An effect of vagal nerve stimulation (VNS) on cortical synchronization has been postulated but remains to be verified. In this study we investigated the impact of VNS on functional connectivity (Fc) using direct intracerebral recordings (stereotactic EEG, SEEG). Five patients with epilepsy who underwent SEEG recordings during ongoing VNS therapy were investigated. Interdependencies between twenty-six selected bipolar SEEG channels were estimated by nonlinear regression analysis during ON and OF periods of stimulation. In comparison with OFF periods, the ON periods disclosed higher values for four patients (P1, P3, P4, P5) and lower values for one patient (P2). From thresholded graphs, we observed increased connections between several brain regions in P1 and P5 and decreased connections in P2. Finally, the only decreased Fc occurring during VNS corresponded to the responder patient, suggesting that therapeutic impact might be related to this mechanism. (C) 2016 Elsevier B.V. All rights reserved.