Ambient air pollution and functional brain network development in adolescence

Abstract

Air pollution is linked to neurodevelopmental delays, but its association with brain network development has yet to be investigated utilizing a longitudinal cohort. We aimed to characterize the relationship between PM2.5, O3, and NO2 exposure at ages 9-10 years and 2-year longitudinal changes in functional connectivity (FC) in regions important for emotional and cognitive functioning, namely the salience, frontoparietal, and default-mode brain networks as well as the amygdala and hippocampus. 7719 participants from the Adolescent Brain Cognitive Development (ABCD) Study® were included. Annual averages of pollutants 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 at baseline and follow-up visits. Single- and multi-pollutant mixed-effect linear models, with subject and study site as random effects, were constructed to examine the putative exposure effect on intra-network, inter-network, and subcortical-to-network FC change, by testing age-by-pollutant interactions and adjusting for sex, race/ethnicity, household income, parental education, handedness, scanner type, and motion during scanning. After Bonferroni correction, single- and multi-pollutant models revealed inter-network FC increased with age for individuals with higher PM2.5 exposure but decreased with age for those with higher NO2 exposure. Similarly, subcortical-to-network FC increased with age for those with higher PM2.5 exposure but decreased with age for individuals with higher O3 exposure. There were no significant intra-network associations with pollutant-by-age interactions. PM2.5 and O3 were negatively correlated (r=-0.18, p<2.2e-16); PM2.5 and NO2 were positively correlated (r=0.20, p<2.2e-16); no correlation existed between O3 and NO2 (r=-0.02, p=0.15). In normative development, inter-network segregation is expected. Our findings indicate that higher levels of exposure to PM2.5 in childhood relate to distinct changes in age-related patterns of network segregation, suggesting functional network immaturity. However, functional network segregation does not seem to be hindered by increased exposure to NO2 and O3.