Linking functional and structural brain organisation with behaviour in autism: a multimodal EU-AIMS Longitudinal European Autism Project (LEAP) study
Authors: Oblong Lennart M. , Llera Alberto , Mei Ting , Haak Koen , Isakoglou Christina , Floris Dorothea L. , Durston Sarah , Moessnang Carolin , Banaschewski Tobias , Baron-Cohen Simon , Loth Eva , Dell’Acqua Flavio , Charman Tony , Murphy Declan G. M. , Ecker Christine , Buitelaar Jan K. , Beckmann Christian F. ,   The EU-AIMS LEAP Group, Ahmad Jumana , Ambrosino Sara , Auyeung Bonnie , Banaschewski Tobias , Baron-Cohen Simon , Baumeister Sarah , Beckmann Christian F. , Bölte Sven , Bourgeron Thomas , Bours Carsten , Brammer Michael , Brandeis Daniel , Brogna Claudia , de Bruijn Yvette , Buitelaar Jan K. , Chakrabarti Bhismadev , Charman Tony , Cornelissen Ineke , Crawley Daisy , Dell’Acqua Flavio , Dumas Guillaume , Durston Sarah , Ecker Christine , Faulkner Jessica , Frouin Vincent , Garcés Pilar , Goyard David , Ham Lindsay , Hayward Hannah , Hipp Joerg , Holt Rosemary J. , Johnson Mark H. , Jones Emily J. H. , Kundu Prantik , Lai Meng-Chuan , D’ardhuy Xavier Liogier , Lombardo Michael V. , Loth Eva , Lythgoe David J. , Mandl René , Marquand Andre , Mason Luke , Mennes Maarten , Meyer-Lindenberg Andreas , Moessnang Carolin , Mueller Nico , Murphy Declan G. M. , Oakley Bethany , O’Dwyer Laurence , Oldehinkel Marianne , Oranje Bob , Pandina Gahan , Persico Antonio M. , Price Jack , Rausch Annika , Ruggeri Barbara , Ruigrok Amber N. V. , Sabet Jessica , Sacco Roberto , Cáceres Antonia San Jóse , Simonoff Emily , Spooren Will , Tillmann Julian , Toro Roberto , Tost Heike , Waldman Jack , Williams Steve C. R. , Wooldridge Caroline , Ilioska Iva , Mei Ting , Zwiers Marcel P. , Forde Natalie J. 
Published: August 2023

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 (uncorrectedp < 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.