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Background: Previous studies have reported evidence of structural and functional abnormalities in the anterior cingulate cortex of patients with schizophrenia. METHOD: The authors studied 19 male patients with chronic schizophrenia and 15 healthy male comparison subjects with functional magnetic resonance imaging and the novel Multi-Source Interference Task, a task designed to elicit robust dorsal anterior cingulate cortex activation in individual subjects. Group averaged and individual (region-of-interest-based) brain activation patterns were compared during the performance of control and interference trials. RESULTS: Performance (reaction times and accuracy) did not differ between healthy subjects and patients with schizophrenia. Comparison of interference and neutral blocks revealed activation in the medial wall of the prefrontal cortex in 93% (N=14) of the healthy subjects and 84% (N=16) of the subjects with schizophrenia. Sixty-seven percent (N=10) of the healthy subjects but only 16% (N=3) of the subjects with schizophrenia displayed maximum medial wall activation within the dorsal anterior cingulate cortex. CONCLUSIONS: The Multi-Source Interference Task produced robust activation in the medial wall of the prefrontal cortex during cognitive interference. Analysis of individual activation patterns revealed medial wall abnormalities in schizophrenia patients.