The role of the orbitofrontal cortex and medial striatum in the regulation of prepotent responses to food rewards.

An impairment in learning to inhibit prepotent responses to positive stimuli is associated with damage to the orbitofrontal cortex (OFC) in rats, monkeys, and humans performing discrimination reversal, extinction, and detour reaching tasks. In contrast, a recent study showed that OFC-lesioned rhesus monkeys could learn to select the smaller of 2 quantities of food reward in order to receive the larger reward, at an equivalent rate to controls, despite the requirement to inhibit a prepotent response. Given this result, the aim of the present study was to further specify the contexts under which the OFC regulates responding and to identify additional components of limbic circuitry that contribute to such regulation. Marmosets with lesions of the OFC and medial striatum (MS), but not the amygdala, made more prepotent responses to a clear Perspex box containing high incentive food before learning to choose the box containing low incentive food, to obtain reward. However, having learned the incongruent incentive discrimination OFC- and MS-lesioned monkeys were impaired upon reversal of the reward contingencies, repeatedly selecting the previously rewarded low incentive object. These findings identify the critical contribution of the OFC and MS in the regulation of responding by affective cues.