Transcranial ultrasound stimulation of motor networks in Parkinson’s disease informed by local field potential dynamics
Can Sarica, Ghazaleh Darmani, Hamidreza Ramezanpour, Marcus Callister, Brendan Santyr, Talyta Grippe, Regina Annirood, Nasem Raies, Jean-Francois Nankoo, Nardin Samuel, Mandy Yi Rong Ding, Artur Vetkas, Anton Fomenko, Jeffrey D. Schall, Mojgan Hodaie, Suneil K. Kalia, Agessandro Abrahao, Renato P. Munhoz, Alfonso Fasano, Samuel Pichardo, Robert Chen, Andres M. Lozano
Science Translational Medicine 2026 · 10.1126/scitranslmed.ady1883
Abstract
Transcranial ultrasound stimulation (TUS) is a promising noninvasive technique for modulating deep brain targets and circuits with high spatial precision. For its successful clinical translation, confirmation of target engagement, together with a deeper understanding of the effects of TUS, is essential. To advance these goals, we obtained direct measures of neural activity using electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) during TUS of deep and superficial targets, guided by magnetic resonance imaging-based acoustic modeling and real-time neuronavigation. Seventeen patients were studied in the on-medication and off-deep brain stimulation states. Each patient received one active and one sham session in a randomized order, and 13 of 17 patients (76%) completed a third session, which was always active. Each active condition targeted a single site-either the primary motor cortex (M1), the globus pallidus internus (GPi), or the occipital cortex (control site)-with 10 patients per active target. TUS effects on the STN were found to be target specific. Stimulation of the M1 reduced STN beta oscillation activity compared with sham stimulation and was associated with improvements in motor signs. These effects were brain state specific, showing distinct modulation patterns at rest versus during movement. In contrast, TUS targeting the GPi increased beta activity relative to control conditions and did not improve motor signs. Our results provide mechanistic evidence that TUS can safely and selectively modulate pathological brain rhythms in the STN in PD, supporting its potential as a targeted, noninvasive therapeutic modality.
Abstract via europepmc.
Exposures
Exposure 1: M1
Target: primary motor cortex — “primary motor cortex (M1)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS system, four-element handheld transducer ✓
| Waveform | theta burst | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | ⚑ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| 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) | 3.2 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
Theta-burst TUS (tbTUS) lasting 120 s per hemisphere, delivered with neuronavigation to the M1; active sessions at least 1 week apart; LFP recorded during sonication and at 10, 30 and 45 min after.
Exposure 2: GPi
Target: globus pallidus internus — “globus pallidus internus (GPi)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS system, four-element handheld transducer ✓
| Waveform | theta burst | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| 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) | 4.4 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
Theta-burst TUS (tbTUS) lasting 120 s per hemisphere, delivered with neuronavigation to the GPi; active sessions at least 1 week apart; LFP recorded during sonication and at 10, 30 and 45 min after.
Exposure 3: Occ (active control)
Target: occipital lobe — “occipital cortex (Occ; active control)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS system, four-element handheld transducer ✓
| Waveform | theta burst | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| 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) | 5 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
Theta-burst TUS (tbTUS) lasting 120 s per hemisphere, delivered with neuronavigation to the Occ (active control); active sessions at least 1 week apart; LFP recorded during sonication and at 10, 30 and 45 min after.
Flags from extraction
exposures[0].fundamental_frequency_khz— Carrier frequency, pulse duration, PRF and duty cycle of the tbTUS protocol are not stated in the main text (Fig. 1B legend only defines TBD, PRI, SD abbreviations).exposures[0].timing.sonication_duration_s— 120 s per hemisphere comes from the Fig. 1 legend, not the Methods.exposures[0].free_field.isppa_w_cm2— 30 W/cm2 is the simulated free-water Isppa used for planning (maximum output of the device), not a measurement; in situ values are per-target BabelBrain simulation means across 20 hemispheres of 10 patients.n_sessions_per_subject— Every patient had one sham and one active session; 13 of 17 had a third active session; recorded as [2,3].exposures[2].target.terms— Occipital target given as middle occipital gyrus in the Discussion; recorded as occipital lobe.direction_of_effect— M1 tbTUS reduced STN beta and raised theta, GPi tbTUS increased beta; direction depends on target.