Neuroinformatics For Neuropsychology

Neuroinformatics for Neuropsychology
Vinoth Jagaroo
Neuroinformatics
for Neuropsychology
123
Vinoth Jagaroo
Department of Communication Sciences
& Disorders
Emerson College
120 Boylston Street
Boston, MA 02116
USA
vinoth_jagaroo@emerson.edu
and
Department of Psychiatry and the

Behavioral Neuroscience Program
Boston University School of Medicine
715 Albany Street
Boston, MA 02118
USA
jagaroo@bu.edu
ISBN 978-1-4419-0059-3 e-ISBN 978-1-4419-0060-9

DOI 10.1007/978-1-4419-0060-9
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I dedicate this book to my parents,
Barath and Sona
Preface
The idea for this book was conceived over many years and through many influences.
The fields of neuropsychology, general neuroscience, and information technology
were certainly among the main influences. It was in particular an unusual context
in which I was on the one hand exposed to academic and clinical neuropsychology
and on the other to information technology that gave rise to the ideas that would
eventually lead to this work.
I began thinking about informatics for neuropsychology more than a decade ago
as a graduate student in behavioral neuroscience at Boston University School of
Medicine. My track in this broad interdisciplinary area cut across neuropsychology,
neuroanatomy and neurobiology, and my focus was visual cognitive neuroscience.
I had concurrently held a position in a large information technology unit at the
university where I gained experience in computer networks and database program-
ming. The neuropsychology component of my training involved neuropsychological
assessment, which was carried out at the Boston Veterans Administration Hospital,
one of the teaching hospitals of Boston University Medical School. It was at these
institutions that many legendary neuropsychologists had pioneered their craft and
where some famous assessment instruments were developed.
As I engaged in carrying out neuropsychological assessment, I could not help
being struck by how comfortably this subspecialty of neuropsychology had con-
tained critical problems tied to its origins and its development. Psychometric testing
had played a huge part in the shaping of neuropsychological batteries and in some
cases assessment batteries were nothing more than modified psychometric tests.
When tests were developed from scratch in clinical neuropsychology, they were
typically developed around symptom clusters or operational tasks. Assessment
tools bore little tie to highly defined neuroanatomic systems or to rich conceptual
frameworks of cognition. Where was the alignment between neuropsychological
assessment tools, which were developed in earlier generations, and that rich body
of theory on neurocognitive principles that had arisen through cognitive neuro-
science and cognitive neurobiology, in a more recent generation? The “decade of
the brain” had brought forth so many neural systems and modules that related, with
relative precision, cognitive processes to the brain. In comparison, neuropsycholog-
ical assessment tools and neuropsychological models of cognition appeared rather
unsophisticated. It would have been possible to strive for reconciliation between
vii
viii Preface
assessment tools and functional neuroanatomic/neurocognitive systems if assess-

ment took on a more computational dimension, but again, this consideration was
absent in neuropsychology.
My interest in the representational model of spatial neglect had me comb-
ing through primate neuroscience literature on posterior parietal mechanisms for
coordinate-based spatiotopic transformations. The conventional assessment tools
for neglect, e.g., line bisection, letter cancellation, and clock and figure drawings,
by virtue of their simplicity, could generate dramatic pictures of neglect, but had no
potential to relate to neural models of neglect. It was this problem that made me look
to computerized methods, which in this case could be devised to tap into the com-
plexities of neglect. I began work on an informatics system involving a grid-based
screen interfaced with a database. The coordinates of presented visual stimuli and
the gradients of neglect could be recorded and subjected to various kinds of analysis
(this is described in a subsection of this book).
Exploring informatics systems for neuropsychological applications inevitably
had me surveying the larger field of biological informatics (bioinformatics) and its
subspecialty in the neurosciences (neuroinformatics). The levels of sophistication
attained by these disciplines were astounding as was the unique and transforma-
tive potential that they conferred. It was evident that modern biomedical science
was inseparable from bioinformatics. The Human Genome Project was in large
part a bioinformatics project and so much of the Human Brain Project centered
on neuroinformatics.
The absence of neuropsychology on the vast and flourishing landscape of
neuroinformatics was stark and striking. The scenario was that most of the sub-
disciplines in neuroscience had discovered a powerful new technology, enabling
novel methods of research, data analysis, problem solving, and knowledge build-
ing. With neuroinformatics, they could capture, manipulate, and visualize data in
ways never before conceived. Neuropsychology, however, remained quite oblivious
to this informatics-based revolution in the neurosciences. Neuropsychology, espe-
cially clinical neuropsychology, had by the 1980 s solidified an identity that had
been shaped over many decades. It had developed a modus operandi that was inti-
mately tied to its tools and models, most of which were rooted in periods that long
preceded the modern era of cognitive-brain sciences. By the late 1990 s, informat-
ics had become a tour de force in neuroscience, but neuropsychology, lying snug
under its canopy of conventions, showed almost no awareness or understanding of
the potential that was spelled by neuroinformatics.
In February 2005, I presented a paper at the US annual meeting of the Interna-
tional Neuropsychological Society, in St. Louis, Missouri. The paper described the
impact of neuroinformatics in neuroscience, and a case was laid out for neuroinfor-
matics in neuropsychology. I soon after began to structure the paper as a manuscript
for a review publication. Research for the paper brought me into contact with a small
but steadily increasing number of individuals whose work in neuropsychology tied
in with informatics. They shared valuable data with me and were also keen about
a larger account of neuroinformatics in neuropsychology. During this period, the
Internet had also been transitioning from its first generation to its second, marked
Preface ix
by a host of web-based technologies for data modeling and collective knowledge

building. Needless to say, with all these factors, what began as manuscript for a
review publication quickly evolved into a book.
This book introduces the field of neuroinformatics to neuropsychologists. It tours
the field of neuroinformatics and articulates ways by which neuroinformatics can
be integrated with neuropsychological research and practice. It describes various
applications for neuropsychology. The book is an ambitious first account of neu-
roinformatics for neuropsychology – it discusses the kinds of changes required in
the discipline for a successful integration with neuroinformatics, and it also lays out
various issues that are likely to arise as neuroinformatics becomes an everyday part
of neuropsychology. It presents a vision of 21st century neuropsychology defined
by neuroinformatics.
The book is aimed at neuropsychologists and to those in related disciplines
– behavioral neurology, psychiatry, clinical psychology, speech-language pathol-
ogy, cognitive psychology, and cognitive neuroscience. The introduction offered by
this book is non-technical. The reader does not require a background in computer
science or computational neuroscience. A reader of general neuropsychological
literature will have no problem understanding the material presented.
Numerous possibilities for the realization of neuroinformatics in neuropsy-
chology are conveyed by this book. It is the author’s hope that the book will
help accelerate discussion and enhance awareness of neuroinformatics for neu-
ropsychology. A theme carried throughout the book is that neuroinformatics for
neuropsychology is not an option but an inevitability brought about by technological
and theoretical advances of our time.
Boston, Massachusetts Vinoth Jagaroo

Acknowledgements
I am grateful to the many individuals who helped make this book possible.
The encouragement and support I received from my colleagues, Daniel Kempler,
Cynthia Bartlett, and David Maxwell in the Department of Communication Sciences
and Disorders at Emerson College, was simply invaluable. The very same must be
said of the many years of generous support that I have received from Marlene Oscar
Berman of the Behavioral Neuroscience Program and the Department of Anatomy
and Neurobiology at Boston University School of Medicine.
Research for a core section of the book, on neuroinformatics applications and
models for neuropsychology, could not have been completed were it not for the
cooperation that I received from twelve individuals – who graciously addressed my
inquiries and provided me valuable data on their work: Dennis Reeves and Joseph
Bleiberg (automated neuropsychological assessment); Mark Baggett, Mark Kelley,
and Daniel Christensen (Internet-enabled assessment systems pioneered in clinical
research programs of the US Army); Ho-Chuan Huang (computerized cancellation
test system); Frank Guenther (computational model of speech production); Huber-
tus Axer and Jan Jantzen (aphasia database); Carol Neidle (sign language database
project); Curtis Deutsch (behavioral phenomics and dysmorphology); and Robert
Bilder (cognitive and neuropsychiatric phenomics).
I also wish to thank Stephen Koslow, the former director of the Office of Neu-
roinformatics at the US National Institutes of Health, for reviewing my synthesis
of the Human Brain Project, the Neuroinformatics Program of the National Insti-
tutes of Health, and the Neuroinformatics Working Group of the Organization of
Economic Cooperation and Development.
Jane Emes, my diligent graduate student assistant deserves enormous credit for
her assistance with research and preparation of the manuscript.
Finally, I am indebted to my colleague and friend, Jon Hemperley, the former
manager of Information Technology at Office of the President at Boston University,
for years of mentorship on information technology systems.
xi
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 An Overview of Bioinformatics . . . . . . . . . . . . . . . . . 1
1.2 What Is Neuroinformatics? . . . . . . . . . . . . . . . . . . . . 2
1.3 Bringing Neuroinformatics to Neuropsychology . . . . . . . . . 3
2 Current Neuroinformatics Applications and Infrastructure . . . . 7
2.1 Brain Image Construction, Analysis, and Morphometric
Tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.1.1 Examples of Image Construction, Analysis,
and Morphometric Tools . . . . . . . . . . . . . . . . 8
2.2 Brain Image Atlases, Databases and Repositories . . . . . . . . 10
2.2.1 Examples of Image Databases . . . . . . . . . . . . . 10
2.3 Tools and Databases for Mapping Neural Structure
and Connectivity Patterns . . . . . . . . . . . . . . . . . . . . 12
2.3.1 Examples of Tools and Databases for the Study
of Neural Architecture . . . . . . . . . . . . . . . . . 12
2.4 Tools and Methods for the Simulation of Neurons
and Neural Circuits . . . . . . . . . . . . . . . . . . . . . . . . 13
2.4.1 Examples of Tools for the Simulation of Neurons . . . 14
2.5 Database and Knowledge Discovery Systems for
Clinical and Academic Research . . . . . . . . . . . . . . . . . 18
2.6 Neuroinformatics Management and Infrastructure . . . . . . . . 20
2.6.1 Examples of NI Organizations, Infrastructure,
and Management . . . . . . . . . . . . . . . . . . . . 21
3 Neuroinformatics for Neuropsychology . . . . . . . . . . . . . . . . 25
3.1 Differentiating Between the General Computer
Applications in Neuropsychology and Neuroinformatics
Systems for Neuropsychology . . . . . . . . . . . . . . . . . . 25
3.2 Defining Neuropsychology-Specific Neuroinformatics
Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.3 Neuroinformatics Applications and Models for
Neuropsychology . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.3.1 General Neuropsychological Assessment . . . . . . . . 32
xiii
xiv Contents
3.3.2 Visuospatial Processing, Visual Attention, and

Spatial Neglect . . . . . . . . . . . . . . . . . . . . . 43
3.3.3 Speech, Language, and Aphasia . . . . . . . . . . . . 58
3.3.4 Phenomics and Neuropsychology . . . . . . . . . . . . 75
4 Obstacles and Aids to Neuroinformatics in Neuropsychology . . . . 85
4.1 Data Sharing and Issues of Privacy . . . . . . . . . . . . . . . . 86
4.2 Standardization, Taxonomies, and Ontologies
for Neuropsychological Data . . . . . . . . . . . . . . . . . . . 88
4.3 Attitudes, Re-organization, and Training . . . . . . . . . . . . . 91
5 An International Society for Neuroinformatics in
Neuropsychology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
6 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . 99
6.1 Collaborative Knowledge Building in the Next Wave
of the Internet: Web 2.0, Neuropsychology 2.0,
and Global Network Innovations . . . . . . . . . . . . . . . . . 100
6.2 The Promising Politics of Informatics Infrastructure . . . . . . 102
6.3 Prologue to Neuropsychology for the 21st Century . . . . . . . 103
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Chapter 1
Introduction
1.1 An Overview of Bioinformatics
Over the past 25 years, the biomedical sciences have seen an unparalleled explosion
in the amount of research data generated. The mission of understanding complex
systems at discrete levels of analysis, be they protein structure or gene expression,
and the devising of complex tools to carry out such studies have inevitably led to
massive amounts of data and the need to process the data. Large-scale undertakings
in certain biomedical avenues, such as the mapping of the human genome, have
meant that large data sets would be generated by multiple research teams. Often
these teams would be working across disciplines and across international borders,
each team dealing with an aspect of the greater research project. In such contexts,
the need to rapidly code and index data, share the data in a common database, and
devise flexible cross-referencing and retrieval systems would be vital to the success
of the undertaking.
Occurring in parallel and serving as the critical enabler of biomedical research
have been the many strident advances in computer technology. Cheap and powerful
relational databases, Internet-accessible database systems, server–client computer
architecture, and visualization and simulation software have provided the essen-
tial tools that have greatly propelled biomedical research. So much of modern
biomedical research is so integrally woven with computational technology that the
computational environment is built into the very identity of biomedical research.
Bioinformatics is the name given to the discipline that has been formed around
this very specialized application of computer science and information technology
to conceptual, investigative, and cataloguing challenges in biology and medicine.
Bioinformatics, as a discipline, has carved a distinct identity between general bio-
logical science and computer science. It arises from both these disciplines but gains
its distinction from its very unique crafting and application of computational tech-
nologies to biological complexities that can be effectively investigated only with the
application of these computer-based methods. Numerous bioinformatics books and
journals have been published over the past two decades and many undergraduate
and graduate bioinformatics programs have emerged.
Genetics and molecular biology are the biomedical subdisciplines that first real-
ized a research dependence on informatics systems. Hence these disciplines were
V. Jagaroo, Neuroinformatics for Neuropsychology, 1

DOI 10.1007/978-1-4419-0060-9_1, ! C Springer Science+Business Media, LLC 2009
2 1 Introduction
the first to boast elaborate informatics systems and a very well developed bioin-
formatics infrastructure. The most well-known bioinformatics undertaking has been
the Human Genome Project (HGP), coordinated by the National Institutes of Health
and the US Department of Energy (see Collins et al. 2003; http://www.genome.gov/;
http://doegenomes.org/). The HGP ran from 1990 to 2003 and was a visionary
project. Its primary goals were to identify all the genes of human DNA (the human
genome) and the sequences of their base pairs. The project was officially completed
ahead of schedule, in 2003, when its central goal – the sequencing of the human
genome – was met but work continues on some remaining goals. Well represented
within the HGP were numerous aspects of a large-scale bioinformatics undertaking.
It grew out of the need to process massive amounts of data and elaborate data sets
in order to understand a complex biological system. It encouraged innovative com-
puterized tools designed to capture data and it shared these tools among the HGP
community. The data generated were fed into centralized databases, easily accessi-
ble to research teams internationally. The data had multiple uses. Analytic tools were
devised for the specialized assessment of the data (and some teams would focus only
on the assessment of captured data). The HGP involved biologists, mathematicians,
computer scientists, and IT specialists, melding their skills in various ways. It was
an international collaborative research effort with well-defined goals and it had a
centralized coordinating body. A clear understanding of the distribution of tasks
and the establishment of uniform research protocols and IT platforms made for a
streamlined global mission, maximizing resources while minimizing redundancy of
effort. The HGP had strong organizational leadership that guaranteed funding and
infrastructure for continuity of the project.
As indicated by the example of the HGP, there are many levels at which bioinfor-
matics can be practiced. Bioinformatics can refer simply to algorithms, databases,
and analytic tools used to further biomedical research. At broader levels, it may
encompass a large organizational system for project coordination and an IT infras-
tructure for integration of data sets. Genetics research and informatics systems have
defined such a powerful interface that the term genomics was coined to describe
this area. Similarly, the extent of informatics dependency in studying protein struc-
ture has given rise to the field of proteonomics. Numerous other subdisciplines in
biology and medicine have since inevitably been drawn into bioinformatics.
1.2 What Is Neuroinformatics?
The broad field of neuroscience has clearly been a burgeoning field. It has continued
to face ever-complex research questions and large data volumes. It is not surprising
therefore that neuroscience has taken to bioinformatics. The many applications of
bioinformatics in the neurosciences have come to be labeled by the term "neuroin-
formatics" (Huerta and Koslow 1996; Shepherd et al. 1998). Neuroinformatics is in
itself a richly constituted subdiscipline with avenues that extend from neuroimaging
to neurobiology. Some respective examples are databases of fMRI images and sets
of algorithms to help connect functional patterns; computerized simulation tools
1.3 Bringing Neuroinformatics to Neuropsychology 3
for neuronal conduction and dendritic branching; and a data mining system that
can search published neuroscience data (electronic files) and then generate probable
relational patterns between data fragments.
Initially neuroscience was slow to adapt to a bioinformatics approach when com-
pared to genetics and molecular biology (Koslow 2000). In more recent years,
however, neuroinformatics has rapidly gained momentum, as will be illustrated
through the many examples described in Chapter 2. A major initiative in neuroin-
formatics has been the Human Brain Project (detailed in following chapters). It was
sponsored by the National Institutes of Health and a few other US federal agencies,
with the explicit aim of furthering brain research through application of informatics
(Huerta et al. 1993; Shepard et al. 1998). The project has been in essence a neu-
roinformatics initiative – to database the brain – and it has supported many types
of projects that have been drawn into this central goal. Its significance to the brain
sciences has been as great as the significance of the Human Genome Project to the
field of genetics. It has spawned a number of major neuroinformatics developments.
These developments together with many independently developed neuroinformat-
ics tools and networks have come to be spread over almost every subdiscipline of
neuroscience.
The Digitization of Neuroscience Data: Common to many of the facets of
neuroinformatics (NI) are a few essential features to do with the digitization of neu-
roscience data. With the aid of computers, other specialized hardware, and database
applications, data are first captured at very fine levels. The data may then be stored,
manipulated, analyzed, and reconstructed. This general digital format and the com-
putational platform offer a greatly enhanced degree of complexity in describing
structural or functional properties of the nervous system. The key features in the
NI approach to data are summarized in Table 1.1.
With the digital approach to data capture, the degree of data complexity can be
more closely in tune with the actual biological complexity of the object of function
being studied. The richness of the data capture is often enabled by specialized hard-
ware. These tools are quite unique as are the kinds of analyses and relationships that
can be derived from the data they generate. Conceptually and operationally, they are
on a very different level when compared to conventional tools or methods. These
are the features that make NI a very unique and powerful avenue in neuroscience
research.
1.3 Bringing Neuroinformatics to Neuropsychology
In neuropsychology, the application of NI is yet to be realized. NI perspectives

in neuropsychology are presently seen only in quite a few projects in develop-
ment but the field of neuropsychology lacks awareness of the importance of NI.
NI has transformed neuroscience and is bound to have far reaching effects in
neuropsychology.
A case for the systematic incorporation of NI in neuropsychology was articulated
by the author in February 2005 meeting of the International Neuropsychological
4 1 Introduction
Table 1.1 Key features of the NI approach to data
Aspects of data
processing Key considerations
a. Data capture • Emphasis on digitizing the data – capturing or coding the data in ways
that can be stored and manipulated by computers.
• Capturing data at multiple levels of abstraction – data about all levels of
structure/function and data on as many variables as feasible.
• Indexing the data in ways that are optimal for database queries/searches
and pattern-seeking algorithms.
b. Data storage • Databases with data fields to accommodate multiplicity and breadth of
and sharing data to enable multiple levels of inference and analysis.
• Tagging or coding data; saving text, images, and data about spatial and
functional relationships.
• Web-accessible centralized databases or shared databases through
server networks.
• Data availability for current or future use – prospective and
retrospective study needs.
c. Data analysis, • Data mining – statistical techniques designed to mine the data for
modeling, patterns and relationships; search algorithms tuned to complex
manipulation, relationships among the data.
rendering, and • Data modeling – manipulate one or more variables; an application can
knowledge use real or hypothetical contingencies to model the effect of one set of
discovery data on another.
• Reconstruction – using the binary data to create realistic 3D spatial
renderings of structures, or probabilistic maps; semantic relationships
among text data can be expressed in spatial form.
• Ontology building – computer readable models of the properties and
relationships of elements of a data domain; aids the knowledge
discovery process
Society (INS) in St. Louis, Missouri. At the June 2008 INS meeting in Hawaii and
at the February 2009 meeting, Robert Bilder laid out compelling perspectives on
informatics frameworks for neuropsychology (these are discussed at length in later
chapters).
Both clinical and experimental neuropsychology have certainly built an increas-
ingly close relationship with specialty subdisciplines like neuroimaging, to which
NI is central. Yet, neuropsychology in itself has not yet realized the application of
NI to subject areas that are definitive to the field of neuropsychology. Traditional
neuropsychological research on the functional domains of language, visuospatial
function, memory, etc., tests and assessment batteries used in neuropsychologi-
cal assessment, and neuropsychological models for describing clinical syndromes
remain starkly unengaged with the activities of NI when compared to other subdis-
ciplines of the brain–behavioral sciences. Because neuropsychology is concerned
more with cognitive behavior and deals with the brain at a level that does not delve
into the minutiae of laboratory-style bench neuroscience, it could appear that it is
incongruous with the very technical stance of NI. This book attempts to demonstrate
1.3 Bringing Neuroinformatics to Neuropsychology 5
instead that neuropsychology can utilize NI as richly as NI has been exploited by

the other areas of neuroscience.
The purpose of this book is to describe the relevance of NI to neuropsychology.
With some innovation and creativity, NI systems can be tailored for every context
of neuropsychology. Computer hardware and software can be modified to capture
neuropsychological data in digital format especially with regard to clinical assess-
ment. The data can automatically be fed into databases. Pattern-seeking algorithms
can mine these data and seek logical relationships between data sets. Neuropsy-
chologists can decide on how to structure centralized computer platforms for the
sharing of primary data. Modeling tools can be devised to refine both neuropsy-
chological models of normal cortical function and models of neuropsychological
disorders. NI techniques can also help better integrate neuropsychological data with
converging results from other subdisciplines of neuroscience. In short, NI tools and
database techniques can be used to capture a much finer grain of neuropsychological
data. The renderings of complexity and the computational sophistication that NI can
bring to neuropsychology lie in contrast with the fundamental limits of conventional
or non-computational neuropsychology. NI can add a new dimension to neuropsy-
chology, giving the field a much enhanced level of investigative, descriptive, and
conceptual power.
The Structure of the Book: Demonstrating the relevance of NI to neuropsy-
chology requires that the application of NI in other areas of neuroscience first be
sampled. In making this illustration, the objective is to provide more than just a tour
of the field of NI. Only by conveying some important details of various NI examples
across the neurosciences can the extrapolation of NI to neuropsychology be appre-
ciated. Chapter 2, therefore, surveys numerous NI applications in the neurosciences
and describes NI management and organizational structures.
Chapter 3 begins by placing neuropsychology in the current NI landscape.
It critically distinguishes between (a) the general application of computers in
neuropsychology (including computerized assessment) and (b) NI systems for neu-
ropsychology. Criteria are suggested for defining tools that can be considered NI
tools specific to neuropsychology. Nine examples of NI applications or models for
neuropsychology are then presented. Seven of them relate to three broad areas of
neuropsychology: assessment and test-battery development; research and assess-
ment of visuospatial processes; and research on speech, language, and aphasia. Two
examples relate to the field of cognitive phenomics.
Brief summary of the examples of NI applications/models for neuropsychology
discussed in Section 3.3:
• An automated, digitized assessment battery structured in a highly modular fash-

ion where each subtest generates a unique data file; all data files can be seamlessly
uploaded to a database where queries can be applied to sort the data in various
ways or search for patterns among the data.
• An Internet-enabled neuropsychological assessment battery linked to a cen-
tral server/database, allowing for ease of inter-subject comparisons and
6 1 Introduction
population profiling, and especially suited to assessment carried out at remote

locations.
• A computational, screen-based grid system that captures spatial coordinates of
the visual field, offering a digital approach to analyzing neglect and to introducing
perceptual dynamics that can alter the gradient of neglect.
• A computerized tool that records visual search and visual attention patterns and
applies algorithms for graphical analysis of the visual search/attentional patterns.
• A theoretical and computer-simulated model of speech motor skill acquisition
and speech production that can intelligently use motor and acoustic cues to
modulate vocal tract movement.
• An online database of symptomological and neuroanatomic data in aphasia,
designed as a research tool to help clarify aphasic syndromes that have over-
lapping symptoms.
• A multimedia tool for transcription, analysis, and databasing of signs and
gestures in visual/gestural communication.
• A database initiative for the mapping of relationships between craniofacial
features and neuropsychological features in neurodevelopmental and neuropsy-
chiatric disorders.
• A research consortium for neuropsychiatric phenomics that is developing
numerous novel NI tools tied to data integration and knowledge building in
neuropsychology.
A considerable degree of background is described before the examples are pre-

sented. This helps to give perspective to the gains brought by NI in each of the
examples.
Chapter 4 also considers various obstacles and aids neuropsychology can expect
in adopting an informatics approach. These are grouped into three broad classes per-
taining to data sharing/privacy, standardization of methods in neuropsychology, and
general reorganization in the field. Ways of overcoming the obstacles are discussed,
drawing on lessons learnt from the practice of NI in general neuroscience to date
and on some trends in neuropsychology.
Chapter 5 describes the mission of the newly formed organization, The Society
for Neuroinformatics in Neuropsychology (SCNN). The need for a forum for discus-
sion and communication about NI in neuropsychology is laid out, as are the plans
of SCNN to address the needs.
Chapter 6 offers some concluding remarks.
Chapter 2
Current Neuroinformatics Applications
and Infrastructure
Neuroinformatics is a multifaceted field. It is as broad as the field of neuroscience.

The various domains of NI may also share some common features such as databases,
data mining systems, and data modeling tools. NI projects are often coordinated
by user groups or research organizations. Large-scale infrastructure supporting NI
development is also a vital aspect of the field.
There are many possible ways of describing the field of NI. Descriptions of NI
can vary depending on the research area and the type of NI application of interest.
The areas of NI surveyed in this section are among the most commonly described
clusters in the NI landscape (see Amari et al. 2002; Gorin et al. 2001; Huerta and
Koslow 1996; Shepherd et al. 1998). They provide a sampling of the field. Some of
the examples describe smaller projects and some describe major developments.
It will be noteworthy to consider the following questions while going through
this section for they may be parallels when addressing NI applications for neu-
ropsychology: What forces in the field led to the development of the NI tool or
user network? What is the research or conceptual problem being addressed and
how is NI applied? What are the unique elements that NI brings in addressing
these research questions? What impact has the example of NI had? How have user
groups shaped the field and why is a coordinating body important when developing
a new area of NI? How can conceptually similar NI applications be developed for
neuropsychology?
There are a few fundamental concepts and methods (e.g., data mining) that apply
broadly across NI, which are also referenced throughout the book. They are briefly
clarified in this section as they are encountered. There are also variations in the use
of terminology in NI and these are also clarified at different points.
2.1 Brain Image Construction, Analysis,

and Morphometric Tools
Functional magnetic resonance images are the “end products” of an elaborate and
complex sequence of experimental steps and computerized data processing. The
variables involved in the process are immense (see Buxton 2001; Huettel et al.
2004). The raw data that are captured are typically in the form of numerous graphed
signals tied to voxels (and they have the appearance of approximated sine wave

8 2 Current Neuroinformatics Applications and Infrastructure
or time-series graphs). The raw data look nothing like the colorful brain images
that are synonymous with fMRI. The data are fed into computerized tools that fil-
ter and analyze the data in terms of signal strength, temporal properties, etc. They
then necessarily use a 3D brain coordinate system so that the data can be viewed
(transposed) as a neuroanatomic activation pattern in the brain. A suite of comput-
erized tools enable the transformations from raw data to 2D images, 3D volumetric
reconstructions, surface maps, etc.
The generation of 3D images from 2D image slices in a single subject typically
involves steps such as image slice assembly formatted for a particular computer
application for image analysis; image quality checks; realignment and smoothing
of the assembled slices; removal of non-brain imaged parts/structures; time-series
analysis stimulus and inter-stimulus activity; corrections for artifacts (e.g., head
movement); and segregation in differential patterns of activations (blobs and regions
of interest). In experiments involving multiple subjects the same steps apply to each
subject but the activations blobs are averaged across subjects.
Each and every one of these steps is dependent on highly specialized comput-
erized tool sets. These are powerful informatics tools without which fMRI images
would not be possible. A few examples of such tools are described below (and the
aim of this subsection is merely to describe some of these tools, not the specialized
domain of brain imaging).
2.1.1 Examples of Image Construction, Analysis, and

Morphometric Tools
Analysis of Functional Neuroimages (AFNI): AFNI is a set of programs for fMRI

image processing, analysis, and visualization. Altogether, these programs also con-
stitute a technique and an environment for mapping and displaying functional brain
activity. AFNI is primarily a research tool. Robert Cox leads the development of
AFNI at the National Institutes of Health (he began writing the AFNI suite in 1994 at
the Medical College of Wisconsin). The initial impetus for the development of AFNI
was the need to view (transform) fMRI results in “Talairach space,” a 3D coordi-
nate system used to describe the locus of brain structures and activation patterns.1
Various programs and data sets were added and by 1996 AFNI was established as
1 Brain coordinate systems are used to define a “standard brain” against which to describe the locus
of neuroanatomic structures and activation patterns. They are necessary to imaging – data sets are
“normalized” to the space defined by a particular coordinate system (a process of stereotaxic trans-
formation) so that voxel-based computations can be carried out. One such system is the Talairach
system that derives from the Talairach and Tournoux Atlas, which was based on the brain of a
single individual (see Talairach and Tournoux 1988; 1993). Another is the MNI system developed
at the Montreal Neurological Institute in collaboration with the International Consortium for Brain
Mapping (see Section 2.2). This system was developed from a sample of 152 individuals and is
currently the most commonly used template for brain imaging. Some imaging software suites can
convert data between the Talairach and MNI systems.
2.1 Brain Image Construction, Analysis, and Morphometric Tools 9
a comprehensive suite for fMRI data processing. AFNI’s basic unit of data is a set
of 3D volumetric data – an array of voxels, for which AFNI codes various voxel
values. AFNI provides a number of ways of viewing the imaged data, for example,
in axial, sagittal, and coronal views; one slice at a time; many slices at once; with
functional overlay (merging two data sets); with anatomical overlay (merging a sub-
ject’s functional data with anatomic data from a database); as volumetric renderings;
as time-series graphs; etc.
AFNI has evolved into a very comprehensive image analysis package, currently
consisting of about 300 external programs and plug-ins that work with the core
application. Each deals with a very specific aspect of image analysis or rendering.
AFNI has been able to achieve this level of sophistication in part because it is also
an open source platform for development of new software. Users can download and
compile AFNI source code to program new features. Core developers of AFNI at
the NIH and the AFNI user community work together to iron out bugs and address
questions via the AFNI website. AFNI is a prime example of a dynamic platform
for neuroinformatics development. (URL: http://afni.nimh.nih.gov/afni)
Computerized Anatomical Reconstruction and Editing Toolkit (CARET): Devel-
oped at Washington University School of Medicine (St. Louis), CARET is a
powerful software application for generating and manipulating cortical surface
reconstructions. It is an open source software available to researchers and is accom-
panied by comprehensive online tutorials. CARET is designed to accommodate
various kinds of experimental data (neural connectivity patterns, anatomically or
functionally defined cortical geography, neuroimaging scans, etc.), which it can use
to produce surface reconstructions of cortical gyri. For example, CARET can use
a few neuronal connectivity maps of a gyral region or a few functional images
of the gyral region and from the data, it can project a gyral surface contour map.
It can also piece together individual image sections to create an entire gyral sur-
face. It can further manipulate the reconstruction to generate, for example, flat
maps (an unfolded gyrus) and inflated maps. Surface maps can be thought of as
a generic form of expressing brain images and neural organization. The advan-
tage of these maps is that they can represent the integration of various data types
arising from different studies. In accommodating different data types, CARET also
serves as a repository that successfully brings together and compares the data. (URL:
http://brainmap.wustl.edu/)
3D Slicer and FreeSurfer: Both 3D Slicer and FreeSurfer are software packages
freely downloadable from the Biomedical Informatics Research Network (BIRN),
an informatics consortium. The 3D Slicer utility has similarities with CARET in that
it enables neuroanatomic visualization and image segmentation. It can, for example,
process a segment from each of three brain scan slices (axial, sagittal, and coronal
planes) and then produce a 3D surface model highlighting the segmented region,
a function particularly important in the visualization of tumors or other lesions.
The development of this software is ongoing. It is the product of collaboration
between the Artificial Intelligence Laboratory at Massachusetts Institute of Tech-
nology and the Surgical Planning Laboratory at the Brigham & Women’s Hospital
(Boston). FreeSurfer is a set of software tools that can also reconstruct a cortical
surface using imaging data. Using data about functional characteristics of a corti-
cal region it can then overlay these data on the reconstructed cortical surface. This
functionality is well geared to extract cortical regional correspondence across large
data sets. FreeSurfer has been developed at the Center for Biomedical Imaging at
Massachusetts General Hospital with support from the BIRN, the NIH, and other
agencies.
The examples described above are a sample of the range of tools avail-
able for imaging analysis. Without these tools, the elaborate forms of data
image manipulation and data modeling that stem from imaging data would
not be possible. Recognizing that “[I]nformatics tools are key at all stages
of neuroimaging, allowing scientists to control highly sophisticated imaging
instruments and to make sense of the vast amounts of complex data gen-
erated by them” (http://nifti.nimh.nih.gov/background), the NIH launched the
Neuroimaging Informatics Technology Initiative (NIfTI). Its mission is to help
researchers enhance the utility of such tools and to foster unification of
tool platforms between different research groups using a community-based
approach. (URLs: http://nbirn.net/research/morphometry/visualization_tools.shtm
http://surfer.nmr.mgh.harvard.edu/)
2.2 Brain Image Atlases, Databases and Repositories
With the advent of computerized neuroimaging and the churning out of brain images
came the need to store the images. Brain image databases would serve as image
repositories, enable rapid retrieval of images (scans), and provide a means to com-
pare images. The emergence of functional neuroimaging only solidified the need
for imaging databases. Brain image databases have also meant that increased atten-
tion would be given to the processing of imaging data, post acquisition. As Wong
and Huang (1996) have highlighted, (a) this post-acquisition image analysis capa-
bility allows for the maximal analysis of the data, even long after the data have been
acquired, and (b) the informatics tools for managing and sharing these data have the
potential to reshape the clinical environment in the decades ahead.
2.2.1 Examples of Image Databases

The Whole Brain Atlas: The Whole Brain Atlas is an example of a relatively sim-
ple open access online utility. It offers a variety of images and some useful ways
of manipulating neuroanatomic and scanning variables. Scans obtained through
CT, PET, SPECT, and MRI are organized along five categories: normal brains,
cerebrovascular disease, neoplastic disease, degenerative disease, and inflamma-
tory or infectious disease. More than a hundred brain structures are highlighted
in the images of normal brains. With many of the images, the screen interface
allows the user to adjust the position of the scan axis to produce a correspond-
ing image slice. This allows for navigation through successive slices across a
2.2 Brain Image Atlases, Databases and Repositories 11
particular axis (horizontal, coronal, and sagittal). Some of the images can be regen-
erated by changing the weighting parameters (e.g., T1 vs. T2), thereby reflecting
differences in tissue-image characteristics. A well-organized database of images
presented through a simple online interface makes the Whole Brain Atlas a com-
pact and powerful utility. The image data can be used simply to tour the brain
slice by slice or as a brain scan reference for normal and diseased brains. (URL:
http://www.med.harvard.edu/AANLIB/home.html)
The International Consortium for Brain Mapping (ICBM) Subject Database:
The ICBM Subject Database is one component of a multifaceted neuroinformat-
ics project based at the University of California, Los Angeles. It is a web-interfaced
database of images and is at the center of a much broader NI infrastructure. Among
the goals of this NI infrastructure is the fostering of unification in (a) the collection
of images from various sources and (b) the organization these images and their dis-
semination among researchers. The ICMB database is also a large and continually
growing image database. Its sophistication lies in its powerful functionality: Vari-
ables and attributes relating to the subject (individual) and to the actual scan can be
set in order to refine a query. The query interface offers, for example, search fields
for the sex and weight of the subject and image attribute search fields for modal-
ity (MRI, PET, etc.), weighting, pulse thickness, slice thickness, and acquisition
plane. A collaborator registered with the ICBM can use this unified set of data fields
to upload images and view customized representations of the larger data set. By
bringing organization and structure to image data set collection, the ICMB subject
database provides an effective and convenient system for collaborators to archive,
share, and retrieve image data. (URL: http://www.loni.ucla.edu/ICBM/Databases/)
The Database of the NIH MRI Study of Normal Brain Development: The NIH
MRI Study of Normal Brain Development is a large-scale, multi-centered study that
tracks normal brain development in healthy children and adolescents. The greater
goal of the study is to provide a large reference data set on normal brain maturation
that will aid in understanding a range of neurodevelopmental conditions. The study
has recorded MRI and cognitive/neuropsychological data from approximately 500
children, from newborns to age 18, across the United States. Data collection began
in 2001 and was completed in 2007. It is, to date, the most extensive MRI study
of normal brain development in children. The study is sponsored by the NIH and
involves seven participating pediatric centers in the United States and the Montreal
Neurological Institute (MNI) in Canada, which acts as the data coordinating center
(see Almli et al. 2007; Evans 2004; Evans and the Brain Development Coopera-
tive Group 2006). A study of this scale overcomes problems of small sample sizes
and problems of different data types being spread across different (incompatible)
databases.
The pediatric MRI data repository that has resulted from the study resides at
MNI and contains a unique collection of multi-spectral structural MRI images. The
images were fed into the databases via the web network linking the participating
centers. Since the database also contains behavioral data, it allows researchers to
relate cognitive and motor changes in growth to changes in brain anatomy. The
database is web accessible and is available internationally to qualified researchers.
As with any NI project of this type and scale, new NI methods are devel-
oped in the process. The NIH/MNI MRI data repository demonstrated new
methods for MRI segmentation, web-accessible image databasing, and a work-
able architecture for large-scale collaboration. (URL: http://www.bic.mni.mcgill.ca/
nihpd/info/index.html)
2.3 Tools and Databases for Mapping Neural Structure

and Connectivity Patterns
The study of neural connectivity patterns and neuronal structure using staining and
tracing methods constitutes one of the most major areas of neuroscience research.
Many decades of work on the neural mapping of mammalian (and non-mammalian)
brains have produced masses of data on neural architecture. A commonly occurring
problem in this research has to do with correspondence between maps produced by
different research teams – also known as the parcellation problem. There has been
a lack of shared coordinate reference system when describing neural patterns at the
microanatomic level. If, for example, there are numerous research findings about the
connection patterns between two regions of the cortex, there needs to be a way of
extracting a pattern common to all the findings. This is particularly so if the findings
are to assist in functional interpretations. Other challenges have been encountered
in the study of ultrastructural neurocytology. Here, many of the technical problems
have had to do with the parsing out and visualization of extremely small cellular
structures – often in the range of less than 1 nanometer to a few nanometers. It is no
surprise then that with the advent of neuroinformatics, the study of neural architecture
is seeing rapid reorganization, sprouting off an array of tools and databases.
2.3.1 Examples of Tools and Databases for the Study of Neural

Architecture
Collations of Connectivity Data on the Macaque Brain (CoCoMac): CoCoMac is a

set of databases aimed at collating all known neural wiring patterns in the primate
brain. It is run by the Computational Systems Neuroscience Group at the Vogt Brain
Research Institute in Düsseldorf, Germany, with institutional collaborations across
Germany, the US, and the UK. Tracer is the main CoCoMac database containing
data on cortical neural connectivity patterns extracted from many thousands of stud-
ies. In addition to data about labeled (stained) cortical sites, their laminar patterns,
etc., Tracer also stores information about the experimental conditions and method-
ologies of the studies that produced the data. A significant feature of CoCoMac is
the mathematical method it uses to overcome the parcellation problem. Data on a
particular cortical region collected from divergent brain maps are converted into a
data set that is independent of the coordinates of each map. This is done through
algorithms that take into account the relative arrangement of structures described in
the divergent brain maps. CoCoMac data can also be exported to CARAT. Such inter-
face between NI tools signals an unimaginable potential of NI systems developing
meta-NI networks in the future.
2.4 Tools and Methods for the Simulation of Neurons and Neural Circuits 13
The parcellation problem is also attended to by other computer applica-

tions and graphical databases such as XANAT (http://redwood.psych.cornell.edu/
bruno/xanat/xanat.html), which provides a standardized format for putting the
results of tracer studies and a means to query the net result of connections to a
cortical region. (URL: http://cocomac.org/home.asp)
BrainMaps.org: BrainMaps.org provides an extensive compilation of very high
resolution histological images of the rhesus monkey brain. Numerous stained prepa-
rations sectioned at very close serial intervals across the coronal, sagittal, and
horizontal planes are provided through a convenient web interface. Before being
input into the database, the images are magnified greatly and then scanned at very
high resolution. The scale of the resolution of the images (ranging roughly from 0.5
to 8 microns per pixel) serves more than just a primary need for image clarity. Using
image-viewing software integrated into the website a user can zoom into any part of
an image resulting in the same kind of magnification quality that a user experiences
when zooming with a microscope. The resolution of images is such that the user
can essentially view them at the gross anatomical level or zoom into them at a sub-
neuronal level. Since the image slices across a plane are sectioned serially at close
(micron-scale) intervals, virtual 3D navigation between images is also made possi-
ble. A remarkable level of functionality is achieved with the simple combination of
high-resolution images, a web-accessible database, and appropriate image-viewing
software. (URL: http://brainmaps.org/)
Synapse Web: Synapse Web is a portal that describes a method and provides a
software tool for digitally rendering 3D images of neuronal ultrastructure. Creating
a realistic 3D graphical reconstruction of a neuronal segment such as a dendritic
protrusion is a challenge. Multiple images of the structure (on a scale of microns)
must first be captured, and the final 3D rendering must ideally convey the details
observed at the microscopic level. Synapse Web describes a method that employs
stained serial tissue slices, electron microscopy, and specialized software for image
reconstruction. A high-magnification (electron microscope) view of each serial slice
is photographed. Subcellular structures in the nanometer range are captured in these
images. Digitized photographs are then sequenced to match the respective posi-
tions of slices of the original structure. Using a piece of specialized software called
Reconstruct images can be appropriately cropped, scaled, and aligned so as to pro-
duce a 3D extraction of the structure of interest. The reconstruction can be viewed
in static form or in a virtual reality format.
NI tools developed to map out neural architecture and to render views of neu-
ral structure provide an obvious breakthrough in studying these complex systems.
(URL: http://synapses.clm.utexas.edu/)
2.4 Tools and Methods for the Simulation of Neurons

and Neural Circuits
Just as the biophysical properties of neurons and neural conduction are of interest to
cell biologists, the dynamics of neural functioning and neural circuitry are of interest
to computational neuroscientists – those who deal with mathematical modeling of
neural systems. Observing intercellular and intracellular neural events is extremely

difficult. This is the case not only because of the microscopic scale of the environ-
ment but also because of the multitude of variables and permutations involved with
neurons. Computer modeling of these neural processes therefore provides a means
for understanding these events. Modeling may relate to events tied to a neuron (e.g.,
ion transfer across a membrane) or the collective workings of circuits of neurons
(neural networks).
Two examples of neural simulation tools are described below. Both of the tools
relate primarily to events tied to neurons as opposed to properties of a large neu-
ral circuit. The latter case is primarily the focus of the field of neural modeling –
the modeling of neural circuitry in order to mimic neural information processing.
Neural modeling is a specialized subdiscipline that is not necessarily related to
bioinformatics. However, bioinformatics applications or methods commonly apply
modeling techniques. A brief recap is given to neural modeling further in this sub-
section because it can apply so broadly to NI (and a few of the NI applications
discussed in subsequent sections do incorporate modeling methods).
2.4.1 Examples of Tools for the Simulation of Neurons
General Neural Simulation System (GENESIS) is a computer platform for general-

purpose simulations of a range of neural systems from subcellular components to
larger neural networks (see Bower and Beeman 1998; Bower et al. 2003). The devel-
opment of GENESIS began at California Institute of Technology but has since been
spread across a few US institutions and internationally. GENESIS is focused on
structurally realistic computer simulations of neural functioning. Consider an exam-
ple in which a section of an axon needs to be simulated: One component of the
GENESIS platform, the Object Library, can provide a building block object (cylin-
drical shape). To this, the experimenter can add membrane channels and a synapse
at the terminal end. Various neuronal properties such as the makeup of intracellular
ions or the number of dendritic channels can be entered into a simulation or gen-
erated as a result. Another component of the platform, the Kinetic Library, allows
for high level of molecular modeling using parameters as specific as a molecular
reaction. The various “libraries” of the platform enable the user to obtain pre-made
components that have been programmed to realistically simulate a neural compo-
nent. The Channel Library, for example, contains many types of potassium, sodium,
and calcium channels; a library of single neurons contains small section of varied
neurons. To fully set up and run the simulation the user has to write some com-
mands (using a simulation language). As with many advanced computer programs,
commonly used programming sequences are packaged as scripts which the user can
simply apply. Because of this object-oriented approach to simulation, a user with
limited programming skills can successfully carry out some kinds of simulations.
More advanced users can program more complex sets of variables and parameters
into a simulation. Not uncommon in NI, the open platform environment of GENE-
SIS confers enormous power on this simulation system. It provides its users with a
well-provisioned modeling workspace. Bearing testament to the story of GENESIS

are many hundreds of users and more than 60 institutions across numerous countries
where GENESIS is used for educational purposes (Bower et al. 2003). GENESIS is a
good example of dynamic, continually expanding NI platform, shaped by its users.
(URL: http://genesis-sim.org/)
Neuron: Neuron is another simulation environment for empirically based mod-
eling of neurons and neural networks (see Hines 1994; 1998; Hines and Carnevale
2001; 2003). It originated at the Department of Neurobiology at Duke University
and has since become a collaborative project with various departments at Yale Uni-
versity. Neuron places more emphasis on simulating the biophysical events to do
with signal transmission within a neuron. Its simulation schemes are well attuned to
variables of a neuron’s membrane properties, ion channels, cytoplasm, etc., but as a
general simulation platform, Neuron is much more flexible. Neuron is also centered
on simulating these physical and biochemical neural processes without indulging in
a heavily mathematical/computational level of analysis. This makes Neuron ideal
for those interested in the essential neuroscience of a functioning neuron. Neuron
also uses an object-oriented system to set up a simulation model. Among its many
features is CellBuilder, a utility with which a user can simply build a model by
adding pre-built components. For example, a section of membrane containing ion
channels that operate along Hodgkin–Huxley principles can simply be added to a
neuron model. A user can also modify a component without having to directly edit
the program code (application language). User groups, tutorials, and meetings to do
with Neuron help expand this powerful simulation platform.
Tied to the Neuron simulation environment are some specialized databases and
modeling tools concerning neural structure and function (accessible via the Neuron
URL). NeuronDB is a database of neurotransmitter substances, neural receptors, and
types of voltage-gated conductance. SenseLab is a collection of neuronal and neural
system models that apply to the olfactory system. ModelDB provides a platform to
store and utilize published computational models of neurons, especially models that
have arisen using the data from NeuronDB.
Some Basics of Neural Modeling2 (See McClelland et al. 1986; Churchland
and Sejnowski 1994; Arbib 1995; Rowe 1995; O’Reilly et al. 2000; Dayan and
Abbot 2005).
The terms computational modeling, neural network modeling, or neural mod-
eling all describe the mathematical modeling of biological neural networks. An
artificial neural network, or simply a neural network, is the resulting computer-
based model that is to some degree modeled on neural networks in the brain.
Modeling is especially useful in understanding parallel processing that is typical
in large, widely distributed neural networks, hence the term parallel distributed
2 Computational modeling is the dominant method of simulating neuronal circuits and as such is
briefly covered in this subsection. The outline of main concepts given here will also aid in better
understanding a few of the NI examples that the reader will encounter in Section 3. A comprehen-
sive description of neural modeling is well outside the scope of this book. The interested reader is
referred to the original sources cited.
processing. In such a system, the net function is the result of the entire network,
while each neuron is defined by connectional and functional properties that give it
a distinct role in the collective function. Modeling can be viewed as a way of draw-
ing abstractions of workings of a complex system such as the brain and thereby
approximate neural functioning. There are a few areas of concentration in the field.
There is a lot of focus on understanding actual neural systems in terms of their
functional neurobiology and their role in cognition and then attempting to model
these systems. On the application end, artificial neural networks are often the basis
for artificial intelligence; hence neural modeling is closely tied to practical applica-
tions of robotics and engineering initiatives to develop computers that closely mimic
human information processing.3 Though artificial neural networks (hereon referred
to as “neural networks”) are generally much more simplified than actual networks
in the brain, they help to guide research.
Structure of Neural Networks: An artificial neuron (or processing unit) is the
building block of a network. These units are interconnected such that they can influ-
ence each other and in this way modulate the larger outcome of the system. The term
node may describe a single neuronal unit or a cluster of them that serve a common
function in the network. Neurons can be arranged in various ways, for example, a
network can have 100 neurons divided into 10 clusters and each cluster can be linked
to each other, or a network may be built of multiple layers of neurons, each layer
carrying out a distinct function and feeding information to the next layer. A certain
pattern of input to the first layer of the network results in a differential pattern of
activation across its neurons. Different “afferent” signals are then propagated and
are received by the next layer. Successive stages of processing are carried across the
network until an output layer generates a final result.
There are many variables and functional parameters involved in neural networks
and many of these are specified when designing neural networks. They include a
host of neuronal properties such as pattern of conduction (influenced by ion channel
properties), types of dendritic formations, numbers and strengths of synapses, how
a neuron summates its signals, the rate of firing, and the action of neurotransmitters
and receptors. In general, the closer the neurons of a network simulate integration of
3 Some readers may have encountered the term “Cognitive Informatics,” a term coined by Wang
(2002). The claim has been made that cognitive informatics is a new, innovative, emerging dis-
cipline concerned with (a) mathematical and computational approaches to understanding neural
and cognitive systems, especially in terms of how they represent abstract knowledge, and (b) how
this understanding can potentially lead to new types of computer architecture (see Wang 2003a,b;
2006; 2007a,b). These two goals, however, have been at the core of cybernetics and neural model-
ing for more than five decades (see sources cited earlier on neural modeling). On closer inspection,
“cognitive informatics” is largely an approach to modeling influenced by a bit of philosophy
about knowledge representation. Specifically, it is an approach predicated on a set of descriptive
mathematical (algebraic) methods around which an elaborate set of propositions, corollaries, and
theorems have been built (see Wang 2003b; 2006; 2007b). This clarification is being made here as
a caution to the reader not to confuse “cognitive informatics” with neuroinformatics for neuropsy-
chology. “Cognitive informatics” is an approach to modeling, and the relevance of modeling to NI
in neuropsychology is articulated in this subsection.
information from multiple synapses and at finer levels of neuronal detail, the more
the network approximates spatial and temporal dynamics of an actual neural system.
Neural networks are developed with computer programs, and a large variety of
software packages are available. The software enables the user to select types of net-
work topologies, types of neurons and various neuronal variables, different methods
to train the network, and ways of testing the network.
How Networks Learn: An important aspect of complex network is the bidirec-
tional flow of information – when information from later nodes can be fed back
to earlier nodes so as to adjust their properties. A network is trained by learning
rules (algorithms) that serve to adjust parameters (e.g., synaptic strength) of earlier
layers. Back-propagation is a commonly used training method by which the values
of data output from the output layer of a network are compared to expected val-
ues. Discrepancy values are propagated backwards in the network as feedback data
that the network uses to adjust its synaptic strengths. With continued training of the
network in this manner the network can achieve an output that is consistent with an
expectation. An adaptive network is one where connections and other network prop-
erties are automatically adjusted based on the input to the network and on how the
information flows through the network during the training/learning phase. In neural
modeling, neural networks are often configured as adaptive networks. They have a
powerful capacity to adjust to new data and to outcomes.
Core Application Functions of Neural Networks: Computer and mathematical
models based on neural networks have wide ranging applications beyond theoreti-
cal models of brain function. They may be applied, for example, in everything from
camera surveillance software to weather forecasting applications. In most cases, the
role of the neural network model is just one or more of a few common, sometimes
overlapping, functions. These have to do with algorithms that reduce or compress a
large mass of data to a manageable form and algorithms that mine the data for sim-
ilar temporal, spatial, or physical patterns or clusters; algorithms that match input
patterns (physical, spatial, temporal, numerical, etc.) and match them to stored data
so as to recognize the stimulus pattern or classify and store the pattern; algorithms
that extrapolate or approximate existing data to derive an approximate value for an
unknown value; and algorithms that do the same but on a temporal scale so as to
predict data sequences or event occurrences.
Relevance of Neural Modeling in Neuroinformatics: Neural networks are fun-
damentally methods of modeling data that have complex, non-linear relationships.
Neural modeling is by and large mathematical and statistical and can be described as
mathematical or statistical methods for the capture, classification, and matching of
data and predictions based on these data. Bioinformatics and NI have the same goals
relating to data but are not necessarily tied to statistical methods. Neural network
methods can be applied to NI when data volume or data complexity warrants the
application. They are hugely applicable in data mining – to help filter and condense
the data, find relationships between variables, etc. Essentially, modeling is a tool
that can directly tackle the larger NI goals of working out patterns and relationships
by clarifying the complex layers between input and output data patterns.
Neural networks are particularly relevant to NI in neuropsychology in areas of

visual processing including face recognition/object/text recognition, speech recog-
nition and speech synthesis, gestural recognition, and decision making (its relevance
to NI in neuropsychology is illustrated a little further in Chapter 3). (URLs:
http://neuron.duke.edu/ or http://www.neuron.yale.edu/neuron)/
2.5 Database and Knowledge Discovery Systems for Clinical

and Academic Research
Some of the NI examples surveyed above make evident that a database is often
the nucleus of the NI environment. More than a mere repository, a database allows
for selective querying and combining of data. When databases have to be designed
for clinical and research environments, they face some unique design challenges
brought about by the multi-tiered, multi-faceted nature of these environments. Large
clinical and research settings involve many data sources and data types and call
for numerous uses and applications of the data. A clinical setting typically also
includes multiple users with varying levels of data access privileges. In the academic
neuroscience research environment, massive volumes of data are churned out at rates
faster than any single scientist can reasonably integrate. The volume of published
literature is on a scale so enormous that it becomes impractical to grasp.
Spread throughout the strata of clinical and research environments are valuable,
often untapped data. Masses of data in databases cannot be manually examined
for relationships among the data. Special procedures are required to mine the data
for trends and patterns that may exist therein. The potential of the data is realized
through data mining and related methods of knowledge discovery.
Data Mining and Knowledge Discovery: Data mining refers to the process of
applying statistical, modeling, and visualization methods to large databases in
order to bring forth patterns and relationships that may lie obscured in the vastness
of the data (see Piatetsky-Shapiro and Frawley, 1991; Lavrač 1999; Prather et al.
1997; Zupan et al. 1999; Zhang et al. 2004). It serves to extract useful information
from the data by sifting out regularities or irregularities among the data. Since data
mining applies to databases and serves knowledge discovery, the process has come
to take on the name “Knowledge Discovery in Databases” (KDD). Data mining is
a crucial step in the overall process. Typically, before data mining procedures can
be applied, the data are cleaned and may be arranged in ways that facilitate specific
data mining techniques.
Data mining is ultimately concerned with drawing comparisons and viewing
interactions among the data (Kötter 2001) and using the data to discover hidden
correlations which may then be used to draw hypotheses (Wong and Huang 1996;
Wong et al. 2004). Data mining has therefore come to constitute an actual method of
research (Shepard et al. 1998). An entire branch of neuroscience research can be cre-
ated just by mining the data that lies within the multiple strata of its subdisciplines.
Ontology and Knowledge Discovery: In informatics, the term ontology refers to
a model that lays out the relationships and properties of the features that constitute
2.5 Database and Knowledge Discovery Systems for Clinical and Academic Research 19
a domain of data (see Gruber 1995; Maedche 2002; Staab and Studer 2004). The
model has a format that is readable by informatics tools and attempts to represent
concepts and their relationships in a manner that is approximate to how they occur in
reality. Ontologies attempt to conceptualize a data/knowledge domain by specifying
possible data sets, data classes, data concepts, and features, rules, and relationships
that possibly describe the data. By defining a common vocabulary and relational
structure, ontologies aid researchers in organizing the data of a knowledge domain,
which in turn makes for efficient ways of knowledge sharing.
Ontologies are used to guide data mining but they are also modified and adjusted
over time as more data are accumulated. Ontologies are crucial for knowledge
discovery in informatics because (a) they guide the choice and structure of the
data mining methods and (b) they critically influence results obtained through data
searches and data mining. In other words, relationships in the data as brought forth
by data mining are influenced by the ontology that guides the data mining pro-
cedure. Ontology that more accurately represents properties and relationships of a
domain as they occur in the real world will generate more accurate results through
KDD. This in turn can be used to refine the original ontology. Ontology develop-
ment in NI is a highly specialized area. Ontology building is essential to semantic
tools in knowledge discovery that enable the mapping of semantic relations among
large data sets. Semantic web technologies and a suite of “onto-tools” help provide
semantic frameworks for organizing the data and “engineering knowledge.”
There has been a clear trend in neuroscience toward centralized databases in
which the data are laid out along semantic categories (see Gorin et al.). Complex
programs using semantic criteria work to archive, index, or retrieve the data.
The NeuroScholar project (www.neuroscholar.org) is an example of database
system for the mining of neuroscience data for research purposes (see Burns
2001a, b; Burns et al. 2003). NeuroScholar is designed to index multiple sources of
neuroscience data such as published literature, websites, and laboratory-based data
files. It utilizes techniques from software engineering to construct its knowledge
model. Using NeuroScholar a user can, for example, extract the parts of pub-
lished papers that are most relevant to a question the user may seek to understand.
NeuroScholar terms these information parts “fragments,” which may be textual or
graphical in form. In a workspace provided by the system, the user can then decide
on the extent of linkage between the generated fragments. The user may also cre-
ate fragments. Once the user establishes a linkage between a set of fragments, the
relational pattern may then be stored on the system. This relational pattern may now
constitute an interpretation of data fragments, providing a model for knowledge
representation. NeuroScholar offers the facility to build complex neuroscientific
relationships using isolated fragments of neuroscience data. A host of support-
ing tools also enables the NeuroScholar user to carry out other operations such as
computational analysis of the knowledge representations.
The Neuroinformatics Database System (Wong et al. 2002; Wong et al. 2004)
is a database system for disease-oriented neuroimaging research, implemented at
the University of California, San Francisco. It is an example of a system tailored
to data integration within a clinical setting. In its current rendering, it contains data
relating to patients with intractable temporal lobe epilepsy (TLE) – it serves and
is served by clinicians and scientists involved with TLE treatment or research. In a
large clinical setting, some of the departments that would typically be involved with
intractable TLE patients are neurology, radiology, and surgery. In a typical hospital’s
information system, each department inputs its data on a patient into the system. All
departments may have access to the patient file and can therefore view the patient’s
results from each department (presuming the hospital’s privacy policy makes the
allowance) and this is usually the extent of data interconnectedness. Hospital infor-
mation systems are designed to serve the essential functions of data input, storage,
and retrieval. The Neuroinformatics Database System (NIDS) is an integrated sys-
tem that builds on an existing hospital computer infrastructure. It is designed to
draw multiple data types from multiple sources (departments) and offers special-
ized analytic and statistical components for data meta-analysis. NIDS can extract
and replicate information from the hospital’s primary information system without
interfering with patient records. “Warehousing” the data as NIDS does and then
applying a range of analytic algorithms to the data enables a clinician or researcher
to search for correlations and patterns that otherwise could not be gleaned from the
standard database.
The emerging role of NI-oriented databases and data mining systems for neuro-
science cannot be underestimated. It is only through the NI-enabled integration of
diverse data types that many complex relationships in neuroscience can be viewed.
This idea has been succinctly expressed by Wong and Huang (1996): “[T]he motive
is to realize the greatest possible benefit from the data that already exist. The new
megachanges of the next 20 years will center around gathering, managing and using
multimedia clinical information.” (p. 285).
2.6 Neuroinformatics Management and Infrastructure
The neuroinformatics applications and projects sampled above often require a great
deal of management, funding, and coordination. Proper management infrastructure
is particularly important for an emerging multifaceted discipline like NI. The sup-
port structure can (a) provide an effective forum for exchange and communication of
ideas, (b) help formally identify areas of research and development, (c) coordinate
projects among research teams at national and international levels thereby maxi-
mizing research potential, (d) provide centralized databases and tool repositories,
and (e) provide funding sources for NI projects. The scale of a support structure for
NI can vary depending on the extent to which it serves one or more of the above
considerations.
A less obvious but equally crucial function that may be served by an organizing
body for NI has to do with formative decisions regarding tool and database designs,
modeling schema, and data-sharing protocols. These have the potential to influence
the entire NI landscape over the long term. This consideration addresses the fol-
lowing questions: What data entry fields and querying procedures should be created
when designing a database? What kinds of coding systems should be implemented
2.6 Neuroinformatics Management and Infrastructure 21
in developing a modeling platform for neural circuits, or how should a multicen-

tered NI collaboration be structured? These are just sample questions that are better
addressed at the onset if any part of the project is going to be open to multiple
individuals or research teams. As is the case with any kind of informational man-
agement project, an early determination of the optimum ways to break down and
organize the data can avoid many potential future complications. At the same time,
the NI system’s design has to be flexible enough to accommodate later needs without
major disruption to the overall function. Bearing on such factors are plain organi-
zational, logistical, and systems-engineering considerations that are by no means
unique to the NI environment. An organizing body can integrate diverse needs of NI
researchers and implement designs and protocols to greatly facilitate sharing of the
NI platform.
Strong sources of potential funding are especially vital to promote and sustain NI.
Funding can range from startup funds for a single researcher’s software-related ini-
tiative to major long-term support for a multi-centered collaboration. Ideal funding
agencies for NI are those that fully appreciate the interdisciplinary nature of NI and
the potential that NI brings to neuroscience. As described below, there are now in
place organizations that aim specifically to advance the field of NI by funding NI
projects. Some of these initiatives are so important to NI that they are simply infused
with the field.
2.6.1 Examples of NI Organizations, Infrastructure,

and Management
The Human Brain Project and the Neuroinformatics Program of the National Insti-
tutes of Health: As alluded to earlier, the Human Brain Project (HBP) has been a
major NI initiative aimed broadly at all disciplines involved with brain-behavioral
sciences. Launched in April 1993, the explicit purpose of the Human Brain Project
(HBP) was to foster the development of NI. This initiative had been sponsored by
four US federal agencies, the National Institutes of Health (NIH), the National Aero-
nautics and Space Administration, the National Science Foundation, and the U.S.
Department of Energy. At least 12 organizations within the NIH were involved with
the HBP. The HBP was the product of a coordinated effort among these federal
agencies to support the field of NI. The HBP was created in response to the emer-
gence of large volumes of neuroscience data. It recognized the need for integration
of data from multiple avenues of neuroscience in order to achieve cohesive and
broader understanding of the brain. It also recognized the potential that computers
and information systems offered in dealing with such data (Huerta et al. 1993).
The formation of the HBP is often traced back to a few key historical events (see
HBP website; Huerta et al. 1993; Huerta and Koslow 1996; Shepard et al. 1998). In
the early 1980 s, neuroscientists had begun formal discussions on the potential of
general computer technology in furthering neuroscience research. The actual tech-
nology available at the time was, however, not on par with the ideas about their
potential facilitating role. By the late 1980 s, computer technology had made few
leaps and the promise of applied information technology was already being seen
in molecular biology projects such as the Human Genome Project and the C. ele-
gans research database (a database for mapping the genome of the roundworm,
Caenorhabditis elegans). Encouraged by these promising developments, the NIH
and NSF, in 1989, asked the National Academy of Sciences’ Institute of Medicine
(IOM) to create a working group of scientists that would explore the feasibility of
developing a national database resource for neural circuitry. The group engaged in
extensive discussion and consultations, and in 1991, published a report in which
the idea of integrating computational technology with neuroscience was firmly
endorsed (see Pechura and Martin 1991). Evolving from this initiative, the HBP was
launched in 1993, formalizing a structure for neuroinformatics. Incorporating many
of the recommendations made by the IOM’s working group in 1991, the HBP’s
coordinating committee shaped a guiding strategy for the project.
The HBP would aim to support research in all areas of neuroscience at both
federal and public institutions. It would call for the research to show a clear involve-
ment of both neuroscientists and technology specialists (computer/informational,
mathematical, engineering, etc.). Very importantly, the HBP would require a certain
degree of communication between the projects it would sponsor and it would require
that NI tools and technologies developed under its sponsorship be compatible across
research teams, and hence be easily shareable. The idea of the neuroscience com-
munity richly interlinked by a system of shared computer networks databases was
articulated in the IOM’s working group. It is one of the main ideas that have shaped
the HBP’s outlook.
The HBP has been conducted along three phases (see Huerta and Koslow 1996;
Huerta et al.; Gorin et al. 2001). In phase 1, it sought development of prototype
NI tools for capturing, analyzing, and manipulating information digitally. Much of
the emphasis in this phase was on tools and databases relating to (a) functional
neuroimaging and (b) neuronal structure and circuitry (see Shepard et al.). In phase
2, it encouraged the refinement and integration of the tools and systems developed
in phase 1. Attention was given to computerized methods of integrating graphical
data (of the type generated with phase 1 tools) and non-graphical (e.g., theoretically
described) neuroscience data. Phase 3 took the developments from phases 1 and 2
to shared platforms (e.g., Internet-accessible databases), making them available to
the broader neuroscience community.
High priority has been given to projects relating to data storage, data access, and
data mining; digital brain atlases and related tools; simulation and visualization soft-
ware; and Internet-based platforms for tool and data sharing and for collaboration
between research teams and sharing. After more than a decade of successful ini-
tiatives, the HBP has turned its focus to how these initiatives can be more broadly
applied in advancing research (HBP website). It is not, at the present time, soliciting
new funding applications but many other divisions of the NIH continue to call for
informatics-related projects.
The HBP has greatly propelled and shaped the field of NI. It started with a
visionary idea, which was translated into an effective plan of action. In addition
to providing management and funding, the HBP has placed emphasis on the
2.6 Neuroinformatics Management and Infrastructure 23
cross fertilization between the neurosciences and information sciences; it has

placed a premium on data sharing and the tools to bring about this sharing. The
results have been many powerful NI tools and databases and many national and
international collaborations that have assailed traditional research obstacles. (URL:
http://neuroscienceblueprint.nih.gov/neuroscience_resources/neuroinformatics.htm)
The Neuroinformatics Working Group of the Organization for Economic Coop-
eration and Development: The Paris-based Organization for Economic Cooperation
and Development (OECD) is a forum that brings together the governments of
some 30 member countries to tackle a range of social, economic, and trade issues.
Economic development especially via advances in science and technology is a sig-
nificant area of emphasis of the OECD. The OECD Global Science Forum (GSF)
seeks to promote international cooperation in basic science research. As part of its
science forum, the OECD established a Biological Informatics Working Group in
1996. In 2000, this group established the Neuroinformatics Working Group (NWG).
The impetus for this group was, again, the recognition of the utility of NI in deal-
ing with complex problems, great data volume, and multiple research teams in
neuroscience and the potential it holds in leading to solutions for nervous system
disorders. The NWG was given a 2-year mandate to develop guidelines for NI at the
international level, to create resources for NI, and to propose measures for sustaining
NI globally. It was chaired by Stephen Koslow (formerly of the NIH) and co-chaired
by Shun-ichi Amari (RIKEN Brain Science Institute, Japan) and Sten Grillner
(Karolinska Institute, Sweden). The activities, accomplishments, and proposals of
the NWG have been detailed in two major reports compiled by the members of
the NWG: Report on Neuroinformatics (OECD-GSF, 2002) and Neuroinformatics:
The Integration of Shared Databases and Tools Towards Integrative Neurosceince
(Amari et al. 2002). A few points from these reports are summarized here.
The NWG stressed the need for international collaboration in data acquisition,
research tools, and theoretical models in neuroscience. It also placed emphasis on
unifying neuroscience research databases. Standardization in data dissection com-
bined with a global network of databases has the potential to overcome common
obstacles to data integration, such as socio-political and cultural boundaries, and
intellectual property issues. To this end, it drafted a set of guidelines on database
standardization. To sustain multileveled NI initiatives, a two-pronged strategy was
suggested: local NI initiatives should be supported and ideally networked to cre-
ate a larger global NI network (a bottom-up NI development framework). At the
same time, international NI coordination should help synchronize local initiatives
and facilitate interoperability between these local NI systems (a top-down NI devel-
opment framework). To promote both these trajectories, the NWG proposed (a) the
creation of an International Neuroinformatics Coordinating Council (INCC), and
(b) the establishment of an international NI funding mechanism, a Programme in
International Neuroinformatics (PIN). The INCC would serve the functions of inter-
national NI coordination. It would allocate tasks to the various national nodes and
would optimize the use of international resources.
The above recommendations made by the NWG to the OECD in 2002 were
endorsed by OECD science ministers in 2004. In 2006, the OECD’s GSF carried
forth the recommendations by launching the International Neuroinformatics Coor-

dinating Facility (INCF). This body evolved after 16 OECD member countries as
well as the European Commission elaborated the initial proposals of the NWG
(www.incf.org). The INCF currently has 10 member countries and the memberships
of several other countries are in process. Its secretariat is based at the Karolinska
Institute. The funding mechanism, PIN, is well on the way of being a reality. The
INCF has already created a framework for this mechanism (see www.incf.org). PIN
will seek to fund NI projects for which national sources of funding may be lacking.
The NWG also initiated two NI portals for international data sharing and
resource exchange. The Neuroinformatics Site (www.neuroinf.org) largely serves
the function of communicating information about NI meetings and workshops
around the world.
The German Neuroinformatics Node (www.neuroinf.de) provides an online
access point through which users can share NI software and databases. It is cur-
rently in its prototype form and is funded through a grant from the German Ministry
of Science Education. Both these portals offer links to numerous other NI resources.
(URL: http://www.neuroinformatics.nl/OECD-GSF-NIWG.html)
Conclusion
The rapid success of NI over the past years is closely linked to organizations like
those discussed above that have made NI imperative. An open but centralized sys-
tem for NI coordination, protocols, and standards for NI data and key funding have
been essential ingredients to the rise of NI. Stable, long-term funding, especially
when integrated with national science/research agendas are critical to large-scale NI
projects. It is still, however, necessary that independent or local NI initiatives con-
tinually sprout new ideas. Whether in the form of exploratory committees, interest
groups, or a small database on an academic department’s computer server it takes
these seeds to grow into larger NI projects which may then become the nodes of a
wider NI network. Small NI initiatives and the larger management structures that
may assist in coordinating these initiatives often co-evolve.
The various areas of NI sampled in this section highlight the definitive role of
databases, computational tools, analytic and modeling software, and frameworks
for data access in NI. Great emphasis is placed on the gathering, organization,
integration, and sharing of data. In some instances, approaches to a problem in neu-
roscience are built around informatics methods that are actively brought to bear on a
research problem. NI influences research questions as much as they influence it. NI
shares great credit in shaping the current era of neuroscience. Almost every avenue
in neuroscience has now incorporated NI.
Chapter 3
Neuroinformatics for Neuropsychology
There is clearly an enormous difference between NI applications and the general use
of computers in the neurosciences. NI is much more than a simple extension of gen-
eral computing. NI applications by definition constitute digital systems for active
information-seeking, problem-solving, and modeling, generally based on strong
theoretical frameworks.
Neuropsychology has always been quick to embrace general computing. Even
prior to the first generation of commercially available personal computers of the
early 1980 s, simple neuropsychological tests began to appear in computerized form
(see Adams and Heaton 1987; Chute 2002). Over the past two decades, arrays of
computerized neuropsychological tests have emerged and these tests have shown
increasing levels of complexity. However, even with the advances carried by these
applications, they still remain far short of incorporating NI functionality.
Neuropsychology features minimally in the landscape of NI. Similarly, NI has
only a small presence in neuropsychology. Yet this small presence is marked by
some powerful NI-oriented neuropsychological applications/models that are rela-
tively new and which have been developed in highly specialized clinical or research
environments. The two key factors marking these examples are that they are con-
cerned with neuropsychological topics and they are designed from an informatics
perspective.
This section begins by spelling out the differences between NI applications for
neuropsychology and the general use of computers in the field. Exactly what it
means to have neuropsychology-specific NI systems is then articulated – an attempt
is made to define core principles of NI approaches in neuropsychology. Following
this, nine NI-based applications or models for neuropsychology are discussed.
3.1 Differentiating Between the General Computer

Applications in Neuropsychology and Neuroinformatics
Systems for Neuropsychology
Consider the everyday clinical or research focus of neuropsychologists. Then
consider the availability of tools and applications that confer NI capabilities
to those tasks specific to neuropsychologists. Are there tools or databases for

26 3 Neuroinformatics for Neuropsychology
neuropsychologists analogous to the tools and databases such as CARAT and CoCo-
Mac that allow neurobiologists to create maps of cortical regions and circuits?
Do neuropsychologists have information sharing systems along the lines of the
ICBM Subject Database that gives users the facility to upload imaging data to
shared platforms and then reap the benefits of the collective data? Why have neu-
ropsychologists not developed a simulation environment for their work while other
neuroscientists have developed simulation environments like GENESIS and Neuron
for modeling neural systems?
The interface between NI and a definitive neuropsychological praxis is largely
an uncharted area. This, of course, does not apply to some subspecialties allied to
neuropsychology such as neuroimaging and clinical electrophysiology. Neuroimag-
ing (see Sections 2.1, 2.2) has certainly become the preferred research mode of
many experimental neuropsychologists but the contexts in which it is used and the
medical/research questions it addresses are far from unique to neuropsychology.
Clinical neurophysiology, especially to do with electroencephalography and evoked
potentials, is now conducted with fully computerized, informatics-heavy tools. Like
functional imaging, computerized electrophysiology is a specialized discipline that
happens to serve neuropsychology but is also applied to studying a range of func-
tions far outside the scope of neuropsychology. The NI seen within neuroimaging
and electrophysiology do not constitute NI applications that can be considered
unique to neuropsychology.
In neuropsychology, the areas of (a) head injury research and (b) computerized
neuropsychological assessment show levels of sophistication in computerized meth-
ods that are almost on the threshold of transitioning to NI methods. Informatics-
reliant functions are steadily filtering into computer applications in these areas
though they remain, for the large part, short of constituting NI functionality (auto-
mated assessment, discussed in Section 3.3, is a clear exception). Nonetheless, they
signal the value of databases and computational methods for neuropsychology.
The purpose of this subsection is to clarify aspects of computerized assessment
that border on NI and aspects that do not constitute NI. A review of computerized
neuropsychological assessment is not a goal of this subsection. Many such excellent
reviews have been conducted and are cited.
Head Injury Research: It has been suggested that a national traumatic brain injury
(TBI) database will help with uniformity in TBI assessment, better communication,
and data sharing among clinicians and improved prediction of clinical outcomes
(Hall 1997; Johnston 1997). These reports have centered more on the general util-
ity of such TBI databases. Hobbs (1999) mentioned “neuroinformatics” and the
Human Brain Project and then described some implications for TBI rehabilitation,
for example, NI-based brain atlases and 3-D reference systems for brain lesions can
be used to model TBI and help to better match treatment with type of injury. In 2002,
the Journal of Head Trauma Rehabilitation published a special edition on neuropsy-
chological technologies. While none of the articles concerned NI, a few touched
on issues that are also encountered in the broader discourse on NI. Schatz and
Browndyke (2002) described scenarios where neuropsychological assessment can
be beneficially carried out on portable computers or workstations and the data then
3.1 Differentiating Between the General Computer Applications 27
uploaded to databases on remote server. Schultheis et al. (2002) described various

applications and benefits of virtual reality technology to neuropsychological assess-
ment. Chute (2002), in a broad survey of neuropsychological technologies, also
acknowledged “neuroinformatics” in describing future scenarios where informatics
systems would be integrated with neuropsychology.
General Computerized Neuropsychological Assessment: Computerized tests for
neuropsychological assessment and for psychometry have been around for more
than three decades. Major neuropsychological assessment batteries as well as stand-
alone tests either offer some parts in computerized form or are available as complete
computerized packages (see reviews by Kane and Kay 1992; 1997; Kane and Reeves
1997; Luciana 2003; Wilson and McMillan 1992). In the latter case, administration,
scoring, and statistical analysis are all carried out using software packages. Com-
puterized assessment applications add some distinct advantages over paper – and
versions of the tests. They can bring greater uniformity to test administration, data
handling and scoring, and they may be easier and less time consuming to administer
(Gur et al. 2001).
Consider a few examples of widely used neuropsychological tests and batteries:
The Wechsler Adult Intelligent Scale III! R
, the Wechsler Memory Test III! R
, and
!R
the Wechsler Individual Achievement Test II can be accompanied by a common
software package that aids in scoring and interpreting results. A computer scoring
option is also available for the Luria-Nebraska Neuropsychological Battery. The
Wisconsin Card Sorting Test! R
is available in a form that can be administered on-
screen. The software can score the patient" s responses, generate reports, and enable
comparison of the patient" s performance across trials or sessions. The patient" s basic
demographic data can also be entered. The California Verbal Learning Test! R
II
comes with a computerized scoring assistant that gives the examiner a range of scor-
ing options. Scoring complexity can be increased mainly by selecting more scoring
variables tied to measures such as learning characteristics, learning interference,
delayed recognition, etc., or by choosing to see more statistical and graphical data.
In stand-alone neuropsychological tests, for example, the Rey Complex Figure Test,
computerized scoring has also been implemented. Using a sensor placed above the
drawing space, a patient" s drawing movements (tip of the pen) can be tracked and the
drawing is automatically converted into a digital image, which can then be analyzed
with a particular quantified approach.
In these examples, a clear trend can be seen towards (a) a greater amount of data
capture or conversion of data to digital form, (b) more accurate computer-driven
scoring systems and (c) some facility for data comparison though almost entirely
intra-subject. All of these functions depend on data files, which in the case of these
computerized assessment applications, are integrated with the computer program as
opposed to being shareable or accessible for manipulation. On the one hand, these
applications are stylistically, informatics-geared. On the other hand, they remain
essentially simple computer applications for scoring tests or applying a variety of
statistical treatments. The application of computers here is limited to the goals of
efficient, standardized test administration and achieving greater statistical analyses
of data. The tests can be described as “computerized” because they are administered
and scored with the aid of computers. The integration of statistical tools with the
assessment programs also accounts for a large part of the computerized functional-
ity conferred by these applications. Successive computerized versions of these tests
are more likely to add small increments of change rather than functionality that con-
fers a potential for research breakthroughs. A hard NI functionality remains absent.
In general, neuropsychology has been using a very simple rubric when structuring
computer applications.
In these scenarios, the computer platform has not been used to dynamically
modify the tests. In contrast, NI offers methods and tools that can be dynami-
cally tuned to the very complexity of neurocognition. The sophistication of its
methods is commensurate with the complexity of cognitive-behavioral patterns that
neuropsychological assessment seeks to describe.
3.2 Defining Neuropsychology-Specific Neuroinformatics

Systems
What then does it mean to have neuropsychology-specific NI systems? How might
NI for neuropsychology be described? What might be achieved by NI-driven neu-
ropsychology that cannot be achieved by conventional methods? The essentials of
NI obviously remain the same no matter the avenue of neuroscience in which it
finds itself being applied. It becomes tailored to a neuroscience subdiscipline when
its methods are brought to bear on research problems unique to the subdiscipline.
Obviously the NI application would need to address clinical or research topics
that are typically neuropsychological. This can only be offered as a general guideline
since there is no distinct border separating neuropsychology from other subdisci-
plines in behavioral neuroscience. It should be expected that neuropsychological NI
applications would address such things as (a) cognitive profiles and neural models
relating to the functional domains of language, memory, spatial processing, etc.;
(b) syndromes such as aphasia and neglect that are uniquely neuropsychological in
that they have distinct neural and cognitive components; and (c) core assessment
methods such as the test batteries used in clinical neuropsychology. Some partic-
ular guidelines can be proposed for creating NI applications that are specific to
neuropsychology:
• The application must render observations and findings that cannot be feasibly
achieved with conventional neuropsychological methods – there has to be a
very clear advance brought by the NI tool over and above the data rendered by
conventional tools.
• Where applicable, the structure of the NI system should be commensurate with
the complexity of neurocognitive mechanisms as described by current theory in
neuroscience, that is, the complexity of an NI system should, as far as possible,
be tuned to the complexity of the neuropsychological phenomenon at which it is
aimed.
3.3 Neuroinformatics Applications and Models for Neuropsychology 29
• Using theoretical and NI frameworks, attempts should be made where possible to

reformulate neuropsychological research issues so as to generate more detailed
or quantified renderings of models, problems and phenomena. This should be
done with the perspective of examining research problems with NI tools. With an
understanding that NI can enable certain data-matching and pattern-seeking func-
tions, neuropsychologists can seek, for example, a finer grain of linkage between
behavioral and neuroanatomic data – relationships that could be overlooked
without the enabling tool.
In devising NI systems for neuropsychology, consideration should be given to

ways by which the data generated by the system can be potentially interfaced, using
NI methods, with data from other research domains (e.g., phenomics). This will
influence both the fineness of the neuropsychological constructs tapped by the NI
system as well as the format of the data sets. Consideration should also be given
to the possibility of the data being part of a larger knowledge-building network, in
which case, data formatting considerations are again critical (this is discussed in
later sections).
The challenge for neuropsychology is to take one or more of the key data seeking
and data handling methods of NI (see Table 3.1) and apply them to neuropsycho-
logical data, research problems and phenomena. To reiterate, these methods have to
do with
(a) Seeking a finer “grain” or increment of data, seeking to capture the data in
digital form or converting the data to digital form, and optimizing it for database
operations.
(b) Aiming to database the data with a breadth of data fields (the fine increments
of data), structuring the databases so that they are optimized for future data
manipulation, and where feasible, using web-accessible and shared-platform
databases.
(c) Applying data mining/pattern-seeking algorithms and data modeling methods
to elicit or test relationships between data sets.
Clinical or research initiatives in neuropsychology can apply these NI methods in

so many ways. These are best illustrated by examining examples of NI applications
in neuropsychology.
3.3 Neuroinformatics Applications and Models for

Neuropsychology
Nine examples of NI applications or models for neuropsychology are described

below. The examples relate to both clinical and experimental neuropsychology.
The examples are grouped into four broad areas: (a) general neuropsychological
assessment; (b) spatial processing, spatial neglect, and visual search/visual atten-
tion; (c) speech/language production, aphasia, and sign language, and (d) phenomics
Table 3.1 Summary of neuroinformatics applications and models for neuropsychology
Areas of
neuropsychology to
which the examples
relate Name of example Functions, innovations, and features
Neuropsychological 1. Automated • Digitization of numerous tests of

assessment and Neuropsychological specific cognitive operations
test/battery Assessment Metrics • Generation of subtest-specific data files
development; clinical (ANAM) • Databasing of test results and other
assessment and subject profile data
clinical research
• Queries to analyze data
especially applicable
• Internet-enabled assessment and
to large sets of
databases
assessment data
2. Internet-Enabled • Centralized database for recording test
Neuropsychological data (especially suited to remote
Assessment of Army assessment)
Aviators (INAAA) • Feasibility test of NI assessment system
connecting remote sites to a central
server
Research on 3. Computational Visual • Coordinate-based mapping and

visuospatial Field for Neglect digitization of the visual (spatial) field
processing, and (CVFN) • Recording/databasing of field
assessment of spatial coordinates and coordinates of stimulus
neglect and visual position
search/visual • Computation of neglect gradient in
attention precise coordinate terms
• Dynamic animated effects to
experimentally manipulate neglect
patterns
4. Computer-Assisted • Tool for graphical analysis of visual

Cancellation Test search patterns and visual attention in
System (CACTS) cancellation tasks
• Database recording of results, and
computations of search patterns
• Pattern identification algorithms for
visuospatial analysis
Research speech, 5. Directions Into • Theoretical and computational model

language, and aphasia Velocities of of speech production and acquisition
Articulators (DIVA) • Modeling of neural and network
dynamics in speech and language
• Model that facilitates NI approaches to
speech and language research in
neuropsychology
6. The Aphasia • Database of diagnostic and
Database symptomological data in aphasia
• Research tool to help clarify different
aphasic syndromes that overlap in
symptoms
• A model for databases and data mining
in aphasia research
Table 3.1 (continued)
Areas of
neuropsychology to
which the examples
relate Name of example Functions, innovations, and features
7. SignStream • Multimedia tool for annotation and

analysis of visual and gestural language
• Digital video database of signs and
gestures
• Model for capturing/analyzing gestural
communication
The Interface of 8. The FaceValue • Database of (a) quantitative

neuropsychology and Database Project measurements of craniofacial
other biomedical dysmorphology in various disorders
disciplines and (b) neuropsychological features
• Exploration of etiological subtypes of
autism and schizophrenia
9. The Consortium for • Transdisciplinary, multileveled
Neuropsychiatric investigative model
Phenomics • Standardized methods for describing
cognitive and neuropsychiatric
phenotypes
• Novel NI tools for knowledge building
in neuropsychology
• Comprehensive NI platform for
collaboration that signals future trends
in neuropsychology
and neuropsychology. For each of these areas, considerable background is first laid
out. Certain conceptual problems and methodological shortcomings in general neu-
ropsychological assessment, the visuospatial domain, and in the neuropsychology
of language, are described so as to highlight the rationale for NI. The examples per-
taining to cognitive phenomics are contextualized by an overview of phenomics
research that is pertinent to neuropsychology. Table 3.1 summarizes all of the
examples.
Many of the examples describe actual informatics applications and databases,
and a few describe theoretical models or integrative research models that are ori-
ented to NI approaches in neuropsychology. Earlier sections of this book illustrated
that the broader landscape of NI is characterized by a variety of NI applications and
systems. NI in neuropsychology is barely in its infancy and shows only a limited
number of developments but these developments are very significant and already
show some variety.
Information on the examples described was gathered using a number of sources:
published literature in neuropsychology and bioinformatics/software engineering,
various websites, and very importantly, from material obtained directly from the
few clinicians and researchers who happen to be working at the intersection of
neuropsychology and NI. Since this field is so new, personal communication with
these individuals proved to be a very fruitful way of gathering pertinent data.1 A
lot of unpublished data, project proposals, and data on projects-in-progress, etc.,
were provided directed to the author in the course of 2006–2008 (see acknowl-
edgements). This material also gave broader perspective to the various researchers’
published data.
3.3.1 General Neuropsychological Assessment

“Further advances in neuropsychological assessment will come about only to the degree that
they are linked to evolving concepts of brain-behavior relationships. Neuropsychologists
now require a deeper understanding of basic neuroscience and cognitive psychology than
was true in the past.” (Benton 1992, p. 407).
In many regards, conventional methods of neuropsychological assessment have a

proven record. They have been very effective, for example, in outlining the exis-
tence of brain damage; inferring the likely site of damage (generally in gross
neuroanatomic terms); identifying cognitive profiles, ranging from subtle to dra-
matic, that may signify types of head injury, degenerative diseases, and infectious
diseases; and pointing to spared cognitive functions with the potential to aid in
rehabilitation (Lezak 1995; Benton 1994; Goldstein et al. 1998).
Neuropsychological assessment is viewed as having a unique role in formally
describing cognitive behavior. It is also often described as a means to draw rela-
tionships between behavior and the underlying neuroanatomic system or region, by
virtue of its sensitivity to dysfunction or cognitive processes (Goodglass and Kaplan
1979; Benton 1994; Goldstein 1998). Yet many tests and some commonly used
batteries used in assessment are derivatives of tests of general intelligence that orig-
inated in the first half of the last century (see Lezak et al. 2004) and bear no direct
tie to neuroanatomic systems. In adapting tests of general intelligence for the neu-
ropsychological context and in formulating new assessment tools, there has been a
tendency to design the tools based primarily on observed deficits. This stands out as
a significant problem with conventional neuropsychological assessment tools – their
construction has been based not on sophisticated, theoretical principles of cognition
and brain function but instead on clinically observed cognitive features (Kolb and
Whishaw 2003). To some extent, this is understandable because the understanding
of functional neuroanatomy in the past was nowhere close to what it is in the present
time. On the other hand though, clinical neuropsychological assessment seems to
have become so comfortably grounded in cognitive features expressed by assess-
ment tools that it has forgotten about the need to constantly sharpen and update the
neuroanatomic reference frames for these features.
1 The author’s descriptions of all examples in this section have been reviewed by the primary
researcher/s associated with the examples. Appreciation is expressed in the Acknowledgements
Another problem with many neuropsychological tests is that multiple cognitive

and neural operations may be called into play by a test. The multifactorial nature of
many tests impacts the validity of the tests – it can blur inference of the causal factor
behind the performance or the score (Walsh 1987). The problem could perhaps give
added reason for Kaplan’s (1988) emphasis on attention to the patient’s process
and types of errors in neuropsychological assessment. Tests that involve multiple
cognitive processes may have utility in tapping large or subtle sets of features, but
they are not ideal to the task of bringing a specific cognitive process to bear on a
precisely defined neuroanatomic system.
In addition to factors of construct validity, factors such as reliability and practi-
cality always concern assessment tools and there is ample room, if not a need, for
improvement on these fronts. In the book Neuropsychological Assessment (Lezak
et al. 2004), in a chapter subsection titled “What can we Expect of Neu-
ropsychological Assessment at the Beginning of this New Century,” the authors
stated
While real progress has been made over the last few decades in understanding cognitive and
other neuropsychological processes and how to assess them, further knowledge is needed
for tests and testing procedures to be sufficiently organized and standardized that assess-
ments may be reliably reproducible, practically valid, and readily comprehensible. . .. One
means for achieving such a goal while retaining the flexibility appropriate for the great vari-
ety of persons and problems dealt with in neuropsychological assessment could be a series
of relatively short fixed batteries designed for use with particular disorders and specific
deficit clusters (e.g., visuomotor dysfunction, short-term memory disorders). Neuropsy-
chologists in the future would then have at their disposal a set of test modules and perhaps
structured interviews (each containing several tests) that can be upgraded as knowledge
increases and than be applied in various combinations to answer particular questions and
meet specific patients’ needs. ( Chapter 1, pp. 13–14)
The statement succinctly describes key aspects of assessment in need of improve-

ment. It essentially calls for some redefinition of assessment tools. It is remarkable
that at the beginning of the 21st century, following many decades of research and
development of assessment tools, such shortcomings in assessment are prevalent
and described here by an authoritative veteran of assessment, Muriel Lezak (and her
colleagues).
The point that even the general notion of NI has not been on the radar of
clinical neuropsychology, has been conveyed earlier in this section. The point
is only reinforced here when one considers that the needs and shortcomings of
assessment as articulated in the above quoted extract are needs that can be compre-
hensively addressed with NI. Neither the major compendia of assessment tests (e.g.,
Spreen and Strauss 1998) nor the major reference texts on assessment (e.g., Lezak
et al. 2004) reflect an awareness of NI and what it means for neuropsychological
assessment.
The Role of NI in General Neuropsychological Assessment: The benefits of NI
when applied to assessment have to do precisely with bringing organization, stan-
dardization, and modularity to the tools. They have to do with bringing technologies
that enable rapid changes to tools so that they can tie in closely with discover-
ies of cognition and functional neuroanatomy as these discoveries unfold. All of
these benefits in turn translate to flexibility and practicality in the usage of tools,
improved organization of assessment protocols, and greater reproducibility of the
results generated.
NI also introduces into clinical assessment one particularly radical idea, an idea
that has been absent in the field of neuropsychology, if not rather alien to the
field, and almost never raised as a possibility: that is, the potential for large-scale
sharing of everyday assessment data. Conventional modes of assessment are such
that the results of tests are stored in office filing cabinets or on the hard drive of
a clinician’s computer. Valuable data go to waste and this has been the case for
decades, as forgotten boxes of paper would go through the process of degeneration
in moldy basements. One of the greatest impediments that the field of assessment
suffers (somewhat unknowingly to the field) is the lack of large, national or inter-
national databases of assessment data. Server–client computer platforms and online
databases make this sharing possible and the potential benefits are unparalleled. Cer-
tainly, the mere allusion to the possibility of large-scale sharing of assessment data
is bound to raise instinctual doubt and disbelief among neuropsychologists. Shar-
ing of patient data is often a violation of patient confidentiality – a code that is set
deep in clinical practice. The issue of data sharing is, of course, fundamental to any
discussion on shared NI systems for assessment. Not surprisingly, this is exactly
the kind of issue that has been at the forefront in the broader discussion of medical
informatics, especially in relation to genetic and imaging data, and many possible
solutions to the problem have been proposed. In view of the centrality of this issue, it
is given special attention within a different section of this book (Section 4.1) and the
current subsection will remain focused on NI systems for assessment. In a similar
vein, issues such as standardization in assessment are not washed over by an enthu-
siastic argument for NI-based assessment. Discussion is best given to such issues in
a separate section where they can be laid out systematically.
There have been some impressive NI developments in neuropsychological
assessment. They relate to such things as (a) computerized tests that tap discrete
cognitive operations; (b) the digitization of neuropsychological batteries so as to
produce sets of data files that can be automatically uploaded to databases; (c) the
structuring of databases for many types of neuropsychological data; and (d) the
use of a, b, and c in conjunction with the internet and highly portable computer
devices for large-scale assessment, data collection and analysis. The dimensions that
NI brings to assessment simply cannot be achieved with conventional assessment
methods.
Two informatics-based neuropsychological assessment initiatives are described
in this subsection. One describes an automated battery of tests interfaced with
a database and with portable assessment devices. The other describes a project
that was designed to test a possible structure for internet-based, database-linked
assessment.
It will be seen through the examples that great emphasis is placed on test mod-
ularity and on data capture. Both projects have served to establish the feasibility of
NI-based assessment. They demonstrate numerous crucial components that make
up a large-scale NI system for assessment.
3.3.1.1 Automated Neuropsychological Assessment

Metrics (ANAM)
(see Reeves et al. 2007a; Friedl et al. 2007; Bleiberg et al. 2004; Dennis Reeves,
personal communication (July 21; August 8, 10; September 26, 27, 2008; March 7,
April 23, 2009); Joseph Bleiberg, personal communication (July 21, September, 23;
2007; February 10, March 7; 2008; April 14, 2009)
URLs: http://www.armymedicine.army.mil/prr/anam.html
http://www.nrhrehab.org/Research/Projects/ATRC+2000/
ANAM/default.aspx
Description and Background: Automated Neuropsychological Assessment
Metrics! R
(ANAM) is a library of numerous computerized tests, structured as a com-
prehensive set of test modules. It has been developed over the past 30 years, largely
as an initiative of the US military and sponsored by the US Department of Defence.
The military saw a great need for standardization in the various neuropsychological
tests and assessment software that it was using. Earlier neuropsychological batter-
ies developed within the military such as the Walter Reed Performance Assessment
Battery (WRPAB) would provide a foundation for the further development of auto-
mated neuropsychological tests. Visionary leadership initiatives to consolidate an
optimal neuropsychological assessment battery for the military then provided criti-
cal thrust that drove the evolution of ANAM (see Friedl et al. and Reeves et al. for a
detailed historical review of ANAM).
ANAM! R
constitutes a test system in that tests or modules can be selectively
grouped as test batteries to assess a target behavior or aspect of cognition. In its cur-
rent form, ANAM includes 31 test modules that run on Microsoft WindowsTM plat-
forms. The tests assess specific aspects of cognitive-behavioral-affective domains
such as attention, memory, spatial processing, psychomotor coordination, mood,
etc., as well as many other aspects of performance, such as concentration and
fatigue, cognitive set switching, and efficiency of mental processing. Examples of
ANAM test modules are: Two-Choice Reaction Time; Digit Set Comparison; Code
Substitution Learning; Matching Grids and Matrix Rotation; Stroop Color Word
Test; Tapping Test; Pursuit Tracking; Automated Aphasia and Memory Scale; Malin-
gering Task; and Mood Affect Scale. Some of the tests are adaptations of earlier
developed tests, for example, the Memory Search test is an adaptation of Sternberg’s
(1966) memory search/reaction time task, and the Tower Puzzle is a considerable
variation of the classic Tower of Hanoi task.
Parameters within each test, for example, rate of stimulus presentation, can be
modified. ANAM! R
is therefore a flexible, modular system of targeted tests. ANAM
has been shaped this way over the course of its evolution because this configuration
has been recognized as being ideally suited to cognitive and performance evaluation
in the military context: there needs to be a practical method for baseline neuropsy-
chological assessment of soldiers; repeated testing of subjects are often required and
this has to be carried out efficiently and uniformly with standardized tools. A test
battery has to be suited to a range of applications in performance training, treatment-
related clinical assessment, cognitive evaluations when neurotoxicological exposure
is suspected; cognitive status monitoring when soldiers are in prolonged, stressful

conditions, often in remote locations, etc. In the clinical realm, the battery must
also be suitable for use with various clinical populations. These considerations can
be summed by an essentially dual nature required for neuropsychological tests for
military use (Friedl et al.): (a) The tests must be tuned to assessing changes in
cognitive performance in healthy individuals as induced by various stressful situ-
ations. This is in contrast to conventional tests, which are structured around losses
in functional domains and specific neurocognitive syndromes. (b) In a clinical con-
text, the tests must also, in the classical sense, be sensitive to cortical dysfunction
following brain injury or other forms of neurological damage and must also provide
clear baseline data. The modular structure of ANAM enables easy configuration
of batteries for different clinical or research scenarios or the use of preconfigured
batteries.
Incorporation of Informatics in ANAM: The development of ANAM has always
been closely tied to developments in computerized test systems. In addition, the
context of the military in which ANAM has evolved has been one of innovative
technological forces aimed at harnessing the utility of computerized-automated
assessment. As a result, ANAM has come to incorporate various computerized func-
tions and design features that comprise core constituents of informatics-structured
assessment tools (see Bleiberg et al. 2004, Reeves et al. 2007a; Cernich et al. 2007).
Multiple Test Parameters and Parameter Modification: As indicated, the clini-
cian has the option of configuring ANAM test modules in various ways. Parameters
such as the number, size, color of stimuli, and inter- and intra-stimulus intervals can
be changed through simple software commands (command line switches). Besides
enabling customized batteries, this function gives the clinician the power to finely
probe a behavioral response by making incremental changes to one or more stimu-
lus variables. Such functions are only feasible with computerized systems (and are
further illustrated by the example discussed in Section 3.3.2.1).
ANAM scores also include a measure of the rate of correct responses per minute.
This measure of cognitive efficiency, called “throughput”, was first introduced by
the WRPAB (see Thorne et al. 1985; Thorne 2006) and has been described by
Reeves et al. (2007a) as being one of the most sensitive measures of changes in
performance.
Uniformity of Data Output and Separated Data Files: The format in which scores
are generated across all the ANAM tests is uniform, i.e., all tests produce a similar
series of scores. Each subtest also produces a data file with a unique file extension,
e.g., “.cds” for the Code Substitution Test and “.pro” for the Procedural Memory
Test. Included in a test data file are the numbers of correct and incorrect responses,
the result for each trial, and statistical and response time measures such as mean
and median response times of various sets of responses. Uniform sets of raw scores
promote easy import of the data into a database. The separation of data files of each
subtest is necessary for various database/query driven inter-test comparisons. The
coding of the raw data in a database compatible format and a diversification of data
types, all contribute to a more complex set of data fields in a database. A subject’s
demographic data are contained in a unique data file.
Data Capture and the ANAM Access Database (AADB): The AADB is a
Microsoft Access database designed to organize raw data files from ANAM tests,
create summaries of the data, and examine or combine the data in relation to one or
more variables of interest (see Bleiberg et al. 2004). ANAM test data files contain-
ing raw data and summary data can be automatically imported into the AADB. Data
import is made very simple, involving a few steps.
Data from ANAM subtests are fed into pre-existing tables in the database. Data
from a particular test are automatically fed into a table for that test (tied to the test’s
unique file extension). The database contains three main types of tables: Header
tables include data such as the subject ID, date and time of testing, and variables
selected for a test and the testing session (Fig. 3.1a). An entry (row) in the header
table corresponds to a single run of a test. If the test is administered twice in a
session, another row of data will be produced in the header table.
Fig. 3.1a Example of a header table for the Code Delayed subtest (showing one row without
data). From the ANAM Access Database User’s Manual (2004); printed with Permission, National
Rehabilitation Hospital.
Item tables contain data about the trials/stimuli of each subtest and the subject’s
responses – correct/incorrect, reaction time, and accuracy (Fig. 3.1b). In this table, a
row of data corresponds to a single trial or item of a subtest. A 15-item subtest will
therefore produce 15 rows of data in its corresponding table in the AADB.
Fig. 3.1b Example of an Item table for the Matching Grids subtest (showing one row without
data). From the ANAM Access Database User’s Manual (2004); printed with Permission, National
Rehabilitation Hospital.
Summary tables essentially summarize ANAM test data files to present informa-
tion such as mean and median scores on a test, number of items correct, number of
lapses, and throughput scores (Fig. 3.1c). A row in a summary table corresponds to
single run of a subtest. If a subtest was administered twice in a session, two rows of
summary data will be produced in the summary table.
Fig. 3.1c Example of a summary table for the Running Memory (continuous performance) subtest
(showing one row without data). From the ANAM Access Database User’s Manual (2004); printed
with Permission, National Rehabilitation Hospital.
The AADB also contains two demographic tables. These tables draw data from
the demographics data file. They include information such as the file location (path)
of the data files, date and time of testing, the subject’s name, age, data of birth, etc.
Queries: Since the AADB is a Microsoft Access database, it is benefited by the
enormous power of querying functions. Queries allow the user to view the data in
various permutations. A query can be used to sift out or analyze data based on some
criteria and combine data from two or more tables. A user can, for example, utilize
a query to select out all subjects in the 22–23 year age range whose scores in one
subtest are lower than scores in another subtest and whose mean ANAM scores are
within a certain range.
A database need not necessarily allow the user to utilize or create queries. Often,
when a database is created for a specific purpose, the user access is limited to data
entry and a limited number of data views. The AADB does not impose such lim-
itations on the user. At the same time, its query process is designed to cater to a
range of users – from those with little database skills to those who can write com-
plex structured query statements. The AADB provides the user with a number of
automated (prewritten) summary queries. The use of summary queries does not
require any training in writing Microsoft Access queries. The user is taken through
a simple wizard that presents choices on tables or variables the user would like
to select, information on various aspects of the query, and instructions on how to
complete the query (see Fig. 3.1d). Traditional queries or manual queries usually
opted for by users familiar with Microsoft Access queries may be written by using
the applications default new query interface window. Here various types of queries
may be written and they may range widely in scope and complexity. Knowledge of
structured query language obviously facilitates this process.
Internet Enabled Assessment, Remote Assessment Devices, and Shared Soft-
ware: ANAM is currently Internet enabled using a “store-and-forward” method
(see Cernich et al.). Test modules can be downloaded from an ANAM server to
a resident computer. The tests can be run off the local computer without need
for continued link to the server (applications designed with platform independent
computer languages such as Java make this possible without too many download
compatibility obstacles). The data can then be uploaded to the server for storage and
analysis. Internet-enabled function is a vital feature of ANAM’s avenues of applica-
tion in remote cognitive assessment and monitoring. An Internet-accessible Oracle
database is currently being developed to store data files from individual ANAM
tests. It will be programmed with pattern-seeking algorithms, i.e., normative patterns
across tests, populations, and test conditions.
The AADB and ClinicView© , a software package for tabular and graphical dis-
plays of ANAM test results, are ANAM software utilities that have been developed
through the National Rehabilitation Hospital (Washington D.C.). These third party
software utilities are available at no cost to the user – see ANAM links above. They
are crucial to the digital capture and display of test data.
Portable Assessment Systems: Another significant ANAM related development
that is aligned with an informatics perspective is that of portable, handheld cog-
nitive screening systems (see Elsmore and Reeves 2004; Elsmore et al. 2007;
3.3
Enter a name for the

table. This table will be
placed in the Table view
when the query is Place a check here to
completed. open the table when
the query is finished.
To automatically export
the created table as an
Excel file, click here.
Add a name for this
excel file and “Browse”
to choose location to
save file.
A series of temporary Place checks in boxes next to

queries and tables are the ANAM subtests that you
created in the would like included in the final
automated query summary table. Use the arrow
process. It is keys to the right of this window
recommended that you to view all available subtests.
select the option to
Neuroinformatics Applications and Models for Neuropsychology
delete these temporary

tables and queries, as
shown here.
Click “Next” to move
to the next screen.
Fig. 3.1d One of the windows of the Query Wizard for automated summary queries in the AADB (the instructions in boxes also appear). From the ANAM
Access Database User’s Manual (2004); printed with Permission, National Rehabilitation Hospital
39
Fig. 3.1e The BrainCheckers handheld device (PDA) displaying a trial of the ANAM Code Substi-
tution Test. From, BrainCheckers User’s Manual (2007); printed with permission, Dennis Reeves,
Behavioral Neuroscience Systems, LLC
Bleiberg et al. 2007; Reeves et al. 2007; Behavioral Neuroscience Systems 2008).
BrainCheckers is a handheld computerized neuropsychological assessment system,
and it is an advanced version of an earlier system called the ANAM Readiness Eval-
uation System (ARES). BrainCheckers runs on the Palm! R
PDA. A re-engineered
version of ANAM adapted to the Palm operating system can be self administered
with the system (Fig. 3.1e). This library of ANAM tests can be configured in many
ways as BrainCheckers is used for different screening, diagnostic, and assessment
purposes. The portability of the BrainCheckers system means that it can be utilized
in emergency rooms, battlefield environments, and other such settings where desk-
top computer-based assessment is impractical. It is also cost effective. Both of these
were major factors that drove its development.
The informatics functionality of this portable system is significant: The sys-
tem records subject information and test data in databases – a database record for
each subject. When the data are uploaded to a personal computer, Dataman, a data
manager and PC-PDA communication program, archives the data directly into a
Microsoft Access database. From the Access database, the data can be easily pasted
to other Windows applications for other kinds of viewing and analysis. A back-end
data viewer enables the examiner to view test results and summary data on the PDA
so that downloads to a personal computer are not required. As described in Part II,
Internet-enabled tools, databases, shared software and devices that help digitize data
are fundamental to the building of an NI environment.
From an informatics perspective, ANAM has been a milestone development in
computerized neuropsychological assessment. ANAM has taken a set of cognitive
tests and has adapted them to a framework that incorporates informatics functional-
ity. ANAM digitizes a wealth of raw data and creates data files that are compatible
with a powerful database application. ANAM’s database is the only database of
its kind available in automated assessment and is the first informatics-enabled
database relating to neuropsychological assessment. The mere option of having

neuropsychological test data in a database where the user has the facility to
structure queries is a hugely innovative step in computerized neuropsychological
assessment. With this kind of power given to the user, data can be viewed from
various angles and with this facility comes the potential for new observations and
discoveries.
As a test battery, ANAM has both modified older tests and structured some new
tests. In doing so, it has also made the critical addition of an informatics compo-
nent, i.e., how the tests are set up so as to gather digitized raw data in the form
of database-compatible data files. ANAM’s informatics has been geared heavily
towards greater data capture from tests that have been used in conventional cog-
nitive/neuropsychological assessment, with emphasis on clearly defined cognitive
operations. Nevertheless, it is recognized that there is some functional overlap in the
subtests of the current version of ANAM and that other NI methods are needed for
ANAM tests to be interpreted with greater precision (see Friedl et al. 2007). As is the
case with many NI projects, ANAM is a work-progress. There are numerous issues
and new features that its developers are addressing (see Reeves et al. 2007a). An
Internet Oracle database, for example, is being developed. This large-scale database
will be capable of holding ANAM data from widespread clinical and situational
conditions, thus facilitating the development of norms and the study of trend pat-
terns. It is not unfeasible that as ANAM further develops, it will have a specialized
team that focuses on algorithms that seek cognitive factors and patterns among
the data.
Since NI is so new to neuropsychology, neuropsychologists may not immediately
realize what an advance ANAM represents in terms of NI for neuropsychology. The
AADB in particular marks not a small, incremental step in computerized assessment
but a strident leap into the realm in NI.
3.3.1.2 Internet-Enabled Neuropsychological Assessment of Army Aviators

(IENAAA)
(Walter Reed Army Medical Center (Personal Communication, Mark R. Baggett
and Mark R. Kelly, September 27, 2007; Daniel Christensen, Oct. 5, 2007)
URLs: http://www.stormingmedia.us/59/5911/A591104.html
http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=
html&identifier=ADA401195
Background and Description: Aviation is one of the specialized areas within the
US Army. Specially structured cognitive tests have traditionally been applied to
assess baseline cognitive screening of army aviators. The critical need to assess spe-
cific cognitive functions in potential aviators or injured aviators is obvious in terms
of fitness to fly or carry out complex support functions. Candidates for flight train-
ing need to have a certain cognitive baseline, especially in functions relating to the
flight environment. A pilot with an injury that brings potential neuropsychological
compromise needs to be assessed in relation to a functional baseline. In addition
to requiring a critical screening tool, the context of army aviation also calls for
standardization in the cognitive assessment tools it uses.
The IENAAA project sought to create an Internet-enabled and database-

linked neuropsychological assessment system for cognitive assessment of avi-
ators. The project was carried out in 2000–2001 and while it is no longer
active, it led the way for informatics-based neuropsychological assessment. The
project was led by MAJ. Mark Baggett, Ph.D. (Deputy Chief of Psychol-
ogy, WRAMC), CPT. Daniel Christensen, Ph.D. (Neuropsychologist, WRAMC),
Dr. Mark Kelly, Ph.D. (Chief, Neuropsychology Service, WRAMC), and LTC.
Gregory Gahm, Ph.D. (Chief, Behavioral Health Clinic, MAMC). The project
would show that automated computer-based assessment could feasibly be deployed
to handle large amounts of data generated through large numbers of service
personnel.
The major objective of the project was to examine how computerized neu-
ropsychological assessment could be carried out at remote locations via portable
computers and how the data could be uploaded to a central server. To this end, a
database (Microsoft SQL 7) was developed for data uploads. Two other objectives
were tied to this main objective: (a) the development of an online neuropsychologi-
cal inventory for demographic and medical background data and (b) the examination
of relationships between sets of similar cognitive measures (subtests) from three bat-
teries, the US Army-Aeromedical Cognitive Assessment Tool (USA-ACAT), which
is a test battery derived from ANAM 2001, SynWin (Synthetic Work for Windows),
and CogScreen. A secure server was set up at Walter Reed Army Medical Cen-
ter. The server enabled downloads of the ANAM, Cogscreen and SynWin tests. The
tests were downloaded at Fort Campbell, Kentucky, the evaluation site, where they
were administered to 100 army pilots via desktop or portable computers. The result-
ing data were then uploaded to the server and the investigators were successful in
accessing the data. Subsequent data collection via the website was also carried out
at Fort Rucker, Alabama, in a related study.
The IENAAA was simply a feasibility study about applying a set of standardized
information-technology protocols to large-scale neuropsychological assessment, but
the project pushed forward the concept of Internet-enabled assessment. It laid sig-
nificant groundwork. From a plain NI-neuropsychological perspective, its initiatives
are examples of critical foundational steps in any NI undertaking of Internet-
enabled neuropsychological assessment: A neuropsychological questionnaire for
demographic data was modified to function as an on-line instrument. The USA-
ACAT was configured as an application that could be downloaded and then run on
a remote computer. The application would package the test results as a data file that
could be uploaded to the database. The SQL server platform lay at the heart of the
project – a cohesive center for application dissemination and data collection and
analysis.
ANAM and its Internet-enabled components now provide the functionality called
for by the IENAAA. Currently, at the Defence and Veteran’s Brain Injury Center
(DVBIC) at Fort Bragg, North Carolina, ANAM systems are used on the sol-
diers of the 82nd Airborne Division to obtain neuropsychological baselines prior
to deployment and for examination following traumatic brain injury. The setup of
the automated assessment system has been modeled on the IENAAA.
Conclusion for Sections 3.3.1.1 and 3.3.2.1

The examples of ANAM and the IENAAA demonstrate the unparalleled gains of
NI-based neuropsychological assessment. The examples represent responses to the
need for streamlining and efficiency in the assessment process, in the context of the
army. They demonstrate the process through which these needs can be met and how
in the same process greater gains in assessment data can be made. Many concepts
are successfully demonstrated by the examples, including the digitizing, databasing,
and mining of assessment data.
On a broader level, the examples described in this subsection illustrate the build-
ing of NI-based assessment systems at multiple levels – from the redesigning of
test batteries to servers at remote locations to which data can be uploaded. The
NI approach to assessment is optimized with attempts to spell out target cognitive
operations with precision. Computerized tests of these operations are then carefully
designed – not simply to be computerized versions of pencil-and-paper tests, but
as tests that can be interfaced with databases. A key objective is to derive rich data
that can be stored, analyzed, and re-rendered. Assessment can then be automated,
Internet-enabled, and thereby be carried out in variety of contexts.
NI methods when applied to assessment add dimensions that cannot be achieved
with conventional or simple computer-assisted assessment tools. The framework of
a shared platform seen in ANAM and the IEAAA provides the discipline of clini-
cal neuropsychological assessment with a view to how a large-scale NI system can
reinvent the discipline.
3.3.2 Visuospatial Processing, Visual Attention, and Spatial

Neglect
Visuospatial function is a major functional domain in cognition and is an area of

significant focus in neuropsychology. It is an immensely broad domain, covering
some aspects of primary perception but largely concerned with high-level vision
(visual and spatial cognition) and visuomotor integration. As a descriptive term,
“visuospatial” embraces a range of spatial processes relating to visual perception of
figures, forms, objects, and body parts; mental/cognitive maps and representations;
and various dimensions of space in which one acts.
Defining Visuospatial Function: The complexity of this domain has made for
an ongoing challenge to neuropsychology. There has been a clear absence of a
breakdown of taxonomy of visuospatial processes for neuropsychologists to ref-
erence in describing the nature of a spatial deficit. (Contrast this with breakdown of
language into units such as phonemes, morphemes, words, syntax, semantics, dis-
course, etc.) As a result, the constructs underlying visuospatial function have been
vague and the terminology used to reference this domain has reflected great confu-
sion: “Attempts to select and organize findings from neuropsychological studies of
visuospatial disorders into a coherent and comprehensive schema are fraught with
problems facing any reviewer in any field, only perhaps to a greater degree. The
nature of the data, the absence of a clearly defined conceptual framework, and a his-
tory of confusing and inconsistent terminology all result in bias and lack of clarity”
(Newcombe and Ratcliff 1990, p. 333). A fundamental problem has been the lack
of agreement regarding the definition of visuospatial function. Further, descriptions
of what is visuospatial in neuropsychology have been crafted largely with reference
to operational definitions as carried by visuospatial tests:
“A common practice is to define the visuospatial dysfunction on the basis of a particular

experimental task rather than on conceptual or anatomic criteria . . . the term visuospatial
must be explicitly defined . . . it is important to precisely specify what is being studied and
how it conceptually relates to the broader theoretical framework of spatial cognition . . . ”
(Levin 1990, p. 161).
In response to such problems, Jagaroo (1999) suggested that when referring to

“visuospatial” function, neuropsychologists should attempt to define the particu-
lar spatial operation/s involved, the spatial frame (e.g. egocentric, topographic) that
may be implicated, and the neuroanatomic systems at play.
Visuospatial tests in neuropsychology have often been “designed to probe the
capacity for visual analysis and synthesis” (Benton 1994, p. 6). Tests such as the
Rey Complex Figure Test, the Hooper Visual Organization Test, and the various
spatial subtests of the WAIS are tests that index amalgams of spatial processes.
They paint a rather general picture of visuospatial integrity. These tests have not
been structured to parse out precise spatial operations in cognitive or neural terms,
and they also happen to be tests that have seen little or no evolution over the past
many decades. The simplicity with which clinical neuropsychology has historically
conceived of the visuospatial domain inevitably elevated the role of simple assess-
ment methods: “The simplest and most direct procedures for revealing deficits in
visuospatial functions involve paper-and-pencil drawings of familiar objects and
geometric forms. Commonly used objects include clock, daisy, house, elephant,
bicycle” (Goodglass and Kaplan 1979, p. 17). As alluded in the preceding sub-
section, among the variables influencing performance in these tests are, perception
(involving multiple levels of processing); high-level spatial representations, and the
generation of a motor plan based on the representations when motor actions are
involved; and feedback between the neural centers involved with all these processes
(see Jagaroo 1998a,b).
Visual and Spatial Processing Described in Cognitive Neurobiology and Cogni-
tive Neuroscience: The problems laid out above constitute a serious and unfortunate
lag in neuropsychology because the study of visual and spatial processing in
neurophysiology and cognitive neuroscience has systematically progressed. It has
described greater and greater levels of complexity in visual and spatial processing
in cognitive terms for which it has identified corresponding and complex neu-
roanatomic systems (see Van Essen et al. 1990; Chalupa and Werner 2004, for
reviews). The pioneering work by Ungerleider and Mishkin (1982) described neural
pathways that project from the visual cortex to inferior temporal and posterior pari-
etal cortices in the macaque brain, carrying visual and spatial information about an
object’s identity and location, respectively. The work provided the first systematic
account of visual-spatial processing beyond the visual cortex, the functional prop-
erties of which had been mapped earlier in cats and monkeys (Hubel and Wiesel
1962; 1978).
Through the 1980 s and 1990 s, neurobiological and neurophysiological stud-
ies on visual and spatial processing (largely in non-human primate brains) saw an
explosion in numbers. They aimed to draw clear associations between visual/spatial
processes and cortical systems. Noteworthy for neuropsychology is the precision
with which they defined visuospatial, perceptual, and cognitive operations. These
studies were concerned with such processes as the mnemonic coding of coordinates
involved with mapping spatial plans for eye movements in the dorsolateral pre-
frontal cortex (Funahashi et al. 1989); spatial frameworks for movement kinematics
and movement control coded by the area 5 of the parietal cortex (Kalaska 1991);
the representation of head-facial profiles in neurons around the superior temporal
sulcus (Perrett et al. 1992); and multimodal spatial coordinate representations and
coordinate transformations in the posterior parietal cortex (Andersen et al. 1993).
Synthesizing such data and the vast amount of data on cortical connections in neu-
robiology, Felleman and Van Essen (1991) compiled a map that indicated some 32
cortical areas involved with visual processing, including more than 300 connections
among these areas and a distinct neural processing hierarchy among these areas. In
visual neuroscience, this often cited map has served as a major reference for the
functional anatomy of visual and spatial processing.
Cognitive science has been equally focused on the “dissection” of visuospatial
processes: Earlier pioneering work laid out, for example, the variables of features
in visual attention and object recognition (Treisman, and Gelade 1980; Treis-
man 1982); graded differential hemispheric processing based on spatial frequency
(Sergent 1982; 1991) and categorical versus coordinate relations (Kosslyn 1987;
Kosslyn et al. 1992) in the visual scene; and the role of representational coordi-
nate systems in mental manipulation (Just and Carpenter 1985). Functional imaging
then signaled the possibility of localizing discrete spatial operations (see Roland
and Friberg 1985; Haxby et al. 1991) and soon the landscape of visual cognition
was transformed. Visuospatial processes would now be gleaned through a range
of cortical regional activation patterns, for example: The posterior parietal area in
relation to 3-dimensional mental rotation/manipulation (Cohen et al. 1996; Richter
et al. 1991); prefrontal, premotor, and occipito-temporal regions in relation to spatial
working memory tasks (Jonides et al. 1993); responses properties of a fusiform gyral
area (the fusiform face area) in relation to faces (Kanwisher et al. 1997; Kanwisher
2000) and its potential to be tuned to sets of objects that share similar looks and
spatial form (Tarr and Gauthier 2000); a parahippocampal gyral area (the “parahip-
pocampal place area”) in relation to visual scenes that convey relative layout of
objects (Epstein and Kanwisher 1998); and a region of the lateral occipitotemporal
cortex (the “extrastriate body area”) with regard to pictures of bodies and non-facial
parts of bodies (Downing et al. 2001). Numerous cortical modules for visuospatial
processing could then feasibly be laid out as functional-anatomic maps built from
functional imaging studies alone (see Grill-Spector and Malach 2004).
Implications for Visuospatial Assessment in Neuropsychology: Against the vast

backdrop of visuospatial research in neurobiology and cognitive neuroscience, the
modes of visuospatial assessment in clinical neuropsychology are baffling. They
are at odds with the type of constructs and the level of cognitive and neuroanatomic
detail with which visuospatial processing is described by these disciplines. Visu-
ospatial assessment simply cannot afford not to look to the data from these
disciplines. The data essentially amount to the finest available grain of spatial
processes and their neuroanatomic systems. This, however, does not mean that
visuospatial assessment should defer to cognitive neuroscience or entirely to the
modality functional imaging for a fine assessment of these functions. Clinical visu-
ospatial assessment can draw on all the types of data laid out above and it can factor
key principles in designing a new arsenal of visuospatial assessment tools. It can,
at the same time, by adopting NI methods, remain fundamentally in the realm of
clinical neuropsychological assessment. To be shaped by the data of visual neuro-
science means that the clinical visuospatial assessment will gain greater construct
validity, greater alignment with neuroanatomic systems, and that its methods will be
conferred with immense research potential.
To accomplish this, NI, once again, is a critical means and there are many
potential applications. The discussion below will focus on one major avenue of
application.
A Role for NI – Coding the Medium of Spatial Tests: One of the reasons for a
general imprecision when addressing visual and spatial operations in neuropsychol-
ogy is the lack of sophisticated tools to code a common medium for visuospatial
assessment – the area of space (a page or a computer screen) on which visuospatial
tests are presented and the stimulus presented within this space. Points in the spa-
tial field of assessment would each need to be coded in some way. There have been
some descriptions of (a) computer interfaced methods and algorithms to enhance
the sensitivity of cancellation tests (Donnelly et al. 1999) and (b) computer record-
ing of coordinate points in line bisection tests (Potter et al. 2000). The studies
are notable for devising simple computer-enhanced methods to code the spatial
field.
A comprehensive informatics system for spatial assessment, on the other hand,
would require a spatial coding system where each point or region in the assessment
space is given an address, and it would also require an array of software modules to
handle the data. With this system, the addresses of all the coordinates that make up
this space could easily be programmed into a database as can the address of an occu-
pying stimulus. Information on varying stimulus patterns and the patient’s responses
to each condition can also be databased. With this data, a wealth of insights can be
gained.
Two NI projects are described below, both to do with NI systems for visuospa-
tial assessment. One places more of an emphasis on decoding patterns of spatial
neglect while the other focuses on visual search and visual attentional patterns. Both
represent significant departures from conventional tools. Their functions enable (a)
databasing and coordinate-based analysis of spatial information and (b) the capture
and rendering of kinematic and temporal spatial data.
3.3.2.1 Computational Visual Field for Neglect (CVFN)

URL: www.cvfn.net
The CVFN is a computational tool designed mainly for assessment and research
of spatial neglect. It is being developed by the author at Boston University and
Emerson College, based on NI architecture described in the past (Jagaroo 2002). A
beta version of the tool is currently being tested in a pilot study.
Background: The phenomenon of spatial neglect has an immense bearing in
neuropsychology. The complexity of the phenomenon draws upon the processes
of attention, motor planning, spatiotopic encoding, and representational (“mental”)
space. A few neuropsychological models have attempted to explain the condition,
especially the predominance of left field neglect following damage to the right
hemisphere (see Farah 2000; Heilman et al. 1993). One of these models, the “repre-
sentational” theory of neglect, suggests that one half of the internal representation of
space is either cut or “extinguished” (Bisiach and Luzzatti 1978; Bisiach et al. 1996)
or that this mental representation of left field hemispace is compressed or distorted
in a manner that can be described with mathematical precision (Burnett-Stuart et al.
1991; Halligan and Marshall 1994; 1998). In hemispatial neglect, it is primarily the
representation of length along the horizontal axis that is distorted (Burnet-Stuart
et al.) though neglect can occur along any axis in the spatial field. The degree of
perceptual distortion and the degree of attentional bias differs for each axis of ori-
entation (imagine the horizontal axis being rotated about its midpoint, traversing
successive axes as it completes a 360◦ rotation). In the line bisection task, a test
that is very sensitive to neglect, patients transect the line significantly to the right of
the true midpoint (see Bisiach et al. 1983) and the degree of transection displace-
ment is linearly related to the length of the line (see Nichelli et al. 1989). Halligan
and Marshall have explained such effects with the notion of distortions in repre-
sentational space that are governed by fixed geometric constraints. They illustrated
through a series of experiments a central idea that right hemisphere damage can dis-
tort the representation of space: “These distortions are fully consistent with a model
whereby points in ‘left space’ are compressed rightwards; the compression function
is linearly proportional to the coordinates of Euclidean space.” (1991, p. 628) This
idea is consistent with animal models of the posterior parietal area (area 7) that sug-
gest it to be a region specialized for coordinate mapping of space (Andersen et al.
1987; 1992; Stein 1991; Duhamel et al. 1991) and with other neuropsychological
models of the area that cast it as a center for spatiotopic coordinate transformations
(Jagaroo 2004). Altogether, these models suggest that representation of the entire
visual field is integrated in the right PPC along spatiotopic principles – a particular
coordinate in external space in mapped to a precise coordinate in the right PPC rep-
resentational matrix. They also suggest intricate spatial dynamics tied to neglect and
how these dynamics might be experimentally manipulated in studying neglect. They
point to the degree to which neglect and the parametric space being neglected can be
deconstructed given their discrete geometric and neural properties. A proper decon-
struction of the hemispatial neglect must therefore take into account the context of
the stimulus within a coordinate-based visual field.
Degree of neglect calculated by counting coordinate cells
Cells of the Grid Major coordinates

recorded in an Excel
Sheet or Access Database
Grid (invisible to patient) Stimulus Item (visible to patient)
Fig. 3.2a Schematic illustration of the grid matrix
The Limits of Conventional Tools in Assessing Neglect: "Paper-and-pencil" tests

have been the primary method of assessing the visuospatial aspects of neglect. Some
examples are the Boston Visuospatial Quantitative Battery, the Rey Complex Figure
Test, and letter cancellation and line bisection tasks. In these forms of assessment, a
sheet of paper or a computer screen containing the target illustration is presented to
the patient. The patient is required to look at the visual stimulus and copy it, repro-
duce it from memory, answer questions about it, or carry out bisection or selective
cancellation tasks. The patient" s reproduced drawing or answers about the visual
stimulus are then qualitatively assessed. Simple quantitative assessment methods
are sometimes manually applied to the patient" s drawings.
There is a huge discrepancy between the neuropsychological complexity of
neglect and the neuropsychological tools used to assess neglect. Paper-and-pencil
tests are fine in terms of the gross assessment of neglect but they provide no
information about the intricate mechanics of the condition. As indicated, simple
illustrated drawings cannot produce information about precise spatial coordinates
of the visual stimulus or the visual field that contains it. Equally limiting, because
these tests are static in form, they are not useful in examining temporal and dynamic
effects – how moment-by-moment incremental changes to a stimulus, for example,
can change the neglect pattern. Many of the more interesting and hidden dynamics
of neglect remain obscured in conventional assessment. In order to capture pre-
cise patterns of visual field gradients in neglect far more complex methods are
needed.
NI Approach to Assessing Neglect: In view of the limitations described, the NI
approach to assessing neglect must involve a digitized visual field and computa-
tional system to map the coordinates of the visual field. This system should be able
to capture the subjective coordinates of a visual stimulus (the perceiver’s response or
production) in two-dimensional Euclidean space and measure this against an objec-
tive reference frame. In clinical assessment, the visual field is typically a parametric
section of space defined by the area of a page or computer screen. The CVFN takes
a large computer screen and turns it into a computational visual field matrix. In this
system, a computer-generated matrix divides the computer screen into many cells
(squares) to produce a grid. The fineness of the grid can also be varied from a few
large cells to thousands of small cells. The cell at the midpoint of the grid is given
the coordinates (0; 0). In one configuration of the grid, cells on the X-axis to the left
of the center are assigned negative coordinates, e.g., from –1 to –40. Cells to the
right are assigned positive coordinates, +1 to +40. Cells along the Y-axis, above cell
(0; 0) are assigned positive coordinates, +1 to +30. Cells below are assigned negative
coordinates –1 to –30. The resulting matrix amounts to a grid of uniform cells, each
with a unique address – a set of unique coordinates (see Fig. 3.2b). The default posi-
tion of the grid is such that coordinate (0; 0) defines the midpoint of the presented
visual field: The Y-axis (–30 to +30) defines the midline separating each hemifield
and the X-axis (–40 to +40) defines the horizontal separation between equal-sized
upper and lower fields. The grid acts as a reference system, i.e., an objective
Euclidean map.
When used in assessment, two computer screens are involved. The examiner
views one screen and the subject views another. Both screens are tied to the same
control system but the grid is invisible on the subject" s screen. On the subject’s
screen, the flower will appear on a plain background. The flower, however, occupies
certain cells on the invisible grid on which it is imposed.
Each cell in the grid is mapped to a database called the Coordinate Recording
Database (CRD). The position of a stimulus placed within the grid is also mapped to
the database. For each cell in the grid, the CRD has other data fields in addition to the
fields the code the cell’s position. The other fields can record attributes such as stim-
ulus color, percentage of the field being occupied, etc. There are a number of other
important programmed components that make up the system: The grid controller
is used to stipulate how many cells should make up the matrix, that is, the cellular
density or complexity of the matrix. It can also elongate cells and cell contents ver-
tically or horizontally to warp regions of space as may be required experimentally.
The option of varying the matrix configuration is an important one. A large-cell grid
configuration, for example, would be better suited to a patient exhibiting very gross
neglect. The coordinate computational kernel (CCK) is a computational engine that
is composed of algorithms and queries. This component essentially converts grid
data to numerical arrays and then compares the data. Computational criteria can be
programmed as needed. A graphics database provides a selection of basic shapes
and patterns and can also accommodate other figures and pictures that may be
inputted for use. A graphics kernel provides a simple graphics editor to alter the
shape, form, size, and color of a stimulus. A patient profile database is comprised
of a set of tables that store the patient’s performance data. It can be programmed
with analytic queries as needed. An analytic module is a set of strings, macros, and
queries that run on the CRD and Patient Profile Database to look for relationships
between stimulus/grid conditions and the patient’s performance and to carry out
inter-subject comparisons.
All the databases included in the system are designed using Microsoft Access;
other components are for the most part programmed with C++. The beta version
of the system employs only some of the components described: The CRD, a sim-
ple Grid Controller (offering 3 three-grid configurations), and the Patient Profile
Fig. 3.2b Schematic illustration of the CVFN’s Coordinate Addressing System. From, Jaga-
roo (2002). Dynamic computational visual field matrices: A computerized mapping system for
the analysis of visual perception, spatial processing and featural recognition. In C.H. Dagli,
A.L. Buczak, J. Ghosh, M.J. Embrechts, O. Ersoy, & S.W. Kercel (Eds.) Smart Engineering System
Design, Neural Networks and Fuzzy Logic, vol. 12. Printed with permission, American Society of
Mechanical Engineers Press
Database. Other components are being worked on as the greater project progresses.
Figure 3.2c provides a schematic of the architecture of the CVFN system.
Functionality Gained Through a Computational Grid Matrix: An infinite number
of stimuli and visual field variables and permutations are enabled by this NI system
GRID CONTROLLER
COORDINATE
VAR (1:8)
COMPUTATIONAL
Controls grid density Seq 1
KERNEL
and enables warping Σ((+3–5), (–5+6))
of grid sections Seq 2
Converts grid data
Σ ((+17–9), (–30+29))
into numerical arrays
If CRD(X,X) = open
Increment = (4) for data comparison
Enter (X,X)
GRAPHICS DATABASE Mark (–1+4)
table[gridpoint]
Begin level {23}
power =3
Offers a selection of Position if ƒ(+2–5)
graphical objects bit (0, α –1, 1, α –5)
(stimuli). Objects bit (3, δ +1, 4, δ –7)
can also be added to Stop Level {45}
this database. End
(+4+3) (+5+7)
(–3+5) (+4–5)
(–23+24) (–30+29)
(+13–14) (+27–18)
(–10+12) (–1–3)
COORDINATE
RECORDING
GRAPHICS KERNEL DATABASE
Simple graphics editor for Records the coordinates

creation and manipulation of each cell in the matrix
of objects: size, color, etc. THE GRID MATRIX as objects places
Composed of numerous cells each in the matrix
with a unique coordinate address
Select Fig 8
Bound M:shape = rec
Border = 6 Subject/Patient 78
Size = DEF ANALYTIC MODULE Run Query C3
Deg vLap (4:7) circ Analyzes performance Adjust with Macro P78
Warp inc=1 down (intra–and inter– Subject/Patient 34
patient) Run Query C3
Adjust with Macro P34
Subject/Patient 10
Assoc String 5 Run Query C3
P1[C3] com P2[C3] Adjust with Macro P10
Dim = tpointt
Write data [Table 10]
PROFILE DATABASE
Stores data on patient’s
responses/performance
Fig. 3.2c Schematic illustration of the CVFN’s Architecture. From, Jagaroo (2002). Dynamic
computational visual field matrices: A computerized mapping system for the analysis of visual
perception, spatial processing and featural recognition. In C.H. Dagli, A.L. Buczak, J. Ghosh,
M.J. Embrechts, O. Ersoy, & S.W. Kercel (Eds.) Smart Engineering System Design, Neural
Networks and Fuzzy Logic, vol. 12. Printed with permission, American Society of Mechanical
Engineers Press
of assessing neglect. Analysis need not be limited to stimuli presented on-screen. A

subject’s drawings of stimuli can be scanned and fed into the system for analysis.
The key advances of the computational grid system over conventional methods may
be summarized as follows:
Coordinate Referencing and Tracking: In line bisection tasks, performance accu-
racy can be systematically improved when the line’s true center is incrementally
moved to the right of the visual field midline (Halligan and Marshall 1995).
Such discoveries have been made when both the line length and the point of
transection have been carefully measured (see Bisiach et al. 1990; Halligan and
Marshall 1991). Such data have been obtained manually, often requiring hundreds
of paper-illustrated variations of a stimulus. The tedium of such manipulations can
discourage further such analyses. With a computerized matrix system, all the follow-
ing data can be preset and/or referenced in seconds: (a) the coordinates occupied by
the line – indexing line length and displacement; (b) the coordinate corresponding to
the point of transection; (c) the relative degree (in numerical units) to which transec-
tion is displaced towards one hemifield; (d) the pattern of the perceiver’s regression
or improvement over a number of trials or over a period of time; (e) the aggregate
critical “sector” of the line where transection occurs (within and across patients);
(f) the average coordinate position of the patient’s (biased) midline based on his/her
line transections; and (g) transection points across varying line lengths.
Stimulus Displacement and Field Gradients: In neglect, a patient’s omissions are
not always limited to the left hemifield (see Small et al. 1994). Omissions may occur
along the midline and in some cases, in the right hemifield. This neglect “gradient”
often defines a patient’s unique neglect profile. Attempts have been made to map
this gradient along a simple 3-point scale (see Small et al.), a system that crudely
neglects large sectors in the hemifields. With a computerized matrix, the gradient
can be generated instantaneously and can be accurate to the point of a matrix cell.
All averaging functions and tracking functions (over time) can be applied to gradi-
ent assessment. The stimulus pattern can also be displaced by very fine increments
towards either hemifield in order to establish the X-axis point at which the gradient
is zero, that is, by displacing the stimulus by precise increments, one cell displace-
ment at a time, it will be possible to compute the patient’s perceived (displaced)
midline.
Masked Stimuli, Global-Local Effects, and Figural Modulation: The system can
be programmed to implement masking effects, obscuring effects, and global-local
effects on visual stimuli, for example, (a) stimuli in one hemifield can be masked
at varying degrees along a fine gradient; (b) featural or outline cues can be added
to one hemifield, again to assess how perception is modulated under these condi-
tions; (c) framing effects, shape modulation, and global cueing effects can also be
incorporated; and (d) the effects of masking or featural cueing on neglect can be
tracked.
Chimaeric Stimuli and Stimulus Compression: Chimaeric stimuli used in the
study of visuospatial processing have produced dramatic results but have been lim-
ited largely to pictures of faces and simple objects (see Young et al. 1992). Again,
practical constraints in manually generating and altering these figures prevent com-
plex permutations. With a matrix-controlled system, almost any aspect of chimaeric
stimuli can be easily adjusted, again, akin to the adjustments allowed by a sim-
ple computer graphics application: (a) the matrix of one hemifield governing the
chimaeric piece in that field will be able to adjust the dimensions and color of the
figure; (b) adjustments can be made to one half of the chimaeric figure so as to make
it incrementally similar or dissimilar to the other half. In this way, the degree of
Blinking arrows in neglected field Center-to-left Arrow Train in neglected Center-to-left Color Wave in neglected
while displaying stimulus item field while displaying stimulus item field while displaying stimulus item
Fig. 3.2d Schematic illustration of dynamic stimuli with movement/animation field-enhancing

effects in the CVFN
“chimaeric gradient” can be manipulated; and (c) differential chimaeric gradi-

ents can be computed for different categories of objects or for different sets of
coordinates.
Animated Priming Effects: Another major innovation of the system has to do with
its capacity to introduce movement or animated effects. In neurocognitive research,
the implementation of animated/movement effects made possible through animation
software offers huge potential. It provides a means of studying motion perception
systems as well as spatial processes that can be modulated by motion dynamics (see
Jagaroo and Wilkinson 2008, for a discussion on this topic). In the CVFN, move-
ment effects can add salience and highlights to the neglected field. Dynamic stimuli
such as blinking arrows, moving trains of arrows, and color waves can be applied to
the background of the neglected field. The aim is to highlight the field and in theory,
to do so using synchronous movement patterns that trigger the dysfunctional neural
centers that may produce some forms of neglect. Figure 3.2d provides a schematic
illustration of a few examples of dynamic stimuli.
In summary, the power of the matrix lies in its computerized (digitized) coor-
dinate structure and function. The system brings computational, graphical, and
database power to neuropsychological assessment of neglect. This NI approach
to studying neglect marks a radical departure from conventional pencil-and-paper
methods. The complexity of the system is attuned to the complex spatial dynamics
of neglect. The system can potentially be adapted to studying a broader range of
visuospatial functions where testing utilizes a parametric visual field.
3.3.2.2 Computer-Assisted Cancellation Test System (CACTS)

(See Huang and Wang 2005; Wang et al. 2006; Huang and Wang 2008; personal
communication, Ho-Chuan Huang, October 19 and 22, 2007; July 21, 27, and
28; 2008)
CACTS is a computerized system for the graphical analysis and assessment of
visual search and visual attention. It is geared primarily for cancellation tasks but
can be adapted to other visual search/attention tasks. CACTS has been developed
through a collaborative effort between information technology and occupational
therapy specialists at the National Kaohsiung University of Applied Sciences and
the National Cheng Kung University, respectively, in Taiwan. Its development has
been supported in part by the National Science Council of Taiwan.
Background: The development of CACTS was motivated by some key factors.
It was recognized that while visual search, scanning, and cancellation tasks have
been widely used in visuospatial assessment, inherent limitations are contained in
the conventional paper-and-pencil nature of these tasks (of the type described in the
preceding subsection). Again, the static nature of these conventional tasks makes
for a poor rendering of the overall visual search and attention process. Informa-
tion about onset time, search paths, search strategies, stops and pauses, etc., can be
captured only crudely. A computerized interface was sought to address these limi-
tations. A second consideration was the need to capture visual search and scanning
trajectories without necessitating the use of eye-tracking devices that usually require
more elaborate hardware and a specialized testing environment. A highly portable
system that would be capable of registering attentional search would be much more
preferable in, for example, a school setting where a clinician may need to assess
visual attention in a large population of children in an efficient manner. CACTS was
therefore developed to utilize only a personal computer and a monitor. The aim was
to create a computer-interfaced system to capture dynamics processes in a subject’s
visual search and attention during cancellation tasks and then apply algorithms to
analyze the attentional pattern.
Design and Architecture of CACTS: The system runs on a personal computer
using Microsoft’s Windows XP platform. The software is programmed in C++. In
the latest setup of CACTS, the hardware consists simply of a tablet computer with
a touch-sensitive screen and a cordless screen pen. When the user applies the pen to
the screen, its pressure-sensitive tip transmits signals to the tablet computer at about
the point of contact. Euclidean (x, y) coordinates together with corresponding time
of the event are automatically recorded in a database.
CACTS involves four software modules (see Fig. 3.3a). A profile module serves
to hold a subject’s general and demographic data such as age, sex, and education
level. A test module is designed to contain various forms of attention/cancellation
tests. An outcome analysis module records and analyses a subject’s attentional pat-
tern and provides the examiner with graphical tools for the analysis. A print module
allows the examiner to be selective in terms of data to be printed. A Microsoft
Access database is used to store the subject’s demographic and test data.
Kinematic and Metric Functionality: One component of the CACTS database,
the process table, stores data on kinematic aspects of the subject’s visual scan path.
General attentional dynamics can subsequently be pictured using this data. Kine-
matic data include response coordinates, distances between consecutive response
coordinates, and pause and completion times between consecutive response coor-
dinates. Total times for movement, pauses, and completion can also be recorded.
The system’s analysis module can use this data together with a pattern identifica-
tion algorithm to construct a scaled figural representation of the subject’s search
sequence and overall scanning strategy (see Fig. 3.3b). Sequential nodes along
the visual scan path can be highlighted. The coordinates marking the subject’s
attentional center can also be highlighted. This convenient function can effectively
Participant Examiner
PROFILE MODULE OUTCOME ANALYSIS MODULE
User Profiles Test Information

Raw Data Analysis Updating of Data
TEST MODULE
Analysis of Analysis of
Search Patterns Scanning Trend
Test Stimuli Type of Presentation
1, 2, 3 A, B, C
(Alphabets)
Structured
(Numbers) PRINTING MODULE
,•
(Symbols)
" and "
Random
(Radicals) Data Printing Graphic Printing
Databases
Fig. 3.3a CACTS System Architecture. Adapted from Wang et al. (2006) and printed with
permission, Elsevier
summarize an individual’s search strategy; it can also sort out different search
patterns among a group of individuals.
In the current version of CACTS, the test module contains four forms of tests
stimuli – numerical forms (0–9); alphabetical forms (A–Z) in upper case; 50 two
symbol forms (example as “ ” and “•”); and 26 basic components of Chinese
alphabetical characters, called radicals (example, “ ” and “ ”). The system also
allows the option of adding new stimulus items to test module. The stimuli may be
presented in random or structured arrays.
As is the case with the CVFN, the center point in the CACTS screen is the 0;0
coordinate point. All other points are referenced in terms of x and y coordinates
relative to the x and y axes (this is a standard method in many image analysis
applications). To aid the examiner with analysis of the subject’s performance, the
coordinates in the CACTS screen can also be grouped into nine regions – a central
circle surrounded by eight circular demarcations. Dividing the screen in this way
allows for a simpler delineation of the response pattern, such as “center,” “left,”
“far left,” etc.
The examiner can view test results with a screen interface of the Outcome Anal-
ysis Module (Fig. 3.3b,c). Different outcome screens offer different data sets or
different levels of detail for a data set. Figure 3.3b is a snapshot of one outcome
screen. It includes some of the subject’s personal data such as name, education
A pie chart showing
56
Total task time, Time, accuracy,

the accuracy (blue and
accuracy, omissions omissions and
yellow for right and left
and commissions on commissions on
screen, respectively;
Personal data the screen the lateral screen
0% forthe inaccuracy).
Records of each
cancellation by
orders
Scan path from

Structured or the first (blue
random arrays circle) to the last
target cancelled
(red square)
Test modes:
star, symbol, Click for the test results in different mode of
etc. cancellation tasks
Fig. 3.3b Snapshot of CACTS outcome analysis screen 1. From, Wang et al. (2006); printed with permission, Elsevier
3 Neuroinformatics for Neuropsychology
Scan path from the first

(blue circle) to the last Duration or distance amplitudes
target cancelled (red of consecutive cancellations
square)
Time, accuracy, omissions and Asymmetry pattern, Attention and

commissions on the lateral screen neglect center with vector
(left column) and the whole screen
(right column)
Fig. 3.3c Snapshot of CACTS Outcome Analysis Screen 2. From, Huang and Wang (2005).
Toward a graphical analysis tool for computer-assisted assessment of visual search patterns. Paper
presented at the Fifth IEEE International Conference on Advanced Learning Technologies; printed
with permission, IEEE (©2005 IEEE)
level, and date of testing. It also shows the number of cancellations made by
the individual in the left and right half-fields; the number of correct responses
in each half-field; total time spent in each half-field, and a graphical depiction
of the subject’s scan path. Another outcome screen, shown in Fig. 3.3c, includes
some of the above data and offers more detailed temporal data tied to the subject’s
scan path.
Cancellation tasks constitute a special category of tests in the assessment of atten-
tion and visuospatial function. Their simplicity, ease of administration, and often
clear results have given them a proven utility in neuropsychology. These factors
have also resulted in the tool remaining essentially unchanged in more than three
decades. So much more data can come from cancellation tests, data that are not fea-
sibly realized by the conventional paper-and-pencil versions of these tests. CACTS
is a system that changes the landscape of cancellation tasks. It adds a powerful
informatics dimension to these tasks. In so doing, valuable hidden information about
attentional strategies and visual field biases is brought to the fore.
Conclusion for Section 3.3.2.1 and 3.3.2.2

Much of visuospatial assessment uses the medium of a spatial field defined by
a sheet of paper or a computer screen. The CVFN and the CACTS systems
demonstrate ways of digitizing this spatial field so that points in the field can be
linked to a database. With this kind of functionality, a subject’s scanning/response
patterns can be tracked with mathematical precision and without the need for
eye-tracking hardware. These systems can practically be used in the clinical envi-
ronment. The dynamic operations enabled by these systems are invaluable is tying
spatial assessment to rich theoretical models of spatial processing. Conventional
tools cannot capture precise spatial and temporal properties of hemifield bias and
coordinate-based processing, neither can they dynamically alter stimuli and record
the effects. Visuospatial processing involves a host of complex operations and none
but informatics tools match up to this complexity.
3.3.3 Speech, Language, and Aphasia
The broad functional domains of speech and language are ripe and ready for neu-
roinformatics. Production and perception of speech and language involve complex
neurocognitive mechanisms. These mechanisms continue to be investigated at an
exciting pace only to unveil an even more multifaceted puzzle. In formulating mod-
els or dealing with assessment of speech and language, neuropsychology is called to
(a) parse out contributing cognitive variables such as phonology, syntax, semantics,
discourse, working memory, auditory and orthographic perception, and sequencing
of cognitive and motor programs, (b) match these functions to their corresponding
neural systems, and (c) determine the nature of disruption to these functions follow-
ing damage to a neural system. The difficulty of such tasks need not be emphasized.
Neuropsychological Models of Language: The evolution of neuropsychologi-
cal models of language, including neuropsychological speech mechanisms, while
marked by numerous epochs, can be viewed in terms of the degree of emphasis
placed on functional-anatomic systems, sensory and motor processes, cognitive pro-
cesses, or neural networks involved with speech and language (Arbib and Caplan
1979; Benson 1993). Neuroanatomic localization of psycholinguistic and speech
sensorimotor processes has been an underlying theme.
The Broca-Wernicke model of language has been a canon in neuropsychol-
ogy. Key events around this model are common historical knowledge in the field
(and even though this model has been described endless number of times in
neuropsychology, a few highlights are called for here to serve the discussion
building up to the need for NI). Broca’s (1861/1865) reports associated motor
speech production with the frontal opercular region. Wernicke’s (1874) extensive
monograph served to delineate processes of sensory (auditory) language compre-
hension tied to the posterior aspect of the superior temporal gyrus and to highlight
the fiber tract linking this area to Broca’s speech motor area. Lichteim’s (1884)
elaboration on Wernicke’s model (the Wernicke-Lichteim model) then consolidated
what would become an anatomic-connectionist perspective of aphasia. This classi-

cal view was famously reformulated by Geschwind (1965): Wernicke’s area codes
complex auditory patterns with meaning, a process that is required in generating
words to be spoken and in recognizing spoken words. Through the longitudinal
white matter pathway of the arcuate fasciculus, the coded information from Wer-
nicke’s area is serially transferred to Broca’s area. Here it is rendered into neural
code for speech motor sequences required for speech production. This reformu-
lation was “disarmingly logical and compelling” (Goodglass 1993, p. 40). It had
practical simplicity in that cardinal features in Broca’s and Wernicke’s aphasia could
neatly be addressed to neuroanatomic sites.2 “But it also comes into conflict with
other clinical observations and with more sophisticated views of possible informa-
tion processing mechanisms used by the brain. Progress toward understanding the
relationship between anatomy and language functions requires a more fine-grained
analysis of anatomical detail in the one hand, and language processes on the other”
(Goodglass 1993, p. 42).
While a century of research on brain and language is not being discounted, it is
the emergence of neural network models of cognition that brought major redirection
in the neuropsychological models of language. “Neurolinguistics must be computa-
tional,” asserted Arbib and Caplan (1979). By the late 1980 s, computational models
of neurocognition offered a plausible framework for neuroanatomic network models
of language and other cognitive functions (see Petersen et al. 1988; Mesulam 1990;
Damasio 1990). In these models, a range of sensory, motor, and cognitive processes
involved with speech and language were tied to many sensory, motor, or association
areas (nodes), altogether constituting a larger, distributed network. A wider range of
symptoms in aphasia could now be explained on the basis of nodes involved with
a symptom or an aspect of the symptom. There was a shift of emphasis to paral-
lel processing across nodes of the network in describing the neuropsychology of
language.
In the current era of cognitive neuroscience, the general framework of a dis-
tributed network for speech and language has been greatly expounded upon through
data from functional imaging studies (see Binder 1997; Binder 2008). Carefully
designed fMRI experiments can aid not only in identifying discrete language areas
but also in distinguishing, for example, how activation for specific cognitive opera-
tions such as working memory is patterned in a linguistic task versus a non-linguistic
task (Smith and Jonides 1998). Activation patterns can offer clues to the dynamics
of neural networks involved with language. Working models for the neuroanatomic
basis of language can be synthesized from fMRI data and a range of findings
across cognitive neuroscience (see Binder 2008). They describe multiple loci, each
addressing an aspect of language such as syntax, phonology, and semantics and alto-
gether constituting a large network. Any component of the model can be expanded.
2 The model has also been advocated (Pinker 1994) as the neural basis of Chomsky’s (1957)
Generative-Transformational model of language. In this context, its shortcomings have been
described from the standpoint of evolutionary neurobiology of language (Deacon 1997; Lieberman
2002, and see Aboitiz and Garcia 1997).
It can flexibly incorporate new research data and allow for greater precision in
associating symptoms of aphasia with neuroanatomic systems.
Limitations of Box-and-Arrow models: A neuropsychological working model of
language that describes wide spread neuroanatomic loci may represent an achieve-
ment over the classical Broca-Wernicke model in that it draws a larger network. It
may recognize that interaction and feedback can occur between the loci. Yet, how-
ever elaborate this kind of “box-and-arrow” model may be, it will always have some
unfortunate limitations: It has neither a way of systematically exploring the relation-
ships between the boxes (nodes) nor a way of dynamically testing the model. The
dynamics of the network cannot easily be studied or rendered with this kind of
model. The model becomes proliferated with more and more boxes-and-arrows (see
Marshall 1986)
Assessment of Language: The assessment of language in clinical neuropsychol-
ogy has hardly been deterred by the difficulty of formulating comprehensive models
of this functional domain. Certainly with regard to aphasia, assessment tools such
as the Boston Aphasia Diagnostic Exam, the Western Aphasia Battery Tap are
well-delineated behavioral features. They strive for well-defined symptomological
categories. As neurocognitive models of speech-language evolve, some challenges
for neuropsychology will be to further clarify symptoms and to match them more
closely with neural systems.
Role of NI: Arbib and Bota (2003), writing about neurolinguistics and neuroinfor-
matics, stated that “ . . . we need neuroinformatics methods to develop in a fashion
which more tightly integrates modeling with databases . . . to allow the more effec-
tive integration of data from neuroanatomy, neurophysiology, brain imaging . . . ”
(p. 1257). Neuroinformatics is integral to the process of clarifying speech and lan-
guage mechanisms in neuropsychology. Coding, sorting, and connecting the myriad
of cognitive and neural variables involved with speech and language is dependent
on NI methods. NI can structure databases of symptoms such that syndromes of
language are indentified. NI can help model discrete neural operations in speech,
which in turn can contribute to complex neural models of speech-language produc-
tion. To further improve models of speech and language, neuropsychology must
expand its scope. It has to borrow concepts from computational neuroscience that
relate to neural coding and representations of data, neural transformations of the
coded data, and feedforward and feedback mechanisms. Models are needed that take
into account the dynamics of speech-language circuitry and NI methods can help
to parse out perceptual and cognitive speech-language processes that result from
these interactive dynamics. A related model is described in this Section (3.3.3.1)
and its significance in fostering NI approaches in the neuropsychology of speech
and language is emphasized.
Sign and Gestural Language: The study of language in neuropsychology has
not been limited to spoken language. Descriptions of the complexity of structure
of sign language (Bellugi and Klima 1976; Klima and Bellugi 1979) prompted
many neuropsychological reports on the neural basis of sign language and gestu-
ral communication (e.g., Hickok et al. 1996; McNeill and Pedelty 1995; Petitto and
Bellugi 1988). Spatial relations and spatial processing involved with sign language
syntax (Poizner et al. 1984; Bellugi et al. 1988), linguistic versus affective facial
expressions in sign language (Corina et al. 1999), and their differential lateraliza-
tion have been among the major topics in this area. More recently, neuroimaging
studies have advanced finer distinctions in the neural mechanisms of sign language,
e.g., for different types of facial expressions, aspects of phonological processing,
and in dissociations between motor and linguistic processes (see Emmorey 2002;
Emmorey et al. 2007; McCullough et al. 2005).
In sign language research, the transcription and analysis of signs and gestures
are fundamental steps, but this is complicated by the fact that signed languages
are visual languages with no standard written form. Thus, transcription from video
involves making annotations of some kind, frequently glossing signs by the nearest
spoken-language equivalents, despite the fact that there is no one-to-one corre-
spondence between a sign in, e.g., ASL, and a word in, e.g., English. Moreover,
it is difficult to capture essential information about non-manual gestures – move-
ments of the head (including periodic movements such as nods or shakes) and upper
body, and facial expressions (e.g., raised or lowered eyebrows, eye aperture, mouth
movements, etc.) that carry important grammatical information – which occur over
phrases (frequently sequences of individual manually produced signs).
Somewhat at odds with sophistication of topics in sign language research has
been a long standing lack of consensus on how to annotate signs and gestures and a
lack of appropriate tools to aid with the transcription (see Miller 2001; Pizzuto and
Pietrandria 2001). One of the reasons for the lack of a standard method has to do
with theoretical and analytical assumptions reflected in symbols and notation sys-
tems (Emmorey and Reilly 1995; Miller 2001). “One of the most difficult issues
for sign language is how to represent space itself and the linguistic distinctions
conveyed by space . . . ” (Emmorey and Reilly, pp. 14–15).
Role of NI: It is precisely on issues such as the annotation and spatial frameworks
for coding sign language that NI offers refreshingly new and efficient options. NI
lends the methods of digital recording and computerized motion analysis in the
capture and analysis of gestures. It also offers ways to database a range of gestures
and signs and to mine this data. The third example in this Section (3.3.3.3) illustrates
the case.
The potential of NI in the neuropsychological study of speech and language in
general is illustrated below through three examples. The first is a computer model
of motor control in speech production, but one that relates to the cortical circuitry
for language, and accounts for various phenomena in speech and language. The
second is a web-based aphasia database designed to help clarify aphasic syndromes
by using computational methods to cluster symptoms. The third is a computerized
tool for digitally annotating and analyzing gestural language.
3.3.3.1 Directions Into Velocities of Articulators (DIVA)

URL: http://speechlab.bu.edu/diva.php
(See Guenther 1994, 1995; 2006; Guenther et al. 2006; Guenther et al. 1998;
Frank Guenther, personal communication (September 25 and 28, October 5 and
6, 2008; April 17, 2009).
DIVA is a computationally defined neural network model of speech produc-

tion and acquisition (SPA). The model describes an adaptive network for acoustic,
somatosensory, and motor components of speech. It takes into account numer-
ous cortical and subcortical areas involved with speech as well as the connections
between these areas. The neural network described by the model uses feedforward
and feedback systems to (a) direct the production of speech, (b) gain input about
acoustic properties of speech and the sensory-proprioceptive properties of oro-facial
muscles, the vocal tract, and other parts of the speech apparatus, and (c) compare
speech sounds produced to learned templates and make adjustments accordingly. A
major aspect of these processes involves the neural coding of desired trajectories
(“directions”) of the speech articulators and the subsequent signal transformation
into calibrated motor commands (“velocities”). Hence the model’s name, Directions
Into Velocities of Articulators.
DIVA integrates many neural principles to describe how various aspects of
speech emerge as dynamics and properties of neural networks. By describ-
ing a comprehensive neural network for SPA, including considerable workings
of the nodes and connections of the network, DIVA is able to account for
a range of phenomena relating to development of speech and speech produc-
tion/perception. It is a highly unified model and therefore, not surprisingly, the
model is at the forefront in contemporary cognitive neuroscience of speech and
language.
How does a model of SPA fit in with a discussion of NI in neuropsychology?
What is the relevance of DIVA to NI in neuropsychology? The examples of NI appli-
cations for neuropsychology discussed so far (3.3.1.1–3.3.1.4) can be characterized
as computer systems with informatics functionality. In this sense, the inclusion of
DIVA may appear to be somewhat at odds with this NI-neuropsychology discussion
– it is a theoretical model of SPA. On the other hand, the modeling routines used
to test DIVA and the computational framework that is so integral to DIVA are part
and parcel of NI. The introduction to Section 3.3.2.1 mentioned the need for NI
modeling as a crucial method for understanding the dynamics of widely distributed
neural system for language – a perfectly valid reason for including DIVA as one of
the examples in this section (a brief introduction to computer modeling is covered
in Section Section 2.4). A reason, perhaps, even more pertinent to this broader
discussion is that DIVA is a type of model that enables and promotes NI approaches
to speech and language in neuropsychology. Criteria for neuropsychology-specific
NI systems suggested in Section 3.2 describe that “the complexity of an NI system
should, as far as possible, be tuned to the complexity of the neuropsychological
phenomenon at which it is aimed . . . [and] using NI frameworks, attempts should
be made where possible to reformulate a neuropsychological research issue so
as to generate a more detailed or quantified rendering of the issue.” While not
purposefully cast as a NI system, DIVA fits these criteria very well. DIVA is
mainly concerned with speech production but its sophisticated theoretical and
computational framework (a) provides a powerful example of the kind of models
that are needed for language in neuropsychology and (b) demonstrates how the
interface for NI approaches in the study of SPA in neuropsychology can be carried
out. It is in this context that attention is given here to DIVA (and this relevance
elaborated later in this subsection).
DIVA is both a neural and computational model of SPA. It is neural in that all its
components are tied to centers of the cortex or cerebellum – it posits a broad neural
network that is informed greatly by neurobiological and neurophysiological data. It
is computational in that (a) many aspects of the model can be simulated in computer
modeling, which includes the learnt control of an artificial voice tract (synthesizer)
and (b) data from other avenues of SPA research, especially fMRI research, can be
modeled in the DIVA framework for further interpretation.
Detailed descriptions of DIVA can be found in the above references.3 A synopsis
is provided below.
Synopsis of DIVA: The DIVA model involves four major classes of information
or reference frames: (a) an acoustic frame that deals with how sounds are coded
as auditory maps; (b) a phonetic frame constituted by sets of speech sounds learnt
through the neural network; (c) a somatosensory (orosensory) frame that receives
sensory/proprioceptive information from the vocal tract to monitor the sound being
produced, and (d) a motor (articulatory) frame that controls the speech musculature.
DIVA also specifies the nature of the relationships or mappings between the four
frames as well as feedforward and feedback systems. Mapping refers to the trans-
formation of a neural representation that occurs between one node of the neural
network and another.
Figure 3.4 is a schematic of the DIVA model. The neural systems underlying the
framework can be grouped as three interacting subsystems involved with the con-
trol of speech production. These are (1) a feedforward motor system and a feedback
system that involves (2) a subsystem for auditory feedback and (3) a subsystem
for somatosensory feedback. A region in the left ventral premotor cortex, within
Broadmann’s areas 6 and 44, is hypothesized to be a starting point in speech sound
production. This area contains speech sound maps, i.e., higher-level motor repre-
sentations of speech sounds. A speech sound refers to any single speech sound unit
such as a phoneme or syllable. When a speech sound map is activated, the three
subsystems are involved in the relay of afferent signals to the motor cortex to drive
and control the production of speech:
The Feedforward Control Subsystem: The feedforward system is involved in the
actual, primary production of a speech sound. Feedforward signals (A) from the pre-
motor speech area have two components, one going directly to areas of the primary
motor cortex and the other going first to the cerebellum and then to motor cortex
speech areas. Target regions are all areas of the motor cortex involved with speech
sounds (e.g., areas controlling tongue, lips, mandible). A region may code the posi-
tion and velocity of a part of the speech apparatus in directing a motor movement.
3 DIVA has been described with immense mathematical and neuroanatomical substantiation and is
best appreciated when viewed against its mathematical and theoretical backing. For these details,
see especially Guenther (1995), Guenther et al. (1998), and Guenther et al. (2006).
Fig. 3.4 Schematic of neural processing stages in speech production and acquisition as described
by the DIVA Model (From, http://speechlab.bu.edu/diva.php; adapted with permission, Frank
Guenther)
The likely cerebellar regions are the anterior parvermal and superior lateral areas as
target input areas and the medial subcortical cerebellum as the output area.
The Feedback Control Subsystem: This subsystem involves auditory and
somatosensory feedback systems.
A set of premotor signals (B) generated by a speech sound map targets the
auditory area/superior temporal cortex. The pathway of this signal encodes the
spatiotemporal auditory properties of the speech sound. When the auditory area
receives feedback (C) via subcortical nuclei (the sound of the produced speech), a
comparison is made between this sound and the expected sound. Two auditory maps
are involved, a state map and an error map. In neural terms, coordinates of activa-
tion in the auditory area (state map) are compared with the expected coordinates of
activation based on previous learning. If a discrepancy occurs between expected and
activated coordinates, an error map is generated. A corrective signal (D) is then sent
to the motor cortex where required motor adjustments are made. The hypothesized
loci of state map cells are the medial aspect of Heschl’s gyrus (primary auditory)
and the anterior planum temporale (association auditory). Auditory error map cells
are thought to lie at the temporoparietal juncture in the left Sylvian fissure or in the
lateral aspect of the posterosuperior temporal gyrus.
Another set of premotor signals (E) generated by a speech sound map targets the
speech areas of the somatosensory cortex. This pathway encodes the spatiotemporal
somatosensory properties of the sound. The somatosensory areas also receive tactile
and proprioceptive feedback signals (F) from the speech articulators during produc-
tion. As with the auditory feedback system, two maps are involved. The occurring
somatosensory activation pattern is compared with the expected pattern (state map)
coded through previous productions. Discrepancies are coded in an error map. It in
turn sends corrective signals (G) to the motor cortex. Somatosensory state maps are
hypothesized to lie in the inferior postcentral regions for the speech; lips, tongue,
larynx, etc. Error maps are thought to lie along the supramarginal gyrus, in the
inferoposterior parietal cortex.
Feedback and Feedforword Process in Speech Acquisition: In the DIVA model,
attempts at production of a speech sound can begin after the acoustic proper-
ties of the sound have been coded, i.e., auditory coding in neural terms has
been established. The first attempt at producing a particular sound will typi-
cally be crude. The feedforward neural circuitry will be operating for the first
time and hence will be greatly reliant on the auditory feedback system for feed-
back of the sound errors. With subsequent attempts, feedback is more smoothly
integrated, the feedforward system becomes smoothly conditioned, now produc-
ing fewer errors and becoming less dependent on auditory feedback. The same
principles would apply to the somatosensory aspects – reliance on propriocep-
tive input is lessened with practice as the sound’s proprioceptive “signature”
gets well coded and the burden of the somatosensory error to state check is
minimized.
With the above described representational and sensorimotor processes, DIVA
provides an account of how individual speech sounds such as phonemes are strung
together in speech acquisition and how neural signals are transformed in produc-
ing fluently sequenced movements of the speech articulators. The framework also
enables DIVA to account for a variety of speech-language phenomena or provide a
unique investigative avenue into these phenomena. Three examples are very briefly
conveyed here:
Infant Babbling: According to the model, it is during the babbling phase that crit-
ical aspects of sensorimotor parameters of speech sounds are tuned. Feedforward
and feedback signals involved with babbling allow the infant to mark the canonical
range or signature of sensory-acoustic, motor, and sensorimotor states tied to par-
ticular speech sounds. This example very well conveys the self-organizing system
described by DIVA where learning is based entirely on sensory and motor neural
information.
Phonetic Categories: The neural dynamics of acoustic representational (neural)
space for phonemic categories are richly detailed in the DIVA model. Phonemic
encoding occurs through a consolidation of neural representational matrices – as a
sound is learnt and successfully produced, the neural cluster encoding the sound
in the auditory/association auditory cortex is tuned to rely on fewer neurons with
a tighter relationship between them. Prototypical sounds learnt in one’s native lan-
guage are, for example, coded in this manner. Later learning of a non-prototypical
sound (a different language) becomes difficult because of the neural re-organization

required.
Neural Decoding of Speech and Neural Prosthetics for Speech: Informed by
the theoretical framework of DIVA, a neural prosthetic/speech-decoding device has
been experimentally tested in a patient with “locked-in syndrome” (near complete
paralysis following a trauma-induced stroke).4 In this case, speech paralysis was
targeted by implanting an electrode in the patient’s premotor speech area (see DIVA
website). The patient’s attempt to produce sequences of vowel sounds presented to
him on a computer screen resulted in premotor neural activity which was captured
by the electrodes and fed to a computer. The signals were analyzed using DIVA’s
association of specific speech premotor signals with specific formants/characteristic
vowel frequencies. These computer-enhanced signals were then fed to a synthe-
sizer, which produced the corresponding vowel sounds. Many trials have been
conducted and at present, the system has seventy-five percent accuracy in producing
the patient’s intended vowels sounds. Needless to say, the results of this work have
reverberated through the field of neuroscience.
DIVA distills the neural processes of SPA, describing crucial neural compu-
tations and their spatiotemporal sequence, spread across a broad network. DIVA
“speaks” of sensorimotor transformations, representational vectors (of sounds), and
orosensory maps. All components of the model are linked to neuroanatomic loci.
The model describes an interplay between speech perception and speech produc-
tion and how a particular neural system can be differentially involved in speech
perception and production. Numerous phenomena and numerous sets of data in
speech-language research can be interpreted using the model.
Why models like DIVA serve NI approaches to speech/language in neuropsychol-
ogy: As indicated, DIVA’s relevance to NI in neuropsychology can well be viewed
in terms of its modeling paradigm or the above described brain-computer interface
to decode neural signals of speech. DIVA simulates many of its components and
mechanisms with computer models. These include, for example, the neural repre-
sentation of speech sounds, the production and combination of learnt sounds, and
neural corrective measures following errors in production.
The greater relevance of DIVA to NI, however, has to do with the conceptual
framework it provides for the study of SPA. The critical mass of research data on
neurocognitive aspects of SPA desperately calls for comprehensive, biologically
plausible models against which the data can be interpreted. NI approaches bring
another dimension of complexity. If NI methods were to be optimally developed or
applied in regard to the data, an ideal condition would be the availability of large
scale, comprehensive theoretical models. This will better contextualize topics for
NI approaches. At the same time, it will promote convergence in the data emerging
4 The case of Erik Ramsey and the DIVA-inspired electrode signal decoding of his premotor speech
neural signals has already received much attention in the popular media (for example, New Scien-
tist, July 9, 2008; CNN, December 14, 2007). A major collaborator on the project has been Dr.
Philip Kennedy at Neural Signals, Inc. in Atlanta, Georgia.
if multiple NI initiatives tackle different problems in speech/language research.

(These points are also conveyed in Section 3.3.2.1 with the example of the Compu-
tational Visual Field for Neglect – how the tool is tuned to properties of coordinate
mapping and compression described by the posterior parietal/representational
model of neglect.)
As with many neuropsychological domains, more and more research in SPA is
being done with functional imaging. With numerous fMRI investigations showing
multiple brain regions of activation in speech production tasks, DIVA “provides a
conceptual and computational framework for interpreting many of these datasets”
(Guenther et al. 2006, p. 280). By laying out a detailed neuroanatomic network
and the nature of activity and information flow within the network, DIVA is able
predict and simulate fMRI activation patterns for a specific speech production task.
It does this by utilizing the SPM2 software package to produce simulated fMRI
activity based on a theoretically specified neural activity. This strategy is useful in
generating hypotheses and guiding fMRI studies tied to SPA.
3.3.3.2 The Aphasia Database

(see Axer et al. 2000a,b,c; Jantzen et al. 1999a,b; Hubertus Axer, personal com-
munication, August 1, 11, 15 and 22, 2008; Jan Jantzen, personal communication,
August 1, 11, 8 and 17, 2008)
URL: http://fuzzy.iau.dtu.dk/aphasia.nsf/htmlmedia/index.html
The Aphasia Database (AD) is a database of diagnostic and symptomological
data drawn from aphasia patients. It serves primarily as a research tool to help
clarify different aphasic syndromes that overlap in symptoms. It also serves as a
model for databases and data mining in aphasia research. The AD is a collaborative
project between the Department of Anatomy at Rheinisch-Westphalian Technical
University (RWTH) in Aachen, Germany, and the Department of Automation at the
Technical University of Denmark in Lyngby. The project has been sponsored by
the European Network for Fuzzy Logic and Uncertainty Modeling in Information
Technology (ERUDIT) and the European Network on Intelligent Technologies for
Smart Adaptive Systems (EUNITE), organizations supported by the European Com-
mission. ERUDIT and EUNITE ran from 1995 to 2003 with a mission of promoting
computational technology development and infrastructure in education and industry.
Rationale and Goals of the Aphasia Database: The AD was created in order to
address problems arising from the classical Broca-Wernicke taxonomy of aphasia
(see discussion earlier in this section). Syndromes of aphasia defined around this
taxonomy overlap in terms of features. This often results in (a) unclear boundaries
between aphasic syndromes, (b) lack of clarity about when and how symptoms are
shared across aphasic syndromes, and (c) no definite way of relating neuropathol-
ogy in aphasia to normal brain language processes. The AD sought to take a set of
uniformly classified cognitive and neuroanatomic aphasic features and then place
the data in a database. Computational methods and neural network models then
applied to the data could potentially yield fine tuned relationships between the data,
advancing significantly over conventional methods of diagnosis. In addition, any
success with a database and computational techniques relating to classification of
such a complex set of syndromes (aphasia) would provide an informatics model for
classification of problems in general medicine.
Structure and Contents of the AD: The AD system uses a server-client set up.
Data for the AD were originally collected in the format of a Microsoft Excel file. The
data were then exported to a Notes/Domino database residing on a Lotus Domino
server5 (in Denmark). Pages of the server website are accessed in database views
in any browser. Data collection for the AD began in 1986 in the Department of
Neurology at the RWTH Aachen. The database currently has 265 records.
Two main types of data are included in the AD, aphasia test profiles and neu-
roanatomic lesion data. Language profiles for the AD are generated by the Aachen
Aphasia Test (AAT), a test battery commonly used in German speaking countries.
The AAT contains six subtests: spontaneous speech, token test, repetition, written
language, confrontation naming, and comprehension, each designed to tap a partic-
ular symptom. All subtests have multiple subcategorical measures, for example, the
repetition subtest, involves tests of single phonemes, monosyllabic nouns, local and
foreign words, compound words, and sentences. Database entries are the numerical
scores of the subtests.
The neuroanatomic data in the AD are lesion profiles obtained through CT scans.
Neuroanatomic data are included for only a subset of 146 patients in which the
lesion sizes were found to be relatively stable. The AD holds a lesion profile as a
set of 3D coordinates of the border lesion. These coordinates are derived from the
Aachen Voxel Model (see Section 2.2) that can be used to describe the locus of a
lesion using standardized 3-dimensional model of a normal brain.
For the 265 records in the database, many types of (aphasia) diagnosis are
included but the most frequently occurring types are Broca’s, Wernicke’s, Global,
and Anomic aphasia.
Neural Modeling and Diagnoses with the AD: The AD and its related modeling
system are geared to standardization and consistency in relating aphasic symptoms
to aphasic syndromes. Tied to the AD is a neural network modeling program. The
point of this artificial neural network is the association of symptoms with diagnoses,
computationally. The neural network is programmed to examine the various symp-
toms, i.e., test scores in the AD. The multilayered network selects and classifies
particular features of the symptoms and outputs diagnoses with a specified degree of
certainty of Broca’s, Wernicke’s, Global, or Anomic aphasia. Figure 3.5 represents
5 The Notes database is a non-relational database. A data object or “note” may consist of any
number or type of data fields, and the database can hold any number of these notes. Because the
database header and note header contain certain kinds of information, a user can search multiple
Notes databases at the same time. This structure is advantageous for the efficient storage of diverse
data types in the same database. Lotus Domino is a very flexible server application that can be used
with a variety of Lotus Notes applications.
Examples of INPUT OUTPUT

(test scores from subtests/items (diagnosis of an
of the Aachen Aphasia Battery) aphasia syndrome
with a certain degree
of certainty)
communicative behavior
articulation Artificial
Neural
automatized language Network Anomic Aphasia
semantic structure (intelligently Broca’s Aphasia

classifies data
phonological structure based on Global Aphasia
particular modeling
syntactic structure parameters) Wernicke’s Aphasia
repetition
reading aloud
Fig. 3.5 Schematic of neural network diagnosis by classification of AD Test Scores. (Adapted
from Axer et al. 2000a,c; and Jantzen 1999a; printed with permission, Elsevier)
this process. The key aspect of the neural network is the classifier. It is capable of
classifying symptoms (score patterns) even if it has not previously encountered these
symptoms. Using a back propagation learning method, the network was trained on
a test set drawn from the database. For example, high scores in measures a, b, and c
combined with low scores in measures x and y and an average score in measure z,
may amount to the profile of a certain type of aphasia. When the network encounters
this pattern consistently, it reinforces its association between the particular symptom
profile and the diagnosis. The classifier can be adjusted in terms of its complexity
and the number of input data. In experimental trials with AD data, one classifier
produced correct diagnosis in 92.4% of test cases (Jantzen 1999).
The AD’s modeling component can also use another approach in searching
for similarities in the language assessment and neuroanatomic data. The nearest-
neighbor approach measures an abstract (standardized) distance between an object
in the database and all other objects across all records or selected records. The
objects most similar to a given object can thus be found. This method can, for exam-
ple, be applied to the lesion data to gauge the average anterior border (coordinates)
among all cases of Broca’s aphasia.
The AD stands as an embodiment of the potential that neuroinformatics holds for
research in language and aphasia. With a relatively small but carefully categorized
data set, it has demonstrated the advantages of digitizing aphasia test data and the
utility of neural network models in analyzing the data. The AD initiative relates
to the need for standardizing aphasia test data, the need to objectively diagnose
a syndrome using a certain data set, and the need to develop ways to accurately
associate the data with neuroanatomic loci. In this regard, AD, a neuroinformatics
system, is an outstanding development in aphasia research and provides a strong
foundation for other NI initiatives in aphasia.
3.3.3.3 SignStream: An Informatics Tool for the Digital Analysis

of Visual/Gestural Language
URL: http://www.bu.edu/asllrp/SignStream/
(See McLaughlin et al. 2000; Neidle 2001; 2002a,b; Neidle and McLaughlin
1998; Neidle et al. 2001; Dreuw et al. 2008; Carol Neidle (personal communication,
October 1 and 2, November 21, 22, and 24, December 27 and 28; 2008)
SignStream! R
is an informatics tool for the annotation and analysis of visual and
gestural communication. It is best known as a tool for transcription and analysis
of signed languages but it can be applied to any form of gestural communication.
The tool offers a comprehensive multimedia platform tied to a database. Gestu-
ral communication is captured through digital video recordings, which can then
be richly annotated. This format, combined with the use of algorithms to search,
combine and manipulate the data, enables sophisticated analysis of communicative
gestures.
SignStream! R
has been led by Carol Neidle and a research team of the Ameri-
can Sign Language Linguistic Research Project at Boston University and various
components have been developed in collaboration with researchers from Rutgers
University and Dartmouth College. The project has been sponsored by the National
Science Foundation. SignStream! R
was introduced in 1997 and has since been
widely distributed. It is made available to the research community on a non-profit
basis. As is the case with most NI tools, its development is ongoing, shaped
by research needs and technological advances. Version 3.0, a Java reimplemen-
tation of SignStream! R
with powerful new features, is expected to be released
in 2009.
SignStream! R
as a Response to Limitations in Sign Language Research: A major
limiting factor in the study of sign/gestural language has been the lack of availability
of a large corpus of language gestures in annotated form. A large corpus would be
crucial to research in that it would provide shared, reusable data from which rela-
tionships and analyses could be conveniently drawn. There were a few key obstacles
to the development of such a corpus: the process of transcribing analogue video
data on manual signing has always been a tedious one. Coding non-manual expres-
sions (e.g., a frown) in these recordings has been even more problematic. Serial
searches through videotapes to locate a specific gesture from a participant would
inevitably be a time consuming and cumbersome process. Further, with written rep-
resentations of the video data, came disagreement about the interpretations of the
data. Altogether, these problems amounted to the lack of a shared objective and
efficient coding system for the rapid capture, retrieval, and analysis of signs and
gestures, as well as the lack of a corpus of gestural language on which to test and
develop this system, which, in turn, would expand the corpus. The lack of such a
system also meant that there would be no effective method of extracting complex
data patterns contained in the kinematics and trajectories of signed gestures, nor
would there be a means for easy comparison of these patterns within and across
individuals. SignStream! R
, as a digital, computational, analytic tool, was developed
in direct response to the problem.6
The General Structure and Functionality of SignStream! R
: At the National Cen-
ter for Sign Language and Gesture Resources (NCSLGR) at Boston University,
a subject’s gestural communication is captured through digital video recordings.
Multiple synchronized digital cameras simultaneously record the subject’s gestures
from different angles. Similar hardware arrangements can be set up at different
research centers with relative ease. The digital video recordings are made publicly
available in multiple movie file formats; SignStream! R
requires formats compati-
TM
ble with QuickTime . Segments are marked that correspond to different gestural
utterances. These individual “units” of utterances are the data units that populate
the SignStream! R
database – which is therefore a collection of utterances. Since an
utterance is usually captured from various angles, more than one video file may be
associated with the utterance. The user first annotates a segment of video by enter-
ing data about the utterance. This produces a corresponding transcription for that
utterance. The SignStream program provides numerous data fields through which
an utterance may be coded. The three main types of data fields are non-manual
fields, gloss fields, and text fields. Types of non-manual gestures (e.g., raised eye
eyebrows, rapid headshake, or squinted eyes) are coded through non-manual fields.
For each event, annotation includes identification of start and end frame, in addi-
tion, potentially, to onsets, offsets, or holds of particular gestures. The ability for
part of speech tagging is included and there is also an English translation field avail-
able. The new version of the program will provide additional tools for fine-grained
phonological analysis (e.g., specification of hand shapes and movement types).
The data fields that are provided (see above snapshot) also allow for distinctions
in the intensity of specific gestures. Non-manual gestures are coded through multiple
fields relating to form, position, and movement of the eyes, head, etc. Head behavior,
for example, is coded through 8 fields that amount to a rich 3-dimensional coding
frame. They address head position at the starting (base) point and then in relation to
x, y, and z coordinates.
SignStream! R
offers some intuitive ways for data entry such as manual typing
into the fields or selections from drop-down menus. It also allows the user to create
new fields that the user may wish to define – enabling the description of new types
of data. Numerous other options are available for screen display parameters and for
audio and video controls.
On the SignStream! R
program’s screen, a video segment and its corresponding
transcription can be viewed in separate adjacent windows at the same time. Up to
four video files may be displayed for each utterance. As a video segment plays, a
media alignment indicator (a vertical bar) moves from left to right in the transcrip-
tion window. This provides for the temporal alignment of the linguistic features
6 There are now also other computer-based tools available for transcription of multimedia data
(e.g., Elan; URL: http://www.lat-mpi.eu/tools/elan/).
Fig. 3.6 Snapshot of SignStream video and gloss windows showing annotated ASL data. (Figure
provided by Carol Neidle and printed with permission. © Boston University/National Center for
Sign Language and Gesture Resources)
described in the transcription window with the visual images in the video window.
Hence, the program offers dynamic linkage of the coded linguistic data with the
visual data.
The SignStream! R
Database: The database links transcription data for an utter-
ance with its respective video files. A sample database accompanies the application.
It contains 10 short American Sign Language (ASL) utterances. It provides the start-
ing point for users to develop their databases. In addition, users may sign on to an
online database ( http://ling.bu.edu/asllrpdata/queryPages /) from which data can
be drawn for analysis. The online database therefore acts both as a distribution point
for SignStream! R
encoded data as well as a data repository serving the ongoing
effort of building large shared corpora of sign and gestural language. At present,
the data in the online database is from native signers of ASL. The online database
now contains over 1300 utterances gathered primarily from four subjects since data
collection began in 1999. It is a constantly expanding database and the brand new
web-based Database Access Interface (DAI) greatly facilitates searching through
the data and downloading subsets of videos and annotations that may be of interest
to particular researchers. The DAI provides an array of search options to the user, as
does the search capability within SignStream! R
itself. Many types of queries rang-
ing from simple to complex may be formulated. Search criteria may be combined, to
search, for example, a specific sign only when it co-occurs with a specified gesture
such as a head tilt to the right. Temporal search criteria may be applied such that a
gesture may be located only when it occurs with, before, or after another gesture.
A script window within SignStream! R
allows the user to select a set of utterances
and position them to be viewed in a particular order, a function that is particularly
useful in teaching and research. Queries and scripts can be saved for future use.
The NCSLGR shared corpus of data has achieved a size and scale such that
subsets of data can be extracted to study a particular feature of gestural commu-
nication. These subsets of data can then be grouped and benchmarked to form
smaller, specialized databases that relate to discrete features. Dreuw et al. (2008)
have reported on three data subsets that relate to language recognition in ASL.
These have been created at Rheinisch-Westphalian Technical University (RWTH) in
Aachen, Germany, drawing from the central database at Boston University. One of
the newly created databases at RWTH is the RWTH-Boston-400, a database of 843
sign language sentences. This is currently the largest publicly available benchmark
corpus for video-based continuous sign language recognition.
Computational Analysis of Gestures: A major aspect of the collaborative research
involving linguists (esp. Carol Neidle) and computer scientists (esp. Stan Sclaroff
at BU and Dimitris Metaxas at Rutgers) has to do with developing algorithms for
the automatic analysis and recognition of gestures and motion in communication.
Algorithms used in computer-based recognition/machine vision are applied in cod-
ing the forms, positions, orientations, and trajectories of the eyes, face, head, hands,
upper body, etc. Because these body parts move simultaneously and often subtly
in communication, it is an enormous challenge to classify their motions and their
relationships with regard to each gesture. Computational algorithms enable this kind
of analysis, and with such a fine-grained analysis comes the potential to sift out rich
yet often-elusive phonological details contained in gestural communication. The
project has given much attention to algorithms for coding head motion in view the
linguistic significance of head/face movements.
In the context of neuroinformatics, SignStream! R
is particularly remarkable. As
a unified platform, it seamlessly integrates so many facets of NI – it offers a com-
puter application geared to the analysis and databasing of gestural language. To aid
the analysis, it develops computational methods for finely deconstructing this com-
plex behavior. It opens itself to the research community worldwide. SignStream! R
provides a well-founded example of neuroinformatics for neuropsychology in

action.
Conclusion for Sections 3.3.3.1, 3.3.3.2 and 3.3.3.3
This subsection has described three major developments that serve NI approaches
to speech-language research. Clearly, there are many ways of applying NI to
neuropsychological research on speech and language.
There are other NI initiatives in this area, either smaller projects or projects indi-
rectly related to neuropsychology. The Aphasia Modeling Project (also known as
Webfit)7 is an online tool for the analysis of aphasia picture naming and repetition
data, using the two-step model of lexical access in language production (see Dell
et al. 1997; Dell et al. 2007; Foygel and Dell 2000). A patient’s picture naming test
data are entered into a program and are mapped to the model’s parameters that fit
normal error patterns. The model can then be “lesioned” by adjusting phonologi-
cal and semantic variables to produce various error patterns. There are also tools
geared to linguistics and normal language. WordNet8 is an online, downloadable
lexical database of English. It contains open class words (nouns, verbs, adjectives,
and adverbs), which it organizes as synonym sets. Lexical, semantic, and conceptual
relationships link these synonym sets such that a word search generates numerous
class and contextual attributes. Such a database of the English lexicon and rela-
tionships of its elements makes for a useful tool in cognitive and computational
linguistics. Latent Semantic Analysis (LSA) is a statistical method for extracting
and representing semantic relationships between words in phrases that are contextu-
ally used in written documents across a body of knowledge (Landauer and Dumais
1997; Landauer et al. 1998).9 The LSA method mathematically decomposes text
into a matrix, which allows for the analysis of each work or passage in relation to
other words and passages. The representation of a particular body of text (e.g. text on
social psychology, cardiac research, French literature) is defined LSA as a semantic
space. Words within this space (i.e., corpus of texts) are mathematically coded in
terms of particular vectorial dimensions and weightings based on their occurrence
in relationship to other words. Using a technique akin to factor analysis, a partic-
ular usage of a word is weighted in terms of the average meaning derived from its
usage throughout the semantic space. The meaning of a passage of text is coded
in relation to the average value/meaning of all its constituent words. LSA therefore
extracts relationships written discourse using a statistical technique as opposed to
using a dictionary, knowledge base, or artificial intelligence program. Its frame of
reference is generated by the semantic space in question and so offers a unique way
of analyzing patterns in the discourse of the texts. LSA is of special relevance to
neuropsychological assessment of language in that its methods can be adapted in
analyzing word usage and discourse in aphasia.
NI brings promising new avenues to the neuropsychology of speech and lan-
guage. The sophistication in the methods and tools of NI are invaluable in matching
up to the cognitive and neural complexity of speech and language.
7 Webfit is a project of the Language Production Laboratory at the University of Illinois Urbana-
Champaign. URL: http://langprod.cogsci.uiuc.edu/cgi-bin/webfit.cgi
8 WordNet is based at the Cognitive Science Laboratory at Princeton University. URL:
http://wordnet.princeton.edu WordNet: An Eletronic Lexical Database (Fellbaum 1998) is a
written guide to the online tool.
9 The Latent Semantic Analysis project is based at the University of Colorado at Boulder URL:
http://lsa.colorado.edu / See also the Handbook of Latent Semantic Analysis (Landauer et al. 2007)
3.3.4 Phenomics and Neuropsychology

Just as the term human genome describes the full compliment of human genes, the
term human phenome refers to the full complement of human phenotypes (Mahner
and Kary 1997). Phenotypes are the outward expression of genes and range from
the physical (e.g., molecules, proteins, cells, organs, morphology) to the cognitive-
behavioral (e.g., perception, impulses/drives, high-level cognition). Genomics and
proteomics were briefly mentioned in Chapter 1 – as transdisciplines that are
dependent on bioinformatics. Similarly, a new discipline, phenomics, has arisen.
Phenomics refers to the systematic study of phenotypes and it is a transdiscipline in
which informatics methods are integral.
The mapping of the human genome, while hugely significant, is but one step in
understanding the workings of genes, which involve pathways of gene expression,
and the outward result of that expression, phenotypes. The discipline of phenomics
is aimed at specifying phenotypes and it aims to draw the data in such ways that
enable their relationships with genotypes to be studied (Bilder et al. b, in press).
“Phenomics approaches require collecting phenotypic information in any given indi-
vidual, at a series of different levels of resolution (molecules, cells, tissues, and
whole organisms) and then determining how these features can profitably be studied
together” (Freimer and Sabatti 2003, p. 16).
This above description was laid out in the authors’ detailed proposal for a system-
atic databasing of phenotypic information. The need to specify phenotypes and reap
maximum advantage of gene mapping studies, they argued, gives primary impe-
tus for such a project. They named the proposed project The Human Phenome
Project (HPP). As is typical in bioinformatics, the project would necessarily involve
a diverse group of biologists, behavioral scientists, informatics, and modeling spe-
cialists. The expressed need for the HPP speaks of the importance of understanding
phenotypic data in the larger context of biology and neurobehavior.
Cognitive and neuropsychiatric phenomics define an area of the discipline con-
cerned with cognitive and behavioral features in normal and clinical populations. It
is the “systematic study of neural systems phenotypes on a genome-wide level, to
bridge the gap between complex behavioral syndromes and their biological mech-
anisms” (Bilder 2007b). It focuses on neurobehavioral phenotypes that can more
accurately reflect a disorder and that can be systematically linked to other levels of
analysis in biology and medicine.
The concept of endophenotypes: An important concept in phenomics is that of
the “endophenotype.” Endophenotypes refer to intermediate traits lying between the
gene level and the disease/syndrome level, that can be precisely defined, quantified,
and which may be causally linked to genotypes (Bearden and Freimer 2006; Flint
and Mufanò 2006). Because of their intermediate position between genes and syn-
dromes, endophenotypes are viewed as more amenable to research and as offering a
more direct path in linking genotypes to phenotypes. The endophenotype concept is
central in phenomics because endophenotypes are considered to be features defined
with relative precision and therefore more accurately indicative of neuropsycho-
logical profiles or complex neuropsychiatric syndromes (see Gottesman and Gould
2003). Because they are associated with causes rather than effects of a condition,
they are viewed as more reliable diagnostic indicators of syndromes (Zobel and
Maier 2004). In contrast, the traditional methods of neuropsychiatric classification
and diagnosis in psychiatry, as embodied by the DSM IV and its predecessors, are
based on general consensus around observed clinical features and are theoretical.
(Clinicians need only be reminded of the vigorous discussion and debates regarding
classification of mental disorders that played out in medical journals over the last
three decades.10 ) Using neurocognitive endophenotypes as markers of neuropsychi-
atric conditions may bring a more scientific, objective dimension to neuropsychiatric
classification and diagnosis.
The role of neuropsychology: Neuropsychology has a crucial role in phenomics
research. Neuropsychological constructs and tools are relied upon to describe cog-
nitive and neuropsychiatric endophenotypes such as response inhibition, attentional
control, and verbal working memory. Consider how performance on the Wiscon-
sin Card Sorting Test is viewed as an index of executive function/set switching and
prefrontal functioning; neuropsychological phenotypes are about such processes but
with a need for more precision in their definition (see Bearden and Freimer 2006;
Kremen et al. 2007).
In the context of phenomics research, neuropsychology also finds itself oper-
ating a sophisticated web of neuroinformatics. Neuropsychology is challenged to
describe cognitive-behavioral phenotypes in highly refined ways and in a manner
that can be interfaced with other levels in inquiry (see Bilder 2007b; Bilder et al.
a, in press). To accomplish this, neuropsychology has to be informatics compatible.
How neuropsychology is integrated in current phenomics projects provides a broad
and compelling illustration of what it means to have the discipline of neuropsychol-
ogy geared for NI, why this should be the case, and ways to go about the process
(Section 3.2 stressed the importance of defining NI systems that can be considered
unique to neuropsychology. It also indicated that NI systems for neuropsychology
should be designed with the view of potentially integrating neuropsychological data
with data from other disciplines. The examples of phenomics research described in
this section, especially the second example, demonstrate particularly well the latter
aspect.)
Two examples of phenomics research are described below. The first concerns a
body of work that seeks relationships between craniofacial dysmorphology, neu-
roanatomy, and neurosychological variables in neurodevelopmental and neuropsy-
chiatric disorders, using informatics methods. The second describes a large-scale,
NIH-funded research consortium for neuropsychiatric phenomics, through which
numerous novel and powerful NI developments in neuropsychology are being pio-
neered. It is a unique example of the kind of informatics infrastructure that serves
knowledge building in neuropsychology.
10 See for example, Spitzer et al. (1975); Spitzer et al. (1980); Williams & Spitzer (1982); Klerman
et al. (1984); Sadler et al. (1994).
3.3.4.1 Neuroinformatics and Neuropsychology in Studies

of Craniofacial and Brain Dysmorphology
(See Matthysse et al. 1992; Deutsch et al. 2000; Deutsch and Joseph 2003; Farkas
and Deutsch 1996; Lainhart et al. 2006; Curtis Deutsch, personal communication,
April 4 and 13, 2007; January 5, 6, and 7, 2009)
URLs: http://www.umassmed.edu/shriver/research/psychological/projects/
cbrsds.aspx
http://www.mclean.harvard.edu/research/mrc/psychlab.php
There has been ongoing collaboration between researchers from the University
of Massachusetts Medical School, the Kennedy Shriver Center (Massachusetts),
the Harvard Center for Genetics and Genomics, McLean Hospital (Massachusetts),
and Boston University Medical School, relating to neurodevelopmental abnormali-
ties in autism, ADHD, schizophrenia, and bipolar disorder (see above references).
One line of research stemming from the collaboration examines brain and craniofa-
cial developmental abnormalities of form/structure and seeks possible relationships
between these two forms of dymorphology (see for example, Deutsch et al. 2000).
The work is funded by grants from the NIH. Specifically, the work is concerned
with (a) how certain forms of craniofacial dysmorphology may signal abnormali-
ties in circumscribed brain regions; (b) how the same pathogenic factors involved
in these abnormalities may be common to different disorders (e.g., schizophrenia
and bipolar disorders); and (c) how neuropsychological features may be linked to
certain dysmorphologic forms.
The work is grounded in a principle of developmental genetics/neurobiology that
has long been established (see Sadler 2004): In embryogenesis and fetal devel-
opment, the formation of different bodily regions and organs takes root from
designated regions of the embryonic cell mass. Specific primordial embryonic cells
are fated to proliferate and differentiate into specific parts of the body and such
relationships are described by embryological fate maps. The brain and the face arise
from a shared embryonic region, a prominence called the anterior neuropore. Hence,
if there is a problem with the genetic program controlling the cells of this region
or if the cell cluster is affected by a toxin during critical periods in embryogene-
sis, abnormalities can be manifested in both the brain and the head/face. Deutsch
et al. (2000) applied a fate map in studying forms of brain and craniofacial dys-
morphology in schizophrenia: They showed that dysmorphology/asymmetry of the
frontonasal-maxillary juncture, common in patients with schizophrenia, could reli-
ably predict the occurrence of midline (longitudinal cerebral fissure) deviation in
the region of the mesencephalic-diencephalic juncture.
Role of NI and Neuropsychology: Deutsch and colleagues have been develop-
ing quantitative methods to detect and measure craniofacial dysmorphology. Their
approach is twofold. First, they utilize reliable, objective anthropometric methods to
quantify facial morphology. Second, they study combination of anomalies derived
from embryologic principles, for instance, combinations of morphological anoma-
lies (by types or regions). To facilitate their research, the team has been building
a large, normative database (Farkas and Deutsch). The database permits quantifi-
cation of craniofacial dysmorphology, in, for example, autism and schizophrenia.
Phase 1 of the database development is complete. It involved the creation of a sim-
ple PC-based tabled database. The database consists of numerous anthropometric
measurements, each entered in separate column and subjects are entered by rows.
Data continue to be added as studies progress. Phase 1 also involved the overall plan
for the incorporation of a neuropsychological data component. Having data on both
physical and neuropsychological features (a) will better enable the search for possi-
ble links between different classes of phenotypes in autism and (b) could possibly
point to etiological subtypes in autism. Deutsch and Joseph (2003) demonstrated this
kind of convergence in a study that linked uneven development of non-verbal/spatial
skills in a subgroup of autism patients who also happened to manifest unusually
large head circumferences (macrocephaly being a frequently seen feature in autism).
In Phase 2, the researchers are now developing database functions that introduce
descriptive statistics and data visualization functions. The aim is to work towards a
larger normative database that will be referenced against a craniofacial atlas.
The studies of craniofacial and brain dysmorphology described above help
to map out complex etiologies in neurocognitive disorders by examining con-
vergences of certain physical and behavioral traits. Matthysse et al. (1992), in
describing a few ways to clarify the complex mix of genetic factors and phe-
notypes in neuropsychiatric conditions, stated that “[i]n the long run, the most
successful method is likely to be direct refinement of non-Mendelian behav-
ioral and physiological traits into more fundamental components” (p. 461). The
behavioral component, to do with defining cognitive-behavioral phenotypes, is
essentially neuropsychological. In such an intensely multivariate research context,
NI offers the enabling framework for the interface between neuropsychological and
physiological data.
3.3.4.2 A Consortium for Neuropsychiatric Phenomics

(See Bilder 2007; 2008a; 2008b; 2008c; Bilder et al. in press a,b,c; Freimer and
Sabatti 2003; Sabb et al. 2008; Krensky 2008; Robert Bilder, personal communica-
tion, January 6, 16; February 5, 6; April 15; June 8, 9, 2009)
URL: http://phenomics.ucla.edu
In the proposal for the HPP mentioned earlier, the authors (Freimer and Sabatti)
also laid out a possible scientific and organizational structure for the project. They
described that the project will need to be a large-scale coordinated effort (akin
to the HGB) that would bring together experts from a variety of disciplines. It
would have to involve numerous databases, holding all levels of phenomics data,
and the data will need to be objectively defined. Quite crucially, it will need to
develop and lay down methods for standardizing the description of phenotypic
data. These methods will not only enable researchers to share a common vocab-
ulary for knowledge development but will also serve the proposed need to relate
different levels of phenotypic data (cellular, neuronal, anatomic, etc.). As was the
case with the HGP, the proposed HPP will require new technologies to automate
complex processes of data analysis, comparison, and modeling. The proposal also
emphasized that novel collaborations and research methods will be essential to the
project.
The Consortium for Neuropsychiatric Phenomics (CNP) is a large, new consor-
tium that is focused on neurobehavioral phenotypes. It can be viewed as the first
large-scale phenomics project/component to be embarked upon that fits in with the
proposed HPP. Thus all that is described in the above paragraph is consistent with
the CNP. The CNP is based at the University of California at Los Angeles and
involves 52 researchers and clinicians from across the institution. Earlier work at
the UCLA Center for Cognitive Phenomics laid the platform for the CNP.
The CNP is funded by 5-year, a 22 million dollar grant from the National Insti-
tutes of Health. Among its strategic initiatives laid down in its 2006 Reform Act (see
Krensky 2008), the NIH established a fund to support transdisciplinary research. It
set forth a series of “Roadmap Initiatives” to fund highly integrative, transformative
biomedical and behavioral research. It stressed research opportunities in emerg-
ing interdisciplinary junctures in medical science and the potential therein to solve
complex medical/health problems. It also stressed the role of bioinformatics as new
pathways to discovery. Nine grants were awarded to research teams around the US.
One was a grant to establish the CNP, which would lead numerous initiatives in
behavioral phenomics.
Of the projects funded by the NIH Roadmap Initiatives program, CNP is the
only one that has a distinct neuropsychological component. Robert Bilder, a clinical
neuropsychologist by training, is the primary investigator and director of CNP. It
should be noteworthy to neuropsychologists, that this groundbreaking, informatics-
infused initiative is led by a neuropsychologist. (At the February 2008 meeting of the
International Neuropsychological Society, in Waikoloa, Hawaii, a continuing edu-
cation course titled “Phenomics for Neuropsychology: Transdisciplinary Strategies
for Research on Brain-Behavior Relations in the Post-Genomic Era” was given by
Robert Bilder.11 )
The Mission and Strategy of CNP: Simply stated, the CNP seeks to identity
neuropsychiatric phenotypes tied to perception, cognition, and emotion. This is
motivated by the complete lack of a knowledge base on cognitive/neuropsychiatric
phenotypes – “there is no coherent knowledge base representing cognitive con-
cepts and cognitive measurements” (Bilder 2008c). Building a knowledge base of
behavioral phenotypes can potentially serve to unravel the mechanisms of neuropsy-
chiatric syndromes and aid in more accurate classification of clinical disorders (see
discussion on endophenotyopes above): It is often the case with neuropsychiatric
disorders that a set of endophenotypes may manifest in more than one disorder, i.e.,
similar behavioral features mediated by common neural mechanisms may manifest
11 The references cited, Bilder 2008b,c, refer to Robert Bilder’s 97 slides presented at the
conference and the audio recording of the lecture, respectively.
in two or more different disorders. This can blur both the scientific understanding of
a disorder and its diagnosis. Of greater value are certain “signature” endophenotypes
or combinations of endophenotypes that may be associated with a neuropsychiatric
condition. Also of interest is how shared endophenotypes may vary in subtle ways
across disorders.
Understanding the behavioral/neural endophenotypes specific to a disorder leads
to the possibility that disorders can be accurately diagnosed by sampling of tar-
get behavioral phenotypes. The idea comes from genome-wide associations studies
(GWAS), where a rapid scanning of genetic markers as opposed to a scan of the
entire genome can reliably signal risk or presence of a condition. If one attempts
to link the rather precise genomics data to neuropsychiatric data, one is forced to
use conventional psychiatric clusters (syndromes) as the neuropsychiatric data set.
There is wide discordance between the two data types – symptom clusters are not
compatible with a scientific structure that seeks to mechanistically link syndromes to
genes. This seriously inhibits linkage between genotypic and phenotypic data in try-
ing to understand neuropsychiatric mechanisms. Hence at one level (“horizontal”),
the CNP seeks a mapping of neuropsychiatric phenotypes to better characterize
neuropsychiatric disorders and link them to underlying genotypes.
The CNP also seeks to describe data such that they can be related to levels of
analysis above and below the level of cognitive phenotypes. Refer to Fig. 3.7a.
The levels above are symptoms and syndromes (and various clinicians and clini-
cal researchers are involved at these levels). The levels below cognitive phenotypes
are those of neural systems, cellular systems, proteins, and genes (each involving
different specialists in biology/neuroscience). These levels of analysis define the
“vertical” structure of the CNP – researchers at each of these levels aim to generate
data relating to the same set of neuropsychiatric disorders. The greater goal of the
Syndromes
Symptoms
Cognitive
Cognitive
Phenotypes
Phenotypes
Neural Systems
Fig. 3.7a Schematic of the
multi-leveled (vertical Cellular Systems/
structure) of the each level, Signalling Pathways
and the position of cognitive
informatics in CNP, the focus Proteins
within relation to the other
levels. From,
Genes
www.phenomics.ucla.edu/index.asp;
printed with permission, Environment
Robert Bilder
CNP is to draw mechanistic links between the gene level and the syndrome level,
through all the other levels. With such a multileveled investigative paradigm and an
emphasis on phenotypes, “we may start to see phenotypes quite different from what
we are used to as the genotype data sets start to come in” (Bilder 2008c).
Neuropsychology and Neuroinformatics in the CNP: Of the CNP’s five interre-
lated research projects, three are concerned with schizophrenia, bipolar disorder,
and ADHD. They presently focus on neurocognitive phenotypes relating to mem-
ory mechanisms and response inhibition, which cut across all three disorders. (Since
the phenome is so vast, a manageable study must limit the number of phenotypes
on which it focuses. The proof-of-concept that is established paves the way for
expansion.)
A current study aims to examine the phenotypes (and their corresponding geno-
types) in a sample of 2000 normal controls and a sample of 300 individuals who
suffer one of the three disorders of interest. In both groups, genotypes and physical
and functional neuroanatomy are examined and cognitive/neuropsychological func-
tions (working memory and response inhibition/cognitive flexibility) are assessed.
For levels of analysis (molecular and cellular) that cannot feasibly be carried out on
human subjects, transgenic mouse models are developed to examine very specific
effects.
In the context of the CNP’s work, neuropsychology bears a very sophisticated
role. This involves defining cognitive/behavioral endophenotypes, which in turn
involves thoroughly examining various cognitive constructs. Existing neuropsycho-
logical tests that may tap an endophenotype has to be selected or new tasks have to
be tailored to an endophenotype. All of this has to be done with the consideration
that the data have to be meaningfully integrated with other levels of analysis and
that comparable tasks have to be constructed when devising animal models.
One of the goals of the CNP is to develop statistical and informatics tools for
analyzing the data across the many research levels of the consortium. The tools
relate to data visualization, modeling, and hypothesis generation (see Bilder et al.
a, in press; Sabb et al. 2008). PubGraph, PubBrain, and Phenowiki are three novel
tools that have been developed by CNP and available for public use:
URLs: http://www.pubgraph.org/
http://www.pubbrain.org/
http://www.phenowiki.org/
PubGraph is a tool for literature mining and for the visualization of the associa-
tions between a set of results. It allows the user to enter one or more search terms,
which it uses to search PubMed/MEDLINE. It then generates a graphical view of the
results, representing resulting terms and concepts as nodes. Lines or “edges” link-
ing the nodes convey coefficient and correlational strengths of associations between
the terms, as statistically inferred through literature mining. Figure 3.7b shows the
resulting graph for the search of the term “schizophrenia.” One way by which the
tool can be utilized is in aiding neuropsychological refinement of a cognitive con-
struct. Strengths of association between the nodes of the graph ultimately reflect
factors and variables common to the nodes. The construct of “cognitive control” as
Fig. 3.7b A PubGraph representation of the literature mining results for the term “schizophrenia”
(results on cognitive/behavioral studies are clustered on the left, and results on genetic/cellular
studies are clustered on the right). From, www.pubgraph.org/; printed with permission, Stott Parker
related in PubMed indexed literature, for example, is closely tied to the constructs
(nodes) of response inhibition, response selection, task/set switching, and working
memory (Bilder 2008b; Sabb et al. 2008).
PubBrain works in a similar fashion – the user inputs search terms, which are
queried in PubMed. The difference is that the results are displayed as a list of search
terms that are extracted from the most frequently occurring search results. Simpli-
fied brain activation maps are generated based on the list of anatomical terms in the
returned list.
Phenowiki is a database-enabled wiki platform for the collaborative building of
cognitive phenotypes. It enables users to explore a concept (e.g., working memory)
by laying out definitions and citations, by describing related concepts, by annotating
the existing content on the wiki, and by linking the descriptions to other resources
such as PubMed, PubGraph, PubBrain, and Wikipedia. Phenowiki provides a space
that promotes incubation, development, and modeling of neurocognitive concepts.
Researchers are given a common medium in which their collective insights can be
brought to bear on ideas and constructs and this is interfaced with other knowledge
building resources.
There are other related developments at CNP: A Cognitive Atlas has being
built for illustrating maps/relationships between cognitive concepts. Cognitive
Ontologies that reflect the sophistication of cognitive concepts and their complex
associations are also being developed. Sophisticated search ontologies (see Section
2.5) are crucial for accurate data retrieval and for the building of detailed knowledge
bases.
These informatics-based tools developed by the CNP are more than just novel.
They are quantitative tools geared for the association of complex data and they are
a vital compliment to large and complex agenda of the CNP.
In the context of the CNP, neuropsychology has to operate in an environment
far different from that in which it evolved. In this kind of research and clinical
environment, the fine granularity on genomic and cellular data pertaining to a dis-
order sets the bar that shapes the entire working environment. Neuropsychology,
as a discipline, is required to apply the data in sharpening cognitive and behav-
ioral constructs. It in turn is relied upon to precisely identify and investigate
cognitive/behavioral phenotypes. It has to deliver neuropsychological data that are
meaningful in the larger scheme of an explanatory framework that stretches from
genomes to phenomes.
The study of cognitive and neuropsychiatric phenotypes is a rapidly emerg-
ing, leading-edge discipline that involves neuropsychology. Once again, being part
of such an enterprise requires that neuropsychology assimilate a rich variety of
informatics methods and tools.
Conclusion for Section 3.3
The nine examples of NI for neuropsychology described in this section embody the
ideas and goals of the NI approach to research and assessment. In relation to their
respective neuropsychological domains, all the examples aspire to “capture, relate
and analyze diverse types of data at multiple levels of abstraction” – the goals of NI
as described by Wong and Koslow (2001, p. 104). All the examples can be described
as responses to fundamental limitations in existing models and research/assessment

methods and all can be viewed as radically new ways of addressing these limitations.
Informed by theory, they deconstruct cognitive functions or neuroanatomic sys-
tems for a fine-grained level of analysis. They modify or devise tools for complex,
multivariate data capture. They begin by testing the NI system on small groups or
hypothetical data sets. They always develop databases to hold their wealth of data.
They search and mine the data for complex relationships between variables. They
look to related disciplines such as computational modeling for novel ways of coding
and analyzing the data and they develop new ways of rendering the results.
Like all areas of NI, the examples in neuropsychology are constantly evolving.
Software is updated. Methods of analysis are improved. Databases grow in size, as
does the user base. The NI system also incorporates new computer and hardware
technologies as these technologies emerge. The initiative, whether at an early stage
of development or one that has been through numerous iterations and has a larger
user base, is always a work in progress. This format allows it to easily adapt, change,
and improve, even while it is being actively used. The format is dynamic.
All of the examples described happen to be projects that have been initiated by
individuals or research groups. Some of the projects, for example, SignStream, have
grown into larger projects involving multiple research teams. Irrespective of the size
of the projects, they generally operate on an open platform and involve collabora-
tion, while maintaining a center of coordination. Methods for deconstructing data
and the designs for databases are often initially determined by the lead team, but
standardization of these protocols is achieved through user input. A good deal of
flexibility is built into the NI tool or database. This enables the user to manipulate
the application with great ease and so tune it to his/her research or assessment needs.
The contribution of data to a shared database is encouraged and the availability of
the database gives the user a convenient reference tool.
These NI applications in neuropsychology greatly empower researchers/
clinicians to clarify questions and clarify data. They generate new models of
neuropsychological functions. Very importantly, they constitute a dynamic, user-
empowered, information-sharing and information-generating environment.
Chapter 4
Obstacles and Aids to Neuroinformatics
in Neuropsychology
The threshold between neuropsychology and NI has been crossed. Neuropsychology

is an established discipline with many long held conventions, and NI is a relatively
new, highly innovative practice, the emergence of which is impossible to ignore.
As these two fields begin to interact, there are bound to be those forces that are
reticent about the prospect of neuropsychology being reinvented by informatics.
There are also bound to be those forces that will eagerly endorse the growth of NI
in neuropsychology, in recognizing enormous potential in NI. Each of these sets
of forces will likely bring strong arguments based on the contexts in which they
were shaped.
Among the major goals of this book is to articulate the case for NI in neuropsy-
chology and to do so in part by illustrating various limitations in neuropsychological
models and assessment methods. This hardly implies a devaluation or dismissal
of an entire tradition. Examining possible ways in which neuropsychology and
NI will relate to each other becomes a complex matter. On the one hand, forces
in neuropsychology likely to impede NI approaches need to be conveyed. These
may relate to attitudes shaped by decades of professional consensus, tradition
(or wisdom); practices imparted by disciplines to which neuropsychology has
been closely tied; practical constraints; and special interests. On the other hand,
bioinformatics has been so widely practiced over the past few decades that a
hard-worn trail has been left: Many specialized disciplines have been through a
reshaping by informatics and have taken the best of it, to emerge more power-
ful than ever before. Issues of data confidentiality and ownership have already
been discussed as other clinical disciplines adopted informatics methods, and solu-
tions have been proposed and implemented. Technical and logistical challenges
have been plentiful and they have only made practitioners more determined to
overcome them.
The larger issue here cannot be cast as neuropsychology versus NI. In each field,
there are such a variety of factors: some that better serve a productive meeting of
the fields and some that do not. This section lays out three broad, related overarch-
ing considerations. Through each, some specific factors that could potentially slow
the implementation of NI in neuropsychology are described, as are factors that can
potentially mitigate the obstacles. The point of this section is to sample some of the
major issues and some ways by which they can be resolved.

86 4 Obstacles and Aids to Neuroinformatics in Neuropsychology
4.1 Data Sharing and Issues of Privacy

Issues of privacy that arise in the discussion of NI in neuropsychology pertain
mainly to (a) confidentiality of patient data generated in clinical settings and how
this should be treated and (b) data generated in academic/research contexts, the shar-
ing of the data with other researchers, and the potential that the identity of research
subjects can be gleaned from the data.
As any clinician knows, rules of patient/data confidentiality apply to almost all
types of clinical practice and clinical research. With its emphasis on fine granular-
ity of data, NI applications may appear unsuited to clinical data since confidential
patient information may be carried in the fine grain. This however is not the prob-
lem nor does it accurately reflect the NI approach. In general, NI approaches seek
fine-grained data. To a great degree, this can be accomplished within the constraints
of ethical and practical boundaries. NI approaches are shaped by greater clinical
and research contexts. Just as a published clinical study may contain a lot of patient
data without revealing patient identity, so can databases (and private and federal
agencies do compile such databases for a variety of purposes). Neuropsychologists
can develop databases for the data generated in their everyday practices. Even under
the patient privacy rules of an institution and under ethical guidelines of a clini-
cal discipline, there is still ample room to database clinical/assessment results that
will otherwise be undocumented or filed away. The examples described in Section
3.3 suggest many ways by which NI can be applied to neuropsychology without
requiring changes to privacy policies.
At the same time, neuropsychologists should actively engage in a re-examination
of privacy codes that have their roots in a bygone (“noninformational”) era, just
as this re-examination has taken place in neuroscience (see Koslow 2000). When
discussions have occurred in neuropsychology about privacy issues brought about
by information technology in clinical practice (for example, report by the National
Academy of Neuropsychology 2000; Bush et al. 2002), the discussions have been no
more than a reiteration of established guidelines. What neuropsychology, especially
clinical neuropsychology, needs to come to terms with is that the issue of privacy
is recognized even at the level of National Research Council as a balancing act
between individual privacy rights and public benefit from shared clinical data (see
report by the National Academy Press/National Research Council 1999).
Issues of data privacy prompted by developments in NI have played out intensely
in the academic/research context. Nowhere has the debate been more vigorous than
in discussions on whether to share functional imaging data. In mid-2000, when
Michael Gazzaniga was director of the then newly created National fMRI Data
Center (a brain image repository) at Dartmouth College, he made an announce-
ment that pulsed the imaging world: Authors submitting imaging studies to the
Journal of Cognitive Neuroscience (of which he was the editor) would also need
to submit their primary data (fMRI scans) to the data center – an open access repos-
itory for research (see Editorial, Nature Neuroscience 2000; Aldous 2000). Many
opposed the idea, citing issues of researcher rights to ownership; access by oth-
ers to the data; and possible misinterpretation; entrustment of the data to another
4.1 Data Sharing and Issues of Privacy 87
institution, etc. Many supported the idea, citing the potential opportunity to review
the work of others; facility to compare similar scans from different studies; and the
building of a large image database – the debate continues. The controversy, said
Gazzaniga, did a service to the field by engaging imaging researchers in an exami-
nation of the data sharing (see Aldhous 2000). “Sharing is justified because analysis
of the same data sets by different scientists might yield a different interpretation and
would not require someone to repeat the whole experiment to query the data with
a different question. Sharing would also provide a rich data source for theoretical
neuroscientists” (Koslow 2002).
Clinical neuropsychologists may sooner or later be engaged in similar debates,
as NI systems become part of their discipline. Some early lessons can be gained by
looking at how issues around data sharing have been mediated in neuroscience. Van
Horn and Gazzaniga (2002) described measures taken by the Dartmouth fMRI Data
Center to ensure subject anonymity and protection:
In compliance with US federal regulation 45 CFR 46 on human subject protection, we
had to address the requirement that any and all information that can be used to identify
a subject must be removed from the data, while maintaining its experimental integrity.
This is accomplished in a two-pronged effort. First, contributing authors remove identi-
fiers before submitting study information the Data Center. Then the Data Center checks for
identifiers that might have been missed by the authors, while removing other potential iden-
tifying subject descriptors To remove [the possibility facial contour reconstruction from
high resolution head images], the high resolution images are stripped of facial features.”
Many proposed methods for data sharing involve design elements in the NI system
to do with controlled access to information (see Lee et al. 2000). Some examples are
(a) A database that holds detailed raw data from multiple researchers but only gives a
researcher access to an index of the data; the index contains the contact information
for the contributor of each data set. With additional permission protocols, the data
set can presumably be obtained from the contributor in a ready-to-use, standard
format. (b) Data can be stored at progressive levels or stages, ranging, for example,
from specific personal descriptors to the broad diagnostic categories and at each
level, it can be divided in sets. Particular configurations of the data grid can be made
available to a researcher based on the level of permission he/she holds (IT network
and personal computer operating systems involve different levels of user rights).
The greater point in this discussion concerns not the exact details of data access
but the need for neuropsychology to recognize that engaging with NI also requires
engaging the question of access to primary data. Stephen Koslow, the former direc-
tor of the Office of Neuroinformatics at the NIH, has argued passionately on this
cause (for data sharing) in articles such as “Should the neuroscience community
make a paradigm shift to sharing of primary data?” (Koslow 2000) and “Sharing
primary data: a threat or asset to discovery” (Koslow 2002). In the current time,
these debates in NI have less to do with the question of whether data should be
shared; that is largely accepted. The questions are about the rules and guidelines
for data sharing that are needed. The need has come about suddenly with a new
enabling technology showing enormous prospects for knowledge discovery through
data sharing.
Clinical neuropsychology especially needs to quickly get on board the discus-

sion on data sharing that has been taking place in NI and neuroscience. Rather than
filing away assessment results on pieces of paper and being unquestioning about pri-
vacy policies, it needs to examine its conventions against the prospect of collective
scientific benefit brought on by NI.
4.2 Standardization, Taxonomies, and Ontologies

for Neuropsychological Data
At a purely practical level, if clinicians or researchers wish to share data in an

expedient manner, the data need to be specified in a common format. There are
various types of data formats depending on the context. For printed journal articles
in neuropsychology and much of the medical field, the proverbial format involves
an abstract, introduction, hypotheses, statement of methods, etc. With digitized data
for NI applications, formats have to be viewed in the contexts of databases designed
to hold the data and algorithms that will work on the data. A key variable relating to
this format of data is the data field, i.e., a piece or unit of data of a certain type that is
entered into the database. When researchers design a database for data sharing, they
first try to establish exactly what kinds of data/data fields they wish to specify, and
once decided, these data fields become a common standard for describing the data.
The concept of throughput in informatics refers to the movement and processing
of data through an informatics system so as to favor production of a desired output.
It is measured by the average rate of successful output. Two main factors influence
throughput, the design of the system and the structure of the initial form of the data.
The latter, again, has to do with how the data are broken down on initial entry into
the system. It also concerns how related pieces of data may be clustered at the data
entry level and the validity of relatedness between elements of the cluster. If the
NI system is to compare to data variables at a later level in its processing and if
the data variables are inadequately specified at the data entry level, then throughput
is affected as are potential comparisons that may require the fields of data. All of
these point to the crucial elements of well-specified data input and uniform sets of
data fields.
A number of issues arise when determining the nature and extent of data fields
for a database related to NI in neuropsychology, for example: Who decides the
data fields? Whose research or clinical interests do they serve? On what theoreti-
cal grounds, if any, are the data fields derived – do they individually or as a cluster
have construct validity? How many data fields should there be? (High levels of data
granularity require many data fields and make for tedious data entry but hold more
potential for complex analysis and vice versa). These are important considerations
in database development. They involve anticipating many of the functions of the
data and confronting potential problems sooner than later in the game. Irrespective
of the complexities, the fact always remains that a particular set of data field will
be common currency when databases are shared. Such standardization also enables
interoperability between NI systems.
4.2 Standardization, Taxonomies, and Ontologies for Neuropsychological Data 89
Increasing throughput may involve among other things a great reliance on auto-
mated and online assessment tools: “Another possibility for increasing throughput
is to adopt less labor-intensive procedures [f]or example, it is possible to collect
information of certain behavioral features through assessment tools that can be
self-administered over the Internet by individuals throughout the world.” (Freimer
and Sabatti 2003). How open will the field clinical neuropsychology be to the
introduction of large-scale automation in such a core component of its charge?
How will these issues play out if neuropsychologists embark on developing an
open-platform online database of results from assessment batteries? What kind of
neuropsychological battery should be used? Would it be an adaptation of the widely
used WAIS? Would it be more akin to ANAM? What if one or the other is considered
inappropriate in terms of the precision with which a perceptual or cognitive feature
is parsed out? If one embarks on a very ambitious NI project such as that conducted
by the Consortium for Cognitive and Neuropsychiatric Phenomics, then it becomes
imperative that the data fields in the database be very finely tuned to a cognitive
phenotype.
Usage of any neuropsychological test or battery presupposes a definition of the
functions being tested (an issue raised many times in Chapter 3). Neuropsychol-
ogy has always been using taxonomies, both implicit and explicit. The big problem
here is that neuropsychology cannot optimally engage with NI without first con-
fronting some of its taxonomies. Some may be simply inaccurate in the light in
newer data and some may be so implicitly held in assessment tools that they have
never been questioned (see Chapter 3). With refined taxonomies, the NI systems
for neuropsychology can build ontologies that are more suited to the classification
of complex data (see Bilder et al. c, in press). Taxonomy and ontology develop-
ment influence each other. Data mining functions require some level of specification
of how groups of data are related and if these relations are inaccurately specified,
subsequent computed relations will be inaccurate (see Sections 2.5).
Almost certainly, the talk of shared databases, open-ware neuropsychological
batteries that will upload to these databases, and the radical reinvention of assess-
ment tools to make them NI capable will raise the ire of certain commercial entities.
These are the entities that have for many decades been pumping out spring-bound
cardboard booklets and painted puzzles, nicely contained in immaculate black brief-
cases. Neuropsychologists, generally well intentioned, have aided in the process by
authoring revisions of the batteries, and the field of neuropsychology has partaken
in establishing assessment norms for various tests. Altogether, the arrangement
has been that neuropsychologists have been dependent on these batteries (there
have been no viable alternatives); this has legitimized the batteries even though
they are based on questionable constructs and have designs that are antithetical to
shared electronic data building; and in return, neuropsychologists have paid pre-
mium prices for copyrighted sheets of paper containing some rows and lines, on
which to score results! In this era of NI, much superior alternatives are afforded.
In fact, if these alternatives are developed under federal funding programs, they
are likely to be freely available to neuropsychologists. How can neuropsycholo-
gists on a global scale achieve the development of assessment tools that are truly
informatics-based and informed by contemporary cognitive neuroscience? Infor-

matics developments for clinical and academic research funded by agencies like
the NIH and the NSF provide the ideal model – bringing the best scientific teams
to create wonderfully sophisticated tools that are then made freely available to an
entire community. Consider some examples described in earlier sections: The Caret
software for surface-based brain atlases is funded by the NIH, NSF, and other fed-
eral agencies. SignStream, the sign language database and analysis tool is funded
by the NSF. PubBrain, PubGraph, and Phenowiki, are all developed at the Consor-
tium for Neuropsychiatric Phenomics with funding from the NIH. These projects
are funded by the public (tax payers); it follows logically that all scientists and clin-
icians have free access to the end results. In precisely the same way that SignStream
has been developed, neuropsychologists need to team up and initiate a federally
funded development of a large, modular, informatics-based assessment battery. To
some degree, this has already been initiated with the development of ANAM in the
context of the army. The civilian population deserves a similar level of protection!
Federal funding agencies are the strongest force behind the idea that research
data be digitally archived and available for public access. Tools/facilities like MED-
LINE and PubMed enable the process. Articles published in the Proceedings of
the National Academy of Sciences as well as in other journals published by fed-
erally funded agencies, are easily and freely available online. Authors submitting
articles to such journals are required to use specific electronic formats that facilitate
the process of online access. In the same way, researchers submitting data to the
NIH’s National Center for Biotechnology Information (NCBI), an integrated one-
stop resource for molecular biologists and geneticists, use standardized methods.
GenBank!, R the NIH database for gene sequences, is part of NCBI. It holds a large
collection of publicly available DNA sequences. This is made possible because data
submission is through a common protocol.
Will future neuropsychological research and practice involve these kinds of data
sharing platforms and coordinating facilities? Will the discipline be able to establish
uniformity in its subject descriptors, in methods of assessing them, and in methods
of relating them? It is hard to imagine that neuropsychology will not reach this stage
or that it will remain delayed. Neuropsychology, as always, is influenced by the
greater contexts of medicine and psychology. Modern medicine, at least, is insep-
arable from the thrust of biomedical research, which is turn has informatics in its
DNA. Neuropsychology will sooner or later be pressured or even mandated to be an
equal player. In his presentation at the 2008 mid-year INS meeting, Robert Bilder
poignantly summed up this complex issue:
“. . . would you be willing to donate data if you had to transform everything so that it fol-
lowed the rules made up by someone in Washington or someone at UCLA . . . and so that
also is a problem; to have uniform ontologies for depositing data becomes a challenge . . .
I think the problem is one of massive proportions almost to the point of being currently
intractable with current methods because of the heterogeneity of collection methods and
the way we go about specifying all of the phenotypic data that we collect . . . ontology
development is already upon us; what is going to happen, the same way that the NIH is
now mandating that genome wide association data be deposited under certain criteria for
exactly how those data need to be deposited, in the future, all phenotypic data are going to
4.3 Attitudes, Re-organization, and Training 91
be required to be deposited following the rules of some federated ontology, so if you have
an index of working memory, you will be able to choose from a menu of what that is . . .
otherwise justify exactly how what you are doing is different and why you are not using
existing techniques. I think that’s where it’s going.” (Bilder 2008c)
Indeed that is where it’s going! All the signs and signals on NI in neuropsychology,
as laid out in Section 3.3 clearly say so. An urgent focus for neuropsychology is a
broad-based examination of how to make this transition as smooth as possible.
4.3 Attitudes, Re-organization, and Training
Major change of paradigms requires change of attitudes, and when paradigms

change through technology, preparation and training are often needed. Strong resis-
tance to NI in neuropsychology is unlikely. Resistance may occur to the extent that
the issues described above (privacy issues and standardized NI methods) will be
debated. Certain commercial interests may try various strategies to maintain their
market share of neuropsychology but none are likely to prevent a major shift to
shared NI systems for neuropsychology.1
Neuropsychological assessment methods have been developed over many
decades. Norms for tests and batteries have been established through large masses
of data gained over hundreds of thousands of clinical hours. The general operating
system for clinical neuropsychology is one that is securely installed. A new tech-
nology that suddenly flies overhead on the trajectory of a sharp new paradigm will
surely be unnerving as it transmits new rules.
Change and the urging of the progress, however, are hardly new in neuropsy-
chology. Pioneers in the field have always issued caution or made calls for revision.
Writing in 1964 about the problem of small sample sizes in lesion studies, Ralph
Reitan stated
“We may be able to accumulate large enough groups within the next 20 years, but we would
hope by that time the results might have lost their significance at least partially through
obsoletion of the test battery!” (Reitan 1964, p. 305)
Benton (1992) reviewed the progress made in clinical neuropsychology over a

period of three decades (1960–1990). He described that neuropsychology in the
1960 s was slow to tap development of the 1950 s in neurology and psychology:
“However, in 1960, neuropsychologists had yet to apply the novel assessment techniques
employed in these studies in their own clinical research and practice. Nor had they taken
advantage of the many tests described in the literature of clinical neurology and the liter-
atures of educational, vocational, industrial and applied psychology that might have been
adapted for neuropsychological use. For the most part, clinical practice in the 1950 s relied
1A commercial entity that produces a NI tool that facilitates information sharing in neuropsychol-
ogy and does not impose numerous limits that serve primarily a profit making interest, cannot be
viewed as an entity that impedes NI in neuropsychology.
on analysis of performance patterns on the Wechsler-Bellevue, which was hardly the opti-
mal instrument for the purpose, or on the first version of the Halstead-Reitan battery.”
(Benton 1992, p. 410)
Benton went on to suggest that assessment in the current era needs to be informed
by contemporary theory just as assessment decades ago needed to be informed by
theory of the time: “Given our present knowledge of brain-behavior relationships,
of cognitive processes . . . are we doing as well as we can? . . . In short, we should
take a hard look at the neuropsychological examination. It deserves its own critical
examination.” (p. 415)
As the discipline faced such cautions and calls for changes, it did apparently
respond – neuropsychology today is not what it was in its infancy and is marked
with many successful efforts towards formalization. What then is different about the
present call for neuropsychology to adopt NI? Will the field just adapt as it faces
the evolutionary pressures on NI? As already conveyed, NI is not just a technol-
ogy that can be tacked on nor does it amount to a retrofitting project. Unlike other
adjustments that neuropsychology may have made in the course of its development
(a tweak here and a recalibration there), NI implies deeply systemic changes. Nev-
ertheless, as the benefits of NI in neuropsychology begin to emerge, the system can
be expected to reorganize.
To aid the process, many simple steps can be taken within the field: Professional
bodies can appoint task forces to examine possible NI approaches and make rec-
ommendations. Conference organizers can aim to build NI themes into conference
agendas. Clinicians and researchers can seek alliances with informatics special-
ists to help design NI systems. Perhaps the most effective (conventional) way to
spread NI consciousness is through neuropsychology journals – by adding a com-
ponent/section devoted to NI or at least encouraging manuscripts on the topic. An
old problem in neuropsychology is that when relevant new technologies emerge
they are often outside the view of the neuropsychologists. Kane and Kay (1992)
noted this problem and Kane (2007) summed it up (referring here to computerized
assessment):
“Information about these efforts was available; however, it was found mostly in technical
reports or in journals not typically monitored by neuropsychologists. Kane and Kay (1992)
noted that the amount, quality and importance of the work being done in the field of com-
puterized assessment was not fully appreciated and was in fact occurring under the radar of
most neuropsychologists. (Kane 2007, p. S3).
Something similar can be said of NI developments that relate to neuropsychol-

ogy. These developments, arguably, have been occurring in full range of the radar
of neuropsychology, but field has just not been tuned to the unique signals of NI.
This is all the more reason that NI should be given coverage in neuropsychology
journals.
While the above measures are needed, the logistical and technical challenges in
reshaping how a discipline is practiced should not be understated. NI can be very
technical, both in theory and application. Programmers, database developers, sys-
tems engineers, IT specialists, computational modeling specialists, etc., are those
4.3 Attitudes, Re-organization, and Training 93
who typically handle the more technical aspects of NI. It is imperative though
that the neuropsychologists familiarize themselves with the field of NI in general.
Neuropsychologists should have a good sense of NI potential – its functions and
capabilities – so that they can at least conceptualize different NI methods when
thinking of clinical and research problems. Of course, keeping abreast of cognitive
neuroscience will also aid the formulation of these ideas. Writing in the context
of automated assessment (see Section 3.1), Schlegel and Gilliland (2007) stated,
“Given the rapidly expanding frontiers of neuroscience, test developers will increas-
ingly have to keep one eye on test programming and one eye on neuroscience
research to remain abreast of construct validity advances.” (p. S54).
Conferring NI perspectives on neuropsychology trainees should be a high prior-
ity. This implies changes to the syllabi and requirements of clinical, doctoral, and
postdoctoral programs. Just as training in psychology generally requires courses
in statistics, budding neuropsychologists should be empowered by courses in NI
for neuropsychology. In making such curricular adjustments, a good resource may
again be federal funding agencies. The NIH, for example, has a funding program
for clinical research curriculum development; it supports the development of formal
courses in many biomedical areas including medical technology.
The more neuropsychology is informed about NI, the smoother its course of
engagement will be. Exposure to existing projects (Section 3.3), understanding
their rationale and their gains, and the emergence of a few more could help cat-
alyze change with the field. Bringing NI to neuropsychology will undoubtedly
be challenging but all that has occurred in NI thus far should be inspiring and
motivating.
Chapter 5
An International Society for Neuroinformatics
in Neuropsychology
URL: www.scnn.org
Neuroinformatics interest groups have steadily emerged within research orga-
nizations and academic societies. The NIH has one, as does the Society for
Neuroscience. These interest groups can vary in scope, from offering platforms for
discussion to acting as central coordinating facilities for global research in NI. The
neuroinformatics interest group of the OECD (see Section 2.6) is an example of
the latter. The importance of NI interest groups has been conveyed throughout this
book – they foster collaboration and promote NI initiatives.
In the course of writing the book, the author developed a collaborative network
with many clinicians and researchers whose projects are described in Section 3.3.
Much of the collaboration involved exchange of information, updates on NI projects,
reviews of data, etc. As noted in the introduction to Section 3.3, essential material
for the book was obtained through this collaboration. By the end of writing the book,
the author had networked a group of researchers with common interests.
A logical step was to form an organization to promote these interests. An inter-
national organization devoted to neuroinformatics for neuropsychology was hence
recently formed. It was named the Society for Neuroinformatics in Neuropsychology
(SCNN). A website for the organization has been launched (see above URL). The
website may be of benefit to researchers interested in NI for neuropsychology.
The SCNN will serve three broad functions: (a) foster discussion on the topic,
(b) compile and communicate resources, and (c) assist in coordination of projects.
These functions will to some degree overlap with each other. Emphasis on each
function will vary at different times depending on the needs expressed by members
and the specific priorities of the organization at a given point. However, the organi-
zation will remain structured around the three main functions. These functions are
summarized below (see Fig. 5.1).
Discussion Forum: A discussion forum will offer researchers the space to explore
ideas for NI in neuropsychology. It will also help to focus discussion on a number
of relevant topics such as
• Database platforms and distributed architecture for large-scale NI systems for
neuropsychological assessment data
• NI systems for the study of specific cognitive functions
• Synchronization of databases, computer platforms, and protocols between multi-
ples teams

96 5 An International Society for Neuroinformatics in Neuropsychology
Examples of Discussion
Topics
-General design of NI systems
Examples of Working Group Projects
-Database/network architecture
-Ontology for data mining
-Synchronization of systems
-NI in neuropsychology
-Theoretical frameworks curricula
-Data privacy -SCNN conferences
-Neuropsychological
PROJECT NI in National Health
DISCUSSION COORDINATION Information Networks
FORUM & WORKING
-Coordination of
GROUPS multiple small
SCNN scale projects
Examples
-Relevant NI projects
-Books, websites, etc
COMMUNICATION
& RESOURCES
-Funding programs
-Meetings, conferences, etc.
-Resources for software/hardware development
Fig. 5.1 Summary illustration of the major functions of the society for neuroinformatics in
neuropsychology
• Theoretical frameworks for neurocognitive functions – to guide NI initiatives

• Ontologies for knowledge discovery in neuropsychology
• Data privacy issues
Communication and Resources: The SCNN aims to communicate developments

in the field. The organization’s website lists a range of resources. Researchers are
encouraged to submit links to other resources. Resource categories are expected to
expand based on user needs and feedback. Resources currently listed include
• Current NI-neuropsychology projects

• Articles, books and websites
• Meetings, conferences, and symposia (in neuropsychology, computational neu-
roscience, informatics, etc.)
• Funding programs that support NI initiatives in neuropsychology
• Academic programs in neuropsychology at universities with bioinformatics
programs
• Various software and hardware resources and vendors
• Software policies and support for open-source developers
5 An International Society for Neuroinformatics in Neuropsychology 97
Project Coordination and Working Groups: As needs and projects arise, the orga-
nization will be able to draw on its network to form working groups and committees.
These may be set up to address, for example, some of the topics in the discussion
forum that may be actively discussed and thereby call for special focus committees.
Working groups could be set up to explore for example, ways of introducing NI in
neuropsychology training curricula, and the place of neuropsychological informat-
ics in the context of national health information networks. Another possible area for
a coordinating committee is the tracking and coordination of many small-scale NI-
neuropsychological efforts around the world so that research groups can consider
ways of making their data sets and NI systems interoperable.
The SCNN is a very new organization and is currently led by the author in col-
laboration with some of the researchers whose work has been described in earlier.
It is hoped that as the group gains a broader membership, more individuals can
contribute to its structure and mission. The SCNN website will provide updates
periodically.
Chapter 6
Concluding Remarks
Neuropsychology has a long and proud history. It grew out of behavioral neurology
and psychology and developed into a full-fledged discipline. So much of cognition
and behavior is meaningful only when studied in relation to the brain – and this
is where neuropsychology has successfully demonstrated its unique focus. Clinical
neuropsychology and experimental neuropsychology have been the tracks that have
formerly defined the discipline for more than half a century.
Since the emergence of “cognitive neuroscience” about three decades ago, there
has been a noticeable “shrinking” of the field of experimental neuropsychology.
Many topics and researchers that once belonged to experimental neuropsychology
have sought a more fitting (and perhaps more prestigious) home in cognitive neu-
roscience. One can debate endlessly the degree of overlap or difference between
experimental neuropsychology and cognitive neuroscience or even whether there
is any difference at all. What is less arguable is that the playing field of the
discipline of neuropsychology changed drastically in the 1980 s and 1990 s as
brain-behavioral research rapidly accelerated in disciplines like neurobiology and
as new imaging methods came onto the scene. The traditional neuropsychological
methods of deconstructing cognitive behavior and seeking relationships between
cognition and neural systems had by this point reached a plateau. Assessment
tests and lesion models in neuropsychology would remain valuable as always
but they had reached fundamental limits. Much clearer, discrete brain-behavioral
associations were being generated through behavioral-neurophysiologic investiga-
tions in primates and through cognitive functional imaging in humans. What was
once a clear transitional zone between neuropsychology and neuroscience started
to see some complex demarcations – making for the emergence of “cognitive
neuroscience.”
Clinical neuropsychology, though influenced by this change in the landscape,
remained largely as it was. Since it was a thriving discipline, established in its own
right, there was no pressure for fundamental shifts from its well-codified tools and
procedures. It continued along with its assessment batteries that had their roots in
psychometry and intelligence testing. It continued with its armament of individual
tests that were tuned to gross cognitive/perceptual complexes. A strong neural-
theoretical basis for many of these tools would remain unclear though the need
was acknowledged. It had revised and formed these tools over many generations

100 6 Concluding Remarks
and they influenced the definition of the functional domains on which clinical neu-
ropsychology traditionally focused. For the most part, the data generated by these
tools were in physical form, viewed by the clinician and then stored away.
As was the case in almost all other disciplines, knowledge building in neuropsy-
chology was a slow and manual process. Data would be published in journal articles,
and over the years, patterns would be observed and models could be built.
A Major Change in the Neuropsychological Landscape: The landscape on which
neuropsychology operates is once again changing. The change began towards the
end of the 20th century. It continues into the beginning of the 21st century and all
indications are that it will transform the way many disciplines are practiced. This
change is all about data. It has to do with how data are extracted and dealt with in
this greater digital informational era. Once upon a time, clinicians and researchers
were relatively disconnected and only got to share their ideas and data in publica-
tions and at conferences. Now, through the Internet, through databases, and a host
of informatics technologies, new and previously unimaginable methods for collab-
oration have been minted. These methods are rapidly becoming the currency for
discovery, effectiveness, and innovation in clinical, research, and academic worlds.
The vast amount of data on the Internet is only one of two key factors in this revo-
lution. The other factor centers on a powerful set of next-generation Internet tools.
These tools facilitate the knowledge building process by enabling individual sets
of data across the web to be integrated and by enabling researchers to dynamically
participate in the process. These changes in how knowledge is built are influencing
all disciplines including the likes of literature and philosophy.
Neuropsychology is at a critical threshold. It faces entry into an altogether new
way of transacting its business. Yet, ironically, the identity that neuropsychology
has so carefully built over the decades seems to have locked in a consciousness that
prevents it from recognizing this change. How it crosses this threshold will have far
flung ramifications. It is imperative that neuropsychology perceives very clearly the
new informational platform that has grown all around it.
6.1 Collaborative Knowledge Building in the Next Wave

of the Internet: Web 2.0, Neuropsychology 2.0,
and Global Network Innovations
The Internet and the abundance of information it has generated have been obvi-
ous definitive features of the past two decades. This larger phenomenon has had
many societal implications, among them, a displacement of the traditional model
of knowledge dissemination (see Jensen 2007). The Internet greatly advanced the
democratization of knowledge. Even specialized knowledge, once held by few as a
scare entity, became commonly available. Expertise became less and less the domain
of a few specialists and more and more spread across a large set of Internet users.
The first generation of the Internet (from the early 1990 s to approximately 2004)
while revolutionizing the spread of information bore some elements of traditional
6.1 Collaborative Knowledge Building in the Next Wave of the Internet 101
knowledge models: It was characterized by a large number of servers that held infor-
mation; users went to these servers and got the information. The sheer number of
servers and users and the resulting global flow of information made for an infor-
mation revolution. Yet the server (vendor) and client (receiver) model was in some
ways reminiscent of information dissemination during the pre-digital age.
In 2004, formal recognition was made of a unique set of practices that had begun
to evolve over the Internet. These practices altogether established ways of collec-
tive knowledge building in which large groups of users became the contributors
and co-developers. “Web 2.0” was the term coined to describe these practices, the
principles behind the practices, the specialized web tools involved, and the radical
shift to a model of networked communities.1 Web 2.0 captures a trend in open plat-
form Internet use that is geared to user-driven online networks and knowledge bases
that constantly change and grow. It is a flexible, user-driven approach to building a
product. “. . . [A] single monolithic approach, controlled by a single vendor, is no
longer a solution, it’s a problem” (O’Reilly 2005, p. 2). Wiki platforms are one of
many tools that enable collaborative knowledge building. The online encyclopedia
wikipedia.org is among the best known examples of a product derived with Web 2.0
principles. Web 2.0 in essence is about (1) harnessing interactive user networks that
stem from the Internet, to (b) collectively develop and customize ideas and products
and (c) refine these ideas or products as more users contribute to them. The result
is a knowledge-oriented participatory environment in which great amounts of data
are integrated and novel products are molded. Dynamic forms of collaboration and
engagement are hallmarks of Web 2.0, and the power of the phenomenon has been
referenced by numerous terms over the past few years, such as digital democracy,
collective intelligence, wisdom of groups, architecture of participation, and dynamic
content creation.
At the February 2009 meeting of the International Neuropsychological Society
in Atlanta, Georgia, Robert Bilder presented a paper titled “Neuropsychology 2.0:
Leveraging Genomics, Phenomics, and the World Wide Web”. Bilder described how
existing technologies (of the Web 2.0 variety) can be used to re-energize the field
in view of the limitations brought about by its outmoded neurobehavioral models
and “instrument inertia.” Bilder proposed an action plan involving web collabo-
rations to build cognitive ontologies, knowledge bases, and automated assessment
instruments.
It is inevitable that such developments will transform neuropsychology, mak-
ing for “Neuropsychology 2.0”. The field is destined to reach a critical point of
departure from its now maladapted tools and traditions. Informatics tools will enable
new modes of data gathering and knowledge building. With NI, neuropsychology
1 An authoritative commentator on the Internet, Tim O’ Reilly, is widely credited with having
coined the term “Web 2.0” in 2004. O’Reilly’s 2005 article, “What Is Web 2.0: Design Patterns
and Business Models for the Next Generation of Software” is considered a landmark refer-
ence on the topic (http://www.oreillynet.com). Numerous informative books on Web 2.0 have
since been written. See for example Jones (2008) and Vossen and Hagerman (2007). See also
http://en.wikipedia.org/wiki/Web_2.0
will also be able to develop sophisticated standardized, high-throughput assessment

tools that will be refined through dynamic user input. As the field embarks on this
change, it will also be building an informatics infrastructure that will serve it for
decades to come. Generations of neuropsychologists stand to benefit from a compre-
hensive global NI-cyber-infrastructure for neuropsychology. This networked system
will feed data onto itself making for a constantly enriched, dynamic data/knowledge
environment.
The concept of utilizing computer networks for experimentation and knowledge
generation is such a powerful one that it is a driving concept for the federally
supported effort to revamp that Internet. The Global Environment for Network
Innovations (GENI) is an NSF sponsored program that tests a range of ideas for
computer network architecture, with a view to improving the existing Internet. What
is unique about the project is that it is about much more than hardware infrastruc-
ture. It recognizes that optimal Internet infrastructure needs to incorporate network
layers and novel communication platforms through which “the dynamic interactions
of physical and social spheres” can be played out (www.geni.net). GENI engages
researchers from academia and industry across a range of disciplines. It solicits
proposals and provides test beds for new forms of network infrastructure. Neu-
ropsychology can take every advantage of such programs to create for itself a digital
sandbox – a network test space.
6.2 The Promising Politics of Informatics Infrastructure

The self-generated, self defined force of the internet may be phenomenal but it is
still influenced by broader social, economic and political factors. Communications
infrastructure, for example, on which the internet depends, is affected by prevail-
ing economic climate. The updating of national information grids to handle greater
data volume and at higher speeds is a common concern and this aspect of internet
development is often tied to federal spending and political agenda.
The lack of a unified health information network (in the USA) is a matter that
has been receiving great attention. Physicians in the USA do not have a nationwide
system for patient health records: Only a small fraction of hospitals and physicians
in private practice have implemented comprehensive information systems for med-
ical records, and different computerized systems are used by different healthcare
networks (see Jha et al. 2009). The result is that billions of dollars are spent annu-
ally on manual transfer of records or the regeneration of records. A bureaucratic
environment, hazardous to patient heath, has emerged. This concern that has been
expressed so strongly in clinical medicine (see Blumenthal 2002; Blumenthal and
Glaser 2007; Jha et al. 2006) is also a concern for clinical neuropsychology as the
field looks to developing an informatics infrastructure.
The problem of the lack of a national heath information network (HIN) has been
deemed so dire that the current president of the USA, soon after being elected,
addressed the issue as part of his economic recovery plan:
6.3 Prologue to Neuropsychology for the 21st Century 103
“In addition to connecting our libraries and schools to the internet, we must also ensure that
our hospitals are connected to each other through the internet. That is why the economic
recovery plan I’m proposing will help modernize our health care system – and that won’t
just save jobs, it will save lives. We will makes sure that every doctor’s office and hospital in
this country is using cutting edge technology and electronic medical records so that we can
cut red tape, prevent medical mistakes, and help save billions of dollars each year” (Obama
2008; excerpt from a radio address delivered on Dec. 6).
The promise drew applause but also words of caution. Some specialists on the topic
responded in an open letter, highlighting among many points, the lack of interoper-
ability among current systems, and the need for some basic steps such as extending
high speed internet access to all practitioners.2 Undaunted by debates on the value
of health information networks or the difficulty of the task, about $20 billion dollars
have been allocated toward health information technology (HIT) through the Amer-
ican Recovery and Reinvestment Act of 2009. The initiative will be overseen by the
newly created Office of the National Coordinator of Health Information Technology
(see Blumenthal, 2009; www.recovery.gov). Discussions and debates around health
information technology and electronic medical records continue and have broadened
into the public domain.3
The issue is very pertinent to neuropsychology as neuropsychology considers
large-scale informatics systems for communication and data sharing. A national
medical informatics system that carries comprehensive health records could likely
hold neuropsychological data as well. Whether or not it does have a place for neu-
ropsychological data may depend on how quickly neuropsychologists ride into this
frontier of health information networks.
To be tuned to such considerations, the discussion on NI for neuropsychology
needs to be all encompassing. It has to consider the broader infrastructure and when
there are planned developments within that can potentially serve neuropsychology,
the opportunity should be promptly examined.
6.3 Prologue to Neuropsychology for the 21st Century
In the course of its historical development, neuropsychology has been very open to
new technology – from brass instruments to EEG, from microcomputers to fMRI.
The discipline has been very good at incorporating new technology into its existing
2 David Kibbe, a senior advisor to the American Academy of Family Physicians, and Bruce
Klepper, a healthcare market analyst, sent an open letter to Barack Obama in which they
outlined key problems and made suggestions regarding electronic health records in the USA.
(www.thehealthcareblog.com/the_health_care_blog/2008/12/where-should-fe.html)
3 For example, the National Public Radio program, All Things Considered, interviewed Dr. Ashish
Jha (Harvard School of Public Health) on March 25, 2009, on the topic on HIN implementa-
tion in USA: “Electronic Medical Record Change Not Easy”. (http://www.npr.org/templates/story/
story.php?storyId=102360638)
structure and then adjusting its focus or developing subspecialties based on insights
gained through the technology.
As great an impact that various technologies have had on the field, none has
implied or required that the discipline of neuropsychology undergo an evaluation
of so many of its fundamental operating principles – relating to its constructs of
cognition, how it assesses these constructs, how its data are gathered and protected,
how inferences are drawn from the data, how models of behavior are built, and how
neuropsychologists communicate as a community. NI has fundamentally different
implications in this regard. NI is much more than just a new technology. It is about
a major change of paradigm on the treatment of neuroscience data at all levels. The
implication for neuropsychology, especially clinical neuropsychology, is that its tra-
ditions and tool sets are going to be widely challenged. From its clinical assessment
methods to its modes of training, clinical neuropsychology is at risk of severe incon-
gruence with a surrounding mass of fine-grained neuroscience data. NI is the great
unifying force for data in the brain sciences. It is undoubtedly a powerful, transfor-
mative force that has reoriented much of neuroscience. This is the brave new world
in which neuropsychology has to function. The effect of NI on neuropsychology
will not be ameliorating but instead greatly enlivening.
It is because of the rich history of neuropsychology and its long line of
remarkable pioneers that the discipline has reached such a high level of distinc-
tion. To continue this legacy, it must embark on entirely new trajectories set
forth by technologies of our time. It should do so with vision and firm embrace.
Neuropsychology in the 21st century will be defined by neuroinformatics.
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Index
Note: Page numbers followed by f indicate figures; t, tables; n, notes.
A Automated Neuropsychological Assessment

Aachen Aphasia test (AAT), 68 Metrics (ANAM)
Adaptive networks, 17 description and background of, 35–38
Algorithm types in neural modeling, 17 informatics incorporated into, 36–41
Amari, Shun-ichi, 23 query functions in, 38, 39 f
American Sign Language Linguistic Research in shared platform, 43
Project, 70–71 tabular summary of, 30t
Analysis of Functional Neuroimages (AFNI), tabular types in, 36–37
8–9
Analytic module (CVFN), 49, 51 f B
ANAM Access Database (AADB), 37–38 Back-propagation, 17
Animated priming effects, 53–54 Baggett, M., 42
Anomic aphasia, 68–69 Behavioral data in children and
Aphasia Database, The (AD) adolescents, 11
description and background of, 67 Benton, A.L., 91
neural modeling and diagnoses with, 68–69 Bilder, R., 4, 75, 90–91, 101
rationale and goals of, 67 Bioinformatics, defined, 1
structure and contents of, 68 Biomedical Informatics Research Network
tabular summary of, 30t (BIRN), downloadable software
Aphasia Modeling Project, 73 from, 9–10
Aphasia/aphasic syndromes Bipolar disorder, 81
neuroinformatic applications for, 6, 58–61 Boston Aphasia Diagnostic Exam, 60
types of, 68–69 Boston Visuospatial Quantitative Battery, 48
Arbib, M.A., 59, 60 Bota, M., 60
Artificial intelligence (AI), 16–17 Brain
Assessment, neuropsychological cortices of visuospatial function, 44–45
cognitive, 41–42 dysmorphology in, 77–78
conventional options for, 28 function-specific areas of, 45
internet-enabled and remote, 38 See also Mapping, brain
portable systems for, 38, 40–41 Brain imaging
visuospatial, 44–46 construction, analysis, and morphometric
Assessment batteries tools for, 8–10
neuroinformatic applications for, 5–6 databases for, 10–12
Wechsler battery of tests, 27–28 five categories of, 10
Attention deficit hyperactivity disorder BrainCheckers software package, 40
(ADHD), 81 Broca, P., 58
Autism, 77 Broca’s aphasia, 69
119
120 Index
Broca-Wernicke Model of Language, 58 neuroinformatics in, 80–81

Browndyke, J., 26–27 tools of, 81–82
Consortium for Neuropsychiatric Phenomics,
C The (CNP)
C. elegans (Caenorhabditis elegans), 22 description and background of, 78–79
California Verbal Learning Test II, 27 mission and strategy of, 79–80
Caplan, D., 59 Coordinate computational kernel (CCK),
CellBuilder software package, 15 49, 51 f
Children and adolescents Coordinate recording database (CRD), 49, 51 f
behavioral data in, 11–12 Cox, Robert, 8
brain development databases for, 11–12 Craniofacial dysmorphology, 76–77
Chimaeric stimuli, 52 Craniofacial features, neuroinformatic
Christensen, D., 42 applications for, 6
Chute, D.L., 27
c
ClinicView! software package, 38 D
A Cognitive Analysis (CNP), 81 Data
Cognitive assessment, 41–42 behavioral, in children and adolescents, 11
Cognitive informatics, 16n capture and manipulation of, 4t, 37
Cognitive neuroscience separated files for, 36
background of, 99 sharing issues in, 86–88
visuospatial research in, 46 standardization of, 88–89
CogScreen software package, 42 uniformity of output, 36
Collations of Connectivity Data on the Data mining
Macaque Brain (CoCoMac), 12–14 neural modeling role in, 16–17
Computational grid matrix, 48 f , 50–53 privacy issues and, 86–88
Computational modeling, see Neural modeling process of, 16
Computational Visual Field for Neglect sharing issues in, 89
(CVFN) taxonomies and ontologies for, 88
coordinate address system of, 48–50 tools for, 18–19
description and background of, 46–47 Data processing, key aspects of, 4t
grid matrix advantages in, 48 f , 50–53 Database Access Interface (DAI), 72
limitations of, 48 Databases
NI approach to, 48–50 for academic and clinical research, 18–20
tabular summary of, 30t of International Consortium of Brain
Computer applications Mapping (ICBM), 11
general for neuropsychology, 25–28 for mapping neural structure and
neuroinformatics for neuropsychology connectivity patterns, 12–13
models of, 29–84, See also structure and functions of, 16–17
Neuroinformatics (NI) Dataman software package, 40
scope and function of, 28–29 Demographic tables (ANAM), 38
Computer-Assisted Cancellation Test System Deutsch, C.K., 77
(CACTS) Diagnostic imaging, see Brain imaging;
description and background of, 53–54 specific modalities
design and architecture of, 54 Digitization of data, 3
four software models of, 54 Directions Into Velocities of Articulators
kinematic and metric functions of, 54–57 (DIVA)
outcome analysis module of, 54 description and background of, 61–62
tabular summary of, 30t feedback and feedforward process in
Computerized Anatomical Reconstruction and speech acquisition, 63–65
Editing Toolkit (CARET), 9 feedback control subsystem, 64–65
Consortium for Neuropsychiatric NI role in, 66
Phenomics, The online information on, 61
levels schematic in, 80 f synopsis of
Index 121
feedforward control subsystem, H

63–64 Halligan, P.W., 47
infant babbling, 65 Head injury research, 26
neural decoding and prosthetics for Header tables (ANAM), 37
speech, 66 Hemispatial neglect, 47
phonetic categories, 65 Hobbs, A., 26
tabular summary of, 30t Hooper Visual Organization Test, 44
Huang, H.C., 20
Human Brain Project (HBP)
E defined, 3
Electronic medical records (EMRs), 103 functions of, 21
Electrophysiology, 26 overview of, 21
Embryogenesis, 77 TBI rehabilitation in, 26
Endophenotypes, 75 Human Genome Project (HGP), 2, 22
Error maps (DIVA), 64 Human Phenome Project (HPP), 75
European Network for Fuzzy Logic
and Uncertainty Modeling in I
Information Technology Interfacing modalities for CoCoMac and
(ERUDIT), 67 CARET, 12
European Network on Intelligent Technologies International Consortium for Brain Mapping
for Smart Adaptive Systems (ICBM), subject database of, 11
(EUNITE), 67 International Neuroinformatics Coordinating
Facility (INCF), 24
International Neuropsychological Society
F
(INS), 3–4
Felleman, D.J., 45 Internet, vast influence of, 100–102
Fetal development, 77 Internet-Enabled Neuropsychological
Flight training, 41–42 Assessment of Army Aviators
FreeSurfer software package, 9–10 (IENAAA)
Freimer, N., 75, 76 description and background of, 41–42
Functional magnetic resonance imaging informatics incorporated into, 42–46
(fMRI) in shared platform, 43
brain imaging tools for, 8–10 tabular summary of, 30t
National fMRI Data Center, 86 Item tables (ANAM), 37
speech and language data from, 59, 66
Funding sources, 20–21, 90 J
Jagaroo, V., 44, 47
Joseph, R.M., 77
G
Journal of Head Trauma Rehabilitation
Gahm, G., 42
(2002), 26
Gazzaniga, M.S., 86–87
General Neural Simulation System K
(GENESIS), 14 Kane, R.L., 92
Genomics, 2 Kay, G.G., 92
Gestural communication, 6, 70–73 Kelly, M., 42
Gilliland, K., 93 Knowledge discovery in Databases (KDD), see
Global aphasia, 69 Data mining
Global Environment for Network Innovations Koslow, S., 22, 83, 87
(GENI), 102
Graphics database (CVFN), 49, 51 f L
Graphics kernel (CVFN), 49, 51 f Language
Grid controller (CVFN), 49, 51 f assessment techniques for, 60
Grillner, Sten, 23 neuroinformatic applications for, 58–61, 73
Gyral surface contour maps, 9, 64 neuropsychological models of, 58–59
122 Index
Language (cont.) Neural connectivity patterns, 12–13

signs and gestures as, 60–61 Neural modeling
Latent Semanitc Analysis (LSA), 74 algorithm types used in, 17
Lezak, M., 33 defined, 14
Lichtheim, L., 58 tools for, 15
Lotus Domino server, 68n Neural networks, structure and functions of,
Luria-Nebraska Neuropsychological 16–17
Battery, 27 Neuroimaging Informatics Technology
Initiative (NIfTI), 10
M Neuroinformatics (NI)
Macaque monkeys applications/models for, 7–24, 46
brain cortices of visuospatial function in, for assessment batteries, 5–6, 35
44–45 attitudes, reorganization, and training in,
Collations of Connectivity Data on the 91–93
Macaque Brain (CoCoMac), 12–13 data sharing issues in, 86–88
Mapping, brain defined, 2
cortical areas of visuospatial processing, 45 digitization of data in, 3
in DIVA model, 63–64 evolution of, 83, 85
of gyral surface contours, 9 frameworks for neuropsychology, 4
of neural structure and connectivity
infrastructure management of, 20–24
patterns, 12–13
neuropsychology-specific systems
Marshall, J.C., 47
Aphasia Database, The (AD), 30t,
Memory Search software package, 35
67–69
Microsoft Access queries, 37–38, 49, 54
applications/models for, 29–84
Microsoft Excel, 68
Automated Neuropsychological
Microsoft SQL, 42
Assessment Metrics (ANAM), 30t,
Military, U.S., Walter Reed Performance
35–41
Assessment Battery (WRPAB), 35
Computational Visual Field for Neglect
Mishkin, M., 44
(CVFN), 30t, 47–53
ModelDB software package, 15
Montreal Neurological Institute (MNI), 11 Computer-Assisted Cancellation Test
MRI Study of Normal Brain Development System (CACTS), 30t, 53–57
database, 11 Consortium for Neuropsychiatric
Phenomics, The, 31t, 78–83
N Directions Into Velocities of
National Academy of Sciences Institute of Articulators (DIVA), 30t, 61–67
Medicine (IOM), 22 Face Value Database Project, The, 31t
National Center for Biotechnology Information Internet-Enabled Neuropsychological
(NCBI), 90 Assessment of Army Aviators
National Center for Sign Language and (IENAAA), 30t, 41–46
Gesture Resources (NCSLGR), scope and function of, 28–29
71, 72 SignStream! R
software package, 31t,
National fMRI Data Center, 86 70–73
National Institutes of Health (NIH) tabular summary of, 30t, 31t
MNI collaboration with, 11 See also as main entries
MRI Study of Normal Brain Development privacy issues in, 86–88
database of, 11–12 Society for Neuroinformatics in
National Center for Biotechnology Neuropsychology (SCNN), 95–97
Information (NCBI) of, 90 storage/warehousing of, 20
Neuroimaging Informatics Technology throughput concept in, 88–89
Initiative (NIfTI) of, 10 Neuroinformatics Database System (NIDS),
role in HBP, 22 19–20
National Science Foundation (NSF), 21–22 Neuroinformatics Portal Pilot, The, 24
Neidle, C., 70–73 Neuroinformatics Site, The, 24
Index 123
Neuroinformatics: The Integration of Shared Personal digital assistants (PDAs), 40

Databases and Tools Towards Phenotypes/phenomics, neuropsychiatric
Integrative Neuroscience defined, 6
(Amari), 23 description and background of, 75
Neuroinformatics Working Group (NWG), 23 neuropsychology role in, 75
Neuron software package, 13–14 research in, 76–83
Neurons Privacy issues, 86–88
3D images of ultrastructure, 13 Programme in International Neuroinformatics
clustered into nodes, 16 (PIN), 23
simulation methods for, 14–18 Proteonomics, 2
structure and connectivity patterns of, PubMed/MEDLINE database, 81
12–13
Neuropsychological Assessment Q
(Lezak, 2004), 33 Query functions in AADB, 38, 39 f
Neuropsychology Query interfacing, 11
changing landscape in, 100, 103–104
neuroinformatic frameworks for, 4 R
NeuroScholar project, 19 Reconstruct software package, 13
Nodes, neuronal, 16 Reeves, D., 36
Notes/Domino database, 68n Reitan, R., 91
Report on Neuroinformatics (2002), 23
O Research, academic and clinical databases and
Obama, B., 103 knowledge discovery systems for,
Online information 18–20
in BrainMaps.org, 13 Resolution of images in BrainMaps.org, 13
for CNP tools, 81 Rey Complex Figure Test, 27, 44, 48
on DIVA, 61 Rheinisch-Westphalian Technical University
HBP website, 21 (RWTH), 67, 73
language-related, 73
for neuron simulation, 15
S
for NI sharing, 23–24
Sabatti, C., 75, 78
on OECD neuroinformatics working
Schatz, P., 26–27
group, 23
Schizophrenia, 77, 81, 82 f
SignStream! R
software package, 70
Schlegel, R.E., 93
for Society for Neuroinformatics in
Schultheis, M.T., 27
Neuropsychology (SCNN), 95–97
Semantic categories, 19
in Synapse Web, 13
SenseLab software package, 15
vast influence of, 100–101
Sharing platforms, 90
See also specific databases/software
Sign language research, 61, 70–73
Ontologies
cognitive, 83 SignStream! R
software package
functions of, 18–19 database of, 71–72
need for, 89 description and background of, 71–72
O’Reilly, Tim, 101n structure and functions of, 71–73
Organization for Economic Cooperation and tabular summary of, 31t
Development-Neuroinformatics Software packages and applications
Working Group (OECD-NIWG), BrainCheckers, 40
23–24 CellBuilder, 15
c
Outcome analysis module (CACTS), 54–57 ClinicView! , 38
CogScreen, 42
P Dataman, 40
Parallel distributed processing, 15–16 3D Slicer, 9–10
Parameter modification in testing, 36 FreeSurfer, 9–10
Patient profile database (CVFN), 49, 51 f Memory Search, 35
124 Index
Software packages and applications (cont.) of neuronal ultrastructure, 13

ModelDB, 15 Tower Puzzle software, 35
Neuron, 13–14 Tracer database, 12
Phenowiki, 81 Traumatic brain injury (TBI), 26, 42
PubBrain, 81
PubGraph, 81, 82 f U
Reconstruct, 13 Ungerleider, L.G., 44
SenseLab, 15 US Army Aeromedical Cognitive Assessment
SignStream! R
, 70–73 Tool (USA-ACAT), 42
SynWin, 42
Tower Puzzle, 35 V
Webfit, 74 Van Essen, D.C., 45
Spatial neglect, 30t, 47–53 Van Horn, J.D., 87
Speech motor skills, neuroinformatic Virtual reality technology, 27
applications for, 6 Visual search/attention patterns
Speech production and acquisition (SPA), CACTS tool for, 53–57
61–62, 66 neuroinformatic applications for, 7
Visual/gestural communication, neuroin-
Speech/language
formatic applications for, 6,
neuropsychological models of, 58–61
70–73
NI role in, 58–61
Visuospatial functioning
production and acquisition (SPA) of,
defined, 45
61–62, 66
NI assessment tools for, 47–48
Standardization of data, 88–89
tests for, 43–46
State maps (DIVA), 65
Sternberg, S., 35
W
Stimulus displacement/manipulation
Walter Reed Performance Assessment Battery
in CACTS tool, 57
(WRPAB), 35
in CVFN tool, 53–57 Web 2.0, 101
Summary tables (ANAM), 37 Wernicke, C., 58
Synapse Web, 13 Wernicke’s aphasia, 68–69
SynWin software package, 42 Western Aphasia Battery Tap, 60
Whole Brain Atlas, 10–11
T Wiki platforms, 101
Tabular types (ANAM), 38 Wisconsin Card Sorting Test!
R
, 27
Talairach space/system, 8 Wong, S.T.C., 18–19, 83
Temporal lobe epilepsy (TLE), 20 WordNet database, 74
Testing, parameter modification in, 36
Three dimentional (3D) imaging X
generation of, 8 XANAT (a graphical anatomical database), 13

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Neuroinformatics for Neuropsychology

Department of Psychiatry and the

ISBN 978-1-4419-0059-3 e-ISBN 978-1-4419-0060-9

© Springer Science+Business Media, LLC 2009

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

assessment tools and functional neuroanatomic/neurocognitive systems if assess-

by a host of web-based technologies for data modeling and collective knowledge

Boston, Massachusetts Vinoth Jagaroo

3.3.2 Visuospatial Processing, Visual Attention, and

1.1 An Overview of Bioinformatics

V. Jagaroo, Neuroinformatics for Neuropsychology, 1

1.2 What Is Neuroinformatics?

1.3 Bringing Neuroinformatics to Neuropsychology

In neuropsychology, the application of NI is yet to be realized. NI perspectives

Table 1.1 Key features of the NI approach to data

instead that neuropsychology can utilize NI as richly as NI has been exploited by

• An automated, digitized assessment battery structured in a highly modular fash-

population profiling, and especially suited to assessment carried out at remote

A considerable degree of background is described before the examples are pre-

Neuroinformatics is a multifaceted field. It is as broad as the field of neuroscience.

2.1 Brain Image Construction, Analysis,

V. Jagaroo, Neuroinformatics for Neuropsychology, 7

2.1.1 Examples of Image Construction, Analysis, and

Analysis of Functional Neuroimages (AFNI): AFNI is a set of programs for fMRI

2.2 Brain Image Atlases, Databases and Repositories

2.2.1 Examples of Image Databases

2.3 Tools and Databases for Mapping Neural Structure

2.3.1 Examples of Tools and Databases for the Study of Neural

Collations of Connectivity Data on the Macaque Brain (CoCoMac): CoCoMac is a

The parcellation problem is also attended to by other computer applica-

2.4 Tools and Methods for the Simulation of Neurons

neural systems. Observing intercellular and intracellular neural events is extremely

2.4.1 Examples of Tools for the Simulation of Neurons

General Neural Simulation System (GENESIS) is a computer platform for general-

well-provisioned modeling workspace. Bearing testament to the story of GENESIS

Neural networks are particularly relevant to NI in neuropsychology in areas of

2.5 Database and Knowledge Discovery Systems for Clinical

2.6 Neuroinformatics Management and Infrastructure

in developing a modeling platform for neural circuits, or how should a multicen-

2.6.1 Examples of NI Organizations, Infrastructure,

cross fertilization between the neurosciences and information sciences; it has

forth the recommendations by launching the International Neuroinformatics Coor-

3.1 Differentiating Between the General Computer

V. Jagaroo, Neuroinformatics for Neuropsychology, 25

uploaded to databases on remote server. Schultheis et al. (2002) described various

3.2 Defining Neuropsychology-Specific Neuroinformatics

• Using theoretical and NI frameworks, attempts should be made where possible to

In devising NI systems for neuropsychology, consideration should be given to

Clinical or research initiatives in neuropsychology can apply these NI methods in

3.3 Neuroinformatics Applications and Models for

Nine examples of NI applications or models for neuropsychology are described

Table 3.1 Summary of neuroinformatics applications and models for neuropsychology

Neuropsychological 1. Automated • Digitization of numerous tests of

Research on 3. Computational Visual • Coordinate-based mapping and

4. Computer-Assisted • Tool for graphical analysis of visual

Research speech, 5. Directions Into • Theoretical and computational model

Table 3.1 (continued)