Transcranial ultrasound stimulation modulates neural activities during NREM and REM depending on the stimulation phase of slow oscillations and theta waves in the hippocampus
Shuxun Dong, Zhenyu Xie, Yi Yuan
Cerebral Cortex 2023 · 10.1093/cercor/bhad174
Abstract
Modulation of the hippocampal neural activity by low-intensity transcranial ultrasound stimulation depends on the phase of theta rhythm and can also regulate sleep rhythm. However, until now, the modulatory effect of ultrasound stimulation on neural activity in different sleep states depending on the phase of local field potential stimulation in the hippocampus was unclear. To answer this question, closed-loop ultrasound stimulation was applied to in-phase (upstate)/out-of-phase slow oscillations in the hippocampus during non-rapid eye movement sleep, and to the peaks and troughs of theta oscillations in the hippocampus during wake in a mouse model. Local field potential of the hippocampus within 3-h after the ultrasound stimulation during light-on sleep cycle was recorded. We found that (i) under slow-oscillation in-phase stimulation, ultrasound stimulation upregulated the non-rapid eye movement ratio and decreased the wake ratio. Furthermore, it increased the ripple density during non-rapid eye movement and enhanced the coupling of the spindle-ripple during non-rapid eye movement as well as the theta-high gamma phase-amplitude coupling during the REM period. In addition, theta during the REM period showed a more stable oscillation mode. (ii) Under slow-oscillation out-of-phase stimulation, ultrasound stimulation increased the density of ripple during non-rapid eye movement and enhanced the theta-high gamma phase-amplitude coupling strength during REM. Furthermore, theta oscillations during REM were significantly slower and showed higher variability. (iii) Under the phase-locked peak and trough stimulation of theta oscillation, ultrasound stimulation increased the ripple density during non-rapid eye movement, weakened the coupling strength of spindle-ripple during non-rapid eye movement, and enhanced theta-high gamma phase-amplitude coupling during REM. However, theta oscillation mode was not changed significantly during REM. The above results suggest that the regulatory effect of ultrasound stimulation on neural activity in different sleep states depends on the stimulation phases of slow oscillations and theta waves in the hippocampus.
Abstract via europepmc.
Exposures
Exposure 1: closed-loop TUS to hippocampus: SO in-phase, SO out-of-phase, theta peak, theta trough
Target: CA1 — “hippocampus (CA1 region)”
Device: Olympus / Panametrics · Olympus · V301-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.8 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 80 | ✓✓✓ |
| Sonication duration (s) | 0.05, 0.4swept | ✓✓✓⚑ |
| 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) | 180 | ✓✓✓⚑ |
Phase-locked closed-loop stimulation: SD 50 ms for theta peak/trough stimulation in wake and 400 ms for slow-oscillation in-phase/out-of-phase stimulation in NREM; each stimulation period lasted 15 min, given daily over 4 days, with 3 h LFP recorded afterwards.
Flags from extraction
n_subjects— n=36 total includes 6 sham mice and 6 mice in the auditory control experiment B.exposures[0].unspecified_domain.pressure_kpa— 'Sound pressure' 0.18 MPa without stating water, skull or simulated; a COMSOL field simulation is described but no value is given.exposures[0].timing.sonication_duration_s— SD 50 ms (theta) and 400 ms (SO); 'SD' defined as stimulation duration; pulse duration not stated so left not_reported.exposures[0].timing.waveform— Four phase-locked protocols with different SD; treated as one exposure at one target and frequency.