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Defining the Pattern

Daniel C. Javitt, MD, PhD; Anne-Marie Shelley, PhD; Gail Silipo, MA; Jeffrey A. Lieberman, MD

Arch Gen Psychiatry. 2000;57:1131-1137.

Background  Brain mechanisms underlying deficits in precision of transient memory storage in schizophrenia were investigated using a combined behavioral and event-related potential approach. Performance was measured simultaneously in 2 tasks: an AX-type visual continuous performance test (AX-CPT), which required subjects to press a button whenever they saw a letter A followed by a letter X, and a mismatch negativity paradigm. The AX-CPT is designed to assess prefrontal function, whereas mismatch negativity assesses functioning of the auditory sensory memory system.

Methods  Subjects were 17 patients with chronic schizophrenia, 13 with recent-onset schizophrenia, and 20 normal comparison subjects. Potentials were recorded from 36 scalp locations in response to cue stimuli in the CPT and to duration- and pitch-deviant stimuli in the mismatch negativity paradigm. Behavioral measures including responses to incorrect cue-target sequences that should have been ignored ("false alarms") were analyzed as a function of cue-target interval.

Results  Chronic and recent-onset schizophrenic patients showed significantly decreased mismatch negativity amplitude but normal latency and topography. In the CPT, patients showed significantly higher rates of false alarms following incorrect cues ("BX" errors) and decreased rates of correct detections. Impaired performance correlated with decreased frontocentral event-related potential activation to incorrect cues that was manifest within several hundred milliseconds of cue presentation. All groups performed worse with increasing cue-target intervals. Patients were no more affected by increased cue-target interval than were controls.

Conclusions  Schizophrenic patients are significantly impaired in their ability to form and utilize transient memory traces to guide behavior. These deficits are associated with failures of cortical activation occurring within several hundred milliseconds of stimulus presentation. A similar pattern of deficit is observed across sensory and cognitive systems.

From the Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY (Drs Javitt and Shelley and Ms Silipo); New York University School of Medicine, New York (Dr Javitt); and Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill (Dr Lieberman).

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