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Effects of Low-Intensity Transcranial Ultrasound Stimulation on Cortical Functional Network Connections and Epileptic Seizures in a Mouse Model of Epilepsy

Na Pang, Qianqian Wang, Hailin Zhang, Rui Su, Jiaqing Yan, Yi Yuan

IEEE Transactions on Neural Systems and Rehabilitation Engineering 2026 · 10.1109/tnsre.2026.3664698

rodentepilepsyinvasive electrophysiology

Abstract

Exploration of the epilepsy cortical network is helpful for understanding the pathophysiological mechanisms of epilepsy and optimizing the treatment direction of epilepsy. Low-intensity transcranial ultrasound stimulation (TUS), characterized by non-invasiveness, high penetration depth, and high spatial resolution, has the potential to modulate brain functional networks. Nevertheless, the specific mechanisms by which TUS influences the cortical network in awake epilepsy model mice remain inadequately understood. Here, we observed that TUS significantly decreased the power of the whole cerebral cortex, diminished the phase lag index functional connectivity strength of the whole cerebral cortex, reduced the strength of cortical network connections, and accelerated the transition process from the epileptic seizure state to the normal state. Taken together, these findings indicated that epileptic seizures were suppressed after TUS modulated cortical functional network connections in mice.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects10, 10swept animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingboth
Anaesthesiaawake
Readoutsinvasive electrophysiology — multi-channel cortical LFP; phase lag index functional connectivity; graph theory metrics; seizure rate
Direction of effectinhibitoryTUS of the hippocampus reduced cortical LFP power, PLI connectivity and network strength and accelerated recovery from seizure state in penicillin-induced epileptic mice.
Adverse eventsnot reportedTemperature rise and MI were calculated theoretically (maximum 0.026 C, MI 0.33); no in vivo safety assessment is described.

Exposures

Exposure 1: hippocampal TUS

Target: hippocampus — “hippocampus”
Device: Olympus / Panametrics · Olympus, USA · V302-SU ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,000✓✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 1 ms (not stated by the paper)⚑
Pulse repetition frequency (Hz)500✓✓✓
Duty cycle (%)50✓✓✓
Sonication duration (s)900✓✓✓⚑
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)330✓✓✓⚑
Protocol, in the paper’s words

Fundamental frequency 1 MHz, PRF 500 Hz, duty cycle 50%, total intervention duration 15 min, acoustic pressure 0.33 MPa, delivered to awake mice 40 min after the pre-TUS baseline period.

Flags from extraction

  • exposures[0].unspecified_domain.pressure_kpa — 0.33 MPa acoustic pressure given without stating the domain
  • exposures[0].timing.pulse_duration_ms — Pulse duration not stated
  • exposures[0].timing.sonication_duration_s — 15 min is the total intervention duration; whether it is continuous pulsed sonication is not detailed
  • sham_type — Sham: collimator did not touch the skull so waves propagated parallel to the skull; classed as aimed away