Ultrasound Neuromodulation Inhibits Seizures in Acute Epileptic Monkeys
Junjie Zou, Long Meng, Zhengrong Lin, Yangzi Qiao, Changjun Tie, Yibo Wang, Xiaowei Huang, Tifei Yuan, Yajie Chi, Wen Meng, Lili Niu, Yanwu Guo, Hairong Zheng
iScience 2020 · 10.1016/j.isci.2020.101066
Abstract
Ultrasound stimulation has recently emerged as a non-invasive method for modulating brain activity in animal and human studies with healthy subjects. Whether brain diseases such as Alzheimer's disease, epilepsy, and depression can be treated using ultrasound stimulation still needs to be explored. Recent studies have reported that ultrasound stimulation suppressed epileptic seizures in a rodent model of epilepsy. These findings raise the crucial question of whether ultrasound stimulation can inhibit seizures in non-human primates with epilepsy. Here, we addressed this critical question. We confirmed that ultrasound stimulation significantly reduced the frequency of seizures in acute epileptic monkeys. Furthermore, the results showed that the number and duration of seizures were reduced, whereas the inter-seizure interval was increased after ultrasound stimulation. Besides, no significant brain tissue damage was observed by T2-weighted MR imaging. Our results are of great importance for future clinical applications of ultrasound neuromodulation in patients with epilepsy.
Abstract via europepmc.
Exposures
Exposure 1: 800 kHz transducer, 15 min
Target: primary motor cortex — “right hand movement area”
Device: IGT / Imasonic · IMASONIC ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 800 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.72 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | 36 | ✓✓✓ |
| Sonication duration (s) | 0.1 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 1,740 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 119.8 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 1.43 | ✓✓✓⚑ |
Low-intensity pulsed ultrasound (PRF 500 Hz, duty cycle 36%) was delivered for 15 minutes, 30 minutes after penicillin injection, to the right hand movement area; the animals were fixed on a primate chair for 7 hours afterwards with video-EEG. Sessions were separated by 14-day intervals.
Exposure 2: 750 kHz transducer (comparison)
Target: primary motor cortex — “right hand movement area”
Device: Sonic Concepts · Sonic Concepts ✓
| Waveform | not reported | |
|---|---|---|
| Fundamental frequency (kHz) | 750 | ✓✓✓ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | not reported |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
A 750 kHz Sonic Concepts transducer was compared with the 800 kHz transducer for parameter selection (Figure 2A); no separate parameters are stated for it.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Methods give 'pulse duration 100 ms' with PRF 500 Hz and duty cycle 36%; these are mutually inconsistent (36%/500 Hz would be 0.72 ms). Recorded as stated.exposures[0].in_situ.pressure_kpa— Paper says pressure was estimated in the brains from skull transmission measured on ex vivo skulls; also says 'pressure amplitude at the focus was 1.74 MPa'. Method labelled measurement (through skull) but could be derating.exposures[0].in_situ.ispta_w_cm2— Paper gives 'less than 1431.71 mW/cm2' (upper bound), converted to 1.43171 W/cm2.n_subjects— Two monkeys; figure legends give n = 8 (sessions/trials).exposures[1]— 750 kHz transducer was used only for parameter selection; no timing or pressure stated for it. Frequency text is 750 kHz.sham_type— Sham stimulation described only as a control group; mechanism not stated.anaesthesia— Stimulation delivered under isoflurane; anaesthesia removed after 15 min and video-EEG continued for 7 h.