Multi-focal ultrasound neuromodulation to the dorsal anterior cingulate cortex disrupts behavioural and neural pain processing
Sophie Clarke, Samuel Mugglestone, Mathilde Lojkiewiez, Joshua Marquez, Nadège Bault, Elsa Fouragnan, Sam Hughes
Nature Communications 2026 · 10.1038/s41467-026-72934-3
Abstract
Transcranial ultrasound stimulation (TUS) is a promising non-invasive neuromodulation technique for pain-related deep brain regions. This study aimed to investigate neural mechanisms underlying TUS effects on pain processing using neuroimaging. Thirty-two healthy participants underwent two double-blind, randomised sessions (active or sham). A tonic cold stimulus was applied during multifocal TUS applied to the dorsal anterior cingulate cortex (dACC), and during functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS). While no significant main effect on pain intensity was observed, active TUS showed a significantly greater reduction in pain ratings between 28- and 55-minutes post-stimulation, suggesting a delayed analgesic effect. Active TUS altered sensory encoding, disrupting the relationship between temperature and pain intensity. There was increased functional connectivity between the dACC and the supplementary motor area, pre-motor cortex, mid-ACC and supramarginal gyrus, and altered salience network connectivity. Overall, these findings suggest dACC-TUS has multidimensional effects across behavioural and neural aspects of pain processing, supporting its potential therapeutic value.
Abstract via europepmc.
Exposures
Exposure 1: Multi-focal TUS to dACC (3 sites)
Target: dorsal anterior cingulate cortex — “dorsal anterior cingulate cortex (dACC)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS TPO system and CTX-500-4 four-element annular transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 10 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓⚑ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 54 | ✓✓✓ |
| 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) | 3.7 | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | not reported |
10 Hz-patterned protocol with 10% duty cycle, pulse duration 10 ms, pulsed every 100 ms, applied for 80 s at each of three dACC targets sequentially (4 min in total), A to C order.
Flags from extraction
n_subjects— 35 recruited, 33 completed, 32 in behavioural data, 29 fMRI, 23 MRS; 33 recorded as exposed (two excluded after the first, imaging-only visit).exposures[0].in_situ.isppa_w_cm2— Mean simulated Isppa in dACC across participants (k-Plan post-stimulation simulation); recorded as mean, SD in quote.exposures[0].in_situ.pressure_kpa— In situ pressure shown only in Fig. 1c; not stated in text.exposures[0].timing.pulse_repetition_frequency_hz— PRF taken from '10 Hz-patterned' and 'pulsed every 100 ms'.sham_type— Sham delivered as matched sound via bone-conduction headphones with same placement; whether the transducer was powered off is not stated.exposures[0].target.terms— Three sites within dACC (MNI -3,37,12; -3,33,17; -3,28,22) listed as one exposure.