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Modulation effect of low-intensity transcranial ultrasound stimulation on REM and NREM sleep

Teng Wang, Xingran Wang, Yanfei Tian, Wei Gang, Xiaoli Li, Jiaqing Yan, Yi Yuan

Cerebral Cortex 2023 · 10.1093/cercor/bhac413

rodenthealthyalzheimers diseaseotherinvasive electrophysiology

Abstract

Previous studies have shown that modulating neural activity can affect rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Low-intensity transcranial ultrasound stimulation (TUS) can effectively modulate neural activity. However, the modulation effect of TUS on REM and NREM sleep is still unclear. In this study, we used ultrasound to stimulate motor cortex and hippocampus, respectively, and found the following: (i) In healthy mice, TUS increased the NREM sleep ratio and decreased the REM sleep ratio, and altered the relative power and sample entropy of the delta band and spindle in NREM sleep and that of the theta and gamma bands in REM sleep. (ii) In sleep-deprived mice, TUS decreased the ratio of REM sleep or the relative power of the theta band during REM sleep. (iii) In sleep-disordered Alzheimer's disease (AD) mice, TUS increased the total sleep time and the ratio of NREM sleep and modulated the relative power and the sample entropy of the delta and spindle bands during NREM and that of the theta band during REM sleep. These results demonstrated that TUS can effectively modulate REM and NREM sleep and that modulation effect depends on the sleep state of the samples, and can improve sleep in sleep-disordered AD mice.

Abstract via europepmc.

Speciesmouse (C57BL/6N; APP/PS1)
Subjects10, 6, 6, 6, 6swept animals
Sessions per subject7
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlcontrol experiment
Readout timingoffline
Anaesthesiaawake
Readoutsinvasive electrophysiology — LFP and EMG sleep scoring (TST, NREM/REM ratios, relative power, sample entropy)
Direction of effectmixed or unclearTUS increased the NREM sleep ratio and decreased the REM ratio in healthy mice without changing total sleep time; in sleep-disordered AD mice it increased total sleep time; effects depended on sleep state.
Adverse eventsnot reportedTemperature rise estimated by calculation as about 9.2e-3 degrees C.

Exposures

Exposure 1: TUS of motor cortex

Target: primary motor cortex — “motor cortex”
Device: Olympus / Panametrics · Olympus · V301-SU ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)50✓✓✓⚑
Pulse repetition frequency (Hz)1✓✓✓
Duty cycle (%)5pulse duration × PRF gives 5%✓✓✓
Sonication duration (s)300✓✓✓⚑
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
Pressure, domain unspecified (kPa)530✓✓✓⚑
Isppa, domain unspecified (W/cm²)9.3✓✓✓
Ispta, domain unspecified (W/cm²)0.466✓✓✓
Protocol, in the paper’s words

500 kHz, PRF 1 Hz, DC 5%, stimulation duration 50 ms. The stimulation pattern was 5 min of stimulation followed by a 5-min interval for a total of 25 min for 7 days.

Exposure 2: TUS of hippocampus

Target: hippocampus — “hippocampus”
Device: Olympus / Panametrics · Olympus · V301-SU ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)50✓✓✓
Pulse repetition frequency (Hz)1✓✓✓
Duty cycle (%)5pulse duration × PRF gives 5%✓✓✓
Sonication duration (s)300✓✓✓
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
Pressure, domain unspecified (kPa)530✓✓✓⚑
Isppa, domain unspecified (W/cm²)9.3✓✓✓
Ispta, domain unspecified (W/cm²)0.466✓✓✓
Protocol, in the paper’s words

500 kHz, PRF 1 Hz, DC 5%, stimulation duration 50 ms. The stimulation pattern was 5 min of stimulation followed by a 5-min interval for a total of 25 min for 7 days.

Flags from extraction

  • n_subjects — Strain totals only (C57BL/6N 56, APP/PS1 12); these include controls and the auditory check animals, so group sizes listed rather than a count of sonicated mice.
  • exposures[0].timing.pulse_duration_ms — Text calls 50 ms 'stimulation duration'; with 5% duty cycle and 1 Hz PRF this is the pulse duration (resolved by arithmetic), while the sonication is 5 min blocks.
  • exposures[0].timing.sonication_duration_s — 5 min of stimulation then 5 min interval, 25 min total per day for 7 days; 300 s per block.
  • exposures[0].unspecified_domain.pressure_kpa — Pressure and intensities given without stating domain.
  • exposures[1].unspecified_domain.pressure_kpa — Same parameters as the motor cortex exposure; hippocampus recordings were in subsets (n=6).
  • sham_type — Control group had amplifier-transducer connection disconnected.
  • auditory_control — Separate experiment: 6 healthy mice stimulated with a specific ultrasound to which they had no auditory response (Supplementary Fig. S5).
  • n_sessions_per_subject — Recorded as 7 from 'for 7 days' (daily stimulation); LFP recorded on days 1, 3 and 7.