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Seizure control by low-intensity ultrasound in mice with temporal lobe epilepsy

Xin Li, Huifang Yang, Jiaqing Yan, Xingran Wang, Yi Yuan, Xiaoli Li

Epilepsy Research 2019, 154, 1-7 · 10.1016/j.eplepsyres.2019.04.002

rodentepilepsyinvasive electrophysiology

Abstract

Background Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Recent studies have demonstrated that ultrasound stimulation can inhibit spontaneous recurrent seizures and improve behavioral outcomes for rodents with TLE. However, the exact underlying mechanism for inhibition of TLE via ultrasound stimulation remains unknown. Methods In this study, low-intensity pulsed ultrasound stimulation (LIPUS) and low-intensity continuous ultrasound stimulation (LICUS) and concurrent local field potentials (LFPs) in the CA3 field of the hippocampus were recorded in the kainite-induced mouse model of TLE. The power spectrum and the phase-amplitude coupling in the LFPs were quantitatively analyzed. Results We found three significant changes in LFPs after ultrasound stimulation: (i) the intensity of the power spectrum in the low frequency ( Conclusions These results indicate that the seizures of TLE can be effectively inhibited by ultrasound stimulation, and this effect is independent of ultrasound type (pulsed or continuous).

Abstract via europepmc.

Speciesmouse
Subjects8, 8, 5, 5swept animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlno treatment control
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiologyLocal field potential (LFP) recordings from CA3; power spectrum and phase-amplitude coupling (PACI) analysis
Direction of effectinhibitoryBoth pulsed (LIPUS) and continuous (LICUS) ultrasound to CA3 reduced low-frequency LFP power, decreased phase-amplitude coupling (delta/theta/alpha to gamma), reduced spike frequency, and lengthened the interval to the next seizure, with no significant difference between LIPUS and LICUS.
Adverse eventsnot reported

Exposures

Exposure 1: LIPUS and LICUS stimulation of hippocampal CA3 in kainate-induced TLE mice

Target: CA3 — “CA3 region of the hippocampus
Device: Olympus / Panametrics · Olympus · V301-SU

Pulse timing
Waveformpulsed, continuous
Fundamental frequency (kHz)500✓✓
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)30✓✓
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)260✓✓
Protocol, in the paper’s words

LIPUS: fundamental frequency 500 kHz, PRF 500 Hz, duty cycle 50%, stimulation duration 30 s. LICUS: continuous 500 kHz sine wave, stimulation duration 30 s. Ultrasound was manually triggered for 30 s once an LFP seizure (amplitude >3x background, lasting >10 s) was detected in the CA3 region via an unfocused transducer coupled through a conical collimator to the skull.

Flags from extraction

  • n_subjectsGroup sizes given for the main LFP cohort (KA+LIPUS n=8, KA+LICUS n=8) and a separate latency-to-seizure cohort (KA+LIPUS n=5, KA+LICUS n=5); no single stated total exposed to ultrasound.
  • exposures[0].unspecified_domain.pressure_kpaPaper does not state whether the 0.26 MPa maximum pressure was measured free-field or through the skull; placed in unspecified_domain.
  • sham_typeThe KA-only group serves as an untreated comparator; no sham ultrasound (e.g. inactive transducer) mechanism is described, so classified as other.
  • exposures[0].timing.pulse_duration_msNot stated directly and not computed from duty cycle/PRF per the burst rule; left not_reported.