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

Liyuan Ren, Zhaolin Zhai, Qiong Xiang, Kaiming Zhuo, Suzhen Zhang, Yi Zhang, Xiong Jiao, Shanbao Tong, Dengtang Liu, Junfeng Sun

Journal of Neural Engineering 2023, 20, 016043 · 10.1088/1741-2552/acb50d

human healthyhealthyemg mepbehaviour

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. Approach . Motor evoked potentials (MEPs) at bilateral M1 were measured at 15 min and 0 min before a 15 min active or sham rTUS intervention on left M1 and at 0 min, 15 min and 30 min 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. Significance . 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.

Abstract via europepmc.

Specieshuman
Subjects20 participants
Sessions per subject1
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingoffline
Anaesthesianot applicable
Readoutsemg mep, behaviourChinese Brief Cognitive Test (C-BCT): trail making test part A (TMT-A), symbol coding, continuous performance test (CPT), digit span
Direction of effectbidirectionalActive rTUS to left M1 increased ipsilateral MEP amplitude (facilitation, lasting up to 30 min) while decreasing contralateral MEP amplitude (inhibition, lasting 15 min), increasing interhemispheric laterality; sham rTUS produced no significant MEP changes.
Adverse eventsnone observedNo participants reported any adverse effects during or after the rTUS intervention; simulation showed a maximum temperature increase of 6.4x10^-3 degC in the skull and 6.1x10^-4 degC in the brain.

Exposures

Exposure 1: rTUS to left M1 (active group)

Target: primary motor cortex — “left M1
Device: Olympus / Panametrics · Olympus NDT · V391-SU

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.5✓✓
Pulse repetition frequency (Hz)100✓✓
Duty cycle (%)5pulse duration × PRF gives 5%✓✓
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)8.09✓✓
Free-field Ispta (W/cm²)0.404✓✓
In-situ estimatesimulationsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)2.85✓✓
In-situ Ispta (W/cm²)0.142✓✓
Protocol, in the paper’s words

The rTUS parameters: duty cycle (DC) 5%, tone-burst-duration 500 microseconds, sonication duration (SD) 500 ms, number of tone-bursts per train 50, PRF 100 Hz, inter-stimulus interval (ISI) 8 s, total stimulation duration 15 min (total on-state duration of rTUS was 2.657 s). For the sham-rTUS group, the ultrasound intensity was set to zero.

Flags from extraction

  • n_subjectsTotal enrolled was 40 (20 sham, 20 active); the sham-rTUS group had ultrasound intensity set to zero, so n_subjects here reflects only the 20 participants who received active rTUS.
  • exposures[0].free_field.isppa_w_cm2The Discussion/safety section restates extracranial intensity as ISPPA=8.053 W/cm2 and ISPTA=0.403 W/cm2 (MI=0.696), slightly different from the Methods values (8.086/0.404, MI=0.698) used here; likely rounding or a typo.
  • sham_typeSham was implemented by setting ultrasound intensity to zero with the same setup in place; classified as inactive_transducer (powered off) though not explicitly described as such.