Instability of prefrontal signal processing in schizophrenia

Georg Winterer, Francesco Musso, Christian Beckmann, Venkata Mattay, Michael F. Egan, Douglas W. Jones, Joseph H. Callicott, Richard Coppola, Daniel R. Weinberger

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Objective: Prefrontal dysfunction is considered a fundamental characteristic of schizophrenia. Recent electrophysiological evidence points to a major instability of signal processing in prefrontal cortical microcircuits because of reduced phase-synchronization (i.e., an increased stimulus-related variability [noise] of single-trial responses in the spatial and time domain). The authors used functional magnetic resonance imaging (fMRI) during a visual two-choice reaction task in order to measure, with higher topographic accuracy, signal stability in patients with schizophrenia and its relationship to more traditional measures of activation. Method: Twelve clinically stable inpatients with schizophrenia and 16 matched comparison subjects were evaluated. Event-related blood-oxygen-level-dependent responses were subjected to an analysis of residual noise variance and to independent data dimension independent component analysis in the medial prefrontal cortex. Results: In patients with schizophrenia, the authors found increased residual noise variance of the blood-oxygen-level-dependent response that predicted the level of prefrontal activation in these subjects. In the left hemisphere, residual noise variance strongly correlated with psychotic symptoms. Independent component analysis revealed a "fractionized" and unfocussed pattern of activation in patients. Conclusions: These findings suggest that unstable cortical signal processing underlies classic abnormal cortical activation patterns as well as psychosis in schizophrenia.

Original languageEnglish (US)
Pages (from-to)1960-1968
Number of pages9
JournalAmerican Journal of Psychiatry
Issue number11
StatePublished - Nov 2006
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


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