A machine learning approach using P300 responses to investigate effect of clozapine therapy

Clozapine (CLZ) is uniquely effective as a treatment for medication resistant schizophrenia. Information regarding its mechanism of action may offer clues to the pathophysiology of the disease and to improved treatment. In this study we employ a machine learning (ML) analysis of P300 evoked potentials obtained from quantitative electroencephalography (QEEG) data to identify changes in the brain induced by CLZ treatment. We employ brain source localization (BSL) on the EEG signals to extract source waveforms from specified regions of the brain. A subset of 8 features is selected from a large set of candidate features (consisting of spectral coherences between all identified source waveforms at multiple frequencies) that discriminate (by means of a classifier) between the pre- and post-treatment data for the schizophrenics (SCZ) most responsive to CLZ. We show these same selected features also discriminate between pre-treatment most responsive SCZ and healthy volunteers (HV), but not after treatment. Of note, these same features discriminate the least responsive SCZ from HV both pre- and post-treatment. This analysis suggests that the net beneficial effects of CLZ in SCZ are reflected in a normalization of P300 brain-source generators.