Interictal discharges spread along local recurrent networks between tubers and surrounding cortex

Abstract

The presence of interictal epileptiform discharges on electroencephalography (EEG) may indicate increased epileptic seizure risk and on invasive EEG are the signature of the irritative zone. In highly epileptogenic lesions - such as cortical tubers in tuberous sclerosis - these discharges can be recorded with intracranial stereotactic EEG as part of the evaluation for epilepsy surgery. Yet the network mechanisms that underwrite the generation and spread of these discharges remain poorly understood, limiting their current diagnostic use.\n\nHere, we investigate the dynamics of interictal epileptiform discharges using a combination of quantitative analysis of invasive EEG recordings and mesoscale neural mass modelling of cortical dynamics. We first characterise spatially organised local dynamics of discharges recorded from 36 separate tubers in 8 patients with tuberous sclerosis. We characterise these dynamics with a set of competing explanatory network models using dynamic causal modelling. Bayesian model comparison of plausible network architectures suggests that the recurrent coupling between neuronal populations within - and adjacent to - the tuber core explains the travelling wave dynamics observed in these patient recordings.\n\nOur results - based on interictal activity - unify competing theories about the pathological organisation of epileptic foci and surrounding cortex in patients with tuberous sclerosis. Coupled oscillator dynamics have previously been used to describe ictal activity, where fast travelling ictal discharges are commonly observed within the recruited seizure network. The interictal data analysed here add the insight that this functional architecture is already established in the interictal state. This links observations of interictal EEG abnormalities directly to pathological network coupling in epilepsy, with possible implications for epilepsy surgery approaches in tuberous sclerosis.\n\nSignificance StatementInterictal epileptiform discharges (IEDs) are clinically important markers of an epileptic brain. Here we link local IED spread to network coupling through a combination of clinical recordings in paediatric patients with tuberous sclerosis complex, quantitative EEG analysis of interictal discharges spread, and Bayesian inference on coupled neural mass model parameters. We show that the kinds of interictal discharges seen in our patients require recurrent local network coupling extending beyond the putative seizure focus and that in fact only those recurrent coupled networks can support seizure-like and interictal dynamics when run in simulation. Our findings provide a novel integrated perspective on emergent epileptic dynamics in human patients.