Voxel-based analysis of P300 electrophysiological topography associated with positive and negative symptoms of schizophrenia

Abstract

Abnormal P300 waveforms of the event-related potentials during the auditory oddball task are one of the most consistent findings in patients with schizophrenia. In the present study, we sought to test the hypothesis that the abnormal P300 waveform results from composite representation of neural activity in anatomically distinct brain regions responsible for the manifestation of positive and negative symptoms. We used the low-resolution brain electromagnetic tomography (LORETA) to obtain current density images of the P300 component from 26 patients with schizophrenia. The statistical parametric mapping (SPM) was applied to the LORETA images in order to identify brain regions that are related with the severity of psychotic symptoms as evaluated by the Brief Psychiatric Rating Scale (BPRS). The BPRS Total score was negatively correlated with the P300 current density in the left superior temporal gyrus (r=−0.615, corrected p=0.009) and that in the right medial frontal region (r=−0.571, corrected p=0.019) by means of SPM single-subject covariates model. These brain regions were included in the region-specific P300 sources as represented by the current density maxima (corrected p<0.05) using SPM one-sample t-test. A subsequent region-of-interest analysis of Pearson correlations revealed specific relationships between the Positive subscale score and the mean current density in the left superior temporal gyrus (r=−0.528, p=0.005) and between the Negative subscale score and the mean current densities in the medial frontal region (r=−0.551, p=0.003) and left superior temporal gyrus (r=−0.499, p=0.009). These results indicate that functional disturbances of neural networks involving the medial prefrontal and superior temporal regions may be responsible for the generation of positive and the negative psychotic symptoms of schizophrenia.