scMRI Reveals Large-Scale Brain Network Abnormalities in Autism

Autism is a complex neurological condition characterized by childhood onset of dysfunction in multiple cognitive domains including socio-emotional function, speech and language, and processing of internally versus externally directed stimuli. Although gross brain anatomic differences in autism are well established, recent studies investigating regional differences in brain structure and function have yielded divergent and seemingly contradictory results. How regional abnormalities relate to the autistic phenotype remains unclear. We hypothesized that autism exhibits distinct perturbations in network-level brain architecture, and that cognitive dysfunction may be reflected by abnormal network structure. Network-level anatomic abnormalities in autism have not been previously described. We used structural covariance MRI to investigate network-level differences in gray matter structure within two large-scale networks strongly implicated in autism, the salience network and the default mode network, in autistic subjects and age-, gender-, and IQ-matched controls. We report specific perturbations in brain network architecture in the salience and default-mode networks consistent with clinical manifestations of autism. Extent and distribution of the salience network, involved in social-emotional regulation of environmental stimuli, is restricted in autism. In contrast, posterior elements of the default mode network have increased spatial distribution, suggesting a ‘posteriorization’ of this network. These findings are consistent with a network-based model of autism, and suggest a unifying interpretation of previous work. Moreover, we provide evidence of specific abnormalities in brain network architecture underlying autism that are quantifiable using standard clinical MRI.

自闭症（Autism）是一种复杂的神经病症，起病于儿童期，以多认知领域功能障碍为特征，涵盖社会情感功能、言语语言功能，以及内部与外部定向刺激的加工处理。尽管自闭症患者的整体大脑解剖结构差异已被充分证实，但近期针对大脑结构与功能的区域差异展开的研究却得出了分歧且看似相互矛盾的结果。区域脑异常与自闭症表型之间的关联机制仍不明确。我们提出假说：自闭症患者的大脑网络级架构存在特异性扰动，且认知功能障碍可通过异常的网络结构得以体现。此前尚未有针对自闭症患者的网络级解剖异常的相关研究报道。我们采用结构协变磁共振成像（structural covariance MRI）技术，对自闭症患者与年龄、性别、智商匹配的健康对照者，在与自闭症高度相关的两大大规模网络——突显网络（salience network）和默认模式网络（default mode network）——中，探究灰质结构的网络级差异。我们观测到，自闭症患者的突显网络与默认模式网络的脑网络架构存在特异性扰动，这与自闭症的临床表现相符。参与环境刺激社会情感调节的突显网络，其范围在自闭症患者中受限。与之相反，默认模式网络的后部区域空间分布范围扩大，提示该网络出现了“后部化（posteriorization）”现象。这些研究结果契合基于网络的自闭症致病模型，可为既往相关研究提供统一的解释框架。此外，我们证实，自闭症患者的大脑网络架构存在特异性异常，这类异常可通过标准临床磁共振成像技术实现量化检测。