Central auditory processing abnormalities as an indicator of pediatric heavy metal neurotoxicity

项目摘要 手工小规模金矿(ASGM)社区具有极高的重金属/类金属风险 接触汞(汞)、铅(铅)、砷(砷)和锰(锰)，具有潜在的不可逆性 对发育中的中枢神经系统(CNS)的影响。儿童时期接触这些金属可能会导致 终身减少教育和就业机会。及早发现重金属神经毒性 具有挑战性，但初步研究表明，中枢听觉处理(CAP)可能与重音相关 金属暴露并与早期神经认知变化相关。通过我们以前的工作，我们有：1) 开发了一种无线的、可现场部署的外设和中央听力评估系统，适用于 发展中世界，2)在尼加拉瓜建立了研究合作，3)证明了 听觉测试可以用来评估大脑功能。这项研究将确定便携、移动 中枢听觉测试可以识别出具有显著重金属神经毒性的儿童。最低限度的训练 技术人员将利用基于移动平板电脑的创新平台进行听力测试和综合 CAP测试[双数字(DD)、反相噪声和信号测试(N0Spi)、间隙检测阈值(GDT)、 拉丁美洲西班牙语噪声测试(LASHINT)和固定电平频率测试(FLFT)] 生活在尼加拉瓜ASGM社区的大量儿童(6-18岁)(200人)。数据将被上载 到移动数据库平台(RedCap)，以及详细的社会经济和风险因素数据。此外, 将采集脚趾甲和干血斑(DBS)样本，并分析其浓度为5种重金属 使用电感耦合等离子体质谱(ICP-MS)分析金属(铅、汞、砷、锰和铝)。这个 这些金属的浓度将与CAP测试性能通过回归分析和 非参数方差分析(Kruskal-Wallis)将被用来评估儿童与儿童之间的差异 高于参考范围的金属水平与参考范围内的比较。拟议的工作将建立在现有的基础上 研究能力和与尼加拉瓜两个主要合作机构的合作：1)发展 研究能力和提供非常适合偏远贫困环境的仪器，2) 调整和培训数据库(RedCap)设计和实施方面的研究人员，3)提供 通过培训为未来的全面流行病学研究奠定基础，4)指导尼加拉瓜 高级研究设计和方法方面的研究人员，5)在专业领域提供额外的专业知识 感兴趣的领域(例如，中枢听觉处理障碍、重金属神经毒性)，6)促进 MMO和Unan-Leon CISTA之间的研究伙伴关系。该项目将提供以下方面的初步数据 重金属暴露和中枢听觉测试表现，将构成后续拨款的基础 我们的尼加拉瓜同事提交了一份意见书，以解决这一重要的环境健康问题。

Project Abstract Artisanal small-scale gold mining (ASGM) communities are at extremely high risk for heavy metal / metalloid exposure including mercury (Hg), lead (Pb), arsenic (As), and manganese (Mn) with potential irreversible effects on the developing central nervous system (CNS). Exposure to these metals in childhood could lead to a lifelong reduction in educational and job opportunities. Early identification of heavy metal neurotoxicity has been challenging, but preliminary work suggests central auditory processing (CAP) may correlate with heavy metal exposure and correlate with early neurocognitive changes. Through our previous work we have: 1) developed a wireless, field deployable peripheral and central hearing assessment system suitable for the developing world, 2) established research collaborations in Nicaragua and 3) demonstrated that central auditory testing can be used to assess brain function. This study will determine whether portable, mobile central auditory testing can identify children with significant heavy metal neurotoxicity. Minimally trained technicians will utilize an innovative mobile tablet-based platform to perform audiometry and comprehensive CAP tests [Dichotic Digits (DD), antiphase noise and signal testing (N0Spi), Gap Detection Threshold (GDT), Latin American Spanish Hearing in Noise Testing (LASHINT), and Fixed Level Frequency Testing (FLFT)] on a large cohort (200) of children (6 – 18 years) living in a Nicaraguan ASGM communities. Data will be uploaded to a mobile database platform (REDCap) along with detailed socioeconomic and risk factor data. In addition, toenail and dried blood spot (DBS) samples will be collected and analyzed for concentrations of 5 heavy metals (Pb, Hg, As, Mn, and Al) using inductively coupled plasma mass spectrometry (ICP-MS) analysis. The concentrations of these metals will be correlated with CAP test performance using regression analysis and non-parametric ANOVA (Kruskal-Wallis) analysis will be used to assess differences between children with metal levels above compared to those within the reference range. The proposed work will build upon existing research capacities and collaboration with two major collaborating institutions in Nicaragua by: 1) developing research capabilities and providing instruments that are ideally suited to remote impoverished environments, 2) adapting and training research personnel in database (REDCap) design and implementation, 3) providing a foundation for future comprehensive epidemiological studies through training, 4) mentoring Nicaraguan researchers in advanced research design and methodology, 5) providing additional expertise in specialized areas of interest (e.g. central auditory processing disorders, heavy metal neurotoxicity), 6) facilitating the research partnership between MMO and UNAN-Leon CISTA. This project will provide preliminary data on heavy metal exposure and central auditory test performance that would form the basis for a follow-up grant submission from our Nicaraguan colleagues to address this important environmental health issue.