Electrophysiological Mapping of the Hyperdirect Pathway and Substantia Nigra in Deep Brain Stimulation for Parkinson's Disease

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established therapeutic intervention for Parkinson’s disease (PD), yet the optimal targets for maximum therapeutic efficacy and reduced side effects remain under investigation. Recently, the hyperdirect pathway (HDP), which links the motor cortex and STN, has garnered attention for its potential role in DBS efficacy, with its stimulation hypothesized to contribute significantly to clinical outcomes. This study aims to map electrophysiological responses in the HDP and substantia nigra (SN) regions using Python and R for data processing and visualization, assessing their distinct roles in DBS effectiveness and side effects.

Methods: We conducted probabilistic mapping on evoked potentials (EPs) captured during low-frequency stimulation at individual DBS contacts across 13 patients. EPs were spatially localized using EEG in each patient’s anatomical space and standardized to Montreal Neurological Institute (MNI) space. Python and R were utilized for voxel-wise and fiber-wise mapping, while topographical analyses were performed to delineate HDP (P3) and SN (P10) hotspots.

Results: Analysis revealed a consistent P3 hotspot in the posterodorsomedial STN region corresponding to the HDP, linked to therapeutic benefits, and a P10 hotspot within the SN, correlated with side effects. Statistical tests showed a significant correlation between P3 activation and clinical improvement, while P10 involvement was related to SN stimulation effects.

Conclusion : This study demonstrates distinct electrophysiological markers within the HDP and SN associated with clinical efficacy and side effects, respectively, in DBS for PD. The findings support the HDP as a critical target for optimizing DBS outcomes and minimizing adverse effects. Our Python and R-based analyses substantiate the role of precise neuroanatomical targeting, potentially enhancing DBS programming and clinical outcomes for PD.