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Patients with autism spectrum disorders display reproducible functional connectivity alterations

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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 & 15 more 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

Original languageEnglish
Article numbereaat9223
JournalScience Translational Medicine
Volume11
Issue number481
DOIs
Publication statusPublished - 27 Feb 2019

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Abstract

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 addressed these questions in four large ASD cohorts. Using rs-fMRI, we identified functional connectivity alterations associated with ASD. We tested for associations of these imaging phenotypes with clinical and demographic factors such as age, sex, medication status, and clinical symptom severity. Our results showed reproducible patterns of ASD-associated functional hyper- and hypoconnectivity. Hypoconnectivity was primarily restricted to sensory-motor regions, whereas hyperconnectivity hubs were predominately located in prefrontal and parietal cortices. Shifts in cortico-cortical between-network connectivity from outside to within the identified regions were shown to be a key driver of these abnormalities. This reproducible pathophysiological phenotype was partially associated with core ASD symptoms related to communication and daily living skills and was not affected by age, sex, or medication status. Although the large effect sizes in standardized cohorts are encouraging with respect to potential application as a treatment and for patient stratification, the moderate link to clinical symptoms and the large overlap with healthy controls currently limit the usability of identified alterations as diagnostic or efficacy readout.

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