Impaired generation of mismatch negativity (MMN) in schizophrenia

Abstract

Human brain has developed the neural system of automatic sound change detection as reflected by the mismatch negativity (MMN) Many studies including “omission‐MMN” study have given evidence for “memory trace theory”. Actually, omission‐MMN was evoked only with SOAs shorter than 160 ms, suggesting the existence of temporal window of integration (TWI) mechanism. This TWI of 160‐170ms corresponds to the length of the sound trace encoded in neural sensory memory. MMN has recently become one of favorable neurophysiological biomarkers in schizophrenia. A definite reduction in early schizophrenia was evident in MMN to duration (dMMN) but not frequency deviants. The impaired dMMN might be caused by the dysfunction of TWI. Importantly, dMMN might provide the prediction of conversion to psychosis when dMMN was recorded in clinically at risk‐mental state (ARMS) individuals. The main MMN generator is located in the superior temporal gyrus (STG) . Several neuroimaging studies have revealed structural abnormalities of STG in schizophrenia. MMN also suggests the impaired function of NMDA receptors. In the postmortem study, DARPP‐32 and calcineurin (CaN) are closely associated with the abnormalities in the dopamine and glutamate systems in schizophrenia. The DARPP‐32 and CaN‐related pathogenesis in schizophrenia were more severe in the STG than previously found in the prefrontal cortex. A meta‐analysis of MMN abnormality in schizophrenia exhibited a large effect size of 0.95 (CI=0.85‐1.04) . Based on the above findings, dMMN impairment in the STG is expected to be a promissing biomarker in schizophrenia.