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Ultrasound stimulation of the motor cortex during tonic muscle contraction

Ian S. Heimbuch, Tiffany K. Fan, Allan D. Wu, Guido C. Faas, Andrew C. Charles, Marco Iacoboni

PLOS ONE 2022 · 10.1371/journal.pone.0267268

human healthyhealthyemg mep

Abstract

Transcranial ultrasound stimulation (tUS) shows potential as a noninvasive brain stimulation (NIBS) technique, offering increased spatial precision compared to other NIBS techniques. However, its reported effects on primary motor cortex (M1) are limited. We aimed to better understand tUS effects in human M1 by performing tUS of the hand area of M1 (M1hand) during tonic muscle contraction of the index finger. Stimulation during muscle contraction was chosen because of the transcranial magnetic stimulation-induced phenomenon known as cortical silent period (cSP), in which transcranial magnetic stimulation (TMS) of M1hand involuntarily suppresses voluntary motor activity. Since cSP is widely considered an inhibitory phenomenon, it presents an ideal parallel for tUS, which has often been proposed to preferentially influence inhibitory interneurons. Recording electromyography (EMG) of the first dorsal interosseous (FDI) muscle, we investigated effects on muscle activity both during and after tUS. We found no change in FDI EMG activity concurrent with tUS stimulation. Using single-pulse TMS, we found no difference in M1 excitability before versus after sparsely repetitive tUS exposure. Using acoustic simulations in models made from structural MRI of the participants that matched the experimental setups, we estimated in-brain pressures and generated an estimate of cumulative tUS exposure experienced by M1hand for each subject. We were unable to find any correlation between cumulative M1hand exposure and M1 excitability change. We also present data that suggest a TMS-induced MEP always preceded a near-threshold cSP.

Abstract via europepmc.

Specieshuman
Subjects10 participants
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlmasking sound
Readout timingboth
Anaesthesianot applicable
Readoutsemg mep — surface EMG of first dorsal interosseous during tonic contraction; TMS-evoked MEP area before and after tUS; cortical silent period (TMS trials)
Direction of effectno effectNo change in FDI EMG during tUS of M1 hand area, and no change in TMS-evoked MEP size one minute after tUS exposure; no correlation between estimated cumulative exposure and excitability change.
Adverse eventsnot reportedIntensities were described as within safe levels (maximum mechanical index 0.8); adverse events are not reported.

Exposures

Exposure 1: Left M1 hand area, 500 kHz, 300 and 500 ms bursts

Target: primary motor cortex — “hand area of M1 (M1hand)”
Device: Blatek · Blatek Industries, Inc., State College, PA · 500-kHz focused piezoelectric transducer (3 cm face width, 3 cm focal point) ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)36✓✓✓⚑
Pulse repetition frequency (Hz)1,000✓✓✓
Duty cycle (%)36pulse duration × PRF gives 3600%, which disagrees with the stated value✓✓✓
Sonication duration (s)0.3, 0.5swept✓✓✓⚑
Pressure and intensity, by domain
Free-field pressure (kPa)1,130, 1,400swept✓✓✓⚑
Free-field Isppa (W/cm²)15.48✓✓✓
Free-field Ispta (W/cm²)5.57✓✓✓
In-situ estimatederatingsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)3.9✓✓✓⚑
In-situ Ispta (W/cm²)1.4✓✓✓
Protocol, in the paper’s words

Single bursts of 300 ms (75% of trials) or 500 ms, each made of pulses repeated at 1 kHz with 36% duty cycle, delivered at the TMS hotspot and two neighbouring targets; 20 trials per condition with a 10 +/- 2 s jittered interval, during tonic FDI contraction.

Consistency checks: pd exceeds period.

Flags from extraction

  • exposures[0].timing.pulse_duration_ms — The paper states pulse length = 36 ms repeated every 1 ms (Fig 1), which is inconsistent with 1 kHz PRF and 36% duty cycle (0.36 ms); recorded as written.
  • exposures[0].free_field.pressure_kpa — 1.40 MPa in water for all subjects except one session at 1.13 MPa; the water-measured value is the temporal-maximum pressure at the focus.
  • exposures[0].in_situ.isppa_w_cm2 — Intracranial intensities estimated by the authors by applying a 12 to 16 dB skull attenuation from earlier work (derating), not from the subject-specific simulations; simulated in-brain pressures are given only in figures and supplementary tables.
  • exposures[0].target.terms — Three trajectories per participant (best TMS hotspot, 2nd and 3rd best); the exposure is recorded once at M1 hand.
  • n_subjects — 10 participants in Experiment 1; 8 of them also took part in Experiment 2.
  • exposures[0].timing.sonication_duration_s — Each trial is a single 300 or 500 ms burst of which the device is on for 108 or 180 ms.