Deep Brain Stimulation Can Differentiate Subregions of the Human Subthalamic Nucleus Area by EEG Biomarkers

Introduction: Precise lead localization is crucial for an optimal clinical outcome of subthalamic nucleus (STN) deep brain stimulation (DBS) treatment in patients with Parkinson's disease (PD). Currently, anatomical measures, as well as invasive intraoperative electrophysiological recordings, are used to locate DBS electrodes. The objective of this study was to find an alternative electrophysiology tool for STN DBS lead localization. Methods: Sixty-one postoperative electrophysiology recording sessions were obtained from 17 DBS-treated patients with PD. An intraoperative physiological method automatically detected STN borders and subregions. Postoperative EEG cortical activity was measured, while STN low frequency stimulation (LFS) was applied to different areas inside and outside the STN. Machine learning models were used to differentiate stimulation locations, based on EEG analysis of engineered features. Results: A machine learning algorithm identified the top 25 evoked response potentials (ERPs), engineered features that can differentiate inside and outside STN stimulation locations as well as within STN stimulation locations. Evoked responses in the medial and ipsilateral fronto-central areas were found to be most significant for predicting the location of STN stimulation. Two-class linear support vector machine (SVM) predicted the inside (dorso-lateral region, DLR, and ventro-medial region, VMR) vs. outside [zona incerta, ZI, STN stimulation classification with an accuracy of 0.98 and 0.82 for ZI vs. VMR and ZI vs. DLR, respectively, and an accuracy of 0.77 for the within STN (DLR vs. VMR)]. Multiclass linear SVM predicted all areas with an accuracy of 0.82 for the outside and within STN stimulation locations (ZI vs. DLR vs. VMR). Conclusions: Electroencephalogram biomarkers can use low-frequency STN stimulation to localize STN DBS electrodes to ZI, DLR, and VMR STN subregions. These models can be used for both intraoperative electrode localization and postoperative stimulation programming sessions, and have a potential to improve STN DBS clinical outcomes.