Evoked Resonant Neural Activity Reveals an Electrophysiologic Sweet Spot for Directional Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

OBJECTIVES

Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) is a well-established treatment for Parkinson's disease (PD), yet programming remains empirical and time-consuming. Evoked resonant neural activity (ERNA), a stimulation-evoked oscillatory response recorded from the STN, has shown promise as a biomarker for optimizing DBS therapy. This study aimed to evaluate the utility of ERNA as a physiologically grounded biomarker for optimizing STN DBS by 1) characterizing its sensitivity to stimulation parameters and directional contact location, 2) identifying its spatial distribution using directional leads, and 3) assessing correspondence between the ERNA-defined sweet spot and established clinical targets.

MATERIALS AND

METHODS

We recorded ERNA intraoperatively from 14 patients with PD who underwent awake STN-DBS implantation with directional leads. ERNA features were analyzed across stimulation amplitudes and contacts. A sweet spot was derived based on the anatomical location of stimulation settings associated with high ERNA magnitudes. Spatial correspondence with previously published clinical sweet spots was evaluated.

RESULTS

ERNA magnitude scaled with stimulation intensity and varied across directional contacts, showing consistent directional tuning across depths. Sweet spot analysis localized high-amplitude ERNA responses to a focal dorsal STN cluster at the motor-associative border. This ERNA-defined sweet spot closely aligned (centroid distance: 1.41-2.08 mm) with four independent clinical targets.

CONCLUSIONS

ERNA is a spatially specific and physiologically meaningful signal that aligns with clinically effective stimulation sites. Its sensitivity to directional stimulation highlights its high spatial resolution, supporting its use as an objective biomarker to guide DBS programming. Future studies should explore its utility in long-term therapeutic settings.

CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT04658641.