Excitatory‐inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex
Tingting Zhang, Bingqi Guo, Zhentao Zuo, Xiaojing Long, Shimin Hu, Siran Li, Xin Su, Yuping Wang, Chunyan Liu
CNS Neuroscience & Therapeutics 2023, 29, 3829-3841 · 10.1111/cns.14303
Abstract
Aims Transcranial focus ultrasound stimulation (tFUS) is a promising non-invasive neuromodulation technology. This study aimed to evaluate the modulatory effects of tFUS on human motor cortex (M1) excitability and explore the mechanism of neurotransmitter-related intracortical circuitry and plasticity. Methods Single pulse transcranial magnetic stimulation (TMS)-eliciting motor-evoked potentials (MEPs) were used to assessed M1 excitability in 10 subjects. Paired-pulse TMS was used to measure the effects of tFUS on GABA- and glutamate-related intracortical excitability and 1 H-MRS was used to assess the effects of repetitive tFUS on GABA and Glx (glutamine + glutamate) neurometabolic concentrations in the targeting region in nine subjects. Results The etFUS significantly increased M1 excitability, decreased short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI). The itFUS significantly suppressed M1 excitability, increased SICI, LICI, and decreased intracortical facilitation (ICF). Seven times of etFUS decreased the GABA concentration (6.32%), increased the Glx concentration (12.40%), and decreased the GABA/Glx ratio measured by MRS, while itFUS increased the GABA concentration (18.59%), decreased Glx concentration (0.35%), and significantly increased GABA/Glx ratio. Conclusion The findings support that tFUS with different parameters can exert excitatory and inhibitory neuromodulatory effects on the human motor cortex. We provide novel insights that tFUS change cortical excitability and plasticity by regulating excitatory-inhibition balance related to the GABAergic and glutamatergic receptor function and neurotransmitter metabolic level.
Abstract via europepmc.
Exposures
Exposure 1: etFUS / itFUS to left M1
Target: primary motor cortex — “left M1 (hand motor cortex)”
Device: custom-built · GreenValley BrainTech Medical Techology Corportion ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.2, 0.4swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 2,000, 50swept | ✓✓✓ |
| Duty cycle (%) | 40, 2swept | ✓✓✓ |
| Sonication duration (s) | 0.5 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 0.616, 2.46swept | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 0.00308, 0.0123swept | ✓✓✓ |
Two parameter sets were used: etFUS (pulse width T1=200 microseconds, pulse-repetition period T2=0.5 ms, burst duration T3=500 ms, burst period T4=2 s, PRF=2000 Hz, DC=40%) produced excitatory effects; itFUS (T1=400 microseconds, T2=20 ms, T3=500 ms, T4=2 s, PRF=50 Hz, DC=2%) produced inhibitory effects. Each was applied for 5 min in Experiments 1 and 2 (with sham in Experiment 1), and 5 min once daily for 7 consecutive days in Experiment 3.
Flags from extraction
n_sessions_per_subject— Session counts differ across the three experiments (up to 3 sessions in Exp 1, up to 2 in Exp 2, 7 consecutive days in Exp 3); a single count could not be given.sham_type— The mechanism of the sham condition (e.g., power off, transducer angled away) is not described in the text.exposures[0].in_situ.reported_as— ISPPA/ISPTA are reported as a min-max range from spatial scanning of the acoustic field through a skull fragment, not as a range across subjects; 'mean_or_range_across_subjects' is the closest available category.exposures[0].in_situ.isppa_w_cm2— Reported as a single measured range without specifying whether it corresponds to the etFUS condition, itFUS condition, or both.