Single Neuron Studies of the Human Brain: Probing Cognition

391 Pages·2014·19.363 MB·English

by  Itzhak Fried (ed.), Ueli Rutishauser (ed.), Moran Cerf (ed.), Gabriel Kreiman (ed.)

Single Neuron Studies of the Human Brain

Single Neuron Studies of the Human Brain
Probing Cognition
edited by Itzhak Fried, Ueli Rutishauser, Moran Cerf, and Gabriel Kreiman
The MIT Press
Cambridge, Massachusetts
London, England
© 2014 Massachusetts Institute of Technology
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Library of Congress Cataloging-in-Publication Data
Single neuron studies of the human brain : probing cognition / edited by Itzhak Fried, Ueli Rutishauser, Moran Cerf,
and Gabriel Kreiman.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-262-02720-5 (hardcover : alk. paper)
I. Fried, Itzhak, editor of compilation. II. Rutishauser, Ueli, editor of compilation. III. Cerf, Moran, editor of
compilation. IV. Kreiman, Gabriel, 1971 – editor of compilation.
[DNLM: 1. Neurons — physiology. 2. Brain — physiology. 3. Brain Mapping. 4. Cognition — physiology.
5. Synaptic Transmission. WL 102.5]
QP360.5
612.8'2 — dc23
2013041744

10 9 8 7 6 5 4 3 2 1
Contents

Open Letter to a Beginning Researcher in the Field of Human Single Neuron Investigations vii
1 Introduction 1
Itzhak Fried, Ueli Rutishauser, Moran Cerf, and Gabriel Kreiman
2 Fifty-plus Years of Human Single Neuron Recordings: A Personal Perspective 7
George Ojemann
I Methodological, Ethical, and Clinical Considerations 17
3 The Neurosurgical Theater of the Mind 19
Itzhak Fried
4 Ethical and Practical Considerations for Human Microelectrode Recording Studies 27
Adam N. Mamelak
5 Subchronic In Vivo Human Microelectrode Recording 43
Richard J. Staba, Tony A. Fields, Eric J. Behnke, and Charles L. Wilson
6 Data Analysis Techniques for Human Microwire Recordings: Spike Detection and Sorting,
Decoding, Relation between Neurons and Local Field Potentials 59
Ueli Rutishauser, Moran Cerf, and Gabriel Kreiman
II Cognitive Neuroscience Findings and Insights 99
7 Single Neuron Correlates of Declarative Memory Formation and Retrieval in the Human
Medial Temporal Lobe 101
Ueli Rutishauser, Erin M. Schuman, and Adam N. Mamelak
8 Visual Cognitive Adventures of Single Neurons in the Human Medial Temporal
Lobe 121
Florian Mormann, Matias J. Ison, Rodrigo Quian Quiroga, Christof Koch, Itzhak Fried, and
Gabriel Kreiman
vi Contents
9 Navigating Our Environment: Insights from Single Neuron Recordings in the Human
Brain 153
Nanthia Suthana and Itzhak Fried
10 Microelectrode Studies of Human Sleep 165
Yuval Nir, Michel Le Van Quyen, Giulio Tononi, and Richard J. Staba
11 Studying Thoughts and Deliberations Using Single Neuron Recordings in Humans 189
Moran Cerf, Hagar Gelbard-Sagiv, and Itzhak Fried
12 Human Single Neuron Reward Processing in the Basal Ganglia and Anterior
Cingulate 205
Shaun R. Patel, Demetrio Sierra-Mercado, Clarissa Martinez-Rubio, and Emad N. Eskandar
13 Electrophysiological Responses to Faces in the Human Amygdala 229
Ralph Adolphs, Hiroto Kawasaki, Oana Tudusciuc, Matthew Howard III, Chris Heller, William
Sutherling, Linda Philpott, Ian Ross, Adam N. Mamelak, and Ueli Rutishauser
14 Human Lateral Temporal Cortical Single Neuron Activity during Language, Recent
Memory, and Learning 247
George Ojemann
III Clinical Neuroscience 273
15 Microelectrode Recordings in Deep Brain Stimulation Surgery 275
C. Rory Goodwin, Travis S. Tierney, Frederick A. Lenz, and William S. Anderson
16 Microstimulation Effects on Thalamic Neurons 295
Sanjay Patra, William D. Hutchison, Clement Hamani, Mojgan Hodaie, Andres M. Lozano, and
Jonathan O. Dostrovsky
17 Human Single Unit Activity for Reach and Grasp Motor Prostheses 305
Arjun K. Bansal
18 Human Single Neuron Recording as an Approach to Understand the Neurophysiology of
Seizure Generation 327
Andreas Schulze-Bonhage and R ü diger K ö hling
IV Conclusions 345
19 The Next Ten Years and Beyond 347
Ueli Rutishauser, Itzhak Fried, Moran Cerf, and Gabriel Kreiman

Contributors 359

Index 363
Open Letter to a Beginning Researcher in the Field of Human Single Neuron
Investigations
From your vantage point as a researcher just entering the field of human single neuron research,
you may already experience the excitement of potential contributions to human knowledge
inherent in directly working with the human brain. However, the neurosurgical theatre of the
mind may often look intimidating and complex, a foreign environment without the reassurance
of complete experimental control. Being in the operating room is an intense experience. Indi-
viduals new to this field of research may easily find themselves overwhelmed by the cast of
characters, doctors, nurses, and other ancillary personnel; by a great variety of instruments, the
life support and anesthetic machinery, and the boundaries of a sterile field; and by the over-
whelming presence of a patient with an exposed brain, sometimes awake during procedures
performed under local anesthesia. On the hospital ward, the situation may be daunting as well,
with an abundance of health care personnel, visitors in the patient’ s room, the constant possibility
of imminent epileptic seizures, and a myriad of noise sources, electrical and psychological. What
advice, then, can help you as a scientist entering this complex field of single neuron recordings
in humans?
T he first step in an organized research project would entail c hoosing the right question.
H owever, contrary to the tradition of carefully preconceived lines of scientific investigation, as
a researcher in t his field, you need to be an experimental opportunist. You cannot choose just
any question and hope to record from the relevant neurons. The sites of recordings will always
be completely determined by the clinical imperative and thus will be fixed in locations that
cannot be altered. The question you elect to explore has to be grounded in animal physiology
and has to build on this knowledge. Yet, the question must also be relevant and unique to the
human condition. In particular, you need to take what we know from nonhuman primate neuro-
physiology to the next level, the human level. Single neuron human neurophysiology is a small
field between animal neurophysiology and human functional neuroimaging and other noninva-
sive methods customarily used in cognitive neuroscience. However, it is not enough to confirm
findings from these areas. To merely confirm results obtained with other methods is to fail to
take advantage of the unique opportunities for advancing knowledge afforded by the methodol-
ogy of human single neuron research. You need to ask the next question, the one which can only
be answered using this technique.
viii Open Letter to a Beginning Researcher in the Field of Human Single Neuron Investigations
When you come to address your question with a designed experiment, you must keep in mind
the most important tenet in this field: It is a privilege to work with patients. Always remember,
patients come first. This might be difficult to keep in mind when all experimental control is lost
because, for example, in the middle of a recording session that was laboriously set up, your
patient has a pressing need. This need comes first. Naturally, individuals who must have total
control of the experimental situation will not thrive in this environment. You need to be able to
listen, to observe, and to not lose a rare moment of insight which may fleet by as your subjects,
patients who can declare their thoughts and wishes, may have an illuminating comment. Indeed,
Penfield was able to listen to his patients as they were lying awake under the surgical drapes
and was able to correlate his stimulation of the temporal lobe with past recollections. In my own
research, it was a particularly verbally gifted and insightful patient who once told me that she
was feeling an urge to move her hand when I was stimulating a site in her supplementary motor
area at a low current, thus providing much welcomed evidence of the importance of this brain
region in volition. However, while having the flexibility to take advantage of research opportuni-
ties that present themselves in the moment is crucial to success in our field, at the same time
you will find that, as a researcher, you need to stick to a paradigm and not change paradigms
too often. It takes a few years to gather a sufficient number of neurons in a region to make a
meaningful statement. Investigators also need to be technically savvy with data analysis (e.g.,
facile with computer programming) and competitive yet collaborative. Above all, achievement
in this field requires that a researcher be someone who is passionate about working with the
living human brain and yet always remembers that at the center of this unique situation is a
courageous patient who is indeed the focus of all our efforts. Finally, the successful human single
neuron researcher is someone who maintains a long-term vision guided by recognition that this
is probably the only opportunity in neuroscience to access, at the most basic level, the substance
that makes us human in patients who can declare and share with us their memories, perceptions,
emotions, and wishes.
B ridging single neurons and human behavior is at the core of the mind– b ody problem. Our
field, then, is challenging but also very rewarding. I hope you will find your journey in these
new territories as meaningful and inspiring as I have.
— Itzhak Fried
1
Introduction
Itzhak Fried, Ueli Rutishauser, Moran Cerf, and Gabriel Kreiman
There has been tremendous progress in our understanding of faraway galaxies, probing the rules
that govern the function of subatomic particles, elucidating the basic principles of life and
describing the biochemical reactions inside cells. Yet, our own brains remain a major frontier
for scientific investigation. Neurons and their interactions must give rise to the bewildering
complexity that underlies our perceptions, memories, intentions and emotions. In a large number
of unfortunate circumstances, malfunctioning of these circuits can give rise to some of the most
devastating disorders. The magic behind the function of the human brain defies our intuitions.
Elucidating this mystery can lead to profound transformations in how we understand ourselves,
how we treat brain disorders, and how we build more intelligent machines.
The last century has seen major strides toward understanding neurons and how they interact,
particularly through the examination of diverse animal models. Pioneers such as Adrian, Sher-
rington, Hodgkin, Huxley, Hubel, Wiesel, and many others paved the way to listen to the activity
of neurons and correlate this activity with sensory, motor, and cognitive phenomena. Through
their work, we have begun to understand specialized subcircuits that represent visual informa-
tion, brain nuclei that can help consolidate experiences into long-term memories, and how cir-
cuits of neurons can orchestrate behavioral output.
While studying many animal species continues to illuminate the road ahead, there remain
multiple phenomena that are difficult to examine outside the human brain. To cite a few, the
nature of language, imagery, subjective feelings, free will, and consciousness are not easy to
rigorously examine in animal models. Multiple techniques exist to study the human brain in a
noninvasive manner including scalp electroencephalography (EEG), magnetoencephalography
(MEG), functional magnetic resonance imaging (fMRI), and transcranial magnetic or electrical
stimulation (TMS, TES). While these techniques have provided important correlations of cogni-
tive phenomena, their spatial and/or temporal resolution is quite limited (see figure 1.1 ). For
example, fMRI and EEG provide information on scales of millimeters to centimeters. A cubic
millimeter contains on the order of 100,000 neurons. In the temporal domain, we know that the
dynamics of brain computations change rapidly on scales of milliseconds whereas fMRI provides
average measurements over scales of seconds. Furthermore, the biophysics underlying such