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

项目摘要/摘要： 唐氏综合症(DS)是导致智力残疾的最常见的遗传原因，与 许多医学合并症，包括高比例的睡眠障碍。正如NIH研究中强调的那样 唐氏综合症研究计划和纳入项目研究计划，迫切需要增加 菲尔德对这些常见健康状况的了解，以提高患有以下疾病的个人的生活质量 DS和普通人群中受影响的人。必须达到的一个重要研究目标，以确保 临床试验研究的成功是对可靠的、患者友好的结果测量和生物标记物的验证 评价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能力受损 功能任务。目前，该领域缺乏对儿童前额叶功能的有效结果测量。 带有DS的样本。因此，拟议的研究旨在通过以下方式促进DS和睡眠的临床试验研究 功能性近红外光谱(FNIRS)联合应用的临床应用评价 适合发育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。拟议的研究试图评估该工具是否对 DS和睡眠障碍，并且可以在患有DS的幼儿中测量。如果得到资助，拟议的研究 将(1)在患有DS的儿童(6-11岁，n=30)的年轻样本中测试使用fNIRS的可行性 通常发展与年龄(TDCA[n=20；6-11岁])或精神年龄(TDMA)相匹配的对照组 [n=20；3-5年])通过量化成功完成fNIRS数据收集的参与者人数 并检查与任务完成成功相关的特征(例如，行为问题、年龄较小)； (2)评价fNIRS能否发现DS患者额叶前部血流动力学反应的差异。 并评估其对睡眠对前额叶影响的敏感度 血流动力学反应；(3)评估基于fNIRS的前额叶血流动力学反应在 DS通过检查基于任务的前额神经效率和真实世界功能之间的关系(即， 适应和不适应行为)。拟议的研究代表着关键的下一步 针对DS和睡眠问题的临床试验研究。没有对关键结果进行有效衡量的情况 这些功能障碍，如前额叶功能，将无法全面评估不同领域的疗效 旨在改善这些群体的生活质量的治疗。

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.