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

年轻成人早期接触农业农药和功能性脑成像

基本信息

批准号：
10303593
负责人：
Allan L Reiss
金额：
$ 21.38万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10303593
关键词：
14 year old 19 year old 5 year old Adolescence Affect Age Agriculture Attention Behavioral Biological Markers Birth Brain Brain imaging Brain region California Child Childhood Chlorpyrifos Clinical Research Cognitive Cohort Studies Data Data Reporting Databases Development Disease Environmental Exposure Exposure to Functional Magnetic Resonance Imaging Future Health Impairment Individual Insecticides Investigation Knowledge Life Link Literature Magnetic Resonance Imaging Measures Mexican Americans Mothers Movement Near-Infrared Spectroscopy New York City Organophosphates Parietal Participant Pattern Pesticides Population Pregnancy Problem behavior Reporting Research Salinas Valley Sampling Short-Term Memory Source Structure Technology Testing Thick Work Youth agricultural community agricultural pesticide autistic base cognitive function cognitive task cohort cost critical period developmental disease early childhood early life exposure executive function flexibility health assessment inorganic phosphate language comprehension multidimensional data neurobehavioral test neurodevelopment neuroimaging neuromechanism neuropsychiatric disorder neurotoxic pesticide exposure population based portability prenatal prenatal exposure relating to nervous system research study residence toxic organophosphate insecticide exposure trait urinary young adult

项目摘要

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.

抽象的自 1999 年起，我们的卫生中心就广泛使用有机磷 (OP) 杀虫剂。萨利纳斯母亲和儿童评估 (CHAMACOS) 研究一直在评估以下因素对健康的影响：加利福尼亚州萨利纳斯山谷农业区的约 600 名墨西哥裔美国青年出生队列中使用 OP 农药。我们报告了产前 OP 农药暴露与认知功能和行为较差之间的关联使用神经影像学进行进一步研究对于从幼儿期到青春期的问题非常重要。阐明：1) 大脑的哪些结构和功能受到 OP 的不利影响；2) 与 OP 相关的使用标准神经行为测试的研究可能无法检测到对大脑功能的影响。神经影像学研究报告了与生命早期 OP 农药接触的关联。 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额叶、颞叶和顶叶区域的皮质厚度 (MRI) 在 95 名 CHAMACOS 参与者的子集中，我们发现在怀孕期间居住地靠近 OP 使用。与功能性近红外光谱（fNIRS）观察到的大脑激活模式改变有关这些初步发现值得在更大的样本中得到证实。在这个项目中，我们建议在大脑发育的关键时期进行高质量的暴露评估。研究生命早期接触 OP 农药与神经激活模式和功能的关联整个 CHAMACOS 年轻人群体（18-19 岁）之间的连通性。我们收集了使用功能性近红外光谱 (fNIRS) 的神经影像数据——功能磁共振成像的替代方案，成本不同以及实地研究的便利优势——我们对 CHAMACOS 队列的 458 名参与者进行了研究。当参与者完成以下任务时，评估前额叶、颞叶和顶叶大脑区域的神经活动对于约 300 名 CHAMACOS 参与者，我们评估了认知灵活性、工作记忆和语言理解能力。已经分析了母体产前和早期的磷酸二烷基酯 (DAP)、非特异性 OP 生物标志物我们对所有 458 名参与者的童年（6 个月至 5 岁）尿液样本进行了估计暴露。根据居住地与农用 OP 农药的邻近程度确定单独的 OP 农药及其混合物使用加州独特的农药使用报告 (PUR) 数据库的应用程序。提供补充暴露措施，以便更全面地检查对于这个项目，我们建议在开发的关键时期使用不同来源的OP农药。对这些多维数据进行深入处理并研究早期生活OP的关联使用 fNIRS 检测农药暴露与皮质神经激活和功能连接。研究将是利用功能神经影像评估农药接触影响的最大规模研究，也是第一个应用 fNIRS 技术来定位与环境暴露相关的神经发育损伤。