Mechanistic Transitions that Shape Typical and Atypical Social Visual Engagement

项目摘要 本申请建立在我们实验室的最近研究的基础上，该研究表明，社会视觉行为-- 婴儿在视觉上探索、参与并最终从周围世界中学习和适应的方式- （1）与遗传变异紧密耦合，同卵双胞胎的一致性等于0.91;（2）高度 在遗传学上是保守的，幼年恒河猴的早期眼睛看起来的模式是惊人的， 与人类婴儿同源;和（3）在后来诊断为ASD的婴儿中的病理性受损， 在初始和重复队列中至少从第2个月开始观察到差异。本申请将 在这些发现的基础上，研究婴儿早期的关键转变，这些转变为未来实现社会目标奠定了基础。 沟通里程碑我们将研究早期婴儿从反射式到意志性社会适应性的转变 产后头2个月的行动（目标1）;互惠和偶然婴儿社会的出现 互动（目标2）;以及非常早期的婴儿社会责任的级联后果-或破坏 在ASD后期，长期的社会交往结果（目标3）。最后，我们将这些 在发展结构和功能脑网络方面采取相应的变化措施（项目III和V）， 口语交流的出现（在项目II中），以及对早期社会互动治疗的反应（在项目II中）。 项目四）。将招募250名婴儿，由自闭症儿童的婴儿兄弟姐妹组成， 患有ASD的高风险（HR-ASD，N=150）以及发育迟缓低风险的婴儿兄弟姐妹， 由于没有ASD家族史，预期具有典型发育（LR-TDx，N=100）。数据将 从出生后第一周开始纵向前瞻性收集。该项目直接针对 美国国立卫生研究院机构间自闭症协调委员会提出的几个自闭症的理想目标， 重点是了解正在展开的发展轨迹，潜在机制， ASD的生物学特征

PROJECT SUMMARY The present application builds on recent research in our laboratory showing that social visual engagement—the way in which infants visually explore, engage, and ultimately learn from and adapt to their surrounding world— is (1) tightly coupled to genetic variation, with concordance in identical toddler twins equal to 0.91; (2) highly phylogenetically conserved, with infant rhesus monkeys exhibiting patterns of early eye-looking that are strikingly homologous to human infants; and (3) pathognomonically impaired in infants later diagnosed with ASD, with differences observed from at least month 2 onwards in initial and replication cohorts. The present application will build on these findings to study pivotal transitions in early infancy that set the stage for future attainment of social- communicative milestones. We will investigate early infant transitions from reflex-like to volitional social adaptive action in the first 2 months post-partum (Aim 1); the emergence of reciprocal and contingent infant social interaction (Aim 2); and the cascading consequences of very early infant social engagement—or the disruption thereof in ASD—on later, long-term social-communicative outcomes (Aim 3). Finally, we will connect these measures to concomitant changes in developing structural and functional brain networks (in Projects III and V), to the emergence of spoken communication (in Project II), and to response to early social interaction therapy (in Project IV). A cohort of 250 infants will be enrolled, consisting of infant siblings of children with autism who are at High Risk for developing ASD (HR-ASD, N=150) as well as infant siblings at Low Risk of developmental delays, with Typical Development expected by virtue of having no familial history of ASD (LR-TDx, N=100). Data will be collected longitudinally and prospectively, beginning in the first week after birth. This project directly addresses several of the aspirational goals for autism set forth by the NIH Interagency Autism Coordinating Committee, with emphasis on understanding the unfolding developmental trajectories, underlying mechanisms, and biological signatures of ASD.