A Model-Based Assessment of the Seizure Onset Zone Predictive Power to Inform the Epileptogenic Zone

Epilepsy surgery is a clinical procedure that aims to remove the brain tissue responsible for the emergence of seizures, the epileptogenic zone (EZ). It is preceded by an evaluation to determine the brain tissue that must be resected. The identification of the seizure onset zone (SOZ) from intracranial EEG recordings stands as one of the key proxies for the EZ. In this study we used computational models of epilepsy to assess to what extent the SOZ may or may not represent the EZ. We considered a set of different synthetic networks (e.g., regular, small-world, random, and scale-free networks) to represent large-scale brain networks and a phenomenological network model of seizure generation. In the model, the SOZ was inferred from the seizure likelihood (SL), a measure of the propensity of single nodes to produce epileptiform dynamics, whilst a surgery corresponded to the removal of nodes and connections from the network. We used the concept of node ictogenicity (NI) to quantify the effectiveness of each node removal on reducing the network's propensity to generate seizures. This framework enabled us to systematically compare the SOZ and the seizure control achieved by each considered surgery. Specifically, we compared the distributions of SL and NI across different networks. We found that SL and NI were concordant when all nodes were similarly ictogenic, whereas when there was a small fraction of nodes with high NI, the SL was not specific at identifying these nodes. We further considered networks with heterogeneous node excitabilities, i.e., nodes with different susceptibilities of being engaged in seizure activity, to understand how such heterogeneity may affect the relationship between SL and NI. We found that while SL and NI are concordant when there is a small fraction of hyper-excitable nodes in a network that is otherwise homogeneous, they do diverge if the network is heterogeneous, such as in scale-free networks. We observe that SL is highly dependent on node excitabilities, whilst the effect of surgical resections as revealed by NI is mostly determined by network structure. Together our results suggest that the SOZ is not always a good marker of the EZ.