Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
02
11
2020
accepted:
20
07
2021
revised:
30
06
2021
pubmed:
13
8
2021
medline:
15
3
2022
entrez:
12
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34381171
doi: 10.1038/s41380-021-01245-4
pii: 10.1038/s41380-021-01245-4
pmc: PMC8873017
mid: EMS131965
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7610-7620Subventions
Organisme : European Research Council
ID : 802371
Pays : International
Organisme : Medical Research Council
ID : MR/K022377/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
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