Loss of neuronal network resilience precedes seizures and determines the ictogenic nature of interictal synaptic perturbations

Chang, Wei-Chih and Kudlacek, Jan and Hlinka, Jaroslav and Chvojka, Jan and Hadrava, Michal and Kumpost, Vojtech and Powell, Andrew D. and Janca, Radek and Maturana, Matias I. and Karoly, Philippa J. and Freestone, Dean R. and Cook, Mark J. and Palus, Milan and Otahal, Jakub and Jefferys, John G. R. and Jiruska, Premysl (2018) Loss of neuronal network resilience precedes seizures and determines the ictogenic nature of interictal synaptic perturbations. Nature Neuroscience, 21. pp. 1742-1752. ISSN 1097-6256

Preview

Text Chang_NN_Manuscript.pdf - Accepted Version Download (1MB)

Abstract

The mechanisms of seizure emergence, and the role of brief interictal epileptiform discharges (IEDs) in seizure generation are two of the most important unresolved issues in modern epilepsy research. Our study shows that the transition to seizure is not a sudden phenomenon,but a slow process characterized by the progressive loss of neuronal network resilience. From a dynamical perspective, the slow transition is governed by the principles of critical slowing, a robust natural phenomenon observable in systems characterized by transitions between dynamical regimes. In epilepsy, this process is modulated by the synchronous synaptic input from IEDs. IEDs are external perturbations that produce phasic changes in the slow transition process and exert opposing effects on the dynamics of a seizure-generating network, causing either anti-seizure or pro-seizure effects. We show that the multifaceted nature of IEDs is defined by the dynamical state of the network at the moment of the discharge occurrence.

Item Type:	Article
Identification Number:	10.1038/s41593-018-0278-y
Dates:	Date Event 15 October 2018 Accepted 26 November 2018 Published Online
Subjects:	CAH01 - medicine and dentistry > CAH01-01 - medicine and dentistry > CAH01-01-01 - medical sciences (non-specific) CAH02 - subjects allied to medicine > CAH02-05 - medical sciences > CAH02-05-04 - anatomy, physiology and pathology CAH02 - subjects allied to medicine > CAH02-02 - pharmacology, toxicology and pharmacy > CAH02-02-01 - pharmacology CAH03 - biological and sport sciences > CAH03-01 - biosciences > CAH03-01-08 - molecular biology, biophysics and biochemistry
Divisions:	Faculty of Health, Education and Life Sciences > College of Health and Care Professions
Depositing User:	Andy Powell
Date Deposited:	05 Nov 2018 09:25
Last Modified:	12 Jan 2022 11:37
URI:	https://www.open-access.bcu.ac.uk/id/eprint/6526

Actions (login required)

View Item