Timing and direction selectivity of subthalamic and pallidal neurons in patients with Parkinson disease

Current models of basal ganglia function suggest that some manifestations of Parkinson disease (PD) arise from abnormal activity and decreased selectivity of neurons in the subthalamic nucleus (STN) and globus pallidus internus (Gpi). Our goal was to examine the timing and direction selectivity of neuronal activity relative to visually guided movements in the STN and Gpi of patients with PD. Recordings were made from 152 neurons in the STN and 33 neurons in the Gpi of awake subjects undergoing surgery for PD. Corresponding EMG data were obtained for half the cells. We employed a structured behavioral task in which the subjects used a joystick to guide a cursor to one of four targets displayed on a monitor. Each direction was tested over multiple trials. Movement-related modulation of STN activity began on average 264±10 ms before movement initiation and 92±13 ms before initial EMG activity, while modulation of Gpi activity began 204±21 ms before overt movement initiation. In the STN, 40% of cells demonstrated perimovement activity, and of these 64% were directionally selective. In Gpi, 45% of cells showed perimovement activity of which 80% were selective. In both nuclei, directionally selective cells had significantly lower baseline firing rates than nonselective cells (41±5 vs 59±4 spikes/s in STN, and 50±9 vs 74±15 spikes/s in Gpi). These results suggest that STN activity occurs earlier than previously reported, and that higher neuronal firing rates maybe associated with decreased direction selectivity in PD patients.