Transcranial ultrasound stimulation in humans is associated with an auditory confound that can be effectively masked
Verena Braun, Joseph Blackmore, Robin O. Cleveland, Christopher R. Butler
Brain Stimulation 2020, 13, 1527-1534 · 10.1016/j.brs.2020.08.014
Abstract
Background Transcranial ultrasound stimulation (TUS) is emerging as a potentially powerful, non-invasive technique for focal brain stimulation. Recent animal work suggests, however, that TUS effects may be confounded by indirect stimulation of early auditory pathways. Objective We aimed to investigate in human participants whether TUS elicits audible sounds and if these can be masked by an audio signal. Methods In 18 healthy participants, T1-weighted magnetic resonance brain imaging was acquired for 3D ultrasound simulations to determine optimal transducer placements and source amplitudes. Thermal simulations ensured that temperature rises were Results We found that participants can hear sound during TUS and can distinguish between stimulation and non-stimulation trials. This was corroborated by EEG recordings indicating auditory activation associated with TUS. Delivering an audio waveform to participants through earphones while TUS was applied reduced detection rates to chance level and abolished the TUS-induced auditory EEG signal. Ex vivo skull experiments demonstrated that sound is conducted through the skull at the pulse repetition frequency of the ultrasound. Conclusion Future studies using TUS in humans need to take this auditory confound into account and mask stimulation appropriately.
Abstract via europepmc.
Exposures
Exposure 1: TUS to right visual cortex (unmasked and masked blocks)
Target: primary visual cortex — “right visual cortex”
Device: Sonic Concepts · Sonic Concepts Inc · H-107 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 500 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Each stimulation trial consisted of a 300 ms burst; 100 unmasked trials (50 stimulation, 50 sham) followed by 100 masked trials (50 stimulation, 50 sham) with a 1 kHz square-wave audio mask starting ~112 ms before TUS onset and lasting 700 ms, played through earphones.
Flags from extraction
sham_type— Sham/no-stimulation trials are described only as trials in which 'no TUS was applied'; the physical mechanism (transducer powered off vs. simply not triggered) is not described.direction_of_effect— This paper's purpose is to characterise an auditory confound rather than an intended neuromodulatory effect at the visual-cortex target, so direction_of_effect is recorded as not_assessed with the confound described in direction_notes.exposures[0].in_situ.pressure_kpa— 0.50 MPa is the group mean modelled (simulated) in-situ pressure at the V1 target reported for a subset of analysis (one participant's context); individual/group range was 0.30-0.60 MPa.n_sessions_per_subject— The paper does not state whether the unmasked and masked blocks (which were always run in that order) occurred within one session or across multiple visits.