The Effect of Low-Intensity Transcranial Ultrasound Stimulation on Neural Oscillation and Hemodynamics in the Mouse Visual Cortex Depends on Anesthesia Level and Ultrasound Intensity
Yi Yuan, Kaiqing Zhang, Yiyao Zhang, Jiaqing Yan, Zhijie Wang, Xingrang Wang, Mengyang Liu, Xiaoli Li
IEEE Transactions on Biomedical Engineering 2021, 68, 1619-1626 · 10.1109/tbme.2021.3050797
Abstract
Objective Low-intensity transcranial ultrasound stimulation (TUS) can induce motor responses, neural oscillation and hemodynamic responses. Early studies demonstrated that the motor responses evoked by TUS critically depend on anesthesia levels and ultrasound intensity. However, the neural mechanism of how anesthesia levels and ultrasound intensity influence on brain responses during TUS has never been explored yet. To investigate this question, we applied different anesthesia levels and ultrasound intensities on the visual cortex of mouse and observed neural oscillation change and hemodynamic responses during TUS. Methods low-intensity ultrasound was delivered to mouse visual cortex under different anesthesia levels, and simultaneous recordings for local field potentials (LFPs) and hemodynamic responses were carried out to measure and analyze the changes quantitatively. Results (i) The change of mean amplitude and mean relative power of sharp wave-ripple (SPW-R) in LFPs induced by TUS decreased as the anesthesia level increased (from awake to 1.5% isoflurane). (ii) The hemodynamic response level induced by TUS decreased as the anesthesia level increased (from awake to1.5% isoflurane). (iii) The coupling strength between neural activities and hemodynamic responses was dependent on anesthesia level. (iv) The neural activities and hemodynamic responses increase as a function of ultrasound intensity. Conclusion These results support that the neural activities and hemodynamic response of the mouse visual cortex induced by TUS are related to the anesthesia level and ultrasound intensity. Significance This finding suggests that careful maintenance of anesthesia level and ultrasound intensity is required to acquire accurate LFP and hemodynamic data from samples with TUS.
Abstract via europepmc.
Exposures
Exposure 1: TUS of visual cortex across anesthesia levels and ultrasound intensities
Target: visual cortex — “mouse visual cortex (AP=-3.8, ML=2.5)”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.5 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 0.4 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 50, 100, 300, 500, 550, 700, 900swept | ✓✓✓⚑ |
| Isppa, domain unspecified (W/cm²) | 0.08, 0.3, 3, 8.3, 10.1, 16.3, 27swept | ✓✓✓ |
A circular skull section (3.5 mm diameter) was removed to expose the visual cortex directly for TUS delivery. Mice were tested under 0% (awake), 0.3%, 0.9% and 1.5% isoflurane using a fixed maximum ultrasound pressure of 0.55 MPa (10.1 W/cm2 Isppa); a separate group of mice was tested at 0.3% and 0.9% isoflurane across a sweep of ultrasound pressures (0.05-0.9 MPa). Sixteen trials were averaged per condition; LFP and hemodynamic responses were quantified over a 0-3 s window from TUS onset.
Flags from extraction
exposures[0].timing.pulse_duration_ms— The 400 ms value is explicitly labelled 'stimulation duration' (SD, recorded as sonication_duration_s) in Methods, but the Discussion separately refers to '0.4s' as 'pulse duration' in a temperature calculation; duty cycle (50%) and PRF (1000 Hz) would imply an internal tone-burst of 0.5 ms, but this is not stated directly and is not computed here.exposures[0].unspecified_domain— Paper does not state whether pressures/intensities are free-field or in-situ; the visual cortex was directly exposed via craniotomy (no skull in the acoustic path), but this is not discussed by the authors as a domain distinction.exposures[0].unspecified_domain.pressure_kpa— List combines the single fixed pressure used in the anesthesia-level experiment (550 kPa) with the separate pressure sweep used in the ultrasound-intensity experiment (50-900 kPa); these are two different sub-experiments, not one continuous sweep.device— No transducer manufacturer or model is given in the main text; setup is described as similar to a previous study by the same group.