Early seizure detection in rats based on vagus nerve activity

Abstract

Continuous, scheduled vagus nerve stimulation (VNS) is used for the treatment of refractory epilepsy. On-demand VNS, started prior to or at the onset of a seizure may improve the effect of the treatment, however, this requires seizures to be predicted or detected early. This study investigates the possibility of early seizure detection based on the cervical vagus electroneurogram (VENG). Fourteen anesthetized rats received an intravenous infusion (IV) of either saline (control, n = 6) or pentylenetetrazol (PTZ) diluted in saline (PTZ-treated, n = 8). A cardiac-related VENG profile (CrVENG) was derived by using R-peak triggered averaging of the VENG energy. Following, changes in this profile were evaluated as a seizure predictor. Using left nerve VENG, seizures were detected in all PTZ-treated rats 103 ± 51 s (mean ± SD) before they developed tonic seizures. Control rats did not develop seizures and our method did also not detected seizures in these rats. Seizures can be early detecting based on left nerve VENG in anesthetized rats. Preictal CrVENG changes may reflect central-mediated changes and/or changes in the relation between the respiration and the cardiac cycle. Further research is needed to evaluate the method in awake and freely moving animals and eventually in humans.

Optimal features for online seizure detection

“…In recent years there has also been significant interest in the development of miniaturised, portable EEG systems for prolonged ambulatory monitoring that incorporate online, realtime, seizure detection within the ambulatory unit [3,12,22,26,32]. This could be used to alert medical practitioners or bystanders of the occurrence of a clinical or sub-clinical seizure, to facilitate closed loop treatment [13], or to collect discontinuous data for sampled review. In these seizure detection systems the computational complexity required to generate each feature is an essential comparison point.…”

Ictal and peri-ictal changes in cervical vagus nerve activity associated with cardiac effects

“…In addition, the electrocorticogram (ECoG), respiration, electromyogram (EMG, from the sternohyoid muscle and from the medial thigh abductor muscles), and electrocardiogram (ECG) were recorded. Details on anesthesia and the recording techniques were described previously [11]. Rats were initially divided into two experimental lots: a lot receiving pentylenetetrazol (PTZ-lot, n = 11) and a lot receiving isotonic saline (control-lot, n = 6).…”

“…The fact that the general VENG power increased in vagotomized rats shows that the vagal efferent activity increases during seizures. Even though the parasympathetic output to the heart may account for part of this increase, its main component probably resulted from respiratory changes during seizures, e.g., those mediated via the efferent A-fibers running through the VN and innervating laryngeal muscles [11,30].…”

“…Therefore, the absolute increase of ictal VN activity was four times higher in the rats with intact nerves versus vagotomized rats. Most probably, this large difference is a result of an ictal increase in the vagal afferent input, including from pulmonary stretch receptors due to increased respiratory rate and lung expansion during seizures [11].…”

“…In addition, VENG may provide a source of information for monitoring seizures, which could be used to modulate VNS timing and intensity relative to the seizure events. We have recently shown that pre-ictal changes in VENG in anesthetized rats could be detected more than 80 s prior to onset of convulsive seizures [11]. In this study, we analyzed the baseline, peri-ictal, and ictal VN activity in relation to cardiac parameters to investigate their potential as indicators of seizures.…”