Neonatal connectome as a predictor of social and attentional impairment in ASD

新生儿连接组作为 ASD 社交和注意力障碍的预测因子

• 批准号: 10240559
• 负责人: KATARZYNA CHAWARSKA
• 金额: $ 24.36万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-07 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240559
• 关键词: Address; Affect; Affective Symptoms; Age; Attention; Birth; Brain; Categories; Child; Clinic; Cognitive; Diagnosis; Diagnostic; Dimensions; Disease; Environment; Exhibits; Face; Female; Foundations; Functional Imaging; Grouping; Impairment; Individual Differences; Infant; Magnetic Resonance Imaging; Monitor; Neonatal; Newborn Infant; Newly Diagnosed; Outcome; Pattern; Performance; Play; Property; Recording of previous events; Rest; Risk; Role; School-Age Population; Science; Severities; Sex Differences; Siblings; Social Development; Social Functioning; Symptoms; Toddler; autism spectrum disorder; autistic children; base; cellular imaging; cognitive development; connectome; executive function; experience; high risk; imaging approach; molecular imaging; neonate; neurodevelopment; psychologic; reduce symptoms; relating to nervous system; sex risk; social; social attention; visual tracking

Limited attention to faces of conspecifics constitutes one of the markers of ASD.1-4 Limited attention to faces is associated with increased severity of autism symptoms and poor adaptive functioning,5-8 and early individual differences in attention to faces contribute to the variability in later social and cognitive outcomes.5 Attention to faces is enhanced in 6-month-old unaffected females at familial risk for ASD and predicts better social functioning 1.5 years later.9 Despite the well-documented role that monitoring faces of conspecifics plays in socio-cognitive development, the brain mechanisms underlying such deficits in ASD are unknown and treatments typically focus on ameliorating symptoms rather than addressing underlying causes. Considering that signs of atypical attention to faces are evident by 6 to 9 months in infants later diagnosed with ASD both in laboratory1-3, 10 and real-world environments, 11-13, [Preliminary Study (PS#1)], we hypothesize that the neural foundations for these impairments are already reflected in functional brain organization (the connectome) at birth. Attentional functions in the brain are subserved by the Salience Network (SN), the Executive Control Network (ECN), and the Default Mode Network (DMN), all of which have been implicated in ASD,14-16 and have been found to be atypical in newborns at risk for ASD due to non-familial factors (PS#2). Here we propose to examine whether, when compared to unaffected high-risk (HR) and low-risk (LR) newborns, HR newborns who, at 24 months, meet criteria for ASD exhibit abnormal strength of functional connectivity within the three networks. We will also examine whether the strength of functional connectivity in the three networks at birth is predictive of later performance on a selective social attention (SSA) eye-tracking task at 6 and 24 months and severity of autism symptoms at 24 months. By targeting neonates, we plan to investigate properties of attentional networks known to be affected in ASD14-16 before they are shaped extensively by extra-uterine experience. To achieve these aims, we propose to study 120 neonates who have an older sibling with ASD (HR) and 30 neonates without familial history of ASD (LR). The neonates will undergo a resting-state functional connectivity MRI (rs fcMRI) at 42-44 post-menstrual weeks and at 6 and 24 months will be administered the SSA task. Performance on this task discriminates between ASD and non-ASD groups during prodromal stages of the disorder in high-risk siblings of children with ASD,1 in clinic-referred toddlers newly diagnosed with ASD,17 and in school-age children (PS#3) and shows strong associations with autism symptom severity5 (PS#3). Diagnostic assessment will be completed at 24 months through which severity of autism symptoms and diagnostic grouping will be determined. The project advances integration of psychological and brain science in autism by investigating whether functional brain organization in ASD is altered at birth and, if so, how this disruption affects social development in infants at risk for ASD.

对特异性面孔的注意力有限构成ASD的标记之一。1-4对面孔的关注有限是 与自闭症症状的严重程度增加和自适应功能不佳有关，5-8和早期个体 对面孔的关注差异有助于以后的社会和认知结果的可变性。5注意 在6个月大的未受影响的ASD风险的6个月大的女性中，面孔得到了增强，并预测更好的社交 1。5年后运行。9尽管有据可查的作用，监测了特定面孔的作用 社会认知发展，ASD中这种缺陷的脑机制是未知的，并且 治疗通常集中于改善症状，而不是解决基本原因。考虑 在后来被诊断为ASD的婴儿中，有6至9个月的ASD都在6至9个月中显而易见地表明了面孔的非典型迹象 实验室1-3、10和现实世界环境，11-13，[初步研究（PS＃1）]，我们假设神经 这些障碍的基础已经反映在功能性脑组织（连接组）中 出生。大脑的注意功能由显着网络（SN）（执行控制）提供 网络（ECN）和默认模式网络（DMN），所有这些网络都涉及ASD，14-16 由于非家族因素，发现有ASD风险的新生儿中发现是非典型的（PS＃2）。在这里我们建议 检查与未受影响的高风险（HR）和低风险（LR）新生儿相比，HR Newborns是否 在24个月时 网络。我们还将检查出生时三个网络中功能连接的强度是否是 预测6个月和24个月的选择性社会关注（SSA）的眼睛追踪任务的后来表现 自闭症症状的严重程度在24个月时。通过针对新生儿，我们计划研究 注意网络已知在ASD14-16中受到影响，然后被外部局部广泛塑造 经验。为了实现这些目标，我们建议研究120名与ASD的兄弟姐妹的新生儿 （HR）和30个没有ASD家族史的新生儿（LR）。新生儿将经历静止状态的功能 连通性MRI（RS FCMRI）在月经后几周和6和24个月时进行 SSA任务。该任务的性能在前驱阶段区分ASD和非ASD组 ASD儿童高风险兄弟姐妹的疾病，诊所引用的1个新诊断的幼儿 ASD，17岁和学龄儿童（PS＃3），并显示自闭症症状严重性的密切关联5 （PS＃3）。诊断评估将在24个月内完成，自闭症症状的严重程度 并将确定诊断分组。该项目推进了心理和大脑的整合 通过调查ASD的功能性大脑组织是否在出生时发生改变，如果是的，则是自闭症科学 这种破坏如何影响有ASD风险的婴儿的社会发展。