TY - JOUR
T1 - Linking functional and structural brain organisation with behaviour in autism
T2 - a multimodal EU-AIMS Longitudinal European Autism Project (LEAP) study
AU - EU-AIMS LEAP group
AU - Oblong, Lennart M.
AU - Llera, Alberto
AU - Mei, Ting
AU - Haak, Koen
AU - Isakoglou, Christina
AU - Floris, Dorothea L.
AU - Durston, Sarah
AU - Moessnang, Carolin
AU - Banaschewski, Tobias
AU - Baron-Cohen, Simon
AU - Loth, Eva
AU - Dell'Acqua, Flavio
AU - Charman, Tony
AU - Murphy, Declan G.M.
AU - Ecker, Christine
AU - Buitelaar, Jan K.
AU - Beckmann, Christian F.
AU - Forde, Natalie J.
N1 - Funding Information:
DLF is supported by funding from the EuroEuropean Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 101025785. TM is supported by the China Scholarship Council (No. 201806010408). This work has also been supported by the EU-AIMS (European Autism Interventions) and AIMS-2-TRIALS programmes which receive support from Innovative Medicines Initiative Joint Undertaking Grant No. 115300 and 777394, the resources of which are composed of financial contributions from the European Union’s FP7 and Horizon2020 Programmes, and from the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in-kind contributions, and AUTISM SPEAKS, Autistica and SFARI. This work has been further supported by the European Union Seventh Framework Programme Grant Nos. 602805 (AGGRESSOTYPE) (to JKB), 603016 (MATRICS) (to JKB), and 278948 (TACTICS) (to JKB); European Community’s Horizon 2020 Programme (H2020/2014-2020) Grant Nos. 643051 (MiND) (to JKB), 642996 (BRAINVIEW) (to JKB) and 847818 (CANDY) (to JKB and CFB); the Netherlands Organisation for Scientific Research VICI Grant No. 2020/TTW/00836465 (to CFB); Wellcome Trust Collaborative Award Grant No. 215573/Z/19/Z (to CFB); the Autism Research Trust (to SBC). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders.
Funding Information:
We thank all participants and their families for participating in this study. We gratefully acknowledge the contributions of all members of the EU-AIMS LEAP group: Jumana Ahmad, Sara Ambrosino, Bonnie Auyeung, Tobias Banaschewski, Simon Baron-Cohen, Sarah Baumeister, Christian F Beckmann, Sven Bölte, Thomas Bourgeron, Carsten Bours, Michael 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 Hipp, Rosemary J Holt, Mark H Johnson, Emily J H Jones23, Prantik Kundu, Meng-Chuan Lai, Xavier Liogier D’ardhuy, Michael V. Lombardo, Eva Loth, David J Lythgoe, René Mandl, Andre Marquand, Luke Mason, Maarten Mennes, Andreas Meyer-Lindenberg, Carolin Moessnang, Nico Mueller, Declan G M 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, Steve C R Williams, Caroline Wooldridge, Iva Ilioska, Ting Mei and Marcel P Zwiers. The EU AIMS LEAP group affiliations: Jumana Ahmad11, Sara Ambrosino4, Bonnie Auyeung7,14, Tobias Banaschewski6, Simon Baron-Cohen7, Sarah Baumeister6, Christian F Beckmann1, Sven Bölte15,16
Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.
PY - 2023/8/31
Y1 - 2023/8/31
N2 - Neuroimaging analyses of brain structure and function in autism have typically been conducted in isolation, missing the sensitivity gains of linking data across modalities. Here we focus on the integration of structural and functional organisational properties of brain regions. We aim to identify novel brain-organisation phenotypes of autism. We utilised multimodal MRI (T1-, diffusion-weighted and resting state functional), behavioural and clinical data from the EU AIMS Longitudinal European Autism Project (LEAP) from autistic (n = 206) and non-autistic (n = 196) participants. Of these, 97 had data from 2 timepoints resulting in a total scan number of 466. Grey matter density maps, probabilistic tractography connectivity matrices and connectopic maps were extracted from respective MRI modalities and were then integrated with Linked Independent Component Analysis. Linear mixed-effects models were used to evaluate the relationship between components and group while accounting for covariates and non-independence of participants with longitudinal data. Additional models were run to investigate associations with dimensional measures of behaviour. We identified one component that differed significantly between groups (coefficient = 0.33, padj = 0.02). This was driven (99%) by variance of the right fusiform gyrus connectopic map 2. While there were multiple nominal (uncorrected p < 0.05) associations with behavioural measures, none were significant following multiple comparison correction. Our analysis considered the relative contributions of both structural and functional brain phenotypes simultaneously, finding that functional phenotypes drive associations with autism. These findings expanded on previous unimodal studies by revealing the topographic organisation of functional connectivity patterns specific to autism and warrant further investigation.
AB - Neuroimaging analyses of brain structure and function in autism have typically been conducted in isolation, missing the sensitivity gains of linking data across modalities. Here we focus on the integration of structural and functional organisational properties of brain regions. We aim to identify novel brain-organisation phenotypes of autism. We utilised multimodal MRI (T1-, diffusion-weighted and resting state functional), behavioural and clinical data from the EU AIMS Longitudinal European Autism Project (LEAP) from autistic (n = 206) and non-autistic (n = 196) participants. Of these, 97 had data from 2 timepoints resulting in a total scan number of 466. Grey matter density maps, probabilistic tractography connectivity matrices and connectopic maps were extracted from respective MRI modalities and were then integrated with Linked Independent Component Analysis. Linear mixed-effects models were used to evaluate the relationship between components and group while accounting for covariates and non-independence of participants with longitudinal data. Additional models were run to investigate associations with dimensional measures of behaviour. We identified one component that differed significantly between groups (coefficient = 0.33, padj = 0.02). This was driven (99%) by variance of the right fusiform gyrus connectopic map 2. While there were multiple nominal (uncorrected p < 0.05) associations with behavioural measures, none were significant following multiple comparison correction. Our analysis considered the relative contributions of both structural and functional brain phenotypes simultaneously, finding that functional phenotypes drive associations with autism. These findings expanded on previous unimodal studies by revealing the topographic organisation of functional connectivity patterns specific to autism and warrant further investigation.
KW - Autism spectrum disorder
KW - Brain-behaviour associations
KW - Linked ICA
UR - http://www.scopus.com/inward/record.url?scp=85169382228&partnerID=8YFLogxK
U2 - 10.1186/s13229-023-00564-3
DO - 10.1186/s13229-023-00564-3
M3 - Article
C2 - 37653516
AN - SCOPUS:85169382228
SN - 2040-2392
VL - 14
SP - 32
JO - Molecular Autism
JF - Molecular Autism
IS - 1
M1 - 32
ER -