Disrupting action control with transcranial ultrasound neuromodulation: a step forward for Tourette syndrome

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.