Enriched neighborhood environments relate to episodic memory through prefrontal rather than medial temporal pathways during late childhood and early adolescence.

Background: Enriched environments support neurodevelopment, yet the neural pathways through which neighborhood enrichment relates to episodic memory remain poorly understood. This study examined whether brain function and structure in episodic memory-implicated neurocircuitry mediate the relationship between neighborhood enrichment and episodic memory performance. Methods: We analyzed data from the Adolescent Brain Cognitive Development Study (n = 9,004) at two timepoints (baseline: age 9-11-years and two-year follow-up: 11-13-years-old). Neighborhood enrichment was estimated at the child's primary residential address using Child Opportunity Index 2.0 (COI). Episodic memory was assessed using the Picture Sequence Memory Test. A multimodal neuroimaging approach examined task-based working memory-related functional activity, brain volume, and resting-state intrinsic activity in 13 bilateral regions (26 total), segmented using the Desikan-Killiany atlas, implicated in episodic memory. Associations were first evaluated using FDR-corrected linear mixed-effects models, followed by prospective statistical mediation analyses, controlling for sociodemographic, neuroimaging, and site-related factors. Results: Greater neighborhood enrichment was associated with better episodic memory, greater prefrontal task-related activation, and larger regional brain volumes. However, prospective statistical mediation analyses identified only task-based prefrontal activation as an indirect pathway linking neighborhood enrichment with later episodic memory. After FDR correction across all 26 regions, only left caudal middle frontal activation remained a statistically significant mediator. Conclusion: Our findings identify prefrontal, but not medial temporal, recruitment during working memory as a candidate neural pathway linking neighborhood enrichment with episodic memory in youth. Future work using longitudinal and experimental designs will be important for determining whether enhancing neighborhood opportunity influences these developmental processes.