A Predictive Coding Perspective on Mismatch Negativity Impairment in Schizophrenia

Mismatch negativity (MMN) is a widely used biological marker for schizophrenia research. Previous studies reported that MMN amplitude was reduced in schizophrenia and that reduced MMN amplitude was associated with cognitive impairments and poor functional outcome in schizophrenia. However, the neurobiological mechanisms underlying the reduced MMN amplitude remain unclear. Recent studies suggest that reduced MMN amplitude may reflect altered predictive coding in schizophrenia. In this paper, we reviewed MMN studies that used new paradigms and computational modeling to investigate altered predictive coding in schizophrenia. Studies using the roving oddball paradigm and modified oddball paradigm revealed that the effects of conditional probability were impaired in schizophrenia. Studies using omission paradigms and many-standards paradigms revealed that prediction error, but not adaptation, was impaired in schizophrenia. A study using a local-global paradigm revealed that hierarchical structures were impaired at both local and global levels in schizophrenia. Furthermore, studies using dynamic causal modeling revealed that neural networks with hierarchical structures were impaired in schizophrenia. These findings indicate that altered predictive coding underlies the reduced MMN amplitude in schizophrenia. However, there are several unsolved questions about optimal procedures, association among paradigms, and heterogeneity of schizophrenia. Future studies using several paradigms and computational modeling may solve these questions, and may lead to clarifying the pathophysiology of schizophrenia and to the development of individualized treatments for schizophrenia.