TY  - JOUR
AU  - Holiga, Štefan
AU  - Hipp, Joerg F.
AU  - Chatham, Christopher H.
AU  - Garces, Pilar
AU  - Spooren, Will
AU  - D’Ardhuy, Xavier Liogier
AU  - Bertolino, Alessandro
AU  - Bouquet, Céline
AU  - Buitelaar, Jan K.
AU  - Bours, Carsten
AU  - Rausch, Annika
AU  - Oldehinkel, Marianne
AU  - Bouvard, Manuel
AU  - Amestoy, Anouck
AU  - Caralp, Mireille
AU  - Gueguen, Sonia
AU  - Ly-Le Moal, Myriam
AU  - Houenou, Josselin
AU  - Beckmann, Christian F.
AU  - Loth, Eva
AU  - Murphy, Declan
AU  - Charman, Tony
AU  - Tillmann, Julian
AU  - Laidi, Charles
AU  - Delorme, Richard
AU  - Beggiato, Anita
AU  - Gaman, Alexandru
AU  - Scheid, Isabelle
AU  - Leboyer, Marion
AU  - d’Albis, Marc-Antoine
AU  - Sevigny, Jeff
AU  - Czech, Christian
AU  - Bolognani, Federico
AU  - Honey, Garry D.
AU  - Dukart, Juergen
TI  - Patients with autism spectrum disorders display reproducible functional connectivity alterations
JO  - Science translational medicine
VL  - 11
IS  - 481
SN  - 1946-6242
CY  - Washington, DC
PB  - AAAS
M1  - FZJ-2019-01861
SP  - eaat9223
PY  - 2019
AB  - 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 synchro-nization of brain activity in ASD. However, no consensus has been reached on the nature and clinical relevance ofthese alterations. Here, we addressed these questions in four large ASD cohorts. Using rs-fMRI, we identified func-tional connectivity alterations associated with ASD. We tested for associations of these imaging phenotypes withclinical and demographic factors such as age, sex, medication status, and clinical symptom severity. Our resultsshowed reproducible patterns of ASD-associated functional hyper- and hypoconnectivity. Hypoconnectivity wasprimarily restricted to sensory-motor regions, whereas hyperconnectivity hubs were predominately located inprefrontal and parietal cortices. Shifts in cortico-cortical between-network connectivity from outside to withinthe identified regions were shown to be a key driver of these abnormalities. This reproducible pathophysiologicalphenotype was partially associated with core ASD symptoms related to communication and daily living skills andwas not affected by age, sex, or medication status. Although the large effect sizes in standardized cohorts areencouraging with respect to potential application as a treatment and for patient stratification, the moderate linkto clinical symptoms and the large overlap with healthy controls currently limit the usability of identified altera-tions as diagnostic or efficacy readout.
LB  - PUB:(DE-HGF)16
C6  - pmid:30814340
UR  - <Go to ISI:>//WOS:000460307000002
DO  - DOI:10.1126/scitranslmed.aat9223
UR  - https://juser.fz-juelich.de/record/861383
ER  -