This application is a request for an ADAMHA Research Scientist Development Award, Level II. The overall aim is to provide time for the PI to engage in a multi-site systematic program of research on attentional and affective dysfunctions in schizophrenia. Attentional and affective dysfunctions have long been considered central deficits in schizophrenia, but have proven complex and difficult to measure. The startle eye-blink modification paradigm is of considerable interest because it promises to be a unique key to understanding these complex dysfunctions. The startle eye-blink paradigm involves the modification of the magnitude of the startle reflex by the presentation of a non-startling stimulus (prepulse) prior to the startle stimulus. In normal subjects, the size of the effect varies reliably with attention to the prepulse and affective properties of the prepulse. Therefore, depending upon the stimulus conditions, measures of startle eye-blink modification can provide non-verbal, non-voluntary indices of basic attentional and affective processes. Three projects are proposed in order to better understand the relationship of impaired startle eye-blink modification to attentional and affective dysfunctions in schizophrenia. The first project aims to test the state versus trait characteristics of startle eye-blink modification, and its attentional modulation, in a longitudinal study of recent-onset schizophrenic outpatients. The second project aims to test whether changes in startle eye-blink modification, and its attentional modulation, are part of early signs of psychotic exacerbation in a repeated-measures study of chronic schizophrenic patients. The third project aims to develop a new startle eye-blink modification paradigm to independently evaluate attentional and affective modulation of the startle reflex, first with college students and later with schizophrenic patients. In addition to these research projects, additional training in clinical science and neuroscience is outlined for the PI.
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