Diagnostic Ultrasound Modulates Human Motor Cortex: Neurophysiological Evidence from Paired-Pulse TMS and Computational Modelling

Background Transcranial ultrasound (tUS) represents a promising brain stimulation technique, yet its physiological effects using standard diagnostic protocols remain poorly characterized. This study examines the impact of conventional diagnostic ultrasound (dUS) on intracortical excitability. Methods Healthy subjects received 30 minutes of transcranial ultrasound (2.0 MHz) over the right motor cortex. Cortical excitation and inhibition were assessed bilaterally via paired-pulse TMS, quantifying resting motor threshold (RMT), short intracortical inhibition (SICI), intracortical facilitation (ICF) and long intracortical inhibition LICI before and after stimulation. The vasomotor reserve (through the breath-holding index) was also assessed. A computational model was developed to confirm the spatial selectivity of our protocol. Non-parametric and Bayesian analyses were used. Results Sixteen healthy adults (mean age 31.9 ± 11.0 years) were enrolled. dUS induced a significant reduction in SICI in the stimulated hemisphere (p = 0.016; Bayes Factor BF = 7.65), and a robust increase in LICI in the control hemisphere (p = 0.010; BF = 7.88). Between hemispheres, SICI was higher in the stimulated than in the control side (p = 0.046; BF = 3.90), while LICI was greater in the control hemisphere (p = 0.015; BF = 10.06). ICF, RMT and BHI showed no significant changes (all p > 0.05). Conclusions dUS elicits focal changes in cortical excitability, towards an overall excitatory effect, in the absence of detectable vascular changes. The observed changes also engage compensatory transcallosal mechanisms, likely involving GABA-B-mediated pathways within the contralateral hemisphere. These findings provide mechanistic evidence supporting further translational investigation.