BACKGROUND Autism spectrum disorder (ASD) is a neurodevelopmental condition with key deficits in social functioning. It is widely assumed that the biological underpinnings of social impairment are neurofunctional alterations in the "social brain," a neural circuitry involved in inferring the mental state of a social partner. However, previous evidence comes from small-scale studies and findings have been mixed. We therefore carried out the to-date largest study on neural correlates of mentalizing in ASD. METHODS As part of the Longitudinal European Autism Project, we performed functional magnetic resonance imaging at six European sites in a large, well-powered, and deeply phenotyped sample of individuals with ASD (N = 205) and typically developing (TD) individuals (N = 189) aged 6 to 30 years. We presented an animated shapes task to assess and comprehensively characterize social brain activation during mentalizing. We tested for effects of age, diagnosis, and their association with symptom measures, including a continuous measure of autistic traits. RESULTS We observed robust effects of task. Within the ASD sample, autistic traits were moderately associated with functional activation in one of the key regions of the social brain, the dorsomedial prefrontal cortex. However, there were no significant effects of diagnosis on task performance and no effects of age and diagnosis on social brain responses. Besides a lack of mean group differences, our data provide no evidence for meaningful differences in the distribution of brain response measures. Extensive control analyses suggest that the lack of case-control differences was not due to a variety of potential confounders. CONCLUSIONS Contrary to prior reports, this large-scale study does not support the assumption that altered social brain activation during mentalizing forms a common neural marker of ASD, at least with the paradigm we employed. Yet, autistic individuals show socio-behavioral deficits. Our work therefore highlights the need to interrogate social brain function with other brain measures, such as connectivity and network-based approaches, using other paradigms, or applying complementary analysis approaches to assess individual differences in this heterogeneous condition.

中文翻译：

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大型自闭症队列心智化过程中的社会大脑激活：纵向欧洲自闭症项目。

背景自闭症谱系障碍（ASD）是一种神经发育疾病，具有关键的社会功能缺陷。人们普遍认为，社交障碍的生物学基础是“社交大脑”的神经功能改变，这是一种参与推断社交伙伴精神状态的神经回路。然而，以前的证据来自小规模研究，结果好坏参半。因此，我们对 ASD 心智化的神经相关性进行了迄今为止规模最大的研究。方法 作为纵向欧洲自闭症项目的一部分，我们在六个欧洲地点对 ASD（N = 205）和典型发育（TD）个体（N = 189) 6 至 30 岁。我们提出了一个动画形状任务来评估和全面描述心理化过程中的社会大脑激活。我们测试了年龄、诊断及其与症状测量的关联，包括对自闭症特征的连续测量。结果 我们观察到任务的稳健效果。在 ASD 样本中，自闭症特征与社交大脑的关键区域之一——背内侧前额叶皮层的功能激活中度相关。然而，诊断对任务表现没有显着影响，年龄和诊断对社会大脑反应没有影响。除了缺乏平均组差异外，我们的数据没有提供证据表明大脑反应测量分布存在有意义的差异。广泛的对照分析表明，病例对照差异的缺乏不是由于各种潜在的混杂因素。结论 与之前的报告相反，这项大规模研究不支持这样的假设，即在心智化过程中改变的社会大脑激活形成 ASD 的常见神经标志物，至少在我们采用的范式中是这样。然而，自闭症个体表现出社会行为缺陷。因此，我们的工作强调了使用其他范式或应用补充分析方法来评估这种异质性条件下的个体差异等其他大脑测量方法（例如连接性和基于网络的方法）来询问社会大脑功能的必要性。这项大规模研究不支持这样的假设，即在心智化过程中改变的社会大脑激活形成了 ASD 的常见神经标志物，至少在我们采用的范式中是这样。然而，自闭症个体表现出社会行为缺陷。因此，我们的工作强调了使用其他范式或应用补充分析方法来评估这种异质性条件下的个体差异等其他大脑测量方法（例如连接性和基于网络的方法）来询问社会大脑功能的必要性。这项大规模研究不支持这样的假设，即在心智化过程中改变的社会大脑激活形成了 ASD 的常见神经标志物，至少在我们采用的范式中是这样。然而，自闭症个体表现出社会行为缺陷。因此，我们的工作强调了使用其他范式或应用补充分析方法来评估这种异质性条件下的个体差异等其他大脑测量方法（例如连接性和基于网络的方法）来询问社会大脑功能的必要性。