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OBJECTIVE: Mania has received little attention from a contemporary neuropsychological perspective despite its clear resemblance to the disinhibition syndrome sometimes seen after frontal brain injury, particularly injury to the inferior aspect of the prefrontal cortex. The purpose of this investigation was to describe the neuropsychological profile of severe acute mania by using a range of tasks selected primarily for the detection of localized neural disruption within the prefrontal cortex. METHOD: Fifteen acutely manic inpatients were compared with 30 nonpsychiatric subjects on tasks from the Cambridge Automated Neuropsychological Test Battery (Tower of London, spatial working memory, intradimensional-extradimensional attentional shift, and rapid visual information processing tasks) and on the Iowa Gambling Task, Stroop Color and Word Test, a verbal fluency task, and the California Verbal Learning Test. RESULTS: Discriminant function analysis identified deficits in sustained attention (on the rapid visual information processing task) and verbal learning (on the California Verbal Learning Test) as the best indicators of manic performance, rather than deficits on any of the tests of executive functioning. The model correctly classified 91% of subjects overall and 87% of manic subjects. Manic patients did not resemble patients with ventromedial prefrontal cortex damage in their performance on the Iowa Gambling Task. CONCLUSIONS: Acute mania is characterized by core deficits in verbal memory and sustained attention against a background of milder impairments in functions that are traditional measures of prefrontal cortex integrity (attentional set shifting, planning, working memory). The data do not implicate ventral prefrontal cortex disruption as a locus of pathology in acute mania. Verbal memory and sustained attention deficits may relate differentially to the state and trait characteristics of bipolar disorder.