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

描述(由申请人提供)：本项目的目标是通过眼球跟踪技术和在观看自然社交情景时对视觉注意力的创新量化来前瞻性地研究患有自闭症谱系障碍(ASD)的婴儿的社交视觉参与的发展。我们将测量(1)在观看以婴儿为导向的方法的成年人时的视觉注视时间，以及(2)在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。将有235名婴儿参加该项目，其中包括患有自闭症儿童的婴儿兄弟姐妹，他们是患自闭症的高危儿童(HR-ASD，N=135)；没有ASD家族史的高危发育迟缓的婴儿(HR-DD，N=50)；以及发育问题风险较低的儿童，预期为典型发育(LR-TD预期，N=50)。验证性诊断评估将在36个月时进行。主要的分析将集中在患有自闭症的儿童与发育迟缓和发育迟缓儿童之间的比较。考虑到ASD的家族性和促进表型调节研究的潜力，还将比较ASD儿童的所有兄弟姐妹(整个HR-ASD样本)与HR-DD和LR-TD预期组的关系。这项工作建立在我们对动态社会刺激的异常视觉注视模式在青少年(R01 HD04217)和24至36个月患有ASD的儿童(U54 MH66494，耶鲁STAART)中的发现的基础上。在这两种情况下，对感兴趣区域(眼睛、嘴巴、身体和物体)的视觉注视总结都是同时进行的、标准化的社会残疾测量的有力预测因素。在这里，我们以两种方式扩展这项工作：(1)我们将使用我们实验室开发的对瞬间视觉扫描行为的新的群体测量，这种测量对婴儿周围环境中自然发生的时间限定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ASD的更高风险的婴儿，量化社会化的关键机制及其在ASD早期发病机制中假想的脱轨的个体发生。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)，以及我们对患有自闭症的幼儿的持续研究所产生的概念和技术进步(项目1，P50 HD055726)。我们的计划目标是(1)研究早期社会化机制以及这些机制在ASD综合征表达异质性中的作用；(2)开发基于绩效的测量方法，能够预测发育和诊断结果，并能够作为ASD高危婴儿的筛查方案。该项目涉及NIH机构间自闭症协调委员会的几个关键行动项目，重点是婴儿发育标记物和筛查以及神经发育过程。公共卫生相关性：在这个项目中，我们将绘制和量化从2个月到24个月大的社会视觉参与的展开，使用视觉注视和视觉扫描的测量来研究自闭症婴儿如何与社交世界互动。通过对患有自闭症的较大儿童的婴儿兄弟姐妹的前瞻性研究，该项目将测量随后被诊断为自闭症谱系障碍的婴儿的社交参与改变的发展过程。这个项目的三个目标是定量诊断标记物、结果预测因子和能够分析更广泛的自闭症谱系的异质性的内表型，这也是NIH机构间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记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.