Abstracts

Rationale: Focal epilepsy is associated with significant morbidity and cognitive impairment. A recent high density EEG study suggested the presence of local connectivity increases in focal epileptic patients compared to controls (Boly et al., Brain 2017). As focal seizures propagate in a nearest-neighbor fashion intracranially, increases in cortico-cortical connectivity may be more pronounced for short distance ranges. We aimed to determine if increases in short-range functional MRI (fMRI) connectivity could differentiate the epileptic network from the rest of the brain in patients with temporal lobe epilepsy (TLE). We also assessed the correlation between abnormal increases in fMRI connectivity, seizure frequency and cognitive impairment. Methods: Data from 35 TLE patients and 31 controls (age range 20- 57) from the Epilepsy Connectome Project (ECP) were analyzed. High resolution anatomical and resting state fMRI data were obtained using 3T MRI Human Connectome Project (HCP) sequences and were preprocessed using the HCP pipeline. For each subject, vertex-wise matrices of correlation between each voxel and its neighbors at predefined short (0-5 mm) and long (150-200 mm) distances were computed. Spatially Z-scored topographies of short and long distance connectivity were compared between TLE patients and controls. In the TLE group, short and long distance connectivity topographies were then correlated with seizure frequency. Finally, average connectivity strength (from 0 to 200 mm) was correlated with IQ, verbal memory (Rey-AVLT) and motor (Grooved Pegboard) performance in both TLE patients and controls, and topographies were compared between the two groups. All analyses used non-parametric statistics and were thresholded at p<0.05 corrected for multiple comparisons using Threshold Free Cluster Enhancement (TFCE) in the HCP workbench. Results: Compared to controls, TLE patients showed increased short-range connectivity in bilateral limbic networks and increased long range connectivity in bilateral motor networks (non-parametric TFCE corrected p<0.05, Figure 1). In the TLE group, seizure frequency was also correlated with increased short-range connectivity in bilateral limbic networks and with increased long range connectivity in bilateral motor networks (non-parametric TFCE corrected p<0.05,Figure 2 A). While in controls, average connectivity strength in limbic networks was positively correlated with both IQ and memory scores, it was paradoxically negatively correlated with IQ and memory scores in the TLE group (non-parametric TFCE corrected p<0.05, Figures 2 B and C). While in controls, motor performance positively correlated with average connectivity strength in bilateral motor cortices, it was positively correlated with connectivity in extra-motor areas in patients with TLE (non-parametric TFCE corrected p<0.05, Figure 2 D). Conclusions: Compared to controls, TLE patients displayed increased short-range connectivity in the epileptic (limbic) network and increased long range connectivity in motor networks. Connectivity changes correlated with both seizure frequency and cognitive impairment in TLE patients. These findings suggest that increased short-range connectivity may help localize focal epileptic networks. The correlations between increased connectivity and both seizure frequency and cognitive impairment in TLE patients also suggest that seizures may induce maladaptive changes. Future studies should correlate short-range fMRI connectivity with surgical outcomes to validate this approach clinically. Funding: NIH ECP