The Role of Autonomic Regulation of Attention in the Emergence of ASD

项目摘要 注意力中断是自闭症谱系障碍（ASD）最早出现的终身特征之一， 研究表明，在新生儿和婴儿早期有一个临界点，在这个临界点上， 可检测的这种中断的时间与神经发育中的关键成熟转变相一致，但 与ASD中注意力中断相关的神经生物学机制仍然难以捉摸。一个神经生物学 从婴儿早期起，调节注意力的系统是自主神经系统（ANS）。宽ANS 在已经诊断为ASD的大龄儿童中观察到ANS功能障碍，但是 导致ASD注意力异常的原因尚不清楚。本研究的总体目标是检查 注意力的非典型自主调节如何与ASD症状的出现相关。一 注意力自主调节的关键标志是心脏定义的注意力。因此，心脏的成熟 在婴儿早期的明确的注意力和发展的后果，其中出现的 互动行为和ASD症状将被检查。这项研究的一个关键创新是利用 三组设计，其中经历ASD症状升高的婴儿（患有ASD的儿童的婴儿兄弟姐妹） ASD; ASIBs）将与典型发育（TD）和早产（PT）对照组进行比较。出生的婴儿 从出生开始就有广泛的ANS功能障碍，将ASIBs与PT进行比较将有助于阐明 注意力特异性ANS功能障碍预测ASD特异性症状的出现。目标1将比较 在神经发育的一个非常关键的时期（1-3个月）出现注意力的自主调节 在ASIBs、PT婴儿和TD婴儿中。目标2将量化心脏定义的注意力之间的关联 在6个月、9个月和12个月的时候， 组Aim 3将利用机器学习技术预测3岁时的ASD症状， 自主和注意力特征（来自目标1-2）。确定自主调节的特异性， 注意力作为与ASD相关的一个关键的、早期出现的特征，对ASD的治疗具有重要的转化潜力。 经济有效的生物标志物。这项工作将告知ASD的发育模型，其中自主神经功能紊乱 注意力的调节对现实世界的互动有近端影响，可能会干扰学习并产生 对长期结果的连锁效应。

PROJECT SUMMARY Disrupted attention is among the earliest-emerging, lifelong features of autism spectrum disorder (ASD) and research suggests a critical point in the neonatal and early infant period at which disrupted attention may be detectable. The timing of this disruption aligns with key maturational shifts in neurodevelopment, but the neurobiological mechanisms associated with disrupted attention in ASD remain elusive. One neurobiological system that regulates attention from early infancy is the autonomic nervous system (ANS). Broad ANS dysfunction is observed in older children already diagnosed with ASD, but whether and when ANS dysfunction contributes to attention abnormalities in ASD remains unknown. The overall goal of this study is to examine how atypical autonomic regulation of attention may be associated with the emergence of ASD symptoms. A key marker of autonomic regulation of attention is heart defined attention. Accordingly, maturation of heart defined attention in the early infant period and the developmental consequences therein for the emergence of interactive behaviors and ASD symptoms will be examined. A critical innovation of this study is leveraging a three-group design in which infants who experience elevated ASD symptoms (infant siblings of children with ASD; ASIBs) will be compared to typically developing (TD) and preterm (PT) control groups. Infants born preterm experience broad ANS dysfunction from birth and comparing ASIBs to PTs will help delineate how attention-specific ANS dysfunction predicts the emergence of ASD-specific symptoms. Aim 1 will compare the emergence of autonomic regulation of attention during a very critical period of neurodevelopment (1-3 months) across ASIBs, PT infants, and TD infants. Aim 2 will quantify the association between heart defined attention and interactive behavior on a moment-to-moment basis at 6, 9, and 12 months, and compare across the three groups. Aim 3 will utilize machine learning techniques to predict ASD symptoms at age 3 years from early autonomic and attentional features (from Aims 1-2). Determining the specificity of autonomic regulation of attention as a key, early emerging feature associated with ASD, has significant translational potential for a cost-effective biomarker. This work will inform developmental models of ASD wherein disrupted autonomic regulation of attention has proximal effects on real-world interactions that may interfere with learning and have cascading effects on long-term outcomes.