Influence of Deep Brain Stimulation and Dopaminergic Therapy on Intrinsic Preference for Free Choice in Patients With Parkinson's Disease.

Abstract

Background: Humans prefer to make choices freely, even when doing so does not maximize future outcomes, which suggests that free choice is intrinsically rewarding. While value-based decision impairments are well documented in Parkinson's disease (PD), the mechanisms that underlie intrinsically motivated behavior remain unclear. In this study, we investigated how the dopaminergic (DAergic) and basal ganglia systems contribute to intrinsic reward in PD.

Methods: We designed a decision-making task to dissociate the intrinsic value of free choice from extrinsic reward. Twenty PD patients with subthalamic nucleus deep brain stimulation (STN-DBS) and 25 on DA therapy completed the task both while ON and OFF treatment. Performance was compared with 20 age-matched healthy control participants. We analyzed DBS electrode contacts, modeled activated tissue volumes, and examined cortico-subthalamic connectivity using high-resolution diffusion magnetic resonance imaging.

Results: PD patients OFF STN-DBS showed reduced preference for free choice, which increased when STN-DBS was ON. This effect was associated with recruitment of the right medial prefrontal cortex (mPFC). Acute ON/OFF DA therapy did not alter free-choice preference. However, patients with lower chronic DA doses-comparable to those in the DBS group-exhibited reduced free-choice preference compared with patients with higher chronic intake.

Conclusions: STN-DBS enhances free-choice preference by modulating the right mPFC-STN network, suggesting that this hyperdirect pathway influences intrinsic valuation of choice. These results indicate that STN-DBS promotes self-determined behavior even in risky contexts. Furthermore, chronic DAergic therapy may influence sensitivity to intrinsic reward.