Effects of ambient fine particulates, nitrogen dioxide, and ozone on maturation of functional brain networks across early adolescence

Abstract

Background: Air pollution is linked to neurodevelopmental delays, but its association with longitudinal changes in brain network development has yet to be investigated. We aimed to characterize the effect of PM_2.5, O₃, and NO₂ exposure at ages 9-10 years on changes in functional connectivity (FC) over a 2-year follow-up period, with a focus on the salience (SN), frontoparietal (FPN), and default-mode (DMN) brain networks as well as the amygdala and hippocampus given their importance in emotional and cognitive functioning.

Methods: A sample of children (N = 9,497; with 1-2 scans each for a total of 13,824 scans; 45.6% with two brain scans) from the Adolescent Brain Cognitive Development (ABCD) Study® were included. Annual averages of pollutant concentrations were assigned to the child's primary residential address using an ensemble-based exposure modeling approach. Resting-state functional MRI was collected on 3T MRI scanners. First, developmental linear mixed-effect models were performed to characterize typical FC development within our sample. Next, single- and multi-pollutant linear mixed-effect models were constructed to examine the association between exposure and intra-network, inter-network, and subcortical-to-network FC change over time, adjusting for sex, race/ethnicity, income, parental education, handedness, scanner type, and motion.

Results: Developmental profiles of FC over the 2-year follow-up included intra-network integration within the DMN and FPN as well as inter-network integration between the SN-FPN; along with intra-network segregation in the SN as well as subcortical-to-network segregation more broadly. Higher PM_2.5 exposure resulted in greater inter-network and subcortical-to-network FC over time. In contrast, higher O₃ concentrations resulted in greater intra-network, but less subcortical-to-network FC over time. Lastly, higher NO₂ exposure led to less inter-network and subcortical-to-network FC over the 2-year follow-up period.

Conclusion: Taken together, PM_2.5, O₃, and NO₂ exposure in childhood relate to distinct changes in patterns of network maturation over time. This is the first study to show outdoor ambient air pollution during childhood is linked to longitudinal changes in brain network connectivity development.

Keywords: Adolescence; Air pollution; Brain development; Functional connectivity; Functional magnetic resonance imaging; Longitudinal; Resting-state.