Abstract
A growing body of evidence suggests that the midbrain dopamine system plays a key role in reinforcement learning and disruption of the midbrain dopamine system in Parkinson's disease (PD) may lead to deficits on tasks that require learning from feedback. We examined how changes in dopamine levels (“ON” and “OFF” their dopamine medication) affect sequence learning from stochastic positive and negative feedback using Bayesian reinforcement learning models. We found deficits in sequence learning in patients with PD when they were “ON” and “OFF” medication relative to healthy controls, but smaller differences between patients “OFF” and “ON”. The deficits were mainly due to decreased learning from positive feedback, although across all participant groups learning was more strongly associated with positive than negative feedback in our task. The learning in our task is likely mediated by the relatively depleted dorsal striatum and not the relatively intact ventral striatum. Therefore, the changes we see in our task may be due to a strong loss of phasic dopamine signals in the dorsal striatum in PD.
Highlights
It has long been hypothesized that the basal ganglia have a specific role in sequential motor control (Marsden, 1982) and to examine this both explicit and implicit sequence learning have been studied in Parkinson’s disease (PD)
We found that PD patients tested “ON” medication performed the worst, followed by the “OFF” medication group, with the healthy controls performing the best
When we examined the temporal evolution of the learning, we found that participants initially showed a negative impact of negative feedback, which may be related to an explorative strategy, as participants would be inclined to ignore some negative feedback early on while they were attempting to determine which sequence was correct
Summary
It has long been hypothesized that the basal ganglia have a specific role in sequential motor control (Marsden, 1982) and to examine this both explicit and implicit sequence learning have been studied in PD. Work has suggested a role for the basal ganglia and especially dopamine in reinforcement learning (RL), or learning from positive and negative feedback (Schultz et al, 1997; Schultz and Dickinson, 2000; Pessiglione et al, 2006). Previous work has shown that patients “ON” medication learn more from positive feedback and less from negative feedback, and patients “OFF” medication have the opposite learning profile (Frank et al, 2004; Cools, 2006; Rutledge et al, 2009)
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