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OBJECTIVE: The authors sought to identify neural correlates of eating disorders in order to contribute to the debate on the genesis and classification of eating disorders and provide endophenotypes for genetic research. METHOD: Twenty-six female patients with eating disorders (10 with bulimia nervosa, 16 with anorexia nervosa) and 19 healthy female comparison subjects matched for age and education were presented with food and aversive emotional images while brain activity was recorded with functional magnetic resonance imaging. RESULTS: Women with eating disorders identified the food stimuli as threatening and disgusting. In response to these stimuli, the women with eating disorders had greater activation in the left medial orbitofrontal and anterior cingulate cortices and less activation in the lateral prefrontal cortex, inferior parietal lobule, and cerebellum, relative to the comparison group. In addition, women with bulimia nervosa had less activation in the lateral and apical prefrontal cortex, relative to the comparison group. Between-group differences in response to nonspecific emotional stimuli were found in the occipital cortex, parietal cortex, and cerebellum. CONCLUSIONS: A medial prefrontal response to symptom-provoking stimuli was identified as a common feature of anorexia and bulimia nervosa. This finding supports a conceptualization of eating disorders as being transdiagnostic at the neural level. The abnormal prefrontal reaction is associated with symptom-related material, whereas the occipital and cerebellar differences are nonspecific. An abnormal propensity to activate medial prefrontal circuits in response to inappropriate stimuli is common to eating, obsessive-compulsive, and addictive disorders and may account for the compulsive features of behavior in these conditions.