Abstracts

Rationale: Executive functioning (EF) encompasses a constellation of higher-level cognitive skills that underlie an individual’s ability to engage in goal-directed behaviors and perform complex tasks over time, including planning, organizing, self-regulation, and working memory. EF deficits are common in youth with epilepsy and are consistently associated with long-term negative outcomes across domains of psychosocial function. Existing research on the neural basis of EF disruptions in pediatric epilepsy is limited. The question of whether differences in the functional connectivity of EF networks are a significant mechanistic driver of EF disruptions observed in children with epilepsy remains unanswered. Methods: A total of 49 adolescents between the ages of 13-17 years participated in the current study. Twenty-nine adolescents had confirmed epilepsy, were on antiepileptic drugs, and had at least one seizure within the last year (M age=15.41, 7 females, n=17 generalized epilepsy, n=6 localization-related and n=6 unclassified). The control group included 20 healthy adolescents (M age=15.35, 8 females) without a history of neurological or psychiatric disease, chronic illness, and not currently taking any prescribed psychoactive medications. Groups did not differ in age, race, body mass index or socioeconomic status.  A 10-min resting state fMRI scan was obtained for all participants (TR/TE =2000/35ms, voxel size 3.75x3.75x5mm), as well as a high-resolution T1 structural image.fMRI Preprocessing: Slice timing correction, motion correction, coregistration and spatial smoothing were implemented in FSL (https://fsl.fmrib.ox.ac.uk/fsl/).  Denoising was done using a CompCor approach with 5 white matter and 5 cerebrospinal fluid principal components, outlier timepoints and motion parameters regressed out of the data.Regions of Interest (ROIs): 12 ROIs identified as being involved in working memory were selected using NeuroSynth (http://neurosynth.org), an online database that uses a meta-analytic approach to synthesize existing neuroimaging literature and generate corresponding statistical maps of common areas of activation.fMRI Connectivity Analysis: NeuroSynth-derived ROIs were used as nodes that comprise the EF network evaluated in the present study (i.e., working memory). Group differences in ROI-to-ROI resting state functional connectivity were examined between adolescents with epilepsy and healthy controls. Functional connectivity was computed as the temporal correlation of fMRI signal fluctuations between any two regions (connectivity index). The epilepsy and control groups were compared using a general linear model approach where connectivity index in each pair of ROIs was modeled as a function of group. Results: Statistical analyses revealed that adolescents in the epilepsy group demonstrated significantly reduced functional connectivity between several pairs of nodes in the working memory network compared to healthy controls (p < .05, FDR corrected, see Figure). Conclusions: The current study provides preliminary evidence of decreased resting state functional connectivity in EF networks among adolescents with epilepsy compared to healthy controls. These findings suggest that the presence of abnormal functional neural networks may underlie the EF disruptions that frequently characterize the neurocognitive profile of youth with epilepsy. Future research is needed to evaluate the prognostic utility of these findings and how they may be used to guide intervention efforts targeting neurocognitive vulnerabilities associated with poor clinical outcomes in this patient population. Funding: Cincinnati Children's Hospital Research and Innovation Pilot Funding