Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes
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. Mehr anzeigen
Persistenter Link
https://doi.org/10.3929/ethz-b-000501365Publikationsstatus
publishedExterne Links
Zeitschrift / Serie
Molecular PsychiatryBand
Seiten / Artikelnummer
Verlag
NatureOrganisationseinheit
03963 - Wenderoth, Nicole / Wenderoth, Nicole
Förderung
173984 - Pharmacogenetic fMRI in brain circuits underlying social motivation and repetitive behavior (SNF)