Co-activation of interictal epileptiform discharges localizes seizure onset zone and fluctuates with brain state

Seizures are increasingly understood as emergent phenomena of complex, pathophysiologic networks. Interictal spikes are ubiquitous markers of paroxysmal synchronization in the epileptic brain and have been shown to co-activate between brain regions with millisecond-scale latencies, suggesting that they can spread through distributed networks of functionally inter-connected neuronal populations. In this study, we examined the relationship between interictal spike co-activation, seizure localization and resting-state EEG activity in children with medically refractory epilepsy. Twenty paediatric patients (mean age: 10.6 years) undergoing invasive EEG investigation with subdural electrodes were examined. Automated techniques were used to extract time-varying interictal spike co-activation networks from full-duration interictal recordings (mean: 108.6 h/patient). Networks were clustered into discrete node communities based on the conditional probability of spike co-activation. Patterns of regional and distributed interictal spike synchrony were investigated over time in relation to variables such as temporal proximity to nearest seizure and background oscillatory coherence. We demonstrate that the irritative neocortex comprises a network of semi-independent, highly cohesive communities with stereotyped local spike propagation patterns. Distributed coupling of spikes between communities was driven by outflow from the seizure onset zone and fluctuated over time in association with inter-regional coherence and temporal proximity to seizures. These results elucidate network dynamics facilitating pathologic hypersynchrony across the epileptic neocortex and further highlight the complex relationship between interictal epileptiform discharges and seizures.