Transcranial Pulse Stimulation Enhances Dexterity in Parkinson's Disease: A Randomized Sham-Controlled Clinical Trial

BackgroundTranscranial focused ultrasound, capable of reaching deep brain areas with exceptional precision, represents cutting-edge technology in non-invasive brain stimulation. Current understanding of the neuromodulatory effects of focused ultrasound in Parkinsons disease (PD) is based on small-scale, exploratory studies, with no available data on functional or structural magnetic resonance imaging (MRI) outcomes. MethodsIn the largest prospective, randomized, sham-controlled clinical trial to date on focused ultrasound neuromodulation in PD, the efficacy of transcranial pulse stimulation (TPS) in alleviating sensorimotor symptoms in patients with mild PD was evaluated. In a crossover design, 30 participants underwent six sessions of both verum and sham TPS targeting the sensorimotor network. Clinical and neuropsychological assessments were administered at baseline, one day post stimulation, and one month post stimulation for both conditions. Structural and functional brain changes were assessed using task-based functional MRI and diffusion tensor imaging (DTI). ResultsManual dexterity, measured via the coin rotation task, showed significantly larger improvement following verum compared to sham TPS. In contrast, gross motor symptoms improved similarly after both verum and sham TPS. Functional MRI during a coin rotation task revealed increased activation in the sensorimotor network following verum stimulation compared to sham. DTI indicated enhanced structural integrity in the primary somatosensory white matter following verum TPS compared to sham. ConclusionThese findings indicate that TPS produces behavioral, neurophysiological, and structural effects within the targeted sensorimotor network, and may represent a safe and effective adjunct to standard PD therapies. Trial registrationThis trial is registered on ClinicalTrials.gov (NCT04333511).