Prefrontal working memory activity partially mediates link between enriched neighborhood environments and episodic memory among 9-13-year-olds

Abstract Background Enriched environments support neurodevelopment. The pathways linking enrichment to cognitive processes such as episodic memory among youth remain unclear. 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 = 9,028) at two timepoints (baseline: 9-11-years-old and two-year follow-up: 11-13-years-old). Neighborhood enrichment was estimated at the child’s primary residential address proxied by the Child Opportunity Index 2.0 (COI). Episodic memory was assessed using the Picture Sequence Memory Test (PSMT). A multimodal neuroimaging approach examined task-based working memory-related functional activity, brain volume, and resting-state intrinsic activity in 26 bilateral brain regions, segmented using the Desikan-Killiany atlas, implicated in episodic memory. Following FDR- corrected linear mixed effects models, controlling for sociodemographic, neuroimaging factors, and site-related variability, two sets of mediation analyses were conducted per time point. Results Greater neighborhood enrichment (i.e., higher COI scores) was directly associated with better episodic memory, prefrontal cortex (PFC) task-based functional activity, and larger PFC and medial temporal lobe volume across timepoints. PFC task-based functional activity, but not brain volume or intrinsic activity, partially mediated these relationships. Specifically, PFC task-activity in the left and right caudal and rostral middle frontal gyri, and left pars opercularis, accounted for ∼2-7% of the mediated effect. Conclusion Our findings contribute to a rapidly growing body of literature linking environmental influences on neurocognitive outcomes during development. Given childhood and adolescence represent sensitive periods for neurodevelopment, interventions aimed at increasing neighborhood access to enriching experiences such as educational opportunities, cognitively stimulating activities, and social support may have lasting benefits for neurocognitive development.