Learning from negative consequences is impaired by STN-DBS and levodopa in Parkinson’s disease

Abstract

CONTEXT: Subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa therapy are reported to produce impulsivity in PD. We tested the hypothesis that STN-DBS enhances impulsive decision-making and that this effect is masked by the beneficial influence of the concomitant reduction in levodopa therapy. AIMS: To compare learning from negative consequences in patients with PD receiving STN-DBS to those without surgery. SETTINGS AND DESIGN: We conducted a prospective study in the Movement Disorder Clinic of a tertiary care university hospital in India, recruiting 26 PD patients treated with STN-DBS (PD-DBS) and 25 matched control patients on medical therapy (PD-MED) alone. METHODS: Impulsivity and decision-making were assessed using the Iowa Gambling Task (IGT) at baseline and 3 months. Dopamine agonist dose was unchanged during the study period. IGT total and block scores were used to assess impulsive decision-making and task learning. STATISTICAL ANALYSIS: General linear mixed model involving repeated measures ANOVA was used to compare IGT total and block scores. RESULTS: There was no independent effect of STN-DBS on the IGT total score (P = 0.198). In the PD-DBS group, block scores worsened after surgery with a negative slope across blocks, suggesting a lack of task learning [TIMEFNx01BLOCKFNx01INTERVENTION [F (4, 46) = 4.810, P = 0.003, partial Eta-squared = 0.095]. In the PD-MED group, block scores were seen to improve from baseline and across the blocks. These contrasting effects remained robust when tested in the Drug ON or OFF states. In the PD-DBS group, better task learning and higher block 5 scores were associated with greater post-operative reductions in total LEDD [TIMEFNx01BLOCKFNx01LEDD [F (4, 46) = 3.818, P = 0.012, partial Eta-squared = 0.077]. CONCLUSIONS: STN-DBS did not independently affect a global measure of decision making. However, STN-DBS and dopaminergic medications were shown to exert subtle yet significant opposing effects on the ability to learn from negative consequences.