The re-organization of functional brain networks in pharmaco-resistant epileptic patients who respond to VNS

Vagal nerve stimulation (VNS) is a therapeutic add-on treatment for patients with pharmaco-resistant epilepsy. The mechanism of action is still largely unknown. Previous studies have shown that brain network topology during the inter-ictal period in epileptic patients deviates from normal configuration. In the present paper, we investigate the relationship between clinical improvement induced by VNS and alterations in brain network topology. We hypothesize that, as a consequence of the VNS add-on treatment, functional brain network architecture shifts back toward a more efficient configuration in patients responding to VNS. Electroencephalographic (EEG) recordings from ten patients affected by pharmaco-resistant epilepsy were analyzed in the classical EEG frequency bands. The phase lag index (PLI) was used to estimate functional connectivity between EEG channels and the minimum spanning tree (MST) was computed in order to characterize VNS-induced alterations in network topology in a bias-free way. Our results revealed a clear network re-organization, in terms of MST modification, toward a more integrated architecture in patients responding to the VNS. In particular, the results show a significant interaction effect between benefit from VNS (responders/non-responders) and condition (pre/post VNS implantation) in the theta band. This finding suggests that the positive effect induced by VNS add-on treatment in epileptic patients is related to a clear network re-organization and that this network modification can reveal the long debated mechanism of action of VNS. Therefore, MST analysis could be useful in evaluating and monitoring the efficacy of VNS add-on treatment potentially in both epilepsy and psychiatric diseases.