Neural correlates of eye gaze processing in Fragile X Syndrome and Autism Spectru

描述（由申请人提供）：该申请代表了启动研究的一小步，以更好地了解脆性X综合征（FXS）和自闭症谱系障碍（ASD）的共同和不同的神经基础，以及扩大我们对这些疾病的心理生理学的知识。虽然FXS和ASD的个体在症状严重程度和智力功能上存在很大差异，但受影响的个体在社交互动方面存在困难，如使用眼神交流、社交焦虑和社交缺陷、感觉超敏感、运动协调不良、语言发育和模仿迟缓。据报道，脆性X染色体患者中自闭症的患病率为18% - 33%（例如[1-6]）；相反，据报道，ASD患者中FXS的患病率约为2-8%[7,8]。共同注意力缺陷是自闭症患者社交和语言缺陷的最一致的早期预测因素之一（例如，bb0）。在FXS中，最值得注意的行为之一是由于过度唤醒或厌恶（[10]）而引起的目光回避。虽然两组人都表现出眼睛注视功能的受损或改变，但尚不清楚这些行为是否具有相同的潜在神经机制。本项目有三个目标：(1)研究使用事件相关电位测量的神经反应的改变是否在ASD和FXS患者异常注意和使用眼睛注视的行为表型中起作用。(2)观察FXS和ASD个体在低社会需求任务中是否能够使用眼神线索促进行为。(3)在社会要求较高的探索性任务中，确定面孔的神经反应速度是否与注视行为的使用有关。到目前为止，还没有研究同时在FXS和ASD匹配的个体群体中检测这些能力。此外，本项目中提出的ERP测量方法可以在整个生命周期中使用，也可以在认知技能有限的个体中使用，从而允许在两种疾病的表型中使用类似的测量方法。长期目标包括研究注视行为与社会缺陷发展的关系，确定ERP对社会刺激的反应与FXS和ASD的行为表型和生物学标记之间的联系，以及利用ERP了解FXS和ASD的社会缺陷病因，帮助预测结果，并绘制发育进展图。该应用程序是一项试点研究，将展示利用电生理测量来表征脆性X综合征（FXS）和自闭症谱系障碍（ASD）的可行性，重点关注行为障碍的一个共同领域——眼睛注视处理。本项目直接解决以下目标：(1)表征和理解FXS和ASD共同的病理生理机制；(2)了解在FXS的病因或病理生理中起作用并可能与自闭症有关的神经通路、电路和系统；(3)提供两种疾病病程中表型和内表型相似性和差异性的详细表征的研究；(4)电生理研究，以确定FXS和ASD患者的特定异常。

DESCRIPTION (provided by applicant): This application represents a small step in initiating studies to better understand the shared and divergent neurologic underpinnings of Fragile X Syndrome (FXS) and Autism Spectrum Disorder (ASD) as well as to expand our knowledge about the psychophysiology of these disorders. Although there is great variability in symptom severity and intellectual functioning among individuals diagnosed with FXS and ASD, affected individuals have difficulties in social interaction such as use of eye contact, social anxiety and social deficits, sensory hypersensitivity, poor motor coordination, and delayed speech development and echolalia. The prevalence of autism in individuals with Fragile X reported at 18- 33% (e.g., [1-6]); conversely, the prevalence of FXS in individuals with ASD has been reported as approximately 2-8% [7, 8]. Shared attention deficits are one of the most consistent early predictors of social and language deficits in autism (e.g., [9]). In FXS, one of the most noted behaviors is eye gaze avoidance due to hyperarousal or aversiveness ([10]). While both groups demonstrate impairments or alterations in the use of eye gaze, it is unclear if these behaviors share the same underlying neural mechanisms. This project has three goals: (1) to investigate whether alterations in neural responses measured using event-related potentials underlie the behavioral phenotype of abnormal attention to and use of eye gaze in individuals with ASD and FXS. (2) To examine if individuals with FXS and ASD are able to use eye gaze cues to facilitate behavior in a task with low social demand. (3) To determine whether speed of neural response to faces is related to behavioral use of eye gaze in an exploratory task that has high social demand. To date, no studies have concurrently examined these abilities in matched groups of individuals with FXS and ASD. Furthermore, the ERP measures proposed in this project can be used across the lifespan as well as with individuals with limited cognitive skills allowing similar measures to be used across the phenotype of both disorders. Long term objectives include investigation of the relation of eye gaze behaviors to the development of social deficits, identification of links between ERP responses to social stimuli and the behavioral phenotype and biological markers of FXS and ASD, and use of ERPs to understand the etiology of social deficits in FXS and ASD, to help predict outcome, and to chart developmental progress. This application is a pilot study that will demonstrate the feasibility of utilizing electrophysiological measures to characterize Fragile X Syndrome (FXS) and Autism Spectrum Disorder (ASD) by focusing on a common area of behavioral impairment - eye gaze processing. This project directly addresses the goals of: (1) characterizing and understanding of pathophysiological mechanisms common to both FXS and ASD; (2) understanding neural pathways, circuits, and systems that play a role in the etiology or pathophysiology of FXS and may be implicated in autism; (3) studies providing detailed characterization of phenotypic and endophenotypic similarities and distinctions in the course of the two disorders; and (4) electrophysiological studies to identify specific abnormalities in patients with FXS and ASD.