Abstract
There is an unmet need to develop robust predictive algorithms to preoperatively identify pediatric epilepsy patients who will respond to vagus nerve stimulation (VNS). Given the similarity in the neural circuitry between vagus and median nerve afferent projections to the primary somatosensory cortex, the current study hypothesized that median nerve somatosensory evoked field(s) (SEFs) could be used to predict seizure response to VNS. Retrospective data from forty-eight pediatric patients who underwent VNS at two different institutions were used in this study. Thirty-six patients ("Discovery Cohort") underwent preoperative electrical median nerve stimulation during magnetoencephalography (MEG) recordings and 12 patients ("Validation Cohort") underwent preoperative pneumatic stimulation during MEG. SEFs and their spatial deviation, waveform amplitude and latency, and event-related connectivity were calculated for all patients. A support vector machine (SVM) classifier was trained on the Discovery Cohort to differentiate responders from non-responders based on these input features and tested on the Validation Cohort by comparing the model-predicted response to VNS to the known response. We found that responders to VNS had significantly more widespread SEF localization and greater functional connectivity within limbic and sensorimotor networks in response to median nerve stimulation. No difference in SEF amplitude or latencies was observed between the two cohorts. The SVM classifier demonstrated 88.9% accuracy (0.93 area under the receiver operator characteristics curve) on cross-validation, which decreased to 67% in the Validation cohort. By leveraging overlapping neural circuitry, we found that median nerve SEF characteristics and functional connectivity could identify responders to VNS.