White Matter Network Abnormalities Are Associated with Cognitive Decline in Chronic Epilepsy

Abstract

Patients with chronic epilepsy frequently display cognitive comorbidity and might have widespread network abnormalities outside the epileptic zone, which might affect a variety of cognitive functions and global intelligence. We aimed to study the role of white matter connectivity in cognitive comorbidity. Thirty-nine patients with nonsymptomatic localization-related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls were included. Whole brain white matter networks were constructed from fiber tractography. Weighted graph theoretical analysis was performed to study white matter network abnormalities associated with epilepsy and cognition. Patients with severe cognitive impairment showed lower clustering (a measure of brain network segregation) and higher path length (a measure of brain network integration) compared with the healthy controls and patients with little or no cognitive impairment, whereas whole brain white matter volume did not differ. Correlation analyses revealed that IQ and cognitive impairment were strongly associated with clustering and path lengths. This study revealed impaired white matter connectivity, associated with cognitive comorbidity in patients with chronic epilepsy. As whole brain white matter volumes were preserved in the patient group, our results suggest an important role for the network topology rather than volumetric changes, in epilepsy with cognitive decline.

Experimental focal neocortical epilepsy is associated with reduced white matter volume growth: results from multiparametric MRI analysis

“…Focal epilepsy is increasingly being recognized as both a gray and white matter disease (Otte et al 2012b;Gross 2011;Salmenpera and Duncan 2005;McMillan et al 2004;Seidenberg et al 2005;Vaessen et al 2011). Nevertheless, how and to what extent focal epilepsy affects the global brain white matter is largely unknown.…”

“…Others studies have provided evidence that focal epilepsy is a large brain network disease [for review see (Stam and van Straaten 2012)]. Interestingly, a recent study that applied structural whole brain network analysis to individuals with chronic TLE revealed impaired white matter networks, while white matter volume was preserved (Vaessen et al 2011). Evidently, more research is needed to elucidate how focal epilepsy affects white matter in general and its volume in particular.…”

Disrupted Global and Regional Structural Networks and Subnetworks in Children with Localization-Related Epilepsy

“…29,30 The WM tracts connecting the frontal lobe to the temporal and occipital lobes have demonstrated smaller volumes in children with FLE compared with controls, 34 indicating impaired structural connections between the frontal and temporal and occipital lobes. Vaessen et al 4 found that the clustering coefficient was significantly positively correlated with IQ, and path length was negatively correlated with IQ in adults with cryptogenic localizationrelated epilepsy. In that study, 4 the patients had a broader range of IQ scores including those who are nonimpaired (mean IQ of 97) and those who are impaired (mean IQ of 85).…”

“…Vaessen et al 4 found that the clustering coefficient was significantly positively correlated with IQ, and path length was negatively correlated with IQ in adults with cryptogenic localizationrelated epilepsy. In that study, 4 the patients had a broader range of IQ scores including those who are nonimpaired (mean IQ of 97) and those who are impaired (mean IQ of 85). In a subsequent study, 10 the same authors did not find an association between the clustering coefficient and path length measures of structural or functional connectivity with a computerized visual searching task in children with FLE.…”

“…4,12 The FMRIB Automated Segmentation Tool (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/fast) 13 was used to segment the individual skull-stripped structural T1 images into gray and white matter. The deep gray matter was manually removed from the whole-brain boundary mask.…”