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

Harreby, Kristian Rauhe; Sevcencu, Cristian; Struijk, Johannes

doi:10.1007/s11517-011-0782-7

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…In their study this drift was not accompanied by a change of the root mean square of successive differences in the RR intervals (r-MSSD), which is an indirect measure for parasympathetic activity. 24 Therefore, this observation might not reflect an increased parasympathetic activity involving the cardiac branch of the vagus nerve. Instead, the constant infusion of saline may increase total blood volume inducing other parasympathetic activation not specific to the seizure but rather due to the experimental procedure.…”

Section: Veng-based Detection Of Acute Ptzmentioning

confidence: 84%

“…Likewise, we see a maximum during the tonic clonic phase of the seizures. 24 Increased parasympathetic activity in relation to epileptic seizures have been reported on multiple occasions. Brotherstone et al described elevated cardiac parasympathetic activity through recording of heart rate variability during generalized subclinical seizures.…”

Section: Veng and Heart Rate During Acute Ptz Induced Seizuresmentioning

confidence: 99%

“…Cardiac related energy and spectral pattern of the VENG have been previously suggested as a possible marker for the detection of seizures. 23,24 Those studies were limited by the lack of independent test and training groups for training of the classifier as well as by the acute, nonimplantable nature of the recording setting. In addition, preliminary results showed an increase of VENG signal power during a seizure in the acute kainic acid (KA) model.…”

Section: Introductionmentioning

confidence: 99%

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

Stumpp

Smets

Vespa

et al. 2021

Int. J. Neur. Syst.

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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.

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Section: Veng-based Detection Of Acute Ptzmentioning

confidence: 84%

Section: Veng and Heart Rate During Acute Ptz Induced Seizuresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Stumpp

Smets

Vespa

et al. 2021

Int. J. Neur. Syst.

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“…In addition, some early studies have focused on VENG recordings during seizures in rats, but these studies were performed with nonimplantable hook electrodes (Harreby et al, 2011b(Harreby et al, , 2011. Cardiac activity related features of the neural signal (energy or spectral pattern) were suggested as a possible marker for seizure activity.…”

Section: Introductionmentioning

confidence: 99%

Recording of spontaneous vagus nerve activity during Pentylenetetrazol-induced seizures in rats

Stumpp

Smets

Vespa

et al. 2020

Journal of Neuroscience Methods

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Background: Vagus nerve stimulation is a treatment for refractory epilepsy. The vagus nerve carries parasympathetic information and innervates multiple organs. As seizures are commonly associated with autonomic manifestations, we believe that biomarkers for diseases affecting autonomic functions such as epilepsy can be found in vagus nerve signals. New method: We present a method to record vagus nerve electroneurogram (VENG) and detect in the VENG single unit activity in anesthetized rats during Pentylenetetrazol induced seizures using a true tripolar cuff electrode.Results: The VENG consisted of high amplitude bursts and lower amplitude bursts synchronous to respiration and heartbeat respectively. The average spikes exhibited a triphasic shape with duration below 1.5ms and root mean square amplitude varied between 5.5 +/-0.2 μV and 11.4 +/-3.1 μV depending on the type of recording. An increase of the contact distance resulted in a signal amplitude increase. Application of Lidocaine led to a total disappearance of the recorded spontaneous spiking of the nerve. Comparison with existing methods: True tripolar cuff electrodes exhibited a better performance in terms of artefact rejection, stability and reproducibility of the signal compared to commonly used hook electrodes which is of special interest in seizures where important motion and EMG artifacts are expected. Conclusion:We present a new method to record single unit activity of the vagus nerve during acute chemically induced seizures in rats and verified the neural origin of the recorded signals. This recording method might be a powerful tool to develop seizure biomarkers based on VENG.Recently, a new model of VNS has been commercialized (AspireSR), which was designed to exploit ictal tachycardia using a patented cardiac-based seizure-detecting algorithm. The device triggers VNS on the basis of tachycardia. The performance of this automated seizure detection was assessed in a prospective observational multi-site study (Boon et al., 2015). Despite the rather accurate system, the expected additional or potential benefit for patients is still a matter of debate. A possible explanation is that a substantial number of patients do not have ictal tachycardia while this is a basic requirement for this "closed loop" system. However, the abortive effect of on demand VNS, prior or soon after seizure onset is being confirmed by several human and

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“…Among the available seizure induction procedures, the use of proconvulsive drugs seems particularly suitable for this task as their administration can be precisely controlled and manipulated by, for example, supplying such drugs in appropriate concentrations and rates. Indeed, aiming to standardize the onset latency, duration, and number of tonic–clonic (TC) seizures in rats for seizure detection purposes , and for testing new anti‐convulsive therapies , we developed a method for controlled infusion of pentylenetetrazol (PTZ), which is one of the most used proconvulsive drugs . In those studies, we observed that the TC seizures were always preceded by brief episodes of spike‐and‐wave (SW) discharges occurring consistently at a PTZ dose of around 25 mg/kg.…”

mentioning

confidence: 99%

A New Rat Model of Seizures Suitable for Screening Antiepileptic Electrical Stimulation Therapies

et al. 2017

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Abstract:The antiepileptic effects of the electrical stimulation therapies developed for patients with intractable epilepsies depend critically on the stimulation parameters, including the pulse duration, current, and frequency. Consequently, optimization of such therapies requires many animals for testing each of the stimulation parameters alone or in combination, which is costly and time consuming. This drawback could be reduced by testing several stimulation paradigms in each animal, but this requires an animal model of long-lasting seizures allowing such repetitive tests. This study was performed to validate such a model of long-lasting seizures. The present analysis was performed on electrocorticogram and intracortical signals collected from the somatosensory cortex of 11 Sprague Dawley rats. A protocol of controlled intravenous infusion of pentylenetetrazol (PTZ) was developed to induce spikeand-wave (SW) seizures and maintain stable those seizures for the whole experimental time. SW discharges were induced and maintained stable for 2 h in all rats through a two-stage infusion of PTZ. During the first stage, the SW discharges were induced by 2.5 min infusion of 10 mg/kg/ min PTZ. During the second stage, the SW discharges were maintained at a stable level of frequency and power for 2 h via a 0.21 mg/kg/min PTZ infusion rate. The proposed animal model of seizures is characterized by SW discharges which remain stable for 2 h. This 2-h long time interval allows repetitive tests with different stimulation parameters in each animal, which may lead to a significant reduction of the number of animals necessary for optimizing electrical stimulation therapies developed to inhibit seizures. Key Words: Pentylenetetrazol-Spike-andwave-Seizures-Model.Although many animal models of seizures have been developed to date, establishing new such models of seizures is currently in focus (1-3) as seizure models that are more suitable for basic research purposes or for testing new antiepileptic therapies are still needed (4). For example, efforts are currently made for developing electrical stimulation therapies for patients with drug-resistant epilepsies. As studies have shown, the antiepileptic effects of such therapies depend critically on the stimulation parameters, such as the duration, current, and frequency of the applied electrical pulses (5-7). Consequently, optimization of these therapies requires many animals for testing the stimulation parameters alone or in the many possible combinations, which is costly and time consuming. This drawback could be minimized by reducing the number of animals necessary for performing such tests, which would also comply with the present ethical demands related to animal studies (8,9). One way to achieve this objective is by developing animal models of longlasting seizures to allow repetitive testing of several stimulation paradigms in each animal. However epilepsy seizures are typically transient episodes (10-12) and, therefore, developing models of longlasting seizures requires method...

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

Cited by 9 publications

References 29 publications

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

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

Recording of spontaneous vagus nerve activity during Pentylenetetrazol-induced seizures in rats

A New Rat Model of Seizures Suitable for Screening Antiepileptic Electrical Stimulation Therapies

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