Accelerated Transcranial Ultrasound Neuromodulation in Parkinson's Disease: A Pilot Study

Abstract Objective Low‐intensity transcranial focused ultrasound (TUS) is a novel method for neuromodulation. We aimed to study the feasibility of stimulating the bilateral primary motor cortices (M1) with accelerated theta‐burst TUS (a‐tbTUS) on neurophysiologic and clinical outcomes in Parkinson's disease (PD). Methods Patients were randomly assigned to receive active or sham a‐tbTUS for the first visit and the alternate condition on the second visit, at least 10 days apart. a‐tbTUS was administered in three consecutive sonications at 30‐minute intervals. We used an accelerated protocol to produce an additive effect of stimulation. Patients were studied in the OFF‐medication state. Transcranial magnetic stimulation (TMS)‐elicited motor‐evoked potentials (MEPs) were used to assess motor cortical excitability before and after TUS. Clinical outcomes after a‐tbTUS administration were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS)‐III. Results A total of 20 visits were conducted in 10 PD patients. Compared to the baseline, TMS‐elicited MEP amplitudes significantly increased following active but not sham sonication ( P = 0.0057). MEP amplitudes were also higher following a‐tbTUS than sham sonication ( P = 0.0064). There were no statistically significant changes in MDS‐UPDRS‐III scores with active or sham a‐tbTUS. Conclusions a‐tbTUS increases motor cortex excitability and is a feasible non‐invasive neuromodulation strategy in PD. Future studies should determine optimal dosing parameters and the durability of neurophysiologic and clinical outcomes in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.