Pivotal Transitions in Early Infancy that Shape Network Development of the Social Brain

项目总结 该项目的目标是绘制婴儿出生后头6个月的大脑和行为变化图。 自闭症谱系障碍(ASD)的高风险和低风险。这项研究的基础是结果表明，一个基本的 社会适应行为的机制--看着别人的眼睛--在前6个月已经在下降 自闭症婴儿的生活质量(Jones&Klin，《自然》，2013年)。有趣的是，这些发现与先前的假设相矛盾。 假设自闭症患者从出生起就缺乏社会适应取向：早期的眼神水平没有 在后来被诊断为ASD的婴儿中立即减少；相反，这些婴儿表现出轻微的 视力在2个月后有统计学意义的增加，然后下降。以及早期的证据 从经验-期待机制的规范性转变(即，主要由亚大脑皮层介导的类似反射的机制) 倾向)到依赖经验的行为(即，在很大程度上是由皮层调节的适应行为 根据早期新生儿经历)，这些数据暗示了ASD的一种非常具体的假说：反射样 倾向可能最初存在，而早期的关键过渡，取决于最初的 倾向被整合到偶然的社交互动中，被打乱了。拟议的研究将直接 检验这一假设。目标1将识别与反射样/经验转换相关的大脑网络- 期待互动/经验依赖的社会适应行动形式，并将确定 发育阶段--经验--期待的或依赖的--在这一阶段中，大脑和 行为最先出现在ASD。目标2和目标3将确定大脑成熟和早期婴儿经历的各个方面 这是必要的和/或足够的，在生命的前6个月指导大脑行为的转变。目标2将 确定大脑成熟的各个方面，这些方面推动了对社会偶发事件的敏感性的出现，这是一个关键 婴儿与照顾者之间的社会互动机制。目标3将确定早期婴儿的各个方面 形成婴儿社会大脑网络发展所必需和/或足够的经验。 大脑-行为转变将在项目I-IV共享的同一组婴儿中进行测量。措施 (在大脑和行为方面)与项目V协调，以促进人类和模型之间的比较 系统。解剖、结构和功能核磁共振扫描将在出生到6岁之间的3个时间点收集 几个月，感兴趣区和网络分析将被用来描述皮质下和皮质下 在婴儿出生后的头6个月里，网络相互作用并进行重组。发展与发展之间的双向关系 大脑的变化和行为的发展变化(在项目I和II中测量)将使用以下方法进行检查 用于建模时变纵向数据和用于检测统计因果关系的创新统计方法 在复杂的系统中。通过深入研究新出现的社会残疾的脑行为基础 早期，这项研究将为ASD的发病机制提供新的机制见解，并确定新的 创新早期干预的目标。

PROJECT SUMMARY The goal of this project is to map transitions in brain and behavior over the first 6 months of life in infants at high- and low-risk for Autism Spectrum Disorders (ASD). This study builds on results demonstrating that a basic mechanism of social adaptive action—looking at the eyes of others—was already in decline in the first 6 months of life of infants with ASD (Jones & Klin, Nature, 2013). Interestingly, these findings contradicted prior hypotheses postulating an absence of social adaptive orientation in ASD from birth: early levels of eye-looking were not immediately diminished in infants later diagnosed with ASD; instead, these infants exhibited a slight but statistically significant increase in eye-looking at 2 months, which then declined. Together with evidence of early normative transitions from experience-expectant mechanisms (that is, largely subcortically-mediated ‘reflex-like’ predispositions) to experience-dependent ones (that is, largely cortically-mediated adaptive actions that build upon early newborn experiences), these data suggest a very specific hypothesis in ASD: reflex-like predispositions may be initially present, whilst early pivotal transitions, dependent upon the way in which initial predispositions are integrated into contingent social interaction, are disrupted. The proposed study will directly test this hypothesis. Aim 1 will identify brain networks associated with transitions from reflex-like/experience- expectant to interactive/experience-dependent forms of social adaptive action, and will identify the developmental phase—experience-expectant or experience-dependent—in which disruptions in brain and behavior first emerge in ASD. Aims 2 and 3 will identify aspects of brain maturation and early infant experience that are necessary and/or sufficient for guiding brain-behavior transitions over the first 6 months of life. Aim 2 will identify aspects of brain maturation that drive the emergence of sensitivity to social contingency, a critical mechanism of social interaction between infant and caregiver. Aim 3 will identify aspects of early infant experience that are necessary and/or sufficient for shaping the development of infant social brain networks. Brain-behavior transitions will be measured in the same cohort of infants shared by Projects I-IV. Measures (in brain and behavior) are harmonized with Project V to facilitate comparisons between human and model systems. Anatomical, structural, and functional MRI scans will be collected at 3 time points between birth and 6 months, and region-of-interest and network analyses will be used to characterize how subcortical and cortical networks interact and reorganize over infants’ first 6 months. Bidirectional relationships between developmental change in the brain and developmental change in behavior (measured in Projects I and II) will be examined using innovative statistical approaches for modeling time-varying longitudinal data and for detecting statistical causality within complex systems. By intensively studying the brain-behavior bases of emerging social disability in very early infancy, this research will offer new mechanistic insight into the pathogenesis of ASD, and identify new targets for innovative early interventions.