Early Identification of ASD: Translating Eye Tracking into Practice

描述（由申请人提供）：目前，家长报告筛选工具（如M-CHAT， CSBS）是儿科医生早期发现自闭症的唯一标准化筛选选项。正如我们之前的工作（1年健康婴儿检查方法，Pierce et al., 2011）所证明的那样，这种筛查具有宝贵的优势，但也有弱点，包括父母特征对他们如何评价孩子行为的影响以及高假阳性率。自闭症是一种疾病，其根源在于早期大脑发育异常，但早期识别主要依赖于父母报告的测量方法，而不是更客观、可量化的行为。为了超越家长报告作为唯一的早期筛查选择，必须研究新的筛查程序。在我们上一个拨款周期中，我们开发了一种新颖的眼球追踪测试，自闭症几何偏好测试（GeoPref test）。这个简单的一分钟测试在电脑显示器的一半显示动态的、彩色的几何运动图案，另一半显示彩色的活跃人物。在使用标准眼动追踪技术测试的bb4040名幼儿中，几乎每一个高频率注视几何图案的幼儿都是ASD，而不是典型的或发育迟缓的。因此，我们的实验室实验表明，GeoPref Test检测ASD的特异性非常高，达到99%。低假阳性率在筛选工具中是必不可少的，因为假阳性会使系统过载并产生焦虑。在这种异质障碍中同样重要的是，1分钟测试确定了37%的ASD幼儿。这比任何其他早期遗传、蛋白质组学、神经影像学或神经行为筛查的比例都要大，而且快速、简单，而且高度特异性。目标1将确定将ASD特异性测试整合到临床实践中的方法，作为未能通过常规第一级铅笔和纸筛查的婴儿的第二级筛查(即，

DESCRIPTION (provided by applicant): Currently, parent report screening tools (e.g., M-CHAT, CSBS) are the only standardized screening options available to pediatricians for the early detection of autism. As demonstrated in our previous work (the 1-Year Well-Baby Check-Up Approach, Pierce et al., 2011), such screens have valuable strengths, but also weaknesses, including the impact of parent characteristics on how they rate their child's behavior and high false positive rates. Autism is a disorder that has its roots in abnormal early brain development, yet early identification rests largely in the hands of parent report measures, rather than in the domain of more objective, quantifiable behavior. To move beyond parent report as the only early screening choice, novel procedures for screening must be researched. During our last grant cycle we developed a novel eye-tracking test, the Geometric Preference Test for Autism (GeoPref Test). This simple one-minute test shows dynamic, colorful geometric moving patterns on half of a computer monitor and colorful active people on the other half. Of >440 toddlers tested using standard eye tracking technology, almost every toddler who fixated at high rates on the geometric patterns was ASD, and not typical or developmentally delayed. Thus, our laboratory experiments demonstrated exceptionally high, 99%, specificity of the GeoPref Test for detecting ASD. A low false positive rate is essential in a screening tool because false positives overload the system and create anxiety. Equally important in this heterogeneous disorder, the 1-min test identified 37% of all ASD toddlers. This is a larger percentage than any other early genetic, proteomic, neuroimaging or neurobehavioral screen, and it is fast, easy, and highly ASD specific. Aim 1 will identify methods to integrate ASD specific test into clinical practice as a 2nd tier screen for babies who fail a routine 1st tier pencil and paper screen (i.e., the CSBS). Results will greatly improve the accuracy of early detection and speed referral of babies for diagnostic and treatment services. Using a portable eye tracker, 39 pediatricians will give the GeoPref Test in their office to toddlers who fail the CSBS who will in turn be referred to our Center for blinded diagnosis. This will be the first translation of an eye tracking finding on ASD into real-world clinical practice. In an effort to fully understand the clinical phenotype of ASD toddlers that "fail" the GeoPref Test, Aim 2 will use novel experimental tests, such as a test of exploration, as well as standardized tests such as the Mullen, to identify clinical profiles tha distinguish these toddlers from others with an ASD. Although the GeoPref Test identifies a large subgroup of 37% of all ASD toddlers, equally fast, and accurate tests are needed to identify the remaining ASD toddlers. Aim 3 proposes to develop new eye tracking tests, specifically novel social orienting and motherese paradigms, to detect these toddlers. Random forest classification algorithms will identify eye gaze signatures that best identify subgroups of ASD toddlers. All toddlers will receive a final blinded diagnosis at 30-36 months.