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交沟通的关键要求。研究大脑对现实生活条件的反应是神经科学中一项具有挑战性的任务，许多研究缺乏生态学有效性。使用自然主义的观看范式，参与者自由地观看电影，同时记录大脑反应，是一种可能性，以调查现实生活条件下的神经反应，具有较高的生态有效性。先前的功能性磁共振成像（fMRI）研究表明，对这种自然主义视听刺激的神经反应及其时间过程（i）在典型发育的成年人中高度相似（即高个体间相关性），但（ii）在患有自闭症谱系障碍（ASD）的成年人中高度可变（即低个体间相关性）。ASD是一种在儿童早期发病的发育障碍，其与受损的社会互动和沟通有关。然而，以前的研究结果对儿童的普遍性，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：（一）在一个大的ASD儿童队列的神经反应自然观看？(ii)ASD患者对自然观视的神经反应如何与症状严重程度相关？(iii)ASD患者对自然观视的神经反应有多具体？我们的目标是解决这些开放的研究问题，通过分析功能磁共振成像数据的自然观从一个正在进行的多中心项目的大队列的儿童和没有ASD。在功能磁共振成像实验中，所有儿童观看同样的电影，其中包含丰富的视听和社会信息。我们计划使用标准方法来确定在这种自然观察期间大脑反应的时间过程，即，学科间相关分析我们的目标是分析至少200名ASD儿童和200名正常发育儿童（年龄，性别和认知能力匹配）的fMRI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名患有注意缺陷多动障碍（ADHD）的匹配儿童的神经反应概况，ADHD是另一种神经发育状况，与ASD有部分共同的病因。将ASD和ADHD儿童进行比较将进一步了解这两种临床疾病的不同和共同特征，从而具有临床意义。此外，我们的研究结果，我们将告知社会加工的基本机制，在非典型以及在典型的发展具有高生态效度。大队列研究将提供高统计可靠性的结果，从而满足目前神经科学不断增长的需求。

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.