Graph theory findings in the pathophysiology of temporal lobe epilepsy

•Graph theory models of brain connectivity can illuminate aspects of temporal lobe epilepsy (TLE) pathophysiology pertaining to ictogenesis, ictal propagation, and the interictal state from a network perspective.•A more regular interictal brain network, increased characteristic path length, and redistribution of hubs in TLE, associated with reduced neuronal tolerance to pathological attack, have been consistently identified.•Integration of multimodal findings calls for additional cell culture and simulated neuron models to highlight the significance of topological changes.

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy. Accumulating evidence has shown that TLE is a disorder of abnormal epileptogenic networks, rather than focal sources. Graph theory allows for a network-based representation of TLE brain networks, and has potential to illuminate characteristics of brain topology conducive to TLE pathophysiology, including seizure initiation and spread. We review basic concepts which we believe will prove helpful in interpreting results rapidly emerging from graph theory research in TLE. In addition, we summarize the current state of graph theory findings in TLE as they pertain its pathophysiology. Several common findings have emerged from the many modalities which have been used to study TLE using graph theory, including structural MRI, diffusion tensor imaging, surface EEG, intracranial EEG, magnetoencephalography, functional MRI, cell cultures, simulated models, and mouse models, involving increased regularity of the interictal network configuration, altered local segregation and global integration of the TLE network, and network reorganization of temporal lobe and limbic structures. As different modalities provide different views of the same phenomenon, future studies integrating data from multiple modalities are needed to clarify findings and contribute to the formation of a coherent theory on the pathophysiology of TLE.