Frequency- and layer-specific effects of high-frequency STN stimulation on mouse motor cortical areas in vivo

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective evidence-based therapy for Parkinson's disease; however, its effects on the motor network are unclear. In anesthetized mice we studied the layer (L)- and frequency-specific effects of DBS on the connectivity between STN and rostral and caudal forelimb area (RFA and CFA) layers, the respective homologs to human premotor and motor cortex. Multi-site extracellular recordings served to quantify local field potential-driven activity at rest and during burst STN stimulation at multiple stimulation-frequencies for 10 min. The combination of frequency-specific coherence and information flow dynamics from effective connectivity (EC) demonstrated that 160 Hz STN stimulation increases the high-gamma power in RFA and CFA. Additionally, 160 Hz STN stimulation reduced the beta- and high gamma-frequency coherence between RFA, CFA, and STN, as well as the EC from STN towards RFA and CFA, but no change in the connectivity from cortex towards STN was attested, demonstrating hyperdirect pathway activation. Our work provides empirical insights into the mechanisms of action of DBS, which represent an important basis for the further development of this therapy.