Disrupting action control with transcranial ultrasound neuromodulation: a step forward for Tourette syndrome
Cyril Atkinson-Clement, Mairi Houlgreave, Aikaterini Gialopsou, Caitlin Mairi Smith, Isabel Farr, Aneta Dvorakova, James Kennaway, Stephen R. Jackson
2025 · 10.1101/2025.10.29.685348
Abstract
Background While Tourette syndrome (TS) is characterised by the presence of tics, premonitory urges are involved in both triggering them and as a lever to control them. The right insular cortex is known to play a key role in these processes, yet its precise functional contribution remains unclear. Transcranial ultrasound stimulation (TUS) is currently one of the only non-invasive neuromodulation techniques capable of safely and precisely modulating the activity of deep brain structures such as the insula. Objective This study used TUS to causally investigate the respective roles of the anterior and posterior insula in urge and action control during a blink suppression task. Methods Twenty healthy adults underwent three TUS sessions targeting the right anterior insula, posterior insula, and posterior ventricle (control site) in a within-subject, crossover design. Behavioural outcomes included blink counts and urge ratings. Additionally, voxel-based correlations were conducted to further estimate the role of each reached area with acoustic stimulation, allowing for a better mechanical understanding. Results TUS of the anterior insula induced a clear and acute increase in blink frequency without altering urge, reinforced by voxel-based analyses, confirming its role in voluntary action control. Posterior insula stimulation induced delayed increases in both blinks and urge, which are essentially explained by an involuntary stimulation of the right inferior frontal gyrus. Ventricular stimulation unexpectedly reduced blink frequency during the stimulation only, correlated with acoustic energy delivered within the posterior internal capsule. No significant side effects or temperature rises were observed. Conclusions These findings provide the first causal evidence that TUS can modulate the two main features of TS: premonitory urge and action control. Distinct effects across targets highlight the anterior insula’s critical role in action control and suggest the internal capsule as a potential therapeutic target for TS.
Abstract via europepmc.
Exposures
Exposure 1: TUS-AntIns
Target: anterior insula — “right anterior insula”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · CTX-500-4CH transducer with NeuroFUS PRO TPO-203 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 54.51 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 386.4 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Single 80 s sonication delivered during block 5 of a 15-block (3 min each) blink suppression task; pulse duration 20 ms, pulse repetition interval 200 ms. Identical parameters at all three targets; one target per visit, three visits at least one week apart.
Exposure 2: TUS-PostIns
Target: posterior insula — “right posterior insula”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · CTX-500-4CH transducer with NeuroFUS PRO TPO-203 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 54.51 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 476.4 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Single 80 s sonication delivered during block 5 of a 15-block (3 min each) blink suppression task; pulse duration 20 ms, pulse repetition interval 200 ms. Identical parameters at all three targets; one target per visit, three visits at least one week apart.
Exposure 3: TUS-Vent
Target: other — “right posterior lateral ventricle”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · CTX-500-4CH transducer with NeuroFUS PRO TPO-203 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 54.51 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 546.8 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Single 80 s sonication delivered during block 5 of a 15-block (3 min each) blink suppression task; pulse duration 20 ms, pulse repetition interval 200 ms. Identical parameters at all three targets; one target per visit, three visits at least one week apart.
Flags from extraction
exposures[1].in_situ.pressure_kpa— Text gives 476.36 kPa for TUS-PostIns but Table 1 mean row gives 479.4; text value recorded. Text gives 546.77 and 386.35 versus table 546.8 and 386.3.exposures[0].in_situ.pressure_kpa— Peak pressure is a k-Plan simulated value in brain tissue, mean across 20 participants (SD in quote).exposures[2].target.terms— Posterior lateral ventricle used as control site; no suitable target id so 'other'.sham_type— No sham; the ventricle target is a real-ultrasound control site.auditory_control— Bone-conduction headphones played a sound imitating TUS plus white noise; participants still detected stimulation above chance in some blocks.