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The Roots of Cognitive
Neuroscience
Behavioral Neurology and Neuropsychology

E D I T E D   B Y A N J A N C H AT T E R J E E

and
H. BRANCH COSLET T

3

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3
Oxford University Press is a department of the University of Oxford.
It furthers the University’s objective of excellence in research, scholarship,
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Inquiries concerning reproduction outside the scope of the above should be sent to the Rights
Department, Oxford University Press, at the address above.
You must not circulate this work in any other form
and you must impose this same condition on any acquirer.
Library of Congress Cataloging-in-Publication Data
The roots of cognitive neuroscience : behavioral neurology and neuropsychology / edited by
Anjan Chatterjee, H. Branch Coslett.
pages cm
Includes bibliographical references and index.
ISBN 978–0–19–539554–9
1. Cognitive neuroscience. 2. Clinical neuropsychology. 3. Neuropsychiatry.
I. Chatterjee, Anjan, editor of compilation. II. Coslett, H. Branch, editor of compilation.
QP360.5.R66 2014
612.8′233—dc23
2013012874

9 8 7 6 5 4 3 2 1
Printed in the United States of America
on acid-free paper

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CONTENTS

Preface

vii

A N J A N C H AT T E R J E E & H . BR A NC H COS L ET T

Contributors
CHAPTER

xi

1.   The Case for Case Reports

1

K ENNETH M. HEILM A N

CHAPTER

2.   We Stand on the Shoulders of Giants: The Golden

Era of Behavioral Neurology 1860–1950 and Its Relevance
to Cognitive Neuroscience Today 11
H EI DI ROT H

CHAPTER

3.   Deconstructing Human Memory: Insights

from Amnesia

53

M I E K E V E R FA E L L I E & M A RG A R ET M . K E A N E

CHAPTER

4.   Semantic Memory

67

A N A STA S I A M . R AY M E R & L E S L I E J . G ON Z A L E Z ROT H I

CHAPTER

5.   Alexias and Agraphias

89

D A V I D P. R O E L T G E N & E L I Z A B E T H   H . L A C E Y

CHAPTER

6.   Face Recognition

105

STEVEN Z. R APCSAK

CHAPTER

7.   Arousal, Attention, and Perception

131

M ARK MENNEMEIER

v

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vi

Contents

8.   Perceptual-Attentional “Where” and Motor-Intentional
“Aiming” Spatial Systems 171

CHAPTER

A.M. BA R R ETT

CHAPTER

9.   Limb Apraxia: A Disorder of Goal-Directed

Actions

187

A N N E L . FOU N DA S

10.   Body Representations: Updating
a Classic Concept 221

CHAPTER

H. BR A NCH COSLETT

CHAPTER

11.   The Neuropathologies of the Self

237

TODD E . FEIN BERG

CHAPTER

12.   The Neurology of Emotional Expression

252

LEE X . BLONDER

CHAPTER

13.   Behavioral and Cognitive Effects of

Antiepileptic Drugs

269

K I M FOR D J . M E A DOR

CHAPTER

14.   Neuropsychopharmacology and Cognition 

DAV I D Q . B E V E R S D O R F

15.   Attractor Basins: A Neural Basis for the
Conformation of Knowledge 305

CHAPTER

ST E PH E N E . N A DE AU

CHAPTER

16.   Plasticity

334

V IC TOR W. M A R K

CHAPTER

17.   Visual Art

349

A NJA N CH ATTERJEE

CHAPTER

18.   Creativity

367

VA L E R I A D R A G O & G L E N R .   F I N N E Y

Afterword

388

K E N N E T H M . H E I L M A N , E D W A R D VA L E N S T E I N & R O B E R T T.   W A T S O N

Index

397

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PR EFAC E

Cognitive neuroscience is in high fashion. Images with colored patches showing brain regions that are active when we think, perceive, feel, and make decisions grace the covers of the most prestigious scientific journals. Every month,
neuroscientists seem to be making new discoveries about why we are the way we
are. Even the general public has an inexhaustible appetite for neural explanations
for our behavior. Advanced technologies promise to demystify the mind as they
reveal detailed workings of the brain. Most research universities now have imaging centers in which scientists can picture brains functioning in vivo. Many use
novel electrical recording techniques and non-invasive stimulation methods to
understand how the brain works. In this climate of progress, driven by technology
that was inconceivable only a generation ago, why publish a book focused on an
old approach to the brain? The answer is simple. As the chapters in this volume
demonstrate, behavioral neurology and neuropsychology remain just as relevant
to advancing our understanding of the biology of cognitive and affective systems
as they were 150 years ago.
Examining the behavior of individuals with neurologic disease, sometimes
referred to as “the lesion method,” informs our understanding of cognitive and
affective systems in several ways. Firstly, as has been noted in the past, patients
reveal how large-scale systems can be “carved at their joints.” Understanding the
nature of these joints and the way that different components articulate reveals the
nature of the system under consideration. Secondly, the lesion method allows us
to test hypotheses about the role of neural structures in a way not possible by other
methods. Whether or not a particular region of the brain is necessary for a mental
operation is tested directly by assessing the consequences of damage to that part
of the brain. Finally, the striking phenomenology in patients, behaviors that most
of us would not have imagined possible, allows us to generate hypotheses about
the organization of the mind. How is it possible for someone to know facts about
the world and not facts about their own life? Why does someone speak, but not
understand? What does it mean for a person to recognize some, but not other
vii

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viii

Preface

parts of their body? How can an intelligent and articulate person behave as if one
side of the universe has vanished? These and many other deeply counterintuitive
phenomena reveal something about the structure of the mind as implemented
in the brain. They generate hypotheses to be tested, and, as occurred with the
most celebrated case in all of behavioral neurology and neuropsychology, Henry
Molaison (better known as H.  M.), they can radically change the basic understanding of how our minds are organized.
Beyond making the case for the central importance of behavioral neurology
and neuropsychology today, we have another aim in publishing this book. We
wish to acknowledge the contributions and influence of our mentor, Dr. Kenneth
M. Heilman. We both have been deeply affected by Dr. Heilman, whom we met
at critical times in our peculiarly similar academic paths. We were both medical students at the University of Pennsylvania (separated by several years) at a
time when a career of studying cognition as a neurologist was at best regarded
with bewilderment, and, more typically, with condescension. After our neurology residencies, we both did post-doctoral fellowships at the University of Florida
under Dr. Heilman’s guidance. Branch went on to work at Temple University for
several years. Anjan started his academic career at the University of Alabama in
Birmingham. In the late 1990s, we both returned to the University of Pennsylvania
to join the neurology department and to work at the Penn Center for Cognitive
Neuroscience. The rise of neuroimaging had made behavioral neurology attractive
even in a place like Penn that had long been a bastion of neuromuscular research.
Over the last 45 years, Dr. Heilman has been and remains one of the most productive and creative thinkers in this field. The chapters in this book, in addition
to showing the relevance of patient studies, reveal Dr. Heilman’s influence, which
extends beyond his own research into his impact on subsequent generations of
neurologists, neuropsychologists, and speech pathologists. These chapters, written by his students, represent but a small sample of those whose thinking has been
touched by his agile mind.

The book begins with a chapter by Dr. Heilman. He reminds us of the importance of single case studies. Th is contribution is followed by a chapter that shows
that the questions asked in the Golden Age of neurology, from the 1860s to the
beginning of the First World War, were prescient in identifying concerns that we
still face when theorizing about how mind arises from brain. The other chapters
cover diverse areas such as language and semantics, emotion, attention, praxis,
body representations, the nature of self, pharmacology, plasticity, and even art and
creativity. Dr. Heilman has made his own mark in each of these fields. However,
the chapters are not reviews of his contribution. Rather, they reflect the current
understanding of these fundamental areas of cognitive neuroscience as informed
by the study of people with neurological disease.
Th is is a book for cognitive neuroscientists, neurologists, psychiatrists, psychologists, physiatrists, and scholars in general interested in the biology of the

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Preface

ix

human mind. Importantly, the book is also aimed at medical, neuroscience, and
psychology students who are still forming their views of cognitive neuroscience. We hope the book will disabuse readers of two (in our view) wrong-headed
notions. The fi rst notion is that cognitive neuroscience is synonymous with functional neuroimaging. Th is misconception confuses a domain of scientific inquiry
with a method. While functional neuroimaging has certainly invigorated cognitive neuroscience, the field has deep roots tracing back at least to the second half
of the 19th century. The second notion is that while patient studies might be of
historical interest, the real way forward is through new technologies such as functional neuroimaging. Th is view is misguided because the interpretation of imaging data is now relatively unconstrained. The widespread use of reverse inferences
(inferring a mental operation based on neural locations of activation patterns)
begs to be corralled. Lesion studies offer the perfect foil for functional neuroimaging studies as a method for confi rming or rejecting hypotheses generated
by activation patterns. The tremendous growth of functional imaging research
makes lesion studies more important than they have ever been, if we are to ground

our cognitive theorizing.
Finally, we should mention that this book would not have been possible without the help and patience of the staff at Oxford University Press. Joan Bossert,
our editor, who also edited Dr.  Heilman and Dr.  Valenstein’s classic Clinical
Neuropsychology, was unfailingly supportive of our efforts
Anjan Chatterjee
H. Branch Coslett

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CONTRIBUTORS

A.M. Barrett
Kessler Institute of Rehabilitation
West Orange, NJ

Anne Foundas
Louisiana State University
New Orleans, LA

David Q. Beversdorf

University of Missouri
Columbia, MO

Kenneth M. Heilman
University of Florida
Gainesville, FL

Lee X. Blonder
University of Kentucky
Lexington, KY

Margaret M. Keane
Wellesley College
Wellesley, MA

Anjan Chatterjee
University of Pennsylvania
Philadelphia, PA

Elizabeth Lacey
Johns Hopkins University
Baltimore, MD

H. Branch Coslett
University of Pennsylvania
Philadelphia, PA

Victor W. Mark
University of Alabama in Birmingham
Birmingham, AL

Valeria Drago
IRCCS Fatebenefratelli, Laboratorio
LENITEM
Brescia, Itlay

Kimford J. Meador
Emory University
Atlanta, GA

Todd Feinberg
Albert Einstein College of Medicine
Bronx, NY

Mark Mennemeier
University of Arkansas for Medical
Sciences
Litt le Rock, AR

Glen R. Finney
University of Florida
Gainesville, FL

Steven E. Nadeau
University of Florida
Gainesville, FL

xi

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xii

Contributors

Steven Rapscak
University of Arizona
Tucson, AZ

Leslie J. Gonzalez Rothi
University of Florida
Gainesville, FL

Anastasia M. Raymer
Old Dominion University
Norfolk, VA

Edward Valenstein
University of Florida
Gainesville, FL

David Roeltgen
Cape Regional Medical Center
Cape May Court House, NJ

MiekeVerfaellie
Boston University
Boston, MA

Heidi Roth
University of North Carolina
Chapel Hill, NC

Robert T. Watson
Florida State University
Tallahassee, FL

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C H A P T ER

1

The Case for Case Reports
Kenneth M. Heilman

In the motion picture Flash of Genius, the engineer who invented the intermittent
windshield wiper sued Ford Motor Company for stealing his idea. A witness for
Ford explained that this engineer did not invent the transistors, condensers, or
other major elements of this wiper system, and that all of this had already been
invented. The engineer who invented this intermittent wiper held up a book, A
Tale of Two Cities, and started reading. He read the fi rst word, “It” and then asked
this witness if Dickens invented the word it? The witness said, “No.” The engineer
then asked if Dickens invented the word was, or the next words, “the best . . . ,” or
any of the words in this book, and the witness said, “No.” He then asked the witness, “If Dickens did not invent these words, why should he get credit for writing

this book?” The engineer won the suit against Ford because it was the means by
which he put these components together to develop a system that he created that
was significant, and creating systems is as important as creating components.
Many basic science researchers do not consider the research performed in
cognitive neuroscience, neuropsychology, and behavioral neurology as sciences
because cognitive systems neuroscientists, unlike basic scientists, do not discover
new proteins, neurotransmitters and neuromodulators, genes, or new structures.
Cognitive systems neuroscientists do, however, discover how complex systems
in the brain perform their functions, and also learn how failures in these systems
adversely influence behavior. Perhaps these same basic scientists would argue
that, since Dickens did not invent words, he should not be given credit for his
great novel.
One of the aspects of behavioral neurology-neuropsychology that is most
despised by many basic as well as clinical scientists is the case study. Recently,
there has been a movement to severely limit these reports because many people
do not consider them scientific. Several journals have also decided not to publish
case studies. For example, Johnston and Hauser (2007), editors of the Annals of

1

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The Roots of Cognitive Neuroscience

Neurology, defi ne case reports as “descriptions of fewer than 10 cases.” They state
that “one must always be concerned about reliability of inference based on an n

of one. No statistics are possible in case reports. Inference is entirely dependent,
then, on subjective judgment.” These editors also noted that, of the various articles published, reviews were the most highly quoted, and that case reports were
the least quoted. Those case reports published in the Annals received 60 percent
fewer citations than “research articles.” Since case reports do receive fewer citations, these editors believe the research community acknowledges the limited
quality of these reports. Based on this reasoning, the editors state that they will
continue to consider case reports. “However, we expect that the vast majority will
be rejected without review.”
The editors of the Annals are not alone in their de-evaluation of case reports. In
an editorial in Brain, John Newsome-David and John Rothwell noted Brain’s high
impact factor and also felt that limiting case reports will help further improve
that impact factor. Recently, we (Torres, Heilman and Poizner, in press) contrasted the reaching movements, in the dark, of patients with Parkinson’s disease
(PD) who have basal-ganglia network dysfunction with those of a patient with
a discrete injury to his posterior parietal cortex (PPCL) under three different
sensory-guidance conditions: (1) brief and temporary viewing of the allocentric
spatial target location and no viewing of the moving forelimb; (2)  continuous
viewing of the spatial target location (allocentric guidance) with no viewing for
the forelimb; and (3) brief and temporary viewing of the target with continuous
viewing of the moving fi nger (egocentric guidance). While the patient with the
PPCL was helped most with continuous allocentric-based guidance, the patients
with PD were helped most with continuous egocentric based guidance. These
results suggest that for the programming and planning of reaching movements,
the basal-ganglia-frontal circuits and the posterior-parietal cortex default to complementary sources of sensory (egocentric versus allocentric) information. We
thought that this fi nding was novel and important and sent this paper to Brain.
The paper was never reviewed, and we received the following response from the
editors, “Thank you for submitt ing the above manuscript which we have considered carefully, but regret to inform you will not be considered further as a submission to Brain. Our current policy is very rarely to publish single case studies . . . ”
Hospital and medical schools often consider surgeons more important than
neurologists because surgeons make much more money than do neurologists,
unless the neurologist brings in large sums of research funding. Recently, I was
told by the director of our Gainesville VAMC Geriatric Research and Educational
Clinical Center (GRECC) that he had to do his yearly report, and he needed to

know about our research activities. When I told him that I would get him a list of
the papers we published this past year, he apologetically told me that, while he was
interested in these papers, the VA director and chief of staff were not interested in
papers; they wanted to know the amount of research funds we brought in.

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The Case for Case Reports

3

There are several serious errors in the Johnston’s and Hauser editorial published in the Annals of Neurology. For example, they state, “No statistics are possible in case reports.” There are many means of performing statistical analyses in
case reports. These statistics can allow the investigator to know whether whatever
is being measured in the case is different from a demographically matched normal
population. There are statistical methods that can also inform the investigators
about the reliability of the fi ndings. Johnston and Hauser also state “Inference is
entirely dependent, then, on subjective judgment.” In single-subject studies, there
are even statistical means of testing possible causation. For example, a patient can
be repeatedly tested until they form a stable baseline, and after a stable baseline
is established, a treatment can be instituted. If this treatment is either beneficial
or harmful, the patient’s performance will be altered from this baseline, and this
alteration can be tested for significance.
Some critics of case reports are of the opinion that many case reports are
nothing more than a serendipitous event. It is possible that a person might have
a genetic defect or some other unique event that caused a disease, and that the
mutation or event that led to this disease is unique to that person; however, while
some case reports of previously unreported diseases do turn out to be rare diseases, the vast majority of case reports are subsequently demonstrated not to be
unique. The knowledge that a clinician has discovered a new and unreported fi nding is also not serendipitous. No matter how many patients a clinician sees in their

practice, it is the prepared mind that discovers the new fi ndings that make a case
reportable. To know that an observation is novel and that this novel observation
is important, the clinician has to know that which is known, that which is not
known, and that which may be important for others to know. Louis Pasteur stated
that, “In the fields of observation, chance favors only the prepared mind.”
Compared with population studies that may examine diagnostic tests or treatments (i.e., “evidence-based medicine”), case reports intensely investigate and
describe the individual with the disease-disorder in the context of comorbidities and individual characteristics. It is often the individual differences that produce variability, and thus, population studies require statistical analyses to learn
whether whatever result they observe is just a random event or unlikely to be a
random event. It is exceedingly rare with a group or population study to have no
variability. Learning the factors that caused this variation may be very important.
However, to learn what caused this variability, the investigators would have to
perform a series of case studies. Unless all subjects in a population study show the
same effect, shouldn’t a clinician and investigator still be concerned about reliability and making inferences based on these population studies?
Many people will state that case reports, case studies, or case series are uncontrolled, and since they are uncontrolled, are likely to be incorrect. When people
prepare to write up case reports or n  =  1 studies to submit to a journal, they
attempt to learn if there have been other similar reports. Now with Internet tools

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4

The Roots of Cognitive Neuroscience

such as PubMed, this task has become relatively easy. If the clinician-investigator
learns that his or her observation has not been previously reported, and that he
or she might have a new observation, this observation should be shared with
others who might see the same phenomenon or who might want to do further
research. However, it is important for this novel contribution to be confi rmed by

future studies and reports. If the clinician investigator does fi nd prior reports of
patients with the same fi nding, he or she might want to perform some type of
meta-analysis that might allow them to fi nd a thread that unites the fi ndings, and
thus leads to them to a new level of understanding.
These anti-case report messages from editors may be a very serious sign of a
deeper sociological disorder, and it is possible that this disorder may seriously
retard medical progress. The editorials mentioned above suggest that the “bean
counters” have even taken control of our journals. And, unfortunately, the
bean-counter mentality appears to be infectious, and is even corrupting the minds
of brilliant scientists who make decisions about the type of papers that should be
accepted for publication. Journals are ranked by “impact factors,” and the impact
factor is highly dependent on citations of the articles published in that journal.
The editors of the Annals of Neurology as well as of Brain boast about their high
impact factor. Thus, editors can increase the prestige of their journal by accepting papers that are likely to be frequently cited, and rejecting those that are cited
less frequently, such as case reports. Review papers rarely present information
that stimulates what Kuhn (1996) termed a “paradigmatic shift .” These papers are
often highly quoted because they summarize advances in a domain of research,
and when people write papers, a reference to a review paper will often reduce the
number of references required. But are citations really a valid means of measuring
an article’s importance? The real measure of the importance of an article is the
novelty of the information, and how this information will affect clinical care as
well as future research.
Jenicek (1999) states that case reports may be the “weakest” level of evidence,
but they often remain the fi rst line of evidence, and it is with the publication of a
case report that discovery and education about a disease often begins. Anyone
who is familiar with the history of neurology knows that most paradigmatic shifts
in neurology have been initiated by case reports. It is difficult to think of a neurological disease that was not originally a case report, or a small series of case
reports. Thus case reports or case studies have been a critical element in advancing neurology, and especially the sub-specialty of behavioral and cognitive neurology (Heilman, 2004).
In the clinic, the clinician-scientist has the opportunity to observe anomalies. By an anomaly, we mean a novel observation (i.e., an observation which has
not been previously reported). The observation of an anomaly suggests that the

scientific theory that attempted to explain the order in a system is inadequate,
and a new theory that can accounts for this anomaly must be developed. The

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The Case for Case Reports

5

development of a major new theory based on the awareness of anomaly would be
a paradigmatic shift.
There are many defi nitions of creativity. In a prior publication, I defi ned creativity as “the ability to understand, develop, and express in a systematic fashion
novel orderly relationships” (Heilman et al., 2003). In this defi nition, novelty is a
critical element of creativity, and novel ideas are a product of disengagement and
divergent thinking. Thomas Kuhn (1996) in his book, The Structure of Scientific
Revolutions, also stated that, “Discovery commences with the awareness of an
anomaly.” Awareness of an anomaly is a whisper of nature, and the people who
hear this whisper are able to recognize that our knowledge is incomplete or that
current theories might be either inadequate or incorrect. When some investigators hear this whisper of nature, they can develop and test new theories that will
help account for these anomalies. These new theories and research that are performed to test these new theories often lead to a paradigmatic shift.
Traditionally, psychiatrists have studied disorders of the mind, and neurologists have studied disorders of the brain; however, it was with the development
of behavioral and cognitive neurology that physicians started to study how
disorders-diseases of the brain caused disorders of the mind. Modern behavioral and cognitive neurology began with four critical papers. The fi rst, was the
report of Phineas Gage by Harlow (1848). Gage, who had a severe frontal injury
from an iron bar that was propelled into his brain, had a profound change in
his personality, and Gage’s story is still quoted in many reports about frontal
lobe function and dysfunction. The interest in Gage has remained so strong
that a reconstruction of Gage’s skull and brain, after his injury, was reported by

Damasio et al in 1994.
The second important paper was that of Paul Broca (1861), who reported a
patient who sustained a left anterior hemispheric stroke that resulted in a loss
of speech fluency. The patient, Leborgne, made few meaningful utterances, but
frequently repeated the word “tan.” Th is patient had relatively intact comprehension, but also impaired naming and ability to repeat. The third report, by Karl
Wernicke (1874), described a patient who, unlike Lebourgne, spoke fluently,
but spoke in jargon, and could not understand or repeat speech. Wernicke not
only reported this patient with what is now known as Wernicke’s aphasia, but
also based his case as well as upon knowing about the patient reported by Broca
Wernicke developed a speech-language information processing model, and based
on this model, he was able to predict the observation of patients with conduction
aphasia. Lichtheim (1885) described two patients with different forms of aphasia. One, like Wernicke’s patient, could not comprehend, but unlike Wernicke’s
patient, could repeat. The other, like Broca’s patient, was non-fluent, but unlike
Broca’s patient, Lichtheim’s patient could repeat. Based on these cases, Lichtheim
modified and enhanced Wernicke’s speech information processing model that
helped to explain several new types of aphasia.

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The Roots of Cognitive Neuroscience

Important case reports which produced paradigmatic shift s are neither limited to speech disorders-aphasia, nor were they just reported at the founding of
behavioral and cognitive neurology in the 19th century. For example, the world
famous patient H. M. recently died. H. M. had epilepsy that could not be controlled by medications. Since he had seizures emanating from both his left and
right anterior-medial temporal lobes, both anterior temporal lobes were surgically removed. When H. M. recovered from surgery, he had a profound deficit of
his episodic memory. H. M. was subsequently studied by more than 100 different investigators, and there have been several hundred papers and reports written

about different aspects of H. M.’s memory. These case studies of H. M. produced
a paradigmatic shift in our understanding of memory. Before the initial report by
Scoville and Milner (1957), it was not known that removal of both hippocampi
would induce this devastating amnesic disorder. Papez posited that a circuit
comprised of the hippocampus, fornix, mammillary bodies, thalamus, cingulate
gyrus, and retrosplenial cortex was important for mediating emotions; however,
the studies initiated by the novel observation that H. M. had impaired episodic
memory, but not impaired semantic or procedural memory after ablation of a portion of this “Papez” circuit (i.e., hippocampus) revolutionized our understanding
of the neural basis of episodic memory.
Temporal lobectomy remains an important treatment of poorly medically
controlled epilepsy, but now, the neurologists, psychologists, and neurosurgeons
who take care of these patients attempt to protect the normal hippocampus in
one hemisphere as well as other portions of the Papez circuit in this hemisphere.
If Scoville and Milner submitted the report of H. M. to Annals of Neurology or
Brain, there is a high probability that it would have been rejected without a review
because it was just a case report.
Since Broca’s and Wernicke’s initial reports, studies of behavioral-anatomic
fractionation have provided cognitive neuroscientists and clinicians with important information as to the modular organization of the brain and how local brain
dysfunction might lead to specific forms of aberrant behavior. Many of the cognitive behaviors performed by humans, such as speech, sensory recognition, and
memory (episodic, semantic, and procedural) are complex functions that are
mediated by systems that have many components, and many of these component
functions are mediated by anatomically distinct areas of the brain.
Caramazza (1986) noted that the experimental method used in a study is heavily dependent on the type of question that this research is attempting to answer.
According to Caramazza, when cognitive scientists are attempting to understand
brain function in normal subjects, as well as how brain function is altered with
injury, the case study methods are highly valuable. Although Caramazza notes
that studies that use large sample of participants do provide information about
this group’s average performance there is the assumption with group data that if
there are individual differences, these differences are random and irrelevant. In

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The Case for Case Reports

7

certain studies this irrelevant assumption might be acceptable; however, if group
data is used to understand the cognitive changes induced by injury, the group
study of patients with brain damage would only be valid if each patient is identical in “all theoretically relevant respects . . . .” When studying patients with brain
damage, such as stroke, it is rare for any two subjects to have exactly the same
anatomic lesion, and even when studying patients with degenerative diseases, it
is rare that all participants will have the same severity and loci of degeneration.
According to Caramazza, since these homogeneity criteria can rarely be met,
grouped observations cannot be validly used to draw inferences about normal
cognitive systems. Caramazza also notes that since group studies do not contain
homogeneous participants, these studies have to use statistical analyses, and any
conclusions drawn from such studies must contain probabilistic statements. In
most group studies, there are no detailed analyses of the exceptions, and as discussed above, it is the exceptions or anomalies that often will provide important
insights that lead to paradigmatic shift s in understanding.
Unfortunately, there is no single perfect method of studying the brain, and
the lesion-case study method, even with double dissociations, also has its limitations. Hughlings Jackson (1932) recognized that with brain injuries, there are
changes in behavior, and that injuries alter behaviors by two major mechanisms.
The injury to a specific area of the brain causes a loss of the functions mediated
by this portion of the brain; however, in addition to mediating specific functions,
the injured area might have been inhibiting another more phylogenetic “primitive” area that performs a more stereotypical form of behavior, and this injury
“releases” these more stereotypical primitive behaviors. In addition, as Monakow
(Finger et al., 2004) noted, brain injury causes diaschisis, in which areas of the
brain that have not been directly damaged, but are connected with the damaged

area, malfunction; malfunction of an area not directly injured can also produce
behavioral changes. Lastly, although a specific portion of the brain might be mediating a function, there might be other areas of the brain that can also perform
this function (functional plasticity), and, with damage to an area, other areas can
compensate for the damaged area. Thus, even damage to an area that mediates a
specific function might not lead to permanent changes in that function.
There are several other theoretical problems-limitations of case reports. When
a report appears in a journal, the authors, editors, and readers want to know
whether that which has been reported is valid (sound and cogent). Validity in medicine and science requires that the fi ndings -observations be replicable-reliable,
and that conclusions drawn from this case report be demonstrated to be correct.
Since case studies are based on individual patients, these observations have not
been replicated, and thus, might not be valid. When reporting a case, the authors
should invite others to replicate the fi ndings of this case to help establish reliability. However, people have to be aware of the disorder before they can attempt
to replicate the prior observations. Validity also depends on further testing of the

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8

The Roots of Cognitive Neuroscience

hypotheses that are raised by the case report, which might include gaining a better understanding of pathophysiology.
For the reasons mentioned above, cognitive-systems neuroscientists have to
be cautious when deducing the function of a specific brain area based on injury
to or degeneration of that area. It is important to obtain converging evidence.
In regard to behavioral neurology, neuropsychology, and speech pathology, in
addition to behavioral analyses designed to determine the functional systems
that are impaired and, by inference, the systems that normally mediate specific
behaviors, there are now many powerful tools that will allow us to provide converging evidence and help understand pathophysiology, including:  electroencephalography and evoked potentials, fMRI, positron emission tomography

(PET), magneto-encephalography, electrical stimulation, magnetic stimulation,
and neurochemical-neurotransmitter analyses.
Case studies can also have an important influence on the training of clinical
investigators. A part of my career that has been very rewarding is introducing new
neurobehavioral fellows into research. Many of the former fellows had never done
research, and were concerned as to whether or not they had the ability to perform
research. One of the things I  do is to remind them that, during their training,
they have already learned to perform research. In their practice, neurologists see
patients who are often referred from other physicians. Typically, based on the history they obtain and their fi ndings on examination, they use convergent thinking
to decide where in the brain-spinal cord-neuromuscular system these patients are
having their dysfunction. Then, based on this localization, they may use divergent
thinking to come up with a list of possible causes, and based on these possibilities,
they may then order tests that will help confi rm or disconfi rm each of the possibilities. In many respects, almost all new patients seen by clinical neuroscientists are research projects in which the clinician, based on her or his observations,
develops a-priori hypotheses, and then tests these hypotheses. Thus, case studies
come closest to the type of clinical functions that the fellows have performed.
There are times when seeing patients, and asking “where, why and how” questions, that there is a surprise fi nding. Th is unexpected or novel fi nding may be an
opportunity to learn something new about the nervous system, and share it with
others who will fi nd this novel fi nding to be important in their understanding of
the nervous system and the diseases that might affect it.
In summary, although there is litt le doubt that controlled studies and
evidence-based medicine are crucial to the advancement of medicine, these
advancements are often initiated by case reports. One of the fundamental components of creativity is novelty, and novelty in the medical, speech, and psychological sciences is often the product of a careful clinical evaluation. In medicine, and
especially in neurology, we are continuing to discover new diseases. Clinicians
and scientists need to know about new diseases so that patients can be diagnosed,
mechanisms can be determined, and treatments developed. The only means of

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The Case for Case Reports

9

reporting the observation of new diseases are case reports and case series. Case
reports and studies also may allow us to uncover the mechanisms of certain diseases. Many medicines currently in use to treat diseases were not developed for
the purpose that they are currently being used, and these beneficial, as well as
adverse, effects were often initially observed and reported as case reports. Just
as hospitals’ administrative “bean counters” are attempting to reduce the time a
physician spends with each patient, several journal editors are trying to reduce
the number of case reports, case studies, and case series reported in journals. By
implementing this policy, these editors may be increasing their journal’s citations and ranking; however, just as seeing patients more rapidly might make more
money for departments, clinics and health centers, this reduction of time spent
with patients reduces the quality of care. Not publishing case studies will no
doubt retard the advancement of medicine. As mentioned by Jenicek (1999), case
reports may be the “weakest” level of evidence, but they often remain the fi rst line
of evidence, and it is in the publication of case reports that discovery and education about a disease often begins.
We have had a neurobehavioral fellowship program at the University of Florida
for almost 40 years. One of the greatest gifts in my life has been the privilege of
helping to train these fellows, many of whom are now leaders in behavioral and
cognitive neurology, neuropsychology, speech therapy and even anthropology.
When many of these fellows started their fellowship, they were concerned about
their ability to perform research, and often it was a case study that introduced them
to research. In this book, several of our most prominent former neurobehavioral
fellows write about some of their important research contributions, including case
studies. It will be apparent to people who read these chapters that case studies have
done much to advance our science, and hopefully they will continue to help.

References
Broca, P. Remarques sur le siege de la faculté de la parole articulée, suives d’une observation

d’aphemie (perte de parole). Bulletins de la Société Anatomique de Paris. 1861; 36: 330–357.
Caramazza, A. The logic of neuropsychological research and the problem of patient classification
in aphasia. Brain and Language. 1984; 21:9–20.
Damasio, H., Grabowski, T., Frank, R., Galaburda, A. M., Damasio, A.R . The return of Phineas
Gage:  clues about the brain from the skull of a famous patient. Science. May 20; 1994;
264(5162): 1102–5.
Finger, S., Koehler, P.J., Jagella, C. The Monakow concept of diaschisis: origins and perspectives.
Archives of Neurology. 2004;61: 283–288.
Harlow, J.M. Passage of an iron rod through the head. The Boston Medical and Surgical Journal.
1848; 39:389–393.
Heilman, K. M., Nadeau, S. E., Beversdorf, D. O. Creative innovation: Possible brain mechanisms.
Neurocase. 2003; 9: 369–379.
Heilman, K.M. Case reports and case studies: An endangered species. Cognitive and Behavioral
Neurology. 2004; 17: 121.

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10

The Roots of Cognitive Neuroscience

Jackson, J.H. Selected Writing of John Hughlings Jackson. Taylor, I., ed. London:  Hodder and
Stoughton, 1932.
Jenicek, M. Clinical Case Reporting. In Evidence Based Medicine, Oxford, U.K , ButterworthHeinemann, 1999.
Johnston, C. and Hauser, S. L. Message from the Editor: The Value of a Case Report. Annals of
Neurology. 2007; 62(2): A11–A12.
Kuhn, T.S. The Structure of Scientific Revolutions, 3rd ed. Chicago: University Chicago Press, 1996.
Lichtheim, L. On aphasia. Brain. 1885; 7:433–485.

Scoville, W.B. and Milner, B. Loss of recent memory after bilateral hippocampal lesions. Journal of
Neurology, Neurosurgery, & Psychiatry. 1957; 20:11–21.
Wernicke, C. Der aphasische Symptomencomplex. Breslau: Frank und Weigert, 1874.

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C H A P T ER

2

We Stand on the Shoulders of Giants:
The Golden Era of Behavioral Neurology
1860–1950 and Its Relevance to Cognitive
Neuroscience Today
Heidi L. Roth

The golden era of behavioral neurology from 1860 to the mid-20th century
generated an enormous literature fi lled with careful clinical observations and
comprehensive models of cognitive function. The extent of this literature can
easily be underappreciated, but a review of publications by leading scientists and
physicians of the time reveals its vastness and depth.
Among other topics, this period is fi lled with active debates and thoughtful
consideration of the neurological organization of language, action, and perception. The models derived from this period have in some cases directly shaped, and
in others, strongly influenced modern models in these areas.
Here, we will examine important models from this period and highlight how
they remain relevant to our current understanding of cognition. We will also
highlight some of the challenges faced by the researchers from the past which are

not unlike those faced by scientists today. Much of this work was based on the
examination of patients with brain lesions. We begin with a review of the challenges faced at the beginning of the 1860s when the concept of modularity of
higher functions was fi rst established by Paul Broca in his reports on his cases of
aphasia in France. After that, we will consider Carl Wernicke’s contribution to the
understanding of language and aphasia and his use of diagrams and connectionist flow models of higher cognitive function. Finally, we will consider subsequent
studies of apraxia and visual agnosia that were influenced by Wernicke’s approach.
Th roughout, we will try to elucidate how and why the early contributions were

11

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The Roots of Cognitive Neuroscience

accepted, the criticisms to which they were vulnerable, and how our current models of function are indebted to them.

Language and Aphasia
B R O C A :   M O D U L A R I T Y O F H I G H E R- L E V E L
F U NCT IONS A N D T H E USE OF T H E
C L I N I C A L - PA T H O L O G I C A L M E T H O D

Language is one of the “highest” cognitive functions, closely associated with a
person’s identity and intelligence. In the early 19th century, there were both scientific and ideological arguments opposing the view that language might be localized in the brain, but the paper entitled “Remarks on the Seat of the Faculty of
Articulate Speech, Followed by a Case of Aphemia (Loss of Speech),” published
in 1861, by Pierre Paul Broca (1824–1880) in represented an important turning
point (Broca 1861/1977). Broca’s report and the debates that followed began to

convince people, at least in France, that higher-level cortical functions might be
associated with injury in a particular area of the brain.
Broca’s description of aphasia was certainly not the fi rst, and there were fairly
detailed reports of the characteristics of aphasic language that had been previously recorded. The fact that language dysfunction could occur from a head
injury was even mentioned in the Egyptian Surgical Papyrus from 2300 B.C.E.
(Breasted, 1930). In the early 19th century, not long before Broca, the phrenological program introduced by Franz Joseph Gall (1758–1828) and popularized by
Johann Spurzheim, posited that psychological/cognitive functions were localized
in circumscribed areas of the cortex. They even proposed that language ability or
verbal memory was located in the front part of the brain. They also suggested that
the size of the cortical regions should correlate with the degree of development of
that function, and that differences between people could be assessed by feeling
bumps on the skull, which would reflect the underlying topography of the brain
(Gall & Spurzheim, 1810–1819, 1835).
By the time Broca was active, the phrenological ideas of Gall had been strongly
discredited, and the enthusiasm for searching for the brain basis for higher-level
cognitive functions had lost momentum. Gall failed to provide scientific evidence
for his theories. At the same time, experimental physiologists failed to fi nd evidence for regional specialization in the cortex of higher-level behavior in their
studies of animals. The most prominent experimental physiologist in France,
Pierre Flourens (1794–1867), ablated parts of the cerebral hemispheres of pigeons
and observed that specific functions in the higher-level domain (excluding respiration and vital functions, which were controlled by the brain stem, and motor functions, which were controlled by the cerebellum) were not affected by where the
ablation took place (Flourens, 1824). He found only that overall loss of function

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