Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, CA, United States.
Center for Cognitive and Brain Sciences, Institute of Collaborative Innovation, University of Macau, Taipa, Macau; Department of Electrical and Computer Engineering, Faculty of Science and Technology, University of Macau, Taipa, Macau.
Neurotoxicology. 2024 Jul;103:206-214. doi: 10.1016/j.neuro.2024.06.011. Epub 2024 Jun 20.
Early life exposure to organophosphate (OP) pesticides is linked with adverse neurodevelopment and brain function in children. However, we have limited knowledge of how these exposures affect functional connectivity, a measure of interaction between brain regions. To address this gap, we examined the association between early life OP pesticide exposure and functional connectivity in adolescents.
We administered functional near-infrared spectroscopy (fNIRS) to 291 young adults with measured prenatal or childhood dialkylphosphates (DAPs) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal study of women recruited during pregnancy and their offspring. We measured DAPs in urinary samples collected from mothers during pregnancy (13 and 26 weeks) and children in early life (ages 6 months, 1, 2, 3, and 5 years). Youth underwent fNIRS while they performed executive function and semantic language tasks during their 18-year-old visit. We used covariate-adjusted regression models to estimate the associations of prenatal and childhood DAPs with functional connectivity between the frontal, temporal, and parietal regions, and a mediation model to examine the role of functional connectivity in the relationship between DAPs and task performance.
We observed null associations of prenatal and childhood DAP concentrations and functional connectivity for the entire sample. However, when we looked for sex differences, we observed an association between childhood DAPs and functional connectivity for the right interior frontal and premotor cortex after correcting for the false discovery rate, among males, but not females. In addition, functional connectivity appeared to mediate an inverse association between DAPs and working memory accuracy among males.
In CHAMACOS, a secondary analysis showed that adolescent males with elevated childhood OP pesticide exposure may have altered brain regional connectivity. This altered neurofunctional pattern in males may partially mediate working memory impairment associated with childhood DAP exposure.
儿童在生命早期接触有机磷（OP）农药会导致神经发育和大脑功能受损。然而，我们对这些暴露如何影响功能连接知之甚少，功能连接是衡量大脑区域之间相互作用的一种方法。为了弥补这一空白，我们研究了生命早期 OP 农药暴露与青少年功能连接之间的关系。
我们对 291 名参加过中心母婴健康评估研究（CHAMACOS）的年轻人进行了功能近红外光谱（fNIRS）检测，这是一项对孕期女性及其后代进行的纵向研究。我们在母亲怀孕期间（第 13 周和第 26 周）和儿童生命早期（6 个月、1 岁、2 岁、3 岁和 5 岁）收集的尿液样本中测量了 DAPs。在 18 岁时，年轻人在执行功能和语义语言任务时接受了 fNIRS 检测。我们使用协变量调整的回归模型来估计产前和儿童时期 DAP 与额叶、颞叶和顶叶区域之间功能连接的关联，并使用中介模型来检验 DAP 与任务表现之间的关系中功能连接的作用。
我们观察到整个样本中产前和儿童时期 DAP 浓度与功能连接之间的关联均为零。然而，当我们寻找性别差异时，我们观察到在男性中，儿童时期 DAP 与右内侧额叶和运动前皮层的功能连接之间存在关联，这与错误发现率校正后一致，但在女性中没有。此外，功能连接似乎介导了 DAP 与男性工作记忆准确性之间的反比关系。
在 CHAMACOS 中，二次分析表明，暴露于高水平儿童期 OP 农药的青少年男性可能存在大脑区域连接改变。男性中这种改变的神经功能模式可能部分介导了与儿童时期 DAP 暴露相关的工作记忆损伤。
