Evidence for abnormal cortical functional connectivity during working memory in schizophrenia

Objective: Disturbed neuronal interactions may be involved in schizophrenia because it is without clear regional pathology. Aberrant connectivity is f urther suggested by theoretical formulations and neurochemical and neuroana tomical data. The authors applied to schizophrenia a recently available fun ctional neuroimaging analytic method that permits characterization of coope rative action on the systems level. Method: Thirteen medication-free patients and 13 matched healthy comparison subjects performed a working memory (n-back) task and sensorimotor baselin e task during positron emission tomography. "Functional connectivity" patte rns, reflecting distributed correlated activity that differed most between groups, were extracted by a canonical variates analysis. Results: More than half the variance was explained by a single pattern show ing inferotemporal, (para-)hippocampal, and cerebellar loadings for patient s versus dorsolateral prefrontal and anterior cingulate activity for compar ison subjects. Expression of this pattern perfectly separated all patient s cans from comparison scans, thus showing promise as a trait marker. This re sult was validated prospectively by successfully classifying unrelated scan s from the same patients and data from a new cohort. An additional 19% of v ariance corresponded to the pattern activated by the working memory task. E xpression of this pattern was more variable in patients during working memo ry but not the control condition, suggesting inability to sustain a task-ad equate neural network, consistent with the disconnection hypothesis. Conclusions: Pronounced disruptions of distributed cooperative activity in schizophrenia were found. A pattern showing disturbed frontotemporal intera ctions showed promise as a trait marker and may be useful for future invest igations.