019582 | ISBN 9780262043243 (hardcover : alk.
paper)
Subjects: LCSH: Neocortex.
Classifi cation: LCC QP383.12 .N44 2019 | DDC 612.8/25--dc23 LC record
available at https://lccn.loc.gov/2019019582
10 9 8 7 6 5 4 3 2 1
Preface
Science is a highly specialized enterprise—one that enables areas of enquiry to
be minutely pursued, establishes working paradigms and normative standards,
and supports rigor in experimental research. Many “problems” addressed by
science, however, do not fall neatly into the scope of any one disciplinary fi eld.
For such topics, specialization can actually hinder conceptualization and limit
the generation of problem-solving approaches.
The Ernst Strüngmann Forum was established in 2006 to address problems
that emerge from ongoing research: topics which transcend classic disciplinary
boundaries, where conceptualization may have stagnated and the way forward
is uncertain. It facilitates open discourse and encourages divergent perspec-
tives, as both are viewed as integral to the expansion of knowledge. Consensus
unto itself is never a goal. Instead, topics are scrutinized from multiple vantage
points to expose existing gaps in knowledge; key questions are then formulated
and ways to fi ll such gaps are put forward.
Topic proposals are received from leading scientists who are active in their
fi elds and reviewed by an independent Scientifi c Advisory Board. Once ap-
proved, a steering committee is convened to transform the proposal into a sci-
entifi c framework that will support the focal meeting, or Forum, which is best
imagined as a week-long intellectual retreat. Formal presentations are taboo.
Instead, invitees engage in an extended dialogue to maximize intellectual out-
put. In preparation, invited papers introduce key topics in advance to expose
issues for discussion at the Forum. Four working groups approach the central
topic from different perspectives. Groups work autonomously yet build on in-
teractions with each other. To ensure that emerging insights do not get lost,
each group generates a draft report during the week.
This 27th Ernst Strüngmann Forum was proposed by Wolf Singer, Terry
Sejnowski, and Pasko Rakic to evaluate how research into cerebral cortex
has progressed over the last three decades. The starting point was a Dahlem
Workshop on the neurobiology of neocortex (Rakic and Singer 1988), followed
by the 5th Ernst Strüngmann Forum on dynamic coordination in the brain (von
der Malsburg et al. 2010). What trajectories did research take? Which ques-
tions are currently being confronted, and what is needed to address these now?
This volume synthesizes the resulting discourse that took place in Frankfurt,
Germany, from April 8–13, 2018, and is comprised of two types of contribu-
tions. Specifi c aspects of the theme are presented in chapters that were origi-
nally drafted before the Forum. These “background papers” have since been
revised, based on extensive peer-review, and offer an up-to-date assessment
on these topics. In Chapters 5, 9, 13, and 17, the working groups provide an
overview of their multifaceted discussions. Edited to ensure accessibility, these
chapters should not be understood as proceedings or consensus statements.
viii The Ernst Strüngmann Forum
Their intent is to summarize perspectives, expose diverging opinions and re-
maining open questions, as well as to highlight areas for future enquiry.
Each Forum creates its own unique dynamics and puts demands on all who
participate. Every invitee played an active role throughout this process, and
for their efforts, I wish to thank them all. I extend a special word of apprecia-
tion to the Program Advisory Committee, to the authors and reviewers of the
background papers, as well as to the moderators of the individual working
groups (Pasko Rakic, Peter Strick, Jennifer Groh, and David Poeppel). Special
recognition goes to the rapporteurs of the working groups (Debra Silver, David
Leopold, Kenneth Harris, and Lucia Melloni), for to draft a report during the
Forum and fi nalize it in the months thereafter is never a simple matter. Finally,
I extend my sincere appreciation to Wolf Singer, Terry Sejnowski, and Pasko
Rakic, whose commitment and enthusiasm for science were essential to the
entire endeavor.
To conduct its work, the Ernst Strüngmann Forum relies on institutional
stability and an environment that encourages free thought. The generous sup-
port of the Ernst Strüngmann Foundation, established by Dr. Andreas and Dr.
Thomas Strüngmann in honor of their father, enables the Ernst Strüngmann
Forum to serve science and pursue its mandate: “to expand knowledge in ba-
sic science and identify directions for future research.” In addition, I wish to
acknowledge the work of our Scientifi c Advisory Board, the supplemental
backing provided by the German Science Foundation, and the support that we
receive from the Frankfurt Institute for Advanced Studies.
Breaking new intellectual ground is never easy, and it can be diffi cult to set
aside long-held views. Yet the will to reexamine the past in the quest to identify
future research strategies is a most invigorating activity. On behalf of everyone
involved, I hope this volume will be successful in guiding and inspiring further
enquiry into the cerebral cortex.
Julia R. Lupp, Director
Ernst Strüngmann Forum
Frankfurt Institute for Advanced Studies (FIAS)
Ruth-Moufang-Str. 1, 60438 Frankfurt am Main, Germany
https://esforum.de/
List of Contributors
Bassett, Danielle S. Department of Bioengineering, School of Engineering
and Applied Sciences, University of Pennsylvania, Philadelphia, PA
19104, U.S.A.
Bruno, Randy M. Columbia University, Department of Neuroscience,
Zuckerman Mind Brain Behavior Institute, New York, NY 10027, U.S.A.
Buffalo, Elizabeth A. Physiology and Biophysics, University of
Washington, Seattle, WA 98195, U.S.A.
Coulter, Michael E. Division of Genetics and Genomics and Howard
Hughes Medical Institute, Boston Children’s Hospital, Departments of
Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115;
and Center for Integrative Neuroscience, University of California San
Francisco, San Francisco, CA 94122, U.S.A.
Cuntz, Hermann Ernst Strüngmann Institute for Neuroscience, 60528
Frankfurt am Main, Germany
Dehaene, Stanislas Collège de France/Inserm, 91121 Gif sur Yvette, France
DiCarlo, James Brain and Cognitive Sciences, MIT, Cambridge, MA
02139, U.S.A.
Fries, Pascal Ernst Strüngmann Institute for Neuroscience, 60528
Frankfurt am Main, Germany; and Donders Institute for Brain, Cognition
and Behaviour, Radboud University Nijmegen, 6525 EN Nijmegen, The
Netherlands
Friston, Karl J. Wellcome Trust Centre for Neuroimaging, London WC1N
3BG, U.K.
Ghazanfar, Asif A. Princeton Neuroscience Institute, Departments of
Psychology, Ecology, and Evolutionary Biology, Princeton University,
Princeton, NJ 08544, U.S.A.
Giraud, Anne-Lise Department of Basic Neuroscience, University of
Geneva/Campus Biotech, 1202 Genève, Switzerland
Gold, Joshua I. Department of Neuroscience, Perelman School of
Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
Grafton, Scott T. Psychological and Brain Sciences, University of
California at Santa Barbara, Ucen Drive, Santa Barbara, CA 93105, U.S.A.
Groh, Jennifer M. Psychology and Neuroscience, Neurobiology, Duke
University, Durham, NC 27708, U.S.A.
Grove, Elizabeth A. Department of Neurobiology, University of Chicago,
Chicago, IL 60637, U.S.A.
x List of Contributors
Haegens, Saskia Department of Neurosurgery, Columbia University
Medical Center, New York, NY 10032, U.S.A.; and Donders Institute for
Brain, Cognition and Behaviour, Radboud University Nijmegen, 6500 HB
Nijmegen, The Netherlands
Harris, Kenneth D. Institute of Neurology, University College London,
London WC1E 6BT, U.K.
Harris, Kristen M. Institute for Neuroscience, Center for Learning and
Memory, The University of Texas at Austin, Austin, TX 78746, U.S.A.
Hatsopoulos, Nicholas G. Department of Organismal Biology and
Anatomy, and Committees on Computational Neuroscience and
Neurobiology, University of Chicago, IL 60637, U.S.A.
Haydar, Tarik F. Department of Anatomy and Neurobiology, Boston
University School of Medicine, Boston, MA 02118, U.S.A.
Hensch, Takao K. Center for Brain Science, Department of Molecular and
Cellular Biology, Harvard University, Cambridge, MA 02138, U.S.A.
Huttner, Wieland B. MPI Molecular Cell Biology and Genetics, 01307
Dresden, Germany
Kaschube, Matthias Computational Neuroscience, Goethe University
and Frankfurt Institute for Advanced Studies, 60438 Frankfurt am
Main, Germany
Laurent, Gilles Neural Systems Department, Max Plank Institute for Brain
Research, 60438 Frankfurt am Main, Germany
Leopold, David A. Laboratory of Neuropsychology, National Institute of
Mental Health, Bethesda, MD 20892, U.S.A.
Leugering, Johannes Institute of Cognitive Science, Department of
Neuroinformatics, Osnabrück University, 49090 Osnabrück, Germany
Lorente-Galdos, Belen Department of Neuroscience and Kavli Institute for
Neuroscience, Yale School of Medicine, New Haven, CT 06510, U.S.A.
MacLean, Jason N. Department of Neurobiology, Committees on
Computational Neuroscience and Neurobiology, University of Chicago,
Chicago, IL 60637, U.S.A.
McCormick, David A. Yale School of Medicine, Yale University, New
Haven, CT 06520-8001; and Institute of Neuroscience, University of
Oregon, Eugene, OR 97403-1254, U.S.A.
Melloni, Lucia Department of Neuroscience, Max Planck Institute for
Empirical Aesthetics, 60322 Frankfurt am Main, Germany
Mitra, Anish Department of Radiology, Washington University School of
Medicine, St. Louis, MO 53110, U.S.A.
Molnár, Zoltán Department of Physiology, Anatomy and Genetics,
University of Oxford, Oxford OX1 3PT, U.K.
List of Contributors xi
Muchnik, Sydney K. Department of Neuroscience and Kavli Institute for
Neuroscience, Yale School of Medicine, New Haven, CT 06510, U.S.A.
Nieters, Pascal Institute of Cognitive Science, Department of
Neuroinformatics, Osnabrück University, 49090 Osnabrück, Germany
Oberlaender, Marcel Max Planck Group: In Silico Brain Sciences,
Center of Advanced European Studies and Research, CAESAR, 52175
Bonn, Germany
Pesaran, Bijan Center for Neural Science, New York University, New
York, NY 10003, U.S.A.
Petkov, Christopher I. Institute of Neuroscience, Newcastle University
Medical School, Newcastle upon Tyne NE2 4HH, U.K.
Pipa, Gordon Institute of Cognitive Science, Department of
Neuroinformatics, Osnabrück University, 49090 Osnabrück, Germany
Poeppel, David Department of Psychology, New York University,
New York, NY 10003, U.S.A.; and Max Planck Institute for Empirical
Aesthetics, 60322 Frankfurt am Main, Germany
Raichle, Marcus E. Department of Radiology and Department of
Neurology, Washington University School of Medicine, St. Louis, MO
53110, U.S.A.
Rakic, Pasko Department of Neuroscience and Kavli Institute for
Neuroscience, Yale School of Medicine, New Haven, CT 06510, U.S.A.
Reynolds, John H. Systems Neurobiology Laboratory, Salk Institute for
Biological Studies, La Jolla, CA 92037, U.S.A.
Raut, Ryan V. Department of Radiology, Washington University School of
Medicine, St. Louis, MO 53110, U.S.A.
Rubenstein, John L. Nina Ireland Laboratory of Developmental
Neurobiology, Department of Psychiatry, Weill Institute for
Neurosciences, University of California San Francisco, San Francisco, CA
94158, U.S.A.
Schwartz, Andrew B. Neurobiology, University of Pittsburgh, Pittsburgh,
PA 15261, U.S.A.
Sejnowski, Terrence J. Salk Institute for Biological Studies and Division
of Biological Sciences, University of California at San Diego, La Jolla,
CA 92093, U.S.A.
Sestan, Nenad Department of Neuroscience and Kavli Institute for
Neuroscience, Yale School of Medicine, New Haven, CT 06510, U.S.A.
Silver, Debra L. Departments of Molecular Genetics and Microbiology,
Cell Biology, and Neurobiology, Duke University Medical Center,
Durham, NC 27710, U.S.A.
xii List of Contributors
Singer, Wolf Ernst Strüngmann Institute for Neuroscience, Max Planck
Institute for Brain Research, and the Frankfurt Institute for Advanced
Studies, 60438 Frankfurt am Main, Germany
Strick, Peter L. Department of Neurobiology, University of Pittsburgh,
Pittsburgh, PA 15261, U.S.A.
Stryker, Michael P. Department of Physiology, University of California,
San Francisco, San Francisco, CA 94143, U.S.A.
Sur, Mriganka Picower Institute for Learning and Memory, Department
of Brain and Cognitive Sciences, Massachusetts Institute of Technology,
Cambridge, MA 02139, U.S.A.
Sutherland, Mary Elizabeth Nature Human Behaviour, New York, NY
10004, U.S.A.
Tosches, Maria Antonietta Max Planck Institute for Brain Research,
60438 Frankfurt am Main, Germany
Tyler, William A. Department of Anatomy and Neurobiology, Boston
University School of Medicine, Boston, MA 02118, U.S.A.
Vinck, Martin Ernst Strüngmann Institute for Neuroscience, 60528
Frankfurt am Main, Germany
Walsh, Christopher A. Howard Hughes Medical Institute, Division of
Genetics and Genomics, Boston Children’s Hospital, and Departments
of Pediatrics and Neurology, Harvard Medical School, Boston, MA
02115, U.S.A.
Zurn, Perry Department of Philosophy, American University, Washington,
DC 20016, U.S.A.
1
Introduction
Wolf Singer, Terrence J. Sejnowski, and Pasko Rakic
As science works to address any number of complex problems, a certain mea-
sure of humility must accompany its quest. Viewed over time, it is clear that
myriad intricacies are often undervalued, as our collective wisdom and col-
laborative efforts have failed to resolve any number of issues. Although ulti-
mate answers may be rare, this should not undercut the process of discovery
or diminish the measurable progress that has been, or is currently being, made.
It simply puts into context a truism: Science is an iterative process. As knowl-
edge expands, each step forward requires us to test the concepts and ideas that
emerge. To do this may require us to develop new methods or tools, which in
turn may lead us to uncover completely new aspects of the problem that had
hitherto escaped attention, thus bringing us back to a point where we need to
evaluate, again, where things stand.
So it is, and has been, with our quest to understand the cerebral cortex.
Three decades ago, two of us (Pasco Rakic and Wolf Singer) chaired a
Dahlem Workshop in Berlin on the neurobiology of neocortex. This gather-
ing brought together forty distinguished neuroscientists from comparative and
evolutionary biology, developmental neurobiology, neuroanatomy, neurophys-
iology, and behavioral neuroscience for an in-depth discussion of the cere-
bral cortex and an assessment of current research. The motivation behind this
Dahlem Workshop was the realization that although research had advanced
system by system and yielded an immense amount of data, the underlying rules
and principles were defi ned for, and understood in, separate research areas,
thus complicating communication and cross-disciplinary research. What was
clearly lacking was an overarching theory of cortical organization—one that
could account for general principles within particular areas as well as for co-
operative interactions between cortical regions and cross-system generalities.
From the numerous peer reviews of the results (Rakic and Singer 19881), this
book captured the conceptual understanding of the time and stimulated future
research in developmental, cellular, functional, and cognitive neuroscience.
Years later, at an annual meeting of the Society for Neuroscience, we started
to refl ect on how the fi eld had changed since that Berlin meeting: What seminal
1
Although out of press, this publication is available freely online at https://esforum.de/publica-
tions/Neocortex_1/chaps/01_Neurocortex_Rakic_and_Singer.pdf (accessed 31.3.19).
2 W. Singer, T. J. Sejnowski, and P. Rakic
discoveries had actually been made? Which questions remained unanswered,
and what might be needed to address these now? Our discussions led us to
explore whether it might be worthwhile to convene another group of experts
to assess where things currently stand, in an effort to position research with the
conceptual means to move ever forward. Marked by the emergence of com-
pletely new disciplines, several key areas demonstrated the extent to which re-
search had expanded dramatically over the past three decades:
• Progress in genetics and molecular biology had revolutionized neuro-
scientifi c approaches in virtually all domains, from investigations of
development all the way to studies of psychiatric conditions.
• The transfection of neurons and glial cells with genetically encoded
marker molecules and the development of t ransgenic animal models
had permitted comprehensive analyses of the brain’s connectome, mas-
sive parallel recording of neuronal activity at the cellular level, as well
as cell-specifi c interference with neuronal activity.
• The advent of noninvasive imaging technologies and methods to stimu-
late selected regions of the human brain had boosted the fi eld of cogni-
tive neuroscience.
• The availability of powerful and affordable computational resources
now allow us to address the large data sets that were produced through
advanced electrophysiological and optical recording methods.
• Last, but not least, the rapidly growing fi eld of computational neuro-
science enables us, for the fi rst time, to test the validity of theories
and concepts through simulation experiments that are able to cope, al-
though still in a rudimentary way, with the mind-boggling complexity
and dynamics of neuronal interactions.
This progress convinced us of the necessity for a new collaboration, yet to do
justice to these novel developments, the scope of expertise needed to be broad-
ened. We found a willing partner in Terry Sejnowski, who worked with us to
develop a proposal for a forum that would explore the extent to which existing
data could be embedded in unifying conceptual frameworks of the neocortex.
As the reader may be aware, major changes in 2006 impacted the Dahlem
Workshops, and the institution no longer exists. Its guiding spirit, philosophy,
and approach, however, continue to fl ourish in Frankfurt under the auspices of
the Ernst Strüngmann Forum. (For an overview of this transition, see Singer
2016:475–476). Briefl y, the Ernst Strüngmann Forum creates an environment
that ensures open discourse and encourages divergent ideas. Long-established
perspectives are questioned and disciplinary idiosyncrasies exposed. Consensus
is never a goal. Instead, topics are examined from multiple perspectives: ex-
isting gaps in knowledge are exposed, key questions formulated, and ways
of fi lling such gaps (through future research) are proposed. From April 8–13,
2018, the 27th Ernst Strüngmann Forum was convened in Frankfurt, Germany,
to which 48 experts from diverse areas in neuroscience participated.
