Objective: To investigate the effect of pallidal deep brain stimulation (DBS) on reward learning in segmental dystonia.

Background: Reversal learning is impaired in patients with idiopathic segmental dystonia. Computational modelling of behavioural data suggests that abnormal D2R-mediated striatal plasticity underpins these findings. Pallidal DBS is an efficacious treatment for dystonia derived from stereotactic lesioning. Pharmacological inhibition of the Globus pallidum pars interna (GPi) in healthy primates leads to impaired learning of novel reward contingencies. How GPi-DBS affects reversal reward-based learning in patients with dystonia remains unclear.

Method: Fourteen patients with segmental dystonia (9f, 59±2.3 years, TWSTRS ON-DBS 9.6±1.6; OFF-DBS 12.9±1.9, s.e.m.) with chronic GPi-DBS performed a reversal learning task ON- and OFF-DBS in a pseudorandomized order. Participants were instructed to choose the most rewarding stimulus of a pair of images presented on a laptop screen. The probability of reward outcome was fixed at 80:20% and reward contingencies were reversed after 60 trials. Behavioural results were fitted into a classic reinforcement learning (RL) model that estimates the learning rate (α) and reward sensitivity (ß) and compared between stimulation conditions (paired t-tests). Statistical significance was set at p<0.05.

Results: While all 14 patients performed the task ON-DBS, three patients declined turning off the stimulation for the study. On average, active GPi-DBS led to slower reaction times compared with OFF-DBS (ON-DBS: 1.26±0.56s; OFF-DBS: 1.20±0.52s; t-test, p=0.0106). Furthermore, the learning rate (α) increased ON-DBS (t-test, p=0.04). Thus, patients were more likely to base their decision upon the shortly learnt value of reward. Reward sensitivity did not differ between stimulation conditions.

Conclusion: We present pilot data indicating that pallidal DBS modifies reward-based reversal learning in patients with segmental dystonia, which reflects in prolonged reaction times and increased learning rate α. While the role of the dopaminergic system on RL has been extensively studied, evidence pointing the GPi as an important mediator for RL – for instance through encoding of error signals – is recent. If pallidal DBS alters learning by modulating striatal plasticity or acting upon efferent projections to the dopaminergic system (e.g. through the lateral habenula) remains to be elucidated.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pallidal-deep-brain-stimulation-alters-reward-learning-in-segmental-dystonia-a-pilot-study/