Asymmetric dopamine loss differentially affects effort to maximize gain or minimize loss

Background: Dopamine (DA) plays an important role in regulating effort expenditure for reward, but whether it is also involved in modulating effort to avoid punishment is not clear. Preference for approach towards rewarding stimuli or away from aversive stimuli is associated with asymmetric activation in anterior brain regions. Asymmetric DA signaling in subcortical-frontal circuits may therefore contribute to differentially energizing behavior towards approach or avoidance behavior. We tested this hypothesis in patients with Parkinson's disease (PD), characterized by asymmetric DA loss. Methods: Patients with greater DA deficit in the left (n=20) or right (n=19) hemisphere, performed a task that measures separately effort to approach (maximize gains) versuseffort to avoid (minimize loss), on and off DA replacement therapy. Results: When tested off medication, patients with relatively greater DA deficit in the left hemisphere showed greater approach deficit (less effort to increase gain than to avoid loss) whereas the opposite pattern of effort expenditure was demonstrated by patients with greater DA deficit in the right hemisphere. Performing the same task when medicated revealed increased willingness to expend effort, such that increased effort to maximize gain was associated left hemisphere improved DA function (reflected by reduced symptoms), while increased effort to avoid loss was related to right hemisphere improvement. Conclusions: These results suggest that asymmetry of DA levels modulates the differential exertion of effort toward attaining rewards versus avoiding aversive consequences, providing new insights into understanding the underlying pathophysiology of behavioral syndromes such as apathy and impulsive-compulsive disorders.