Reproducible functional connectivity alterations are associated with autism spectrum disorder
By
Štefan Holiga,
Joerg F Hipp,
Christopher H Chatham,
Pilar Garces,
Will Spooren,
Xavier Liogier D’Ardhuy,
Alessandro Bertolino,
Céline Bouquet,
Jan K. Buitelaar,
Carsten Bours,
Annika Rausch,
Marianne Oldehinkel,
Manuel Bouvard,
Anouck Amestoy,
Mireille Caralp,
Sonia Gueguen,
Myriam Ly-Le Moal,
Josselin Houenou,
Christian F Beckmann,
Eva Loth,
Declan Murphy,
Tony Charman,
Julian Tillmann,
Charles Laidi,
Richard Delorme,
Anita Beggiato,
Alexandru Gaman,
Isabelle Scheid,
Marion Leboyer,
Marc-Antoine d’Albis,
Jeff Sevigny,
Christian Czech,
Federico Bolognani,
Garry D Honey,
Juergen Dukart
Posted 18 Apr 2018
bioRxiv DOI: 10.1101/303115
Despite the high clinical burden little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical relevance of these alterations. Here we address these questions in the most comprehensive, large-scale effort to date comprising evaluation of four large ASD cohorts. We followed a strict exploration and replication procedure to identify core rs-fMRI functional connectivity (degree centrality) alterations associated with ASD as compared to typically developing (TD) controls (ASD: N=841, TD: N=984). We then tested for associations of these imaging phenotypes with clinical and demographic factors such as age, sex, medication status and clinical symptom severity. We find reproducible patterns of ASD-associated functional hyper- and hypo-connectivity with hypo-connectivity being primarily restricted to sensory-motor regions and hyper-connectivity hubs being predominately located in prefrontal and parietal cortices. We establish shifts in between-network connectivity from outside to within the identified regions as a key driver of these abnormalities. The magnitude of these alterations is linked to core ASD symptoms related to communication and social interaction and is not affected by age, sex or medication status. The identified brain functional alterations provide a reproducible pathophysiological phenotype underlying the diagnosis of ASD reconciling previous divergent findings. The large effect sizes in standardized cohorts and the link to clinical symptoms emphasize the importance of the identified imaging alterations as potential treatment and stratification biomarkers for ASD.
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