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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National Institute of Mental Health (NIMH)
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Clinical Neuroscience and Biological Psychopathology Review Committee (CNBP)
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New York State Psychiatric Institute
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Kayser, Jürgen; Tenke, Craig E; Gil, Roberto et al. (2010) ERP generator patterns in schizophrenia during tonal and phonetic oddball tasks: effects of response hand and silent count. Clin EEG Neurosci 41:184-95
Kayser, Jürgen; Tenke, Craig E; Kroppmann, Christopher J et al. (2010) Current source density (CSD) old/new effects during recognition memory for words and faces in schizophrenia and in healthy adults. Int J Psychophysiol 75:194-210
Kayser, Jürgen; Tenke, Craig E; Gil, Roberto B et al. (2009) Stimulus- and response-locked neuronal generator patterns of auditory and visual word recognition memory in schizophrenia. Int J Psychophysiol 73:186-206
Tenke, Craig E; Kayser, Jurgen; Shankman, Stewart A et al. (2008) Hemispatial PCA dissociates temporal from parietal ERP generator patterns: CSD components in healthy adults and depressed patients during a dichotic oddball task. Int J Psychophysiol 67:1-16
Kayser, Jurgen; Tenke, Craig E; Gates, Nathan A et al. (2007) Reference-independent ERP old/new effects of auditory and visual word recognition memory: Joint extraction of stimulus- and response-locked neuronal generator patterns. Psychophysiology 44:949-67
Kayser, Jurgen; Tenke, Craig E (2006) Principal components analysis of Laplacian waveforms as a generic method for identifying ERP generator patterns: I. Evaluation with auditory oddball tasks. Clin Neurophysiol 117:348-68
Kayser, Jurgen; Tenke, Craig E (2006) Principal components analysis of Laplacian waveforms as a generic method for identifying ERP generator patterns: II. Adequacy of low-density estimates. Clin Neurophysiol 117:369-80
Kayser, Jurgen; Tenke, Craig E; Gates, Nathan A et al. (2006) ERP/CSD indices of impaired verbal working memory subprocesses in schizophrenia. Psychophysiology 43:237-52
Bruder, Gerard E; Wexler, Bruce E; Sage, Mia M et al. (2004) Verbal memory in schizophrenia: additional evidence of subtypes having different cognitive deficits. Schizophr Res 68:137-47
Friedman, M S; Bruder, G E; Nestor, P G et al. (2001) Perceptual asymmetries in schizophrenia: subtype differences in left hemisphere dominance for dichotic fused words. Am J Psychiatry 158:1437-40

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