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Low-Intensity Focused Ultrasound-Mediated Attenuation of Acute Seizure Activity Based on EEG Brain Functional Connectivity

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

Brain Sciences 2021, 11, 711 · 10.3390/brainsci11060711

rodentepilepsyeeg meg

Abstract

(1) Background: Ultrasound has been used for noninvasive stimulation and is a promising technique for treating neurological diseases. Epilepsy is a common neurological disorder, that is attributed to uncontrollable abnormal neuronal hyperexcitability. Abnormal synchronized activities can be observed across multiple brain regions during a seizure. (2) Methods: we used low-intensity focused ultrasound (LIFU) to sonicate the brains of epileptic rats, analyzed the EEG functional brain network to explore the effect of LIFU on the epileptic brain network, and continued to explore the mechanism of ultrasound neuromodulation. LIFU was used in the hippocampus of epileptic rats in which a seizure was induced by kainic acid. (3) Results: By comparing the brain network characteristics before and after sonication, we found that LIFU significantly impacted the functional brain network, especially in the low-frequency band. The brain network connection strength across multiple brain regions significantly decreased after sonication compared to the connection strength in the control group. The brain network indicators (the path length, clustering coefficient, small-worldness, local efficiency and global efficiency) all changed significantly in the low-frequency. (4) Conclusions: These results revealed that LIFU could reduce the network connections of epilepsy circuits and change the structure of the brain network at the whole-brain level.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects7, 7swept animals
Sessions per subject1
Randomisedyes
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutseeg meg32-channel skull-surface EEG electrode array; phase-locking value (PLV) functional connectivity and graph-theoretical brain network indicators (path length, clustering coefficient, small-worldness, local/global efficiency)
Direction of effectinhibitoryLIFU sonication of the hippocampus during kainic-acid-induced seizure significantly reduced EEG amplitude and phase-locking value (network connectivity strength), particularly in the low-frequency (delta/theta) bands, compared with untreated seizure controls, indicating a suppressive effect on epileptic network activity.
Adverse eventsnot reported

Exposures

Exposure 1: LIFU to hippocampus in KA-induced seizure (Group 1) and non-epileptic (Group 3) rats

Target: hippocampus — “hippocampus
Device: other named manufacturer · Goworld, Guangdong, China

Pulse timing
Waveformpulsed
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)not reported
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 estimatesimulationsingle value
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)0.101✓✓
Protocol, in the paper’s words

Kainic acid (6.5 mg/kg i.p.) was used to induce seizures in Group 1 (KA+/LIFU+, n=7) and Group 2 (KA+/LIFU-, n=7, no sonication, served as comparison control); Group 3 (KA-/LIFU+, n=7) received sonication without epilepsy induction. When seizures (forelimb clonus and tail-twitches) lasted 60 s, sonication was applied 5 times to the hippocampus (Stage 3); EEG was recorded continuously through baseline, pre-LIFU, sonication, and post-LIFU (60 s) stages. The waveform used np=200 pulses per burst.

Flags from extraction

  • exposures[0].timing.pulse_duration_msComputed from stated cycles-per-pulse (c.p.p.=150) divided by fundamental frequency (0.5 MHz), a sanctioned unit conversion, not stated directly as a duration in ms.
  • sham_typeGroup 2 (KA+/LIFU-) received no transducer/apparatus at all as the comparison condition, rather than a classic inactive-transducer or active-control-site sham; coded as none.
  • exposures[0].in_situ.ispta_w_cm2Value comes from a finite-element simulation of the sound field in brain tissue; corresponding pressure and ISPPA values are only shown graphically (Figure 8) and not stated numerically in text.