Patterns of connectome variability in autism across five functional activation tasks: findings from the LEAP project
Tristan Looden, Dorothea L. Floris, Alberto Llera, Roselyne J. Chauvin, Tony Charman, Tobias Banaschewski, Declan Murphy, André F. Marquand, Jan K. Buitelaar, Christian F. Beckmann, the AIMS-2-TRIALS group, Jumana Ahmad, Sara Ambrosino, Bonnie Auyeung, Tobias Banaschewski, Simon Baron‐Cohen, Sarah Baumeister, Christian F. Beckmann, Sven Bölte, Thomas Bourgeron, Carsten Bours, Michael J. Brammer, Daniel Brandeis, Claudia Brogna, Yvette de Bruijn, Jan K. Buitelaar, Bhismadev Chakrabarti, Tony Charman, Ineke Cornelissen, Daisy Crawley, Flavio Dell’ Acqua, Guillaume Dumas, Sarah Durston, Christine Ecker, Jessica Faulkner, Vincent Frouin, Pilar Garcés, David Goyard, Lindsay Ham, Hannah Hayward, Joerg F. Hipp, Rosemary Holt, Mark H. Johnson, Emily J. H. Jones, Prantik Kundu, Meng‐Chuan Lai, Xavier Liogier D’ardhuy, Michael Lombardo, Eva Loth, David J. Lythgoe, René C.W. Mandl, André F. Marquand, Luke Mason, Maarten Mennes, Andreas Meyer‐Lindenberg, Carolin Moessnang, Nico Mueller, Declan Murphy, Bethany Oakley, Laurence O’Dwyer, Marianne Oldehinkel, Bob Oranje, Gahan Pandina, Antonio M. Persico, Annika Rausch, Barbara Ruggeri, Amber Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San José Cáceres, Emily Simonoff, Will Spooren, Julian Tillmann, Roberto Toro, Heike Tost, Jack Waldman, Steven Williams, Caroline Wooldridge, Iva Ilioska, Ting Mei, Marcel P. Zwiers
Abstract
BACKGROUND: Autism spectrum disorder (autism) is a complex neurodevelopmental condition with pronounced behavioral, cognitive, and neural heterogeneities across individuals. Here, our goal was to characterize heterogeneity in autism by identifying patterns of neural diversity as reflected in BOLD fMRI in the way individuals with autism engage with a varied array of cognitive tasks. METHODS: All analyses were based on the EU-AIMS/AIMS-2-TRIALS multisite Longitudinal European Autism Project (LEAP) with participants with autism (n = 282) and typically developing (TD) controls (n = 221) between 6 and 30 years of age. We employed a novel task potency approach which combines the unique aspects of both resting state fMRI and task-fMRI to quantify task-induced variations in the functional connectome. Normative modelling was used to map atypicality of features on an individual basis with respect to their distribution in neurotypical control participants. We applied robust out-of-sample canonical correlation analysis (CCA) to relate connectome data to behavioral data. RESULTS: Deviation from the normative ranges of global functional connectivity was greater for individuals with autism compared to TD in each fMRI task paradigm (all tasks p < 0.001). The similarity across individuals of the deviation pattern was significantly increased in autistic relative to TD individuals (p < 0.002). The CCA identified significant and robust brain-behavior covariation between functional connectivity atypicality and autism-related behavioral features. CONCLUSIONS: Individuals with autism engage with tasks in a globally atypical way, but the particular spatial pattern of this atypicality is nevertheless similar across tasks. Atypicalities in the tasks originate mostly from prefrontal cortex and default mode network regions, but also speech and auditory networks. We show how sophisticated modeling methods such as task potency and normative modeling can be used toward unravelling complex heterogeneous conditions like autism.