40 Hz noninvasive transcranial ultrasound stimulation modulates multiscale nonlinear dynamics of hippocampal CA1 neural oscillations of Alzheimer’s mouse model
Jiamin Chen, Hui Ji, Yi Yuan
Journal of Neural Engineering 2026 · 10.1088/1741-2552/ae9eed
Abstract
Objective. Aberrant nonlinear dynamics of hippocampal neural oscillations are a hallmark of early network dysfunction in Alzheimer's disease (AD), with critical roles in memory processing. Although transcranial ultrasound stimulation (TUS) has shown cognitive benefits in AD models and patients, its effects on the nonlinear dynamics of hippocampal CA1 oscillations and their multiscale organization remain unclear. Approach. Here, we applied 40 Hz noninvasive TUS to the hippocampal CA1 region of AD mouse model and recorded local field potentials before, during, and after stimulation. Analyses integrated nonlinear dynamical metrics, power spectral dependencies, cross-frequency coupling, and event-level oscillatory features. Main results. We found that (1) 40 Hz TUS decreases complexity and irregularity of CA1 activity, and enhances dynamical activity and long-range temporal correlations in broadband and high-frequency ranges, increases complexity in the theta and beta bands. (2) TUS also significantly reduced theta-gamma and intra-gamma phase-amplitude coupling, while producing frequency-specific changes in the rate, amplitude, duration, and temporal organization of theta, gamma, and ripple events. (3) Furthermore, the relationship between nonlinear dynamics and power spectral density was modulated across stimulation phases. Significance. 40 Hz TUS can modulate multiscale nonlinear dynamics of neural oscillations in hippocampal CA1 of Alzheimer's mouse model, which lays a theoretical foundation for the clinical intervention of AD via ultrasound stimulation.
Abstract via europepmc.
Exposures
Exposure 1: 40 Hz TUS to hippocampal CA1 in AD (APP/PS1) and wild-type mice
Target: CA1 — “hippocampal CA1 region”
Device: Olympus / Panametrics · Olympus, USA · V302-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 1.25 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 40 | ✓✓✓ |
| Duty cycle (%) | 5 | ✓✓✓ |
| Sonication duration (s) | 10 | ✓✓✓ |
| 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) | 360 | ✓✓✓⚑ |
| Isppa, domain unspecified (W/cm²) | 4.3 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.217 | ✓✓✓ |
Ultrasound stimulation was delivered at a pulse repetition frequency (PRF) of 40 Hz, with a duty cycle of 5% and a duration of 10 s per trial. LFPs were recorded before, during, and after stimulation in awake, head-fixed mice; five experimental groups (WT, AD, AD+TUS, AD+Sham, WT+TUS, n=6 each) were tested in the Morris water maze before and after intervention, with only the AD+TUS and WT+TUS groups receiving real 40 Hz TUS.
Flags from extraction
n_subjects— All five behavioural groups (WT, AD, AD+TUS, AD+Sham, WT+TUS) are reported with n=6 each; only AD+TUS and WT+TUS received real 40 Hz TUS, so those two group sizes are listed rather than summed.exposures[0].unspecified_domain.pressure_kpa— Paper does not state whether the reported acoustic pressure/Isppa/Ispta were measured free-field (e.g. hydrophone in water) or simulated/derated in situ; only a COMSOL finite-element simulation is mentioned for confirming focal targeting, not explicitly linked to these numbers, so values are placed in unspecified_domain.exposures[0].timing.pulse_duration_ms— Only duty cycle (5%) and PRF (40 Hz) are given; the paper does not separately state a pulse duration, and it is not computed here per the burst rule.n_sessions_per_subject— The paper describes a single 10 s per-trial stimulation and pre/on/post LFP recording, but does not state how many trials/days of TUS each animal received before the post-intervention Morris water maze test.sham_type— AD+Sham group underwent 'transducer coupling and the sham stimulation procedure' but the paper does not describe the specific sham mechanism (e.g. power off vs. no coupling).