Predicting seizure outcome of vagus nerve stimulation using MEG-based network topology

Abstract

Vagus nerve stimulation (VNS) is a low-risk surgical option for patients with drug resistant epilepsy, although it is impossible to predict which patients may respond to VNS treatment. Resting-state magnetoencephalography (rs-MEG) connectivity analysis has been increasingly utilized to investigate the impact of epilepsy on brain networks and identify alteration of these networks after different treatments; however, there is no study to date utilizing this modality to predict the efficacy of VNS treatment. We investigated whether the rs-MEG network topology before VNS implantation can be used to predict efficacy of VNS treatment. Twenty-three patients with epilepsy who had MEG before VNS implantation were included in this study. We also included 89 healthy control subjects from the Human Connectome Project. Using the phase-locking value in the theta, alpha, and beta frequency bands as a measure of rs-MEG functional connectivity, we calculated three global graph measures: modularity, transitivity, and characteristic path length (CPL). Our results revealed that the rs-MEG graph measures were significantly heritable and had an overall good test-retest reliability, and thus these measures may be used as potential biomarkers of the network topology. We found that the modularity and transitivity in VNS responders were significantly larger and smaller, respectively, than those observed in VNS non-responders. We also observed that the modularity and transitivity in three frequency bands and CPL in delta and beta bands were significantly different in controls than those found in responders or non-responders, although the values of the graph measures in controls were closer to those of responders than non-responders. We used the modularity and transitivity as input features of a naïve Bayes classifier, and achieved an accuracy of 87% in classification of non-responders, responders, and controls. The results of this study revealed that MEG-based graph measures are reliable biomarkers, and that these measures may be used to predict seizure outcome of VNS treatment.

Keywords: Functional connectivity; Graph measures; Human connectome project (HCP); Magnetoencephalography (MEG); Phase-locking value (PLV); Seizure outcome; VNS efficacy; Vagus nerve stimulation (VNS).

Fig. 1

The global cost efficiency (GCE) versus the ratio of the retained strong connections to the total number of connections, defined as cost, in a representative patient. Note that a cost of approximately 10%, i.e. preserving only 10% of the strongest connections, maximizes the GCE.

Fig. 2

Comparison of the values of the characteristic path length, transitivity, and modularity in three frequency bands in non-responders, responders, and controls.