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037 _ _ |a FZJ-2019-01861
082 _ _ |a 500
100 1 _ |a Holiga, Štefan
|0 0000-0002-6248-2792
|b 0
|e Corresponding author
245 _ _ |a Patients with autism spectrum disorders display reproducible functional connectivity alterations
260 _ _ |a Washington, DC
|c 2019
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520 _ _ |a 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.
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700 1 _ |a Hipp, Joerg F.
|0 0000-0002-7875-2988
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700 1 _ |a Chatham, Christopher H.
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700 1 _ |a Garces, Pilar
|0 0000-0003-4989-0123
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700 1 _ |a Spooren, Will
|0 P:(DE-HGF)0
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700 1 _ |a D’Ardhuy, Xavier Liogier
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700 1 _ |a Bertolino, Alessandro
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700 1 _ |a Bouquet, Céline
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700 1 _ |a Buitelaar, Jan K.
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700 1 _ |a Bours, Carsten
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700 1 _ |a Rausch, Annika
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700 1 _ |a Oldehinkel, Marianne
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700 1 _ |a Bouvard, Manuel
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700 1 _ |a Amestoy, Anouck
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700 1 _ |a Caralp, Mireille
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700 1 _ |a Gueguen, Sonia
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700 1 _ |a Ly-Le Moal, Myriam
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700 1 _ |a Houenou, Josselin
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700 1 _ |a Beckmann, Christian F.
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700 1 _ |a Loth, Eva
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700 1 _ |a Murphy, Declan
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700 1 _ |a Charman, Tony
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700 1 _ |a Tillmann, Julian
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700 1 _ |a Laidi, Charles
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700 1 _ |a Delorme, Richard
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700 1 _ |a Beggiato, Anita
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700 1 _ |a Gaman, Alexandru
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700 1 _ |a Scheid, Isabelle
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700 1 _ |a Leboyer, Marion
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700 1 _ |a d’Albis, Marc-Antoine
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700 1 _ |a Sevigny, Jeff
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700 1 _ |a Czech, Christian
|0 0000-0001-7746-0134
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700 1 _ |a Bolognani, Federico
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700 1 _ |a Honey, Garry D.
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700 1 _ |a Dukart, Juergen
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|e Corresponding author
773 _ _ |a 10.1126/scitranslmed.aat9223
|g Vol. 11, no. 481, p. eaat9223 -
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