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Repeated Application of Transcranial Diagnostic Ultrasound Towards the Visual Cortex Induced Illusory Visual Percepts in Healthy Participants

Nels Schimek, Zeb Burke-Conte, Justin Abernethy, Maren Schimek, Celeste Burke-Conte, Michael Bobola, Andrea Stocco, Pierre D. Mourad

Frontiers in Human Neuroscience 2020 · 10.3389/fnhum.2020.00066

human healthyhealthybehaviour

Abstract

Transcranial magnetic stimulation (TMS) of the visual cortex can induce phosphenes as participants look at a visual target. So can non-diagnostic ultrasound (nDU), delivered in a transcranial fashion, while participants have closed their eyes during stimulation. Here, we sought to determine if DU, aimed at the visual cortex, could alter the perception of a visual target. We applied a randomized series of actual or sham DU, transcranially and towards the visual cortex of healthy participants while they stared at a visual target (a white crosshair on a light-blue background), with the ultrasound device placed where TMS elicited phosphenes. These participants observed percepts seven out of ten times, which consisted of extra or extensions of lines relative to the original crosshair, and additional colors, an average of 53.7 ± 2.6% of the time over the course of the experiment. Seven out of ten different participants exposed to sham-only DU observed comparable percepts, but only an average of 36.3 ± 1.9% of the time, a statistically significant difference ( p < 0.00001). Moreover, on average, participants exposed to a combination of sham and actual ultrasound reported a net increase of 47.9 percentage points in the likelihood that they would report a percept by the end of the experiment. Our results are consistent with the hypothesis that a random combination of sham-only and actual DU, applied directly over the visual cortex of participants, increased the likelihood that they would observe visual effects, but not the type of effects, with that likelihood increasing over the course of the experiment. From this, we conclude that repeated exposures by DU may make the visual cortex more responsive to stimulation of their visual cortex by the visual target itself. Future studies should identify the biophysical mechanism(s) and neural pathways by which DU, in our hands and others, can generate its observed effects on brain function. These observations, consistent with other's observation of effects of DU stimulation of the human motor cortex and amygdala, as well as the FDA approved nature of DU, may lead to increased use of DU as a means of altering brain function.

Abstract via europepmc.

Specieshuman
Subjects11 participants
Sessions per subjectnot reported
Randomisedyes
Blindingsingle
Sham / controlinactive transducer
Auditory controlmasking sound
Readout timingonline
Anaesthesianot applicable
Readoutsbehaviour — self-reported visual percepts (drawings and survey questions) while viewing a crosshair
Direction of effectexcitatoryParticipants given a random mix of sham and actual diagnostic ultrasound reported illusory visual percepts more often (53.7%) than a sham-only group (36.3%), with reporting likelihood increasing over the experiment.
Adverse eventsnot reported

Exposures

Exposure 1: Diagnostic ultrasound (Sonosite L25x) over visual cortex, 15 s exposures

Target: visual cortex — “visual cortex, at the location where TMS elicited phosphenes”
Device: other named manufacturer · FUJI Sonosite, Bothell, WA, USA · L25x 13-6 MHz transducer on a Sonosite M-Turbo Ultrasound system

Pulse timing
Waveformnot reported
Fundamental frequency (kHz)6,000✓✓✓⚑
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)not reported
Duty cycle (%)not reported
Sonication duration (s)15✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported⚑
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Device in penetration mode at highest gain, mechanical index 0.7; each trial was 2 s ramped pink noise, 15 s of sham or actual ultrasound with constant pink noise, then 2 s descending noise, followed by 45 s drawing and 30 s survey. 20 trials after a sham baseline trial: 14 actual and 6 sham in random order for the mixed group; a separate group of 10 received sham only.

Flags from extraction

  • n_subjects — 21 participants took part: 11 received a random mix of sham and actual ultrasound, 10 sham only. Recorded the 11 who received actual ultrasound.
  • exposures[0].fundamental_frequency_khz — Only the transducer band "13-6 MHz" is given, no operating or centre frequency; recorded as the range 6-13 MHz.
  • exposures[0].timing.waveform — Diagnostic scanner; pulse length, PRF and duty cycle never stated (only MI 0.7), so waveform left not_reported.
  • exposures[0].free_field.pressure_kpa — Only a mechanical index of 0.7 is given; no pressure or intensity and no domain.