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OBJECTIVE: The authors used functional magnetic resonance imaging (fMRI) to investigate brain activation in patients with schizophrenia and major depression while they performed two tasks—a vigilance task and a mental arithmetic task—that differed in cognitive complexity. METHOD: In the vigilance task, the participants had to press a response button whenever a specific number was seen on a screen inside the MR scanner. In the mental arithmetic task, the participants had to add two consecutive numbers and press the response button whenever the sum was 10. fMRI was performed with a 1.5-T MR scanner. Twelve patients with recurrent nonpsychotic unipolar major depression, 12 patients with schizophrenia, and 12 healthy comparison subjects were included in the study. RESULTS: Performance data showed that the patients were impaired relative to the comparison subjects and showed no difference in performance between the patient groups. The patients with schizophrenia, but not those with major depression, had less activation in prefrontal brain regions, relative to the comparison participants. However, subtracting brain activation during the vigilance task from activation during the mental arithmetic task showed that the schizophrenia patients had activation in parietal areas. CONCLUSIONS: A double dissociation of parietal and frontal lobe activation was found for the schizophrenia patients and the depression patients. The greater parietal lobe activation in the patients with schizophrenia may reflect a compensatory strategy for the failure to recruit cognitive processes that involve frontal lobe areas when solving a mental arithmetic task.