The effect of transcranial ultrasound pulse repetition frequency on sustained inhibition in the human primary motor cortex: A double-blind, sham-controlled study
Ali K. Zadeh, Hrishikesh Raghuram, Shirshak Shrestha, Mekale Kibreab, Iris Kathol, Davide Martino, G. Bruce Pike, Samuel Pichardo, Oury Monchi
Brain Stimulation 2024, 17, 476-484 · 10.1016/j.brs.2024.04.005
Abstract
Background Non-invasive brain stimulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation hold promise for inducing brain plasticity. However, their limited precision may hamper certain applications. In contrast, Transcranial Ultrasound Stimulation (TUS), known for its precision and deep brain targeting capabilities, requires further investigation to establish its efficacy in producing enduring effects for treating neurological and psychiatric disorders. Objective To investigate the enduring effects of different pulse repetition frequencies (PRF) of TUS on motor corticospinal excitability. Methods T1-, T2-weighted, and zero echo time magnetic resonance imaging scans were acquired from 21 neurologically healthy participants for neuronavigation, skull reconstruction, and the performance of transcranial ultrasound and thermal modelling. The effects of three different TUS PRFs (10, 100, and 1000 Hz) with a constant duty cycle of 10 % on corticospinal excitability in the primary motor cortex were assessed using TMS-induced motor evoked potentials (MEPs). Each PRF and sham condition was evaluated on separate days, with measurements taken 5-, 30-, and 60-min post-TUS. Results A significant decrease in MEP amplitude was observed with a PRF of 10 Hz (p = 0.007), which persisted for at least 30 min, and with a PRF of 100 Hz (p = 0.001), lasting over 60 min. However, no significant changes were found for the PRF of 1000 Hz and the sham conditions. Conclusion This study highlights the significance of PRF selection in TUS and underscores its potential as a non-invasive approach to reduce corticospinal excitability, offering valuable insights for future clinical applications.
Abstract via europepmc.
Exposures
Exposure 1: TUS of left primary motor cortex at 10/100/1000 Hz PRF
Target: primary motor cortex — “primary motor cortex”
Device: Sonic Concepts · Sonic Concepts · H317 (128-element phased array) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | not reported | ⚑ |
| Pulse repetition frequency (Hz) | 10, 100, 1,000swept | ✓✓✓ |
| Duty cycle (%) | 10 | ✓✓✓ |
| Sonication duration (s) | 120 | ✓✓✓ |
| Free-field pressure (kPa) | 980 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 5 | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 0.5 | ✓✓✓ |
Ultrasound delivery in all stimulation sessions consisted of a 120-s train with a DC of 10%, driven at a fundamental frequency of 250 kHz. A total ramping of 25% of the burst duration (12.5% up, 12.5% down) was applied to all PRF conditions to reduce auditory confounds. Each PRF (10, 100, 1000 Hz) and a sham condition were tested on separate days in randomised order; MEPs were assessed at baseline and 5, 30 and 60 min post-TUS.
Flags from extraction
n_subjects— 25 individuals enrolled but 4 withdrew during stimulation visits (irregular attendance, inability to relax, dizziness during TMS), leaving 21 who completed all sessions and were analysed; enrolled figure (25) recorded per enrolled-vs-analysed convention.exposures[0].free_field.pressure_kpa— The 0.98 MPa value comes from the calibration procedure performed at PRF 100 Hz / DC 2% (50-cycle burst) used for focus characterization, not explicitly confirmed as the free-field pressure delivered during the actual DC 10% experimental protocol.exposures[0].in_situ.isppa_w_cm2— The corresponding sentence in the main Methods text has an OCR/typesetting artefact that drops the numeral; the value (5 W/cm2) is only clearly legible in the Fig. 2 caption text, which was used as the quote.exposures[0].timing.pulse_duration_ms— Paper states duty cycle (10%) and PRF (10/100/1000 Hz) but never states pulse duration directly; left not_reported rather than computed from duty_cycle/PRF.