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

点击翻译按钮获取中文摘要

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.