Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings

Abstract

Epilepsy is among the most common brain network disorders, and it is associated with substantial morbidity and increased mortality. While focal epilepsy was traditionally thought of as a regional brain disorder, growing evidence has demonstrated widespread network alterations in this disorder which extend beyond the epileptogenic zone from which seizures originate. The goal of this review is to summarize recent investigations examining functional and structural connectivity alterations in focal epilepsy, including neuroimaging and electrophysiology studies utilizing model-based or data-driven analysis methods. A significant subset of studies in both mesial temporal lobe epilepsy and focal neocortical epilepsy have demonstrated patterns of increased connectivity related to the epileptogenic zone, coupled with decreased connectivity in widespread distal networks. Connectivity patterns appear to be related to the duration and severity of disease, suggesting progressive connectivity reorganization in the setting of recurrent seizures over time. Global resting-state connectivity disturbances in focal epilepsy have been linked to neurocognitive problems, including memory and language disturbances. While it is possible that increased connectivity in a particular brain region may enhance the propensity for seizure generation, it is not clear if global reductions in connectivity represent the damaging consequences of recurrent seizures, or an adaptive mechanism to prevent seizure propagation away from the epileptogenic zone. Overall, studying the connectome in focal epilepsy is a critical endeavor which may lead to improved strategies for epileptogenic zone localization, surgical outcome prediction, and a better understanding of the neuropsychological implications of recurrent seizures.

Functional connectivity disturbances of the ascending reticular activating system in temporal lobe epilepsy

“…It is useful to note that several previous investigations have demonstrated connectivity disturbances in widespread brain networks in TLE8; therefore, connectivity problems in this disorder are not specific to the ARAS alone. Interestingly, in the present study we did not observe significant connectivity differences between patients and controls related to certain other subcortical structures important for arousal, including thalamus and basal forebrain/nucleus accumbens (data not shown).…”

Can we predict drug response by volumes of the corpus callosum in newly diagnosed focal epilepsy?

“…It was supported by our present findings that the volumes of the corpus callous were significantly correlated with the mean diffusion measures, such as FA and MD. Although decreased global connectivity in focal epilepsy was already demonstrated by previous studies, it was not clear whether decreased global connectivity represents the damaging consequences of recurrent seizures or an adaptive mechanism to prevent seizure spread out of the epileptogenic zones (Englot et al, 2016). It was a plausible assumption from our study because global connectivity was associated with the adaptive mechanism for preventing seizures; patients with good responses to AEDs had high global connectivity.…”

“…Growing evidence has suggested that epilepsy is a network disease, and focal epilepsy, traditionally considered to be a regional brain disorder, also has widespread alterations of networks beyond the epileptogenic zone (Englot, Konrad, & Morgan, 2016). Many of the studies regarding brain connectivity in epilepsy have demonstrated that focal epilepsy is associated with increases in regional connectivity at the epileptogenic zone, paired with diminished global connectivity (Englot et al, 2016;Kim, Piao, Liu, Bingaman, & Diehl, 2008;Liu et al, 2015;Miro et al, 2015;Weber et al, 2007).…”

“…Many of the studies regarding brain connectivity in epilepsy have demonstrated that focal epilepsy is associated with increases in regional connectivity at the epileptogenic zone, paired with diminished global connectivity (Englot et al, 2016;Kim, Piao, Liu, Bingaman, & Diehl, 2008;Liu et al, 2015;Miro et al, 2015;Weber et al, 2007). However, few studies have investigated the response to AEDs according to brain connectivity, although the number of studies examining brain connectivity in epilepsy has grown rapidly in recent years (Hu et al, 2015;Szaflarski, Kay, Gotman, Privitera, & Holland, 2013).…”

Cerebrogenic cardiopathy

“…A by-product is that when abnormal interactions occur as in psychiatric disorders or after stroke or seizures (especially when involving the insula), abnormal cardiac regulatory activity may result. Although there is currently little evidence regarding network reconfiguration in these conditions, in focal epilepsy changes are described in network connectivity patterns (including the insula) [91,92]: interictal spikes affected the connectivity strengths between constituent network members. Similar changes could occur with other forms of aberrant cortical activity (generated by stroke or increased stress perception for example) which might dysregulate cardiac neural regulatory efferent activity resulting in the cardiopathic effects detailed in this review.…”