Characterizing Microscale Patient-Specific Motor Cortex Activity and Circuitry after Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease

Introduction: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) is a recognized surgical approach for treating Parkinson’s Disease (PD) symptoms such as bradykinesia and rigidity, thought to work by desynchronizing cortical beta-band activity and entraining gamma-band activity. Precise localization of motor cortex subregions where these spectral changes occur, along with their connectivity to subcortical regions, is crucial for developing personalized closed-loop neuromodulation systems. In this study, we adopted a high-density cortical array to explore the spatiotemporal distribution of motor cortex activity patterns and engaged connectivity profiles after stimulating STN atlas-defined rigidity and bradykinesia “sweetspots”.

Methods: Three PD patients underwent STN-DBS implantation. During surgery, various electrode contacts were stimulated at different amplitudes, with the respective volume of tissue activation modeled to quantify the degree of bradykinesia and rigidity sweetspots stimulated. A 1024-channel cortical grid array was placed on the ipsilateral “hand-knob” region of the primary motor cortex, evaluating changes in beta (13-35Hz) and gamma (35-90Hz) spectral power for each stimulation condition. Spectral power changes were correlated with the degree of sweetspot stimulation and whole-brain functional connectivity patterns derived from group-level, resting-state fMRI for each channel.

Results: Increased stimulation of rigidity and bradykinesia sweetspots led to decreased beta band power in variable regions within motor cortex across patients. Increased gamma power consistently appeared at the anterior-medial portion of the hand-knob region in all patients. Correlations between high-beta and gamma power changes varied (patient 1: r=-0.51, patient 2: r=0.64, patient 3: r=-0.17). In two patients, channels with increased gamma power in the motor cortex were functionally connected to bilateral motor ventrolateral thalamus and putamen.

Conclusion : Our preliminary study suggests that motor cortex subregions where desynchronization of beta band activity following therapeutic STN-DBS may be highly variable across patients. Regions with elevated gamma band activity were localized to anterior-medial “hand-knob” on motor cortex that shares strong functional connections with striatum and thalamus. Using high-density electrode recordings, we identified a motor cortex subregion with elevated gamma power that may further elucidate the therapeutic mechanisms of DBS.