Relating Cortical Atrophy in Temporal Lobe Epilepsy with Graph Diffusion-Based Network Models

Mesial temporal lobe epilepsy (TLE) is characterized by stereotyped origination and spread pattern of epileptogenic activity, which is reflected in stereotyped topographic distribution of neuronal atrophy on magnetic resonance imaging (MRI). Both epileptogenic activity and atrophy spread appear to follow white matter connections. We model the networked spread of activity and atrophy in TLE from first principles via two simple first order network diffusion models. Atrophy distribution is modeled as a simple consequence of the propagation of epileptogenic activity in one model, and as a progressive degenerative process in the other. We show that the network models closely reproduce the regional volumetric gray matter atrophy distribution of two epilepsy cohorts: 29 TLE subjects with medial temporal sclerosis (TLE-MTS), and 50 TLE subjects with normal appearance on MRI (TLE-no). Statistical validation at the group level suggests high correlation with measured atrophy (R = 0.586 for TLE-MTS, R = 0.283 for TLE-no). We conclude that atrophy spread model out-performs the hyperactivity spread model. These results pave the way for future clinical application of the proposed model on individual patients, including estimating future spread of atrophy, identification of seizure onset zones and surgical planning.
Author Summary Medial temporal lobe epilepsy is the most common form of focal epilepsy. In this work we investigate two models describing the dynamics of epilepsy. In the first model the extrahippocampal spread of seizure activity is primarily responsible for the apparent topographic distribution of atrophy. The second hypothesis is that loss of hippocampal neurons leads to remote deafferentation followed by gradual and progressive neuronal loss in connected regions. Impoverishment of hippocampal connections can lead to reduced complexity of remote circuitry. The purpose of this work is to develop network theoretic models of regional atrophy dynamics resulting from each of the above hypotheses, and to statistically determine which model is a better descriptor of the spatial patterning of real TLE atrophy. Both models are based on simple graph theoretic models of influence spread as a network diffusion process, enacted on the brains structural connectivity network.