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- Title
Patients with autism spectrum disorders display reproducible functional connectivity alterations.
- Authors
Holiga, Štefan; Hipp, Joerg F.; Chatham, Christopher H.; Garces, Pilar; Spooren, Will; D'Ardhuy, Xavier Liogier; Bertolino, Alessandro; Bouquet, Céline; Buitelaar, Jan K.; Bours, Carsten; Rausch, Annika; Oldehinkel, Marianne; Bouvard, Manuel; Amestoy, Anouck; Caralp, Mireille; Gueguen, Sonia; Ly-Le Moal, Myriam; Houenou, Josselin; Beckmann, Christian F.; Loth, Eva
- Abstract
Functional connectivity alterations are conserved in multiple cohorts of patients with autism spectrum disorder. Connecting the dots in autism: Multiple studies have shown that patients with autism spectrum disorder (ASD) present alteration in brain functional connectivity; however, the heterogeneity of the findings and the lack of replication in independent cohorts hindered the emergence of a general consensus on the nature and clinical relevance of these changes. Now, Holiga et al. used resting-state functional magnetic resonance imaging to evaluate functional connectivity in four independent cohorts of patients with ASD. The authors identified functional connectivity alterations that were conserved across cohorts and partially correlated with clinical symptoms. Deciphering brain connectivity alterations in ASD might help the development of better diagnostic and therapeutic tools. 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.
- Subjects
AUTISM spectrum disorders; FUNCTIONAL magnetic resonance imaging; PATHOLOGICAL physiology; ASPERGER'S syndrome; RETT syndrome; BRAIN function localization
- Publication
Science Translational Medicine, 2019, Vol 11, Issue 481, pN.PAG
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.aat9223