Neural activity of the subthalamic nucleus during voluntary movements in patients with Parkinson’s disease

Abstract

Microelectrode recording (MER) during electrode implantation for deep brain stimulation (DBS) can determine the boundaries of the subthalamic nucleus (STN), and track neural activity during rest and voluntary movement in Parkinson’s disease (PD) patients. However, the functional role of STN in motor control remains unclear, despite its effectiveness in stimulation. Single unit activity of STN was recorded in 16 patients with PD during implantation of deep brain stimulation electrodes. Electromyograms of forearm muscles and a phonogram featuring verbal commands were simultaneously recorded with MER. The patients were instructed to perform motor tests involving clenching their hand into a fist. Out of the 560 neurons studied, 93 (16.6%) responded to motor tasks. The registered neurons were classified into three patterns using the hierarchical clustering method of histograms of interspike interval density — namely, tonic, burst, and pause patterns. Sensitive neurons were classified according to their responses, with activation (76.9%) and inhibition (23.1%) being the two identified types. In 90% of cases, neuron activation preceded movement. Of the responses, 53.8% were classified as tonic and 46.2% as phasic. Two thirds of inhibitory responses were advanced, occurring 0.2–0.3 seconds before movement onset. One third of neurons were activated after movement initiation with a delay of 0.05–0.2 seconds. 83.3% of the inhibitory neurons responded tonically, while the remaining 16.7% responded phasically. Notably, all phasic reactions occurred before the onset of movement. A comparison of the parameters of sensitive and non-sensitive neurons revealed several differences. The findings suggest a potential physiological distinction between the two neuron types. All three patterns of activity were present in both types of neurons, but sensitive neurons exhibited a wider representation of pause neurons (57.9% vs. 49.5%). Additionally, burst and pause neurons responded to movements that featured significantly lower variance of multiple activity parameters, such as firing rate, burst index, mean burst length, and oscillation scores in the 8–12 and 12–20 Hz range. The distribution of sensitive neurons along the electrode trajectory through the subthalamic nucleus was analyzed. Sensitive neurons were located significantly more dorsally compared to non-sensitive neurons, and no sensitive pause cells were observed in the ventral half of the STN. Based on our findings, it is presumed that the pause pattern plays a critical role in both motor control and its related disorders in Parkinson’s disease. A diverse range of neuronal responses suggests a high degree of heterogeneity among STN neurons implicated in motor control. The presence of both delayed and advanced neural responses suggests that STN involvement in motor control encompasses both the preparation and initiation of movement, as well as the regulation of ongoing movements via afferent feedback. The range of neural responses aligns with the dynamic model of basal ganglia, which suggests that STN can perform distinct functional roles during different stages of movement, including initiation, control, and completion.