Distinct Roles of the Human Subthalamic Nucleus and Dorsal Pallidum in Parkinson's Disease Impulsivity

BACKGROUND: Impulsivity and impulse control disorders are common in Parkinson's disease and lead to increased morbidity and reduced quality of life. Impulsivity is thought to arise from aberrant reward processing and inhibitory control, but it is unclear why deep brain stimulation of either the subthalamic nucleus (STN) or globus pallidus internus (GPi) affects levels of impulsivity. Our aim was to assess the role of the STN and GPi in impulsivity using invasive local field potential (LFP) recordings from deep brain stimulation electrodes. METHODS: We measured LFPs during a simple rewarding Go/NoGo paradigm in 39 female and male human patients with Parkinson's disease manifesting variable amounts of impulsivity who were undergoing unilateral deep brain stimulation of either the STN (18 nuclei) or GPi (28 nuclei). We identified reward-specific LFP event-related potentials and correlated them to impulsivity severity. RESULTS: LFPs in both structures modulated during reward-specific Go and NoGo stimulus evaluation, reward feedback, and loss feedback. Motor and limbic functions were anatomically separable in the GPi but not in the STN. Across participants, LFP reward processing responses in the STN and GPi uniquely depended on the severity of impulsivity. CONCLUSIONS: This study establishes LFP correlates of impulsivity within the STN and GPi regions. We propose a model for basal ganglia reward processing that includes the bottom-up role of the GPi in reward salience and the top down role of the STN in cognitive control.