BRAIN ERPS AND COGNITIVE DEMAND IN SCHIZOPHRENIA

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Schizophrenic patients have shown a reduction in the amplitude of the P30O brain event-related potential (ERP) to tones, which has been reported to be maximal over the left temporal region in some studies. Our preliminary study replicated this finding and found evidence of reduced left brain dominance for dichotic words, which was most marked in schizophrenic patients with positive symptoms. This project aims to determine the effect of cognitive task demands on P300 reduction and asymmetry in schizophrenia, and to examine the relation of abnormal P3OO and dichotic listening asymmetry to symptom features (i.e., thought disorder and auditory hallucinations), gender and familial transmission of schizophrenia. A more long range goal is to determine the potential value of brain ERPs as predictors of therapeutic response to a conventional neuroleptic or to clozapine. ERP task demands will be manipulated using verbal (nonsense syllable) and nonverbal (complex tone) stimuli in easy binaural "oddball" tasks and in more difficult dichotic listening tasks. ERPs and behavioral responses will be recorded in 90 schizophrenic patients and 30 normal controls. Patients will be tested after a minimum 4 week drug-free period and again after 6 weeks of treatment with haloperidol. Treatment nonresponders who receive clozapine will be retested again after 6 weeks on this medication. In addition, ERPs of at least 30 of the schizophrenic patients in the unmedicated period and all normal controls will be measured during a continuous word recognition task, which is thought to reflect left medial temporal lobe function. Clinical ratings will be obtained on several scales including: Positive and Negative Syndrome Scale, Thought Disorder Index, and BPRS. ERP and behavioral measures in the auditory perception and memory tasks should yield converging evidence for evaluating hypotheses concerning the existence of left temporal lobe deficits in a subtype of schizophrenia with positive symptoms and distinctive response to neuroleptics.