Pitch and Duration Mismatch Negativity and Heschl's Gyrus Volume in First-Episode Schizophrenia-Spectrum Individuals.

Background. The mismatch negativity (MMN) brainwave indexes novelty detection. MMN to infrequent pitch (pMMN) and duration (dMMN) deviants is reduced in long-term schizophrenia. Although not reduced at first psychosis, pMMN is inversely associated with left hemisphere Heschl's gyrus (HG) gray matter volume within 1 year of first hospitalization for schizophrenia-spectrum psychosis, consistent with pathology of left primary auditory cortex early in disease course. We examined whether the relationship was present earlier, at first psychiatric contact for psychosis, and whether the same structural-functional association was apparent for dMMN. Method. Twenty-seven first-episode schizophrenia-spectrum (FESz) and 27 matched healthy comparison (HC) individuals were compared. EEG-derived pMMN and dMMN were measured by subtracting the standard tone waveform (80%) from the pitch- and duration-deviant waveforms (10% each). HG volumes were calculated from T1-weighted structural magnetic resonance imaging using Freesurfer. Results. In FESz, pMMN amplitudes at Fz were inversely associated with left HG (but not right) gray matter volumes, and dMMN amplitudes were associated significantly with left HG volumes and at trend-level with right HG. There were no structural-functional associations in HC. Conclusions. pMMN and dMMN index gray matter reduction in left hemisphere auditory cortex early in psychosis, with dMMN also marginally indexing right HG volumes. This suggest conjoint functional and structural pathology that affects the automatic detection of novelty with varying degrees of penetrance prior to psychosis. These brainwaves are sensitive biomarkers of pathology early in the psychotic disease course, and may serve as biomarkers of disease progression and as therapeutic outcome measures.