Infant arousal as a predictor of functional outcomes in Down syndrome (DS)

婴儿觉醒作为唐氏综合症（DS）功能结果的预测因子

• 批准号: 10723792
• 负责人: Rebecca Lynn Grzadzinski
• 金额: $ 17.09万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-09 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723792
• 关键词: Age Months; Amygdaloid structure; Arousal; Behavior; Behavioral; Biological Markers; Biometry; Brain; Brain imaging; Cardiac; Caring; Characteristics; Clinical; Cognitive; Collection; Data; Data Analyses; Data Collection; Databases; Dedications; Development; Diagnostic; Dissection; Down Syndrome; Early Intervention; Early treatment; Ensure; Environment; Etiology; Family; Financial Hardship; Foundations; Genetic; Impaired cognition; Individual; Infant; Intervention Studies; Investments; Knowledge; Learning; Life; Link; Literature; Measurement; Measures; Mentors; Mentorship; Methodology; Neurobiology; Neurodevelopmental Disorder; Occipital lobe; Outcome; Parents; Pathway interactions; Pattern; Phenotype; Physiological; Positioning Attribute; Pre-Clinical Model; Process; Quality of life; Reporting; Research; Research Personnel; Research Project Grants; Resources; Sampling; Sensory; Series; Site; Sleep; Social Behavior; Stimulus; Stress; Supervision; Testing; Time; Training; United States National Institutes of Health; Work; autism spectrum disorder; behavioral phenotyping; career development; clinically actionable; cognitive ability; cognitive skill; cohort; cost; design; experimental study; frontal lobe; functional improvement; functional outcomes; genetic testing; habituation; imaging study; improved; infancy; interest; multimodality; multisensory; neuroimaging; novel; novel therapeutics; parent project; peer; phenotypic data; pre-clinical research; respiratory; response; social; social skills; visual processing; visual tracking

PROJECT SUMMARY This mentored career development proposal will 1) generate a novel multimodal arousal-based objective biomarker of cognitive, social, and sensory outcomes in infants with DS and 2) establish Dr. Rebecca Grzadzinski as an independent clinical researcher in behavioral and neurobiological characteristics of infants with DS. The overarching hypothesis is that atypical arousal patterns in early life influence how an infant with DS interacts with, samples from, and learns within a multisensory environment. Building upon neurobiological findings in typical and neurodevelopmental disorders, we hypothesize that 1) social arousal is associated with parent- reported social skills as well as amygdala volume, 2) non-social arousal is associated with parent-reported sensory reactivity and occipital volumes, and 3) habituation to stimuli is associated with estimates of cognitive ability and frontal lobe volumes. By identifying these arousal patterns in real-time in response to specific, well- controlled stimuli, we can begin to develop novel early interventions that are tailored to the infant's unique arousal profile. Linking arousal dynamics with underlying neurobiology not only validates the constructs but also provides targets for dissection in preclinical models of DS. This proposal is an unprecedented and time-sensitive opportunity to capitalize on the largest longitudinally followed sample of infants with DS with robust behavioral and neurobiological phenotyping. The foundation of this work leverages the ongoing data collection pipeline of infants with DS from 6 to 24 months of age within the multi-site, longitudinal Infant Brain Imaging Study (IBIS; PI: Piven; R01MH118362; PI: Botteron; R01HD088125-01A1). With the support of this proposal, stimuli designed to elicit arousal-based responses will be added to the standard IBIS battery. Parent report and direct assessment measures will be extracted from the IBIS database and arousal biometrics will be linked with concurrent and longitudinal metrics of cognitive, social, and sensory behaviors in infants with DS. Dr. Grzadzinski has assembled an expert mentorship team, including Drs. Piven (Director of IBIS) and Hazlett (UNC Site PI), who will mentor her during completion of this project and ensure she has access to all the IBIS resources necessary to bring this project to fruition. Drs. Lynch, Rodriguez-Romaguera, and Vora complete her mentorship team by adding methodological, translational, and clinical expertise needed to guide Dr. Grzadzinski toward independence. This project is a groundbreaking opportunity to validate early arousal biomarkers of cognitive, social, and sensory outcomes in infants with DS and ultimately guide early intervention and preclinical research in DS. This proposal aligns with the NIH INCLUDE Project Research Plan to collect deep phenotyping data on individuals with DS by linking with existing cohorts and will position Dr. Grzadzinski to be a highly successful independent clinical researcher dedicated to improving the lives of individuals with DS and their families.

项目总结 这个有指导的职业发展建议将1)产生一个新的基于多模式唤醒的目标 患有DS的婴儿认知、社交和感觉结果的生物标记物2)建立了Rebecca Grzadzinski博士 作为一名独立的临床研究人员，研究DS婴儿的行为和神经生物学特征。这个 最重要的假设是，早期的非典型唤醒模式会影响患有DS的婴儿的互动方式 在多感官环境中学习，从多感官环境中学习。建立在神经生物学发现的基础上 典型的神经发育障碍，我们假设1)社交唤醒与父母-- 报告的社交技能和杏仁核体积，2)非社会性唤醒与父母报告的 感觉反应性和枕骨体积，以及3)对刺激的习惯性与认知能力的估计有关 能力和额叶体积。通过实时识别这些唤醒模式来响应特定的、良好的- 通过控制刺激，我们可以开始开发新的早期干预措施，这些干预措施是为婴儿独特的唤醒量身定做的 侧写。将唤醒动力学与潜在的神经生物学联系起来不仅验证了这些结构，而且还提供了 DS临床前模型的解剖靶点。这项提议是史无前例的，而且具有时效性。 利用行为强健的DS婴儿的最大纵向跟踪样本的机会 和神经生物学表型。这项工作的基础是利用正在进行的数据收集管道 在多部位、纵向婴儿脑成像研究(IBIS； PI：Piven；R01MH118362；PI：Botteron；R01HD088125-01A1)。在这项提议的支持下，刺激计划设计了 为了引起基于唤醒的反应，标准的IBIS电池将被添加到电池中。家长报告和直接评估 将从IBIS数据库中提取措施，并将唤醒生物识别与并发和 DS婴儿认知、社交和感觉行为的纵向测量。Grzadzinski博士已经组装好 一个专家指导小组，包括Piven博士(IBIS主任)和Hazlett博士(北卡罗来纳大学现场PI)，他们将指导 并确保她有权获得所有必要的IBIS资源，以实现此 投射到结果。Lynch博士、Rodriguez-Romaguera博士和Vora博士通过添加 指导Grzadzinski博士走向独立所需的方法学、翻译和临床专业知识。这 该项目是验证认知、社交和感觉的早期唤醒生物标记物的突破性机会 对DS婴儿的转归，并最终指导DS的早期干预和临床前研究。这 建议与NIH包括项目研究计划保持一致，以收集关于个人的深层表型数据 通过与现有队列的联系与DS合作，并将使Grzadzinski博士成为一名非常成功的独立 临床研究人员致力于改善DS患者及其家人的生活。