Dynamic network drivers of seizure generation, propagation and termination in human epilepsy

Abstract: Drug-resistant epilepsy is traditionally characterized by pathologic cortical tissue comprised of seizure-initiating foci'. Thesefoci' are thought to be embedded within an epileptic network whose functional architecture dynamically reorganizes during seizures through synchronous and asynchronous neurophysiologic processes. Critical to understanding these dynamics is identifying the synchronous connections that link foci to surrounding tissue and investigating how these connections facilitate seizure generation and termination. We use intracranial recordings from neocortical epilepsy patients undergoing pre-surgical evaluation to analyze functional connectivity before and during seizures. We develop and apply a novel technique to track network reconfiguration in time and to parse these reconfiguration dynamics into distinct seizure states, each characterized by unique patterns of network connections that differ in their strength and topography. Our approach suggests that seizures are generated when the synchronous relationships that isolate seizure `foci' from the surrounding epileptic network are broken down. As seizures progress, foci reappear as isolated subnetworks, marking a shift in network state that may aid seizure termination. Collectively, our observations have important theoretical implications for understanding the spatial involvement of distributed cortical structures in the dynamics of seizure generation, propagation and termination, and have practical significance in determining which circuits to modulate with implantable devices.