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info:eu-repo/semantics/published

info:eu-repo/semantics/published

Objective. In 1/3 of patients, anti-seizure medications may be insufficient, and resective surgery may be offered whenever the seizure onset is localized and situated in a non-eloquent brain region. When surgery is not feasible or fails, vagus nerve stimulation (VNS) therapy can be used as an add-on treatment to reduce seizure frequency and/or severity. However, screening tools or methods for predicting patient response to VNS and avoiding unnecessary implantation are unavailable, and confident biomarkers of clinical efficacy are unclear.Approach. To predict the response of patients to VNS, functional brain connectivity measures in combination with graph measures have been primarily used with respect to imaging techniques such as functional magnetic resonance imaging, but connectivity graph-based analysis based on electrophysiological signals such as electroencephalogram, have been barely explored. Although the study of the influence of VNS on functional connectivity is not new, this work is distinguished by using preimplantation low-density EEG data to analyze discriminative measures between responders and non-responder patients using functional connectivity and graph theory metrics.Main results. By calculating five functional brain connectivity indexes per frequency band upon partial directed coherence and direct transform function connectivity matrices in a population of 37 refractory epilepsy patients, we found significant differences (p< 0.05) between the global efficiency, average clustering coefficient, and modularity of responders and non-responders using the Mann-Whitney U test with Benjamini-Hochberg correction procedure and use of a false discovery rate of 5%.Significance. Our results indicate that these measures may potentially be used as biomarkers to predict responsiveness to VNS therapy., SCOPUS: ar.j, info:eu-repo/semantics/published

info:eu-repo/semantics/published

Infrared neural stimulation (INS) is a neuromodulation technique that involves short optical pulses delivered to the neural tissue, resulting in the initiation of action potentials. In this work, we studied the compound neural action potentials (CNAP) generated by INS in five ex vivo sciatic nerves. A 1470 nm laser emitting a sequence of 0.4 ms light pulses with a peak power of 10 W was used. A single 4 mJ stimulus is not capable of eliciting a nerve response. However, repetition of the optical stimuli resulted in the induction of CNAPs. Heat accumulation induced by repetition rates as high as 10 Hz may be involved in the increase in CNAP amplitude. This sensitization effect may help to reduce the pulse energy required to evoke CNAP. In addition, these results highlight the importance of investigating the role of the slow nerve temperature dynamics in INS., info:eu-repo/semantics/published

Vagus nerve stimulation (VNS) is an adjunctive therapy for drug-resistant epilepsy. Noninvasive evoked potential recordings in laryngeal muscles (LMEPs) innervated by vagal branches may provide a marker to assess effective vagal nerve fiber activation. We investigated VNS-induced LMEPs in patients with epilepsy in acute and chronic settings.

The vagus nerve is considered to play a key role in the circadian rhythm. Chronic continuous analysis of the vagus nerve activity could contribute to a better understanding of the role of the vagus nerve in light-dark modulations. This paper presents a continuous analysis of spontaneous vagus nerve activity performed in four rats.We analyzed the vagus electroneurogram (VENG) and electroencephalogram (EEG) over a recording period of 28 d. Spike activity and heart rate estimation were derived from the VENG, and slow-wave activity was derived from the EEG. The presence of repetitive patterns was investigated with periodograms, cosinor fitting, autocorrelation, and statistical tests. The light-dark variations derived from the VENG spikes were compared with EEG slow waves, an established metric in circadian studies.Our results demonstrate that light-dark variations can be detected in long-term vagus nerve activity monitoring. A recording period of about 7 d is required to characterize accurately the VENG light-dark variations.As a major outcome of this study, vagus nerve recordings hold the promise to help understand circadian regulation.

The scope of this thesis was to develop novel human biomarkers to optimise Vagus Nerve Stimulation (VNS) for epilepsy, which is currently ineffective in up to one third of the implanted patients. The research addressed two axes: the peripheral activation of vagal fibres and the central effects of VNS on the brain. The explorations were aimed at understanding the acute effects in epileptic patients, with particular regard to their intensity-dependency. Hence, both dosing biomarkers – aiming to optimize the choice of stimulation parameters – and response biomarkers – which could correlate with a successful clinical success – were sought. Experiments involving peripheral electrophysiology research were conducted, with the aim to develop and validate the novel technique of VNS-induced Laryngeal Motor Evoked Potentials (LMEPs), a potential marker of effective nerve activation. At central level, electroencephalography was applied to search for VNS response biomarkers, by means of connectivity and network analyses. Furthermore, a proof-of-concept research led to the characterisation of acute VNS-induced pupillary responses., Cette thèse a pour but de développer de nouveaux biomarqueurs pour l’amélioration de la thérapie par stimulation du nerf vague (VNS) dans l’épilepsie, qui est à présent inefficace jusqu’à un tiers des patients implantés. La recherche porte sur deux axes : au niveau périphérique, sur l’exploration de l’activation des fibres nerveuses vagales ; au niveau central, sur les effets de la VNS sur le cerveau. Cette thèse a abordé les effets aigus de la VNS, en insistant particulièrement sur l’influence de l’intensité de stimulation. Ainsi, tant des biomarqueurs visant à optimiser le choix des paramètres de stimulation, que des biomarqueurs de réponse ont été explorés. Les expériences d’électrophysiologie périphérique ont mené au développement des potentiels évoqués moteurs du larynx (LMEPs), qui sont proposés comme marqueur d’activation nerveuse induite par la VNS. Sur le plan central, l’électroencéphalographie a été étudiée afin d’extraire des biomarqueurs de réponse à la VNS, moyennant des analyses de connectivité fonctionnelle et de réseau. En outre, des réponses pupillaires induites par la VNS ont été prouvées et proposées comme biomarqueurs centraux., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022

This work presents a setup for chronic monitoring of spontaneous epileptic seizures in rats under kainic acid. The system allows to record the vagus nerve electroneurogram at 40 kS/s and the electroencephalogram at 250 S/s using an USB-6212 multifunction I/O-device. The system includes a video channel (20 fps) controlled by a Raspberry Pi 4 Model B. A slipring allows the rat to move freely. Quick cage cleaning is possible through a movable base. The chronic setup was tested on a Wistar rat after status epilepticus induction, using kainic acid. The system appears to be robust and reliable enough to record status epilepticus, making it suitable for more extended experiments in epileptic rats.

This work describes the fabrication of a lab-made cuff electrode intended for rat vagus nerve electroneurography. The cuff electrode is built around 50 µm platinum wires contacts in tripolar configuration, 4mm contact spacing. The body is made of silicone rubber and four surgical threads. In vivo validation allowed to record respiration and cardiac related activity from the vagus nerve. The results show that our electrodes are a suitable low-cost alternative for our preclinical studies.

This work presents an automated analysis algorithm to detect action potentials (APs) in a nerve and quantify its activity. The algorithm is based on template matching. The templates are automatically adapted to individual AP shapes that vary depending on the nerve fibers from which the AP originates, and the recording setup used. The algorithm was validated by quantifying vagus nerve activity recorded during in vivo experiments in a rat model. The MATLAB version of the code is available in open access on GitHub1

Background Modulation of the locus coeruleus (LC)-noradrenergic system is a key mechanism of vagus nerve stimulation (VNS). Activation of the LC produces pupil dilation, and the VNS-induced change in pupil diameter was demonstrated in animals as a possible dose-dependent biomarker for treatment titration. Objective This study aimed to characterize VNS-induced pupillary responses in epileptic patients. Methods Pupil diameter was recorded in ten epileptic patients upon four stimulation conditions: three graded levels of VNS intensity and a somatosensory control stimulation (cutaneous electrical stimulation over the left clavicle). For each block, the patients rated the intensity of stimulation on a numerical scale. We extracted the latency of the peak pupil dilation and the magnitude of the early (0–2.5 s) and late components (2.5–5 s) of the pupil dilation response (PDR). Results VNS elicited a peak dilation with longer latency compared to the control condition (p = 0.043). The magnitude of the early PDR was significantly correlated with the intensity of perception (p = 0.046), whereas the late PDR was not (p = 0.19). There was a significant main effect of the VNS level of intensity on the magnitude of the late PDR (p = 0.01) but not on the early PDR (p = 0.2). The relationship between late PDR magnitude and VNS intensity was best fit by a Gaussian model (inverted-U). Conclusions The late component of the PDR might reflect specific dose-dependent effects of VNS, as compared to control somatosensory stimulation. The inverted-U relationship of late PDR with VNS intensity might indicate the engagement of antagonist central mechanisms at high stimulation intensities.

Infrared Neural Stimulation (INS) is a novel neuromodulation technique involving a rapid temperature increase of the neuron membrane, resulting in action potential triggering. This paper describes an experimental setup developed to measure the spatiotemporal temperature gradients at the surface of an ex vivo sciatic nerve. The setup is also designed to measure the conduction velocity of the nervous fibers excited by INS, with the aim of determining the type of fibers activated during optical stimulation. Two animal experiments successfully validated the setup and provided encouraging results on (1) the impact of heat accumulation on INS and (2) the difference in nerve fibers excited by optical and electrical nerve stimulation.