Differential Cortical Responses of Functional and Sensory Electrical Stimulation in Closed-Loop Tremor Suppression for Parkinson's Disease.

Functional electrical stimulation (FES) and sensory electrical stimulation (SES) are widely used in tremor suppression for Parkinson's disease (PD), however, their therapeutic efficacy varies significantly across individuals. This study investigated the differential cortical effects of FES and SES during closed-loop tremor suppression in PD patient, aiming to identify neurophysiological biomarkers for guiding personalized neuro modulation strategies. We developed an inertial based closed-loop tremor suppression system that delivers out-of-phase FES and continuous SES based on real-time tremor detection. Fifteen PD patients were recruited in tremor suppression trials while surface electroencephalography (EEG) and inertial-based movements of hand and forearm were measured. Both FES and SES significantly reduced tremor amplitude, with FES showing overall greater suppression (hand suppression rate: 60.72% vs. 48.31%, p >0.05; forearm suppression rate: 62.25% vs. 54.41%, p >0.05) where substantial inter-individual variability was observed. EEG analysis revealed that FES induced contralateral beta-band event-related desynchronization ( $\beta $ -ERD), whereas SES elicited beta-band event-related synchronization ( $\beta $ -ERS). These distinct cortical response patterns were significantly correlated with tremor suppression performance (FES $\beta $ -ERD: r = -0.629, p = 0.012; SES $\beta $ -ERS: r = 0.679, p = 0.005). Resting-state spectral analysis further revealed modality-specific changes in alpha power across sensorimotor regions. These findings revealed functional neurodynamic signatures associated with individual responsiveness to stimulation. The observed $\beta $ -band oscillatory responses may serve as candidate biomarkers for predicting individual treatment outcomes, offering a potentially biomarker-guided approach for personalized neuromodulation for PD tremor.