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.
Javitt
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Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA. javitt@nki.rfmh.org
D001288:Attention / Q000502:physiology; D001303:Auditory Cortex / Q000503:physiopathology*; D001308:Auditory Perceptual Disorders / Q000503:physiopathology; D003265:Contingent Negative Variation / Q000502:physiology*; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D017397:Prefrontal Cortex / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D012565:Schizophrenic Psychology
D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid