Objective: Impaired cognitive-behavioral flexibility is regarded as a trait marker in anorexia nervosa patients. The authors sought to investigate the neural correlates of this deficit in executive functioning in anorexia nervosa. Method: Fifteen women with anorexia nervosa and 15 age-matched healthy comparison women underwent event-related functional MRI while performing a target-detection task. The task distinguished between shifts in behavioral response and shifts in cognitive set. It involved infrequent target and non-target distractor stimuli embedded in a sequence of prepotent standard stimuli. Results: Relative to comparison subjects, anorexia nervosa patients showed a significantly higher error rate in behavioral response shifting, independent of whether those runs also involved cognitive set shifting. During behavioral response shifting, patients showed reduced activation in the left and right thalamus, ventral striatum, anterior cingulate cortex, sensorimotor brain regions, and cerebellum that differed significantly from the comparison group but showed dominant activation in frontal and parietal brain regions. These differential activations in patients and comparison subjects were specific to shifts in behavioral response: except for thalamic activation, they were not observed in response to non-target distractor trials that required no alteration in behavioral response. Conclusion: Impaired behavioral response shifting in anorexia nervosa seems to be associated with hypoactivation in the ventral anterior cingulate-striato-thalamic loop that is involved in motivation-related behavior. In contrast, anorexia nervosa patients showed predominant activation of frontoparietal networks that is indicative of effortful and supervisory cognitive control during task performance.