Suppression of pathological oscillations with transcranial focused ultrasound in Parkinson's disease.

Transcranial ultrasound stimulation (TUS) is an emerging method for non-invasive neuromodulation of deep brain structures. However, to date, there is no evidence that TUS can directly modulate disease-related pathological oscillations in the same direction as known therapies. Inspired by clinical deep brain stimulation, in this randomised controlled cross-over study we probed the effects of pallidal TUS pulsed at 130 Hz on subthalamic beta-band activity, a biomarker in Parkinson's Disease (PD) in four male participants with PD. Beta-band power reduced in the ipsilateral subthalamic nucleus (STN) by 10.34% (95% CI:3.81% to 16.87%, p < 0.05, false discovery rate (FDR) adjusted). Beta power reduction was correlated between the ipsilateral (R2 = 0.980, p < 0.05, FDR adjusted), but not contralateral, STN and primary motor cortex. Bradykinesia, as measured by change in reaction time, was also reduced by 17.70% (95% CI:8.95% to 26.41%, p < 0.05, FDR adjusted). In this proof of concept study, we demonstrate that TUS can suppress pathological oscillations, potentially opening the door for therapeutic TUS (NCT06932185).