Dopaminergic medication affects choice bias in Parkinson's disease

Objective: Assess dopaminergic effects on choice bias in Parkinson's disease (PD). Background: Bradykinesia, rigidity and resting tremor are the core symptoms of PD, but many patients also suffer from cognitive dysfunction. For instance, PD patients have an increased tendency to learn from aversive outcomes, and this tendency is reversed by dopaminergic medication. A prominent theory accounts for those observations by suggesting that phasic dopamine in the striatum couples motor and motivational functions, linking reward to action and punishment to inhibition. Accordingly, we hypothesized that this coupling is altered as dopamine is progressively depleted in PD, and might be restored by dopaminergic medication. As the main relay nucleus in striato-cortical projections, we hypothesize that GABAergic inputs to the thalamus mediate individual differences in the effects of medication on the coupling of motivation and action in PD. Methods: We included 30 patients with idiopathic PD without severe cognitive dysfunction (MMSE>26, FAB>13). Patients were measured in pseudorandomised order, both OFF (>12 hours after last dose) and ON dopaminergic medication (standardized dose of 200/50nmg of levodopa-benserazide dispers). In both sessions, patients performed a reinforcement learning task to disentangle the separate but interacting axes of motor response requirement (Go/NoGo) and motivational valence (reward/punishment). We investigated the effect of dopamine (OFF vs. ON) on choice and response speed. In both sessions, we quantified GABA concentration using magnetic resonance spectroscopy in the thalamus, a key relay node in the cortico-striatal circuit. Results: Behaviorally, levodopa improved patients' ability to learn to make the correct response (Go/Nogo), suggesting a cognitive enhancing effect (p=.072). Furthermore, patients ON medication responded faster to get a reward, yet were slower to avoid a punishment (p=.062). Conclusions: These preliminary statistical trends suggest that effects of dopamine in PD should be understood as a stronger coupling of action to reward, rather than a simple change in reward/punishment sensitivity. The study will include more patients to substantiate these findings, and test whether individual differences in the behavioral observations are related to thalamic GABA levels.