Early Identification of ASD: Translating Eye Tracking into Practice

描述（由申请人提供）：目前，父报告筛选工具（例如，M-CHAT，CSBS）是儿科医生早期发现自闭症的唯一标准化筛查选择。正如我们以前的工作（1年健康婴儿检查方法，皮尔斯等人，2011年），这样的屏幕有宝贵的优势，但也有弱点，包括父母的特点对他们如何评价孩子的行为和高假阳性率的影响。自闭症是一种根源于早期大脑发育异常的疾病，但早期识别主要取决于父母报告的措施，而不是更客观、可量化的行为。为了超越父母报告作为唯一的早期筛查选择，必须研究新的筛查程序。 在上一个资助周期，我们开发了一种新的眼动追踪测试，自闭症几何偏好测试（GeoPref测试）。这个简单的一分钟测试在电脑显示器的一半上显示动态的、彩色的几何运动图案，在另一半上显示彩色的活跃人物。在使用标准眼动追踪技术测试的>440名幼儿中，几乎每个以高比率注视几何图案的幼儿都是ASD，而不是典型或发育迟缓。因此，我们的实验室实验证明GeoPref检测ASD的特异性非常高，达到99%。低假阳性率在筛查工具中至关重要，因为假阳性会使系统过载并产生焦虑。同样重要的是，在这种异质性疾病中，1分钟测试确定了37%的ASD幼儿。这是一个比任何其他早期遗传，蛋白质组学，神经影像学或神经行为屏幕更大的百分比，它是快速，简单，高度ASD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，作为常规第一层铅笔和纸筛查失败的婴儿的第二层筛查（即， CSB）。结果将大大提高早期发现的准确性，并加快婴儿转诊接受诊断和治疗服务的速度。39名儿科医生将使用便携式眼动追踪器，在办公室为未通过CSBS的幼儿进行GeoPref测试，然后将他们转介给 盲法诊断中心这将是将ASD的眼动追踪结果首次转化为现实世界的临床实践。为了充分了解“未通过”GeoPref测试的ASD幼儿的临床表型，Aim 2将使用新的实验测试，如探索测试，以及标准化测试，如马伦，以确定将这些幼儿与其他ASD幼儿区分开来的临床特征。虽然GeoPref测试识别了所有ASD幼儿中37%的大亚组，但需要同样快速和准确的测试来识别其余的ASD幼儿。目标3建议开发新的眼动追踪测试，特别是新的社会定向和母性范式，以检测这些幼儿。随机森林分类算法将识别最能识别ASD幼儿亚组的眼睛注视特征。所有幼儿将在30-36个月时接受最终盲法诊断。

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.