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Cited by 102Autism Spectrum Disorder ResearchFunctional Brain Connectivity StudiesGenetics and Neurodevelopmental Disorders

Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes

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Zerbi, V., Pagani, M., Markicevic, M., Matteoli, M., Pozzi, D., Fagiolini, M., Bozzi, Y., Galbusera, A. +10 more·2021·Molecular Psychiatry
DOI 10.1038/s41380-021-01245-4PMC PMC8873017

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Abstract

Autism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy and relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation of fMRI-based connectivity in the mouse, in which specific ASD-relevant mutations can be isolated and modeled minimizing environmental contributions. By performing brain-wide connectivity mapping across 16 mouse mutants, we show that different ASD-associated etiologies cause a broad spectrum of connectional abnormalities in which diverse, often diverging, connectivity signatures are recognizable. Despite this heterogeneity, the identified connectivity alterations could be classified into four subtypes characterized by discrete signatures of network dysfunction. Our findings show that etiological variability is a key determinant of connectivity heterogeneity in ASD, hence reconciling conflicting findings in clinical populations. The identification of etiologically-relevant connectivity subtypes could improve diagnostic label accuracy in the non-syndromic ASD population and paves the way for personalized treatment approaches.

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Cited by

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Authors
Zerbi, V., Pagani, M., Markicevic, M., Matteoli, M., Pozzi, D., Fagiolini, M., Bozzi, Y., Galbusera, A., Scattoni, M. L., Provenzano, G., Banerjee, A., Helmchen, F., Basson, M. A., Ellegood, J., Lerch, J. P., Rudin, M., Gozzi, A., & Wenderoth, N.
Affiliations
  • ETH Zurich (CH)
  • Italian Institute of Technology (IT)
  • IRCCS Humanitas Research Hospital (IT)
  • Humanitas University (IT)
  • Boston Children's Hospital (US)
  • University of Trento (IT)
  • Istituto Superiore di Sanità (IT)
  • University of Zurich (CH)
  • King's College London (GB)
  • Hospital for Sick Children (CA)
  • University of Toronto (CA)
Corresponding author
Gozzi, A.
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2021-08-11
Volume
26
Issue
12
Pages
7610-7620
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-021-01245-4
PMC
PMC8873017
OpenAlex
W3189427940
Cited by
102
References
11
Citations by year
2026: 14 · 2025: 26 · 2024: 21 · 2023: 18 · 2022: 16 · 2021: 5 · 2020: 2
FWCI
7.85
Type
journal article
Language
en
Update notices
correction (2022-03-23)
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Iris (University of Trento) (submittedVersion, cc-by)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection (cc-by)
Funders
  • Simons Foundation (400101, SFARI 400101)
  • National Alliance for Research on Schizophrenia and Depression (25861)
  • Simons Foundation Autism Research Initiative (400101)
  • European Commission (HORIZON2020, 802371, 845065)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PZ00P3_173984/1, 173984, Ambizione (PZ00P3_173984/1))
  • Fondazione Telethon
  • Fondazione Cariplo
  • National Institutes of Health
  • Medical Research Council (MR/N026063/1, MR/K022377/1, MR/W006251/1)
  • National Institute of Mental Health (R21MH116473)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
autism spectrum disorder, brain functional connectivity, mouse models of autism, etiologic heterogeneity, network dysfunction, cross-center validation, personalized treatment
MeSH terms
Autism Spectrum Disorder, Animals, Autistic Disorder, Brain, Brain Mapping, Magnetic Resonance Imaging, Neural Pathways, Mice

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