Altered functional network connectivity and working memory dysfunction in adolescents with epilepsy

Abstract

Adolescents with epilepsy are at risk for deficits in working memory, which could lead to learning difficulties and poor academic outcomes. We used task-based functional magnetic resonance imaging (fMRI) to examine potential disruption in working memory function in adolescents with epilepsy as compared to healthy controls. We recruited 29 adolescents (13-17 years) with non-lesional epilepsy and 20 healthy controls. All participants performed an N-back fMRI task and neuropsychological testing. A general linear model approach was used to create group activation maps of N-back fMRI for epilepsy and control groups and both groups combined (p < 0.05 corrected for multiple comparisons). Functionally defined regions of interest (ROIs) were identified based on clusters of combined group activation (z > 5). Subsets of these functional ROIs corresponding to cingulo-opercular and fronto-parietal networks were selected and differences in functional connectivity between the epilepsy and control groups were assessed. Adolescents with epilepsy had significantly poorer working memory scores compared to controls. For the N-back fMRI task, there were no significant differences in group activation. Functional connectivity was significantly reduced between the left frontal operculum and anterior cingulate gyrus (cingulo-opercular network) in adolescents with epilepsy compared to controls. This study demonstrates working memory deficits and an altered pattern of connectivity in brain networks supporting working memory in adolescents with epilepsy. Working memory performance was worse in adolescents with epilepsy; though scores were not directly correlated with reduced connectivity. These results suggest the neural substrates of working memory in adolescents with epilepsy may differ from those in typically-developing adolescents, and require further investigation to understand the reasons for poorer working memory performance.

Keywords: Adolescents with epilepsy; Cingulo-Opercular network; Functional connectivity; N-back task; Working memory.