Authors :
Presenting Author: Ana Marta Dias, MSc – Université Catholique de Louvain
Marie Dawant, MSc – Université Libre de Bruxelles
Venethia Danthine, MD – Université Catholique de Louvain
Inci Cakiroglu, MSc – Université Catholique de Louvain
Enrique Germany Morrison, PhD – Université catholique de Louvain
Antoine Nonclercq, PhD – Université Libre de Bruxelles
Riëm El Tahry, MD, PhD – Institute of Neurosciences, UCLouvain, Brussels, Belgium
Rationale:
Vagus nerve stimulation (VNS) has been established as a safe and effective therapy for drug-resistant epilepsy (DRE), which represents about one-third of the epilepsy patients worldwide. However, its underlying mechanisms of action are not yet fully understood and lack optimization. Recent evidence highlights modulation of the locus coeruleus (LC)-noradrenergic system as a key pathway supporting the antiepileptic effect of VNS (Surg Neurol Int. 2012;3:S255-9). Furthermore, LC activity influences pupil dilation response (PDR), the latter emerging as a potential biomarker for personalizing VNS. A well-established manner of activating the LC, thus evoking pupillary dilation, is the auditory oddball paradigm (Front Neurosci. 2016;10:43). This study aims at identifying early clinical biomarkers of VNS response using oddball-induced PDR.
Methods:
Oddball-induced PDR recordings were longitudinally collected from five DRE patients receiving VNS: before implantation, at 3, and at 6 months post-VNS (only three patients reached the latter). VNS was turned off during post-VNS recordings. The auditory oddball task comprised a two-stimulus paradigm, with random target probability of 20%. The patients were asked to discriminate target sounds by actively clicking a button. Data was preprocessed by removing blink artifacts and by band-pass filtering within the frequency range of 0.025Hz - 0.75Hz. Then, epochs were segmented to include 0.5s before and 1.5s after the target stimuli, and further baseline corrected. Mean PDR, area under the curve (AUC), and peak dilation were computed as metrics characterizing PDR for the left eye (ipsilateral to the VNS). To assess PDR differences post-VNS compared to baseline, a Wilcoxon signed-rank test was computed. Finally, to assess these differences across response groups: responder (R, N = 2), non-responder (NR, N = 2), and partial responder (PR, N = 1), a Kruskal-Wallis test was applied to the PDR differences between visits. Both statistical tests were Bonferroni-corrected.Results:
Significantly increased oddball-induced PDR was observed at both 3 months (p = 0.002) and 6 months (p = 0.008) post-VNS compared to baseline (Figure 1). Among response groups, NRs showed the largest increase in PDR, with significant differences at 3 months (p = 0.005) and a trend toward significance at 6 months (p = 0.058) (Figure 2).
Conclusions:
These findings suggest that responders may exhibit a distinct functional state of the vagal afferent–LC-NE network. Individuals with reduced baseline LC-NE activity may represent a subgroup particularly responsive to neuromodulatory interventions targeting this system, such as VNS.
Funding:
This work was funded by Innoviris (Brussels Institute for Research and Innovation).