Neural mechanisms of naturalistic viewing in children with autism or ADHD

快速、准确地处理复杂、动态的听觉和视觉信息是成功的社会沟通的关键要求。在神经科学中，研究大脑对现实环境的反应是一项具有挑战性的任务，许多研究缺乏生态有效性。使用自然观影范式，即参与者自由地观看电影，同时记录大脑的反应，是研究神经对现实生活条件的反应的一种可能性，具有很高的生态有效性。以往的功能性磁共振成像（fMRI）研究表明，正常发育成人对这种自然视听刺激及其时间过程的神经反应(i)高度相似（即高个体间相关性），但（ii）自闭症谱系障碍（ASD）成人对这种自然视听刺激的神经反应（ii）高度可变（即低个体间相关性）。ASD是一种发生在儿童早期的发育障碍，与社会互动和沟通障碍有关。然而，既往结果在儿童中的普遍性、与ASD症状严重程度的关系以及对ASD的特异性尚不清楚。在这里，我们的目标是解决以下三个新的研究问题：(i)在一大群自闭症儿童中，自然观看的神经反应是什么？（ii） ASD对自然观看的神经反应与症状严重程度有何关系？（iii）自闭症患者对自然观看的神经反应有多特异性？我们的目标是通过分析来自正在进行的多中心项目的大量有和没有ASD的儿童的自然观察的fMRI数据来解决这些开放的研究问题。在fMRI实验中，所有的孩子都观看了同样的电影，这些电影包含了丰富的视听和社会信息。我们计划用一种标准的方法，即主体间相关分析，来确定这种自然观看过程中大脑反应的时间过程。我们的目标是分析至少200名自闭症儿童和200名正常发育儿童（年龄、性别和认知能力相匹配）的功能磁共振成像数据。我们将分析ASD亚型，使用标准诊断评分将这些神经反应与症状严重程度联系起来。为了研究ASD的特异性，我们还将分析和比较至少200名匹配的注意缺陷多动障碍（ADHD）儿童的神经反应谱。ADHD是另一种神经发育疾病，被认为与ASD有部分共同的病因。比较ASD和ADHD儿童将进一步了解这两种临床状况的不同和共同特征，从而具有临床相关性。此外，通过我们的研究结果，我们将了解具有高生态效度的非典型发展和典型发展的社会加工的基本机制。对大型队列的调查将提供高统计可靠性的结果，从而满足当前神经科学日益增长的需求。

The fast and accurate processing of complex, dynamic auditory and visual information is a key requirement for successful social communication. Investigating brain responses to real-life conditions is a challenging task in neuroscience and many studies lack ecological validity. The use of naturalistic viewing paradigms, where participants freely watch a movie while brain responses are recorded is one possibility to investigate neural responses to real-life conditions with high ecological validity. Previous functional magnetic resonance imaging (fMRI) studies showed that the neural responses to such naturalistic audio-visual stimuli and its time courses are (i) highly similar across typically developing adults (i.e. high inter-individual correlation) but (ii) highly variable (i.e. low inter-individual correlation) across adults with an autism spectrum disorder (ASD). ASD is a developmental disorder with onset in early childhood which is associated with impaired social interaction and communication. However, the generalisability of previous results to childhood, the relation to ASD symptom severity and the specificity to ASD are unclear. Here, we aim to address the following three novel research questions: (i) What are the neural responses to naturalistic viewing in a large cohort of children with ASD? (ii) How are the neural responses to naturalistic viewing related to symptom severity in ASD? (iii) How specific are the neural responses to naturalistic viewing for ASD? We aim to address these open research questions by analysing fMRI data on naturalistic viewing from large cohorts of children with and without ASD from an ongoing multi-center project. During the fMRI experiment, all children watch the same movies, which contain rich audio-visual and social information. We plan to identify the time courses of brain responses during this naturalistic viewing using a standard approach, i.e., inter-subject correlation analysis. We aim to analyse fMRI data from at least 200 children with ASD and 200 typically developing children (matched on age, sex and cognitive abilities). We will analyse ASD subtypes to relate these neural responses to symptom severity using standard diagnostic scores. To investigate the specificity for ASD, we will additionally analyse and compare the neural response profiles from at least 200 matched children with attention deficit hyperactive disorder (ADHD), another neurodevelopmental condition with an assumed partly common aetiology with ASD. Comparing children with ASD and ADHD will further inform about distinct and common features of the two clinical conditions and will thus have clinical relevance. Further, with our results, we will inform about basic mechanisms of social processing in atypical as well in as in typical development with high ecological validity. The investigation of large cohorts will provide results of high statistical reliability and thus meet a currently growing demand in neuroscience.