Objective: Acute mania is characterized by increased responsiveness to positive incentives and underestimation of risks and potential punishments, suggesting alterations in the mesolimbic-cortical dopaminergic reward system. In this functional magnetic resonance imaging study, we examined neural correlates of monetary reward and punishment anticipation in manic patients compared with healthy controls.

Methods: Fifteen manic patients and 26 matched controls participated in a monetary incentive delay task, during which subjects anticipated to win or lose a varying amount of money. 7 patients were re-tested after remission. Varying both magnitude and valence (win, loss) of incentive cues allowed us to isolate the effects of magnitude, valence and expected value (magnitude-by-valence interaction).

Results: Both groups activated according to cued incentive magnitude bilaterally in the ventral striatum. These effects did not differ between groups. VS responses increased with increasing magnitudes, regardless whether gains or losses were anticipated. Differential effects were found for the magnitude*valence interaction in the left orbitofrontal cortex. Manic patients showed a positive and healthy controls tended to show a negative interaction effect in this region. Patients’ OFC responses increased as cued reward magnitude increased, and OFC responses decreased as cued punishment magnitude increased, whereas no such or even the inverse effect was observed in controls.

Conclusions:
The observed alterations are consistent with a state-related affective processing bias during the expectation of gains and losses which may contribute to clinical features of mania, such as the enhanced motivation for seeking rewards and the underestimation of risks and potential punishments.