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Nat Neurosci. 2018 Dec;21(12):1742-1752. doi: 10.1038/s41593-018-0278-y. Epub 2018 Nov 26.

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

Author information

1
Neuronal Networks Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
2
Faculty of Veterinary Medicine and Neuroscience Center, University of Helsinki, Helsinki, Finland.
3
Department of Developmental Epileptology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
4
Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic.
5
Department of Complex Systems, Institute of Computer Science of the Czech Academy of Sciences, Prague, Czech Republic.
6
Department of Cybernetics, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic.
7
Department of Life Science, School of Health Sciences, Birmingham City University, Birmingham, UK.
8
Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
9
Department of Pediatric Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
10
The Graeme Clark Institute & Department of Medicine St. Vincent's Hospital, The University of Melbourne, Melbourne, Australia.
11
Department of Biomedical Engineering, The University of Melbourne, Melbourne, Australia.
12
Neuronal Networks Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK. john.jefferys@pharm.ox.ac.uk.
13
Department of Pharmacology, University of Oxford, Oxford, UK. john.jefferys@pharm.ox.ac.uk.
14
Department of Developmental Epileptology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic. jiruskapremysl@gmail.com.

Abstract

The mechanism 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. We found that the transition to seizure is not a sudden phenomenon, but is instead a slow process that is 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 that is observable in systems characterized by transitions between dynamical regimes. In epilepsy, this process is modulated by 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 found that the multifaceted nature of IEDs is defined by the dynamical state of the network at the moment of the discharge occurrence.

PMID:
30482946
DOI:
10.1038/s41593-018-0278-y
[Indexed for MEDLINE]

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