Vagus Nerve Electroneurogram-Based Detection of Acute Pentylenetetrazol Induced Seizures in Rats

Abstract

On-demand stimulation improves the efficacy of vagus nerve stimulation (VNS) in refractory epilepsy. The vagus nerve is the main peripheral parasympathetic connection and seizures are known to exhibit autonomic symptoms. Therefore, we hypothesized that seizure detection is possible through vagus nerve electroneurogram (VENG) recording. We developed a metric able to measure abrupt changes in amplitude and frequency of spontaneous vagus nerve action potentials. A classifier was trained using a “leave-one-out” method on a set of 6 seizures and 3 control recordings to utilize the VENG spike feature-based metric for seizure detection. We were able to detect pentylenetetrazol (PTZ) induced acute seizures in 6/6 animals during different stages of the seizure with no false detection. The classifier detected the seizure during an early stage in 3/6 animals and at the onset of tonic clonic stage of the seizure in 3/6 animals. EMG and motion artefacts often accompany epileptic activity. We showed the “epileptic” neural signal to be independent from EMG and motion artefacts. We confirmed the existence of seizure related signals in the VENG recording and proved their applicability for seizure detection. This detection might be a promising tool to improve efficacy of VNS treatment by developing new responsive stimulation systems.

Optical birefringence changes in myelinated and unmyelinated nerves: A comparative study

“…In the context of clinical applications, while techniques relying on scattering changes seem more appropriate than those based on birefringence changes for sciatic nerves, the latter method could still be promising for nerves containing less myelinated axons. It is the case, for instance, for the vagus nerve, showing a specific clinical interest in epilepsy [64]. To which extend polarization techniques could be implemented for monitoring neural activity in vagus nerves remains an open question and requires further investigations.…”

The GABAergic System and Endocannabinoids in Epilepsy and Seizures: What Can We Expect from Plant Oils?

“…Diverse drugs such as pilocarpine or kainic acid have been used as chemoconvulsants in animal models of epilepsy for testing new ACD candidates [ 50 ]. One of the gold-standard models for the screening of new ACDs involves the chemical induction of seizures with pentylenetetrazol (PTZ), which is capable of generating acute seizures [ 51 , 52 , 53 ]. The mechanism of action of PTZ consists of noncompetitive blocking of GABA A receptors through inhibition of the chloride channel associated with the receptor complex.…”

Chronic recording of the vagus nerve to analyze modulations by the light–dark cycle

“…(b) During the chronic experiment, electrodes impedances were controlled. (c) We used a previously validated spike detection algorithm [16] to quantify spike activity in the VENG signal acquired chronically. The shape of the spikes was also visually validated.…”

“…The VENG was software filtered between 300 and 3000 Hz (2nd order Butterworth). The number of spikes per second obtained for each hour of the recording was computed using a spike detection algorithm adapted from [16,18,23,24]. Spike are detected based on their waveform (template matching), with templates that are automatically adapted to each subject (subject-specific templates) and based on specific features of the waveform (spike slope, curvature, and duration).…”

“…Recently, the chronic recording of the vagus nerve has been developed and several studies reported the feasibility of such recordings [11][12][13][14]. Chronic continuous analysis of the vagus nerve activity could contribute to the understanding of the role of the vagus nerve in the circadian oscillations in general, and could be of special interest in the frame of epilepsy [15,16]. In this paper, we present for the first time the 24 h patterns of spontaneous vagus nerve activity found in continuous chronic vagus nerve recordings performed in four rats, which was previously reported only by indirect measurement.…”