Subthalamic Activity Is Associated With Proactive Inhibition in Parkinson's Disease Patients

Abstract

The subthalamic nucleus (STN) is a key element of the indirect pathway of the basal ganglia (BG) and an effective target for improving motor symptoms in Parkinson's disease (PD) using deep brain stimulation (DBS). While dopamine neuron loss in PD results in a net shift towards increased inhibitory output from the BG, the precise mechanisms by which STN contributes to diminished movement remain unclear due to the complexity and multiplicity of processes underlying response inhibition. We used a modified Go/NoGo task varying uncertainty about Go or NoGo responses to determine how changes in response inhibition are related to STN local field potentials measured in 19 PD patients operated for STN-DBS. When engaged in the task, low-frequency band (LFB, 2–7 Hz; including the theta band, 4–7 Hz) power was significantly increased by dopamine treatment. LFB power significantly increased when there was uncertainty about the requirement of executing or withholding a response compared to when a response was certain. Increases in LFB power in individual trials were also significantly associated with faster reaction times. By contrast, beta band (12–30 Hz) power exhibited an inverted profile: It was significantly decreased by dopamine treatment, increased by response certainty and associated with slower reaction times. Our results suggest that STN low-frequency activity during voluntary behaviour may complement and enhance information obtained from the beta band and should be considered as a possible biomarker for the regulation of inhibition in uncertain contexts.