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000861383 1001_ $$00000-0002-6248-2792$$aHoliga, Štefan$$b0$$eCorresponding author
000861383 245__ $$aPatients with autism spectrum disorders display reproducible functional connectivity alterations
000861383 260__ $$aWashington, DC$$bAAAS$$c2019
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000861383 520__ $$aDespite the high clinical burden, little is known about pathophysiology underlying autism spectrum disorder(ASD). Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchro-nization of brain activity in ASD. However, no consensus has been reached on the nature and clinical relevance ofthese alterations. Here, we addressed these questions in four large ASD cohorts. Using rs-fMRI, we identified func-tional connectivity alterations associated with ASD. We tested for associations of these imaging phenotypes withclinical and demographic factors such as age, sex, medication status, and clinical symptom severity. Our resultsshowed reproducible patterns of ASD-associated functional hyper- and hypoconnectivity. Hypoconnectivity wasprimarily restricted to sensory-motor regions, whereas hyperconnectivity hubs were predominately located inprefrontal and parietal cortices. Shifts in cortico-cortical between-network connectivity from outside to withinthe identified regions were shown to be a key driver of these abnormalities. This reproducible pathophysiologicalphenotype was partially associated with core ASD symptoms related to communication and daily living skills andwas not affected by age, sex, or medication status. Although the large effect sizes in standardized cohorts areencouraging with respect to potential application as a treatment and for patient stratification, the moderate linkto clinical symptoms and the large overlap with healthy controls currently limit the usability of identified altera-tions as diagnostic or efficacy readout.
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000861383 7001_ $$00000-0002-7875-2988$$aHipp, Joerg F.$$b1
000861383 7001_ $$0P:(DE-HGF)0$$aChatham, Christopher H.$$b2
000861383 7001_ $$00000-0003-4989-0123$$aGarces, Pilar$$b3
000861383 7001_ $$0P:(DE-HGF)0$$aSpooren, Will$$b4
000861383 7001_ $$0P:(DE-HGF)0$$aD’Ardhuy, Xavier Liogier$$b5
000861383 7001_ $$0P:(DE-HGF)0$$aBertolino, Alessandro$$b6
000861383 7001_ $$0P:(DE-HGF)0$$aBouquet, Céline$$b7
000861383 7001_ $$00000-0001-8288-7757$$aBuitelaar, Jan K.$$b8
000861383 7001_ $$00000-0001-9760-3059$$aBours, Carsten$$b9
000861383 7001_ $$0P:(DE-HGF)0$$aRausch, Annika$$b10
000861383 7001_ $$0P:(DE-HGF)0$$aOldehinkel, Marianne$$b11
000861383 7001_ $$00000-0001-5963-0304$$aBouvard, Manuel$$b12
000861383 7001_ $$00000-0001-6544-0152$$aAmestoy, Anouck$$b13
000861383 7001_ $$0P:(DE-HGF)0$$aCaralp, Mireille$$b14
000861383 7001_ $$0P:(DE-HGF)0$$aGueguen, Sonia$$b15
000861383 7001_ $$00000-0003-2769-456X$$aLy-Le Moal, Myriam$$b16
000861383 7001_ $$0P:(DE-HGF)0$$aHouenou, Josselin$$b17
000861383 7001_ $$0P:(DE-HGF)0$$aBeckmann, Christian F.$$b18
000861383 7001_ $$0P:(DE-HGF)0$$aLoth, Eva$$b19
000861383 7001_ $$00000-0002-6664-7451$$aMurphy, Declan$$b20
000861383 7001_ $$00000-0003-1993-6549$$aCharman, Tony$$b21
000861383 7001_ $$00000-0001-9574-9855$$aTillmann, Julian$$b22
000861383 7001_ $$0P:(DE-HGF)0$$aLaidi, Charles$$b23
000861383 7001_ $$0P:(DE-HGF)0$$aDelorme, Richard$$b24
000861383 7001_ $$00000-0002-7374-0275$$aBeggiato, Anita$$b25
000861383 7001_ $$00000-0001-8084-6505$$aGaman, Alexandru$$b26
000861383 7001_ $$00000-0003-2035-4706$$aScheid, Isabelle$$b27
000861383 7001_ $$0P:(DE-HGF)0$$aLeboyer, Marion$$b28
000861383 7001_ $$0P:(DE-HGF)0$$ad’Albis, Marc-Antoine$$b29
000861383 7001_ $$00000-0003-0974-6434$$aSevigny, Jeff$$b30
000861383 7001_ $$00000-0001-7746-0134$$aCzech, Christian$$b31
000861383 7001_ $$0P:(DE-HGF)0$$aBolognani, Federico$$b32
000861383 7001_ $$0P:(DE-HGF)0$$aHoney, Garry D.$$b33
000861383 7001_ $$0P:(DE-Juel1)177727$$aDukart, Juergen$$b34$$eCorresponding author
000861383 773__ $$0PERI:(DE-600)2518839-2$$a10.1126/scitranslmed.aat9223$$gVol. 11, no. 481, p. eaat9223 -$$n481$$peaat9223$$tScience translational medicine$$v11$$x1946-6242$$y2019
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