The neurophysiology of information processing and cognition.

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THE NEUROPHYSIOLOGY

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OF INFORMATION PROCESSING AND COGNITION E. Roy John 1 and Eric L. Schwartz2,

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Department of Psychiatry, Brain Research Laboratories, New York University. Medical Center, 550 First Avenue, New York, NY 10016

In the first textbook of physiological psychology in 1874, Wundt (128) expressed his conviction that the central problem of the field was the analysis of the physiologi cal bases of consciousness and subjective experience. Two generations later, the behaviorist movement, motivated partly by the excesses of introspective psychology and partly by imitation of operationalism in physics, succeeded in exorcizing both the language of conscious experience and the study of consciousness and mental states. Ever since, the dominant trend in studies of learning, including the neuro physiology of learning, has followed a strict behaviorist line. Reductionist ap proaches, such as the measurement of habit strengths and response rates and the tracing of neural circuits, have led to the accumulation of a vast amount of empirical knowledge but little insight into basic mechanisms. Sensory neurophysiology has followed a similar philosophical and methodological program, culminating for some in the extreme position that entire percepts may be represented by the firing of one or a few neurons

(3, 69), or that higher order perceptual and cognitive functions are

represented in localized anatomical regions. However, the study of how univariate sensory features, or stimulus attributes, differentially affect various anatomical structures ignores the problem of how the organism constructs an integrated, mul tivariate, and multidimensional perception of its environment. 'This work has been supported by Grant #G007604516 from the Office of Education, Grant #ERP72-0349A from the National Science

Foundation/RANN,

and Grant

#5ROI

MH20059 from ADAMHA. 2Grant #IF32MH0536701 from ADAMHA. 3We thank Dr. Robert Thatcher for many useful discussions and Arthur Weissman for his editorial help in preparing this review.

0066-4308/78/0201-0001$01.00


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The major source of information concerning the neurophysiology of cognitive processes in humans is the scalp-recorded event-related potential (ERP). Clear evidence exists that short latency or exogenous components accurately reflect a wide variety of stimulus attributes. These exogenous components must be related to the spatiotemporal encoding of information by the afferent sensory systems. Abundant additional evidence shows that other portions of the ERP, especially the longer latency or endogenous components, are not stimulus bound but reflect both non specific and specific aspects of the subjective evaluation of the significance or mean ing of the prior input. Such subjective influences upon ERP features have been found in studies involving arousal, attention, selective attention, emotional valence, assess ment of novelty, time estimation, uncertainty, detection of targets, differential iden tification of stimuli independent of size and shape, and the semantic classification of linguistic symbols. In order to understand such cognitive processes it would seem necessary to take into consideration how information about present events is represented in the brain and how information about prior events is stored and retrieved. Most of our knowl edge about the neural encoding, storage, and retrieval of information comes from electrophysiological studies of single neurons, mUltiple units, and sensory evoked potentials in acute and chronic animal experiments, whereas the vast bulk of infor mation presently available about the neurophysiology of cognitive processes comes from event-related potentials (ERP) in human subjects. The goal of this chapter is not to provide a review but an overview of thes,e separate domains, and to integrate the salient features of human ERP studies of cognitive processes with the insights obtained from animal studies of sensory coding, learning, and memory. The term "information processing and cognition" is meant to underscore our concern, not so much for mechanisms of learning or response selection, but for insight into the processes involved in "knowing," "understanding," and "thinking." NEURONAL INFORMATION PROCESSING The Identification of Neuronal Trigger Features with Feature Extraction

The extraction of salient features of the enviJrOnment is an essential capacity of sensory systems. In recent years, the idea that the activity of single cells might encode selected stimulus attributes or even the presence of complex percepts has been termed the "feature extractor" hypothesis. Surprisingly, there has been rela tively little published criticism of the basic assumptions or logical consequences of this line of reasoning. In a classic paper, Lettvin et al (73) discovered that cells in the optic tectum of the frog are sensitive to well-defined stimulus characteristics such as convexity, size, direction of movemenlt, etc. The possibility that the brain might use specialized neurons to classify evems in the visual world into a limited set of possible perceptual categories, each sensed by one type of feature extractor cell, stimulated an enormous amount of experimental and theoretical work. Several years later Hubel & Wiesel (48) described thn:e categories of "feature extractors" in the striate cortex of the cat: simple, compllex, and hypercomplex cells, which seemed to respond to progressively more general characteristics of the environment.


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They suggested that these three categories were the lower levels of an hierarchical system which functioned to abstract the salient information (such as edges, angles, etc) from the visual world. This suggestion implied that single cells at the top of the hierarchy might represent complete percepts. Following this early work, Barlow et al (4) found that cortical neurons in the cat were tuned to binocular disparity, and it was claimed that the neuronal basis for stereopsis had been discovered. Ulti mately, Gross et al (42) reported the observation, in the primate inferotemporal cortex, of a cell that appeared to respond preferentially to the shape of a monkey's hand. In the 14 years that had elapsed between the work of Lettvin et al and that of Gross et ai, many felt that the basic groundwork had been laid for relating higher order perceptual activity to basic neuronal properties. There are serious problems with both the experimental basis and the logical conclusions of these ideas. The nature of the problem was perhaps earliest recog nized by Sherrington (103), who introduced the notion of "one ultimate pontifical nerve cell . . . the climax of the whole system of integration," and immediately rejected the concept in favor of mind as a "million fold democracy whose each unit is a cell." There is considerable danger in allowing a technique (such as microelec trode recording) to determine a theoretical position; the extreme feature extractor position taken by such workers as Konorski (69) and Barlow (3) is merely the most recent in a long series of reductionist attempts to explain psychological processes. Barlow's neuron doctrine for perceptual psychology is based upon the assumption that "a description of [the] activity of a single nerve cell . . . is a complete enough description for functional understanding of the nervous system . . . The firing of a given neuron corresponds to a high degree of confidence that . . . the percept is present in the external world" (3). The logical problem with this position begins with uniquely specifying the trigger properties of a single cell. The edge response of visual cortex cells is a prominent but by no means unique aspect of their activity; the angle of tilt of the body axes has been reported to affect orientation tuning (47), as does auditory stimulation in the location of the visual receptive field (32, 75). The firing rate of hypercomplex cells is defined as a bivariate function of stimulus angle and length (48), and this end-stopping property has been claimed for the simple and complex cells as well (91). In general, the firing rate of a cortical cell will be a multivariate function of angle, length, direction of movement, velocity of movement, binocular disparity, vestibular and auditory stimulation. The response rate of cortical cells to an edge stimulus is a continuous variable that is logarithmically proportional to contrast at the edge (46). Many of the multivariate stimulus features that contribute to the firing rate of a single cortical cell (and it must be assumed that the list presented above is only partial) have been discovered by the strongest adherents of a single neuron approach to perception. But how is it logically possible from the firing rate of a single neuron to determine the presence in the visual field of a high contrast edge at one orienta tion, a lower contrast edge at a more favored orientation, a short edge moving at high velocity, a long edge moving at a less favored velocity but a more favored direction, or influences from the auditory, vestibular, or oculomotor systems? Trig-


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ger features for which a cell will increase its firing rate are readily found; the converse operation, inferring the presence of unique features in the environment from the fact that a given cell is firing at a particular rate, seems to be logically impossible. The very richness of the repertoire of trigger features seems to under mine the theoretical position that has been inferred from their existence. Finally, the hierarchical arrangement of feature detectors, in the simple-complex-hypercomplex hypothesis of Hubel & Wiesel (48), has receive:d a strong experimental challenge: the latency of simple cells in the cortex of the cat is longer than that of complex cells (109), thus makjng less plausible the idea that the simple cell is the first rung in the ladder leading up to the "cardinal cell" of Barlow (3). Hypercomplex cells, originally suggested as the third level of this hierarchy, may be merely an extension of the simple cell category (91, 94). Neuronal feature extractor theories are difficult to disprove; it is highly unlikely to find the particular few cells that encode the percept "grandmother sitting in a rocking chair and smoking a cigar" (particularIy during the limited lifetime of the cigar) among the hundreds of millioll of cells of the visual system. Therefore, failure to find high-order feature extractors does not prove that they do not exist. Only low-order feature detectors are likely to be encountered and convincingly character ized in any feasible experimental situation. The extended contours of a stimulus, whether or not reflected demonstrably by the firing rate of certain cortical neurons, may not be of central importance to the analysis of form. Random dot stereograms (61) which contain no monocular con tour information are capable of producing vivid perception of three-dimensional form arising solely from the existence of binocular correlations. Conversely, clusters of rotating line segments, which differ from the surround only in their speed of rotation, are not readily detectable, despite th,� fact that they are seemingly well matched to the trigger features of cortical cells (62). Furthermore, the powerful contribution made to a visual percept by extended contours need not arise from actual physical contours in the stimulus. Illusory contours due to Gestalt comple tion processes, as well as the apparently related fusion of random dot stereograms, suggest that higher order processes related to form vision may be considerably more complex and globally organized than the extreme feature detector theories would suggest. Spatial Frequency Analysis

Neurophysiological and psychophysical evidence suggests that spatial frequency analysis may provide a fundamental mechanism of visual perception (101). Pollen & Ronner (83) and Glezer et al (38) have argued that the tuning curves of cat visual cortex cells suggest that they function as "feature detectors" for spatial frequency. The substitution of spatial frequency for edge detection as the basic property upon which higher perceptual processes are built has I�ertain advantages. Fourier analysis is intrinsically global and greatly facilitates the performance of cross-correlation and autocorrelation (29); Uttal (121) has pointed out the potential significance of auto correlation in regard to the associational and Gestalt aspects of visual perception. The field of Fourier optics, of which holographic image processing is a significant



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part, is an exercise in the practical implementation of spatial frequency analysis by optical devices (40), and holography has captured the imagination of some workers in the neurosciences. The distributed and associational character of holographic images is suggestive of certain aspects of brain function (S7). Nevertheless, a detailed model of how the brain might keep track of the phases and the frequencies necessary to perform spatial frequency analysis has not been presented. The model of Pollen et al (S2) is merely an analogy between the visual system and a digital computer radio telescope application. Subsequent work on spatial frequency analysis has tended to focus on the phenomenological details, such as the bandwidth of "spatial frequency channels," and has ignored the crucial question of how spatial frequency information could possibly be organized into an ordered percept by the brain. Kelly (64) has pointed out that a certain degree of spatial frequency sensitivity is expected to occur, based on partial regularity of cell packing in the retina, and therefore the observed spatial frequency sensitivity of the human and cat visual systems to the spatial frequency content of stimuli could be epiphenomenal. Thus, although they constitute a promising line of analysis, spatial frequency models have not been adequately developed in anatomical, physiological, or percep tual terms. To the extent that spatial frequency is added to the list of "single cell feature extractors," this approach suffers from the same logical problems as the classical feature extractor position. This position, explicitly held by relatively few neurophysiologists and psychologists, is nevertheless the implicit basis of much of ongoing theoretical and experimental work. Several theoretical approaches to the view that spatiotemporal patterns of neural activity are the basis of neural informa tion processing will be discussed next. Distributed Representation of Information

There is abundant evidence that information (and function) must be distributed across extensive anatomical domains, based on the relative effects of single and multiple stage lesions ( liS). This approach, which compares organisms with the same residual brain tissue but different temporal sequences of experimental lesion or injury, has yielded unequivocal evidence concerning the impressive capability of the brain for the reorganization of information processing. Dru, Walker & Walker (2S) found that the behavioral experience of rats subjected to two-stage cortical lesions was critical to the recovery of visual function. Rats that received no pat terned stimuli between the two lesions remained functionally blind. Rats that were passively moved through a patterned environment also remained functionally blind. Only rats that were allowed to actively explore a patte�ned visual environment between the two lesions showed retention of visually guided behavior after the second lesion. The recovery of function after brain damage is not solely determined by anatomical factors, but depends critically on the behavioral trajectory of the organism. Radical hemispherectomy in humans has provided an interesting parallel to the multiple-stage animal lesions. A recent report of this surgical procedure describes a patient who received a severe closed head injury at age 5 and by age 20 suffered from intractable epileptic seizures (22). Prior to surgery, neurological examinations


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revealed bilateral optic atrophy with concentric retraction of both visual fields, as well as left hemiplegia, with atrophy of both limbs and marked spasticity. After right hemispherectomy, bilateral optic atrophy persisted but the left eye was practically blind, with vision reduced to perception of light. A marked improvement in motor performance was noted. Almost normal vision was found on the right, with no hemianopia. The visual field was enlarged. This puzzling finding, along with the absence of the expected hemianopia, was attributed to an adaptation of the superior collicuius which had been released by the lack of corticofugal control previous to surgery. This suggestion receives support from the (animal) work of Sprague (107), who found that ablation of the colliculus contralateral to a previous cortical lesion restored vision to the visual half field lost after the cortical lesion. Griffith & Davidson (41) report a right hemispherectomy performed on a patient who had intractable seizures at age 10, left hemiplegia by age 12, and right hemi spherectomy at age 19. This patient showed a WAIS IQ score of 101 (verbal) and 63 (performance) before surgery, and 12 1 (verbal) and 91 (performance) tested at IS years following surgery. Smith & Sugar (:104) have also reported that above normal intelligence and linguistic ability may develop following left hemispherec tomy at age 5�. In each of the human cases cited above, an early lesion (caused by accident or disease) was followed by a second stage lesion (surgical hemispherectomy). The recovery of function in these cases was dramatilc and paralleled some of the results that have been found in the literature of multiple-stage lesions in animals. The conclusions that follow from these observations are these: 1. It is important to recognize that severe brain damage need not I�ause irreversible functional deficit, even if it occurs relatively late in life. The human cases cited above involved childhood damage, with surgical intervention performed in adulthood. However, cases of functional recovery following hemispherectomy performed as late as 47 years have been reported (104). The possibility that behavioral experience and rehabilitative conditions markedly affect the probability of functional recovery after brain damage is suggested by both the animal and human literature. 2. Information and function in any one sensory modality is redundantly distributed throughout anatomically extensive regions, with varying signal-to-noise ratio. Normally the brain may rely primarily on the activity of a particular region (or group of regions) for a particular function. The occurrence of localized damage, coupled with behav ioral circumstances that allow an adjustment of the thresholds in remaining brain regions, apparently allow the possibility of using the functional capability of anatomical areas that were previously suboptimal in signal-to-noise ratio. Lashley (71) long ago suggested that the apparent elusiveness of the location of information and function in the brain was due to the overlapping of neuronal fields, to "equipo tentiality." Luria (74) has reviewed the long history of this line of thought and has proposed a unified view concerning "multipotentiality" and redundancy of function in the brain. Finally, Bartlett & John (5) havl� performed a quantitative analysis demonstrating multipotentiality with respect to the distribution of exogenous and endogenous components of the sensory evoked potentials in behaving cats.


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i Additional insight comes from the study of human patients in whom severe t:pilepsy was treated by section of the cerebral commissures. Only after subtle 'behavioral and perceptual testing was performed on these patients was it realized that remarkable functional abberations had occurred. In certain respects, these "split-brain" patients behave as if they had two different brains, each perceiving different aspects of reality (37). The dramatic evidence of hemispheric specialization further demonstrates that perception involves cooperative transactions which inte grate the activity of large numbers of neurons in a complex dynamic system. There fore, the bases of perceptual and cognitive processes would seem to be more profitably sought in the system organization than in the properties of unitary ele ments (single cells, local anatomical structure). Reductionist attempts to localize function parallel the reductionist approach to perception that is exemplified by feature extractor theory. These positions are conceptually simple and lead to well defined strategies. Nevertheless, they fail to confront the fact that complex percep tual and cognitive processes involve dynamic integration of vast regions of the brain.

Theoretical Formulations for Distributed Representation The previous discussion has been directed toward demonstrating that the reassuring theoretical and experimental arguments for localizationist approach to brain func tion must be critically reevaluated. To a certain extent these reductionist positions have been internalized by many workers in the neurosciences, and the difficult but necessary step of facing the complexity entailed by a global or statistical point of view has been avoided. Exactly what is meant by statistical, or distributed, or global neural function, and what experimental strategies might be devised to explore these alternative theoreti cal positions? A large amount of theoretical speculation has certainly been accumu lated; however, relatively little of this work directly addresses the constraints imposed by the anatomical and physiological details of real nervous systems. In the following brief discussion, several theoretical approaches to the functional utiliza tion of temporal and spatial patterns of neural activity will be presented, which are characterized by a close relationship to experimental data. The position that temporally coherent neural activity may reflect the sensory perceptual and cognitive bases of subjective experience has been outlined by John in two recent articles (53, 54). In these papers, a "statistical configuration" theory was developed. This theory holds that the critical event in learning is the establish ment in different parts of the brain of systems of neurons whose temporal activity has been affected in a coordinated way by the stimuli presented during the learning experience. Since this coordinated activity is effectively a trace of the experience, the term "representational system" is used to refer to this pattern of coherent neural activity. The same neural ensemble can represent many different items of informa tion, each with its characteristic pattern of coherent deviation from random or baseline activity. This theory is configurational in that new behavioral responses are based upon the establishment of new temporal patterns of ensemble activity rather than elab-


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oration of new pathways or connections. Learning increases the probability that particular patterns of activity will occur in coupled ensembles of neurons. A repre sentational system acquires the capability of re:leasing the specified common mode of activity as a whole if some significant portion of the system enters the appropriate mode because of extero- or interoceptive influences. The released activity pattern can serve as a template against which incoming information can be matched for recognition. In a recent book, Freeman (33) has confronted the question of "what are the neural mechanisms and the behavioral significance of the E.E.G." This work repre sents one of the most advanced approaches to t he problem of characterizing neural activity in mathematical terms. A major theoretical proposal in this work is the theory of "K sets," named after the late Israeli biophysicist Aaron Katchalsky. K-sets constitute a hierarchical system of groupings of neurons into "neural masses," based on the nature of their mutual excitatory and inhibitory interactions. An impressive ability is demonstrated, based on the use of K-sets and systems theory, to generate successful characterization of electrophysiological measurement. Freeman's theoretical position, like John's, is based on the importance of spa tiotemporal structure in patterns of neural activity. John's theory emphasizes the temporal structure of coherent activity in neural masses, whereas Freeman's theory emphasized the phase difference of temporal patterns between different neural masses as the significant carrier of information. Both approaches concur on the importance of temporal patterns for the processing of information in the brain; most of the data upon which these theories are base:d derive from study of neural firing sequences. Spatial aspects of information coding have not been stressed, partially due to the paucity of data from large-scale spatial arrays. A recent mathematical approach to the functional significance of spatial mapping in the nervous system has been developed by Schwartz (95-97). The retinotopic mapping of the primate striate cortex is characterized by a complex logarithmic (conformal) mapping of the visual field (or surface of the retina) to the surface of the striate cortex. This statement concisely summarizes the cortical magnification data, the scaling of receptive field size, and the mapping of global visual field landmarks. This mathematical description allows the calculation of the spatial configuration of an arbitrary visual stimulus as it would appear across layer IV of the striate cortex. Although the retinotopic mapping is certainly nonlinear, the particular mathematical form of this mapping shows that rotations and size dilata tions of a visual stimulus result in a translational shift of the cortical image without a change in its size or rotational aspect. Up to this rectilinear shift, the cortical image is size and rotation invariant. Thus the anatomical (spatial) structure of the visuo topic mapping may simplify recognition of invariant aspects of visual stimuli, and this could be of considerable importance to stereopsis, where the left and right images (which in general differ in their rotational and size details) must be corre lated. Similar uses of the complex logarithmic mapping have been proposed for use in computer oriented (G. Chaikin & C. Weiman, in preparation) and optical (18) pattern recognition, and the latter work has demonstrated that correlation of images is greatly facilitated by a complex logarithmic preprocessing step.


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The complex logarithmic function seems to describe the mappings of the second ary and tertiary visual cortex, the inferior pulvinar, and even the somatosensory map (97). Perhaps the most intriguing aspect of this work has been the observation that the sequence regularity property of cortical neurons described by Rubel & Wiesel (49) implies that the local columnar structure of the visual cortex may be described by the same mathematical mapping that describes the global structure (97). This idea has been developed in detail, and a geometric model has been presented in which the neuronal properties of orientation tuning, sequence regularity, binocular disparity tuning, and ocular dominance ratios are shown to be logically consistent with a logarithmic geometric structuring of the afferent input to the cortex (95). The neurophysiology of the visual cortex may be more aptly described in terms of "computational geometry" rather than "neuronal feature extraction. " Finally, the developmental plausability of conformal mapping in the nervous system follows directly from the observation that analytic or conformal mappings describe the "smoothest" possible mapping of one tissue surface onto another, subject to the boundary conditions of the available tissue surfaces. The detailed structure of recep totopic mappings thus may be encoded by minimal rules of neural development (96). HOW DOES EXPERIENCE CHANGE THE PROCESSING OF INFORMATION? The study of learning and memory is currently pursued simultaneously on the molecular level, the invertebrate level, and the vertebrate level. The basic experimen tal data span the range from pharmacology, neurochemistry, and electrophysiology to purely psychological studies of behavior. Electrophysiologists are further subdi vided into practitioners of single cell, multiple unit, and evoked potential techniques. Increasing specialization is erecting almost impenetrable barriers and an adversary relationship between adherents of different research strategies, although the ultimate goals may be quite similar. Regrettably, a particular subfield of neurophysiology has tended to indulge in extravagant claims of significance; in a recent review (70) of the electrophysiology of learning and memory it was stated that "it is only in simplified preparations . . . such as invertebrates that it is possible to do . . . experi ments that definitely establish (neuronal mechanisms) of learning and memory." Although it is clear that the study of invertebrate and simplified neural systems has led to important insights concerning basic neurophysiological mechanisms, it should be clear that the significance of this research for higher order processes rests on a single (unverified) assumption: the operation of the (human) nervous system may be reduced to a combination of the operations of its atomistic parts. If this assump tion fails (and considerable effort has been devoted in the first part of this review to the suggestion that it will fail), then the study of invertebrate preparations, from the point of view of a psychologist, could be nothing more than "interesting games quite irrelevant to an understanding of learning in higher vertebrates" (119). It seems clear that the study of event-related potentials in human beings, single cell, multiple unit, and evoked potential studies in intact, behaving vertebrate prepara tions, as well as single cell studies in simplified vertebrate and invertebrate prepara-


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tions will all make invaluable contributions to an overall understanding of the neurophysiology of information processing and cognition. The following discussion of how information processing is altered by experience will be divided into two parts: the first will deal with animal studies that examine the changes in electrophysiological activity which take place during learning, using either single unit, mUltiple unit, or evoked potential observations; the second part will review human studies in which changes occur in scalp-recorded event-related potentials as subjects evaluate the meaning of stimuli under different circumstances. These are usually not learning situations, but rather require the subjects to monitor the environment for particular events, extract differential information from events, or think about stimuli in a particular way. In both of these types of studies, the experimenter faces a difficult problem: how does one distinguish between correlates of the operation of a system as it processes information and correlates of the content upon which the system is operating? In analogy to the functioning of a computer, how does one distinguish between the program and the data upon which the program operates? Although both are repre sented identically (by strings of bits in some magnetic or electronic medium) there is a clear conceptual distinction. This problem will be repeatedly obvious in the subsequent discussions. Eiectrophysiologicai Studies of Learning and Memory in Animals WIDESPREAD RESPONSES TO SENSORY STIMULI The discussion in the first section of this chapter led to the conclusion that information about a sensory stimulus was not represented, in general, by activity localized in a particular cell or set of cells, nor even within a narrowly circumscribed anatomical region. This conclusion is supported by direct electrophysiological evidence which has long been available. After extensive and careful single unit studies, in which the firing pattern of single units was measured in a wide variety of cortical regions in the cat, Burns & Smith (14) revealed two conclusions of far-r·eaching significance: most neurons in the brain display incessant activity, and every cell encountered, if observed long enough, could be demonstrated to show a significant alteration in its firing pattern as a result of the presentation of an arbitrarily defined stimulus. A rich variety of anatomical pathways exist to each cell, and consequently any single pathway is unlikely to be sufficient to represent any item of information unequivocally. A similar conclusion follows from the more recent observations of the trigger features of cortical cells reviewed earlier. The firing pattern of a single cell is, in general, a multivariate variable which is insufficient, except in an ensemble sample, to yield unambiguous information about the specific nature of the sensory stimulus. DURING LEARNING Other reviews have documented the evidence for the statement that widespread changes in evoked potential waveships and in unit activity occur during learning. Recent studies of changes in neuronal activity during learning provide further corroboration of this fact. Marked changes in unit activity correlated with conditioning were observed in visual and auditory cortex (7, 67, 80) hippocampus (II, 45, 80, 100), dentate gyrus WIDESPREAD CHANGES IN ACTIVITY

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(100), prefrontal cortex (35), peri- and postcruciate cortex (31, 79, 126, 127), somatosensory cortex (106), medial geniculate nucleus (36, 93), and the nucleus medialis dorsalis (45). In many of these studies, the proportion of units responding to the conditioned stimulus (CS) increased during conditioning. However, no direct measure of coherence was obtained in these studies, nor could one have been inferred, since only the total amount of firing rather than the temporal details of the poststimulus histogram was typically observed. OPERATION VERSUS CONTENT One plausible explanation for the existence of widely distributed changes in brain unit activity following conditioning is that this increased activity simply reflects general, unspecific arousal due to the presence of stimulation or of reinforcement per se. For example, Khachaturian (66) subjected flaxedilized cats to a relevant CS consisting of a train of 4 flashes or clicks, inter spersed with continuous irrelevant stimuli (IS) consisting of clicks or flashes during habituation, conditioning, and extinction procedures. Widespread changes in the amplitudes of the evoked potentials were observed; in the pulvinar, these changes were specific only to the CS, while other structures examined showed change both to the CS and the IS. This ingenious paradigm offers a powerful technique to discriminate continuously between specific effects due to conditioning and non specific effects due to arousal, attention, or motivation. An alternative explanation for the widespread distribution of changed neuronal activity following conditioning might be that the increased activity reflected general operations, rather than the processing of specific information about the meaning or content of the stimulus. Examples of such general operations might be selective attention to a certain modality of input, the set to respond, or the preparation to make a certain movement or receive a particular type of reinforcement. These operations are not unspecific in the sense that they are focused rather than global, yet they are not related to specific informational processes. Changes in body orienta tion or response bias are examples of such general operations. Preparation to "go" under certain circumstances would be another example. In order to discriminate between these various possibilities, it is necessary to use sophisticated behavioral paradigms-noncontingent stimulus (66), differential generalization (55), choice reaction time (8), delayed matching from sample and delayed response (34, 35) as well as sophisticated data analysis approaches that concentrate on the detailed spatial and temporal nature of the neuronal response. MAJOR CURRENT RESEARCH STRATEGIES AND FOCI Several recent reviews may be consulted for a detailed enumeration of current research (15, 72, 118, 119); the following is a brief list of the major foci (in our opinion) of ongoing research into the neuronal bases of learning.

Rerouting 0/ responses In a characteristically systematic and brilliant series of papers during the last 4 years, aids and his colleagues have pursued a strategy based on the assumption that learning involves the rerouting of information about the CS and that learning centers and new pathways could be mapped by measuring changes in unit response latencies in different regions during differential conditioning (23,


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45, 80, 100). Rats implanted with chronic microwire electrodes were differentially reinforced with food after presentation of two different tones serving as CS+ and CS-. One day of pseudoconditioning, one day of conditioning, and one day of extinction were used routinely. Short latency changes were observed in many brain regions, in the following sequence: pontine reticular formation (before any behavioral changes), medial fore brain bundle, ventral thalamic n., dentate gyrus,. posterior thalamic n., basal ganglia, sensory cortex, field CA3 of hippocampus (oftt::n associated with overt CR appear ances), inferior colliculus, motor cortex, and field CAl of hippocampus. Many of these changes did not appear during pseudoconditioning, occurred only with sys tematic CS-US pairing, and were differential in intertrial activity was noted, tonic changes in arousal seemed unlikely. Detailed analyses suggested that changes in the posterior nucleus and the medial forebrain bundle were specific, probably related to motivational effects. Specific and marked effects were noted especially in the pontine reticular formation and in field CA3 of hippocampus. Some reservations must be voiced about these experiments, although they repre sent an ingenious and promising approach. The exceptionally short latency changes found in some regions suggest that they may be due to centrifugal processes anala gous to differential tuning, which Olds himself suggested. Gabriel et at (36) have demonstrated extremely short latency (10- 15 ms) changes in medial geniculate units, and have suggested that such changes might reflect tuning of cells by centrifu gal influences to increase the response to CS+ and decrease it to CS-. Such tuning, while resulting from the specific effects of differential conditioning, need not have its origin in the cells displaying the short latency changes. In order to answer these and other reservations, future experiments should perhaps use differentiated "go go" responses and be designed to show the generalizability of the result to other types of stimuli and behaviors; controls are needed to rule out the possibility of undetected centrifugal influences. The tragic death of James Olds is not only a great loss to his many friends and colleagues, but a major setback to this field of research. We hope that the competent research team that he assembled will surmount this setback and continue this important line of investigation. The conditioned eye blink The classical conditioning of eye blink, nose twitch, or nictitating membrane response present marked advantages in terms of ease of estab lishment and relatively restricted neural mediation. Woody et at (126, 127) have studied units in the pericruciate cortex which respond to a click stimulus. During conditioning the click was followed by a glabellar tap eliciting eye blink. Micro stimulation of the cortical unit and electromyographic recording of the orbicularis oculi characterized the projection of the unit to the musculature. A fter conditioning, many units showed decreased latencies and threshold. The number of cells project ing to the eyelid were observed to increase. Similar results were obtained using a conditioned nose twitch. Woody ( 126) has conduded that the code for the memory of the learned task was not an increase in the absolute amount of unit firing, but rather in the number of cells projecting to the mediating musculature: postsynaptic responses were faciliated in an ensemble of cells projecting to a particular muscle



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group, caused specifically by conditioning but probably mediated by mechanisms in other regions. Berger et al (11) trained rabbits to a conditioned eye blink, using tone as the CS and an air puff as the US. Hippocampal activity was not elicited by the CS or the US initially, nor did it accompany the unconditioned response. A marked increase in unit activity in the hippocampus was observed early in training, which did not appear during pseudoconditioning, and preceded the CR by a substantial interval. This unit activity was seen only in the pyramidal layer of CA l , CA3, and CA4, and in the granule cells of the dentate. Similar effects were observed in the lateral but not the medial septal nucleus. It was suggested that these changes might be an early stage of engram formation, although it was recognized that other regions might be involved earlier, subsequently relaying responses to the hippocampus. Although there was a psuedoconditioning control in these studies, the possibility that these results reflect sensitization or response bias cannot yet be excluded. Further studies exploring the possibility of sensitization and utilizing differential discrimination seem desirable before one could conclude that the reported phenomena were specific to learning. The role of the hippocampus For more than a decade (52) the hippocampus has been implicated in learning, although the role of this structure still remains obscure. Thompson et al (119) point out that the earliest changes noted in conditioning appeared in the pyramidal layers CA l , CA3, CA4 of the hippocampus and in the dentate. An intriguing feature of the results of Olds, cited earlier, was that CA3 displayed altered unit responses later in conditioning than the dentate, but CA3 responses were of shorter latency than dentate responses. Further analysis showed that the flow of activity was from medial septum to CA3 to CA1 to lateral septum to dentate to entorhinal cortex. From entorhinal cortex, activity left the limbic system via cingulate and subiculum, but also fed back to CA3. Segal (99) suggested that the entorhinal response had a very long offset, producing long EPSPs in CA3 via the dentate: This tonic influence caused heterosynaptic facilitation of CA3 to subsequent septal input. This model attributes a critical role in short-term memory to CA3. Were this hypothesis true, longer intertrial intervals should cause poorer learning, contrary to fact. Further, the proposed mechanisms would seem to lead to sensitization to any stimulus during the sustained EPSP, rather than specific differentially enhanced responsiveness. Nonetheless, the relationship between the anatomy and the sequence and latency observed by several workers strongly sug gests the utility of further study of this system. Along this line of exploration, Izquierdo (50) has marshalled an impressive array of facts implicating the hippocampus in storage of short-term memories. Wallen stein (123) demonstrated marked theta activity (4--7 Hz) in CA3 during motionless arousal to the CS after but not before avoidance conditioning. Nicholas et al (78) shows that rats that received electroconvulsive shock (ECS) in the starting box of an appetitive maze showed less theta activity and greater amnesic effects (more errors) than rats that received ECS in another location. This finding suggests that placement in a task-related environment activates hippocampal circuits that pro duce theta related to release of a specific memory pattern and that ECS during that

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time may selectively inhibit the neural system that produced the released activity pattern, resulting in poorer retrieval of information later. Finally, Altschuler (1) showed that 10 weeks of exposure of young rats to a learning enriched environment caused a doubling of the density of synapses in area CA3. While none of these findings alone establishes a pivotal role for CA3 in learning, the cumulative effect is undeniably enough to suggest that further intensive study of this region is highly desirable. Differential generalization John and his coll(�agues (6, 55, 56, 58, 68, 88) hav� attempted to provide intrinsic controls for a wide variety of possible nonspecific factors that might contribute to altered ERP waveshapes or unit firing patterns by the use of a differential generalization paradigm. In the typical differential general ization experiment, cats were trained to differentiate between visual (V) and/or auditory (A) repetitive stimuli. Stimuli presented at frequency I (VI or AI) were the cue for conditioned response 1 (CRI), while stimuli at frequency 2 (V2 or A2) were the cue for conditioned response 2 (CR2). CR1 and CR2 were approach-approach, avoidance-avoidance, or approach-avoidance responses. After overtraining ranging from several months to several years, evoked potentials or unit responses were recorded during a number of long sessions of differential generalization: i.e. a novel visual or auditory stimulus at frequency 3 (V3 or A3), midway between frequencies I and 2, was occasionally interspersed within a long sequence of stimuli at the two conditioned frequencies, I and 2. Six kinds of stimulus response contingencies were possible during differential generalization sessions: CSICRI (correct), CSICR2 (error), CS2CR2 (correct), CS2CR1 (error), CS3CRI (CS1 like generalization) CS3CR2 (CS2 like generalization). The basic observation (55) was that in some anatomical structures, ERP waveforms during eS1CR!> CS2CR!> and CS3CR1 trials were similar but different from those observed during CS2CR2, CS1CR2, and CS3CR2 trials, which resembled one another. Computer pattern recognition methods were used to show that in each trial a variety of single evoked responSe waveforms (modes) would be observed and that the most prevalent mode was predictive of subsequent behavioral decision. Thus it became clear that the waveshape of the ERP under these circumstances was not solely determined by the physical stimulus but reflected the interpretation of the meaning of Ithe afferent input by the evaluating animal. Since the waveshape of the ERP was not stimulus bound but did correspond to the shape usually elicited by the appropriate cue for the response that was subsequently performed, it was concluded that the ERP waveshape could be sub stantially determined by a template at "readout" from memory. Thus it appeared that part of the ERP reflected afferent input (exogenous) while part reflected inter pretation of the meaning of that incoming information (endogenous). Since evidence exists that some interactions within ERPs are approximately linear, it was consid ered reasonable to treat ERPs obtained in differential generalization as a composite of exogenous and endogenous processes which could be separated by appropriate algebraic manipulation (5). Were this assumption valid, identical residual waves should result from algebraic manipulation of ERP waveshapes from appropriately selected combinations of trials with different stimulus-response contingencies.



15

Cross correlation between the appropriate corresponding residual waveshapes obtained by such computer implemented algebraic manipulation provided a quanti tative scale for the variance in the ERP from any brain region contributed by stimulus-bound exogenous and memory-related endogenous processes. This analysis revealed a systematic relationship, namely, that in any region the variance in the ERP due to endogenous processes was logarithmically proportional to the variance due to exogenous processes. The variance due to exogenous processes in any region reflects the local signal-to-noise ratio (SIN). In brief, the results showed that differ ential information about the sensory stimuli was widely distributed, with the highest SIN in structures belonging to the classifically defined specific sensory system of the given stimulus modality. Further, each region participated in representation of the past stimulus to an extent logarithmically proportional to the SIN of the stimulus in the region (5). These findings suggested a reconciliation between localizationist views and antilo calizationist views. Were Lashley's views of equipotentiality correct (71), the SIN for exogenous processes would have been equal in all regions, instead of showing the strong bias toward classical sensory-specific structures which was found. Con versely, were strict localizationist reasoning correct, only the sensory-specific struc tures would have displayed significant SIN instead of the continuous gradient which was observed. Thus both extreme positions are partly wrong and partly right. Sensory stimuli do appear to cause a specific informationally useful response in widespread anatomical regions, while at the same time, the SIN is markedly supe rior for any stimulus in the "sensory-specific" structures of the stimulus modality. These findings are highly relevant to the issues of compensation for brain damage in multiple-stage lesions discussed earlier. Ramos et al (88) used a chronically implanted movable microelectrode to study the activity of single units and ERP waveshapes in cats during differential general ization. Stringent criteria for identification of the single units were used (98), as well as for evaluation of poststimulus histogram patterns, indicating latency regions of unit responses which showed significant differences in fine structure: 29% of the units examined in visual cortex and lateral geniculate showed statistically significant differences in the 60-200 ms latency domain when data from trials resulting in different behavioral outcomes to the same neutral generalization stimulus were compared. Only 1 of 56 cells showed significant differences in the early components of response (less than 60 ms), suggesting that the observed differences cannot be attributed to nonspecific influences on the afferent input. These results were inter preted to indicate that two classes of cells exist in thalamus and cortex. "Stable" cells were those whose average firing patterns were determined by parameters of the physical stimulus. "Plastic" cells were those whose response patterns in late compo nents vary depending upon the meaning attributed to the afferent input. Stable cells thus appear to be those whose activity corresponds to the short latency, exogenous components of ERPs, while plastic cells are those whose activity corresponds to longer latency, endogenous processes. Bekhtereva (10) reviews theoretical specula tion concerning the stable and plastic cell approach to learning, as well as some of the experimental literature on this subject.


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An interesting feature of these studies was the relationship between unit firing patterns and local ERP waveshapes. Not only was no invariant relationship ob served between increased or decreased unit firing and polarity, but individual units which displayed one relationship over a period of time were observed to change to different relationships to the ERP waveshape somewhat later. These observations suggest that while local polarity and amplitude may have statistical significance for local ensembles as a whole, there is no a priori unit relationship which can be presumed to hold for all neural elements in a local ERP field (89). These data are difficult to reconcile with the belief, so widely held among researchers who study human ERPs, that a voltage peak at a particular latency in an ERP represents activity in a specific anatomical system. Ensembles of neurons in the cortex, as in every other region, are subject to a wide variety of synaptic drives. The polarity and latency of ERPs recorded from any brain region vary with dynamic changes in the configuration of synaptic inputs to the region, and cannot be interpreted as a static reflection of anatomical relations. How Does the ERP Reflect Subjective Processes?

The analysis of event-related potentials has become the most active branch of human neurophysiological research. Abundant evidence has accumulated that the short latency components of ERP faithfully reflect parameters of the physical stimulus. There is also widespread agreement that longer-latency portions of the ERP are not stimulus bound but reflect sUbjective reactions and stages of information processing related to the meaning or significance of the afrerent input. (For reviews see 15, 26, 59, 90). In view of the numerous parallels which hav!! been demonstrated between animal and human ERP phenomena, it seems reasonable to equate the short-latency, stimu lus-bound portion of the human ERP with the exogenous processes and the long latency, evaluative portions of the human ERP with processes identified as endogenous in animal research. As the voluminous literature on endogenous processes in humans is examined, one encounters a diversity of phenomena and becomes aware of a number of ener getic controversies. The diverse phenomena are produced from studies which differ in their research strategies, ranging across a wide spectrum from relatively univari ate, molecular questions to more multivariate or molar questions. Many of these different lines of investigation share a common feature, which is to evaluate the extent to which a representational system or model, constructed in the organism by some type of previous experience, alters the features of the ERP subsequently observed in that person. The exact experimental basis on which the representational system is constructed varies from strategy to strategy, but the changed ERP features can be interpreted as the result of a matching process between an endogenous representation and a subsequent exogenous input (114). As definite findings have emerged in the phenomena yielded from one or another of these strateies, they have almost immediately generated heated controversies. Again, these various controver sies also share a common feature, which is seldom whether the reported findings can be reliably and unequivocally demonstrated, ibut rather whether they can be ex-



17

plained as the result of some nonspecific factors such as pupillary dilatation, change in arousal level, subvocal verbalization, etc, not whether they necessarily reflect factors related to the past experiences which constructed a hypothetical representa tion system for specific information. Even when such specificity is conceded, there are closely related controversies about whether the observed ERP features are to be interpreted as reflecting the operation of an information evaluating system in the brain or the content of the operation ( 1 14, l iS). Undoubtedly there is a level on which each of these detailed issues can be legiti mately raised, and meticulous answers should and can be provided. On the other hand, it seems not only possible but probable that exclusive focus on trees entails the danger of delaying recognition that there is a forest. These diverse strategies are all lines of a common body of inquiry, and that inquiry might benefit from unequivo cal, overt identification. The inquiry is whether current techniques enable the clear demonstration of neurophysiological correlates of mental processes. By mental processes here is meant the same problem domain that was of paramount concern to Wundt and many of his contemporaries and that has so long been excluded from the domain of legitimate scientific inquiry-processes such as subjective experience, meaning, awareness, and consciousness. While valid objections and reservations can certainly be voiced about one or another aspect of many of the experiments in this field, the genre of endogenous ERP phenomena are most parsimoniously explicable as reflections of mental processes. By integration of human and animal studies carried out under conditions carefully constructed to be as comparable as possible, great progress may now be made .in analysis of the neurophysiological bases of conscious experience. The purpose of the remainder of this chapter is to provide a brief overview of the major lines of ERP evidence supporting these conclusions, also recognized by other recent reviewers ( IS, 1 14, 1 16). AROUSAL, HABITUATION, AND DISHABITUATION It has long been known that arousal enhances components of ERPs, while numerous articles have docu mented diminution of the ERP during habituation. It was probably Hernandez Peon (43) who first proposed that habituation was a form of dynamic inhibition in which a neural model or template formed during experience was used to exclude trivial or unimportant information from higher levels of the brain. Dishabituation, caused by mismatch between this internal representational system and reality, caused enhancement of the previously suppressed input, analogous to the effects of arousal. In other words, that which was predictable or had low information value was gradually excluded from exerting strong influences on neural activity, while unexpected events with greater information value achieved a higher SIN. Kha chaturian and his colleagues (65, 66) have devoted a great deal of meticulous attention to partialling out the contribution of increased arousal to the ERP changes reported when stimuli acquire meaning. Teyler et al (1 13) have ingeniously con structed an approach to the question of whether ERPs reflect specific semantic meaning, using a paradigm based upon the rudimentary processes of habituation and dishabituation. These workers used projected visual stimuli in three classes:


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geometric forms, linguistic stimuli with similar meaning (which might vary in every dimension except meaning), linguistic stimuli with different meaning (physically similar but semantically different). Habituation was achieved by presenting a series of stimuli of one class, and generalization was tested by presenting test stimuli of the same or different class. Dishabituation or generalization to these test stimuli was measured by the amplitude of the voltage between ERP peaks N} and P2 as a percentage of the excursion in the response to the habituated stimuli. Different anatomical regions displayed different ERP features in these studies. It was found that semantically similar stimuli do not dishabituate responses from temporal deri vations while semantically different stimuli do. These studies suggested that re peated presentation of a stimulus with a specific semantic meaning resulted in the construction of a representational system inhibiting neural response to physically different stimuli with the same meaning, but dishabituating when physically similar but semantically different words occurred. These workers obtained results suggest ing that a representational system can be built embodying an idea shared by a set of semantically similar stimuli. Picton et al (81) have recently reviewed ERP effects of attention. In general, increasing vigilance or directing attention to certain stimuli by counting them or otherwise making them relevant enhances ERP amplitude and particularly the N }-P2 component, even if the subject cannot predict the occurrence of relevant stimuli. However, in numerous studies of this genre the subject has been able to predict the time or modality of occurrence of relevant events. When such prediction is possible, it is well known that a negative DC shift (the contingent negative variation, or CNV) will occur. Thus it became controversial whether the enhanced N}-P2 simply reflected the buildup or collapse of the CNV and whether the observed effects were due to general arousal or specific f,:>cus of attention. Donchin et al (27) have ruled out this explanation, showing that the P300 component is independent of the CNV. Buser (15) points out the need to distinguish between unspecific arousal effects (intensive attention) and processes eliminating the effects of irrelevant stimuli (selective attention). Vidal et al (122) have de:veloped an elegant procedure using stepwise discriminant analysis to classify single ERPs to identical sensory stimuli with different expectations, which seems satisfactory to exclude the possibility of unspecific arousal effects since no a priori prediction by the subject is possible and since single ERPs can be classified without any necessity for averaging. This power ful approach offers the possibility of resolving many of these methodological philosophical issues. ATTENTION

SELECTIVE ATTENTION Unequivocal resolution of whether the effects of atten tion on the ERP are specific or nonspecific requ:ires a differential design, or a selective attention paradigm. By selective attention is meant attention to stimuli in one but not another modality or attention to one but not another dimension of stimuli within the same modality. The numerous experiments of this genre are intended to establish whether selective attention is based upon the selective blocking of afferent impulses in only one modality or a similar specification of admissible input within a modality



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accomplished by efferent tuning of afferent pathways (36). Such a mechanism would be a prestimulus, passive selective state. If selective attention cannot be explained by such efferent control, then differential ERP effects of relevant and irrelevant stimuli demand dynamic evaluation of the relevance of incoming information. Re viewing the extensive literature, Naatanen (77) concluded that most ERP studies of this issue are confounded either by inadequate controls over peripheral sensory parameters or by the possibility for the subject to predict the stimulus sequence. A similar position was earlier presented by Karlin (63). One early exception to these shortcomings is the work of Sutton, Tueting, Zubin & John ( I l l). This study showed that some but not other features of ERPs elicited by compound stimuli were attenuated depending upon the salient stimulus dimen sion established by an instructional set. In this study, both the relevant and irrele vant stimulus dimension were within the same sensory modality. However, the stimulus sequence could be predicted since instructions pertained to blocks of stimuli. A recent experiment by Hillyard et al (44) has neither of these shortcomings. The stimulus sequence was not predictable and all stimuli were within the auditory modality, effectively dealing with both of the major objections to studies of selective attention. Subjects listened to two random but concurrent series of tone pips sepa rately presented to the two ears. A small percentage of the tone pips in either ear had a slightly higher frequency than the standard, constituting signals. Component NJ, but not P2, was larger to stimuli presented to the attended ear. Responses to signals showed a large enhancement of a component much later than Nl or P2, the so-called P300 component whose peak occurs at about 300 msec. It was concluded that N I reflected stimulus set, by which was meant a subsequent processing stage matching the input against a memorized model. Other evidence (81) based on evaluation of far-field ERP established that there were no changes in the cochlear nerve response, showing that these changes were not due to selective gating of input but to differential processing of relevant input. These findings again emphasize the need to consider the ERP from a multivariate viewpoint rather than focusing exclusively upon any individual component. The preceding discussion exemplifies the ubiquitous ap pearance of a late positive component, LPC or P300, first described by Sutton, Braren, Zubin & John (110), which has subsequently been found in a host of studies involving the differential processing of information. Depending upon the specific experimental paradigm and the amount of information processing required, the latency of this late positive component (LPC) ranges from 210 to 6001 msec, as reviewed by Thatcher (114). It has been suggested that LPC represents the reaction of the subject to the significance or utility of the incoming information (77, 110, 111). These endogenous processes in the human ERP seem to correspond to the read out processes analyzed in animals by John and his group, cited earlier, which. are extensively distributed anatomically and are cortico-reticulofugal in origin. Niiiitiinen (77) argues that LPC is too late to reflect decision making but may be a nonspecific change of state after decision. This is contradicted by the work of Posner et al (84), who showed that differences in the ERP in a match-mismatch paradigm

THE P300 COMPONENT


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were clearly apparent in N,-P2 (140-200 msec) and P2-N2 (200-280 msec) as well as in P300, while choice reaction time was usually 250-340 msec. These findings again emphasize the necessity of evaluating the ERP as an overall process rather than as conceptually independent components. Alternatively, Donchin et al (24) have suggested that P300 represents feedback influence readjusting representational systems for future decision on the basis of previous outcomes, a position implicitly assuming a matching process. P300 has variously been attributed to the resolution of uncertainty, orientation to unexpected input, the activation of attention, the amount of stimulus information, activation of specific response systems appropriate to processed information, stimu lus-independent perceptual decisions, the detection of monitored events, matching of neural templates, or the amount of utilizatilon of cortical information processor (25, 39, 44, 112). It is clear from a study of this literature that there exists not one but many late positive components, with variable latencies reflecting the type and amount of information processing required by the task. DETECTION Squires et al (112) used a rating scale to evaluate the sUbjective confidence that a target signal had been detected. They concluded that the amplitude of N, reflected the quantity of signal informati.on received, while P300 reflected the certainty of the decision based on that information. Other work showed that P300 could be subdivided into an earlier PJA, related to unpredictability, and a later P3B, related to the processing of that information. In a paradigm far more natural than most ERP experiments, Cooper et al (21) combined eye movement and EEG measures to show that when an observer detected a target display in a landscape, a large positive wave appeared. This experiment suggests that a P300-like event occurs when an observer detects a member of a class of events defined as important, even though the stimulus was previously present. INFORMATION PROCESSING In a thorough review, Tueting (120) has docu mented the evidence that LPCs are related to information processing and has pinpointed a set of central issues about the inlterpretation of these phenomena. She raises the question of whether in a real world selective filtering of a passive sort can be of functional utility in view of the unpredictable sequence of events, suggesting that dynamic templates must be utilized. Evidence is summarized that P300 can be elicited by any significant event in any modality and is related to specific cognition and stimulus identification. Different scalp distributions and latencies at LPC under different analytical processes can contribute to electrical events in this latency domain. Campbell & Picton (17) concluded that the major determinant of P300 was the amount of task relevant information pfOl;essing. Surprisal, or probability, ex erted a relatively minor effect. Ruchkin & Sutton (92) introduced the conc:ept of equivocation, relative to P300. They suggest that the lower the a priori probability of an event, the greater the information provided if it occurs. The information received by the subject equals the information provided, minus the subjective uncertainty of perception, and equivoca tion is the difference between the information provided and received. These authors



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argue that for a fixed level of uncertainty, P300 will be smaller if the equivocation is bigger, but for fixed equivocation, P300 will be larger the greater the uncertainty. Again this supports the necessity of multivariate rather than univariate studies of the factors determining these complex electrophysiological phenomena. In technically as well as theoretically important work, Vidal et al ( 122) have shown that it is possible to replace the ERP by an event-related informatiom wave (ERIW) in which the dynamic spatiotemporal distribution of the mutual informa tion in the ERP caused by a discriminative stimulus can be mapped. These studies point the way to the mathematical technique for replacement of crude ERP features by precise informational quantification, and again emphasize that 'informational events are distributed through space and time in the ERP which must be analyzed using multivariate techniques. EXPECTED EVENTS In animal studies of responses to novel stimuli after training to familiar conditioned stimuli, John (51) described the production of emitted potentials in certain brain regions when expected events failed to occur. Subse quently, Sutton et al ( I I I) showed similarly that a human subject expecting an event produced a potential related to the nonoccurrence of that event. Since those early observations, a host of studies has appeared showing that positive voltages appear in the EEG at the time when absent events are expected to occur [reviewed in John et al (55)]. These studies suggest that a model of temporal sequences of past events has been constructed in the brain and is imposed upon afferent pathways as a monitor, such that a positive potential occurs when a mismatch takes place between the model and the sequence of events in reality.

In much of the literature reviewed above, the amplitude or latency of LPC could be interpreted as a nonspecific reflection of the operation of an informa tion processing system in the brain. Evidence that the particular LPC features elicited in a particular paradigm reflect the specific informational significance or meaning attributed to a stimulus came initially from studies of differential general ization in animals (5, 51, 55, 56) and has received corroboration from human ERP studies. Perhaps the first demonstration that the waveshape of the human ERP was determined by meaning as well as by the physical parameters of the stimulus was provided by John et al (57), who showed that large and small versions of the same geometric form elicited markedly similar ERPs. Brown et al (12) demonstrated that ERP differences were elicited by auditory words that had ambiguous meanings depending upon their context. Johnston & Chesney (60), using a symbol that could be interpreted as either a number or a letter of the alphabet, found that ERP waveshape in frontal but not occipital regions depended upon the contextual mean ing attributed to the stimulus. Grynberg-Zylberbaum & John (unpublished) con firmed these results, showing that parietal regions displayed ERP features related to meaning, while occipital regions reflected physical parameters of the visual stimuli. Begleiter et al (9) showed that ERP features elicited by a neutral stimulus reflected the nature of the expected rather than the actual stimulus in a design

MEANING


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closely similar to the differential generalization paradigm used in animals by John et al (55). In studies notable for their clear clinical implications, Shelburne (102) found that dyslexic children showed no difference in ERP amplitude response to consonant-vowe1-consonant trigrams which were either words or nonsense syllables, whereas good readers showed a larger amplitude to ERP to stimuli in the third trigram position of meaningful sequences. Buchsbaum et al (13) showed, using the congruence illusion, that the ERP amplitude of early (100-140 msec) components at the vertex was determined by the extent of departure of a generalization stimulus from an experimentally defined model. Begleiter & Porjesz (8) showed that ERP waveshapes to a medium intensity light flash randomly interspersed among bright and dim flashes depended upon the judged intensity, especially in the 140-250 msec latency domain, suggesting that the ERP waveshape activated a "memory trace about a specific experience." Chapman (19) averaged ERPs to sets of words in different meaning classes and used factor analysis to show that waveshape reflected semantic meaning independent of phonemic structure, similar to the results ob tained by Teyler (1 1 3), who used homophone:s to observe effects of specific word meanings in different contexts while controlling for acoustic pattern. All of the preceding experiments constitute critical challenges of the contention that ERP waveshape is determined by nonspe:cific factors, in that the ERP wave shape elicited by the same physical auditory or visual stimulus was found to be dependent upon contextual or semantic meaning and not upon physical parameters. It is difficult to account for any, let alone all of the observed effects, in terms of nonspecific factors. These experiments transcend the selective attention or differen tial relevance designs of the preceding sections" counterbalancing all features except meaning by their carefully devised experimental paradigms. Most of the experimental strategies described above can be conceptu alized by a model in which a representational system constructed by prior experi ence is matched against incoming information, with ERP spatial and latency features determined by the amount and type of information to be evaluated. Posner et al (85) directly explored the relevance of this model. They used the known fact that providing a model of the stimulus to be matched improves reaction time (RT) and accuracy to an extent not accountable by increased alertness. Using a letter match-mismatch paradigm, they showed that if the second letter was the same as the first (match), N]-P2 and P2-N2 were smalle:r than if mismatch occurred, and the significant ERP differences were often of shorter latency (225-350 msec) than RT (260-330 msec). Mismatch cases showed two clear positive peaks, while these seemed to merge in the match cases, perhaps because N2 was smaller. Using words as stimuli, they showed that attending to matches enhanced positive processes from 200 to 340 msec, whereas attending to mismatches yielded later ERP differences beginning at about 3 1 5 msec. They argued that enhancement of the late positive components to the matching stimulus occurred because of "pathway facilitation": the presentation of a letter excites particular pathways so that subsequent presentation of an identical or conMATCHING



23

cordant letter results in facilitation of processing to that letter (match condition). In the mismatch case there is less pathway facilitation and thus a longer latency and greater attenuation of the P300. Thatcher (1 14-1 17) has carried out the most detailed exploration of the match mismatch paradigm to date in an ingenious series of studies which yielded several important findings. These studies used a paradigm in which geometric forms, letters of the alphabet, or words emerged from a series of random dot displays which constituted a temporal noncontingent information probe reminiscent of Kha chaturian's paradigm. In this series of energy-equated displays, an initial informa tional stimulus emerged, to' be followed by a second concordant or discordant informational stimulus. Match and mismatch conditions were equi-probable. Sig nificant differences in the 250-350 msec latency domain were noted between random dot probes and informational stimuli, while differences between match and mis match stimuli were primarily detected between 300-400 msec. For linguistic stimuli these differences were maximal in occipital, parietal, and posterior temporal deriva tions. These studies showed conclusively that the features of the ERP in different anatomical regions were not determined by the actual physical stimulus but by the semantic context of the second informational stimulus. If the LPC was determined by a comparator operation involving cognitive rather than physical features in an internal representation. then similar LPCs should occur to stimulus pairs with similar meaning (semantic representation) even though physical features differed. When semantic identity occurred between the first and second words (e.g. synonyms and antonyms), prominent LPCs in the 440-460 msec latency domain were found. When the semantic meaning was compared, these differences were larger in left hemisphere derivations, particularly in parietal and posterior temporal regions. These data not only suggested that semantic congruence between a representational model and a subsequent stimulus elicited a characteristic, late (440-460 msec) LPC, but that linguistic mediation of the stimulus information differentially involved loci on the left hemisphere (114). In an extension of this paradigm, utilizing intervening logical operations. Thatcher (1 14) and Thatcher & Maisel (in preparation) showed that similar en hancement of LPC occurred in posterior but not anterior leads when a statement made by the second informational stimulus was logically true in terms of a logical operation defined by an intervening instruction, such as "is not equal to," etc. The findings reported in this series of papers seem to establish that although the LPC displays a strong effect of operations of the hypothetical central processor, a clear although weak effect of the content of the operation can also be discerned. These studies and the related studies reviewed in these articles provide compelling evidence that the features of the ERP are influenced dramatically by subtle semantic relations such as whether stimuli are synonyms or antonyms. whether they are bilingual equivalents or not, or whether they are logically true or not. The changing latency and/or anatomical locus of the LPC differences, observed as these informa tional parameters shift within an overall match-mismatch paradigm of otherwise

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constant design, provide perhaps the most convincing evidence that these ERP features relate to cognitive mental processes rather than the nonspecific or physical factors in these experiments. HEMISPHERIC LATERALIZATION In many of the studies reviewed in the pre ceding sections, clear evidence of differential, informational specific influences on ERP features has been provided. However, particularly interesting evidence of informational specificity of these phenomena comes from studies of the hemispheric differences in ERPs elicited by verbal and nonverbal stimuli. The interpretation of such differences is based Obviously upon the I!vidence of differential hemispheric specialization of informational processes obtained from studies of human patients with surgical separation of the cerebral hemispheres. Sperry (105), in a review of data from such patients, concluded that the left hemisphere is primarily responsible for mediation of verbal tasks, while the right hemisphere is more involved in nonver bal tasks such as perception of spatial relations. Although the evidence is not unequivocal (25), a large number of studies (re viewed in 116) suggest that tasks involving linguistic mediation show enhanced ERP components, especially LPCs, on left hemisphere locations, while nonverbal tasks seem to involve the right hemisphere differentially. Anderson (2) has raised the · possibility that these effects were related to the demonstrated right word shift of the eyes during decision about verbal meanings, but controls in other studies (116, 117) rule out this explanation. Fenelon (30), Callaway (16), Preston et al (86), and Conners (20) have presented evidence that poor readers show significant departures from the usual spatial pattern of ERP in verbal and nonverbal tasks. H. Ahn (unpublished doctoral dissertation) has obtained evidence strongly suggesting a left-hemispheric departure from normal ERP patterns in language underachievers, while arithmetic underachievers show a markedly different pattern which includes right hemispheric features significantly different from children with mathematical skills at grade level. These findings of ERP features differentially localized in the cerebral hemispheres in a fashion corresponding to known anatomical lateralization of abstract functions provide further evidence supporting the notion that ERP features reflect specific mental functions. Already they have been used! in clinical applications for the early differential diagnosis of learning disability (59).

CONCLUSIONS The preceding overview of the human event-rellated potential (ERP) and the animal single-cell, multi-unit, and sensory evoked potential studies of information process ing and cognition warrants the following conclusions: I . Reductionist attempts to ascribe perceptual or cognitive function to th'e activity of single cells or localized anatomical regions are both experimentally and logically untenable. They are based on an implicit nostalgia on the part of psychologists for the achievements of the "harder" sciences such as physics and molecular biology. Although atoms and E coli have proved to be fertile experimental and conceptual models in these disci-


25

plines, it should be realized that the problems faced by physiological psychology are unique and will ultimately be solved only by confronting the theoretical and experi mental perspectives demanded by the global, statistical, or Gestalt aspects of the nervous system.

2.

Theoretical perspectives that deal directly with the spatiotem

poral and configurational characteristics of neuronal activity and neuroanatomy offer promising leads in this direction.

3. The multiple-lesion literature (both human

and animal) suggests that function is not strictly localized but that multi potential and dynamic functional landscapes may be reordered, following brain damage, by appropriate behavioral experience.

4.

The most parsimonious explanation of en


dogenous processes in ERPs is that they reflect the subjective evaluation of incoming information in the context of expectations derived from previous experience.

5. Such

"representational systems" are anatomically extensive and may project a dynamic sensory template upon afferent sensory pathways.

6. Relative latencies of different

ERP processes probably reflect serial transfer between successive brain regions, but they must be analyzed as a multivariate process rather than a series of univariate steps.

7. The study of endogenous processes as reflected in the ERP and the analysis

of the underlying neuronal interactions has important clinical applications as well as philosophical implications. The neurophysiology of information processing and cognition is still in . the early stages of infancy (just as are parallel attempts in the area of computer pattern recognition and artificial intelligence). Much work remains to be done, even at the level of defining the questions that are to be asked and the experimental techniques that are to be used. Nevertheless, physiological psychology is at the threshold of reaching the stage of development where some of the aspirations of its founders may be within our grasp. Literature Cited

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