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

Abstract

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.

Pathological responses to single‐pulse electrical stimuli in epilepsy: The role of feedforward inhibition

“…Next, based on connectivity analysis of ER networks (Hebbink et al, 2019;van Blooijs et al, 2018), we concluded that DRs are indirect responses to the stimulation. Model simulations show that they may arise from feedforward propagation of ER activity and notably projections to inhibitory populations that normally restrain neural activity.…”

“…We use the detected ERs to construct a network representing effective connectivity (Entz et al., ; Hebbink et al., ; Keller et al., ; van Blooijs et al., ). Each electrode represents a node in this network.…”

“…The SPES protocol has been described in detail (van Blooijs et al, 2018;van 't Klooster et al, 2011). In short, pairs of adjacent electrodes along the length of the grid receive ten monophasic electrical pulses with a duration of 1 ms, at an interval of 5 s and a typical intensity of 8 mA.…”

“…These networks (partly) explain ipsilateral seizure propagation (Enatsu et al., ; Mouthaan et al., ) in contrast to contralateral seizure spread (Jiménez‐Jiménez et al., ). Moreover, network measures calculated from these ER networks exhibit differences between nodes in and outside the resected area and SOZ (Boido et al., ; van Blooijs, Leijten, van Rijen, Meijer, & Huiskamp, ).…”

Computational modelling and electrical stimulation for epilepsy surgery

“…SPES networks might be a good alternative as such models would incorporate more physiological connections. Moreover, SPES ER networks contain information about both the seizure onset zone [37,38] and seizure propagation [35,36]. It would therefore be interesting to compare SPES and ictal networks.…”