Identification of infants at high‐risk for autism spectrum disorder using multiparameter multiscale white matter connectivity networks

Abstract Autism spectrum disorder is a highly prevalent and highly heritable neurodevelopmental condition, but studies have mostly taken traditional categorical diagnosis approach (yes/no for autism spectrum disorder). In contrast, an emerging notion suggests a continuum model of autism spectrum disorder with a normal distribution of autistic tendencies in the general population, where a full diagnosis is at the severe tail of the distribution. We set out to investigate such a viewpoint by investigating the interaction of polygenic risk scores for autism spectrum disorder and Age2 on neuroimaging measures (cortical thickness and white matter connectivity) in a general population (n = 391, with age ranging from 3 to 21 years from the Pediatric Imaging, Neurocognition and Genetics study). We observed that children with higher polygenic risk for autism spectrum disorder exhibited greater cortical thickness for a large age span starting from 3 years up to ∼14 years in several cortical regions localized in bilateral precentral gyri and the left hemispheric postcentral gyrus and precuneus. In an independent case–control dataset from the Autism Brain Imaging Data Exchange (n = 560), we observed a similar pattern: children with autism spectrum disorder exhibited greater cortical thickness starting from 6 years onwards till ∼14 years in wide-spread cortical regions including (the ones identified using the general population). We also observed statistically significant regional overlap between the two maps, suggesting that some of the cortical abnormalities associated with autism spectrum disorder overlapped with brain changes associated with genetic vulnerability for autism spectrum disorder in healthy individuals. Lastly, we observed that white matter connectivity between the frontal and parietal regions showed significant association with polygenic risk for autism spectrum disorder, indicating that not only the brain structure, but the white matter connectivity might also show a predisposition for the risk of autism spectrum disorder. Our findings showed that the fronto-parietal thickness and connectivity are dimensionally related to genetic risk for autism spectrum disorder in general population and are also part of the cortical abnormalities associated with autism spectrum disorder. This highlights the necessity of considering continuum models in studying the aetiology of autism spectrum disorder using polygenic risk scores and multimodal neuroimaging.

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Relationship Between Cortical Gyrification, White Matter Connectivity, and Autism Spectrum Disorder

Cerebral Cortex ◽

10.1093/cercor/bhw098 ◽

2016 ◽

Vol 26 (7) ◽

pp. 3297-3309 ◽

Cited By ~ 40

Author(s):

C. Ecker ◽

D. Andrews ◽

F. Dell'Acqua ◽

E. Daly ◽

C. Murphy ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

White Matter ◽

Autism Spectrum ◽

Spectrum Disorder ◽

White Matter Connectivity

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Fiber clustering based white matter connectivity analysis for prediction of Autism Spectrum Disorder using diffusion tensor imaging

2016 IEEE 13th International Symposium on Biomedical Imaging (ISBI) ◽

10.1109/isbi.2016.7493331 ◽

2016 ◽

Cited By ~ 5

Author(s):

Fan Zhang ◽

Peter Savadjiev ◽

Weidong Cai ◽

Yang Song ◽

Ragini Verma ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Connectivity Analysis ◽

Fiber Clustering ◽

White Matter Connectivity

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Altered gray-white matter boundary in toddlers at risk for autism relates to later diagnosis of Autism Spectrum Disorder.

10.21203/rs.3.rs-118792/v1 ◽

2020 ◽

Author(s):

Michel Godel ◽

Derek Sayre Andrews ◽

David Gil Amaral ◽

Sally Ozonoff ◽

Gregory S. Young ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

White Matter ◽

High Risk ◽

Early Onset ◽

Structural Mri ◽

Autism Spectrum ◽

Developmental Trajectory ◽

Spectrum Disorder ◽

Typical Development ◽

Diagnostic Outcome

Abstract Background: Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the sharpness of the gray-white matter boundary is decreased in adults with ASD. To determine how the gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index called the gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD. Methods: We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n=20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at three years of age for diagnostic outcome. Three outcome groups were defined (ASD, n=9; typical development, n=8; non-typical development, n=3).Results: ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e. prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.Limitations: Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but the limited size of our sample warrants further replication in independent and larger samples. Conclusion: These results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread areas. Early onset of symptoms constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.

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Altered Gray-White Matter Boundary Contrast in Toddlers at Risk for Autism Relates to Later Diagnosis of Autism Spectrum Disorder

Frontiers in Neuroscience ◽

10.3389/fnins.2021.669194 ◽

2021 ◽

Vol 15 ◽

Author(s):

Michel Godel ◽

Derek S. Andrews ◽

David G. Amaral ◽

Sally Ozonoff ◽

Gregory S. Young ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

White Matter ◽

High Risk ◽

Early Onset ◽

Brain Regions ◽

Autism Spectrum ◽

Developmental Trajectory ◽

Spectrum Disorder ◽

Typical Development ◽

Diagnostic Outcome

BackgroundRecent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD.Materials and MethodsWe used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n = 20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at 3 years of age for diagnostic outcome. Three outcome groups were defined (ASD, n = 9; typical development, n = 8; non-typical development, n = 3).ResultsASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e., prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.LimitationsOur study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples.ConclusionThese preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.

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Altered white matter connectivity as a neural substrate for social impairment in Autism Spectrum Disorder

Cortex ◽

10.1016/j.cortex.2014.10.014 ◽

2015 ◽

Vol 62 ◽

pp. 158-181 ◽

Cited By ~ 149

Author(s):

Stephanie H. Ameis ◽

Marco Catani

Keyword(s):

Autism Spectrum Disorder ◽

White Matter ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Social Impairment ◽

Neural Substrate ◽

White Matter Connectivity

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Altered gray-white matter boundary in toddlers at risk for autism relates to later diagnosis of Autism Spectrum Disorder.

10.21203/rs.3.rs-118792/v2 ◽

2021 ◽

Author(s):

Michel Godel ◽

Derek Sayre Andrews ◽

David Gil Amaral ◽

Sally Ozonoff ◽

Gregory S. Young ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

White Matter ◽

High Risk ◽

Early Onset ◽

Structural Mri ◽

Autism Spectrum ◽

Developmental Trajectory ◽

Spectrum Disorder ◽

Typical Development ◽

Diagnostic Outcome

Abstract Background: Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the sharpness of the gray-white matter boundary is decreased in adults with ASD. To determine how the gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index called the gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD. Methods: We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n=20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at three years of age for diagnostic outcome. Three outcome groups were defined (ASD, n=9; typical development, n=8; non-typical development, n=3).Results: ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e. prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.Limitations: Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but the limited size of our sample characterizes its exploratory nature and warrants further replication in independent and larger samples. Conclusion: These results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread areas. Early onset of symptoms constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.

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Alterations of White Matter Connectivity in Preschool Children with Autism Spectrum Disorder

Radiology ◽

10.1148/radiol.2018170059 ◽

2018 ◽

Vol 288 (1) ◽

pp. 209-217 ◽

Cited By ~ 6

Author(s):

Shi-Jun Li ◽

Yi Wang ◽

Long Qian ◽

Gang Liu ◽

Shuang-Feng Liu ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Preschool Children ◽

White Matter ◽

Children With Autism ◽

Autism Spectrum ◽

Spectrum Disorder ◽

White Matter Connectivity

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Altered Gray-White Matter Boundary Contrast in Toddlers at Risk for Autism Relates to Later Diagnosis of Autism Spectrum Disorder.

10.21203/rs.3.rs-118792/v3 ◽

2021 ◽

Author(s):

Michel Godel ◽

Derek Sayre Andrews ◽

David Gil Amaral ◽

Sally Ozonoff ◽

Gregory S. Young ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

White Matter ◽

High Risk ◽

Early Onset ◽

Brain Regions ◽

Autism Spectrum ◽

Developmental Trajectory ◽

Spectrum Disorder ◽

Typical Development ◽

Diagnostic Outcome

Abstract Background: Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD. Methods: We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n=20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at three years of age for diagnostic outcome. Three outcome groups were defined (ASD, n=9; typical development, n=8; non-typical development, n=3).Results: ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e. prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network.Limitations: Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples. Conclusion: These preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.

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