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

项目摘要 这个有指导的职业发展提案将1）产生一个新颖的基于多模式觉醒的目标 DS婴儿认知、社会和感觉结果的生物标志物; 2）Rebecca Grzadzinski博士 作为一个独立的临床研究者在行为和神经生物学特征的婴儿与DS。的 总体假设是，早期生活中的非典型唤醒模式会影响DS婴儿的互动方式 在一个多感官环境中进行体验、采样和学习。基于神经生物学的发现， 典型的神经发育障碍，我们假设1）社会唤醒与父母有关， 报告的社会技能以及杏仁核体积，2）非社会唤醒与父母报告的 感觉反应性和枕叶体积，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，嗯- 控制刺激，我们可以开始开发新的早期干预措施，针对婴儿独特的唤醒 profile.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， DS临床前模型中的解剖靶点。这是一个前所未有的和时间敏感的建议。 有机会利用最大的纵向跟踪样本的婴儿与DS与强大的行为 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， 在多中心、纵向婴儿脑成像研究（IBIS; PI：Piven; R01MH118362; PI：Botteron; R01HD088125 - 01A1）。在这一建议的支持下，刺激设计 将被添加到标准IBIS电池中。上级报告和直接评估 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婴儿的认知、社会和感觉行为的纵向指标。格扎津斯基博士已经召集了 一个专家指导团队，包括Piven博士（IBIS主任）和Hazlett博士（研究中心PI），他们将指导 她在完成这个项目，并确保她有机会获得所有必要的IBIS资源，使这个 项目取得成果。Lynch，Rodriguez-Romaguera和Vora通过添加以下内容来完成她的导师团队 方法学，翻译和临床专业知识需要指导Grzadzinski博士走向独立。这 该项目是一个突破性的机会，以验证认知，社会和感官的早期唤醒生物标志物 结果，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，以收集个体的深层表型数据 与DS通过与现有的同伙联系，并将定位博士Grzadzinski是一个非常成功的独立 致力于改善DS患者及其家人的生活的临床研究人员。

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.