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

摘要 有机磷农药是一种广泛使用的杀虫剂。自1999年以来，我们的健康中心 萨利纳斯母亲和儿童评估研究一直在评估 在加州农业区萨利纳斯山谷出生的约600名墨西哥裔美国青年中，OP农药的含量。 我们已经报道了产前OP农药暴露与认知功能和行为能力较差的相关性。 从幼儿期到青春期的问题。使用神经影像学的进一步研究对于 阐明：1）大脑中的哪些结构和功能受到OP的不利影响; 2）OP相关 对大脑功能的影响可能在使用标准神经行为测试的研究中未被发现。只有两 神经影像学研究报告与早期OP农药暴露有关。第一组包括一群 40名纽约市儿童，发现产前接触OP毒死蜱与减少 结构磁共振成像显示的额叶、颞叶和顶叶皮质厚度 （MRI）。在一个由95名CHAMACOS参与者组成的子集中，我们发现，在怀孕期间， 与功能性近红外光谱（fNIRS）观察到的脑激活模式改变有关 执行功能的任务。这些初步调查结果需要在更大的样本中得到证实， 在大脑发育的关键窗口期间进行高质量的暴露评估。在这个项目中，我们建议 研究生命早期暴露于OP农药对神经激活模式和功能的影响 在整个CHAMACOS年轻人（18-19岁）队列中的连接。我们收集了 使用功能性近红外光谱（fNIRS）的神经成像数据-一种具有不同成本的功能性MRI的替代方法 和方便的优势，以实地为基础的研究-在458名参与者的CHAMACOS队列。我们 当参与者完成以下任务时，评估了前额叶、颞叶和顶叶大脑区域的神经活动： 认知灵活性、工作记忆和语言理解。对于约300名CHAMACOS参与者，我们 已经分析了产妇产前和早期的磷酸二烷基酯（DAP），非特异性OP生物标志物 儿童（6个月- 5岁）尿液样本。对于所有458名参与者，我们估计了 根据居民区与农业有机磷农药的接近程度确定的有机磷农药及其混合物 使用加州独特的农药使用报告（PUR）数据库。尿DAP和PUR数据 提供补充的暴露措施，以便更全面地审查 关键发展时期不同来源的有机磷农药。在这个项目中，我们建议 对这些多维数据进行深入处理，并调查早期生活OP的相关性， 农药暴露与皮质神经激活和功能连接使用fNIRS。我们提出的 这项研究将是使用功能性神经成像评估农药暴露影响的最大规模研究， 应用fNIRS技术定位与环境暴露相关的神经发育损伤。

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.