Transcranial ultrasound stimulation modulates the interhemispheric balance of excitability in human motor cortex

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.

Early-phase neuroplasticity induced by offline transcranial ultrasound stimulation in primates

“…TMS-induced MEP). In a series of work combining offline TUS and TMS in humans, MEP amplitudes were amplified by repetitive low PRF offline TUS (PRF range 5-100 Hz, see Table 1 for details of the protocols) [22][23][24]. Facilitatory effects were still present 30 minutes post-sonication in one study [24], confirming the duration of offline TUS effects on neural transmission.…”

“…In a series of work combining offline TUS and TMS in humans, MEP amplitudes were amplified by repetitive low PRF offline TUS (PRF range 5-100 Hz, see Table 1 for details of the protocols) [22][23][24]. Facilitatory effects were still present 30 minutes post-sonication in one study [24], confirming the duration of offline TUS effects on neural transmission. Contrasting with these results, Zhang et al [11] found excitatory effects in the form of decreased intracortical inhibition produced by a high PRF protocol (2000Hz) and inhibitory effectsreduced MEP amplitudes, increased intracortical inhibition and decreased intracortical facilitationwith a lower PRF protocol (50Hz).…”

Effects of the motor cortical theta‐burst transcranial‐focused ultrasound stimulation on the contralateral motor cortex

“…Several studies have shown that inhibitory NIBS protocols increase the excitability of the contralateral M1 (Chen et al., 1997; Gilio et al., 2003; Huang et al., 2005; Suppa et al., 2008; Takamatsu et al., 2021) and excitatory NIBS protocols decrease the excitability of the contralateral M1 (Suppa et al., 2008). One group found that 15 min of repetitive TUS increased ipsilateral MEP amplitudes and decreased contralateral MEP amplitudes (Ren et al., 2023). Consistent with these findings, we found that left M1 tbTUS increased right M1 excitability.…”

A review of functional neuromodulation in humans using low-intensity transcranial focused ultrasound

“…In the case of Zhang et al (2021) [24], tFUS administered for 15 min increased MEP amplitudes for ~30 min and improved inhibitory control function in the tasks conducted immediately after tFUS. Using the same sonication parameters, Ren et al (2023) [25] reported that tFUS to the left M1 increased the ipsilateral M1 excitability for ~30 min while decreased the contralateral M1 excitability for ~15 min, as assessed by TMS-induced MEP amplitudes, along with improved cognitive performance. In 2022, with a tFUS transducer, and no interference between tFUS and TMS was reported.…”

“…In another study, Samuel et al (2023) [71] delivered in stroke treatments, utilizing NIBS such as repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS) to normalize interhemispheric imbalances in stroke patients. In the case of tFUS, although not a study involving stroke patients, Ren et al (2023) [25] (listed in Table 2) observed that the excitatory effects of tFUS stimulation on the unilateral M1 in humans were accompanied by decreased excitability in the contralateral M1, suggesting the potential of tFUS in clinical interventions such as a rebalancing modality of the interhemispheric imbalances in stroke.…”