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

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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: https://doi.org/10.1038/s41593-018-0278-y
Date: 26 November 2018
Subjects: A100 Pre-clinical Medicine
A300 Clinical Medicine
B100 Anatomy, Physiology and Pathology
B200 Pharmacology, Toxicology and Pharmacy
C700 Molecular Biology, Biophysics and Biochemistry
Divisions: Faculty of Health, Education and Life Sciences > School of Health Sciences
Depositing User: Andy Powell
Date Deposited: 05 Nov 2018 09:25
Last Modified: 23 Jun 2020 13:55
URI: http://www.open-access.bcu.ac.uk/id/eprint/6526

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