Abstract
In childhood frontal lobe epilepsy (FLE), cognitive impairment and educational underachievement are serious, well-known co-morbidities. The broad scale of affected cognitive domains suggests wide-spread network disturbances that not only involves, but also extends beyond the frontal lobe. In this study we have investigated whole brain connectional properties of children with FLE in relation to their cognitive impairment and compared them with healthy controls. Functional connectivity (FC) of the networks was derived from dynamic fluctuations of resting state fMRI and structural connectivity (SC) was obtained from fiber tractograms of diffusion weighted MRI. The whole brain network was characterized with graph theoretical metrics and decomposed into modules. Subsequently, the graph metrics and the connectivity within and between modules were related to cognitive performance. Functional network disturbances in FLE were related to increased clustering, increased path length, and stronger modularity compared to healthy controls, which was accompanied by stronger within- and weaker between-module functional connectivity. Although structural path length and clustering appeared normal in children with FLE, structural modularity increased with stronger cognitive impairment. It is concluded that decreased coupling between large-scale functional network modules is a hallmark for impaired cognition in childhood FLE.
Highlights
Frontal lobe epilepsy (FLE) is considered to be, after temporal lobe epilepsy, the second most common type of the localizationrelated epilepsies of childhood and accounts for 20–30% of partial epilepsies [1]
Mean Functional connectivity (FC) was not significantly correlated with age or with computerized visual searching task (CVST) scores
Mean structural connectivity was not correlated with CVST score or age
Summary
Frontal lobe epilepsy (FLE) is considered to be, after temporal lobe epilepsy, the second most common type of the localizationrelated (partial) epilepsies of childhood and accounts for 20–30% of partial epilepsies [1]. Pediatric FLE, even when cryptogenic in nature, is frequently complicated by the impairment of a broad range of cognitive problems, behavioral disturbances, and therapy resistance [2]. In childhood the brain is at its most vulnerable state and neurologic disturbances such as FLE can have an impact on brain maturation and the development of cognitive skills, with potentially severe consequences for school performance [3]. The broad range of affected cognitive domains suggests a global network disturbance, rather than perturbations of localized individual processes. Cerebral connectivity may either be of functional or structural nature. Functional connectivity (FC) can be measured by correlating blood-oxygen-dependent oxygenation (BOLD) related dynamic fluctuations of gray matter activity between different brain regions [5] and structural connectivity (SC) can be obtained by tracing fiber bundles through the white matter with fiber tractography [6]
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