Common and unique multimodal covarying patterns in autism spectrum disorder subtypes

• Type of Material: Article
• Authors: Shile Qi, Emory University; Robin Morris, Georgia State University; Jessica A. Turner, Georgia State University; Zening Fu, Emory University; Rongtao Jiang, Chinese Academy of Sciences; Thomas P. Deramus, Emory University; Dongmei Zhi, Chinese Academy of Sciences; Vince D. Calhoun, Emory University; Jing Sui, Emory University
• Language: English
• Date: 2020-12-18
• Publisher: BMC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13229-020-00397-4
• Title of Journal or Parent Work: MOLECULAR AUTISM
• Volume: 11
• Issue: 1
• Start Page: 90
• End Page: 90
• Grant/Funding Information: This work is supported in part by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDBS32040100), China Natural Science Foundation (No. 61773380), Beijing Municipal Science and Technology Commission (No. Z181100001518005), the National Institute of Health (1R01MH117107, R01EB020407, 1R01EB005846, 1R01MH094524, P20GM103472, P30GM122734) and the National Science Foundation (1539067).
• Keywords: CONNECTIVITY; Multimodal fusion; Neurosciences; HETEROGENEITY; Life Sciences & Biomedicine; DEFICITS; BRAIN; Genetics & Heredity; Autism spectrum disorder; Asperger’ Autistic disorder; Science & Technology; Pervasive developmental disorder-not otherwise specified (PDD-NOS); s disorder; NEUROMARKERS; Heterogeneity; Neurosciences & Neurology
• Research Categories: Biology, Neuroscience; Biology, Genetics; Psychology, Cognitive

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. LIMITATIONS: This study is male based, which cannot be generalized to the female or the general ASD population.