Effects of feedback delay on learning from positive and negative feedback in patients with Parkinson's disease off medication.

Phasic dopamine (DA) signals conveyed from the substantia nigra to the striatum and the prefrontal cortex crucially affect learning from feedback, with DA bursts facilitating learning from positive feedback and DA dips facilitating learning from negative feedback. Consequently, diminished nigro-striatal dopamine levels as in unmedicated patients suffering from Parkinson's Disease (PD) have been shown to lead to a negative learning bias. Recent studies suggested a diminished striatal contribution to feedback processing when the outcome of an action is temporally delayed. This study investigated whether the bias towards negative feedback learning induced by a lack of DA in PD patients OFF medication is modulated by feedback delay. To this end, PD patients OFF medication and healthy controls completed a probabilistic selection task, in which feedback was given immediately (after 800 ms) or delayed (after 6800 ms). PD patients were impaired in immediate but not delayed feedback learning. However, differences in the preference for positive/negative learning between patients and controls were seen for both learning from immediate and delayed feedback, with evidence of stronger negative learning in patients than controls. A Bayesian analysis of the data supports the conclusion that feedback timing did not affect the learning bias in the patients. These results hint at reduced, but still relevant nigro-striatal contribution to feedback learning, when feedback is delayed.