This study demonstrates that an automated programming algorithm using intraoperatively recorded evoked resonant neural activity (ERNA) produces acute motor improvements equivalent to expert clinician and imaging-guided STN-DBS settings in Parkinson's patients, with ERNA recordings taking under one…

Offers a rapid, objective biomarker-driven approach to standardize and scale DBS programming—improving consistency, enabling workflow efficiency and potential closed-loop neuromodulation—representing high translational clinical value though not a novel molecular therapeutic target.

BACKGROUND: Optimal outcomes from subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson's disease (PD) depend on accurate stimulation of an ideal functional target within the dorsolateral STN. Clinical programming is heuristic, and objective methods are needed to improve efficiency and consistency. OBJECTIVES: This study aimed to investigate the feasibility and acute motor benefit of STN-DBS programming, guided by intraoperatively recorded evoked resonant neural activity (ERNA) in patients with PD. METHODS: We assessed 12 patients with anatomically well-placed leads, 4-6 months following STN-DBS. The worst hemibody was tested off-medication. Acute motor benefit was double-blind assessed for three programming configurations: (i) chronic expert clinician settings, (ii) imaging guided, and (iii) an ERNA automated algorithm. We also compared therapeutic and side effect thresholds and the spatial distribution of fractionated current. RESULTS: ERNA programming improved hemibody Movement Disorder Society-Unified Parkinson's Disease Rating Scale-Part III scores by 75.7% (median) compared with off-stimulation. This was not different from imaging (81.6%, P = 0.19) or clinician programming (68.8%, P = 0.33). Therapeutic thresholds (P = 0.90) and side effect thresholds (P = 0.57) did not differ across conditions. ERNA programming was 0.8-1 mm ventral and 0.3 mm posterior to imaging and clinician programming. CONCLUSIONS: A programming algorithm based solely on ERNA achieved acute motor efficacy and tolerability equivalent to expert clinical and imaging-based approaches. ERNA recordings took <1 min, under awake and general anesthetic conditions. These findings suggest that intraoperative ERNA can provide a rapid, objective, and practical starting point for STN-DBS programming. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.