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Transcranial focused ultrasound neuromodulation of the human primary motor cortex

Wynn Legon, Priya Bansal, Roman Tyshynsky, Leo Ai, Jerel K. Mueller

Scientific Reports 2018, 8 · 10.1038/s41598-018-28320-1

human healthyhealthyemg mepbehaviour

Abstract

Transcranial focused ultrasound is an emerging form of non-invasive neuromodulation that uses acoustic energy to affect neuronal excitability. The effect of ultrasound on human motor cortical excitability and behavior is currently unknown. We apply ultrasound to the primary motor cortex in humans using a novel simultaneous transcranial ultrasound and magnetic stimulation paradigm that allows for concurrent and concentric ultrasound stimulation with transcranial magnetic stimulation (TMS). This allows for non-invasive inspection of the effect of ultrasound on motor neuronal excitability using the motor evoked potential (MEP). We test the effect of ultrasound on single pulse MEP recruitment curves and paired pulse protocols including short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). In addition, we test the effect of ultrasound to motor cortex on a stimulus response reaction time task. Results show ultrasound inhibits the amplitude of single-pulse MEPs and attenuates intracortical facilitation but does not affect intracortical inhibition. Ultrasound also reduces reaction time on a simple stimulus response task. This is the first report of the effect of ultrasound on human motor cortical excitability and motor behavior and confirms previous results in the somatosensory cortex that ultrasound results in effective neuronal inhibition that confers a performance advantage.

Abstract via europepmc.

Specieshuman
Subjects50 participants
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer, active control site
Auditory controldeafened subjects
Readout timingonline
Anaesthesianot applicable
Readoutsemg mep, behaviourSingle-pulse TMS motor evoked potential (MEP) recruitment curves; paired-pulse short interval intracortical inhibition (SICI) and intracortical facilitation (ICF); simple visual stimulus-response reaction time task with EMG from abductor pollicis brevis
Direction of effectinhibitoryUltrasound to M1 significantly attenuated single-pulse MEP amplitude across tested TMS intensities (largest at 90-100% stimulator output) and attenuated intracortical facilitation (ICF, ISI 10-15 ms) without significantly affecting short-interval intracortical inhibition (SICI, ISI 1-5 ms); ultrasound to the APB M1 representation significantly reduced simple reaction time relative to both active (vertex) and passive (M1) sham.
Adverse eventsobservedNo severe symptoms were reported by the 20/50 participants (40%) who responded to a follow-up symptoms questionnaire; mild and moderate symptoms included neck pain, sleepiness, muscle twitches, itchiness and headache, none of which persisted or worsened.

Exposures

Exposure 1: Primary motor cortex (M1): hand-knob/FDI hotspot (single- and paired-pulse MEP experiments) and APB hotspot (reaction time experiment)

Target: primary motor cortex — “primary motor cortex (M1) hand-knob representation; FDI hotspot for the MEP experiments and APB hotspot for the reaction time experiment
Device: custom-built

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓
Pulse duration (ms)0.36✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 36%
Sonication duration (s)0.5✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)17.12✓✓
Free-field Ispta (W/cm²)6.16✓✓
In-situ estimatesimulationsingle value
In-situ pressure (kPa)120✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Channel 1 was set to deliver tFUS at a pulse repetition frequency (PRF) of 1 kHz and channel 2 was set to drive the transducer at 500 kHz in burst mode using channel 1 as the trigger; channel 2 delivered 180 cycles per pulse and channel 1 delivered 500 pulses, resulting in a 500 msec duration waveform. For the single- and paired-pulse experiments, ultrasound was time-locked to occur 100 msec prior to the TMS pulse; for the reaction time experiment, ultrasound was time-locked to occur 100 msec prior to the visual stimulus. The sham condition involved turning over the transducer so no ultrasound was delivered while maintaining contact and equitable auditory artifact.

Flags from extraction

  • exposures[0].timing.pulse_duration_msPulse duration was not stated directly in ms; it was converted from the stated '180 cycles per pulse' at the stated 500 kHz drive frequency (180/500000 Hz = 0.36 ms), the schema's sanctioned cycles-per-pulse-to-duration unit conversion.
  • exposures[0].in_situ.pressure_kpaValue ('~120 kPa') is an approximate figure from the Discussion referring to the modeled intracranial pressure, not a table/methods value with full precision.
  • randomisedExperiments 1 and 2 describe conditions as 'counterbalanced across participants' while Experiment 3 explicitly states order was 'randomized across participants'; recorded as true for the whole study but the terminology differs by sub-experiment.
  • auditory_controlPaper describes provision of ear protection to mask any audible transducer buzzing rather than a listed auditory-control vocabulary mechanism; recorded as 'other'.