The Ontogeny of Social Visual Engagement in Infants at Risk for Autism

描述（由申请人提供）：本项目旨在通过眼动追踪技术和创新的视觉注意力量化方法，前瞻性地研究自闭症谱系障碍（ASD）婴儿在观看自然社会情境时的社会视觉参与发展。我们将测量(1)观看参与婴儿导向方法的成人时的视觉注视时间，以及(2)观看参与游戏的婴儿时的时间敏感视觉扫描模式。实验数据将在2、4、6、9、12、18和24个月时收集。该项目将纳入235名婴儿，包括自闭症儿童的婴儿兄弟姐妹，他们有发展为ASD的高风险（HR-ASD， N=135）；无ASD家族史的发育迟缓高危婴儿（HR-DD， N=50）；发育问题低风险儿童与典型发育预期（LR-TD预期，N=50）。确诊性诊断评估将在36个月时进行。主要的分析将集中在自闭症儿童与DD和TD儿童之间的比较。考虑到ASD的家族性以及对介导表型研究的推进潜力，我们还将对ASD患儿的所有兄弟姐妹（整个HR-ASD样本）与HR-DD和lr - texpected组的关系进行比较。这项工作建立在我们对青少年（R01 HD04217）和24- 36个月大的ASD患者（U54 MH66494, Yale STAART）对动态社会刺激的异常视觉固定模式的发现之上。在这两种情况下，对感兴趣的区域（眼睛、嘴巴、身体和物体）的视觉固定总结是并发的、标准化的社会残疾措施的有力预测因素。在这里，我们将从两个方面扩展这项工作：(1)我们将采用我们实验室开发的即时视觉扫描行为的新群体测量方法，这种方法对婴儿周围环境中自然发生的有时间界限的社会和身体线索特别敏感；(2)我们将通过纵向研究一组患自闭症风险较高的婴儿，量化自闭症早期发病机制中社会化关键机制的个体发生及其假设的脱轨。我们利用了一个专注于同一队列的详细临床特征的项目（项目1，PO1 HD003008），以及我们对幼儿ASD的持续研究所带来的概念和技术进步（项目1，P50 HD055726）。我们的项目目标是：(1)研究社会化的早期机制以及这些机制在ASD综合征表达异质性中的作用；(2)制定能够预测发育和诊断结果的基于绩效的措施，并能够作为有ASD风险的婴儿的筛查方案。该项目涉及NIH跨机构自闭症协调委员会的几个关键行动项目，重点是婴儿的发育标记和筛查，以及神经发育过程。公共健康相关性：在这个项目中，我们将绘制和量化2至24个月大的社会视觉参与的展开，使用视觉固定和视觉扫描的测量来研究自闭症婴儿如何与社会世界互动。通过对年龄较大的自闭症儿童的兄弟姐妹进行前瞻性研究，本项目将测量随后被诊断为自闭症谱系障碍的婴儿社会参与改变的发展过程。该项目的三个目标是定量诊断标记、结果预测因子和能够分析更广泛自闭症谱系异质性的内表型，这也是NIH跨机构自闭症委员会的关键目标。与委员会的行动项目一样，该项目强调婴儿的发育标志和筛查，以及神经发育过程，因此与公共卫生高度相关。

DESCRIPTION (provided by applicant): The goal of this project is to study prospectively the development of social visual engagement in infants with autism spectrum disorders (ASD) by means of eye-tracking technology and innovative quantification of visual attention during viewing of naturalistic social situations. We will measure (1) visual fixation time during viewing of adults engaged in infant-directed approaches, and (2) temporally-sensitive visual scanning patterns during viewing of infants engaged in play. Experimental data will be collected at 2, 4, 6, 9, 12, 18, and 24 months. A cohort of 235 infants will be enrolled in this project, consisting of infant siblings of children with autism who are at High Risk for developing an ASD (HR-ASD, N=135); infants at High Risk for Developmental Delays without familial history of ASD (HR-DD, N=50); and children at Low Risk of developmental problems with Typical Development expected (LR-TD expected, N=50). Confirmatory diagnostic assessment will take place at 36 months. The primary analyses will focus on comparisons between children who develop an ASD in comparison with DD and TD children. Given the familial nature of ASD and the potential for advancing research on mediating phenotypes, comparisons will also be made between all siblings of children with ASD (entire HR-ASD sample) in relation to the HR-DD and LR-TDexpected groups. This work builds on our findings of anomalous visual fixation patterns to dynamic social stimuli in adolescents (R01 HD04217) and in 24- to 36-month-olds (U54 MH66494, Yale STAART) with ASD. In both cases, summaries of visual fixation on regions of interest (eyes, mouth, body, & object) were strong predictors of concurrent, standardized measures of social disability. Here we extend this work in two ways: (1) we will employ novel group measures of moment-by-moment visual scanning behavior developed by our lab which are particularly sensitive to time-delimited social and physical cues occurring naturally in infants' surrounding environment; and (2) we will quantify the ontogeny of a key mechanism of socialization and its hypothesized derailment in the early pathogenesis of ASD by studying longitudinally a group of infants at greater risk for developing the disorder. We capitalize on a project focused on the detailed clinical characterization of the same cohort (Project 1, PO1 HD003008), and on the conceptual and technological advancements resulting from our continuing studies of young children with ASD (Project 1, P50 HD055726). Our programmatic goals are to (1) study early mechanisms of socialization and the role of these mechanisms in the heterogeneity of syndrome expression in ASD; and (2) to develop performance-based measures capable of predicting developmental and diagnostic outcome and able to serve as screening protocols for infants at risk for ASD. This project addresses several key action items of the NIH Interagency Autism Coordinating Committee, with emphasis on developmental markers and screening in infants, and neurodevelopmental processes. PUBLIC HEALTH RELEVANCE: In this project we will map and quantify the unfolding of social visual engagement from 2 to 24 months of age, using measures of visual fixation and visual scanning to study how infants with autism interact with the social world. Through a prospective study of the infant siblings of older children with autism, this project will measure the developmental course of altered social engagement in infants subsequently diagnosed with an autism spectrum disorder. The three goals of this project quantitative diagnostic markers, predictors of outcome, and endophenotypes capable of parsing the heterogeneity of the broader autism spectrum are also key objectives of the NIH Interagency Autism Committee. Like the Committee's action items, this project emphasizes developmental markers and screening in infants, as well as neurodevelopmental processes, and is, therefore, highly relevant to public health.