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Modulation effect of mouse hippocampal neural oscillations by closed-loop transcranial ultrasound stimulation

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

Journal of Neural Engineering 2022 · 10.1088/1741-2552/aca799

rodenthealthyinvasive electrophysiology

Abstract

Objective . Closed-loop transcranial ultrasound stimulation (TUS) can be applied at a specific time according to the state of neural activity to achieve timely and precise neuromodulation and improve the modulation effect. In a previous study, we found that closed-loop TUS at the peaks and troughs of the theta rhythm in the mouse hippocampus was able to increase the absolute power and decrease the relative power of the theta rhythm of local field potentials (LFPs) independent of the peaks and troughs of the stimulus. However, it remained unclear whether the modulation effect of this closed-loop TUS-induced mouse hippocampal neural oscillation depended on the peaks and troughs of the theta rhythm. Approach . In this study, we used ultrasound with different stimulation modes and durations to stimulate the peaks (peak stimulation) and troughs (trough stimulation) of the hippocampal theta rhythm. The LFPs in the area of ultrasound stimulation were recorded and the amplitudes and power spectra of the theta rhythm before and after ultrasound stimulation were analyzed. Main results . The results showed that (a) the relative change in amplitude of theta rhythm decreases as the number of stimulation trials under peak stimulation increases; (b) the relative change in the absolute power of the theta rhythm decreases as the number of stimulation trials under peak stimulation increases; (c) the relative change in amplitude of the theta rhythm increases nonlinearly with the stimulation duration (SD) under peak stimulation, and; (d) the relative change in absolute power exhibits a nonlinear increase with SD under peak stimulation. Significance . These results suggest that the modulation effect of closed-loop TUS on theta rhythm is dependent on the stimulation mode and duration under peak stimulation. TUS has the potential to precisely modulate theta rhythm-related neural activity.

Abstract via europepmc.

Speciesmouse (C57BL)
Subjects25 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controldeafened subjects
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology — hippocampal LFP theta amplitude and power
Direction of effectmixed or unclearTheta amplitude and absolute power increased after TUS while relative power decreased; the relative change depended on trial number and stimulation duration under peak stimulation only.
Adverse eventsnot reported

Exposures

Exposure 1: Closed-loop TUS at theta peak, trough or random phase

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

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
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)0.02, 0.06swept✓✓✓
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)180✓✓✓⚑
Protocol, in the paper’s words

Ultrasound triggered at the predicted peak, trough or a random phase of the hippocampal theta rhythm; PRF 1 kHz, DC 30%, stimulation duration 20-60 ms, 1-6 stimulation trials (SD 50 ms for the trial experiments, six trials for the duration experiments). Experiments repeated 16 times per setting with 5 s intervals and 15 min between settings.

Flags from extraction

  • exposures[0].unspecified_domain.pressure_kpa — Paper says 'sound pressure of 0.18 MPa' without stating whether water or in-brain; recorded as unspecified. Intensity is mentioned as a setting but no value is given.
  • exposures[0].timing.pulse_duration_ms — Pulse duration not stated (DC 30% and PRF 1 kHz given); left not_reported per no-arithmetic rule.
  • exposures[0].timing.protocol_description — Closed-loop phase-locked stimulation; number of stimulation trials (1-6) per theta peak/trough and stimulation duration (20-60 ms) varied. Paper text also says the transducer was aligned to the motor cortex in one sentence, inconsistent with the hippocampal target.
  • exposures[0].target.label — Hippocampus coordinates given (2 mm right, 2 mm posterior of bregma); section 2.4 mentions aligning to the motor cortex, likely a copy-over.