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Noninvasive closed-loop acoustic brain-computer interface for seizure control

Junjie Zou, Houminji Chen, Xiaoyan Chen, Zhengrong Lin, Qihang Yang, Changjun Tie, Hong Wang, Lili Niu, Yanwu Guo, Hairong Zheng

Theranostics 2024, 14, 5965-5981 · 10.7150/thno.99820

rodentepilepsyeeg meghistology molecularother mri

Abstract

Rationale: The brain-computer interface (BCI) is core tasks in comprehensively understanding the brain, and is one of the most significant challenges in neuroscience. The development of novel non-invasive neuromodulation technique will drive major innovations and breakthroughs in the field of BCI. Methods: We develop a new noninvasive closed-loop acoustic brain-computer interface (aBCI) for decoding the seizure onset based on the electroencephalography and triggering ultrasound stimulation of the vagus nerve to terminate seizures. Firstly, we create the aBCI system and decode the onset of seizure via a multi-level threshold model based on the analysis of wireless-collected electroencephalogram (EEG) signals recorded from above the hippocampus. Then, the different acoustic parameters induced acoustic radiation force were used to stimulate the vagus nerve in a rat model of epilepsy-induced by pentylenetetrazole. Finally, the results of epileptic EEG signal triggering ultrasound stimulation of the vagus nerve to control seizures. In addition, the mechanism of aBCI control seizures were investigated by real-time quantitative polymerase chain reaction (RT-qPCR). Results: In a rat model of epilepsy, the aBCI system selectively actives mechanosensitive neurons in the nodose ganglion while suppressing neuronal excitability in the hippocampus and amygdala, and stops seizures rapidly upon ultrasound stimulation of the vagus nerve. Physical transection or chemical blockade of the vagus nerve pathway abolish the antiepileptic effects of aBCI. In addition, aBCI shows significant antiepileptic effects compared to conventional vagus nerve electrical stimulation in an acute experiment. Conclusions: Closed-loop aBCI provides a novel, safe and effective tool for on-demand stimulation to treat abnormal neuronal discharges, opening the door to next generation non-invasive BCI.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjectsnot reported animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlundescribed
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutseeg meg, histology molecular, other mriSeizure number/duration from EEG; c-Fos immunofluorescence in hippocampus, amygdala, NTS, LC, DRN; RT-qPCR for Piezo1/Piezo2 mRNA in nodose ganglion; H&E staining; 9.4T MRI and thermal imaging for safety
Direction of effectinhibitoryClosed-loop and open-loop aBCI stimulation of the vagus nerve reduced PTZ-induced seizure number and duration and suppressed c-Fos-indexed neuronal hyperexcitability in hippocampus, amygdala and NTS; effects required a PRF near 20 Hz, adequate acoustic pressure, and an intact, mechanosensitive-channel-competent vagus nerve (abolished by vagotomy or GsMTx4).
Adverse eventsnone observedMRI showed intact brain structure with no edema or necrosis after stimulation; H&E staining of vagus nerve and vasculature showed no inflammation or necrosis; local neck/vagus nerve temperature increased by less than 1 C during 15-minute aBCI stimulation.

Exposures

Exposure 1: Acoustic (aBCI) stimulation of the cervical vagus nerve

Target: vagus nerve — “cervical vagus nerve
Device: Sonic Concepts · Sonic Concepts · H-115

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)250✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)1, 20, 1,000swept✓✓
Duty cycle (%)10✓✓
Sonication duration (s)5✓✓
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)450, 900, 1,800swept✓✓
Ispta, domain unspecified (W/cm²)0.0822, 0.329, 1.31swept✓✓
Protocol, in the paper’s words

Ultrasound was delivered to the vagus nerve in 5 s trains (SD) separated by a 5 s inter-stimulus interval (ISI), at PRF 1/20/1000 Hz and DC 10%, for a total insonation time of 15 or 30 minutes, at acoustic pressures of 0.45/0.90/1.80 MPa; parameters were screened sequentially and 20 Hz PRF, 15 min insonation and 0.90 MPa were selected as optimal. In the closed-loop aBCI system, ultrasound stimulation was triggered on detection of a seizure and delivered for up to 60 seconds (matched to typical single-seizure duration) until epileptic discharges resolved.

Flags from extraction

  • n_subjectsThe paper reports many separate rat cohorts across sub-experiments (PRF screening n=6 per arm; insonation-time n=12/8; pressure n=13/13; vagotomy n=8; closed-loop main test: random aBCI n=12, closed-loop aBCI n=7; Piezo qPCR n=11; GsMTx4 experiment n=8/8; c-Fos experiment n=8) but never states a combined total; n_subjects here lists only the initial PRF dose-finding cohort (the sub-experiment most directly tied to the recorded exposure's PRF sweep).
  • exposures[0].unspecified_domain.pressure_kpaPaper does not state whether the reported acoustic pressure/ISPTA values were measured in water (free field) or at/near the vagus nerve (in situ); recorded as unspecified domain.
  • exposures[0].timing.sonication_duration_sA separate 60-second stimulation duration is described for the closed-loop system (set to match typical single-seizure duration), differing from the 5 s 'SD' listed in Table 1 for the open-loop dose-finding experiments; both durations are noted in protocol_description.
  • exposures[0].timing.pulse_duration_msDuty cycle (10%) and PRF are given but pulse duration is never stated directly; left not_reported rather than computed from duty_cycle/PRF.
  • sham_typeSham condition is described only as 'sham group was not stimulated'; the physical implementation (e.g. transducer powered off vs. removed) is not described, so mechanism is unclear.