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

• 批准号: 10283797
• 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
• 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/10283797
• 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

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.

这个独立之路奖（K99/R 00）将有助于我过渡到一个独立的科学家， 唐氏综合征（DS）发育和认知风险结果的机制和途径的创新研究。 唐氏综合征是最常见的儿童遗传性疾病，其特征是大量的表型损伤 在几个发展领域，包括运动，注意力，沟通和认知。实际上， 然而，没有对运动或注意力早期表型损伤的发育途径进行调查，或者 他们的作用，为受损的认知或沟通结果的DS的决定因素。运动和注意力是关键 发展领域毫不费力地协调，以支持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实现-特别是姿势控制-对患者的运动能力有严重影响。 婴儿注意力的发展，以及与沟通和认知功能有关的结果， 影响学习机会。因此，我建议调查姿势控制之间的动态影响， 和注意力，并确定他们在受损的沟通和认知中的相互或不同的作用。 DS中24个月时的结局。我将描述姿势控制的行为和生理特征， 通过量化姿势变化的运动学和定义注意力的心率阶段来确定注意力。我将研究 这些特征在离散的学习机会中如何相互影响的动态，以及 发展，告知他们的作用，在DS的沟通和认知风险结果的决定因素。检查 这些结构之间的生物行为一致性是一种创新的，精确的，多方法的方法，可以产生 更好地了解DS的发展复杂性。这将通过三项互补研究来完成 将提供高级培训并采用尖端方法。将完成培训举措 在辅导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R 00阶段。这些研究的具体目标是：1）确定生理和 12个月时注意力的行为方面及其在24个月时沟通和认知技能结果中的作用， DS婴儿（K99期）的姿势控制功能; 2）确定生物行为方面的一致性 注意力和生物行为注意力和姿势控制之间的相互关系，在9个月，12个月和18个月， DS婴儿（K99/R 00期）;和3）表征DS婴儿的生物行为途径和发育动力学， 在9个月，12个月和18个月的注意力和姿势控制，并测试这些领域是否有共同的或独特的 DS（R 00阶段）24个月时对沟通或认知技能结局的影响。这种新颖的多种方法 生物行为学方法将有助于阐明DS运动和注意力受损的发病机制。此外，调查结果将 有助于DS婴儿发育的先进表型分析方法，并作为 制定有针对性的干预措施。我的团队非常强大的导师和一个合作者是独一无二的准备， 协助和促进我的培训和研究目标，并确保我成功地过渡到一个独立的科学家。