Time-evolving controllability of effective connectivity networks during seizure progression

Abstract: Over one third of the estimated 3 million people with epilepsy in the US are medication resistant. Responsive neurostimulation from chronically implanted electrodes provides a promising treatment option and alternative to resective surgery. However, determining personalized optimal stimulation parameters, including when and where to intervene to guarantee a positive patient outcome, is a major open challenge. Network neuroscience and control theory offer useful tools that may guide improvements in parameter selection for control of anomalous neural activity. Here we use a novel method to characterize dynamic controllability across consecutive effective connectivity (EC) networks based on regularized partial correlations between implanted electrodes during the onset, propagation, and termination phases of thirty-four seizures. We estimate regularized partial correlation adjacency matrices from one-second time windows of intracranial electrocorticography recordings using the Graphical Least Absolute Shrinkage and Selection Operator (GLASSO). Average and modal controllability metrics calculated from each resulting EC network track the time-varying controllability of the brain on an evolving landscape of conditionally dependent network interactions. We show that average controllability increases throughout a seizure and is negatively correlated with modal controllability throughout. Furthermore, our results support the hypothesis that the energy required to drive the brain to a seizure-free state from an ictal state is smallest during seizure onset; yet, we find that applying control energy at electrodes in the seizure onset zone may not always be energetically favorable. Our work suggests that a low-complexity model of time-evolving controllability may offer new insights for developing and improving control strategies targeting seizure suppression.