Vagus Nerve Stimulation (VNS) is used as an adjunctive treatment for drug-resistant epilepsy. Despite its clinical efficacy in half of the implanted patients, the choice of stimulation parameters is performed empirically, and no biomarkers of effective nerve activation are currently available. This project aims to identify biomarkers of VNS effectiveness, which may be used to guide more rationally the titration of its parameters. For this purpose, we will study the links between peripheral nerve activation and the central therapeutic effects induced by VNS. First, we aim to validate the use of Laryngeal Motor Evoked Potentials (LMEPs), as a non-invasive marker of clinical response. Since LMEPs characteristics express the excitability of vagal fibers, we hypothesize that they will reflect signs of dysfunctional nerve activation, which may distinguish non-responders from good responders to VNS. Moreover, we will explore the dose-response curves of LMEPs, correlating thresholds and saturation values with the intensity values needed for clinical efficacy. Secondly, we aim to determine the dose-dependency of afferent VNS-induced brain effects, which will be assessed through pupillary measurement and functional connectivity (FC) derived from electroencephalogram (EEG) . We expect to find, as a function of the increase of VNS intensity, an increase of VNS-induced pupillary dilation and a decrease of the FC indexes of synchronization. Finally, we will study the ratio between the values of LMEPs dose-response curves, reflecting the excitation properties of vagal A-fibers, and the dose-response curve values of the central VNS biomarkers as previously studied. By correlating their respective dose-dependent properties, we aim to elucidate the fiber type involved in the central effects of VNS and to validate LMEPs as a read-out for titration in individual patients.
We are looking preferably for a medical doctor or a student with master in neurosciences