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bioRxiv · 10.1101/2025.11.13.688261

Multivariate environmental exposures are reflected in whole-brain functional connectivity and cognition in youth

Lichenstein, S. D.·Weng, Y.·Robinson, H.·Rodriguez, L.·Babaeianjelodar, M.·Maynard, J.·Metayer, M.·Suneja, S.·Horien, C.·Greene, A. S.·Constable, R. T.·Moore, T. M.·Barzilay, R.·Yip, S. W.·Keller, A. S.
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Abstract

Each individuals complex, multidimensional environment, known as their "exposome", plays an essential role in shaping cognitive neurodevelopment. Understanding the mechanisms whereby childrens exposome influences their development is crucial to facilitate the design of interventions to foster positive developmental trajectories for all youth. Recent work has identified a general exposome factor associated with socio-economic inequality that is strongly related to cognition and individual differences in the spatial organization of functional brain networks in youth. Building on these findings, the current study explores whether alterations in functional connectivity may represent a potential mechanism linking variation in the exposome to cognitive performance. We apply a data-driven, cross-validated, whole-brain machine learning approach, connectome-based statistical inference, to identify patterns of functional connectivity associated with exposome scores among early adolescents enrolled in the Adolescent Brain Cognitive Development (ABCD) Study using data collected during three cognitive tasks and during rest. Additionally, we investigate whether the identified patterns of functional connectivity relate to individual differences in cognitive performance across three domains: General Cognition, Executive Functioning, and Learning/Memory. Models incorporating 10-fold cross-validation over 100 iterations identified consistent functional connections associated with the exposome across task and rest conditions (model performance: ns = 6,137 - 8,391, rs = 0.34 - 0.44, ps <.001). Results were robust across data collection sites and functional connections common across all significant models were associated with cognitive performance across domains (ps < 0.0009). Collectively, these findings reveal that multidimensional environmental exposures are reflected in patterns of functional connectivity and relate to cognitive functioning among youth. HighlightsO_LIPatterns of functional connectivity reflect multivariate environmental exposures. C_LIO_LIConsistent exposome-related connectivity patterns were observed across brain states. C_LIO_LIThe identified general exposome network was associated with cognitive performance across domains. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/688261v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@b5cc3aorg.highwire.dtl.DTLVardef@172f954org.highwire.dtl.DTLVardef@14f0d01org.highwire.dtl.DTLVardef@deccb5_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Lichenstein, S. D., Weng, Y., Robinson, H., Rodriguez, L., Babaeianjelodar, M., Maynard, J., Metayer, M., Suneja, S., Horien, C., Greene, A. S., Constable, R. T., Moore, T. M., Barzilay, R., Yip, S. W., Keller, A. S.. 2025-11-13. Multivariate environmental exposures are reflected in whole-brain functional connectivity and cognition in youth. https://doi.org/10.1101/2025.11.13.688261

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