Intracortical Mechanisms of Mismatch Negativity Dysfunction in Schizophrenia

Event-related potentials provide an objective index of neurocognitive dysfunction in schizophrenia. Schizophrenia subjects show a decreased mismatch negativity (MMN) amplitude relative to age- and sex-matched controls, along with a characteristic pattern of MMN dysfunction across conditions. Deficits in MMN generation are accompanied by (1) impaired precision of auditory sensory memory performance and (2) an interstimulus-interval-dependent deficit in auditory N(1) generation. Similar deficits are observed following systemic or local infusion of N-methyl-D-aspartate (NMDA) antagonists, supporting glutamatergic and phencyclidine/NMDA models of the disorder. Deficits in MMN generation may also be seen following focal cortical damage, especially to the dorsolateral prefrontal cortex. MMN thus provides a useful tool for investigating mechanisms underlying brain dysfunction in schizophrenia.