Exercise-Induced Modulation of Subthalamic Activity and Intra-Nuclear Connectivity

Treatments for Parkinson's disease (PD) include medications like levodopa, surgical interventions such as deep brain stimulation (DBS), and rehabilitative approaches like exercise. While levodopa and DBS effects on the subthalamic nucleus (STN) are well studied, how exercise modulates this circuitry is less clear. This study investigates the acute and long-term effects of a monthlong motorized cycling intervention on STN activity, using local field potential (LFP) recordings from 29 electrodes placed in 18 STNs across nine PD patients (8/1 M/F; age 66.4 ± 9.7 years, UPDRS 20.7 ± 2.56). While the acute changes were minimal, the long-term changes in LFP features were more pronounced in the dorsal STN compared with its ventral region. Repeated exercise sessions produced a progressive increase in total LFP power in the dorsal STN, driven by elevations in the aperiodic background; the ventral STN showed no significant change over the same interval. This aperiodic modulation parallels increases typically observed with levodopa or STN-DBS, suggesting engagement of overlapping-but not identical-neuromodulatory mechanisms. To probe intra-STN coupling, we quantified dorsal-ventral interactions using the imaginary part of coherency (iCOH) and the phase slope index (PSI). PSI values remained near zero (|PSI| < 0.05), indicating minimal directed coupling, whereas iCOH increased in the 24-29-Hz range. Given the absence of connection and nonzero iCOH, we posited a shared upstream driver acting on both subregions. Using a statistical SSTr framework mathematically able to confirm the presence of this upstream "hidden" source.