Preoperative MEG reveals differential brain network characteristics in drug-resistant epilepsy patients based on vagus nerve stimulation response

Comprehensive Summary

This article examines whether resting-state magnetoencephalography (MEG) connectivity patterns can predict responsiveness to vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE). Although VNS is a widely used neuromodulatory treatment, only a few patients experience meaningful seizure reduction, making the identification of reliable preoperative biomarkers a critical clinical challenge. To address this, the authors analyzed and compared MEG recordings and classified them as responders if they achieved a greater than 50% reduction in seizure frequency 1 year after implantation. Using the amplitude envelope correlation, the study found that 7 of the 18 patients had more than 50% reduction in frequency and that it was also possible to assess connectivity and delta frequency in the brain's cortical regions. In non-responders to VNS, abnormalities in brain connectivity were observed across nearly all frequency bands, particularly in higher-frequency ranges associated with epileptogenic activity. Overall, they exhibited 359 increased and 249 decreased connections relative to healthy controls, indicating widespread network disorganization. Responder VNS patients showed fewer deviations, with no significant differences relative to controls. These findings indicate that VNS responders had more organized functional networks prior to treatment, which may have increased the effectiveness of neuromodulation.

Outcomes and Implications

This research is important because determining responders and nonresponders to VNS treatment will improve patient selection and personalized treatment plans for epilepsy. The study suggests that VNS efficacy is strongly influenced by the pre-existing state of brain networks, with patients showing relatively intact functional organization being more likely to benefit from stimulation. This supports the idea that VNS functions as a modulatory intervention and is most effective when targeting functional circuits. In patients with widespread hyper- and hypoconnectivity, such as in non-responder VNS individuals, disorganization reduces effective neuromodulation. Clinically, this work shows the potential of preoperative MEG connectivity analysis as a noninvasive biomarker for VNS responsiveness. The authors stated that, once validated, it could help physicians avoid unnecessary implantations and provide more diverse options for addressing epilepsy care. Additionally, MEG's ability to capture high-frequency activity and bands will increase the precision with which the type and pattern of epilepsy and its treatment can be determined.