Mesial temporal lobe epilepsy with hippocampal sclerosis is a network disorder with altered cortical hubs

Abstract

SUMMARYObjective: Electrophysiologic hubs within the large-scale functional networks in mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS) have not been investigated. We hypothesized that mTLE with HS has different resting-state network hubs in their large-scale functional networks compared to the hubs in healthy controls (HC). We also hypothesized that the hippocampus would be a functional hub in mTLE patients with HS. Methods: Resting-state functional networks, identified by using magnetoencephalography (MEG) signals in the theta, alpha, beta, and gamma frequency bands, were evaluated. Networks in 44 mTLE patients with HS (left mTLE = 22; right mTLE = 22) were compared with those in 46 age-matched HC. We investigated betweenness centrality at the source-level MEG network. Results: The main network hubs were at the pole of the left superior temporal gyrus in the beta band, the pole of the left middle temporal gyrus in the beta and gamma bands, left hippocampus in the theta and alpha bands, and right posterior cingulate gyrus in all four frequency bands in mTLE patients; all of which were different from the main network hubs in HC. Only patients with left mTLE showed profound differences from HC at the left hippocampus in the alpha band. Significance: Our analysis of resting-state MEG signals shows that altered electrophysiologic functional hubs in mTLE patients reflect pathophysiologic brain network reorganization. Because we detected network hubs in both hippocampal and extrahippocampal areas, it is probable that mTLE is a large-scale network disorder rather than a focal disorder. The hippocampus was a network hub in left mTLE but not in right mTLE patients, which may be due to intrinsic functional and structural asymmetries between left and right mTLE patients. The evaluation of cortical hubs, even in the spike-free resting-state, could be a clinical diagnostic marker of mTLE with HS.

Medial temporal lobe epilepsy associated with hippocampal sclerosis is a distinctive syndrome

“…This suggests a specific network of propagations and a large-scale functional network as recent functional imaging studies, especially connectivity studies, have revealed it [16,17].…”

Organization and control of epileptic circuits in temporal lobe epilepsy

“…This changed connectivity could certainly be important given that limbic seizures are known to propagate through the thalamus in both human and animal models (Blumenfeld et al, 2004; Guye et al, 2006; Patel et al, 1988; Sloan et al, 2011). Additionally, MEG analysis was able to demonstrate the presence of hub-like regions in both temporal cortex and hippocampus of patients with TLE that do not exist in control subjects, and the importance of hubs to excitability was discussed earlier (Jin et al, 2015). …”

Network analysis for a network disorder: The emerging role of graph theory in the study of epilepsy

“…In TLE, while most seizures originate in the hippocampus [66], the epileptogenic network has been shown to often extend to entorhinal, lateral temporal, and inferior frontal cortices as well, together with subcortical nuclei, such as the amygdala and medial thalamus [61,62]. Offering a synoptic view on brain dynamics at a millisecond scale, electrophysiological studies employing electroencephalography (EEG) and magnetoencephalography (MEG) not only have been of high utility in characterizing changes at seizure onset but also could reveal chronic changes in local and distributed activity [67,68]. Notably, studying statistical relationships between time series has been used to evaluate dynamic changes in interregional connectivity; moreover, electrophysiological techniques provide a range of spectral (i.e., frequency-dependent) markers that have the potential to probe tissue epileptogenicity in vivo.…”