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.

对同种人的面孔注意力有限是 ASD 的标志之一。1-4 对面孔的注意力有限是 与自闭症症状严重程度增加和适应功能差相关，5-8 和早期个体 对面孔的关注差异会导致后来的社交和认知结果的差异。5 对面孔的关注 6 个月大、未受影响、有自闭症谱系障碍家族风险的女性的面部表情增强，并预示着更好的社交能力 1.5 年后开始运行。9 尽管监控同种人的面孔在 社会认知发展，自闭症谱系障碍中这种缺陷背后的大脑机制尚不清楚， 治疗通常侧重于改善症状，而不是解决根本原因。考虑到 在后来被诊断为自闭症谱系障碍 (ASD) 的婴儿中，到 6 至 9 个月时，对面部的非典型关注迹象就很明显。 实验室1-3、10和现实世界环境11-13，[初步研究（PS#1）]，我们假设神经网络 这些损伤的基础已经反映在功能性大脑组织（连接组）中 出生。大脑中的注意力功能受到显着网络（SN）的支持，即执行控制 网络 (ECN) 和默认模式网络 (DMN)，所有这些都与 ASD 相关，14-16 并且具有 被发现在因非家族因素而有 ASD 风险的新生儿中不典型 (PS#2)。在此我们建议 检查与未受影响的高风险 (HR) 和低风险 (LR) 新生儿相比，HR 新生儿是否 24 个月时，符合自闭症谱系障碍 (ASD) 标准的人在三个方面表现出异常的功能连接强度 网络。我们还将检查出生时三个网络的功能连接强度是否 预测 6 个月和 24 个月时选择性社会注意力 (SSA) 眼动追踪任务的后续表现 24 个月时自闭症症状的严重程度。通过针对新生儿，我们计划研究 已知在 ASD14-16 中注意力网络在被子宫外广泛塑造之前受到影响 经验。为了实现这些目标，我们建议对 120 名有患有 ASD 的哥哥姐姐的新生儿进行研究 (HR) 和 30 名无 ASD 家族史的新生儿 (LR)。新生儿将经历静息态功能 将在月经后 42-44 周以及 6 个月和 24 个月时进行连通性 MRI (rs fcMRI) SSA 任务。在前驱阶段，自闭症谱系障碍组和非自闭症谱系障碍组在这项任务上的表现存在差异 患有自闭症谱系障碍 (ASD) 儿童的高危兄弟姐妹中患有这种疾病的情况，1 在临床转诊的新诊断患有自闭症谱系障碍 (ASD) 的幼儿中 自闭症谱系障碍 (ASD)17 和学龄儿童 (PS#3) 与自闭症症状严重程度密切相关5 （PS＃3）。诊断评估将在 24 个月时完成，在此期间自闭症症状的严重程度 并确定诊断分组。该项目促进心理和大脑的整合 自闭症科学通过调查自闭症患者的大脑功能组织在出生时是否发生改变，如果是这样， 这种破坏如何影响有自闭症谱系障碍风险的婴儿的社会发展。