The neural basis of executive functioning deficits in adolescents with epilepsy: a resting-state fMRI connectivity study of working memory.

Working memory deficits are common in youth with epilepsy and consistently associated with long-term negative outcomes. Existing research on the neural basis of working memory disruptions in pediatric epilepsy is limited. The question of whether differences in the functional connectivity of neural networks underlie working memory disruptions in pediatric patients with epilepsy remains unanswered. A total of 49 adolescents between the ages of 13-17 years participated in this study. Twenty-nine adolescents had confirmed epilepsy (n = 17 generalized epilepsy, n = 6 localization-related, n = 6 unclassified). The control group included 20 healthy adolescents. A total of 10-min resting state functional magnetic resonance imaging was obtained for all participants. NeuroSynth-derived regions of interest were used as nodes that comprise working memory neural networks. Group differences in resting state functional connectivity were examined between adolescents with epilepsy and controls. Functional connectivity was computed as the temporal correlation of functional magnetic resonance imaging signal fluctuations between any two regions of interest. Compared to controls, adolescents in the epilepsy group demonstrated both hypoconnectivity and hyperconnectivity in cortical areas that map onto fronto-parietal and cingulo-opercular networks, as well as cerebellar regions. Functional connectivity between pairs of regions of interest was also significantly associated with behavioral measures of working memory across epilepsy and control groups. This study demonstrates that the presence of abnormal patterns in resting state neural network connectivity may underlie the working memory disruptions that frequently characterize the neurocognitive profile of youth with epilepsy.