Dopamine Selectively Modulates the Outcome of Learning Unnatural Action-Valence Associations

Learning the contingencies between stimulus, action, and outcomes is disrupted in disorders associated with altered dopamine (DA) function in the BG, such as Parkinson disease (PD). Although the role of DA in learning to act has been extensively investigated in PD, the role of DA in "learning to withhold" (or inhibit) action to influence outcomes is not as well understood. The current study investigated the role of DA in learning to act or to withhold action to receive rewarding, or avoid punishing outcomes, in patients with PD tested "off" and "on" dopaminergic medication (n = 19) versus healthy controls (n = 30). Participants performed a reward-based learning task that orthogonalized action and outcome valence (action-reward, inaction-reward, action-punishment, inaction-punishment). We tested whether DA would bias learning toward action, toward reward, or to particular action-outcome interactions. All participants demonstrated inherent learning biases preferring action with reward and inaction to avoid punishment, and this was unaffected by medication. Instead, DA produced a complex modulation of learning less natural action-outcome associations. "Off" DA medication, patients demonstrated impairments in learning to withhold action to gain reward, suggesting a difficulty to overcome a bias toward associating inaction with punishment avoidance. On DA medication, these patterns changed, and patients showed a reduced ability to learn to act to avoid punishment, indicating a bias toward action and reward. The current findings suggest that DA in PD has a complex influence on the formation of action-outcome associations, particularly those involving less natural linkages between action and outcome valence.