Impaired and facilitated functional networks in temporal lobe epilepsy

Abstract

How epilepsy affects brain functional networks remains poorly understood. Here we investigated resting state functional connectivity of the temporal region in temporal lobe epilepsy. Thirty-two patients with unilateral temporal lobe epilepsy underwent resting state blood-oxygenation level dependent functional magnetic resonance imaging. We defined regions of interest a priori focusing on structures involved, either structurally or metabolically, in temporal lobe epilepsy. These structures were identified in each patient based on their individual anatomy. Our principal findings are decreased local and inter-hemispheric functional connectivity and increased intra-hemispheric functional connectivity ipsilateral to the seizure focus compared to normal controls. Specifically, several regions in the affected temporal lobe showed increased functional coupling with the ipsilateral insula and immediately neighboring subcortical regions. Additionally there was significantly decreased functional connectivity between regions in the affected temporal lobe and their contralateral homologous counterparts. Intriguingly, decreased local and inter-hemispheric connectivity was not limited or even maximal for the hippocampus or medial temporal region, which is the typical seizure onset region. Rather it also involved several regions in temporal neo-cortex, while also retaining specificity, with neighboring regions such as the amygdala remaining unaffected. These findings support a view of temporal lobe epilepsy as a disease of a complex functional network, with alterations that extend well beyond the seizure onset area, and the specificity of the observed connectivity changes suggests the possibility of a functional imaging biomarker for temporal lobe epilepsy.

Seizure Frequency Can Alter Brain Connectivity: Evidence from Resting-State fMRI

“…We found that patients in the frequent-seizure group had increased connections within the temporal lobes bilaterally involving the seizure-prone medial temporal structure and bilateral primary auditory cortex, and those in the infrequent-seizure group had increased connections of the DMN. Observations of increased connectivity with other types of epilepsy, such as in the medial temporal lobes with mesial temporal sclerosis, 8,10 the lateral orbitofrontal lobes with absence seizures, 37 and frontal lobes with idiopathic generalized epilepsy, 38,39 make us surmise that increased connections are probably more specific to understand epileptogenesis. Previous studies also pointed to a temporal lobe origin in 67%-100% of patients with HWE.…”

“…Similarly, hemispheric connectivity analysis in patients with unilateral mesial temporal sclerosis revealed decreased local and intrahemispheric connectivity and increased interhemispheric connectivity. 10 In contradistinction to the aforementioned results, there have been reports on increased hippocampal connectivity that was presumed to be a compensatory mechanism because it linearly correlated with a disease duration of Ͼ10 years. [1][2][3][4]6 Graph-theory analysis of resting-state fMRI data from patients with epilepsy also revealed decreased functional nodal topologic properties of the DMN that were positively correlated with disease duration.…”

“…8,[11][12][13][14] Regional homogeneity analysis of resting-state fMRI data was even used as a presurgical tool for seizure identification in patients with MR-negative focal epilepsy. 15 Thus, various models of data analysis have helped in understanding epilepsy further, and now there is increasing interest in using these models to reclassify epilepsy as a focal epileptogenic area 10,15 or as a network of seizure-generating areas. [16][17][18] Gower's clinical observation that "seizures beget seizures" in 1881 triggered several studies, especially animal models that addressed the genesis of epilepsy.…”

Influence of Resting-State Network on Lateralization of Functional Connectivity in Mesial Temporal Lobe Epilepsy

“…2 However, investigations involving large-scale network analysis have challenged this traditional conceptualization. 3,[5][6][7] Furthermore, several studies have reported an mTLE-related decrease in basal RS-FC in the epileptogenic hemisphere in brains of patients with mTLE, accompanied by contralateral compensatory mechanisms. 8,9 Many mTLE studies have focused on the epileptogenic zone, and most analyses that have investigated regions outside the hippocampus have focused on structural imaging technology.…”

“…1,10,11 In contrast, few whole-brain functional network analyses of mTLE have been conducted. Structural MRI or electroencephalography or both incompletely measure temporal changes during the disease process, 5 while resting-state fMRI takes serial images during a time period that can capture the dynamic and evolving changes related to epilepsy. 12 The RS-FC derived from the fMRI images reflects functional aberrations and offers a network perspective on the psychiatric and cognitive complications of mTLE.…”