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Low-Intensity Transcranial Ultrasound Stimulation Improves Motor Behavior and Modulates Cortical Functional Network Connectivity in Mice with Ischemic Stroke

Shaopo Wan, Qianqian Wang, Yanan Wang, Dongyang Huang, Jiaqing Yan, Honglei Jiao, Xiao Zhang, Yi Yuan

The Journal of Neuroscience 2026 · 10.1523/jneurosci.2329-25.2026

rodentstrokeinvasive electrophysiologybehaviourhistology molecular

Abstract

The recovery of motor function in patients with ischemic stroke is closely related to the plastic remodeling of cortical functional networks. Low-intensity transcranial ultrasound stimulation (TUS) has been shown to improve motor behavior in patients with ischemic stroke and modulate cortical functional networks in healthy individuals. However, whether motor improvement after TUS is associated with cortical functional network reorganization remains unclear. Therefore, in this study, we constructed a mouse model of ischemic stroke using male C57BL/6 mice and simultaneously recorded the local field potential and gait behavior data of the whole-brain cortex of mice in a free-walking state before and after ultrasound intervention. Gait parameters, cortical functional network connectivity (CFNC), and topology were systematically analyzed, and the correlations between behavioral indicators and network connectivity were explored. Our findings revealed that TUS significantly improved motor function in the mouse model, modulated CFNC to restore it to a healthy state, enhanced global information integration ability, optimized local separation efficiency, and restored gait phase transition control. Furthermore, the TUS-induced changes in the cortical functional network were positively correlated with behavioral improvement. This study confirmed that motor improvement after low-intensity TUS is accompanied by cortical functional network reorganization and that such reorganization may contribute to post-stroke functional recovery.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects11 animals
Sessions per subject7
Randomisedyes
Blindingnot reported
Sham / controlundescribed, no treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesianot reported
Readoutsinvasive electrophysiology, behaviour, histology molecular — cortical LFP (wPLI functional connectivity, graph theory); gait analysis; TTC infarct staining
Direction of effectmixed or unclearAfter 7 days of TUS, gait indices recovered faster than sham and cortical network connectivity shifted toward the healthy pattern; effect persisted to Day 14 and weakened by Day 21.
Adverse eventsnot reportedMechanical index calculated as about 0.19 and theoretical temperature rise about 0.0008 C; no adverse-event assessment reported.

Exposures

Exposure 1: TUS of infarct area

Target: cerebral cortex — “infarct area”
Device: Olympus / Panametrics · Olympus · V301-SU (nonfocused; driven by TUNSS-1) ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,000✓✓✓
Pulse duration (ms)50✓✓✓
Pulse repetition frequency (Hz)1✓✓✓
Duty cycle (%)5pulse duration × PRF gives 5%✓✓✓
Sonication duration (s)300✓✓✓
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 estimatemeasurementsingle value
In-situ pressure (kPa)186✓✓✓⚑
In-situ Isppa (W/cm²)1.15✓✓✓
In-situ Ispta (W/cm²)0.057✓✓✓
Protocol, in the paper’s words

FF 1 MHz; PRF 1 Hz; pulse train duration 5 min; DC 5%; PD 50 ms; interstimulus interval 5 min; stimulation once daily for 15 min, for 7 consecutive days starting on Day 1 after stroke.

Flags from extraction

  • exposures[0].target.label — Target is described only as the infarct area (distal MCA occlusion, right hemisphere); cortex term chosen by inference from the model.
  • n_subjects — 33 mice in three groups of 11; 11 received TUS (stroke + TUS group).
  • exposures[0].in_situ.pressure_kpa — Pressure measured with a hydrophone behind the skull; the Discussion says ex vivo skull. Isppa and Ispta were calculated by the authors from it.
  • exposures[0].timing.protocol_description — Pulse train 5 min with 5 min ISI within a 15 min daily session; PRF 1 Hz with PD 50 ms gives 5 % as stated.
  • sham_type — Sham stimulation mechanism not described; normal group received no stimulation.
  • exposures[0].device.family — TUNSS-1 is the driving device; transducer maker is Olympus.