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Different Modes of Low-Frequency Focused Ultrasound-Mediated Attenuation of Epilepsy Based on the Topological Theory

Minjian Zhang, Bo Li, Yafei Liu, Rongyu Tang, Yiran Lang, Qiang Huang, Jiping He

Micromachines 2021 · 10.3390/mi12081001

rodentepilepsyeeg meghistology molecular

Abstract

Epilepsy is common brain dysfunction, where abnormal synchronized activities can be observed across multiple brain regions. Low-frequency focused pulsed ultrasound has been proven to modulate the epileptic brain network. In this study, we used two modes of low-intensity focused ultrasound (pulsed-wave and continuous-wave) to sonicate the brains of KA-induced epileptic rats, analyzed the EEG functional brain connections to explore their respective effect on the epileptic brain network, and discuss the mechanism of ultrasound neuromodulation. By comparing the brain network characteristics before and after sonication, we found that two modes of ultrasound both significantly affected the functional brain network, especially in the low-frequency band below 12 Hz. After two modes of sonication, the power spectral density of the EEG signals and the connection strength of the brain network were significantly reduced, but there was no significant difference between the two modes. Our results indicated that the ultrasound neuromodulation could effectively regulate the epileptic brain connections. The ultrasound-mediated attenuation of epilepsy was independent of modes of ultrasound.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects8, 8, 1, 1swept animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlno treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesianot reported
Readoutseeg meg, histology molecular — 32-channel EEG, power spectral density, phase lag index and network metrics; H&E staining
Direction of effectinhibitoryBoth pulsed-wave and continuous-wave sonication reduced EEG power spectral density and brain network connection strength in KA-treated rats, with no difference between modes.
Adverse eventsnone observedNo obvious adverse reaction was observed in rats over 24 h; H&E sections showed no tissue damage or immune cell infiltration.

Exposures

Exposure 1: pulsed-wave and continuous-wave sonication

Target: other — “ultrasound stimulation region”
Device: other named manufacturer · Goworld ✓

Pulse timing
Waveformpulsed, continuous
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)0.3✓✓✓⚑
Pulse repetition frequency (Hz)1,500✓✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 45%
Sonication duration (s)40✓✓✓
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)657✓✓✓⚑
Protocol, in the paper’s words

Pulsed wave: 0.5 MHz, 150 cycles per pulse, PRF 1.5 kHz; continuous wave: 0.5 MHz. Both were applied for 40 s after 60 s of epileptic EEG, followed by 60 s of recording.

Flags from extraction

  • exposures[0].timing.pulse_duration_ms — Not stated; 0.3 ms derived from 150 cycles per pulse at 0.5 MHz (cycles per pulse divided by frequency). Pulsed wave only.
  • exposures[0].unspecified_domain.pressure_kpa — Maximum pressure 0.657 MPa for both modes, measured with a hydrophone; the paper does not say whether this is free field or through skull.
  • n_subjects — 27 rats in total, of which 24 were assigned to groups of 8 and 3 were used for histology (two sonicated, one untouched). The group descriptions are internally confusing (two different 'control' groups).
  • exposures[0].target.terms — The stimulation site is given only as coordinates (ML 3 mm, AP -4.5 mm, DV 3 mm); no region is named.
  • anaesthesia — Isoflurane is described for electrode surgery; anaesthetic state during sonication is not stated.
  • exposures[0].timing.waveform — Two modes (pulsed and continuous) at the same target and frequency are recorded as one exposure.