Greater left than right reductions of P3 amplitude in schizophrenia during auditory oddball tasks have been interpreted as evidence of left-lateralized dysfunction. However, the contributions of methodological factors (response mode, stimulus properties, recording reference), which affect event-related potential (ERP) topographies, remain unclear. We recorded 31-channel ERPs from 23 schizophrenic patients and 23 age- and gender-matched healthy controls (all right-handed) during tonal and phonetic oddball tasks, varying response mode (left press, right press, silent count) within subjects. Performance accuracy was high in both groups but patients were slower. ERP generator patterns were summarized by temporal Principal Components Analysis (PCA; unrestricted Varimax) from reference-free current source density (CSD; spherical spline Laplacians) waveforms, which sharpen scalp topographies. CSD represents the magnitude of the radial current flow entering (source) and leaving (sink) the scalp. Both patients and controls showed asymmetric frontolateral and parietotemporal N2 sinks peaking at 240 ms and asymmetric parietal P3 sources (355 ms) for targets (tonal R < L, phonetic L > R), but frontocentral N2 sinks and parietal P3 sources were bilaterally reduced in patients. A response-related midfrontal sink and accompanying centroparietal source (560 ms) were highly comparable across groups. However, a superimposed left temporal source was larger for silent count compared to button press, and this difference was smaller in patients. In both groups, left or right press produced opposite, region-specific asymmetries originating from central sites, modulating the N2/P3 complex. The results suggest bilaterally reduced neural generators of N2 and P3 in schizophrenia during auditory oddball tasks, but both groups showed comparable topographic effects of task and response mode. However, additional working memory demands during silent count may partially overlap in time the generation of the N2/P3 complex and differentially affect the asymmetry of P3 subcomponents, particularly when employing conventional ERP measures.
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