Impaired Mismatch Negativity Generation Reflects Widespread Dysfunction of Working Memory in Schizophrenia

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Abstract
Background: Impaired P300 (P3) generation is one of the most robust indices of brain dysfunction in schizophrenia. This study investigates the integrity of cognitive eventrelated potentials that precede P3 in an "oddball" paradigm to determine the earliest stages at which auditory information processing is impaired in schizophrenia. Methods: Cognitive event-related potential components including mismatch negativity (MMN), N2, and P3 were recorded from subjects with chronic schizophrenia who were receiving medication (n=20), from those who were withdrawn from drug treatment (n=11), and from healthy volunteers (n=11) during an auditory oddball paradigm. Recordings were made in both passive and active response conditions. The MMN, N2, and P3 amplitudes were compared across groups and the degree of MMN deficit was correlated with the degree of P3 reduction as a function of diagnostic group. Results: Schizophrenic subjects showed severe impairments in the generation of MMN and N2 as well as P3. Across groups, the decrement in MMN amplitude correlated significantly with the decrement in P3 amplitude. There were no significant between-group differences in MMN topography. Conclusions: The present study demonstrates that the neurophysiological deficits associated with schizophrenia, as reflected in cognitive event-related potential generation, are pervasive, extending even to the level of the sensory cortex. Mismatch negativity indexes the functioning of an automatic alerting mechanism designed to stimulate individuals to explore unexpected environmental events. Dysfunction of this mechanism may contribute to the deficit state associated with schizophrenia.