Human seizures couple across spatial scales through travelling wave dynamics

L-E Martinet,W Truccolo,G Fiddyment,M A Kramer,J R Madsen,E N Eskandar,S S Cash,U T Eden

doi:10.1038/ncomms14896

Abstract

Epilepsy—the propensity toward recurrent, unprovoked seizures—is a devastating disease affecting 65 million people worldwide. Understanding and treating this disease remains a challenge, as seizures manifest through mechanisms and features that span spatial and temporal scales. Here we address this challenge through the analysis and modelling of human brain voltage activity recorded simultaneously across microscopic and macroscopic spatial scales. We show that during seizure large-scale neural populations spanning centimetres of cortex coordinate with small neural groups spanning cortical columns, and provide evidence that rapidly propagating waves of activity underlie this increased inter-scale coupling. We develop a corresponding computational model to propose specific mechanisms—namely, the effects of an increased extracellular potassium concentration diffusing in space—that support the observed spatiotemporal dynamics. Understanding the multi-scale, spatiotemporal dynamics of human seizures—and connecting these dynamics to specific biological mechanisms—promises new insights to treat this devastating disease.

Highlights

Epilepsy—the propensity toward recurrent, unprovoked seizures—is a devastating disease affecting 65 million people worldwide
We conclude with a computational model that captures the observed seizure dynamics and leads to suggestions of specific mechanisms—namely, the effects of an increased extracellular potassium concentration diffusing in space—that support the observed inter-scale spatiotemporal dynamics of human seizure
Microscopic data were recorded from a 10-by-10 microelectrode array (MEA, red in Fig. 1a) with electrode spacing of 0.4 mm

Summary

Introduction

Epilepsy—the propensity toward recurrent, unprovoked seizures—is a devastating disease affecting 65 million people worldwide Understanding and treating this disease remains a challenge, as seizures manifest through mechanisms and features that span spatial and temporal scales. How to optimally assemble and understand these diverse spatiotemporal datasets across spatial scales—especially in behaving humans—remains unknown We address this challenge in the specific context of understanding human epileptic seizure, itself a multi-scale phenomenon, spanning microscopic channelopathies to macroscopic clinical manifestations[2,3]. Both in vivo microelectrode recordings[15,16,17] and in vitro recordings from resected tissue[18,19] provide detailed dynamic and mechanistic insight into the behaviour of single neurons and small neural populations during human seizure How these phenomena relate to the activity of large scale cortical networks recruited during seizure remains unknown. Such improvements are essential as little substantial progress in seizure control for pharmacoresistant patients has been made over the past 40–50 years[29,30]

Methods

Results

Conclusion