fNIRS as an outcome measure of the prefrontal hemodynamic response in Down syndrome

项目概要/摘要： 唐氏综合征（DS）是智力残疾最常见的遗传原因，与 许多医学合并症，包括高睡眠障碍率。正如NIH研究所强调的那样， 根据《唐氏综合症防治计划》和《纳入项目研究计划》，迫切需要加强 领域的了解，这些常见的健康状况，以改善个人的生活质量， DS和普通人群中受影响的患者。一个重要的研究目标，必须满足，以确保 临床试验研究的成功是可靠的、患者友好的结果测量和生物标志物的验证 以评估不同治疗方法的疗效。DS和睡眠障碍都与 非典型额叶结构和功能以及前额叶介导的执行功能受损 功能任务。目前，该领域缺乏有效的儿童前额叶功能的结果措施， DS样品因此，拟议的研究旨在促进DS和睡眠的临床试验研究， 评估使用功能性近红外光谱（fNIRS）结合 发展适当的执行功能测试组合作为前额叶的结果测量 血流动力学反应。拟议的研究旨在评估这一工具是否对以下因素的影响敏感： 这两个DS和睡眠障碍，并可以测量在年幼的儿童与DS。如果获得资助，拟议的研究 将（1）测试使用fNIRS与DS儿童（年龄6-11岁，n=30）的年轻样本的可行性， 典型的发展中对照组与实足年龄（TDCA [n=20; 6-11岁]）或心理年龄（TDMA）相匹配 [n=20; 3-5年]），通过量化成功完成fNIRS数据收集的参与者数量 并检查特征（例如，行为问题，年龄较小）与任务完成成功相关; (2)评价fNIRS是否可以检测DS中前额叶血流动力学反应相对于 时间和心理年龄的期望，并评估其敏感性的影响，睡眠对前额叶 血流动力学反应;（3）评估基于fNIRS的前额叶血流动力学反应的临床效用， DS通过检查基于任务的前额叶神经效率和现实世界功能之间的关系（即， 适应性和适应不良行为）。拟议的研究代表了关键的下一步， 临床试验研究DS和睡眠问题。如果没有有效的关键成果衡量标准， 这些障碍，如前额叶功能，该领域将无法充分评估不同的疗效 旨在改善这些群体生活质量的治疗。

Project Summary/Abstract: Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with numerous medical comorbidities, including high rates of sleep disturbance. As highlighted in the NIH Research Plan on Down Syndrome and the INCLUDE Project Research Plan, there is an urgent need to augment the field's understanding of these commonly occurring health conditions to improve quality of life for individuals with DS and those affected in the general population. An important research objective that must be met to ensure the success of clinical trials research is the validation of reliable, patient-friendly outcome measures and biomarkers to evaluate the efficacy of different treatment approaches. Both DS and sleep disturbances are associated with atypical frontal lobe structure and function as well as impaired performance on prefrontally-mediated executive function tasks. Currently, the field is lacking in valid outcome measures of prefrontal functioning for pediatric samples with DS. Thus, the proposed research aims to facilitate clinical trials research for both DS and sleep by evaluating the clinical utility of using functional near infrared spectroscopy (fNIRS) in conjunction with a developmentally appropriate executive function test battery as an outcome measure of the prefrontal hemodynamic response. The proposed study seeks to evaluate whether this tool is sensitive to the effects of both DS and sleep disturbance and can be measured in young children with DS. If funded, the proposed research will (1) test the feasibility of using fNIRS with a young sample of children with DS (ages 6-11 years, n=30) and typically developing controls matched on chronological age (TDCA [n=20; 6-11 years]) or mental age (TDMA [n=20; 3-5 years]) by quantifying the number of participants who successfully complete fNIRS data collection and examining characteristics (e.g., behavior problems, younger age) associated with task completion success; (2) evaluate whether fNIRS can detect differences in the prefrontal hemodynamic response in DS relative to chronological and mental age expectations and asses its sensitivity to the effects of sleep on the prefrontal hemodynamic response; (3) assess the clinical utility of the fNIRS-based prefrontal hemodynamic response in DS by examining relations between task-based prefrontal neural efficiency and real-world functioning (i.e., adaptive and maladaptive behavior) in this group. The proposed research represents a critical next step in clinical trials research for both DS and sleep problems. Without valid measures of key outcomes of interest for these disorders, such as prefrontal functioning, the field will be unable to fully evaluate the efficacy of different treatments that aim to improve quality life in these groups.