Abstracts

Rationale: Activation differences between epilepsy patients (EPI) and typically developing controls (TD) using fMRI have been examined. However, another fMRI parameter, functional connectivity (FC), may provide novel information in terms of comparing network-level differences, as FC takes into account the temporal synchrony of different regions. The majority of studies is in adults using resting-state paradigms looking at degree of FC. We examine laterality of FC (FC-LI) during a language task in children.Methods: We assessed FC-LI during an age-adjusted language task (Auditory Description Decision Task) in right-handed children with left-hemisphere focal epilepsy (LH-EPI) and normal MRI (n=15; mean age=10.1; SD=2.1) compared to TD controls matched on age (n=36; mean age=9.9; SD=1.9). Given the impact of motion of FC calculation, all subjects passed stringent motion criteria. fMRI data underwent standard preprocessing and denoising pipeline using CONN FC toolbox, with additional task conditions and motion problematic volumes (FD>.5mm) regressed out, filtered above .01Hz, and downsampled to 4x4x4mm for computational efficiency. Within gray matter, a data-driven voxelwise FC map was calculated for each subject. For each voxel we counted how many ipsilateral voxels (Intra) and how many contralateral voxels (Inter) are connected to it at connectivity of r>.25. FC-LI was then calculated [(Intra-Inter)/(Intra+Inter)]. We compared FC-LI values between groups and across language performance (Expressive One-Word Vocabulary Test, EOWPVT) using GLM Flex Fast. Results were corrected at p<.005, k>20 (1280mm3) based on Monte Carlo simulation.Results: Across TD and LH-EPI, we found that FC-LI was positively correlated with EOWVT in left precentral gyrus, left posterior ITG, right calcarine, and right superior temporal pole, but negatively correlated in right mesial ITG. For patients, increased FC-LI in left IFG and left SFG were correlated with better EOWPVT (IFG: r=.74, p<.01;SFG: r=.79, p<.01) but not for TD controls (IFG: r=-.11,p>.5;SFG: r=-.29,p>.05). This result is likely not related to location of focus, as only four patients had a frontal lobe focus. LH-EPI (Mean SS=103+15) performed lower than TD controls (Mean SS=116+17) on the EOWPVT (p<.01). After accounting for EOWPVT differences, TD controls had no regions with greater FC-LI than LH-EPI; however, LH-EPI had higher FC-LI in left ITG, left IFG , left MFG, right MFG/SFG, right precuneus, and right angular gyrus.Conclusions: We defined FC-LI as an indication of how connected a region is intra- or inter-hemispherically. Our results suggest that language performance was associated with better intra-connectivity mainly in temporal regions, while group differences were largely found in the left frontal regions. Group differences in FC-LI showed greater intra-connectivity for patients in the left fronto-temporal language network and in right regions likely involved in the executive control of language. This metric accounted for over 50% of the variance in language performance for epilepsy patients and may be a novel marker of cognitive outcomes.