Abstracts

Rationale: Resting-state functional connectivity is a valuable tool for examining the integrity of hippocampal circuitry in epilepsy. Previous studies have revealed asymmetrical hippocampal functional connectivity in temporal lobe epilepsy patients. Recently, a novel method named connectopic mapping allows researchers to examine continuous functional connectivity changes (gradients) within the hippocampus usually focusing on the primary gradient along the hippocampal anterior-posterior axis (Przeździk et al., 2019). However, there is a lack of research on examining hippocampal gradients in pediatric epilepsy patients and whether those gradients show any asymmetrical patterns.

Methods: Leveraging our multi-center pediatric epilepsy consortium, we examined functional connectivity of 60 pediatric focal epilepsy (FE) patients (13.1±4.9yo, 31F). In addition, we also collected 18 age- and gender-matched controls (12.3±3.5yo, 8F). The 3T resting-state data underwent standard preprocessing using fMRIprep and then projected to fsLR32k CIFTI surface space. We employed hippunfold to conduct automated hippocampal unfolding for better inter-subject alignment (DeKraker et al., 2022). Following harmonization, we performed connectopic mapping analysis to extract hippocampal gradients using diffusion map embedding on hippocampal-cortical connectivity profiles of left and right hippocampus, respectively. These gradients reflect the principal dimensions of variation of the hippocampal-cortical connectivity space. Gradient symmetry was measured by correlating the left and right hippocampal gradients for each individual.


Results: We observed a primary gradient along the anterior-posterior axis explaining 48% of variance of hippocampal-cortical connectivity and a second hippocampal gradient along the medial-lateral axis explaining 10.6% of variance (Fig. 1). The first two gradients were highly consistent across groups (intraclass correlation coefficient, ICC > 0.95), consistent with our previous findings. Consistency was lower for the third gradient (ICC = 0.79) explaining 7.9% of variance, which did not follow as clear a pattern the first two gradients. Furthermore, using a linear mixed-effects model, we found that the second gradient was more asymmetrical in FE patients than in TDs (p = 0.04, FDR corrected, Fig. 2), after controlling for hippocampal volume, age, and gender. No significant results were found for the first and third gradients.


Conclusions: Using connectopic mapping, we revealed similar group-level hippocampal gradients in pediatric epilepsy patients and TDs. However, at the individual level, we found the second gradient was significantly more asymmetrical for pediatric epilepsy patients. Focal epilepsy may disrupt the hippocampal-cortical connectivity pattern along the medial-lateral axis, and the medial-lateral gradient has been shown to be correlated with proxies of myelination (Vos de Wael et al., 2018). Future studies should examine whether the degree of disruption is related to the seizure focus and age at seizure onset.


Funding: K23 NS093152; P50 HD105328; American Epilepsy Society Infrastructure Grant