Abstracts

Rationale:
Resting-state functional connectivity offers a non-invasive way to study brain development in typically developing (TD) children and children with neurological conditions, such as focal epilepsy. Studying the continuous functional topography (gradient) of the hippocampus aids in understanding the region’s functional connections to the cortex. Despite its utility for guiding temporal lobe resection and post-surgical outcomes, hippocampal gradients have not been studied in pediatric patients with focal epilepsy.
Methods:
We used the Human Connectome Project-Development dataset with 598 TD participants (age=14.7 ± 3.9yo) and 26 pediatric patients with focal epilepsy (age=15.0 ± 4.2yo) collected at the Children’s National Hospital. Resting-state data underwent standard preprocessing using fMRIprep. Using connectopic mapping (Haak et al.,2018), we conducted functional gradient analysis by applying Laplacian Eigenmap for left and right hippocampus. After aligning individuals’ gradients to their group average, we computed the projection maps of the aligned gradients to measure connectivity between hippocampal gradients and the rest of the brain. We then used a whole-brain surface atlas (Ji et al., 2019) to parcellate projection maps to predict episodic memory in TDs. The final cross-validated model was validated on patients with epilepsy.

Results:
For both TD and epilepsy patients, an anterior-posterior hippocampal gradient was observed similar to findings in TD adults (Przeździk et al., 2019; Figure 1a and c) and the gradients were highly consistent across groups (ICC_LH=0.77, ICC_RH=0.80). The projection map in TD children showed a gradual change in connectivity from anterior to posterior hippocampus (Figure 1b), with anterior mapping onto regions associated with higher-order conceptual representations (mesial temporal lobe, angular gyrus), cognitive control (medial prefrontal cortex) and language processing (inferior frontal gyrus), and posterior hippocampus mapped onto those subserving visual and spatial processing (visual cortex, superior parietal lobule) and executive functioning. The projection maps of patients with focal epilepsy were disrupted, especially for regions coupled with anterior hippocampus (Figure 1d). We successfully predicted out-of-sample episodic memory scores using the left hippocampal projection map in TDs (p < 0.001, Fig. 2a), which was validated in patients. The most memory-predictive regions were distributed across the brain, concentrating on the default mode network and were also more left lateralized (Figure 2c).