Effects of Transcranial Ultrasound Stimulation on Trigeminal Blink Reflex Excitability
Andrea Guerra, Edoardo Vicenzini, Ettore Cioffi, Donato Colella, Antonio Cannavacciuolo, Silvia Pozzi, Barbara Caccia, Giulia Paparella, Giulia Di Stefano, Alfredo Berardelli, Matteo Bologna
Brain Sciences 2021 · 10.3390/brainsci11050645
Abstract
Recent evidence indicates that transcranial ultrasound stimulation (TUS) modulates sensorimotor cortex excitability. However, no study has assessed possible TUS effects on the excitability of deeper brain areas, such as the brainstem. In this study, we investigated whether TUS delivered on the substantia nigra, superior colliculus, and nucleus raphe magnus modulates the excitability of trigeminal blink reflex, a reliable neurophysiological technique to assess brainstem functions in humans. The recovery cycle of the trigeminal blink reflex (interstimulus intervals of 250 and 500 ms) was tested before (T0), and 3 (T1) and 30 min (T2) after TUS. The effects of substantia nigra-TUS, superior colliculus-TUS, nucleus raphe magnus-TUS and sham-TUS were assessed in separate and randomized sessions. In the superior colliculus-TUS session, the conditioned R2 area increased at T1 compared with T0, while T2 and T0 values did not differ. Results were independent of the interstimulus intervals tested and were not related to trigeminal blink reflex baseline (T0) excitability. Conversely, the conditioned R2 area was comparable at T0, T1, and T2 in the nucleus raphe magnus-TUS and substantia nigra-TUS sessions. Our findings demonstrate that the excitability of brainstem circuits, as evaluated by testing the recovery cycle of the trigeminal blink reflex, can be increased by TUS. This result may reflect the modulation of inhibitory interneurons within the superior colliculus.
Abstract via europepmc.
Exposures
Exposure 1: Superior colliculus TUS
Target: superior colliculus — “superior colliculus”
Device: other named manufacturer · Siemens Medical Solutions · 4 P1 probe (Siemens S2000 apparatus) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,750 | ✓✓✓⚑ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | 4,340 | ✓✓✓⚑ |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 180 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 152 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Standard diagnostic transcranial imaging settings (B-mode with simultaneous pulsed-wave Doppler, 2 MHz, PRF 4340) with the mechanical index at 100% (1.4; TIC 2.2) and the probe frequency reduced to 1.75 MHz; the target nucleus was kept on screen and insonated for 180 s. Sham used the 'freezing' machine ultrasound option.
Exposure 2: Nucleus raphe magnus TUS
Target: raphe nuclei — “nucleus raphe magnus”
Device: other named manufacturer · Siemens Medical Solutions · 4 P1 probe (Siemens S2000 apparatus) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,750 | ✓✓✓ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | 4,340 | ✓✓✓ |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 180 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 152 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Standard diagnostic transcranial imaging settings (B-mode with simultaneous pulsed-wave Doppler, 2 MHz, PRF 4340) with the mechanical index at 100% (1.4; TIC 2.2) and the probe frequency reduced to 1.75 MHz; the target nucleus was kept on screen and insonated for 180 s. Sham used the 'freezing' machine ultrasound option.
Exposure 3: Substantia nigra TUS
Target: substantia nigra — “substantia nigra”
Device: other named manufacturer · Siemens Medical Solutions · 4 P1 probe (Siemens S2000 apparatus) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,750 | ✓✓✓ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | 4,340 | ✓✓✓ |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 180 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 152 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Standard diagnostic transcranial imaging settings (B-mode with simultaneous pulsed-wave Doppler, 2 MHz, PRF 4340) with the mechanical index at 100% (1.4; TIC 2.2) and the probe frequency reduced to 1.75 MHz; the target nucleus was kept on screen and insonated for 180 s. Sham used the 'freezing' machine ultrasound option.
Flags from extraction
exposures[0].fundamental_frequency_khz— Diagnostic probe frequency lowered to 1.75 MHz for B-mode; the pulsed-wave Doppler ran at 2 MHz simultaneously. Recorded 1750 kHz.exposures[0].timing.pulse_repetition_frequency_hz— PRF 4340 is the pulsed-wave Doppler PRF as written (no unit given; presumably Hz). Pulse duration and duty cycle are not stated; the imaging B-mode pulse timing is not described.exposures[0].in_situ.pressure_kpa— Single simulated (k-Wave) pressure of 152 kPa 'in the brainstem' applied to all three targets; the paper does not give per-nucleus values and gives no intensity.n_sessions_per_subject— Four sessions per subject include one sham session (three TUS sessions).exposures[0].target.terms— Targets were identified on transcranial B-mode imaging; ~15 mm target area, substantial overlap between nuclei likely. Nucleus raphe magnus mapped to raphe_nuclei.sham_type— Sham used the 'freezing' option of the ultrasound machine; classed as inactive_transducer.n_subjects— Spelled out as 'Sixteen' in the text.