Altered Connectivity Between Cerebellum, Visual, and Sensory-Motor Networks in Autism Spectrum Disorder: Results from the EU-AIMS Longitudinal European Autism Project

Marianne Oldehinkel (1, 2, 3) , Maarten Mennes (3) , Andre Marquand (1, 3, 4) , Tony Charman (4) , Julian Tillmann (4) , Christine Ecker (4) , Flavio Dell'Acqua (4, 5) , Daniel Brandeis (6, 7, 8) , Tobias Banaschewski (9) , Sarah Baumeister (6) , Carolin Moessnang (6) , Simon Baron-Cohen (10) , Rosemary J Holt (10) , Sven Bölte (11, 12) , Sarah Durston (13) , Prantik Kundu (14) , Michael V Lombardo (10, 15) , Will Spooren (16) , Eva Loth (4) , Declan G. Murphy (4) , Christian Beckmann (1, 3, 17) , Jan Buitelaar (1, 3) , Jumana Ahmad (4) , Sara Ambrosino (13) , Bonnie Auyeung (18) , Thomas Bourgeron (19) , Carsten Bours (1) , Michael Brammer (4) , Claudia Brogna (20) , Yvette de Bruijn (1) , Bhismadev Chakrabarti (21) , Ineke Cornelissen (1) , Daisy Crawley (4) , Flavio Dell’acqua (4) , Guillaume Dumas (19) , Jessica Faulkner , Vincent Frouin , Pilar Garcés (16) , David Goyard (22) , Lindsay Ham (23) , Hannah Hayward , Joerg Hipp (16) , Mark C. Johnson (24) , Emily J.H. Jones , Meng-Chuan Lai (25) , Xavier Liogier D’ardhuy , David J Lythgoe (4) , René Mandl (13) , Luke Mason (26) , Andre Meyer-Lindenberg , Nico Mueller , Declan G.M. Murphy , Bethany Oakley , Laurence O’dwyer (1) , Bob Oranje (13) , Gahan Pandina (27) , Antonio M Persico (20) , Barbara Ruggeri (4) , Amber N V Ruigrok (10) , Jessica Sabet (4) , Roberto Sacco , Antonia San José Cáceres , Simon Simonoff , Roberto Toro (19) , Heike Tost (6) , Jack Waldman (10) , Steven C.R. Williams , Caroline Wooldridge , Marcel Zwiers (1)

1 Radboud University Medical Center [Nijmegen]
2 Monash University [Melbourne]
3 Donders Institute for Brain, Cognition and Behaviour
4 Institute of Psychiatry, Psychology & Neuroscience, King's College London
5 Goethe-University Frankfurt am Main
6 Universität Heidelberg [Heidelberg]
7 UZH - Universität Zürich [Zürich] = University of Zurich
8 ETH Zürich - Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich]
9 Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim]
10 CAM - University of Cambridge [UK]
11 Karolinska Institutet [Stockholm]
12 Stockholm County Council
13 University Medical Center [Utrecht]
14 MSSM - Icahn School of Medicine at Mount Sinai [New York]
15 UCY - University of Cyprus [Nicosia]
16 pRED - Roche Pharma Research and Early Development [Basel]
17 University of Oxford [Oxford]
18 University of Edinburgh
19 GHFC (UMR_3571 / U-Pasteur_1) - Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions
20 UCBM - Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome
21 UOR - University of Reading
22 DCM - Département de Chimie Moléculaire
23 F. Hoffmann-La Roche [Basel]
24 UON - University of Nottingham, UK
25 University of Toronto
26 Centre for Brain and Cognitive Development [Birkbeck College]
27 Janssen Research & Development

BACKGROUND: Resting-state functional magnetic resonance imaging-based studies on functional connectivity in autism spectrum disorder (ASD) have generated inconsistent results. Interpretation of findings is further hampered by small samples and a focus on a limited number of networks, with networks underlying sensory processing being largely underexamined. We aimed to comprehensively characterize ASD-related alterations within and between 20 well-characterized resting-state networks using baseline data from the EU-AIMS (European Autism Interventions-A Multicentre Study for Developing New Medications) Longitudinal European Autism Project. METHODS: Resting-state functional magnetic resonance imaging data was available for 265 individuals with ASD (7.5-30.3 years; 73.2% male) and 218 typically developing individuals (6.9-29.8 years; 64.2% male), all with IQ > 70. We compared functional connectivity within 20 networks-obtained using independent component analysis-between the ASD and typically developing groups, and related functional connectivity within these networks to continuous (overall) autism trait severity scores derived from the Social Responsiveness Scale Second Edition across all participants. Furthermore, we investigated case-control differences and autism trait-related alterations in between-network connectivity. RESULTS: Higher autism traits were associated with increased connectivity within salience, medial motor, and orbitofrontal networks. However, we did not replicate previously reported case-control differences within these networks. The between-network analysis did reveal case-control differences showing on average 1) decreased connectivity of the visual association network with somatosensory, medial, and lateral motor networks, and 2) increased connectivity of the cerebellum with these sensory and motor networks in ASD compared with typically developing subjects. CONCLUSIONS: We demonstrate ASD-related alterations in within- and between-network connectivity. The between-network alterations broadly affect connectivity between cerebellum, visual, and sensory-motor networks, potentially underlying impairments in multisensory and visual-motor integration frequently observed in ASD.

Keywords: Resting-state fMRI; Sensory networks; Visual-motor integration; Autism; Cerebellum; Functional connectivity

Domains: Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]

Marianne Oldehinkel, Maarten Mennes, Andre Marquand, Tony Charman, Julian Tillmann, et al.. Altered Connectivity Between Cerebellum, Visual, and Sensory-Motor Networks in Autism Spectrum Disorder: Results from the EU-AIMS Longitudinal European Autism Project. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2018, ⟨10.1016/j.bpsc.2018.11.010⟩. ⟨pasteur-02029576⟩