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

项目摘要 该项目的目标是绘制婴儿出生后前6个月大脑和行为的转变， 自闭症谱系障碍（ASD）的高风险和低风险。这项研究建立在结果表明，一个基本的 社会适应行动的机制--看别人的眼睛--在头6个月已经在下降 ASD婴儿的寿命（Jones & Klin，Nature，2013）。有趣的是，这些发现与先前的假设相矛盾。 假定ASD患者从出生起就缺乏社会适应性取向： 在后来被诊断为ASD的婴儿中，这些婴儿立即减少;相反，这些婴儿表现出轻微的但 在2个月时，眼睛注视的统计学显著增加，然后下降。与早期的证据一起 从经验预期机制（即，主要是皮层下介导的“反射样”）的规范性转变 倾向）经验依赖的（也就是说，主要是皮质介导的适应性行为，建立 根据早期新生儿的经验），这些数据表明ASD中有一个非常具体的假设：反射样 倾向可能是最初存在的，而早期的关键转变，取决于最初的方式， 倾向被整合到偶然的社会互动中，被破坏。该研究将直接 测试这个假设。目标1将识别与反射样/经验转换相关的大脑网络- 期望互动/经验依赖形式的社会适应行动，并将确定 发展阶段-经验-预期或经验-依赖-在这一阶段， 行为首先出现在ASD中。目标2和3将确定大脑成熟和早期婴儿经验的各个方面 这是必要的和/或足够的指导大脑行为过渡的前6个月的生活。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然性的敏感性的出现，这是一个关键的 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 这些经验对于塑造婴儿社会大脑网络的发展是必要的和/或足够的。 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 (in大脑和行为）与Project V相协调，以促进人类和模型之间的比较 系统.将在出生至6岁之间的3个时间点收集解剖、结构和功能MRI扫描结果。 几个月，感兴趣的区域和网络分析将用于表征皮层下和皮层 在婴儿的头6个月里，网络相互作用并重新组织。发展之间的双向关系 大脑的变化和行为的发育变化（在项目I和II中测量）将使用 用于建模时变纵向数据和检测统计因果关系的创新统计方法 在复杂的系统中。通过深入研究大脑行为基础的新兴社会残疾， 在婴儿早期，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.