TY - JOUR
T1 - Connectome-wide Mega-analysis Reveals Robust Patterns of Atypical Functional Connectivity in Autism
AU - Ilioska, Iva
AU - Oldehinkel, Marianne
AU - Llera, Alberto
AU - Chopra, Sidhant
AU - Looden, Tristan
AU - Chauvin, Roselyne
AU - Van Rooij, Daan
AU - Floris, Dorothea L.
AU - Tillmann, Julian
AU - Moessnang, Carolin
AU - Banaschewski, Tobias
AU - Holt, Rosemary J.
AU - Loth, Eva
AU - Charman, Tony
AU - Murphy, Declan G.M.
AU - Ecker, Christine
AU - Mennes, Maarten
AU - Beckmann, Christian F.
AU - Fornito, Alex
AU - Buitelaar, Jan K.
N1 - Funding Information:
This work was primarily supported by the EU-AIMS consortium (European Autism Interventions), which receives support from Innovative Medicines Initiative Joint Undertaking (Grant No. 115300), the resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (Grant No. FP7/2007-2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions; and by the Autism Innovative Medicine Studies-2-Trials consortium, which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (IMI 2JU) (Grant No. 777394), and this Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program, and The European Federation of Pharmaceutical Industries and Associations and AUTISM SPEAKS, Autistica, Simons Foundation Autism Research Initiative. The views expressed are those of the author(s) and not necessarily those of the IMI 2JU. II is supported by an internal grant by RadboudUMC/Donders Center for Medical Neuroscience (2018–2022) (to JKB and AF). MO is supported by ZonMW Rubicon (Grant No. 452172019). This work has been further supported by the European Community’s Horizon 2020 Programme (H2020/2014–2020) (Grant No. 643051 [MiND] [to JKB], Grant No. 642996 [BRAINVIEW] [to JKB], and Grant No. 847818 [CANDY] [to JKB and CFB]). AF was supported by the Sylvia and Charles Viertel Charitable Foundation and National Health and Medical Research Council (ID: 3274306 ).
Funding Information:
This work was primarily supported by the EU-AIMS consortium (European Autism Interventions), which receives support from Innovative Medicines Initiative Joint Undertaking (Grant No. 115300), the resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (Grant No. FP7/2007-2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions; and by the Autism Innovative Medicine Studies-2-Trials consortium, which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (IMI 2JU) (Grant No. 777394), and this Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program, and The European Federation of Pharmaceutical Industries and Associations and AUTISM SPEAKS, Autistica, Simons Foundation Autism Research Initiative. The views expressed are those of the author(s) and not necessarily those of the IMI 2JU. II is supported by an internal grant by RadboudUMC/Donders Center for Medical Neuroscience (2018–2022) (to JKB and AF). MO is supported by ZonMW Rubicon (Grant No. 452172019). This work has been further supported by the European Community's Horizon 2020 Programme (H2020/2014–2020) (Grant No. 643051 [MiND] [to JKB], Grant No. 642996 [BRAINVIEW] [to JKB], and Grant No. 847818 [CANDY] [to JKB and CFB]). AF was supported by the Sylvia and Charles Viertel Charitable Foundation and National Health and Medical Research Council (ID: 3274306). The EU-AIMS LEAP group consists of Jumana Ahmad, Sara Ambrosino, Sarah Baumeister, Carsten Bours, Michael Brammer, Daniel Brandeis, Claudia Brogna, Yvette de Bruijn, Ineke Cornelissen, Daisy Crawley, Guillaume Dumas, Jessica Faulkner, Vincent Frouin, Pilar Garcés, David Goyard, Joerg Hipp, Rosemary Holt, Meng-Chuan Lai, Xavier Liogier D'ardhuy, Michael V. Lombardo, David J. Lythgoe, René Mandl, Andre Marquand, Maarten Mennes, Andreas Meyer-Lindenberg, Nico Mueller, Bethany Oakley, Laurence O'Dwyer, Marianne Oldehinkel, Gahan Pandina, Barbara Ruggeri, Amber Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San José Cáceres, Emily Simonoff, Will Spooren, Roberto Toro, Heike Tost, Jack Waldman, Steve C.R. Williams, Caroline Wooldridge, and Marcel P. Zwiers. This work was previously published as an abstract and poster at the Organization for Human Brain Mapping 2020 conference, June 23–July 3, 2020, which was held online. A previous version of this article was published as a preprint on medRxiv: https://www.medrxiv.org/content/10.1101/2022.01.09.22268936v2. JKB has been a consultant to/member of advisory board of/and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen, and Servier in the past 3 years. He is not an employee of any of these companies and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. TC has served as a paid consultant to F. Hoffmann-La Roche Ltd. and Servier and has received royalties from Sage Publications and Guilford Publications. CFB is the director and shareholder in SBGNeuro Ltd. TB served in an advisory or consultancy role for ADHS digital, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker's fee by Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. DGMM has been a consultant to and advisory board member for Roche and Servier. He is not an employee of any of these companies and not a stock shareholder of any of these companies. The present work is unrelated to the above grants and relationships. All other authors report no biomedical financial interests or potential conflicts of interest.
Publisher Copyright:
© 2022 Society of Biological Psychiatry
PY - 2023/7/1
Y1 - 2023/7/1
N2 - BackgroundNeuroimaging studies of functional connectivity (FC) in autism have been hampered by small sample sizes and inconsistent findings with regard to whether connectivity is increased or decreased in individuals with autism, whether these alterations affect focal systems or reflect a brain-wide pattern, and whether these are age and/or sex dependent.MethodsThe study included resting-state functional magnetic resonance imaging and clinical data from the EU-AIMS LEAP (European Autism Interventions Longitudinal European Autism Project) and the ABIDE (Autism Brain Imaging Data Exchange) 1 and 2 initiatives of 1824 (796 with autism) participants with an age range of 5–58 years. Between-group differences in FC were assessed, and associations between FC and clinical symptom ratings were investigated through canonical correlation analysis.ResultsAutism was associated with a brainwide pattern of hypo- and hyperconnectivity. Hypoconnectivity predominantly affected sensory and higher-order attentional networks and correlated with social impairments, restrictive and repetitive behavior, and sensory processing. Hyperconnectivity was observed primarily between the default mode network and the rest of the brain and between cortical and subcortical systems. This pattern was strongly associated with social impairments and sensory processing. Interactions between diagnosis and age or sex were not statistically significant.ConclusionsThe FC alterations observed, which primarily involve hypoconnectivity of primary sensory and attention networks and hyperconnectivity of the default mode network and subcortex with the rest of the brain, do not appear to be age or sex dependent and correlate with clinical dimensions of social difficulties, restrictive and repetitive behaviors, and alterations in sensory processing. These findings suggest that the observed connectivity alterations are stable, trait-like features of autism that are related to the main symptom domains of the condition.
AB - BackgroundNeuroimaging studies of functional connectivity (FC) in autism have been hampered by small sample sizes and inconsistent findings with regard to whether connectivity is increased or decreased in individuals with autism, whether these alterations affect focal systems or reflect a brain-wide pattern, and whether these are age and/or sex dependent.MethodsThe study included resting-state functional magnetic resonance imaging and clinical data from the EU-AIMS LEAP (European Autism Interventions Longitudinal European Autism Project) and the ABIDE (Autism Brain Imaging Data Exchange) 1 and 2 initiatives of 1824 (796 with autism) participants with an age range of 5–58 years. Between-group differences in FC were assessed, and associations between FC and clinical symptom ratings were investigated through canonical correlation analysis.ResultsAutism was associated with a brainwide pattern of hypo- and hyperconnectivity. Hypoconnectivity predominantly affected sensory and higher-order attentional networks and correlated with social impairments, restrictive and repetitive behavior, and sensory processing. Hyperconnectivity was observed primarily between the default mode network and the rest of the brain and between cortical and subcortical systems. This pattern was strongly associated with social impairments and sensory processing. Interactions between diagnosis and age or sex were not statistically significant.ConclusionsThe FC alterations observed, which primarily involve hypoconnectivity of primary sensory and attention networks and hyperconnectivity of the default mode network and subcortex with the rest of the brain, do not appear to be age or sex dependent and correlate with clinical dimensions of social difficulties, restrictive and repetitive behaviors, and alterations in sensory processing. These findings suggest that the observed connectivity alterations are stable, trait-like features of autism that are related to the main symptom domains of the condition.
KW - Canonical correlation
KW - Functional connectivity
KW - Hyperconnectivity
KW - Hypoconnectivity
KW - Networks
KW - Resting-state
UR - http://www.scopus.com/inward/record.url?scp=85150753559&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2022.12.018
DO - 10.1016/j.biopsych.2022.12.018
M3 - Article
C2 - 36925414
AN - SCOPUS:85150753559
SN - 0006-3223
VL - 94
SP - 29
EP - 39
JO - Biological psychiatry
JF - Biological psychiatry
IS - 1
ER -