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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要这个有指导的职业发展建议将 1) 产生一个新颖的基于唤醒的多模式目标 Rebecca Grzadzinski 博士建立了 DS 婴儿认知、社交和感觉结果的生物标志物，2) 建立作为 DS 婴儿的行为和神经生物学特征的独立临床研究员。这总体假设是，生命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进行采样并学习。基于神经生物学发现典型的神经发育障碍，我们假设 1）社交唤醒与父母相关报告的社交技能以及杏仁核体积，2）非社交唤醒与父母报告的相关感觉反应性和枕叶体积，3）对刺激的习惯与认知估计相关能力和额叶体积。通过实时识别这些唤醒模式以响应特定的、良好的受控刺激后，我们可以开始开发针对婴儿独特唤醒的新颖的早期干预措施轮廓。将唤醒动力学与基础神经生物学联系起来不仅验证了该结构，还提供了 DS 临床前模型的解剖目标。这项提议是史无前例的，而且具有时效性。有机会利用具有稳健行为的 DS 婴儿的最大纵向跟踪样本和神经生物学表型。这项工作的基础利用了持续的数据收集管道多中心、纵向婴儿脑成像研究 (IBIS；IBIS； PI：皮文； R01MH118362； PI：波特龙； R01HD088125-01A1)。在该提案的支持下，设计了刺激措施以引发基于唤醒的反应将被添加到标准 IBIS 电池中。家长报告和直接评估测量将从 IBIS 数据库中提取，唤醒生物识别技术将与并发和 DS 婴儿认知、社交和感觉行为的纵向指标。 Grzadzinski 博士已集合专家指导团队，包括博士。 Piven（IBIS 总监）和 Hazlett（北卡罗来纳大学站点 PI）将担任指导她在完成该项目期间确保她能够获得实现该项目所需的所有 IBIS 资源项目取得成果。博士。林奇、罗德里格斯-罗马格拉和沃拉补充了她的导师团队指导 Grzadzinski 博士走向独立所需的方法学、转化和临床专业知识。这该项目是验证认知、社交和感觉的早期唤醒生物标志物的突破性机会 DS 婴儿的结局，并最终指导 DS 的早期干预和临床前研究。这该提案与 NIH INCLUDE 项目研究计划保持一致，旨在收集个人的深层表型数据通过与现有群体联系来与 DS 合作，将使 Grzadzinski 博士成为一位非常成功的独立人士临床研究人员致力于改善 DS 患者及其家人的生活。