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.

Department of Biomedical Engineering The University of Melbourne Melbourne Australia

Department of Circuit Theory Faculty of Electrical Engineering Czech Technical University Prague Prague Czech Republic

Department of Complex Systems Institute of Computer Science of the Czech Academy of Sciences Prague Czech Republic

Department of Cybernetics Faculty of Electrical Engineering Czech Technical University Prague Prague Czech Republic

Department of Developmental Epileptology Institute of Physiology of the Czech Academy of Sciences Prague Czech Republic

Department of Life Science School of Health Sciences Birmingham City University Birmingham UK

Department of Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Pediatric Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Pharmacology University of Oxford Oxford UK

Faculty of Veterinary Medicine and Neuroscience Center University of Helsinki Helsinki Finland

Neuronal Networks Group School of Clinical and Experimental Medicine University of Birmingham Birmingham UK

The Graeme Clark Institute and Department of Medicine St Vincent's Hospital The University of Melbourne Melbourne Australia

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Epilepsy Curr. 2019 Mar-Apr;19(2):115-116. doi: 10.1177/1535759719835349. PubMed

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