Individualized non-invasive deep brain stimulation of the basal ganglia using transcranial ultrasound stimulation
Ghazaleh Darmani, Hamidreza Ramezanpour, Can Sarica, Regina Annirood, Talyta Grippe, Jean-Francois Nankoo, Anton Fomenko, Brendan Santyr, Ke Zeng, Artur Vetkas, Nardin Samuel, Benjamin Davidson, Alfonso Fasano, Milad Lankarany, Suneil K. Kalia, Samuel Pichardo, Andres M. Lozano, Robert Chen
Nature Communications 2025, 16 · 10.1038/s41467-025-57883-7
Abstract
Transcranial ultrasound stimulation (TUS) offers precise, non-invasive neuromodulation, though its impact on human deep brain structures remains underexplored. Here we examined TUS-induced changes in the basal ganglia of 10 individuals with movement disorders (Parkinson's disease and dystonia) and 15 healthy participants. Local field potentials were recorded using deep brain stimulation (DBS) leads in the globus pallidus internus (GPi). Compared to sham, theta burst TUS (tbTUS) increased theta power during stimulation, while 10 Hz TUS enhanced beta power, with effects lasting up to 40 min. In healthy participants, a stop-signal task assessed tbTUS effects on the GPi, with pulvinar stimulation serving as an active sham. GPi TUS prolonged stop-signal reaction times, indicating impaired response inhibition, whereas pulvinar TUS had no effect. These findings provide direct electrophysiological evidence of TUS target engagement and specificity in deep brain structures, suggesting its potential as a noninvasive DBS strategy for neurological and psychiatric disorders.
Abstract via europepmc.
Exposures
Exposure 1: GPi tbTUS and 10 Hz TUS (Experiment I patients; Experiment II healthy participants)
Target: globus pallidus internus — “globus pallidus internus (GPi)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · CTX-500 (NeuroFUS TPO) ✓
| Waveform | theta_burst, pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20, 30swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5, 10swept | ✓✓✓ |
| Duty cycle (%) | 10, 30swept | ✓✓✓ |
| Sonication duration (s) | 120, 40swept | ✓✓✓ |
| 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) | 2.5, 7swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.25, 2.1swept | ✓✓✓⚑ |
In Experiment I (GPi-DBS patients), each electrophysiology visit began with a sham (active or passive) followed one hour later by real TUS (tbTUS or 10 Hz TUS) applied bilaterally, sequentially to left then right GPi via neuronavigation; order of sham type and TUS protocol was randomized. In Experiment II (healthy participants), the same tbTUS protocol was applied bilaterally to the GPi (2 min per side, two rounds) in a separate session from pulvinar stimulation, with a stop-signal task performed before and after each round.
Exposure 2: Pulvinar tbTUS (Experiment II, active control site)
Target: pulvinar — “pulvinar”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · CTX-500 (NeuroFUS TPO) ✓
| 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) | 2.3, 9swept | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 0.25, 0.95swept | ✓✓✓ |
In healthy participants, the pulvinar was targeted bilaterally with the same tbTUS protocol as the GPi (2 min per side, two rounds) in a session separate from GPi stimulation, serving as an active control site for the stop-signal task; side of head and GPi/pulvinar session order were randomized.
Flags from extraction
n_subjects— Paper reports two separate experiments with different cohorts (10 DBS-implanted movement-disorder patients in Experiment I; 15 healthy participants in Experiment II); no combined total is stated, so recorded as a list of group sizes.exposures[0].in_situ.ispta_w_cm2— ISPTA range differs by protocol within the same GPi target/frequency (tbTUS 0.25-0.7 W/cm2; 10 Hz TUS 0.75-2.1 W/cm2); recorded as a nested list [[tbTUS range],[10 Hz TUS range]] to preserve both; Experiment II (healthy participants, tbTUS only) separately reports GPi ISPTA range 0.2-0.85 W/cm2, not merged into this value.exposures[1].in_situ.isppa_w_cm2— Experiment II pulvinar-specific range (2.3-9 W/cm2, in situ) used; this experiment (healthy participants) is distinct from Experiment I's GPi DBS-patient simulations.blinding— Paper explicitly states patients were blinded to condition ('administered in a blinded manner'); no statement about blinding of the experimenter/analyst, so coded as single rather than double.readout_timing— LFP was recorded before, during (T0) and after (T10/T25/T40) TUS (online+offline); behavioural stop-signal task was assessed only offline (pre/post blocks); coded as both at the paper level.n_subjects— Second group size (15 healthy participants) is stated separately in Experiment II Methods: 'Fifteen healthy participants (age range:18-35 years...) participated in this experiment.' Only the Experiment I quote is stored due to one-quote-per-field limit.