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OBJECTIVE: Neurodegenerative or traumatic lesions of the frontal lobes often lead to abnormally aggressive behavior. The authors hypothesized that the imaginal evoking of scenarios involving aggressive behavior would be associated with a modulation of the functional activity in the human frontal cortex. METHOD: Regional cerebral blood flow (rCBF) determinations by positron emission tomography and psychophysiological measures of emotional responsivity were obtained in a group of 15 young healthy volunteers with good visual imagery abilities and no history of abnormal behavior while they imagined the same scenario with four variations involving emotionally neutral behavior and aggressive behavior. RESULTS: Compared to the imagined neutral scenario, the imagined scenarios involving aggressive behavior were associated with significant emotional reactivity and rCBF reductions in the ventromedial prefrontal cortex, suggesting that a functional deactivation of this cortical area occurs when individuals respond to the eliciting of imagined aggressive behavior. CONCLUSIONS: These results in healthy subjects further expand previous findings from animal and human studies by providing an in vivo functional demonstration of the involvement of the orbitofrontal cortex in the expression of aggressive behavior. They are also consistent with the hypothesis that a functional alteration of this cortical region may be present in individuals with pathological aggressive behavior.