Charles Shagass - US grants

This long-term program of research into electrophysiological correlates of psychiatric illness aims to provide objective aids to psychiatric diagnosis and also clues to the dysfunctional neurophysiological mechanisms underlying these disorders. EEG and evoked potentials (EPs) are recorded in different, clinical groups and analyzed by computer. The rheoencephalogram (REG) is recorded; it is a noninvasive method for measuring regional cerebral blood flow by impedance plethysmography. Subjects are assessed clinically by standardized interviews, rating scales and personality inventories to provide systematic diagnostic, symptom pattern, and personality classification criteria that can be related to electrophysiological measures. Patients are retested in various stages of treatment. EPs are recorded from 16 locations in two paradigms: a) under passive conditions, with intermingled stimuli of several sensory modalities (electrocutaneous over left and right median nerves, visual pattern, auditory click); b) selective attention, subject required to count one of four randomly intermingled stimuli. Brainstem potentials are also recorded in the paradigm (a) session. Specific aims include: a) Replication and extension of previously found EP and EEG correlates of psychopathology, e.g., differences between schizophrenics and neurotics and between neurotics and normals. b) Determination of psychoactive drug effects on EP and EEG measures. c) Development and validation of an electrodiagnostic system based on EP and EEG measures that give replicable discriminations and are relatively insensitive to drugs. d) Determination of REG correlates of psychopathology, including discrimination between dementia and depression. e) By comparing attention-related changes in sequential EP events, to define the stages at which sensory information processing may be defective in various psychiatric disorders; a specific hypothesis to be tested is that defects in sensory "filtering" occur earlier in schizophrenia than in major depression. Disciplines involved include psychiatry, electrophysiology, clinical psychology and psychobiology.

This long-term program of research aims to elucidate deviate neurophysio processes associated with psychiatric disorders and to develop evoked potential (EP) and EEG indicators as objective aids to diagnosis and monitoring of treatments. Numerous EP and EEG differences between clinical groups have been demonstrated, but most are not sufficiently precise for immediate clinical application. The proposed research Involves two main lines of inquiry aimed at: 1. increasing the specificity of clinical differentiation through subtyping; 2. elucidating some basic netiropilysiological aspects of somatosensory EPs (SEPS) that relate to previously found correlates of psychopathology. Both approaches include evaluation of functional topography by "brain mapping" and also determination of effects of psychoactive drugs. 1. in . A series of subtyping hypotheses will be tested, utilizing available data for about 800 subjects. For example, with respect to predominance of negative or positive symptoms in schizophrenics, it is predieted that SEPs of positive symptom patients will contain higher amplitude early components than those of negative symptom patients. 2. SEP recovery functions. Our previous studies showed early SEP recovery to be deviant in many psychiatric disorders, but the SEPs that were measured represented a mixture of precentral and postcentral events that now can be separately identified and measured by means of topographic and recovery function methods. Recovery function measurements will focus on 7 components from 15 to 60 msec poststimulus; probable cortical generators have been identified for these components. Eight interstimulus intervals, from 0 to 90 msec will be used. The recovery measures will permit evaluation of dynamic - physiological properties of several cortical areas; these will be correlated with psychopathologic criteria. Repeat studies will be conducted to determine whether SEP recovery deviations in the major psychoses vary in relation to changes in clinical state.