Transcranial Ultrasound Stimulation of Internal Globus Pallidus Region and Motor Cortex in Parkinson's Disease
Yi‐Ying Lin, Nasem Raies, Talyta Grippe, Carolyn A. Gunraj, Can Sarica, Utpal Kumar Saha, Amitabh Bhattacharya, Ghazaleh Darmani, Robert Chen
Movement Disorders 2026, 41, 416-425 · 10.1002/mds.70095
Abstract
Background Many patients with Parkinson's disease (PD) have motor impairments despite dopaminergic therapy. Low-intensity transcranial ultrasound stimulation (TUS) is a non-invasive neuromodulation method with high spatial precision. The effects of motor cortex (M1) and internal globus pallidus (GPi) TUS on PD motor signs and cortical excitability are still uncertain. Objectives To compare the effects of M1 theta burst TUS (tbTUS), GPi region tbTUS, and dual-site (M1 + GPi region) tbTUS on neurophysiology and motor signs in PD patients. Methods Sequential bilateral real M1/sham GPi, real GPi/sham M1, and simultaneous dual-site tbTUS were administered in three separate study visits in random order to 13 PD patients. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III) scores and transcranial magnetic stimulation measures of cortical excitability were recorded at baseline and at several time points up to 60 min after sonication. Results MDS-UPDRS-III scores and bradykinesia subscores decreased compared with baseline after GPi tbTUS at 30 min after sonication. Motor evoked potential (MEP) ratio to baseline increased after M1 tbTUS compared with GPi tbTUS at 10 min after sonication (T10). The stimulation intensity to elicit 1 mV MEP ratio to baseline in the GPi tbTUS condition was higher compared with baseline and with M1 tbTUS and dual-site tbTUS at T10. MEP amplitudes and MDS-UPDRS-III scores did not significantly change after the M1 and dual-site tbTUS conditions. Conclusions Bilateral GPi region tbTUS is a potential non-invasive approach for improving motor signs in PD patients, particularly bradykinesia. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Abstract via europepmc.
Exposures
Exposure 1: Theta burst TUS (tbTUS) of primary motor cortex (M1)
Target: primary motor cortex — “motor cortex (M1)”
Device: Sonic Concepts · Sonic Concepts Inc. · custom two-element annular array ultrasound transducer (64 mm diameter, 500 kHz) ✓
| Waveform | theta burst | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 120 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 20 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Bilateral M1 theta burst TUS delivered to the motor hot spot determined by TMS, at a targeted depth of 30 mm. Sham used identical settings with ISPPA set to 0 W/cm2. White noise was played through earbuds during sonication to mask auditory cues.
Exposure 2: Theta burst TUS (tbTUS) of internal globus pallidus (GPi) region
Target: globus pallidus internus — “internal globus pallidus (GPi) region”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-500 (four-element annular array) ✓
| Waveform | theta burst | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 120 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 30 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 2.83, 5.33swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
Bilateral GPi-region theta burst TUS targeted via BabelBrain acoustic/thermal simulation and Brainsight neuronavigation to MNI coordinates x,y,z = 20,8,4 (individualized depth). Acoustic field simulation showed the sonicated volume also covered the external globus pallidus and putamen, so the target is referred to as the 'GPi region'. Sham used identical settings with ISPPA set to 0 W/cm2; white noise was played through earbuds during sonication.
Flags from extraction
n_subjects— 15 participants were enrolled/recruited but only 13 completed the study and were analysed; enrolled figure (15) is reported here per instructions.blinding— Only the offline video-based MDS-UPDRS-III rater is explicitly stated as blinded; blinding of participants to real vs sham sonication is not explicitly described.exposures[1].target.terms— Acoustic field simulation showed the sonicated volume also covered the external globus pallidus and putamen, so effects attributed to 'GPi tbTUS' may partly reflect neighbouring structures.