Is source-resolved magnetoencephalographic mismatch negativity a viable biomarker for early psychosis?

Mismatch negativity (MMN) is an auditory event-related response reflecting the pre-attentive detection of novel stimuli and is a biomarker of cortical dysfunction in schizophrenia (SZ). MMN to pitch (pMMN) and to duration (dMMN) deviant stimuli are impaired in chronic SZ, but it is less clear if MMN is reduced in first-episode SZ, with inconsistent findings in scalp-level EEG studies. Here, we investigated the neural generators of pMMN and dMMN with MEG recordings in 26 first-episode schizophrenia spectrum (FE sz ) and 26 matched healthy controls (C). We projected MEG inverse solutions into precise functionally meaningful auditory cortex areas. MEG-derived MMN sources were in bilateral primary auditory cortex (A1) and belt areas. In A1, pMMN FE sz reduction showed a trend towards statistical significance (F (1,50)  = 3.31; p = .07), and dMMN was reduced in FE sz (F (1,50)  = 4.11; p = .04). Hypothesis-driven comparisons at each hemisphere revealed dMMN reduction in FE sz occurred in the left (t (56)  = 2.23; p = .03; d = .61) but not right (t (56)  = 1.02; p = .31; d = .28) hemisphere, with a moderate effect size. The added precision of MEG source solution with high-resolution MRI and parcellation of A1 may be requisite to detect the emerging pathophysiology and indicates a critical role for left hemisphere pathology at psychosis onset. However, the moderate effect size in left A1, albeit larger than reported in scalp MMN meta-analyses, casts doubt on the clinical utility of MMN for differential diagnosis, as a majority of patients will overlap with the healthy individual's distribution.