Neural assays and longitudinal assessment of infants at very high risk for ASD

自闭症谱系障碍极高风险婴儿的神经分析和纵向评估

• 批准号: 8426256
• 负责人: SCOTT P JOHNSON
• 金额: $ 18.6万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-06 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8426256
• 关键词: Age; Age-Months; Arousal; Attention; Auditory; Autistic Disorder; Behavior; Behavioral; Binding; Biological Assay; Biological Markers; Biological Markers; Birth; Brain; Child; Cognitive; Cueing for speech; Detection; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Distress; Early treatment; Electrophysiology (science); Event; Eye; Face; Family; Functional Magnetic Resonance Imaging; Genes; Goals; Image; Individual; Infant; Infant Development; Instruction; Language; Learning; Life; Link; Magnetic Resonance Imaging; Measures; Modeling; Mydriasis; Names; Outcome; Pathway interactions; Pattern; Phenotype; Process; Proxy; Quality of life; Reaction; Research; Rest; Rewards; Risk; Sampling; Screening procedure; Shapes; Siblings; Social Interaction; Social Values; Speech; Stimulus; Testing; Toddler; Visual; Work; auditory stimulus; autism spectrum disorder; base; disorder risk; effective intervention; frontal lobe; genetic risk factor; high risk; high risk infant; improved; infancy; innovation; joint attention; language processing; neuromechanism; relating to nervous system; response; sample fixation; sequence learning; skills; social; visual stimulus; white matter

It is essential to identify the early signs of autism spectrum disorders (ASD) in order to improve developmental outcomes. While recent evidence suggests that the assessment of a wide range of skills and behaviors may help identify signs of ASD in the second year of life, the search for behavioral markers of ASD in the first 12 months has proven particularly challenging. This challenge is likely due to the limited behavioral repertoire of infants in the first year of life, thus motivating the search for more sensitive biomarkers. Informed by our own (and others') work on the neural basis and early indicators of ASD, the overarching aim of Project I is to identify reliable biological markers of ASD in infants at ultra-high risk (UHR) for the disorder, i.e. having more than one older sibling with ASD. We are taking an innovative, hypothesis driven, multi-modal approach, which uses eye tracking, pupillometry, electrophysiology (EEG), and magnetic resonance imaging (MRI) to track these infants' development in the first year of life, with focus on social attention, implicit learning, and brain connectivity. Accordingly, we will quantify the development of attention to, and engagement with, socially relevant stimuli, using eye-tracking and pupillometry paradigms capturing dynamic social interactions. We will examine the neural correlates of implicit learning using innovative event-related electrophysiological measures and functional MRI. And we will characterize the development of functional and structural connectivity using EEG and MRI. Overall, we expect to detect altered developmental pathways in these social and cognitive domains and neural processes in UHR infants, as compared to low risk infants (LR), and that the proposed measures will be predictive of an ASD diagnosis at 36 months.

为了改善发育结果，识别自闭症谱系障碍（ASD）的早期症状至关重要。虽然最近的证据表明，对广泛的技能和行为的评估可能有助于在生命的第二年识别自闭症谱系障碍的迹象，但在头12个月寻找自闭症谱系障碍的行为标志被证明是特别具有挑战性的。这一挑战可能是由于婴儿在出生后第一年的行为能力有限，因此促使人们寻找更敏感的生物标志物。根据我们自己（和其他人）在自闭症谱系障碍的神经基础和早期指标方面的工作，项目1的总体目标是在自闭症超高风险（UHR）婴儿（即有一个以上的兄弟姐妹患有自闭症谱系障碍）中确定可靠的自闭症谱系障碍生物学标志物。我们正在采用一种创新的、假设驱动的、多模式的方法，使用眼动追踪、瞳孔测量、电生理（EEG）和磁共振成像（MRI）来追踪这些婴儿在生命第一年的发展，重点关注社会注意力、内隐学习和大脑连接。因此，我们将量化对社会相关刺激的关注和参与的发展，使用眼球追踪和瞳孔测量范式捕捉动态社会互动。我们将使用创新的事件相关电生理测量和功能MRI来检查内隐学习的神经相关性。我们将用脑电图和核磁共振成像来描述功能和结构连接的发展。总的来说，与低风险婴儿（LR）相比，我们期望在UHR婴儿中检测到这些社会和认知领域以及神经过程的发育途径的改变，并且建议的措施将在36个月时预测ASD诊断。