Network connectivity underlying episodic memory in children: Application of a pediatric brain tumor survivor injury model.

Abstract

Episodic memory involves personal experiences paired with their context. The Medial Temporal, Posterior Medial, Anterior Temporal, and Medial Prefrontal networks have been found to support the hippocampus in episodic memory in adults. However, there lacks a model that captures how the structural and functional connections of these networks interact to support episodic memory processing in children. Using diffusion-weighted imaging, magnetoencephalography, and memory tests, we quantified differences in white matter microstructure, neural communication, and episodic memory performance, respectively, of healthy children (n=23) and children with reduced memory performance. Pediatric brain tumor survivors (PBTS; n=24) were used as a model, as they exhibit reduced episodic memory and perturbations in white matter and neural communication. We observed that PBTS, compared to healthy controls, showed significantly (p<0.05) (1) disrupted white matter microstructure between these episodic memory networks through lower fractional anisotropy and higher mean and axial diffusivity, (2) perturbed theta band (4-7Hz) oscillatory synchronization in these same networks through higher weighted phase lag indices (wPLI), and (3) lower episodic memory performance in the Transverse Patterning and Children's Memory Scale (CMS) tasks. Using partial-least squares path modeling, we found that brain tumor treatment predicted network white matter damage, which predicted inter-network theta hypersynchrony and lower verbal learning (directly) and lower verbal recall (indirectly via theta hypersynchrony). Novel to the literature, our findings suggest that white matter modulates episodic memory through effect on oscillatory synchronization within relevant brain networks. RESEARCH HIGHLIGHTS: Investigates the relationship between structural and functional connectivity of episodic memory networks in healthy children and pediatric brain tumor survivors Pediatric brain tumor survivors demonstrate disrupted episodic memory, white matter microstructure and theta oscillatory synchronization compared to healthy children Findings suggest white matter microstructure modulates episodic memory through effects on oscillatory synchronization within relevant episodic memory networks.