Subthalamic Activity for Motor Execution and Cancellation in Monkeys

Abstract

The subthalamic nucleus (STN) receives cortical inputs via thehyperdirectandindirectpathways, projects to the output nuclei of the basal ganglia, and plays a critical role in the control of voluntary movements and movement disorders. STN neurons change their activity during execution movements, while recent studies emphasize STN activity specific to cancellation of movements. To address the relationship between execution and cancellation functions, we examined STN activity in two Japanese monkeys (Macaca fuscata, both sexes) who performed a goal-directed reaching task with a delay that included Go, Cancel, and NoGo trials. We first examined responses to the stimulation of the forelimb regions in the primary motor cortex and/or supplementary motor area. STN neurons with motor cortical inputs were found in the dorsal somatomotor region of the STN. All these STN neurons showed activity changes in Go trials, suggesting their involvement in execution of movements. Part of them exhibited activity changes in Cancel trials and sustained activity during delay periods, suggesting their involvement in cancellation of planed movements and preparation of movements, respectively. The STN neurons rarely showed activity changes in NoGo trials. Go- and Cancel-related activity was selective to the direction of movements, and the selectivity was higher in Cancel trials than in Go trials. Changes in Go- and Cancel-related activity occurred early enough to initiate and cancel movements, respectively. These results suggest that the dorsal somatomotor region of the STN, which receives motor cortical inputs, is involved in preparation and execution of movements and cancellation of planned movements.Significance StatementThe dorsal somatomotor region of the subthalamic nucleus, which receives motor cortical inputs, is important for motor control: Its lesion induces abnormal involuntary movements known as hemiballism; its increased and/or oscillatory activity is observed in Parkinson's disease; and its coagulation or deep brain stimulation ameliorates parkinsonian symptoms. Here, we examined neuronal activity of this region in monkeys while they performed a reaching task with a delay including Go, Cancel, and NoGo trials and demonstrated that its activity is involved in multiple motor functions: preparation and execution of movements and cancellation of planned movements. The present results will benefit our understanding of the neuronal mechanism of STN-related movement disorders and their better therapeutics targeting the STN in the near future.