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Interactive effect between transcranial focused ultrasound and transcranial magnetic stimulation on human motor cortex

Kai-Hsiang Stanley Chen, Yih-Chih Jacinta Kuo, Chang-Yu Cheng, Yan-Siou Dong, Anton Fomenko, Jean-François Nankoo, Yi-Ping Liu, Robert Chen

Clinical Neurophysiology 2024, 167, 92-105 · 10.1016/j.clinph.2024.09.001

human healthyhealthyemg mep

Abstract

Objective Transcranial focused ultrasound (TUS) can suppress human motor cortical excitability. However, it is unclear whether the TUS may interact with transcranial magnetic stimulation (TMS) when they co-delivered in multiple trials. Methods Nineteen subjects received three different TUS-TMS co-stimulation protocols to the motor cortex including concurrent stimulation (TUS-TMS-C), separated stimulation (TUS-TMS-S), and TMS only. In each condition, two runs of 30 stimulation trials were conducted with a five-minute rest between runs. Motor-evoked potentials (MEP) were recorded during stimulation and at 0, 10, 20, and 30 min after stimulation. The MEP amplitudes after intervention were normalized to the mean pre-intervention MEP amplitude and expressed as MEP ratios. An additional test with TUS alone was applied to all participants to assess whether TUS itself can elicit after-effects. Results There were no significant after-effects of all three interventions on MEP ratios. However, 11 subjects who showed online inhibition (OI + ) during the TUS-TMS-C protocol, defined as having MEP ratio less than 1 during TUS-TMS-C, showed significant MEP suppression at 10, 20 and 30 min after TUS-TMS-C. In 8 subjects did not show online inhibition (OI-), defined as having MEP ratios greater than 1 during TUS-TMS-C, showed no significant inhibitory after-effects. OI + and OI- status did not change in a follow-up repeat TUS-TMS-C test. TUS alone did not generate inhibitory after-effects in either OI + or OI- participants. Conclusions Our results showed that co-delivery of TUS and TMS can elicit inhibitory after-effect in subjects who showed online inhibition, suggesting that TUS and TMS may interact with each other to produce plasticity effects. Significance TUS and TMS may interact with each other to modulate cortical excitability.

Abstract via europepmc.

Specieshuman
Subjects19 participants
Sessions per subject4
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlmasking sound
Readout timingboth
Anaesthesianot applicable
Readoutsemg mep
Direction of effectbidirectionalSubjects showing online inhibition (OI+) during TUS-TMS-C had suppressed MEPs with suppressive after-effects at 10-30 min; subjects without online inhibition (OI-) showed facilitated MEPs and no suppressive after-effects.
Adverse eventsnone observedNo participants reported any adverse effects.

Exposures

Exposure 1: TUS_0.5 (motor cortex TUS-TMS co-stimulation)

Target: primary motor cortex — “motor cortex (FDI hotspot)
Device: Sonic Concepts · Sonic Concepts Inc · H246

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.3✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)30pulse duration × PRF gives 30%✓✓
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)612✓✓
Free-field Isppa (W/cm²)9.38✓✓
Free-field Ispta (W/cm²)2.81✓✓
In-situ estimatederatingsingle value
In-situ pressure (kPa)183.6✓✓
In-situ Isppa (W/cm²)0.84✓✓
In-situ Ispta (W/cm²)0.252✓✓
Protocol, in the paper’s words

Each paradigm included two sets of 30 trials of stimulation separated by 5 min (60 trials total), trials delivered 5 s apart. TUS-TMS-C delivered TMS 10 ms before the end of the 500 ms sonication (0.49 s after onset); TUS-TMS-S delivered TMS 2.5 s after the end of sonication (3 s after onset); TMS only used identical timing with TUS stimulation intensity set to 0 W.

Flags from extraction

  • exposures[0].in_situ.pressure_kpaIn-situ pressure/intensity derived by assuming a 30% (70% drop) transmission based on a literature range (Liu et al., 2014), not measured or simulated for this cohort's skulls.
  • exposures[0].timing.pulse_duration_msPaper states PRF (1000 Hz), duty cycle (30%) and sonication duration (500 ms) but never states pulse duration explicitly; not computed per protocol.
  • blindingPaper does not explicitly state whether participants/experimenters were blinded to TUS-TMS-C/S vs TMS-only conditions beyond masking sound.