Mismatch negativity (MMN) is a robustly abnormal brainwave in chronically ill schizophrenia that has generated interest as a disease presence biomarker. Reports of MMN reduction in first-episode schizophrenia have been equivocal, raising uncertainty about its reduction at first psychotic break. Here we tested 29 schizophrenia-spectrum participants under 1 year from their first hospitalization for psychosis and 40 age-, gender-, parental socioeconomic status-, and Wechsler Adult Intelligence Scales III Information-matched healthy controls on both pitch and duration MMN. Participants performed a visual checkerboard tracking task while standard (1kHz, 50ms, 80%), pitch-deviant (1.2kHz, 50ms, 10%) and duration-deviant (1kHz, 100ms, 10%) tones were presented over headphones (75 dB) and EEG was recorded. Independent component analysis was used to remove eye movements and visual stimulus processing activity. Groups did not differ in pitch MMN or duration MMN amplitudes. Smaller pitch and duration MMN amplitudes were associated with lower estimates of premorbid intellect in all participants and independently with greater positive symptoms in first hospitalized schizophrenia. Overall MMN reduction was not present in these relatively high functioning individuals at the first episode of schizophrenia, and therefore is not a good disease presence biomarker for this sample. Future research is warranted to determine the degree of MMN reduction at the first episode of psychosis across a greater range of cognitive impairment, the utility of MMN as an indicator of risk or diagnosis, and its role for understanding pathophysiological mechanisms in emerging psychosis.

Background: Functional connectivity abnormalities between Broca’s and Wernicke’s areas and the putamen revealed by functional magnetic resonance imaging (fMRI) are related to auditory hallucinations (AH). In long-term schizophrenia, reduced white matter structural integrity revealed by diffusion imaging in left arcuate fasciculus (connecting Broca’s and Wernicke’s areas) is likely related to AH. The structural integrity of connections with putamen and their relation to AH are unknown. Little is known about this relationship in first-episode psychosis (FEP), although auditory transcallosal connections were reported to play a role. White matter in the Broca’s-Wernicke’s-putamen language-related circuit and auditory transcallosal fibers was examined to investigate associations with AH in FEP.Methods: White matter connectivity was measured in 40 FEP and 32 matched HC using generalized fractional anisotropy (gFA) derived from diffusion spectrum imaging (DSI).Results: FEP and HC did not differ in gFA in any fiber bundle. In FEP, AH severity was significantly inversely related to gFA in auditory transcallosal fibers and left arcuate fasciculus. Although the right hemisphere arcuate fasciculus-AH association did not attain significance, the left and right arcuate fasciculus associations were not significantly different.Conclusions: Despite overall normal gFA in FEP, AH severity was significantly related to gFA in transcallosal auditory fibers and the left hemisphere connection between Broca’s and Wernicke’s areas. Other bilateral tracts’ gFA were weakly associated with AH. At the first psychotic episode, AH are more robustly associated with left hemisphere arcuate fasciculus and interhemispheric auditory fibers microstructural deficits, likely reflecting mistiming of information flow between language-related cortical centers.