Eyeblink conditioning in school-aged children with ASD

描述(由申请人提供)：我们的项目寻求应用脑功能的客观行为测量，可以确定自闭症谱系障碍(ASD)中神经功能障碍的部位。我们的范例将是一种强大的联想学习措施-巴甫洛夫眨眼条件反射(EBC)-评估患有自闭症的学龄儿童大脑高级功能的基本组成部分可能会受到破坏。受试者将是99名10岁的儿童，他们目前正在参加两项纵向研究中的一项：1)早期行为干预对自闭症儿童认知发展的影响；2)导致自闭症的神经化学和神经结构风险因素。值得注意的是，我们所有的受试者在24个月大的时候都进行了神经化学和结构成像，以及到目前为止正在进行的纵向临床和行为评估。该项目建立在强有力的初步数据的基础上，表明ASD的严重程度与EBC的表现缺陷是相关的。我们的目标是将EBC应用于一组控制良好的儿童，这些儿童的ASD病史已被广泛记录，以确定EBC是否有助于了解长期的发育结果。由于这些儿童在大约24个月大的时候接受了高分辨率的大脑解剖扫描和神经化学成像，我们现在可以将EBC表现的变异性与早期大脑形态和新陈代谢的变化联系起来。EBC的一个优点是它不需要语言、社交或积极参与。 因此，EBC可以同样适用于高功能和极低功能的自闭症儿童，这些儿童的行为发育定量测量很难获得。该项目将产生以下影响：1)它将解决对ASD发育过程和结果的长期结果研究的关键需求；2)它将有助于确定ASD的潜在神经机制；3)它可能指向在更早的年龄实施EBC，以评估ASD的风险。

DESCRIPTION (provided by applicant): Our project seeks to apply an objective behavioral measure of brain function that may identify sites of neural dysfunction in autism spectrum disorder (ASD). Our paradigm will be a robust measure of associative learning - Pavlovian eyeblink conditioning (EBC) - to assess how fundamental building-blocks of higher brain function may be disrupted in school-aged children with ASD. The subjects will be 99 10-year-old children that are currently participating in one of two longitudinal studies examining: 1) the effet of an early behavioral intervention on the cognitive development of children with ASD; and 2) the neurochemical and neurostructural risk factors for developing ASD. Of note is that all of our subjects have had neurochemical and structural imaging at 24 months of age along with ongoing longitudinal clinical and behavioral assessments up to the current time. The project builds upon strong preliminary data demonstrating that ASD severity and EBC performance deficits are related. Our goal is to apply EBC in a well-controlled group of children whose ASD history has been extensively documented to determine whether EBC can aid in understanding long-term developmental outcome. Because the children had high-resolution anatomical brain scans and neurochemical imaging at approximately 24 months of age, we can now relate variability in EBC performance to alterations in early brain morphology and metabolism. An advantage of EBC is that it does not require language, social interaction, or active participation. Thus, EBC can be applied equally to high-functioning children and very low- functioning children with ASD for whom quantitative measures of behavioral development are difficult to obtain. The project will have the following impact: 1) it will address a crucial need for long-term outcome studies of developmental processes and outcomes in ASD; 2) it will help to identify the underlying neural mechanisms of ASD; 3) it could point to implementing EBC at earlier ages to assess ASD risk.