Event-related potentials and factor Z-score descriptors of P3 in psychiatric patients.
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Biomedical subjects
Publications and source records attributed to E R John.
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While reports of EEG correlates of psychiatric disorders date back five decades, clinical sensitivity of the EEG to psychiatric disorders has been greatly enhanced with the advent of quantitative methods of analysis (QEEG). Using a QEEG methodology known as neurometrics we have identified distinctive electrophysiological profiles associated with different psychiatric disorders. With this method quantitative features are extracted from 2 minutes of artifact- free eyes closed resting EEG data, log transformed to obtain Gaussianity, age-regressed, and Z-transformed relative to population norms. Using small subsets of neurometric features, multiple stepwise discriminant analyses were used to construct mathematical classifier functions, the values of which are different for members of different a priori defined diagnostic groups. Using this approach, we have demonstrated high discriminant accuracy in independent replications separating many populations of psychiatric patients from normal as well as from each other, including major affective disorder, schizophrenia, dementia, alcoholism, and learning disabilities, as well as high accuracy of discrimination between known subtypes of depression (unipolar vs bipolar). The use of classification accuracy curves (CACs) which allow one to assess the sensitivity and specificity achieved by the discriminant functions is discussed. In addition, using cluster analysis, neurometric subtypes can be identified in several clinically homogenous populations. Preliminary results suggest that baseline membership in some neurometric subtypes may be highly correlated with response to treatment.
We have previously reported successful classification of patients with a variety of psychiatric disorders, using multiple discriminant functions based upon selected neurometric QEEG variables. In independent replications, these functions accurately separate patients with different DSM-III-R diagnoses from one another and from normals. This capability demonstrates that distinctive and replicable patterns of neurometric abnormalities are correlated with the clinical symptom clusters upon which DSM-III-R diagnostic criteria are based. However, patients with the same clinical diagnoses often respond very differently to the same treatments. Similar symptoms may arise from different pathophysiology. This study explored the 'natural structure' of a population of psychiatric patients in 8 diagnostic categories, using uninformed cluster analysis based upon the same set of neurometric variables found useful in separating each of these categories from normal. This preliminary numerical taxonomic approach reveals that groups of patients in each of these DSM-III-R categories contain subtypes with markedly different pathophysiology; further, patients in different DSM-III-R categories were aggregated together within each cluster, displaying similar pathophysiological profiles. Objective classification based on such physiological measurements may add information useful to improve treatment outcomes.
Changing the source and intensity of the auditory signal to six trained cats responding to meaningful auditory stimuli permits exogenous and endogenous processes in the auditory evoked potential to be separated. For short-latency exogenous processes, latency and amplitude depend on the parameters of the physical stimulus. However, the amplitude and shape of longer-latency endogenous processes are essentially independent of the location and intensity of the signal source and seem to be invariant concomitants of the significance of the signal.
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A movable microelectrode was implanted in adult cats trained to respond differentially to two different frequencies of light flicker. Unit responses were recorded along cortical and thalamic trajectories. The late components of the poststimulus response of 29% of the cells examined showed statistically significant differences when data from different behavioral outcomes to the same neutral generalization stimulus were compared.
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Cats with permanently implanted electrodes were trained to discriminate between trains of flashes or clicks at two different repetition frequencies. After substantial overtraining with these sensory stimuli, high levels of stimulus generalization were obtained to electrical stimulation of the reticular formation at either frequency stimultaneously with contradictory flicker or click stimulation at the opposite frequency resulted in control of the behavior by the reticualr stimulus. Lateral geniculate stimulation failed to show this effect.
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Cats were trained to discriminate between two different repetition rates of flicker and of click. Both approach-approach and avoidance-avoidance discriminations were used. After substantial overtraining, transfer of frequency discrimination was initiated to stimulation of the reticular formation using bursts of electrical pulses at the same two repetition rates. Significant levels of discriminated performance were obtained in all cats very quickly, indicating good cross-modal transfer between the peripheral discriminanda and the central stimuli. The literature on stimulus generalization and cross-modal transfer is reviewed and the findings of this experiment are discussed in that context. Certain conditions are defined which, if satisfied, justify the interpretation that stimulus generalization or rapid cross-modal transfer indicate that facilitation of subsequent tasks in a training sequence can be attributed to mediation by a specific neuronal mechanism established by training on a previous task. The present experiment was designed in view of such criteria. The evidence of good cross-modal transfer is interpreted to mean that brain mechanisms storing memories about discriminations between visual or auditory stimuli with different repetition rates can be effectively activated by gross electrical stimuli at the same repetition rates. Conflict trials were then carried out in which flicker or click at either frequency was contradicted by concurrent RF stimuli at the other frequency. As the current level of RF stimuli was parametrically increased, it was found that the central stimuli achieved almost complete control over the behavioral outcome in most cases. Concurrent transfer of training, using a counterbalanced training sequence, was then carried out to stimulation of the visual cortex, lateral geniculate, medial geniculate, and the intralaminar nuclei of the thalamus. In each case, rapid transfer was displayed by at least one animal. Once performance to brain stimulation at a given repition rate was established, little change was observed when the fine structure of the stimulus was altered by changing parameters of the stimulus burst. These findings are interpreted as providing support for a statistical theory of memory, since they constitute evidence that previously learned discriminative behavior can readily be elicited by compelling large ensembles of neurons in various brain regions to discharge with particular temporal patterns. It is difficult to reconcile these results with theories which postulate that learning establishes new synaptic pathways in which discharge must occur for memories to be retrieved.
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The ratio of standard deviation to mean, of the amplitude spectrum of well resolved single units, is shown to scale exponentially. This scaling is explained on the basis of a consideration of the relationship of extracellular voltage to voltage gradient, in a dendritic neuron model. A method is then advanced to extract, from multi-unit data, normally distributed amplitude spectra which are indistinguishable from those of well resolved single units. This method is suggested as a means of characterizing, in general, the unit activity obtained from chronically implanted preparations.
Adult cats were implanted with a movable microelectrode, and trained to respond differentially to two different frequencies of light flicker. Unit responses and evoked potentials were recorded along trajectories in the visual cortex and lateral geniculate nucleus. Although strong correlations are shown to exist between certain components of the evoked potential and peaks in the poststimulus histogram, it is demonstrated that it is impossible to specify a causal, predictive relationship.
Adult cats were implanted with a movable microelectrode and were trained to perform for food reward in response to diffuse light flicker at two different frequencies. After substantial overtraining, the patterns of cell response (poststimulus histogram) were obtained during generalization trials, using an intermediate frequency stimulus. An average of 29% of the cells examined in lateral geniculate nucleus and visual cortex traverses showed statistically significant differences in the late component of the neuronal response when different responses to the same generalization stimulus were compared.