The heterogeneity inherent in autism spectrum disorder (ASD) presents a substantial challenge to diagnosis and precision treatment. Heterogeneity across biological etiologies, genetics, neural systems, neurocognitive attributes and clinical subtypes or phenotypes has been observed across individuals with ASD. In this study, we aim to investigate the heterogeneity in ASD from a multimodal brain imaging perspective. The Autism Diagnostic Observation Schedule (ADOS) was used as a reference to guide functional and structural MRI fusion. DSM-IV-TR diagnosed Asperger’s disorder (n = 79), pervasive developmental disorder-not otherwise specified [PDD-NOS] (n = 58) and Autistic disorder (n = 92) from ABIDE II were used as discovery cohort, and ABIDE I (n = 400) was used for replication. Dorsolateral prefrontal cortex and superior/middle temporal cortex are the primary common functional–structural covarying cortical brain areas shared among Asperger’s, PDD-NOS and Autistic subgroups. Key differences among the three subtypes are negative functional features within subcortical brain areas, including negative putamen–parahippocampus fractional amplitude of low-frequency fluctuations (fALFF) unique to the Asperger’s subtype; negative fALFF in anterior cingulate cortex unique to PDD-NOS subtype; and negative thalamus–amygdala–caudate fALFF unique to the Autistic subtype. Furthermore, each subtype-specific brain pattern is correlated with different ADOS subdomains, with social interaction as the common subdomain. The identified subtype-specific patterns are only predictive for ASD symptoms manifested in the corresponding subtypes, but not the other subtypes. Although ASD has a common neural basis with core deficits linked to social interaction, each ASD subtype is strongly linked to unique brain systems and subdomain symptoms, which may help to better understand the underlying mechanisms of ASD heterogeneity from a multimodal neuroimaging perspective. This study is male based, which cannot be generalized to the female or the general ASD population.

中文翻译：

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自闭症谱系障碍亚型中常见和独特的多峰共变模式

自闭症谱系障碍 (ASD) 固有的异质性对诊断和精准治疗提出了重大挑战。在 ASD 个体中观察到了生物病因、遗传学、神经系统、神经认知属性和临床亚型或表型的异质性。在这项研究中，我们旨在从多模态脑成像的角度研究 ASD 的异质性。自闭症诊断观察表 (ADOS) 被用作指导功能和结构 MRI 融合的参考。来自 ABIDE II 的 DSM-IV-TR 诊断出的阿斯伯格症 (n = 79)、广泛性发育障碍 - 未另作说明 [PDD-NOS] (n = 58) 和自闭症 (n = 92) 被用作发现队列，而 ABIDE I (n = 400) 用于复制。背外侧前额叶皮层和上/中颞叶皮层是阿斯伯格、PDD-NOS 和自闭症亚组共享的主要常见功能-结构共变皮层大脑区域。三种亚型之间的主要区别是皮层下脑区的负功能特征，包括阿斯伯格亚型特有的负壳核 - 海马旁低频率波动幅度分数 (fALFF)；PDD-NOS 亚型特有的前扣带皮层 fALFF 呈阴性；和阴性丘脑 - 杏仁核 - 尾状核 fALFF 是孤独症亚型独有的。此外，每个亚型特定的大脑模式都与不同的 ADOS 子域相关，社交互动是共同的子域。确定的亚型特异性模式仅能预测相应亚型中表现出的 ASD 症状，但不是其他亚型。尽管 ASD 具有与社交互动相关的核心缺陷的共同神经基础，但每个 ASD 亚型都与独特的大脑系统和子域症状密切相关，这可能有助于从多模态神经影像学的角度更好地理解 ASD 异质性的潜在机制。本研究以男性为基础，不能推广到女性或一般 ASD 人群。