A Peri-Ictal EEG-Based Biomarker for Sudden Unexpected Death in Epilepsy (SUDEP) Derived From Brain Network Analysis

Uilki Tufa; Adam Gravitis; Katherine Zukotynski; Yotin Chinvarun; Orrin Devinsky; Richard Wennberg; Peter L Carlen; Berj L Bardakjian

doi:10.3389/fnetp.2022.866540

A Peri-Ictal EEG-Based Biomarker for Sudden Unexpected Death in Epilepsy (SUDEP) Derived From Brain Network Analysis

Front Netw Physiol. 2022 Apr 26:2:866540. doi: 10.3389/fnetp.2022.866540. eCollection 2022.

Authors

Uilki Tufa¹, Adam Gravitis¹, Katherine Zukotynski^{2

3}, Yotin Chinvarun⁴, Orrin Devinsky⁵, Richard Wennberg⁶, Peter L Carlen^{1

5

7}, Berj L Bardakjian^{1

2}

Affiliations

¹ Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
² Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada.
³ Department of Radiology and Medicine, McMaster University, Hamilton, ON, Canada.
⁴ Comprehensive Epilepsy Program and Neurology Unit, Phramongkutklao Hospital, Bangkok, Thailand.
⁵ Department of Neurology, New York University School of Medicine, New York, NY, United States.
⁶ Division of Neurology, Toronto Western Hospital, Toronto, ON, Canada.
⁷ Department of Physiology, University of Toronto, Toronto, ON, Canada.

Abstract

Sudden unexpected death in epilepsy (SUDEP) is the leading seizure-related cause of death in epilepsy patients. There are no validated biomarkers of SUDEP risk. Here, we explored peri-ictal differences in topological brain network properties from scalp EEG recordings of SUDEP victims. Functional connectivity networks were constructed and examined as directed graphs derived from undirected delta and high frequency oscillation (HFO) EEG coherence networks in eight SUDEP and 14 non-SUDEP epileptic patients. These networks were proxies for information flow at different spatiotemporal scales, where low frequency oscillations coordinate large-scale activity driving local HFOs. The clustering coefficient and global efficiency of the network were higher in the SUDEP group pre-ictally, ictally and post-ictally (p < 0.0001 to p < 0.001), with features characteristic of small-world networks. These results suggest that cross-frequency functional connectivity network topology may be a non-invasive biomarker of SUDEP risk.

Keywords: SUDEP (sudden unexpected death in epilepsy); brain dynamics; brain networks; electroencephalography; epilepsy; functional brain connectivity; seizures.

Grants and funding

BB acknowledges support by (a) the Natural Sciences and Engineering Research Council of Canada (NSERC), (b) EpLink - the Epilepsy Research Program of the Ontario Brain Institute. (The Ontario Brain Institute is an independent non-profit corporation, funded partially by the Ontario government. The opinions, results and conclusions are those of the authors and no endorsement by the Ontario Brain Institute is intended or should be inferred), and c) The SciNet HPC Consortium which is funded by the Canada Foundation for Innovation; the Government of Ontario; Ontario Research Fund - Research Excellence; and the University of Toronto.