Subthalamic nucleus single-unit activity in humans with Parkinson's Disease encodes both the rate of change and the magnitude of force during a sustained grip-force task

Abstract

The subthalamic nucleus (STN) is a primary target for Parkinson's disease (PD) neuromodulation therapies, yet its role in sensorimotor neural circuits remains unclear. We investigated the neuronal activity in the dorsolateral STN during a visually cued isometric grip-force task in the contralateral hand in humans with PD who were undergoing deep brain stimulation surgery. We found significant force-related changes in STN unit activity, especially immediately after force onset and offset, but minimal changes during movement preparation. The most substantive changes in single-unit activity occurred with changes in grip force (15 of 21 units, 71%) rather than during sustained grip (12 of 21, 57%). During sustained force, the neuronal spike frequency positively correlated with force magnitude in seven units (33%), and the spike frequency during the applied force differed from baseline in nine (43%) units, all clustered in the dorsolateral STN. During a phase of the task when force changes, six units increased their spiking, while four units decreased their activity. Units with increases in activity discharged at a median of 56.5 (IQR: 25 to 156) ms after mechanical squeeze onset, whereas units with decreases preceded squeeze onset by 69.5 (23 to 79) ms. When force was released, five units increased their activity, while eight units decreased their activity, at latencies of 153.0 (84 to 260) ms and 58.0 (38 to 76) ms after release onset, respectively. Our findings suggest that neurons in the dorsolateral STN encode dynamic changes in force to a greater extent than sustained force magnitude and may play greater roles in sensory feedback and movement refinement rather than movement preparation.