Closed-loop wearable ultrasound deep brain stimulation system based on EEG in mice
Yongsheng Zhong, Yibo Wang, Zhuoyi He, Zhengrong Lin, Na Pang, Lili Niu, Yanwu Guo, Min Pan, Long Meng
Journal of Neural Engineering 2021 · 10.1088/1741-2552/ac1d5c
Abstract
Objective . Epilepsy is one of the most common severe brain disorders. Ultrasound deep brain stimulation (UDBS) has shown a potential capability to suppress seizures. However, because seizures occur sporadically, it is necessary to develop a closed-loop system to suppress them. Therefore, we developed a closed-loop wearable UDBS system that delivers ultrasound to the hippocampus to suppress epileptic seizures. Approach. Mice were intraperitoneally injected with 10 mg kg -1 kainic acid and divided into sham and UDBS groups. Epileptic seizures were detected by applying both long short-term memory (LSTM) and bidirectional LSTM (BILSTM) networks according to EEG signal characteristics. When epileptic seizures were detected, the closed-loop UDBS system automatically activated a trigger switch to stimulate the hippocampus for 10 min and continuously record EEG signals until 20 min after ultrasonic stimulation. EEG signals were analyzed using the MATLAB software. After EEG recording, we observed the survival rate of the experimental mice for 72 h. Main results. The BiLSTM network was found to have preferable classification performance over the LSTM network. The closed-loop UDBS system with BiLSTM could automatically detect epileptic seizures using EEG signals and effectively reduce epileptic EEG power spectral density and seizure duration by 10.73%, eventually improving the survival rate of early epileptic mice from 67.57% in the sham group to 88.89% in the UDBS group. Significance. The closed-loop UDBS system developed in this study could be an effective clinical tool for the control of epilepsy.
Abstract via europepmc.
Exposures
Exposure 1: Closed-loop ultrasound deep brain stimulation of the hippocampus, triggered by detected seizures
Target: hippocampus — “hippocampus”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 800 | ✓✓✓ |
| Pulse duration (ms) | 0.4 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 40pulse duration × PRF gives 40% | ✓✓✓ |
| 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 | measurementsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 1.09 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.436 | ✓✓✓⚑ |
When a seizure lasting more than 10 s was detected the system stimulated the hippocampus for 10 min while EEG was recorded until 20 min after stimulation. Fig. 2(c) parameters: PRF 1 kHz, TBD 0.4 ms, DC 40 %, FF 800 kHz, ISI 3.6 s; the sonication duration per train is not given in the text.
Flags from extraction
exposures[0].timing.sonication_duration_s— Text gives 10 min of stimulation per detected seizure and an ISI of 3.6 s; the length of one uninterrupted train (SD) is only in Fig. 2(c), so left not_reported.exposures[0].timing.pulse_duration_ms— Pulse duration given as TBD in the Fig. 2 caption; 0.4 ms is consistent with DC/PRF (40 % / 1 kHz). Not computed by the extractor.exposures[0].in_situ— Intensities are stated to be 'after passing through the fresh skull' with a hydrophone in a water tank; classed as in_situ (measurement). No pressure value is given, only 18 % attenuation and MI 0.21.exposures[0].in_situ.ispta_w_cm2— Reported as 436.36 mW cm-2; recorded as 0.43636 W/cm2.n_subjects— UDBS group n = 36 in the survival experiment; separate mice (4 for c-Fos, 3 for HE/Nissl) were also sonicated; sham n = 37. Enrolled and analysed counts for EEG are n = 8.n_subjects— Survival rate in UDBS group is given as 88.89 % in the abstract and 89.89 % in the results text.blinding— Only the EEG, c-Fos and histology analysers are stated to be blinded; no statement about blinding of the stimulation arms.sham_type— Sham for c-Fos experiment is power turned off; sham for the closed-loop arm is not described separately.exposures[0].device— No transducer maker or model named; only the amplifier (Electronics & Innovation 2100L) and generator (Rigol DG4162).anaesthesia— Surgery under isoflurane; stimulation and EEG in free-moving, awake mice.