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Low-intensity transcranial ultrasound stimulation suppresses abnormal neural oscillations in the motor cortex by stimulating STN in α-synucleinA53T mice

Qianqian Wang, Shuxun Dong, Zhe Zhao, Zhenfang Ma, Xiaoli Li, Jiaqing Yan, Yi Yuan

Acta Neuropathologica Communications 2026 · 10.1186/s40478-026-02344-5

rodentparkinsons diseaseinvasive electrophysiologybehaviourhistology molecular

Abstract

Previous studies have shown that low-intensity transcranial ultrasound stimulation (TUS) of the subthalamic nucleus (STN) in mice with Parkinson's disease (PD) effectively suppresses pathological discharge activities in motor cortex. However, how TUS modulates the neural activity of the STN-motor cortex circuits, and the long-term effects of suppressing abnormal neural oscillations in α-synuclein A53T (α-syn) mice remain unclear. Here, we conducted STN-targeted ultrasound in α-syn mice, and examined the treatment efficacy via behavior test and electrophysiology in vivo. Alterations in neural activity patterns were specifically assessed in α-syn mice during pre- and post-therapeutic interventions. We found that TUS targeted at STN significantly (1) ameliorated abnormal neural activity in the STN, (2) reduced the neural correlation between STN and motor cortex, and (3) improved locomotor capability in α-syn mice. Thus, our results demonstrated that STN-targeted TUS rebalanced the neural activity in STN-motor cortex circuit, which was causally linked to the improvement of motor function in α-syn transgenic mice.

Abstract via europepmc.

Speciesmouse (B6-Tg alpha-synuclein A53T)
Subjects8, 10swept animals
Sessions per subject1, 7swept
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer, no treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology, behaviour, histology molecular — STN and M1 LFP (theta/beta power, PAC, STN-M1 correlation); M1 single-unit firing; open field; rotarod; histology for tissue damage
Direction of effectinhibitorySTN-targeted TUS reduced theta and beta power and theta-beta PAC in STN and M1, lowered STN-M1 LFP correlation and M1 firing rates, and improved open-field and rotarod performance; the effect after 7 days persisted to Day 14 and weakened over time.
Adverse eventsnone observedHistological analysis 7 days after stimulation with the same parameters showed no tissue damage in the STN or adjacent regions; temperature rise calculated as about 0.02 C.

Exposures

Exposure 1: TUS of left STN

Target: subthalamic nucleus — “left STN”
Device: Olympus / Panametrics · Olympus · V301-SU ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.05 ms (not stated by the paper)⚑
Pulse repetition frequency (Hz)1,000✓✓✓⚑
Duty cycle (%)5✓✓✓
Sonication duration (s)0.05✓✓✓
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)390✓✓✓⚑
Isppa, domain unspecified (W/cm²)5.1✓✓✓
Ispta, domain unspecified (W/cm²)0.255✓✓✓
Protocol, in the paper’s words

500 kHz, PRF 1 kHz, duty cycle 5%, 'stimulation duration' 50 ms, total stimulation time 30 min per session, under 0.6% isoflurane. One session before testing on Day 1 (part 1) or 30 min on 7 consecutive days with testing on Days 7 and 14 (part 2).

Flags from extraction

  • n_subjects — Group sizes of the alpha-syn + TUS group in part 1 (8) and part 2 (10); 42 WT and 132 alpha-syn mice were used overall, most not exposed to ultrasound.
  • exposures[0].timing.pulse_duration_ms — 'Stimulation duration' of 50 ms is stated alongside a 1 kHz PRF and 5% duty cycle; 50 ms is incompatible with a 1 ms period, so the pulse duration is left not_reported.
  • exposures[0].timing.pulse_repetition_frequency_hz — 1 kHz PRF as stated, which looks inconsistent with the 50 ms 'stimulation duration'; recorded as written.
  • exposures[0].unspecified_domain.pressure_kpa — Maximum sound pressure and intensities are given without a stated domain; Ispta 255 mW/cm2 recorded as 0.255 W/cm2.
  • exposures[0].target.label — Target STN recorded as left STN; the beam was angled at 30 degrees to reach it.