Multi-focal ultrasound neuromodulation to the dorsal anterior cingulate cortex disrupts behavioural and neural pain processing.

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.