Effect of Vagus Nerve Stimulation on Electroencephalogram Synchronization: A Longitudinal Study Using a Clinical-Research Response Scale

Venethia Danthine; Enrique Ignacio Germany Morrison; Lise Cottin; Giulia Liberati; Inci Cakiroglu; Vincent Joris; André Mouraux; Roberto Santalucia; Alexane Fierain; Pascal Vrielynck; Susana Ferrao Santos; Antoine Nonclercq; Riëm El Tahry

doi:10.1016/j.neurom.2025.03.068

Effect of Vagus Nerve Stimulation on Electroencephalogram Synchronization: A Longitudinal Study Using a Clinical-Research Response Scale

Neuromodulation. 2025 May 7:S1094-7159(25)00132-1. doi: 10.1016/j.neurom.2025.03.068. Online ahead of print.

Affiliations

¹ Institute of NeuroScience, Catholic University of Louvain, Ottignies-Louvain-la-Neuve, Belgium. Electronic address: venethia.danthine@uclouvain.be.
² Institute of NeuroScience, Catholic University of Louvain, Ottignies-Louvain-la-Neuve, Belgium; Walloon Excellence in Life Sciences and Biotechnology (WELBIO), WEL Research Institute, Wavre, Belgium.
³ Bio- Electro- And Mechanical Systems, Université Libre de Bruxelles, Brussels, Belgium.
⁴ Institute of NeuroScience, Catholic University of Louvain, Ottignies-Louvain-la-Neuve, Belgium; Institute of Psychology, Catholic University of Louvain, Ottignies-Louvain-la-Neuve, Belgium.
⁵ Institute of NeuroScience, Catholic University of Louvain, Ottignies-Louvain-la-Neuve, Belgium; Department of Neurosurgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
⁶ Institute of NeuroScience, Catholic University of Louvain, Ottignies-Louvain-la-Neuve, Belgium.
⁷ Institute of NeuroScience, Catholic University of Louvain, Ottignies-Louvain-la-Neuve, Belgium; Department of Child Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
⁸ Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Reference Center for Refractory Epilepsy, Catholic University of Louvain, William Lennox Neurological Hospital, Ottignies-Louvain-la-Neuve, Belgium.
⁹ Reference Center for Refractory Epilepsy, Catholic University of Louvain, William Lennox Neurological Hospital, Ottignies-Louvain-la-Neuve, Belgium.
¹⁰ Institute of NeuroScience, Catholic University of Louvain, Ottignies-Louvain-la-Neuve, Belgium; Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
¹¹ Institute of NeuroScience, Catholic University of Louvain, Ottignies-Louvain-la-Neuve, Belgium; Walloon Excellence in Life Sciences and Biotechnology (WELBIO), WEL Research Institute, Wavre, Belgium; Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

PMID: 40338763
DOI: 10.1016/j.neurom.2025.03.068

Abstract

Objectives: No reliable biomarkers exist for predicting and assessing vagus nerve stimulation (VNS) response. While VNS induces acute electroencephalography (EEG) desynchronization after implantation, longitudinal evaluations of EEG synchronization changes are lacking. This study constitutes the first prospective investigation evaluating EEG synchronization before and after VNS device implantation and correlating it with the clinical response to VNS.

Materials and methods: High-density EEG recordings were obtained from 12 adults with drug-resistant epilepsy before and after VNS device implantation (one, three, and six months). EEG resting state (180 seconds), with eyes open and eyes closed (EC), was recorded in VNS ON and OFF conditions. The global weighted phase lag index (wPLI) was computed as an EEG phase-synchronization measure and correlated with the VNS response using various assessment methods, including binary classification (>50% or <50% seizure frequency reduction), percentage of seizure reduction, and the newly developed Clinical-Research Response Scale (CRRS).

Results: We observed a progressive decrease of wPLI in the delta band during the EC VNS OFF condition, which correlated with the VNS response over time, particularly when assessed using the new CRRS compared with other assessment methods. Additionally, a higher preimplant global wPLI predicted a better outcome of VNS, as did an early magnet response.

Conclusions: Overall, VNS may positively influence specific brain states, with a time-dependent evolution of EEG synchronization reflecting therapeutic efficacy. Preimplantation EEG synchronization and an early magnet response may predict VNS response. Moreover, the CRRS could constitute a more sensitive method for characterizing VNS response compared with traditional assessment methods.

Keywords: Biomarkers; electroencephalography; functional connectivity; refractory epilepsy; vagus nerve stimulation.