Summary It has been 40 years since the report of long-term synaptic plasticity on the rodent brain. Transcranial ultrasound stimulation (TUS) shows advantages in spatial resolution and penetration depth when compared with electrical or magnetic stimulation. The repetitive TUS (rTUS) can induce cortical excitability alteration on animals, and persistent aftereffects were observed. However, the effects of rTUS on synaptic plasticity in humans remain unelucidated. In the current study, we applied a 15-min rTUS protocol to stimulate left primary motor cortex (l-M1) in 24 male healthy participants. The single-pulsed transcranial magnetic stimulation-evoked motor evoked potential and Stop-signal task was applied to measure the rTUS aftereffects. Here, we report that conditioning the human motor cortex using rTUS may produce long-lasting and statistically significant effects on motor cortex excitability as well as motor behavior, without harmful side effects observed. These findings suggest a considerable potential of rTUS in cortical plasticity modulation and clinical intervention for impulsivity-related disorders.

No abstract

Background: Low-intensity transcranial ultrasound stimulation (TUS) could induce both immediate and long-lasting neuromodulatory effects in human brains. Interhemispheric imbalance at prefrontal or motor cortices generally associates with various cognitive decline in aging and mental disorders. However, whether TUS could modulate the interhemispheric balance of excitability in human brain remains unknown. Objective: This study aims to explore whether repetitive TUS (rTUS) intervention can modulate the interhemispheric balance of excitability between bilateral motor cortex (M1) in healthy subjects. Methods: Motor evoked potentials (MEPs) at bilateral M1 were measured at 15min and 0min before a 15 min active or sham rTUS intervention on left M1 and at 0min, 15min and 30min after the intervention, and the Chinese version of brief neurocognitive test battery (C-BCT) was conducted before and after the intervention respectively. Cortical excitability was quantified by MEPs, and the long-lasting changes of MEP amplitude was used as an index of plasticity. Results: In the active rTUS group (n=20), the ipsilateral MEP amplitude increased significantly compared with baselines and lasted for up to 30 min after intervention, while the contralateral MEP amplitude decreased lasting for 15 min, yielding increased laterality between bilateral MEPs. Furthermore, rTUS intervention induced changes in some C-BCT scores, and the changes of scores correlated with the changes of MEP amplitudes induced by rTUS intervention. The sham rTUS group (n=20) showed no significant changes in MEPs and C-BCT scores. In addition, no participants reported any adverse effects during and after the rTUS intervention, and no obvious temperature increase appeared in skull or brain tissues in simulation. Conclusions: rTUS intervention modulated the plasticity of ipsilateral M1 and the interhemispheric balance of M1 excitability in human brain, and improved cognitive performance, suggesting a considerable potential of rTUS in clinical interventions.