Neuronavigated Repetitive Transcranial Ultrasound Stimulation Induces Long-Lasting and Reversible Effects on Oculomotor Performance in Non-human Primates
Pierre Pouget, Stephen Frey, Harry Ahnine, David Attali, Julien Claron, Charlotte Constans, Jean-Francois Aubry, Fabrice Arcizet
Frontiers in Physiology 2020, 11 · 10.3389/fphys.2020.01042
Abstract
Since the late 2010s, Transcranial Ultrasound Stimulation (TUS) has been used experimentally to carryout safe, non-invasive stimulation of the brain with better spatial resolution than Transcranial Magnetic Stimulation (TMS). This innovative stimulation method has emerged as a novel and valuable device for studying brain function in humans and animals. In particular, single pulses of TUS directed to oculomotor regions have been shown to modulate visuomotor behavior of non-human primates during 100 ms ultrasound pulses. In the present study, a sustained effect was induced by applying 20-s trains of neuronavigated repetitive Transcranial Ultrasound Stimulation (rTUS) to oculomotor regions of the frontal cortex in three non-human primates performing an antisaccade task. With the help of MRI imaging and a frame-less stereotactic neuronavigation system (SNS), we were able to demonstrate that neuronavigated TUS (outside of the MRI scanner) is an efficient tool to carry out neuromodulation procedures in non-human primates. We found that, following neuronavigated rTUS, saccades were significantly modified, resulting in shorter latencies compared to no-rTUS trials. This behavioral modulation was maintained for up to 20 min. Oculomotor behavior returned to baseline after 18-31 min and could not be significantly distinguished from the no-rTUS condition. This study is the first to show that neuronavigated rTUS can have a persistent effect on monkey behavior with a quantified return-time to baseline. The specificity of the effects could not be explained by auditory confounds.
Abstract via europepmc.
Exposures
Exposure 1: rTUS to frontal eye field (FEF)
Target: frontal eye field — “frontal eye field (FEF)”
Device: Sonic Concepts · Sonic Concept, Bothell, WA, United States · H115 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 320 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 30pulse duration × PRF gives 30% | ✓✓✓ |
| Sonication duration (s) | 20 | ✓✓✓ |
| Free-field pressure (kPa) | 760 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 19 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 5.7 | ✓✓✓ |
| In-situ estimate | deratingmean or range across subjects | |
| In-situ pressure (kPa) | 440 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 6.5 | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 1.9 | ✓✓✓ |
Each experimental session contained one practice block followed by 7 blocks of 100 antisaccades (50 each side, randomly distributed); rTUS (20-s train) was delivered only after the first (pre-rTUS) block, and saccade behaviour was compared across the six subsequent post-rTUS blocks versus matched no-rTUS sessions. The pulse duration was 30 ms with a 1 ms rise/fall time to avoid abrupt pressure changes that generate brief white noise.
Exposure 2: rTUS to supplementary eye field (SEF)
Target: other — “supplementary eye field (SEF)”
Device: Sonic Concepts · Sonic Concept, Bothell, WA, United States · H115 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 320 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 30pulse duration × PRF gives 30% | ✓✓✓ |
| Sonication duration (s) | 20 | ✓✓✓ |
| Free-field pressure (kPa) | 760 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 19 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 5.7 | ✓✓✓ |
| In-situ estimate | deratingmean or range across subjects | |
| In-situ pressure (kPa) | 440 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 6.5 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 1.9 | ✓✓✓ |
Same protocol as the FEF exposure (7 blocks of 100 antisaccades, rTUS 20-s train delivered after block 1) but with the transducer targeting the SEF (monkey G) instead of the FEF (monkeys L and S).
Flags from extraction
exposures[0].in_situ.isppa_w_cm2— The paper also reports a separate, higher, k-Wave-simulation-based in-situ estimate for the FEF target (Isppa 21.2 W/cm2, Ispta 6.4 W/cm2, from a whole-head CT-based finite-element model), which conflicts with the skull-transmission-measurement-based estimate used here (Isppa 6.5+/-1.8 W/cm2, Ispta 1.9 W/cm2, tied explicitly to the applied 30% duty cycle); the measurement-based value was used as it is directly linked to the delivered protocol.sham_type— Control conditions comprised both no-rTUS sessions with the transducer placed but inactive (inactive_transducer) and active rTUS delivered to control brain regions (V1 or M1; active_control_site); the control-region exposures are not given separate exposure entries since the paper treats them as behavioural controls rather than a primary study target.target— 'Supplementary eye field (SEF)' has no exact match in the target vocabulary (it is distinct from supplementary_motor_area); coded as 'other' with the paper's own label retained.n_sessions_per_subject— The paper states a total of 40 sessions (20 in ROI + 20 in control areas) across all three monkeys combined but does not give a clear per-subject session count.