Abstract

Network neuroscience applied to epilepsy holds promise to map pathological networks, localize seizure generators, and inform targeted interventions to control seizures. However, incomplete sampling of the epileptic brain because of sparse placement of intracranial electrodes may affect model results. In this study, we evaluate the sensitivity of several published network measures to incomplete spatial sampling and propose an algorithm using network subsampling to determine confidence in model results. We retrospectively evaluated intracranial EEG data from 28 patients implanted with grid, strip, and depth electrodes during evaluation for epilepsy surgery. We recalculated global and local network metrics after randomly and systematically removing subsets of intracranial EEG electrode contacts. We found that sensitivity to incomplete sampling varied significantly across network metrics. This sensitivity was largely independent of whether seizure onset zone contacts were targeted or spared from removal. We present an algorithm using random subsampling to compute patient-specific confidence intervals for network localizations. Our findings highlight the difference in robustness between commonly used network metrics and provide tools to assess confidence in intracranial network localization. We present these techniques as an important step toward translating personalized network models of seizures into rigorous, quantitative approaches to invasive therapy.

Highlights

  • Epilepsy is a significant cause of disability worldwide, among the one third of patients whose seizures cannot be controlled by medications (Kwan, Schachter, & Brodie, 2011; Wiebe, Eliasziw, Bellhouse, & Fallahay, 1999)

  • Based upon the assumption that the main drivers of epilepsy network behavior might localize to an epileptogenic region, we ask to what extent electrode contacts far away from the seizure onset zone impact the estimated values of various network metrics, and whether subsampling that targets the seizure onset zone disproportionately affects network statistics compared with subsampling that spares the seizure onset zone

  • When we compare metric agreement removing all seizure onset zone electrode contacts as opposed to removing only non-seizure onset zone electrode contacts, there was again no significant difference in metric agreement between the seizure onset zone-sparing and seizure onset zone-targeted approach for any metric. These findings suggest that sparing versus targeting seizure onset zone electrode contacts for removal has equivalent effects on most network statistics

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Summary

Introduction

Epilepsy is a significant cause of disability worldwide, among the one third of patients whose seizures cannot be controlled by medications (Kwan, Schachter, & Brodie, 2011; Wiebe, Eliasziw, Bellhouse, & Fallahay, 1999) While these patients may benefit from surgery or implanted devices, many continue to experience seizures after invasive therapies (Engel, 1996; Englot, Birk, & Chang, 2017; Noe et al, 2013; Wiebe, Blume, Girvin, & Eliasziw, 2001). These network measures have been used to predict neuronal firing as seizures begin and spread, track seizure progression, identify the seizure onset zone, and predict surgical outcome (Burns et al, 2014; Fletcher & Wennekers, 2018; Panzica, Varotto, Rotondi, Spreafico, & Franceschetti, 2013; Ponten, Bartolomei, & Stam, 2007; Sinha et al, 2017; Wilke et al, 2011)

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