BackgroundTo progress adolescent mental health research beyond our present achievements—a complex account of brain and environmental risk factors without understanding neurobiological embedding in the environment—we need methods to uncover relationships between the developing brain and real-world environmental experiences. MethodsWe investigated associations between brain function, environments, and emotional and behavioral problems using participants from the Adolescent Brain Cognitive Development (ABCD) Study (n = 2401 female). We applied manifold learning, a promising technique for uncovering latent structure from high-dimensional biomedical data such as functional magnetic resonance imaging. Specifically, we developed exogenous PHATE (potential of heat-diffusion for affinity-based trajectory embedding) (E-PHATE) to model brain-environment interactions. We used E-PHATE embeddings of participants’ brain activation during emotional and cognitive processing tasks to predict individual differences in cognition and emotional and behavioral problems both cross-sectionally and longitudinally. ResultsE-PHATE embeddings of participants’ brain activation and environments at baseline showed moderate-to-large associations with total, externalizing, and internalizing problems at baseline, across several subcortical regions and large-scale cortical networks, compared with the zero-to-small effects achieved by voxelwise data or common low-dimensional embedding methods. E-PHATE embeddings of the brain and environment at baseline were also related to emotional and behavioral problems 2 years later. These longitudinal predictions showed a consistent moderate effect in the frontoparietal and attention networks. ConclusionsThe embedding of the adolescent brain in the environment yields enriched insight into emotional and behavioral problems. Using E-PHATE, we demonstrated how the harmonization of cutting-edge computational methods with longstanding developmental theories advances the detection and prediction of adolescent emotional and behavioral problems.
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