Subthalamic deep brain stimulation and chronic dopaminergic therapy enhance free-choice seeking in patients with Parkinson's disease

Abstract

BackgroundHumans prefer making choices freely, even when they dont maximize future outcomes, suggesting free-choice is intrinsically rewarding. However, whether reward-related brain networks influence choice preference remains unclear. In Parkinsons disease (PD), value-based decision impairments are well-documented, but mechanisms underlying intrinsically motivated behavior are poorly understood. This study investigates how the dopaminergic and basal ganglia systems encode intrinsic reward in PD. MethodsWe designed a decision-making task dissociating free-choices intrinsic value from extrinsic reward. Twenty PD patients with subthalamic deep brain stimulation (STN-DBS) and twentyfive on dopamine (DA) therapy performed the task ON and OFF their treatments. Their performances were compared to twenty age-matched healthy controls. To explore neural mechanisms, we analyzed DBS active contacts, modeled the volume of tissue activated, and examined cortico-subthalamic connectivity using high-resolution diffusion MRI. ResultsPD patients OFF STN-DBS exhibited reduced free-choice preference, which increased when STN-DBS was ON, particularly in risky choices. This effect correlated with the recruitment of the right medial prefrontal cortex (mPFC). DA therapy did not modulate free-choice preference acutely, but higher chronic DA levels correlated with increased free-choice preference. ConclusionsOur findings suggest STN-DBS enhances free-choice preference via the right mPFC-STN network, while chronic DA therapy amplifies free-choice sensitivity. This implies that freechoice preference is influenced by mPFC modulation, increasing impulsivity toward risky choices, and dopamines role in enhancing sensitivity to both extrinsic and intrinsic rewards.