Schizophrenic patients have shown a reduction in amplitude of the P3 brain ERP to tones, which was maximal over left temporal lobe sites. In the initial project period, the investigator replicated this finding in a dichotic complex tone task and found reduced N2 amplitude and asymmetry in schizophrenic patients in a dichotic syllable task. This suggests that left hemisphere dysfunction in schizophrenia for verbal processing occurs as early as 200 ms after stimulus onset. N2 abnormalities in schizophrenic patients were present in both auditory and visual tasks, whereas P3 abnormalities appear to be modality specific. The investigator proposes to conduct four studies to determine the task and patient characteristics necessary for producing these ERP abnormalities and to further resolve their neurophysiologic mechanisms. Study 1 will record ERPs in a large sample of schizophrenic patients (n=120) and normal controls (n=40) on verbal and nonverbal binaural oddball tasks, and will assess the influence of response mode (silent counting, right hand or left hand). These large samples will enable the investigator to examine the relation of ERP abnormalities in schizophrenia to symptom features, outcome of treatment with neuroleptics, familial history of schizophrenia, and neuroimaging measures. Study 2 will develop and apply new verbal and nonverbal tasks that incorporate advantages of dichotic listening procedures, but utilize a simple oddball paradigm. Study 3 compares ERPs of schizophrenic patients and controls in auditory and visual continuous word recognition tasks, which are thought to reflect left medial temporal lobe function. Study 4 continues the investigator's study of visuospatial processing in schizophrenia using a revised paradigm designed to disentangle effects of selective attention and later cognitive processing. Patients will be tested while off medication and again after six weeks of treatment with haloperidol or an atypical neuroleptic (clozapine or risperidone). A more long range clinical goal is to contribute toward the development of tests that could predict response to treatment with conventional or atypical neuroleptic medications for schizophrenia.
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