Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, GA, 30303, USA.
Department of Psychology and Neuroscience Institute, Georgia State University, Atlanta, GA, 30302, USA.
Mol Autism. 2020 Nov 18;11(1):90. doi: 10.1186/s13229-020-00397-4.
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.
自闭症谱系障碍（ASD）固有的异质性对诊断和精准治疗构成了重大挑战。在 ASD 患者中，生物病因、遗传学、神经系统、神经认知特征和临床亚型或表型方面都存在异质性。
本研究旨在从多模态脑影像角度研究 ASD 的异质性。采用自闭症诊断观察量表（ADOS）作为指导功能和结构 MRI 融合的参考。从 ABIDE II 中选择 DSM-IV-TR 诊断的阿斯伯格障碍（n=79）、广泛性发育障碍未特定型[PDD-NOS]（n=58）和孤独症（n=92）作为发现队列，ABIDE I（n=400）作为复制队列。
背外侧前额叶皮层和上/中颞叶皮层是阿斯伯格、PDD-NOS 和孤独症亚组共有的主要功能-结构共变皮质脑区。三个亚型之间的关键差异是皮质下脑区的负性功能特征，包括阿斯伯格亚型特有的负性纹状体-海马旁回低频振幅（fALFF）；PDD-NOS 亚型特有的前扣带回皮质负性 fALFF；孤独症亚型特有的丘脑-杏仁核-尾状核负性 fALFF。此外，每种亚型特异性脑模式与 ADOS 不同亚域相关，以社会互动为共同亚域。确定的亚型特异性模式仅可预测相应亚型表现出的 ASD 症状，而不能预测其他亚型。
尽管 ASD 具有与社会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亚域症状密切相关，这可能有助于从多模态神经影像学角度更好地理解 ASD 异质性的潜在机制。
本研究是基于男性的，不能推广到女性或一般 ASD 人群。
