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3
Four New Technologies:
Research Findings
This chapter provides technical discussions of each of the four
technologies examined by the committee. Each discussion covers
four areas: a brief description, the background of relevant research
findings, an assessment of the likelihood that progress will be made,
and an outline of opportunities for basic and applied research. Our
assessments of the likelihood of progress are based on the most recent
developments in empirical research, which are reviewed in varying
amounts of detail depending on the field. Implications are drawn
from the best experimental work reported to date. Research oppor-
tunities are discussed in terms of the conceptual foundations estate
fished by the current research and the technological breakthroughs
that make possible finer definition of brain functions involved in
cognitive processes. One unport ant and general conclusion emerges
from these discussions, namely the importance of exploiting the com-
plementary advantages of the different technologies as, for example,
employing both PET and MRl methodologies for solving problems
of anatomical localization of physiological processes. Progress will
depend, however, on solving the problems considered In detail in
Chapter 4.
E:VENT-RE:LATED BRAIN POTENTLA[S
Event related brain potentials (ERPs) are obtained by placing
electrodes on a person's head and recording electroencephalographic
(EEG) activity while the subject is engaged in a task. By means of
signal averaging it is possible to extract from the EEG (a voltage x
18
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RESEARCH FINDINGS
19
time function) estimates of the portion of the voltage (the ERP) that
is time-Iocked to events associated with the task. These ERPs rep-
resent the synchronized activity of neuronal ensembles whose fields
are so aligned that they sumrnate to produce potentials that are
large enough to be recorded over the scalp. The ERP consists of a
sequence of named components whose amplitude, latency, and scalp
distribution vary systematically with the conditions of stimulation,
with the subject, and with the processing required by the eliciting
events. Variations in the behavior of the components of the ERP
can be used in the study of sensory and cognitive function (Caliaway,
Tueting and KosIow, 1978; Hillyard and Kutas, 1983~.
Background of Researth Fm~mgs
The ERPs provide a rich class of responses that may, within
the appropriate research paradigm, allow the study of processes that
are not readily accessible to experimental psychologists by other
means. The key assumption of cognitive psychophysiology ~ that
ERP components are manifestations at the scalp of the activity
of specific intracranial processors. The reference is not to specific
neuroanatom~cal entities,but rather to specific functional processors.
While networks of nuclei may be involved in a dynamic fashion in
the activity represented by each ERP component, our current under-
standing of the underlying neuroanatomy is, for most components,
insufficient to generate meaningful neuroanatom~cal hypotheses. But
the available data regarding the consistency with which certain com-
ponents measured at the scalp behave permit us to hypothesize that
these components do signal the activation of internal subroutines.
These remarks do not imply that the electrical activity recorded
at the scalp is itself of functional significance. For our purposes, the
ERPs may be due solely to the fortuitous summation of electrical
fields that surround active neurons. Although some have argued
that EEG fields do have functional significance (Freeman, 1975), we
remain agnostic on this issue. We are not asserting that the ERPs
are epiphenomena. Rather, we are saying that from the perspective
of the cognitive scientist, it is sufficient to elucidate the functional
role, in information-processing terms, of the subroutines manifested
by the ERP components.
Once the existence of a component is well established, the es-
sential tools of the cognitive psychophysiological paradigm are used
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20
BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
to identify the subroutine it manifests and to articulate its param-
eters. This search and analysis require that: (~) we elucidate the
antecedent conditions under which the component is elicited, from
which (2) we derive a mode} of its subroutine that (3) we test by pre-
dicting the consequences of "calling the subroutines (i.e., of engaging
the processes whose activation is manifested at the scalp). With the
information thus gained, psychophysiology provides a repertoire of
tools, a collection of components, each of which can be used in the
appropriate circumstances to augment the armamentarium of the
cognitive scientist (Donchin, 1981~.
Likelihood That Progress WiB be Made
The ensemble of information-processing activities manifested by
the ERPs is already quite rich. Additional components are being
discovered and deeper understanding is being reached of components
that have been known since the 1960s. In principle, all these compo-
nents can be used in cognitive psychophysiology. A good start has
been made and, as is made clear in subsequent pages, the area is rich
in promise and substantive progress.
The following paragraphs list some of the components that have
attracted the most substantial investigative efforts. Components are
labeled as egative or ositive to indicate the direction of
the voltage change from the base line. The number following the
character refers to the modal latency, in milliseconds (msec), of the
component, measured from the onset of the precipitating event.
N100 Direction of Attention
Hillyard and his associates have shown that the N100 component
is affected by the directions of the subject's attention. Events in the
focus of attention tend to elicit a somewhat larger N100. The effect
is reliable and can be used to monitor changes in the direction of at-
tention or changes in the attentional level. Thus, the N100 can play
a role either in ascertaining whether the subject ~ actually following
instructions with regard to the allocation of attention or in deter-
m~ning whether events in the environment have caused the subject
to shift attention. Research on the behavioral correlates of N100,
and other negative components, is a very active field of investigation.
There ~ considerable interest in resolving the many different negative
components that appear in the first 200 msec following the eliciting
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RESEARCH FINDINGS
21
event and in elucidating their functional significance (for reviews see
Nastanen and Picton, 1987, and Hillyard and Hansen, 1986~. There
is an active examination of the differences and similarities In the
nature of selective attention in different sensory modalities. E`urther-
more, extensive work that illuminates central issues in the theory of
attention is being done (HiDyard and Hansen, 1986~.
N200~Detection of Mismatch
Considerable evidence exists that the N200 ~ elicited by events
that violate a subject's expectations, even if they occur outside the
focus of attention. Thus, the N200 seems to be a manifestation
of the activation of a mismatch detector. This component seems
to be the least susceptible to control by the subject's voluntary
actions. The occurrence of any deviation from regularity, indeed any
rn~smatch between an event and its immediate predecessor, elicits
an N200. Examination of these components continues and is being
extended to fairly abstract information-processing activities. Thus,
for example, there ~ considerable interest ~ the role that these
negative components play in studies of lexical decision (Nastanen,
1982~.
P30~A Manifestation of Strategic Proce - sing
When subjects are presented with events that are both task rel-
evant and rare, a prominent positive component with a latency of at
least 300 msec is elicited. The literature concerned with the P300
is quite extensive (see Donchin et al., 1986; Pritchard, 1981; and
Rossler, 1983, for reviews). Johnson (198S, in press) has summarized
much of the evidence concerning its antecedent conditions and has
concluded that the elicitation and amplitude of the P300 depends
on a multiplicative relationship between the subjective probability
of events (the rarer the event, the larger the P300) and the amount
of information and the utility of the information to the subject (the
more information, the larger the elicited P300~. Donchin and his
colleagues have interpreted these data within the context of a mode}
that assumes that the P300 is a manifestation of the revision of
mental models (see Donchin and Coles, in press; Donchin, 1981~.
Much empirical evidence supports a wide variety of applications of
the P300, including the measurement of mental workload (Gopher
and Donchin, 1986; Donchin et al., 1986), analyses of memory mech-
anis~rm (Neville et al., 1986; Karis, Fabiani, and Donch~n, 1984), and
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BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
concession making in bargaining situations (Druckman, Karis, and
Donchin, 1983; Karm, Druckman, Lmsak, and Donchin, 1984~. The
latency of the P300 has also proven to be of use. It can be shown
to be relatively independent of response execution processes and can
thus serve as a pure measure of mental timing (Kutas, McCarthy,
and Donchin, 1977; McCarthy and Donchin, 1983~.
N400 Semantic Mismatth
Kutas and HiDyard (1980, 1984) have shown that words that are
in some way incongruous or unexpected in a semantic sense within a
discourse elicit an ERP component that is negative and has a latency
of about 400 msec (see Kutas and Van Petten, 1987, for a review).
Kutas and her coworkers have subsequently shown that the ampli-
tude of the N400 is inversely proportional to the degree to which the
context constrains the word eliciting the N400. The measurement of
N400 makes it possible to address unresolved issues in psycholinguis-
tics. Thus, for example, Van Petten and Kutas (1987) show rather
persuasively that they can measure the degree to which sentences im-
pose constraints on their constituent words by examining the N400
elicited by these words. This application of N400 in psycholinguistics
is increasingly active (touchier et al., 1983, 1985, 1987~.
The Readmese Potential and the Contmgent
Negative Variation—Preparation to Respond
Kornhuber and Deecke (1965) have shown that voluntary re-
sponses are preceded by a slow negative wave, which they labeled
the readiness potential (RP). Walter and hm colleagues (1964) have
demonstrated that a slow negative wave develops between a first
stimulus, which heralds the later arrival of a second stimulus, to
which the subject must respond. They called this wave the contin-
gent negative variation (CNV). (Note the different labeling systems.)
As on a map of lower Manhattan, the orderly system of letters and
numbers used to label the faster components gives way to a system in
which each component carries a name given it by its discoverer. The
RP and the CNV are among several ERP components that are callecl
event-prececling negativities. They are quite clearly related to the
activation of preparatory, often unconscious, processes by the sub-
ject. Their usefulness in the study of cognitive processes is extensive.
For example, Coles and his colleagues (1985) have shown that it is
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RESEARCH FINDINGS
23
possible to deterrn~ne, from the extent to which these potentials are
larger over one hemisphere than the other, which response the sum
ject was contemplating regardless of the response that has actually
been made.
Opportunities for Basic and Applied Regears
It is not possible in this brief review to do justice to so active
a research enterprise. The work reviewed above refers to some of
the welI-established research activities. It may be useful, however, to
note a number of developing research areas that are likely to play a
central role in the coming decade.
One of the more significant efforts is the increasing practicality
of elucidating the intracranial origin of the components. We referred
elsewhere to this work, but it is important to underline the fact that
much of the technological and conceptual development required has
become readily available only very recently. Several laboratories had
access to patients with indwelling electrodes from the earliest days of
ERP research. However, only within the last decade has it become
possible to deal with the massive data base generated in such studies.
Furthermore, there are significant developments in the theoretical un-
derstanding of the nature of the models needed to relate intracranial
activity to scalp recorded activity (see, for example, Scherg and Von
Carmon, 1985; Nunez, 1981~. There also is an increasing number
of investigations of analogous processes in nonhuman species (Dead-
wyler et al., 1985; Arthur and Starr, 1984~. The work in humans
using indwelling electrodes, neuromagnetic recording, and clinical
observations on the effects of lesions (Johnson and Fedio, 1986) is
likely to combine in the near future with the work in animals to yield
much deeper understanding of the neurophysiological basis of the
ERPs.
The development of display methodology is likely to affect prog-
ress in the field, as noted below. It ~ largely the case that inves-
tigators are forced to select a very small portion of their data for
display and analysis. The number of waveforms analyzed is generally
much smaller than can be easily acquired, and the number of mea-
surements made on these waveforms Is also rather small. The ability
to summarize and combine much larger masses of data provided by
mapping approaches is likely to transform the field. However, this
will be true only if the summaries and the displays are guided by
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BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
proper statistical and substantive theories. It ~ to this area of re-
search that much attention needs to be paid in the near term (see,
for example, Skrandies and Lehman, 1982~.
Much work in cognitive psychophysiology is motivated by applied
interests. The use of ERPs recorded from the brainstem is routine in
neurology and audiology, as are various diagnostic procedures that
measure the speed of neuronal conduction in the response of various
systems to changes in steady-state stimuli. More controversial at this
time are applications of some of the components in the diagnosis of
neurological and psychiatric disorders. There is extensive interest in
a report (Goodin, Squires, and Starr, 1978) that interpretation of
the latency of the P300 may allow a diagnosis of either dementia or
depression. Begleiter and his associates (1984) have been applying
ERP measures in studies of the familial risk for alcoholism.
In addition to the clinical work, there is active interest in the
feasibility of using ERPs and other psychophysiological measures
in the field known as engineering psychology. Human Factors, the
official journal of the Human Factors Society, devoted a special is-
sue (Kramer, 1987) to examine psychophysiological measures. The
usefulness of the P300 as a measure of mental workload has been
examined in some detail by Donchin and his colleagues free Go-
pher and Donchin, 1986, for a review). The work ~ continuing and
diversifying.
Methodological Moues
Data acquisition is not a source of serious problems in ERP
research, depending as it does on established technologies. However,
experimental design, measurement, and data analysis present serious
challenges that require attention. We briefly discuss three parts of
the methodology: recording techniques, data analysis, and display
methodologies.
The technology required for recording ERPs ~ largely mature.
It is identical to that required for recording the EEG. The EEG is
digitized, either on-line or off-line, and the ERP, whose amplitude
ranges between 5 and 10 m~crovolts, ~ extracted by signal averaging.
This well-established procedure capitalizes on the fact that the part
of the signal that is time-Iocked to events has a constant time course
following the event while all other activity follows a randomly varying
time course.
The data base acquired in ERP experiments does present formi-
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RESEARCH FINDINGS
25
cable problems of analysis. Typically, 5 to 10 subjects are run, each
in several sessions. In each session, data may be acquired for 5 to 10
separate conditions, where each condition requires the presentation
of 30 to 200 repetitions of the same stunulus. For each presentation,
the EEG Mom 5 to 32 recording channels is digitized over an epoch
lasting as long as 2 to 3 seconds at the digitizing rate of 100 to 500
samples per second.
All these data are typically stored on magnetic tape. Full stor-
age of single trial data is preferable, especially in studies of cognitive
function, because it has proven useful to consider the subject's actual
performance on each trial in extracting the ERPs. Thus, for exam-
ple, it may be of interest to examine separately trials on which the
subject's response was fast and those on which the response was slow.
Such selective averaging is one of the most powerful tools available to
the cognitive psychophysiologist. Note that saving of the single trials
allows the use of off-line filtering of artifacts. This strategy prevents
the loss of trials. Currently available procedures render obsolete any
study in which a substantial percentage of the data Is rejected. In any
event, even when just the average ERPs are retained, the analytical
tasks are formidable. An extensive literature beyond the scope of
this report is concerned with these issues (see Coles et al., 1986, for
a review).
Even though considerable sophistication ~ invested in the anal-
ysis of data obtained in ERP experunents, the visual inspection of
the data remains critically important. It would be rare for a study
of ERPs to be published without a visual display of the waveforms.
The mere tabulation of measures and the associated statistical tests
would be considered inadequate, as they do not allow an evaluation of
the quality of recordings. In the past, data were presented largely in
the form of plots of voltage changes as a function of tune, one plot for
each electrode site; this remains the modality of choice. However, the
reduced cost of computing power and the increased sophistication of
graphic display devices triggered the emergence of displays that map
the variations of the voltage over the head at successive instants in
time. These Brain maps represent the changing pattern of activity
at varying points In tone in a two-dimensional and easily visualizable
display. However, all the mapping techniques discussed in this re-
port, including brain mapping, would greatly benefit from an effort
to develop statistical methods that can cope with this complex data
base.
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BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
NEUROMAGNETISM: THE MAGNETOENCEPHA[OGRAM
The term neuromagnetism refers to the study of the magnetic
fields that accompany the flow of ionic currents inside neurons, as
opposed to the flow of current within the overall volume of the cranial
contents. Neuromagnetic methods are employed in the study of ex-
tracranial magnetic fields. By analogy with electroencephalography,
which involves the study of electrical potential differences between
electrodes attached to the scalp, magnetoencephalography (MEG) is
now the standard term used to refer to the study of the brain's vary-
ing magnetic field. In addiiton, by analogy with ERPs, extracranial
magnetic fields that are t~me-Iocked to physical stimuli (e.g., changes
in visual patterns, noise bursts) are referred to as event-related fields
(ERFs). As in the study of evoked potentials, it is customary to dis-
t~nguish between steady states and transient responses, except that
the measures used are time-varying amplitudes of neuromagnetic
fields rather than of voltages.
Background of Research Fm~mgs
The first systematic studies of neuromagnetism appeared in 1975.
At first, they took the form of demonstrating that it was possible
to detect visually evoked fields. These were rapidly followed by
the demonstration that fields also could be evoked by auditory and
somatosensory stimuli, and that fields systematically preceded the
occurrence of simple motor acts. In 1975, a singularly interesting
finding was reported: it was found that the amplitude of the field
associated with stimulation of the little finger had a different dis-
tribution on the scalp than that associated with stimulation of the
thumb (Brenner, Williamson, and Kaufman, 1975~. This led almost
immediately to the notion that the mapped field could be compared
with that which would be produced by an equivalent current dipole
source, and the source could be located within the three-dimensional
volume of the brain.
The magnetic field is associated with the intracellular currents of
a limited population of neurons in the brain. The field produced by
these neurons is essentially indistinguishable from that which would
be produced by an arbitrarily small segment of current. This small
segment is commonly referred to as a current dipole.
Various groups began to use this approach, which entailed taking
sequential measurements from many places on the head. Since the
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RESEARCH FINDINGS
27
only available instrument at that time incorporated a single super-
conducting quantum interference device (SQUID) and sensing coil,
the task proved to be very laborious and subject to errors in position-
ing the sensing coil over the head. It quickly became apparent that
multiple sensors would be necessary to realize the full potential of the
technique. The main advantage of magnetic recording Is that, using
a m~nnnum number of assumptions, it is possible to determine the
three-~unensional location, geometric orientation, and strength of
equivalent current dipole sources. This advantage makes it possible
to distinguish between changes in field intensity due to a change in
amount of neural activity resulting from an experimental manipula-
tion and changes in source location and orientation. Multiple sensors
are needed for this purpose.
The group at the Helsinki Technological University was the first
to construct a multichannel system. This included four SQUlDs
and four sensing coils. Owing to a specific feature of the Finnish
design, one of the four channels was never used in the many useful
experiments conducted by that group (Hari et al., 1982, 1984~; their
system was functionally a three-channel system.
At about the same time, the group at New York University
collaborated with the S.H.E. Corp. of San Diego (now Biomagnetic
Technologies, Inc.) in designing and developing a five-channl! system
that incorporated the newer and more sensitive dc SQUlDs. Actually,
nine SQUlDs were used: five were used for sensing the brain's field;
three were used for monitoring the field in the x, y, and z axes;
and one was used for monitoring the spatial gradient of the field
along the z axis of the dewar. In effect, these channels were used
to monitor the ambient field. Their gains were empirically adjusted
and their outputs subtracted from those of the signal channels to
reduce the effect of this ambient noise. This was the first system to
employ electronic noise cancellation techniques. It was introduced
into the laboratory in 1983 and proved extremely effective, even in
the absence of shielding, in making measurements more quickly and
accurately than was possible previously.
Based on their experience in constructing a five-channel sys-
tem, Biomagnetic Technologies, Inc., went on to develop a similar
seven-channel system. Such systems are now installed at New York
University, the National Institutes of Health, Vanderbilt University,
the Scripps Clinic in La JolIa, the Los Alamos National Laboratory,
the Free University in West Berlin, the University of Texas School of
Medicine in Galveston, and at Henry Ford Hospital in Detroit and
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BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
in other laboratories in Europe. In some cases two such instruments
are present in the same laboratory, thus providing a total of 14 sens-
ing channels for concurrent use. CTF, a Vancouver based company,
manufactured a single-channel system that ~ in use at Simon Frazer
University and at the University of Wisconsin. It should be noted
that only three laboratories are devoting a substantial effort to the
study of cognitive processes, the rest focusing on clinical problems.
[ike];hood That Progress WiB Be Made
All this ferment in the development of the technology of neuro-
magnetism is undoubtedly related to the very strong cianns made on
its behalf. The strongest of these claims is related to the presump-
tion that the extracellular volume currents that underlie the EEG
and the ERP do not contribute substantially to the magnetic field.
Furthermore, the neuromagnetic and electrical methods yield differ-
ent and complementary results. Since the distribution of intracranial
volume currents is strongly influenced by features of the skull such as
the orbits of the eyes, the sutures in the skull, and other anisotropies
of conductivity, source localization using s~rnple concentric sphere
models should be subject to considerable error. If it is true that
these same conditions have little effect on the extracranial magnetic
fielcI, then relatively simple models of the head should permit excel-
lent source localization. One strong cistern is that it is possible to
locate intracranial sources of neuromagnetic fields with a precision
that is not possible when using similar electrical measurements. To
the extent that investigators find it important that activity of par-
ticular portions of the brain be identified with processes underlying
cognition, this attribute of neuromagnetism may be of great value.
There are empirical bases for this strong claim that we review below.
One of the more impressive experiments, demonstrating the abil-
ity of neuromagnetic methods to resolve sources, described the tono-
topic organization of a portion of the human auditory cortex (Ro-
mani, Williamson, and Kaufman, 1982~. Tone stunuli of different
frequencies were modulated by a 32 Hz sinusoid. The steady-state
evoked field at the frequency of the modulating sinusoid was mea-
sured at many places on the side of the head. All the carrier fre-
quencies were presented at each position of the single-channel sensor;
the sensor was then moved and the responses measured again at an-
other position. After the experiment was completed, all the averaged
responses associated with each carrier frequency were collected and
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BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
responses to novel stimuli. This wave is probably related to the neg-
ativity that was described by Hillyard et al. (1973), and its magnetic
counterpart appears also to have its source near auditory cortex.
Still another contribution of ERF studies is the first report that
the equivalent current dipole source of the P300 is in or near the hip-
poca~npal formation (Okada, Kaufman, and Williamson, 1982~. This
finding is consistent with data obtained using indwelling electrodes in
epileptics. But electrical studies in which patients having unilateral
temporal lobectom~es show no shift in the distribution of the P300,
and studies involving anunal models show results that in some cases
are inconsistent with this interpretation and consistent with those of
other studies (e.g., Buchwald, 1987~. These inconsistencies remain
to be resolved.
The literature concerning the relationship between neuromag-
netism and cognition is quite slender. As stated earlier, until now the
main focus of basic research has been on sensory processes. There are
currently several major efforts getting under way that are designed to
test the usefulness of neuromagnetism in medical practice, and three
laboratories are currently investigating neural processes involved in
cognitive processes. Publications should be imTn~nent.
While little has been accomplished in directly contributing to
cognitive neuroscience, it is clear that the necessary foundations for
future progress have been laid. The emergence of multiple sensor
neuromagnetometers and of theory and algorithm that allow the
processing of data from many such channel is particularly impor-
tant. It has led to a growing awareness that source localization and
resolution are possible only when an adequate number of sensors is
used, whether these be magnetic field sensors or electrodes. At the
present time it is possible to study the activity of limited regions of
the brain and how this activity IS affected by factors such as cognitive
Toad or changes in perception. It seems likely that many studies will
employ the paradigms already used with so much success in ERP
research in an effort to determine which parts of the brain are actu-
ally involved. This modest approach promises to be useful in that
it wid enable ERP researchers to determine if a given component
they observe is attributable to a single source or to several widely
separated sources whose activity overlaps in time. Such efforts will
undoubtedly sharpen the skills of workers in neuromagnetism, and
they will ultimately result in branching out to develop paradigms
that are uniquely suited to their own methodology.
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RESEARCH FINDINGS
33
Opportunities for Basic and Applied ResearEh
Several problems associated with the interpretation of ERP re-
sults can now be addressed. These include deciding whether the
N100 and P200 are attributable to multiple sources and the degree
to which the variance in the electrical P300 can be accounted for by
changes in the magnetic P300. Such studies will require the joint
use of ERP and ERF techniques. The urgent need for concurrent
recording of electrical and magnetic data cannot be overstated. Un-
less precise and quantitative procedures are employed, it will not be
possible to determine the degree to which one of these measurement
modalities reveals information that cannot be obtained by means of
the other modality.
Among the most promising future developments IS the advent of
truly large arrays of neuromagnetic sensors. The study of correlated
activity among ah of these sensors will make it possible to examine the
waxing and waning of activity of multiple sources in the spontaneous
MEG ant] also when specific event-related tasks are performed. The
complex chains of events occurring at many places within the brain
during high-level tasks, e.g., retrieving memories, engaging in speech
production, perceiving stereoscopic depth, etc., are very difficult to
study with existing instruments. Current topographical EEG studies
are essentially two dunensional, and the locations of the sources of
the potentials cannot be estimated accurately, even with the use of 30
to 60 electrodes. The promise of this approach can best be realized
using large arrays of sensors and analytical tools that will reveal
the changes that occur over time in brain activity within a three-
dimension e] volume. ~ principle, there is no technical reason why
this cannot be achieved, especially if complementary technologies are
brought to bear on the problem of how to constrain solutions to the
inverse problem, discussed in Chapter 4.
As we have already stressed, there are some inherent ambiguities
in interpreting neuromagnetic measures. It is not known whether
there is a flow of current ~ opposed directions at the same time in
many portions of the cortex. If this is a significant occurrence, then it
leaves us with an apparently weak response although the underlying
activity is in fact very strong. Animal models and methods of current
source density analysis applied to their exposed brains should help to
clarify this issue. So too would correlated brain imaging studies (see
the next section). These, however, should not be mere replications
of experiments across different populations of subjects; they should
involve the same subjects and the experimenters should have the
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BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
broad biophysical skills needed to interpret such data. In this same
connection, it may be instructive to conduct studies involving clinical
populations, including patients with split brams, so that it becomes
relatively easy to isolate anatomically symmetrical regions from each
other. Thus, the use of both electrical and magnetic measures in
split brain patients (and of the many techniques developed to study
such patients) can lead to very suggestive results.
IMAGING TECHNIQUES I:
POSITRON EMISSION TOMOGRAPHY
Positron emission tomography (PET) is a nuclear medicine tech-
nique that produces an image of the distribution of a previously
administered radioactively labeled compound in any desired section
of the body (Ra~chie, 1983~. Radioactive labeling is the chemical syn-
thesis of a compound in which one of the atoms ~ radioactive. PET
images are highly faithful representations of the spatial distribution
of these radioactively labeled compounds at selected planes through
the tissue. These images reflect the behavior of the particular com-
pound that has been labeled. A wide variety of compounds have been
labeled permitting measurements of local blood flow, metabolism,
and chemistry.
Background of Researth Findings
Using i8F-labeled fluor>deoxyglucose, PET investigators
(Phelps et al., 1979; Reivich et al., 1979) quickly adapted the success-
fuT deoxyglucose autoradiographic technique (Sokoloff et al., 1977)
for measuring local brain glucose metabolism. PET tended to be-
come synonymous with deoxyglucose measurements of local brain
glucose metabolism in humans. Many attractive, color-coded images
of normal as weld as diseased human brains at work soon appeared in
the scientific literature, at scientific meetings, and even in the media.
What escaped the notice of many was that PET employs a vari-
ety of quantitative tracer techniques. Each of these techniques uses
a different mathematical mode! and a different radio-labeled com-
pound. These techniques can now be used to make measurements
of many different variables, such as local blood flow (Raichie et al.,
1983), blood volume (Martin, Powers, and RaichIe, 1987), oxygen
consumption (Mintun et al., 1984), pH (Brooks et al., 1984), perme-
ability (Herscovitchet al., 1987), receptor binding (PerImutter et al.,
OCR for page 35
RESEARCH FINDINGS
35
1986) and transmitter metabolism (Garnett, Firnau, and Nahm~as,
1983~. It can be anticipated that additional PET techniques will be
developed In response to new and important biological questions that
justify the time (often 2 to 5 years) and expense required to develop
the relevant radio-pharmaceuticals and tracer strategy.
Likelihood That Progress WiB Be Made
The capacity of PET to contribute to a better understanding of
brain function has been demonstrated. Abundant evidence indicates
that functional activity, such as somaesthesis, audition, movements
of all types, vision, and language, cause striking changes in local
brain blood flow and glucose uptake, which can be quite dramatically
demonstrated with PET (Raichie, 1987~. Analysis of such images has
progressed from simple qualitative, uncontrolled demonstrations of
anticipated changes to more sophisticated studies using rigorously
controlled experimental paradigms and precise analytical techniques
(Petersen et al., 1988~.
In the studies by Petersen et al. the objective was to use PET
measurements of blood flow to locate the regions of the human cere-
bral cortex concerned with the elementary mental operations of visual
and auditory word processing. Four behavioral conditions formed a
three-level subtractive hierarchy: passively viewing a cross hairs on
a television monitor; passively viewing or hearing single words at
one per second; repeating the words; and generating a use for the
words. Each task state was assumed to add a single process to
those of its subordinate control state. Direct evidence to support
this assumption is in press (Petersen et al., 1988~. Because of the
short measurement tune and the repeatability of the measurement,
all tasks were performed by each subject ~ the study. The first-
leve] comparison, the presentation of single words without a lexical
task, was compared with visual fixation without word presentation.
No motor output nor volitional lexical processing was required in
this task; rather simple sensory input and involuntary word-form
processing were targeted by this subtraction. In the second-level
comparison, speaking each presented word was compared with word
presentation without speech. Areas involved in output coding and
motor control were targeted by this comparison. In the third-level
comparison, saying a use for each presented word (e.g., if "cake"
was presented, to say "eat"), was compared with speaking presented
OCR for page 36
36
BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
words. This comparison targeted areas involved in the task of semen
tic processing (ver~noun association) as distinguished from speech
sensory input, and involuntary word-form processing.
Images were analyzed by paired intrasubject subtraction. Task-
state minus control-state subtractions created images of the regional
blood flow changes associated with the operations of each cognitive
level. Intersubject averaging was used to increase the ~i~nal-t~n`,i~e
ratio of these subtracted images.
.,
O _ ~ _
The results of this complex study provide evidence for multiple,
parallel routes between localized sensory-specific, phonological, ar-
ticulatory, and semantic coding areas. More important, this study
may be a prime example of what is required to make elective use
of PET in cognitive psychophysiology. The study combined state-of-
the-art PET techniques with sophisticated stimulation paradigms;
it arose from close collaboration among investigators with exper-
tise in PET, human neurobiology, and cognitive neuropsychology.
The study seems to provide unique new insights into the functional
anatomy of perception, motor control, and language.
It should be clear from the above material that PET will play a
significant role in understanding the function of the human brain.
Opportunities for Basic and Applied Research
It may be argued by some that despite the developments de-
scribed in this report, it is virtually impossible for PET to reveal the
underlying neuronal events participating in such changes (e.g., blood
flow and volume or transmitter metabolism), and hence it can con-
tribute little to our understanding of how the brain works. However,
it seems fair to assume that once PET has safely identified a specific
area of normal human or primate cortex involved in a well-defined
type of information processing (a task it is uniquely equipped to
do), other neurobiological techniques can be brought to bear on the
exact nature of the process. Complementary interaction of this type
between cognitive psychophysiology and neurobiology can serve to
further our understanding of the human brain.
IMAGING TECHNIQUES II:
MAGNETIC RESONANCE IMAGING
Magnetic resonance imaging (MRI) is based on the fact that some
atomic nuclei act like tiny bar magnets when placed in a magnetic
OCR for page 37
RESEARCH FINDINGS
37
field. When they are aligned in a magnetic field they can be excited
in controlled ways by irradiation with radio frequency energy. During
recovery from such manipulations, these tiny bar magnets or dipoles
Ernst radio frequency signals that contain a great deal of information
about their chern~cal environment. Depending on the strength of
such signals, unages of sections of the body can be obtained with
this technique. From such images one can obtain quantitiative infor-
mation about tissue biochemistry, acidity, and met embolism as well as
anatomy.
Background of Research Fm~mge
Abundant evidence now supports the use of proton MR! in clini-
cal medicine as an excellent way to obtain anatomical information of
the human brain in viva. ~ many respects, the images are superior
to those produced by X-ray computed tomography (CT). The pri-
mary contribution of proton MR! to neurobiology wiD be similar to
that of CT, providing accurate information for correlations between
specific lesions and the signs and symptoms of ilIne - .
Many nuclei other than hydrogen can be studied with MRI. Of
the biologically unportant ones, 3iP, 23Na, and i3C have received the
most attention. In a recent review of in viva spectroscopy techniques
(now often referred to as MRS or magnetic resonance spectroscopy)
using these nuclei, Prichard and Schulman (1986) have provided
exciting new data from an increasing number of studies showing
that it is feasible to measure brain ATP, PCr, Pi, and intracellular
pH in viva with phosphorous MRI. Using refined techniques for the
hydrogen nuclei, it ~ possible to measure brain lactate concentrations
in humans and a variety of amino acids in animals. Techniques still
under development with i3C MR! suggest that it may be possible to
monitor a number of specific biochemical reactions in viva with MR!
spectroscopy.
[likelihood Mat Progress WiB Be Made and
Opportunities for Research
MRI has played a role ahnost identical to that of X-ray computed
tomography in providing ever more refined anatomical unages of
the living human brain. This permits detailed cI~nical-anatomical
correlations. Because of its lack of temporal resolution, however,
MRI will not replace PET in the area of functional brain mapping.
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38
BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
Because of the exquisite anatomical detail provided by MRI pro-
ton images, this technique will probably become the technique of
choice for detailed clinical-anatorrucal correlations. In addition, one
can anticipate that MRI proton images wall also be used to anatomi-
cally constrain PET images with their somewhat poorer anatomical
resolution. Thus, brain edges and ventricles can be identified and
radioactive counting data blurred into these regions on PET moved
back into the brain. Such interaction will require PET and MRI
scans in each subject with proper alignment of the planes of section.
This wiD be both expensive and time-consuming; however, at least in
selected cases (e.g., cases of aging and dementia with brain atrophy),
such an interaction wiD be essential. More speculative will be the use
of MRI to further constrain PET data by defining gray-white matter
differences.
COGNITIVE CONSEQUENCES OF BRAIN DAMAGE
OR ALTERATIONS
This approach allows for insights into the functioning of the nor-
mal human brain. Dissociations, disabilities, and other phenomena
instruct the student of cognition at two levels. First, studies on
brain-damaged patients are suggestive of the functional architecture
of cognition. Second, with the advent of new brain unaging tech-
niques, these same studies can also be suggestive of the brain areas
involved with particular functions. This is true not only for cases of
hemispheric disconnection but also for the correct characterization
of patients with focal brain damage (Jouandet et al., 1987, 1988~.
Background of Research Findmge
There are two main views on how brain-damaged patients can be
used to study cognitive processes. The first assumes that psycholog-
ical processes are localized in discrete brain areas and that damage
to these areas will provoke discrete psychological disturbances. In
terms of the doctrine of modularity in cognitive science, the approach
hopes to identify brain areas that subserve particular functions as
specified in perceptual and cognitive models. With the proliferation
of models that become more complex in terms of the processes and
subprocesses that are active in perceptual and cognitive processes,
the hope has been that new and better brain imaging techniques will
assist in a finer-grained identification of the brain areas involved in
OCR for page 39
RESEARCH FINDINGS
39
cognitive and perceptual activities. This position has traditionally
not entertained the view that focal brain damage may reveal deficits
that are part of a larger process. It has maintained that discrete
deficits following prescribed lesions are managed by the brain site in
question. This limitation has given rise to an alternative view of how
to gain knowledge about cognition from "broken brains."
The second view holds that, since psychological or cognitive
processes are widely distributed throughout neural networks, both
focal and diffuse brain damage can reveal clues only to the functional
structure of cognitive processes; direct clues to brain correlates of
cognitive processes are not revealed. The idea here is that cognitive
processes are generated by interactions of neural systems that are
widely distributed In the brain, and that damage to one area affects
other areas. This makes it difficult to ascertain which brain area
actually controls a particular function. Yet what is learned, by
deduction, is how the cognitive system is structured given how it
works in physical disrepair.
The brain lesion approach has yielded some of the most semi-
nal and basic observations to date about brain function. In animal
research, many of the major functional areas of the brain have been
described (Mishk=, 1982~. In humans, the clinical cases have offered
major insights into the mechanisms of memory (MiIner, 1970; Squire,
1987), perception (We~skrantz et al., 1974; Holtzman, 1984), atten-
tion tHillyard and Picton, 1987), language (Zurif and Caramazza,
1976), and cerebral lateral specialization (Gazzaniga and Sperry,
1967), to mention a few areas. It was the work on humans, for exam-
ple, that first implicated the hippocampus in memory mechanisms
and gave the first physical evidence that the distinctions between
short- and long-term memory were useful for both the brain and
psychological sciences. Recent work by Poener has underlined how
attentional processes, viewed through cases of brain damage, can be
thought of as working independently of other mental structures and
yet contributing to most of them. Work on aphasia has made im-
portant distinctions about the structure of language, suggesting that
different brain areas contribute to syntax as opposed to semantics.
The split-brain work that emphasizes the separate capacities of each
half brain has now shown how dominant the left brain is for most
computational skills, including thinking (Gazzaniga, 1985), imagery
(Kosslyn et al., 1985), and belief generation (Gazzaniga, 1985~. Fi-
nally, work on perceptual processes has continued to identify discrete
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40
BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
brain areas associated with particular properties of the visual system
such as color and motion detection.
Likelihood That Progress Win Be Made
In the continuing effort to bring greater and greater specificity
to structure-function correlates, studying the partially disconnected
human brain has been iDum~nating. Now, using MRI in cases of
inadvertent sparing, during brain surgery, of the major fiber pathway
in the brain (the corpus caDosum), it has been possible to make an
exact identification of what the small and discrete fiber systems
transmit that is of psychological interest (Gazzaniga et al., 1985~.
Using this approach, the high degree of specificity of this fiber system
for perceptual and cognitive functions Is now being demonstrated.
The use of MRI for categorizing cortical brain lesions is just beginning
(as noted in the previous section).
The localization of function in the human brain has been one
of the great classical themes in neurology since at least the time of
Paul Broca (1861~. Since then, many authors have attempted to
correlate various sensory, motor, language, and other higher associ-
ational functions to various cortical structures. These results have
helped to delineate the functional territories of the human cerebral
cortex (Jackson, 1864; Gudden, 1870; Fritsch and Hitzig, IS70; Wer-
nicke, 1864; Dusser de Barrenne, 1916; Gushing, 1932; Gazzaniga
and Sperry, 1967~.
Today, many workers in this field seem uncomfortable vnth the
functional maps of the human cortex as they now stand: these maps
appear insufficiently differentiated, whereas more accurate maps
would reveal highly specialized functional processes correlated to
highly circumscribed zones in the cortical mantle.
Over the last century, there have been three major obstacles to
the development of more highly differentiated functional maps of the
human cortex. First, the field of experimental cognitive psychology
has had to grow in sophistication; it has and no longer poses an
obstacle. But cognitive dysfunction still had to be correlated with
some localized cortical damage. This was difficult to do in the days
before CT and MRI; then it was necessary either to do a craniotomy
or to wait for the final pathology report in order to localize a cortical
lesion independently of signs and symptoms. The development of CT
and MRI, which precisely and immediately identify the anatomical
locations and extents of intracerebral lesions, has removed this major
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RESEARCH FINDINGS
41
obstacle. MRT, for example, has already allowed for the identification
of discrete callosal fiber systems with their functional role specified
(Gazzaniga et al., 1985; Gazzaniga, l98Ba, 198Bb). There remains,
however, the problem of obtaining accurate maps of the human
cortex, especially when one considers the incredible variation that
exists in the patterning of the gyri and suIci, a pattern apparently as
diverse as are fingerprints in the population.
It remains unclear to what extent a lesion in a given gyrus in
one individual Is functionally comparable to a similarly placed le-
sion In the same gyrus in another individual. The degree to which
the functional fields are similarly distributed across individuals, the
randomness with which secondary and tertiary suIcal folds position
themselves during the growth of the cortex in late prenatal develop-
ment, and the randomness with which various subzones of the func-
tional fields are either entrapped within the suIcal walls or exposed
on the gyral crests still remain to be determined. These questions
might be approachable given techniques allowing us to look beyond
the suici to examine the full expanse of the cortical mantle.
Opportunities for Basic and Applied Research
The next generation of cortical maps should allow identification
of landmarks both on the surface of the gyri and within the depths
of the suici, permitting measurement of the dimensions of cortical
areas and lesions and clarifying the relations of damaged zones to
surrounding cortical regions. Two kinds of cortical flat map tech-
niques, straight line (SL) maps and contour (Ct) maps have emerged
in the literature in the last several years. Until recently, these tech-
niques have been applied only to studies of restricted cortical regions
in nonhuman primates and cats. Each technique has as its goal the
unfolding of the rounded, three-dimensional cerebral cortex into a
map having the geometry of a table top, and each has its respective
advantages and disadvantages.
The major goal of some new studies has been to demonstrate that
stra~ght-line two-~mensional (SL2D) flat maps can be constructed to
represent extensive areas of the human cortex (Jouandet et al., 1987,
in press). These studies chose not merely to open a restricted area
of cortex, but undertook the most challenging test possible: the full
unfolding of the entire human cerebral cortex. While MR] renders
the human cortex immediately accessible, it remains very difficult
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42
BRAIN AND COGNITION: SOME NEW TECHNOLOGIES
to appreciate the Mansion and relation of a cortical lesion vi~a-
vis other cortical landmarks, when portions of the lesion and the
landmarks are distributed over several individual brain slice images.
SL2D maps take the next step in organizing the data. They open
and unfold the cortex, simplify neocortical geometry, preserve the
richness of its complexity, and fully represent the cortical territories
in a manner providing the only adequate structural foundation on
which functional information may, in the future, be interfaced In the
construction of highly difl5erentiated correlative maps. The promise
of this new technique is that once users familiarize themselves with
it, they will be able to see beyond the suici and behold a landscape
rich in previously obscured information and possibilities.
Bringing greater specificity to brain areas involved in cognition
is the task of many enterprises, including the imaging techniques
reviewed in the previous section. It is at this junction that the sep-
arate technologies begin to converge on common problems. Within
the context of traditional neuropsychology, MRI combined with flat
mapping of the cortical mantle wild begin to provide the kind of
greater specificity called for by modern cognitive theories.
The discussion in this section is not intended to convey the im-
pression that all that is needed to understand human brain function
are more detailed road maps of the human brain, particularly of
the neocortex. The mapping techniques are discussed only as an-
other technological accomplishment with implications for research
on human brain processes and functions. It may well be the case
that even the most up-to-date mapping wiD not provide a complete
understanding of the dynamic patterns of activity in cortical neural
processing. These ongoing patterns are the neurochemical bases for
the observed plasticity of human behavior as manifested in devel-
opment and change thoughout the life-span. Of particular interest
is the transmission of nerve impulses and those processes associated
with the ability of neurons to produce and release neurotransr~iit-
ters (Iverson, 1979~. Further research may address such questions
as "Which neurotransm~tters moderate or enhance which cognitive
functions?" (See I,erner, 1984, for a theoretical discussion of these
issues.)
Representative terms from entire chapter:
cognitive processes
