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Effect of low-intensity transcranial ultrasound stimulation on theta and gamma oscillations in the mouse hippocampal CA1

Zhen Li, Rong Chen, Dachuan Liu, Xizhe Wang, Wei Yuan

Frontiers in Psychiatry 2023 · 10.3389/fpsyt.2023.1151351

rodenthealthyinvasive electrophysiology

Abstract

Previous studies have demonstrated that low-intensity transcranial ultrasound stimulation (TUS) can eliminate hippocampal neural activity. However, until now, it has remained unclear how ultrasound modulates theta and gamma oscillations in the hippocampus under different behavioral states. In this study, we used ultrasound to stimulate the CA1 in mice in anesthesia, awake and running states, and we simultaneously recorded the local field potential of the stimulation location. We analyzed the power spectrum, phase-amplitude coupling (PAC) of theta and gamma oscillations, and their relationship with ultrasound intensity. The results showed that (i) TUS significantly enhanced the absolute power of theta and gamma oscillations under anesthesia and in the awake state. (ii) The PAC strength between theta and gamma oscillations is significantly enhanced under the anesthesia and awake states but is weakened under the running state with TUS. (iii) Under anesthesia, the relative power of theta decreases and that of gamma increases as ultrasound intensity increases, and the result under the awake state is opposite that under the anesthesia state. (iv) The PAC index between theta and gamma increases as ultrasound intensity increases under the anesthesia and awake states. The above results demonstrate that TUS can modulate theta and gamma oscillations in the CA1 and that the modulation effect depends on behavioral states. Our study provides guidance for the application of ultrasound in modulating hippocampal function.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects42 animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesiaboth
Readoutsinvasive electrophysiology — local field potential in CA1: theta and gamma power, theta-gamma phase-amplitude coupling
Direction of effectbidirectionalTUS increased theta and gamma absolute power and theta-gamma PAC under anaesthesia and awake states but not (PAC decreased) in the running state; relative power trends with intensity were state dependent.
Adverse eventsnot reported

Exposures

Exposure 1: TUS of CA1, anaesthesia, awake and running states

Target: CA1 — “CA1”
Device: not reported

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)2,250✓✓✓
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✓✓✓
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)150, 300, 450, 600, 750swept✓✓✓⚑
Isppa, domain unspecified (W/cm²)0.75, 3, 6.75, 12, 18.75swept✓✓✓
Protocol, in the paper’s words

16 trials per animal; each trial 400 ms stimulation duration at 1 kHz PRF and 50% duty cycle. Intensity 0.45 MPa for the theta/gamma comparison across states; five intensities for the intensity series.

Flags from extraction

  • n_subjects — 42 mice in total: 21 for state comparison, 21 for the intensity series (7 per state in each).
  • exposures[0].timing.pulse_duration_ms — Pulse duration not stated; 400 ms is the stimulation duration (train), not the pulse.
  • exposures[0].unspecified_domain.pressure_kpa — Intensities given in MPa without stating whether water or in situ; converted 0.15-0.75 MPa to kPa. Focused beam at about 45 degrees into the brain.
  • exposures[0].device.family — Transducer not described; refers to previous papers.
  • anaesthesia — 0.5% isoflurane in the anaesthesia group; awake and running groups head-fixed without anaesthesia.