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Five Hz sinusoidal amplitude-modulated focused ultrasound regulates hippocampal oscillations and alleviates cognitive impairment in 5xFAD

Ruru Wang, Xin Wang, Jingna Jin, He Wang, Xiaoqing Zhou, Ren Ma, Tao Yin, Zhipeng Liu

Alzheimer's Research & Therapy 2026 · 10.1186/s13195-026-02211-4

rodentalzheimers diseaseinvasive electrophysiologybehaviour
Speciesmouse (5xFAD transgenic; C57BL/6J wild-type littermates)
Subjects8 animals
Sessions per subject14
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingboth
Anaesthesianot reported
Readoutsinvasive electrophysiology, behaviour — Hippocampal DG/PP LFP power, PLV, coherence, theta-gamma PAC; Y-maze; novel object recognition; Morris water maze
Direction of effectmixed or unclear5 Hz AM-FUS reduced elevated theta power, increased high-gamma power, restored PP-DG synchrony and improved learning and memory in 5xFAD mice.
Adverse eventsnot reported

Exposures

Exposure 1: 5 Hz sinusoidal AM-FUS to hippocampus

Target: hippocampus, dentate gyrus — “hippocampus (DG and perforant pathway)”
Device: other named manufacturer · Institute of Acoustics, Chinese Academy of Sciences · 0.5 M-D20-F20 ✓

Pulse timing
Waveformother patterned
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.4 ms (not stated by the paper)⚑
Pulse repetition frequency (Hz)1,000✓✓✓
Duty cycle (%)40✓✓✓
Sonication duration (s)1✓✓✓⚑
Pressure and intensity, by domain
Free-field pressure (kPa)380✓✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)0.3✓✓✓⚑
In-situ estimatederatingsingle value
In-situ pressure (kPa)180✓✓✓⚑
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)0.0683✓✓✓
Protocol, in the paper’s words

500 kHz carrier, 1 kHz PRF, 40% duty cycle, mixed with a 2.5 Hz sine wave giving an effective 5 Hz envelope; 150 trials each 1 s with a 3-s interval; daily 20-min session for 14 days.

Flags from extraction

  • n_subjects — Only the 8 AD AM-FUS mice were sonicated; 16 5xFAD plus 8 WT mice purchased, sham and WT groups had amplifier off
  • exposures[0].timing.pulse_duration_ms — Pulse duration not stated; carrier is 1 kHz PRF at 40% duty cycle under a 2.5 Hz sinusoidal envelope (effective 5 Hz); not computed
  • exposures[0].timing.waveform — Amplitude-modulated carrier (sinusoidal envelope) classed as other_patterned
  • exposures[0].timing.sonication_duration_s — 1-s sonications repeated in 150 trials with 3-s intervals; 20-min daily session
  • exposures[0].free_field.ispta_w_cm2 — Quoted as 300 mW/cm2; converted to W/cm2
  • exposures[0].in_situ.pressure_kpa — Derated with an ex vivo skull transmission coefficient of 47.73%; peak negative pressure
  • anaesthesia — Anaesthesia during stimulation not stated; isoflurane only for electrode surgery
  • readouts — Behavioural tests after 14 days, LFP on days 1, 7, 14 and acute pre/during/post