A deep representation learning model to predict response to vagus nerve stimulation

Implantable neurotechnologies are increasingly used to reduce seizure burden in pediatric epilepsy. Vagus nerve stimulation (VNS), the most common option, is effective for only half of patients, with no means to predict outcome prior to surgery. As a result, many children undergo invasive and costly procedures without benefit. Although T1-weighted magnetic resonance imaging (T1w) is routinely acquired presurgically and may capture structural brain differences relevant to treatment outcome, its high dimensionality relative to sample sizes has limited its utility in predictive modelling. To address this challenge, we present VQ-VNS, a deep representation learning model to predict VNS outcome based on preoperative T1w (n = 263). First, we present data from the largest paediatric VNS cohort (n = 1046), wherein presurgical clinical data could not predict response (AUC 0.54,p > 0.99). Next, VQ-VNS was pretrained on 7433 T1w images to learn compact anatomical representations enabling its classifier to predict VNS response (AUC = 0.73,p = 0.007). Model predictions localized to serotonin-rich brain regions and inferred large-scale disruptions in network connectivity among non-responders. This biologically interpretable predictor based on routine structural imaging improves upon current clinical decision-making.