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Closed-Loop Transcranial Ultrasound Stimulation Based on Deep Learning Effectively Suppresses Epileptic Seizures in Mice

Na Pang, Jingyan Sun, Hailin Zhang, Rong Chen, Jiaqing Yan, Yi Yuan

IEEE Transactions on Neural Systems and Rehabilitation Engineering 2025 · 10.1109/tnsre.2025.3589089

rodentepilepsyinvasive electrophysiology

Abstract

Transcranial ultrasound stimulation is a non-invasive neuromodulation technique characterized by its high spatial resolution and penetration depth, and it has shown an inhibitory effect on epilepsy. However, current applications predominantly employ open-loop transcranial ultrasound stimulation, which lacks the capacity to dynamically respond to seizures. In the present study, we designed and implemented a closed-loop transcranial ultrasound stimulation (CTUS) system comprising a signal acquisition module, a signal preprocessing module, a deep learning network model-based epileptic signal recognition module, and an ultrasound stimulation module to enable real-time detection and ultrasound intervention in the hippocampus of penicillin-induced epileptic mice. The results indicated that the CTUS system could accurately identify epileptic signals, significantly reduce the seizure firing rate, decrease the power intensity and phase-amplitude coupling, and enhance the sample entropy. These findings demonstrated that the deep learning-based CTUS system was efficient in suppressing seizures in mice.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects5 animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingboth
Anaesthesiaawake
Readoutsinvasive electrophysiology — LFP power, phase-amplitude coupling, sample entropy, seizure firing rate (deep-learning detection)
Direction of effectinhibitoryClosed-loop TUS of the hippocampus reduced the seizure firing rate and LFP power and phase-amplitude coupling, and increased sample entropy, versus sham in penicillin-induced epileptic mice.
Adverse eventsnot reportedAuthors state pressure, MI, calculated Isppa and temperature rise are below damage levels and cite a previous H&E study showing no damage; no safety assessment reported in this study.

Exposures

Exposure 1: Closed-loop TUS (CTUS) of hippocampus

Target: hippocampus — “hippocampus of penicillin-induced epileptic mice”
Device: Olympus / Panametrics · Olympus · 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)5✓✓✓⚑
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✓✓✓⚑
Isppa, domain unspecified (W/cm²)3.6✓✓✓⚑
Protocol, in the paper’s words

Closed loop: LFP segments identified by a deep learning model at 0.2 s intervals; on detecting a seizure signal a 5 s TUS (1 MHz, PRF 500 Hz, DC 50%, 0.33 MPa) was triggered, then recognition resumed and the cycle repeated. Open-loop comparison group received continuous 15 min TUS with the same parameters.

Flags from extraction

  • exposures[0].unspecified_domain.isppa_w_cm2 — Isppa 3.6 W/cm2 is described as calculated; domain not stated.
  • exposures[0].unspecified_domain.pressure_kpa — Acoustic pressure 0.33 MPa, domain not stated.
  • n_subjects — Ten mice allocated to CTUS and Sham (five each); the open-loop OTUS group (n = 5) is compared with a previous study. Only the CTUS group is counted as sonicated.
  • exposures[0].timing.sonication_duration_s — Each triggered stimulation lasted 5 s; number and spacing depend on detected seizures.