Dynamic network properties of the interictal brain determine whether seizures appear focal or generalised

Abstract

Current explanatory concepts suggest seizures emerge from ongoing dynamics of brain networks. It is unclear how brain network properties determine focal or generalised seizure onset, or how network properties can be described in a clinically-useful manner. Understanding network properties would cast light on seizure-generating mechanisms and allow to quantify to which extent a seizure is focal or generalised. Functional brain networks were estimated in segments of scalp-EEG without interictal discharges (68 people with epilepsy, 38 controls). Simplified brain dynamics were simulated using a computer model. We introduce: Critical Coupling (C c), the ability of a network to generate seizures; Onset Index (OI), the tendency of a region to generate seizures; and Participation Index (PI), the tendency of a region to become involved in seizures. C c was lower in both patient groups compared with controls. OI and PI were more variable in focal-onset than generalised-onset cases. In focal cases, the regions with highest OI and PI corresponded to the side of seizure onset. Properties of interictal functional networks from scalp EEG can be estimated using a computer model and used to predict seizure likelihood and onset patterns. This may offer potential to enhance diagnosis through quantification of seizure type using inter-ictal recordings. Brain function is increasingly understood in terms of large-scale brain networks. Disruptions to these networks can lead to a range of neurological conditions, including seizure disorders and epilepsy 1. In focal epilepsy, the conventional concept is that a single abnormal brain region generates seizures. However, this concept does not explain the re-emergence of seizures after apparently successful surgical resection of the presumed seizure focus 2 , or that failure of epilepsy surgery can be predicted by features of an extended brain network beyond the seizure focus 3-7. In generalised epilepsy, the conventional concept is that seizures emerge without focal onset. However, this concept does not explain focal driving nodes in animal models of generalised spike-wave discharges 8. We previously proposed a theoretical framework that could reconcile these observations, showing the interplay between dynamics in localised brain regions and the pattern of connections between them is fundamental to whether a brain network can generate seizures, and whether seizures appear focal or generalised 9. Recognising that the historic dichotomy or either focal or generalised onsets does not reflect the richness of epilepsies presenting clinically, classification schemes have been evolving to reflect this new understanding of large-scale network mechanisms 10,11. A rigorous, quantitative, framework is required to underpin these new classifications of focal, generalised, combined focal and generalised and unknown epilepsies, in particular to quantify: (i) the propensity of a brain to generate seizures; (ii) how localised is the generation of a seizure; and (iii) how seizure activity propagates through l...

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