Early life exposure to agricultural pesticides and functional brain imaging in young adults

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ABSTRACT Organophosphate (OP) pesticides are widely used insecticides. Since 1999, our Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study has been assessing the health effects of OP pesticides among a birth cohort of ~600 Mexican American youth in California’s agricultural Salinas Valley. We have reported associations of prenatal OP pesticide exposure with poorer cognitive function and behavioral problems from early childhood through adolescence. Further investigation using neuroimaging is important for elucidating: 1) which structures and functions in the brain are adversely affected by OPs; and, 2) OP-related impacts on brain function that may be undetected in studies using standard neurobehavioral tests. Only two neuroimaging studies report associations with of early life OP pesticide exposure. The first includes a cohort of 40 New York City children, which found associations of prenatal exposure to the OP chlorpyrifos with reduced cortical thickness of frontal, temporal, and parietal regions shown by structural magnetic resonance imaging (MRI). In a subset of 95 CHAMACOS participants we found that residential proximity to OP use during pregnancy was associated with altered brain activation patterns observed with functional near infrared spectroscopy (fNIRS) during tasks of executive function. These preliminary findings warrant corroboration among a larger sample with high quality exposure assessment during critical windows of brain development. In this project, we propose to investigate associations of early life exposure to OP pesticides on neural activation patterns and functional connectivity among the entire CHAMACOS cohort of young adults (18-19 years old).We have collected neuroimaging data using functional near-infrared spectroscopy (fNIRS) – an alternative to fMRI with distinct cost and convenience advantages for field-based research – in 458 participants of the CHAMACOS cohort. We assessed neural activity in the prefrontal, temporal and parietal brain regions as participants complete tasks of cognitive flexibility, working memory, and language comprehension. For ~300 CHAMACOS participants, we have already analyzed dialkyl phosphates (DAPs), non-specific OP biomarkers, in maternal prenatal and early childhood (6 months – 5 years) urinary samples. For all 458 participants, we have estimated exposure to individual OP pesticides and their mixtures based on residential proximity to agricultural OP pesticide applications using California’s unique Pesticide Use Reporting (PUR) database. Urinary DAPs and PUR data provide complementary exposure measures, allowing for a more comprehensive examination of the effects of OP pesticides from different sources during critical periods of development. For this project, we propose to conduct the intensive processing of these multi-dimensional data and investigate associations of early life OP pesticides exposure with cortical neural activation and functional connectivity using fNIRS. Our proposed research will be the largest to assess impacts of pesticide exposure using functional neuroimaging, and the first to apply fNIRS technology to localize impairments in neurodevelopment related to an environmental exposure.