Esstim: Non-invasive Synergistic Application of Transcranial Ultrasound and Tdcs for Motor Improvement in Parkinson’s Disease

Introduction: Motor symptoms are a major contributor to disability in Parkinson’s Disease (PD) and remain inadequately addressed by standard pharmacological therapy. This study evaluated the efficacy of Electrosonic Stimulation (ESStim), a novel non-invasive technique combining transcranial ultrasound stimulation (TUS) and transcranial direct current stimulation (tDCS), compared with TUS, tDCS, and SHAM.

Methods: In this single-center, randomized, double-blind trial at Spaulding Rehabilitation Hospital, 48 patients with probable PD on stable medication ≥30 days were randomized to ESStim, tDCS, TUS, or SHAM. Participants received 10 daily sessions (20 min each) targeting the primary motor cortex (M1) over two weeks. Follow-up assessments occurred at 1, 2, 4, and 6 weeks post-intervention. Primary outcome was change in motor score (UPDRS3, “ON” state). Secondary measures included SCOPA-Cog, electroencephalography, neurological examination, and sensor-based quantitative movement analysis. Analysis used intention-to-treat with last observation carried forward.

Results: One participant withdrew before stimulation; 47 completed the intervention (ESStim = 12, tDCS = 12, TUS = 12, SHAM = 11). Baseline UPDRS3 scores (mean = 22.5) did not differ between groups. Two-way ANOVA revealed a significant main effect of stimulation type (p < 0.001). Post-hoc analysis showed ESStim produced significantly greater motor score improvement than all other groups. tDCS and TUS did not differ from SHAM in absolute UPDRS3 change; however, relative change analysis showed tDCS differed from SHAM but remained significantly less effective than ESStim. The mean UPDRS3 improvement from the final stimulation to the last follow-up was approximately 4.7 points. No significant cognitive, safety, or EEG changes were observed.

Conclusion: ESStim was safe and yielded superior, sustained motor score improvement compared with TUS, tDCS, or SHAM. These findings support ESStim as a promising non-invasive neuromodulatory therapy for PD motor symptoms.