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Phase-locked closed-loop ultrasound stimulation modulates theta and gamma rhythms in the mouse hippocampus

Zhenyu Xie, Jiaqing Yan, Shuxun Dong, Hui Ji, Yi Yuan

Frontiers in Neuroscience 2022 · 10.3389/fnins.2022.994570

rodenthealthyinvasive electrophysiology

Abstract

Previous studies have demonstrated that open-loop transcranial ultrasound stimulation (TUS) can modulate theta and gamma rhythms of the local field potentials (LFPs) in the mouse hippocampus; however, the manner in which closed-loop TUS with different pressures based on phase-locking of theta rhythms modulates theta and gamma rhythm remains unclear. In this study, we established a closed-loop TUS system, which can perform closed-loop TUS by predicting the peaks and troughs of the theta rhythm. Comparison of the power, sample entropy and complexity, and phase-amplitude coupling (PAC) between the theta and gamma rhythms under peak and trough stimulation of the theta rhythm revealed the following: (1) the variation in the absolute power of the gamma rhythm and the relative power of the theta rhythm under TUS at 0.6-0.8 MPa differ between peak and trough stimulation; (2) the relationship of the sample entropy of the theta and gamma rhythms with ultrasound pressure depends on peak and trough stimulation; and (3) peak and trough stimulation affect the PAC strength between the theta and gamma rhythm as a function of ultrasound pressure. These results demonstrate that the modulation of the theta and gamma rhythms by ultrasound pressure depends on peak and trough stimulation of the theta rhythm in the mouse hippocampus.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects16 animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology — hippocampal LFP theta and gamma power, sample entropy, Lempel-Ziv complexity, theta-gamma phase-amplitude coupling
Direction of effectmixed or unclearAbsolute theta and gamma power rose with pressure while relative theta power fell; at 0.6-0.8 MPa trough-locked stimulation gave higher gamma absolute power, theta relative power and PAC than peak-locked stimulation.
Adverse eventsnot reported

Exposures

Exposure 1: closed-loop theta peak- or trough-locked TUS of CA1

Target: CA1 — “CA1 region of the hippocampus”
Device: Olympus / Panametrics · Olympus · V301-SU ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)2,250✓✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.3 ms (not stated by the paper)⚑
Pulse repetition frequency (Hz)1,000✓✓✓
Duty cycle (%)30✓✓✓
Sonication duration (s)0.1✓✓✓⚑
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)50, 800swept✓✓✓⚑
Protocol, in the paper’s words

Closed-loop stimulation triggered at the peak or trough of the hippocampal theta rhythm; stimulation duration 100 ms, PRF 1 kHz, duty cycle 30% within the stimulation, stimulation interval 3 s.

Flags from extraction

  • exposures[0].timing.pulse_duration_ms — Burst rule: DC 30% / PRF 1 kHz implies 0.3 ms pulses, so the 100 ms 'stimulation duration' is the train; pulse duration is not stated and was not computed.
  • exposures[0].unspecified_domain.pressure_kpa — Pressure swept from 0.05 to 0.8 MPa; the paper does not say whether this is free-field or through the skull (the field map is described as 'under the skull').
  • auditory_control — Auditory confounds are discussed citing earlier deaf-mouse work by the same group; no control was run in this study.
  • exposures[0].timing.sonication_duration_s — Only the 100 ms stimulation duration is given; total number of stimuli per animal is not stated.