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

识别自闭症谱系障碍（ASD）的早期体征以改善发育结果至关重要。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ASD的迹象，但在前12个月寻找ASD的行为标志物已被证明特别具有挑战性。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。通过我们自己（和其他人）对ASD的神经基础和早期指标的研究，项目I的总体目标是确定ASD超高危（UHR）婴儿的可靠生物标志物，即有一个以上的ASD哥哥姐姐。我们正在采取一种创新的、假设驱动的、多模式的方法，该方法使用眼动跟踪、瞳孔测量、电生理学（EEG）和磁共振成像（MRI）来跟踪这些婴儿在生命第一年的发育，重点关注社会注意力、内隐学习和大脑连接。因此，我们将使用眼动追踪和瞳孔测量范式捕捉动态的社会互动，量化注意力的发展，并与社会相关的刺激参与。我们将使用创新的事件相关电生理测量和功能磁共振成像来研究内隐学习的神经相关性。我们将使用EEG和MRI表征功能和结构连接的发展。总的来说，我们希望检测到UHR婴儿在这些社会和认知领域以及神经过程中的发育途径改变，与低风险婴儿（LR）相比，并且所提出的措施将预测36个月时的ASD诊断。

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.