Early Developmental Determinants and Pathways in Down syndrome

唐氏综合症的早期发育决定因素和途径

基本信息

批准号：
10466961
负责人：
Elizabeth Will
金额：
$ 14.55万
依托单位：
UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10466961
关键词：
Achievement Affect Area Attention Award Behavior Behavioral Childhood Cognition Cognitive Collaborations Communication Communication impairment Complex Custom Development Developmental Process Dimensions Down Syndrome Early Diagnosis Ensure Genetic Diseases Goals Heart Rate Impaired cognition Impairment Infant Infant Development Intellectual functioning disability Intervention Investigation Learning Life Light Link Longitudinal Studies Measurement Mentors Methodology Methods Modeling Motor Musculoskeletal Equilibrium Nature Outcome Pathogenesis Pathway interactions Phase Phenotype Physiological Posture Prevalence Process Research Resources Risk Role Scientist Series Severities Stimulus Strategic Planning Testing Time Training United States National Institutes of Health attentional control biobehavior career cognitive function cognitive skill computerized data processing discount discrete time heart rate variability improved infancy innovation insight kinematics motor impairment novel programs success virtual

项目摘要

This Pathway to Independence Award (K99/R00) will facilitate my transition to an independent scientist who conducts innovative research on mechanisms and pathways of developmental and cognitive risk outcomes in Down syndrome (DS). Down syndrome is the most common childhood genetic disorder and characterized by substantial phenotypic impairments across several areas of development, including motor, attention, communication, and cognition. There has been virtually no investigation, however, into the developmental pathways of early phenotypic impairments in motor or attention, or their role as determinants for impaired cognitive or communication outcomes in DS. Motor and attention are key developmental domains effortlessly coordinated to support communication and cognitive learning in typical development. Delayed achievement of key motor milestones in DS – postural control in particular – has serious implications for the development of infant attention, as well as for outcomes related to communicative and cognitive functioning through compromised learning opportunities. Therefore, I propose to investigate the dynamic influence between postural control and attention in infants with DS and determine their mutual or distinct role in impaired communication and cognitive outcomes at 24-months in DS. I will characterize the behavioral and physiological features of postural control and attention by quantifying the kinematics of postural variability and defining heart-rate phases of attention. I will examine the dynamics of how these features influence one another during discrete learning opportunities, and also across development to inform their role as determinants on communication and cognitive risk outcomes in DS. Examining the biobehavioral concordance between these constructs is an innovative, precise, and multi-method approach that can yield better insight into the developmental complexity in DS. This will be accomplished across three complementary studies that will provide advanced training and employ cutting-edge methodology. Training initiatives will be accomplished across two studies implemented during the mentored K99 phase, and then systematically applied to a longitudinal study during the independent R00 phase. The specific aims across these studies are: 1) Identify differences in physiological and behavioral facets of attention at 12-months and their role in communication and cognitive skill outcomes at 24-months as a function of postural control in infants with DS (K99 phase); 2) Determine the concordance across biobehavioral facets of attention and the reciprocal association between biobehavioral attention and postural control at 9, 12, and 18-months in infants with DS (K99/R00 phase); and 3) Characterize the biobehavioral pathways and developmental dynamics of attention and postural control across 9, 12, and 18-months and test whether these domains have a shared or unique influence on communication or cognitive skill outcomes at 24-months in DS (R00 phase). This novel and multi-method biobehavioral approach will shed light on the pathogenesis of impaired motor and attention in DS. Further, findings will contribute to advanced phenotyping approaches of infant development in DS and serve as an initial step in the development of targeted interventions. My team of incredibly strong mentors and one collaborator is uniquely poised to assist and promote my training and research goals, and to ensure my successful transition to an independent scientist.

这项获得独立奖的途径（K99/R00）将有助于我向独立科学家的过渡唐氏综合症（DS）的发育和认知风险结果的机制和途径的创新研究。唐氏综合症是最常见的童年遗传疾病，其特征是实质性障碍在多个发展领域，包括运动，注意力，沟通和认知。实际上有但是，没有投资于运动或注意力中早期表型损伤的发展途径，或它们是DS中认知或交流结果受损的作用。运动和关注是关键发展领域毫不费力地协调了典型发展中的沟通和认知学习。 DS中关键运动里程碑的延迟成就 - 尤其是姿势控制 - 对通过与交流和认知功能相关的结果的发展以及通过损害学习机会。因此，我建议研究姿势控制之间的动态影响和患有DS的婴儿的注意力，并确定其在沟通和认知受损中的相互作用或独特的作用 DS的24个月的结果。我将表征姿势控制的行为和身体特征，通过量化姿势变异性的运动学和定义注意力的心率阶段来注意。我会检查的这些特征如何在离散学习机会以及跨越彼此影响的动态开发以告知他们作为DS中沟通和认知风险结果的决心的作用。检查这些结构之间的生物行为一致性是一种创新，精确和多方法的方法，可以产生更好地了解DS中的发展复杂性。这将在三个完整的研究中完成这将提供高级培训和员工尖端方法。将完成培训计划在修改K99阶段实施的两项研究中，然后系统地应用于纵向研究在独立的R00阶段。这些研究的具体目的是：1）确定生理学和在12个月的关注方面及其在24个月的沟通和认知技能结果中的作用 DS婴儿（K99期）的姿势控制的功能； 2）确定跨生物行为方面的一致性在9、12和18个月的生物行为关注与姿势控制之间的关注和相互关联具有DS的婴儿（K99/R00期）； 3）表征生物行为的途径和发展动力学 9、12和18个月的注意力和姿势控制，并测试这些域是否具有共享或独特在DS（R00阶段）24个月的交流或认知技能结果的影响。这本小说和多方法生物行为方法将阐明运动受损和DS中注意力受损的发病机理。此外，发现将有助于DS中婴儿发育的先进表型方法，并成为制定目标干预措施。我的团队非常强大的导师和一名合作者被唯一中毒协助和促进我的培训和研究目标，并确保我成功地过渡到独立科学家。