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Cited by 37Functional Brain Connectivity StudiesAutism Spectrum Disorder ResearchGenetics and Neurodevelopmental Disorders

Functional connectivity subtypes associate robustly with ASD diagnosis

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Urchs, Sebastian GW, Tam, Angela, Orban, Pierre, Moreau, Clara, Benhajali, Yassine, Nguyen, Hien Duy, Evans, Alan C, Bellec, Pierre·2022·eLife
DOI 10.7554/elife.56257PMC PMC9708070

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Abstract

Our understanding of the changes in functional brain organization in autism is hampered by the extensive heterogeneity that characterizes this neurodevelopmental disorder. Data driven clustering offers a straightforward way to decompose autism heterogeneity into subtypes of connectivity and promises an unbiased framework to investigate behavioral symptoms and causative genetic factors. Yet, the robustness and generalizability of functional connectivity subtypes is unknown. Here, we show that a simple hierarchical cluster analysis can robustly relate a given individual and brain network to a connectivity subtype, but that continuous assignments are more robust than discrete ones. We also found that functional connectivity subtypes are moderately associated with the clinical diagnosis of autism, and these associations generalize to independent replication data. We explored systematically 18 different brain networks as we expected them to associate with different behavioral profiles as well as different key regions. Contrary to this prediction, autism functional connectivity subtypes converged on a common topography across different networks, consistent with a compression of the primary gradient of functional brain organization, as previously reported in the literature. Our results support the use of data driven clustering as a reliable data dimensionality reduction technique, where any given dimension only associates moderately with clinical manifestations.

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  • Abnormalities in the corpus callosum and interhemispheric connectivity are linked to many neurodevelopmental disorders, including ASD and SCZ.

    “a wealth of evidence links abnormalities in the corpus callosum and interhemispheric connectivity (driven by callosal projection neurons) to many neurodevelopmental disorders, among them ASD and SCZ2,3,111,112.”

    From CYFIP1 governs the development of cortical axons by modulating calcium availability (2025) · cites this paper as [111]

    The Results section reports functional-connectivity alterations associated with ASD diagnosis. But the passages do not identify those alterations as interhemispheric or callosal, and the paper's Discussion (Limitations) says its analysis focused on ASD rather than other disorders. The source therefore does not support the corpus-callosum or schizophrenia parts of the claim. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Urchs, S. G., Tam, A., Orban, P., Moreau, C., Benhajali, Y., Nguyen, H. D., Evans, A. C., & Bellec, P.
Affiliations
  • Montreal Neurological Institute and Hospital, McGill University
  • Institut Universitaire de Gériatrie de Montréal (CA)
  • Institut universitaire en santé mentale de Montréal (CA)
  • Centre National de la Recherche Scientifique (FR)
  • The University of Queensland (AU)
  • Montreal Neurological Institute and Hospital (CA)
Corresponding author
Bellec, Pierre
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2022-11-29
Volume
11
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.56257
PMC
PMC9708070
OpenAlex
W4300716292
Cited by
37
References
11
Citations by year
2026: 8 · 2025: 12 · 2024: 10 · 2023: 5 · 2020: 2
FWCI
3.47
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Australian Research Council (DE170101134, DP180101192)
  • Brain Canada Multi Investigator Research Initiative (MIRI) and Azrieli Foundation (3388)
  • Canadian Open Neuroscience Plastudenttform (Student Scholar Award)
  • Courtouis Neuromod Foundation (Graduate Student Funding)
  • Fonds de Recherche du Québec - Santé (Salary Award)
  • Centre de recherche de l'Institut universitaire de geriatrie de Montreal (Graduate Student Funding)
  • Canadian Consortium on Neurodegeneration in Aging (Graduate Student Funding)
  • Healthy Brains, Healthy Lives (Graduate Student Funding)
  • Brain Canada Multi investigator research initiative (Graduate Student Funding)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
autism spectrum disorder, functional connectivity, data-driven clustering, hierarchical clustering, brain network organization, autism heterogeneity, diagnosis, dimensionality reduction
MeSH terms
Autistic Disorder, Brain, Humans, Research Personnel, Cluster Analysis, Neurodevelopmental Disorders

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