Systematic examination of low-intensity ultrasound parameters on human motor cortex excitability and behavior

Anton Fomenko, Kai-Hsiang Stanley Chen, Jean-François Nankoo, James Saravanamuttu, Yanqiu Wang, Mazen El-Baba, Xue Xia, Shakthi Sanjana Seerala, Kullervo Hynynen, Andres M Lozano, Robert Chen

eLife 2020, 9 · 10.7554/elife.54497

human healthyhealthyemg mepbehaviour

Abstract

Low-intensity transcranial ultrasound (TUS) can non-invasively modulate human neural activity. We investigated how different fundamental sonication parameters influence the effects of TUS on the motor cortex (M1) of 16 healthy subjects by probing cortico-cortical excitability and behavior. A low-intensity 500 kHz TUS transducer was coupled to a transcranial magnetic stimulation (TMS) coil. TMS was delivered 10 ms before the end of TUS to the left M1 hotspot of the first dorsal interosseous muscle. Varying acoustic parameters (pulse repetition frequency, duty cycle, and sonication duration) on motor-evoked potential amplitude were examined. Paired-pulse measures of cortical inhibition and facilitation, and performance on a visuomotor task was also assessed. TUS safely suppressed TMS-elicited motor cortical activity, with longer sonication durations and shorter duty cycles when delivered in a blocked paradigm. TUS increased GABA A -mediated short-interval intracortical inhibition and decreased reaction time on visuomotor task but not when controlled with TUS at near-somatosensory threshold intensity.

Abstract via europepmc.

Specieshuman

Subjects16 participants

Sessions per subject3

Randomisedyes

Blindingdouble

Sham / controlinactive transducer

Auditory controlmasking sound

Readout timingonline

Anaesthesianot applicable

Readoutsemg mep, behaviour — TMS-induced motor-evoked potentials (single- and paired-pulse); visuomotor reaching/reaction-time task

Direction of effectmixed or unclearTUS (esp. lower duty cycle, longer sonication duration, and PRF in blocked design) suppressed TMS-evoked MEP amplitude and increased SICI (inhibitory on M1 excitability), while the same basic parameters shortened reaction time in a visuomotor task (facilitatory on behaviour).

Adverse eventsnone observedNo subjects reported any adverse effects, but two (13%) participants reported a transient warm sensation at the sonication site after multiple experimental blocks. Neurological examinations after each experimental visit were normal.

Exposures

Exposure 1: M1 TUS parameter-variation experiments (basic parameters + DC/PRF/sonication-duration sweeps)

Target: primary motor cortex — “primary motor cortex (M1)”
Device: Sonic Concepts · Sonic Concepts Inc, Bothell, Washington · custom two-element annular array ultrasound transducer ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	500	✓✓✓
Pulse duration (ms)	not reported	⚑
Pulse repetition frequency (Hz)	200, 500, 1,000swept	✓✓✓
Duty cycle (%)	10, 25, 30, 50swept	✓✓✓
Sonication duration (s)	0.1, 0.2, 0.3, 0.4, 0.5swept	✓✓✓

Pressure and intensity, by domain
Free-field pressure (kPa)	not reported
Free-field Isppa (W/cm²)	9.26	✓✓✓
Free-field Ispta (W/cm²)	0.93, 2.78, 4.63swept	✓✓✓
In-situ estimate	deratingsingle value
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	0.54, 2.32swept	✓?⚑
In-situ Ispta (W/cm²)	0.23, 0.69, 1.16swept	✓✓✓

Protocol, in the paper’s words

Basic parameters: 500 kHz, PRF=1000 Hz, DC=30%, sonication duration=0.5 s, ISPPA=2.32 W/cm^2, TMS pulse time-locked 10 ms before the end of sonication. Four separate blocked/interleaved sub-experiments then independently varied DC (10,30,50%), sonication duration (0.1-0.5 s), PRF with fixed DC (200,500,1000 Hz), and PRF with adjusted DC to hold burst duration constant (10,25,50% DC for 200,500,1000 Hz respectively). Blocks were 15 consecutive sonications of one parameter value with a 5 s inter-stimulus interval and a 20 s rest between blocks; interleaved delivery used 60 randomized sonications with a 5 s ISI and no rest periods.

Flags from extraction

n_subjects — 18 healthy participants were recruited/enrolled; 2 were excluded before any TUS exposure (excessive TMS stimulator intensity requirement), leaving 16 who actually received TUS.
exposures[0].timing.pulse_duration_ms — Paper gives duty cycle and PRF for each condition but never states pulse (burst) duration in ms directly; computing it (DC/PRF) would be arithmetic we must not perform, so left not_reported. Both DC and PRF values are in protocol_description.
exposures[0].in_situ.isppa_w_cm2 — The value 0.54 W/cm^2 (near-somatosensory-threshold condition) is not explicitly labeled 'intracranial' in its own sentence, but is used interchangeably with the paper's other estimated-intracranial ISPPA value (2.32 W/cm^2) throughout the text; included here by that consistency but flagged as an inferred domain.
direction_of_effect — MEP/SICI readouts show suppression (inhibitory) while the visuomotor reaction-time readout shows facilitation (faster RT); classified as mixed_or_unclear rather than picking one.