Instability of prefrontal signal processing in schizophrenia.
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.


METHODS
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.
Winterer
Georg
G
Genes, Cognition and Psychosis Program, NIH, NIMH, 10 Center Dr., MSC 1379, Bethesda, MD 20892, USA.
Musso
Francesco
F
Beckmann
Christian
C
Mattay
Venkata
V
Egan
Michael F
MF
Jones
Douglas W
DW
Callicott
Joseph H
JH
Coppola
Richard
R
Weinberger
Daniel R
DR
D000328:Adult; D001931:Brain Mapping; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D012559:Schizophrenia / Q000175:diagnosis / Q000503:physiopathology*; D012565:Schizophrenic Psychology
D010100:Oxygen