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Time course of the effects of low-intensity transcranial ultrasound on the excitability of ipsilateral and contralateral human primary motor cortex

Xue Xia, Anton Fomenko, Jean-François Nankoo, Ke Zeng, Yanqiu Wang, Jian Zhang, Andres M Lozano, Robert Chen

NeuroImage 2021, 243, 118557 · 10.1016/j.neuroimage.2021.118557

human healthyhealthyemg mep

Abstract

Low-intensity transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique that can modulate the excitability of cortical and deep brain structures with a high degree of focality. Previous human studies showed that TUS decreases motor cortex (M1) excitability measured by transcranial magnetic stimulation (TMS), but whether the effects appear beyond sonication and whether TUS affects the excitability of other interconnected cortical areas is not known. The time course of M1 TUS on ipsilateral and contralateral M1 excitability was investigated in 22 healthy human subjects via TMS-induced motor-evoked potentials. With sonication duration of 500 ms, we found suppression of M1 excitability from 10 ms before to 20 ms after the end of sonication, and the effects were stronger with blocked design compared to interleaved design. There was no significant effect on contralateral M1 excitability. Using ex-vivo measurements, we showed that the ultrasound transducer did not affect the magnitude or time course of the TMS-induced electromagnetic field. We conclude that the online-suppressive effects of TUS on ipsilateral M1 cortical excitability slightly outlast the sonication but did not produce long-lasting effects. The absence of contralateral effects may suggest that there are little tonic interhemispheric interactions in the resting state, or the intensity of TUS was too low to induce transcallosal inhibition.

Abstract via europepmc.

Specieshuman
Subjects22 participants
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlmasking sound
Readout timingboth
Anaesthesianot applicable
Readoutsemg mepTMS-induced motor-evoked potentials (MEP) from first dorsal interosseous muscle; dual-site paired-pulse TMS for interhemispheric inhibition (IHI); Hall-effect sensor quantification of TMS-induced electromagnetic field
Direction of effectinhibitoryTUS suppressed ipsilateral M1 MEP amplitude from shortly before to about 20 ms after the end of 500 ms sonication, with a stronger effect in the blocked than the interleaved design; no significant effect was found on contralateral M1 excitability.
Adverse eventsnot reported

Exposures

Exposure 1: TUS of left primary motor cortex

Target: primary motor cortex — “left primary motor cortex (M1), hand area
Device: Sonic Concepts · Sonic Concepts Inc. · H246

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.3 ms (not stated by the paper)
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)30✓✓
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)9.26✓✓
Free-field Ispta (W/cm²)2.78✓✓
In-situ estimatederatingsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)2.32✓✓
In-situ Ispta (W/cm²)0.69✓✓
Protocol, in the paper’s words

TUS was delivered via a custom two-element annular array transducer coupled to the underside of (or, in Experiment 2, detached from) the TMS coil, with channel phasing set to a 30 mm sonication depth. TUS was delivered every 6 s. Single-pulse TMS was timed at various intervals before, during and after each 500 ms sonication (interleaved or blocked design) to probe the time course of ipsilateral and contralateral M1 excitability; active sham (transducer flipped away) and inactive sham (active face toward scalp, unpowered) conditions were interleaved with real TUS trials.

Flags from extraction

  • exposures[0].timing.pulse_duration_msTone-burst duration within the 500 ms sonication train is not stated; only PRF and duty cycle are given.
  • exposures[0].in_situIn-situ (intracranial) intensities are derated estimates based on literature skull attenuation values, not direct measurement.
  • randomisedRandomisation refers to the order of within-subject stimulation conditions (including active/sham), not allocation to independent groups.