Graph theoretical analysis of evoked potentials shows network influence of epileptogenic mesial temporal region

Abstract

It is now widely accepted that seizures arise from the coordinated activity of epileptic networks, and as a result, traditional methods of analyzing seizures have been augmented by techniques like single‐pulse electrical stimulation (SPES) that estimate effective connectivity in brain networks. We used SPES and graph analytics in 18 patients undergoing intracranial EEG monitoring to investigate effective connectivity between recording sites within and outside mesial temporal structures. We compared evoked potential amplitude, network density, and centrality measures inside and outside the mesial temporal region (MTR) across three patient groups: focal epileptogenic MTR, multifocal epileptogenic MTR, and non‐epileptogenic MTR. Effective connectivity within the MTR had significantly greater magnitude (evoked potential amplitude) and network density, regardless of epileptogenicity. However, effective connectivity between MTR and surrounding non‐epileptogenic regions was of greater magnitude and density in patients with focal epileptogenic MTR compared to patients with multifocal epileptogenic MTR and those with non‐epileptogenic MTR. Moreover, electrodes within focal epileptogenic MTR had significantly greater outward network centrality compared to electrodes outside non‐epileptogenic regions and to multifocal and non‐epileptogenic MTR. Our results indicate that the MTR is a robustly connected subnetwork that can exert an overall elevated propagative influence over other brain regions when it is epileptogenic. Understanding the underlying effective connectivity and roles of epileptogenic regions within the larger network may provide insights that eventually lead to improved surgical outcomes.

Source-sink connectivity: A novel interictal EEG marker for seizure localization

“…This connectivity asymmetry across hemispheres is in line with findings of other studies, which have demonstrated a decreased functional connectivity within the epileptogenic hippocampal networks with a concurrent increased connectivity in contralateral hippocampal pathways, possibly reflecting compensatory mechanisms with strengthening of alternative pathways in these patients. 110,[114][115][116] To that end, the connectivity patterns and natural sink-like behavior of the hippocampus need to be taken into consideration as results of the source-sink analysis are reviewed and interpreted. Although the tool performs well with the hippocampal electrodes included in the datasets, as reflected by our results, there might be cases where these electrodes could simply be removed (e.g., clinical experts are certain that the hippocampus is not involved in seizure onsetand hippocampus was only targeted to rule out temporal epilepsy or determine spread and thus would ignore these electrodes in their standard of care analyses).…”

“…In patients with electrodes targeting the hippocampal region, the hippocampal contacts were frequently identified as top sinks in the iEEG network. The hippocampus is a highly connected structure, with many bidirectional connections within and to surrounding regions 110 both intra- and inter-hemispherically. 111 Further, studies of mesial temporal lobe epilepsy (MTLE) have demonstrated the existence of strong connections within the hippocampal network bilaterally in both epileptogenic as well as non-epileptogenic hippocampi.…”

“…This connectivity asymmetry across hemispheres is in line with findings of other studies, which have demonstrated a decreased functional connectivity within the epileptogenic hippocampal networks with a concurrent increased connectivity in contralateral hippocampal pathways, possibly reflecting compensatory mechanisms with strengthening of alternative pathways in these patients. 110,114–116…”

“…Several studies have demonstrated a high inward directed influence to the EZ at rest. 55,[67][68][69] In a recent study Narasimhan et al 67 stated that high inward connectivity may reflect inhibitory input from other regions to prevent the onset and spread of seizure activity, but the direction of these signals may flip when seizure activity begins. This is supported by iEEG studies in neocortical epilepsy demonstrating functional isolation of epileptogenic areas at rest 70,71 and that increased synchronization in seizure-onset regions may be suggestive of an inhibitory surround.…”

“…104 In patients with electrodes targeting the hippocampal region, the hippocampal contacts were frequently identified as top sinks in the iEEG network. The hippocampus is a highly connected structure 69,105 and studies of mesial temporal lobe epilepsy (MTLE) have demonstrated the existence of strong connections within the hippocampal network in both epileptogenic as well as non-epileptogenic hippocampi. 69,106,107 As such, the hippocampus is a structure that is highly influenced by other regions and by its nature acts as a sink in the brain network regardless of its epileptogenicity.…”