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Epilepsy was the first clinical entity to which magnetic source imaging was applied; however, the technology available severely limited early studies. The introduction of large-array magnetic source imaging systems has enabled striking advances in the application of magnetic source imaging in epilepsy surgery programs. The superimposition of functional localization of epileptic sources on anatomic images from MR imaging or computed tomography allows precise definition of the area and extent of epileptogenic tissue for possible resection. Concordance of magnetic source imaging indications with other noninvasive studies may reduce that need for invasive studies in certain patient populations.

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Magnetic field tomography is a technique for extracting 3-dimensional estimates of current density in the brain, from non-contact, non-invasive measurements of the magnetic field generated by the brain. It allows visualisation of both cortical and subcortical focal activation patterns at millisecond intervals, and the relative time difference between active cortical areas. We have used this technique to study the activation history of discrete brain regions associated with the preparation for, initiation and inhibition of movement, and movement itself in a CNV paradigm. The strongest focal activities are found within well defined cortical regions, namely the auditory (A1), sensorimotor (SM1), medial parietal area (MPA) and anterior supplementary motor area (SMA). For the movement condition, activation history differs for the warning stimulus and the stimulus initiating movement.

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The P3 component of the auditory evoked potential has been shown to reflect "endogenous" processes related to cognition. This component was measured serially in seven patients who had confusional states or dementing illnesses that fluctuated in severity over time. The latency of P3 component reflected the clinical impression of changes in mental function for each of the patients. These results suggest that the P3 component of the auditory evoked potential provides an objective serial measure of cognitive state that may be useful in following patients with dementing illnesses and in evaluating the effectiveness of any specific therapy.

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A variation in the difficulty of an auditory discrimination was used to investigate the relationship between the event-related P165, N2 and P3 components of the auditory evoked potential. Equivalent increases in the latencies of all 3 components were found with increased task difficulty. The P165 component, however, could be differentiated from the two later components since it increased in amplitude with increased task demands while the N2 and P3 amplitudes remained constant. It is suggested that the P165, N2 and P3 components comprise a functional sequence in the processing of rare events and possibly involved in a subject's preparations for the future.

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Auditory brain stem responses (ABRs) were obtained from 66 chronic alcoholic patients. Forty-one percent of the patients had abnormal ABR indicated by prolonged interwave intervals. The incidence of brain stem abnormalities was related to age, the type and number of alcoholic neurological complications, and cerebral atrophy in computerized tomographic (CT) scan. There was a progressive increase in the incidence of abnormal ABRs with age and the number of alcoholic neurological diseases. Among the neurological complications of alcoholism, patients with cerebellar degeneration had the highest incidence of abnormal ABRs (83%). There was a high correlation between cerebral atrophy in CT scan and abnormal ABRs. The data suggest that laboratory methods such as the ABR and CT scan are useful in evaluating the extent of CNS abnormalities in alcoholic patients.

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The visual evoked response (VER) was monitored in eight women intraoperatively during anesthesia with halothane in oxygen administered via endotracheal tube. Control measurements were made prior to anesthetic induction in these unpremedicated patients. The latency of the positive peak designated P1 increased progressively from a mean of 113 +/- 10 (SD) msec in the awake state to the following values at indicated end-tidal halothane concentrations: 123 +/- 10 msec at 0.75 per cent; 130 +/- 9 msec at 0.90 per cent; 134 +/- 9 msec at 1.13 per cent. The differences among mean latency values at these anesthetic concentrations were insufficient to conclude that VER latency would be a useful monitor of anesthetic depth. However, significant effects were seen at clinical levels of halothane anesthesia, and the prolongation caused by anesthesia must be considered when using VERs to monitor central nervous system function during neurosurgery.

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Auditory brainstem responses were obtained from 52 alcoholic patients with or without neurological complications of alcoholism. Almost half of the patients had abnormal auditory brainstem responses manifested by a prolonged central conduction time (Wave I to V interval) without significant alterations in morphology. The incidence of abnormal auditory responses was related to the type and the number of neurological complications. Patients with Wernicke-Korsakoff syndrome, dementia or cerebellar degeneration had high incidence of brainstem abnormalities. All patients with 3 or more neurological complications had abnormal auditory brainstem responses.

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The late positive component (P3) of the feedback evoked potential was investigated in two tasks: the detection of near-threshold auditory stimuli, and the estimation of 1 s time intervals. When the intensity or probability of the threshold stimuli was varied in the detection task, it became apparent that the feedback P3 was related to the 'contingent probability' of confirming or disconfirming feedback given a particular response. In the time-estimation task the relative probabiliti-s of confirming and disconfirming feedback were altered by changing the time-window wherein a response was judged correct. In these experiments it was found that the feedback P3 component was highly dependent upon the probability of the feedback, and relatively independent of its confirming or disconfirming meaning. With decreasing probability of the feedback stimuli, the P3 component became larger, later, and somewhat more frontal.

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Long-latency auditory evoked potentials were recorded from two groups of patients, with and without dementia, and were compared with those from a population of normal subjects ranging in age from 15 to 76 years. A sequence of tones of two different frequencies (1000 Hz and 2000 Hz) was presented and each patient was asked to count the occurrences of the rare (P = 0.15) tones in the sequence. Evoked potential waveforms were averaged separately for the rare and frequent tone. Of the various evoked potential components elicited by the tones, the P3 component (latency 300-500 ms) was found to be the most sensitive to aging in normal subjects. It was also the only component which could be used to differentiate between the demented patients and the normal subjects or non-demented patients. The non-demented patients did not differ from normal in any waveform measure. The magnitude of the latency change of the P3 component in dementia relative to normal was sufficiently large that it may provide a practical and objective measure of dementia in a clinical setting.

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Auditory brain stem potentials were recorded from unrestrained rats and from cats paralyzed with Flaxedil, before and after ingestion of intoxicating dosages of alcohol. The acute effect of alcohol was a cumulative increase in the central conduction times of successive brain stem potential peaks. Statistically significant latency changes were found for peaks attributed to neural structures as far peripherally as the medulla. This depressive influence of alcohol on sensory transmission was independent of variations in stimulus intensity and body temperature.

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Auditory brain stem evoked responses were in unrestrained rats during periods of acute and chronic alcohol intoxication, alcohol withdrawal, and recovery. Acute alcohol administration altered the auditory brain stem potentials by a prolongation of both peak latency and central conduction time, beginning with early peaks. Similar but lesser effects affecting only the latter peaks were observed during chronic alcohol intoxication. By contrast, alcohol withdrawal resulted in a decrease in the peak latencies of auditory brain stem potentials and a facilitation of central conduction time. Recovery of the auditory brain stem potentials to the normal form required at least three to four weeks. The present study provides the first quantitative data, to our knowledge, on manifestations of alcohol tolerance and withdrawal.

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Auditory brainstem potentials were recorded from human subjects before and after an intoxicating dose of alcohol. Following alcohol ingestion there were significant, progressive increases in the latencies of brainstem potential peaks III through VII. No changes in peak amplitudes were found. The results indicate that alcohol has a depressive effect on neural transmission within the primary auditory brainstem pathway.

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Auditory evoked potentials were recorded from 47 subjects ranging in age from 6 to 76 years in order to assess the effects of maturation and aging on the evoked (N1 and P2) and event-related (N2 and P3) components. Because of clear differences in the effects of age on the event-related components between children (less than 15 years of age) and adults the subjects were divided into two populations for analysis. For adults there was a systematic increase in the latency and decrease in amplitude of each component with age. Also the rate of the age-related increase in latency was proportional to the latency of the component. The scalp distributions of both the stimulus-evoked and event-related components were found to vary with age yielding a more nearly equipotential distribution for older subjects. For children the latencies of the event-related components decreased with age. The stimulus-evoked components had latencies which were not significantly different from those predicted from the adult data. In contrast to the adult data, age affected the scalp distributions of the stimulus-evoked components differently than the event-related components. These results suggest an aging process is relfected in the auditory evoked potential which is not the simple inverse of maturational processes.

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Three experiments were conducted to evaluate the P300 component of the human evoked response as an index of bisensory information processing. On different blocks of trials, subjects were presented with auditory stimuli alone, visual stimuli alone, or with audiovisual compounds. In each series there were two possible stimuli, one of which was presented less frequently than the other; the subjects' task was to count the infrequent stimuli. In the first two experiments the information in the two modalities was redundant, whereas in the third the modalities provided nonredundant information. With redundant information, the P300 latency indicated bisensory facilitation when the unimodal P300 latencies were similar; when the unimodal latencies were dissimilar, the bisensory P300 occurred at the latency of the earlier unimodal P300. Reaction times paralleled P300 latency. When the information in the two modalities was nonredundant, both P300 amplitude and reaction-time data indicated interference between the two modalities, regardless of which modality was task relevant. P300 latency and reaction time did not covary in this situation. These data suggest that P300 latency and amplitude do reflect bisensory interactions and that the P300 promises to be a valuable tool for assessing brain processes during complex decision making.

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Fifteen subjects were presented with series of tones. Any one tone was either loud or soft, and in any one series the probability of one tone intensity was either 0.9 or 0.1. Subjects were instructed to count the frequent tones or to count the rare tones. The stimuli were also presented while the subjects were solving a word-puzzle. Event-related potentials (ERPs) were recorded from 9 scalp locations (F3, C3, P3, FZ, CZ, PZ, F4, C4, P4) referred to linked mastoids. ERP components were measured with a Principal Components analysis and the relations between these measures and the independent variables were evaluated with the ANOVA procedure. This paradigm allowed an evaluation of the effect of stimulus probability, stimulus relevance, and task relevance on the waveform of the ERPs. We conclude that the P350 component is enhanced whenever the eliciting stimulus is both rare and in some sense relevant to the subject's task and the degree of enhancement is greatest when the rare--relevant tone is loud. A "slow wave" component which follows P350 is related to the same variables but has a scalp distribution quite different from that of P350. The slow wave shows a progressive shift in polarity from negative to positive from the frontal to the parietal sites, while the P350 is of nearly equal amplitude (and positive) at the central and parietal sites and has a smaller (positive) and amplitude at FZ. A third prominent component, negative in polarity, peaking at about 210 msec, is most pronounced following rare stimuli, whether or not they were task relevant. The amplitude of N210 tended to be largest at the frontal electrode. This study then demonstrates that when suitable measurement techniques are used, multiple endogenous ERP components can be observed, each related to distinct aspects of cognitive behavior.

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A test of the stepwise discriminant analysis (SWDA) procedure for assessing single-trial event related potentials (ERPs) is presented. Discriminant functions (DFs) were built from a data base composed of single-trial ERPs from sixteen subjects who were presented trains of loud and soft tones. Loud tones occurred randomly on 10% of the trials. Subjects either counted the rare--loud stimuli or solved a hidden-word puzzle. Various DFs at three electrode sites (Fz, Cz and Pz) were obtained to assess the feasibility of performing pairwise discriminations between the various combinations of events which are defined by this procedure. For the pair of events which yielded the most striking differences between their average ERP waveforms it was possible to classify correctly, an average of 84% of the events using information from one electrode site, and 89% of the events if information from multiple electrode sites was used. A "subject-independent" DF was developed from these data and applied to data obtained from seven new subjects. This subject-independent function proved to be sufficiently generalized to classify correctly 81% of the trials. The nature of classification errors by this procedure is discussed.

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The waveform of the cortical event-related potential is extremely sensitive to variations in the sequence of stimuli preceding the eliciting event. The waveform changes were manifested primarily in the amplitudes of the negative component of the potential that peaked at 200 milliseconds, the positive component that peaked at 300 milliseconds, and the slow-wave components. A quantitative model was developed relating the waveform changes to changes in event expectancy. Expectancy is assumed to depend on a decaying memory for events within the prior sequence, the specific structure of the sequence, and the global probability of event occurrence. For stimuli relevant to the task, the less expected the stimulus the larger the amplitudes of late components of the event-related potentials.

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Cortical-evoked potentials were recorded from human subjects performing an auditory detection task with confidence rating responses. Unlike earlier studies that used similar procedures, the observation interval during which the auditory signal could occur was clearly marked by a visual cue light. By precisely defining the observation interval and, hence, syncrhonizing all perceptual decisions to the evoked potential averaging epoch, it was possible to demonstrate that high-confidence false alarms for accompanied by late-positive P3 components equivalent to those for equally confident hits. Moreover the hit and false alarm evoked potentials were found to covary similarily with variations in confidence rating and to have similar amplitude distributions over the scalp. In a second experiment wherein the signal intensity was increased to make signal presence and signal absence clearly discriminable and the a priori probability of signal presentation was varied from .5 to .9, it was demonstrated that correct rejections can be associated with a P3 component larger than that for hits. Thus it was possible to show, within the signal detection paradigm, how the two major factors of decision confidence and expectancy are reflected in the P3 component of the cortical-evoked potential.

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