Evoked directional network characteristics of epileptogenic tissue derived from single pulse electrical stimulation

We investigated effective networks constructed from single pulse electrical stimulation (SPES) in epilepsy patients who underwent intracranial electrocorticography. Using graph analysis, we compared network characteristics of tissue within and outside the epileptogenic area. In 21 patients with subdural electrode grids (1 cm interelectrode distance), we constructed a binary, directional network derived from SPES early responses (<100 ms). We calculated in-degree, out-degree, betweenness centrality, the percentage of bidirectional, receiving and activating connections, and the percentage of connections toward the (non-)epileptogenic tissue for each node in the network. We analyzed whether these network measures were significantly different in seizure onset zone (SOZ)-electrodes compared to non-SOZ electrodes, in resected area (RA)-electrodes compared to non-RA electrodes, and in seizure free compared to not seizure-free patients. Electrodes in the SOZ/RA showed significantly higher values for in-degree and out-degree, both at group level, and at patient level, and more so in seizure-free patients. These differences were not observed for betweenness centrality. There were also more bidirectional and fewer receiving connections in the SOZ/RA in seizure-free patients. It appears that the SOZ/RA is densely connected with itself, with only little input arriving from non-SOZ/non-RA electrodes. These results suggest that meso-scale effective network measures are different in epileptogenic compared to normal brain tissue. Local connections within the SOZ/RA are increased and the SOZ/RA is relatively isolated from the surrounding cortex. This offers the prospect of enhanced prediction of epilepsy-prone brain areas using SPES.