Patterns of connectome variability in autism across five functional activation tasks: findings from the LEAP project

the AIMS-2-TRIALS group

doi:10.1186/s13229-022-00529-y

Patterns of connectome variability in autism across five functional activation tasks: findings from the LEAP project

the AIMS-2-TRIALS group

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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.

Original language	English
Article number	53
Journal	Molecular Autism
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/s13229-022-00529-y
Publication status	Published - Dec 2022

Keywords

Autism
Canonical correlation analysis
fMRI
Functional connectivity
Heterogeneity
Normative modeling

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s13229-022-00529-y

Cite this

@article{564a9a5a809345028646dae1d71f83a9,

title = "Patterns of connectome variability in autism across five functional activation tasks: findings from the LEAP project",

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.",

keywords = "Autism, Canonical correlation analysis, fMRI, Functional connectivity, Heterogeneity, Normative modeling",

author = "{the AIMS-2-TRIALS group} and Tristan Looden and Floris, {Dorothea L.} and Alberto Llera and Chauvin, {Roselyne J.} and Tony Charman and Tobias Banaschewski and Declan Murphy and Marquand, {Andre F.} and Buitelaar, {Jan K.} and Beckmann, {Christian F.} and Jumana Ahmad and Sara Ambrosino and Bonnie Auyeung and Simon Baron-Cohen and Sarah Baumeister and Sven B{\"o}lte and Thomas Bourgeron and Carsten Bours and Michael Brammer and Daniel Brandeis and Claudia Brogna and {de Bruijn}, Yvette and Bhismadev Chakrabarti and Ineke Cornelissen and Daisy Crawley and Acqua, {Flavio Dell{\textquoteright}} and Guillaume Dumas and Sarah Durston and Christine Ecker and Jessica Faulkner and Vincent Frouin and Pilar Garc{\'e}s and David Goyard and Lindsay Ham and Hannah Hayward and Joerg Hipp and Rosemary Holt and Johnson, {Mark H.} and Jones, {Emily J.H.} and Eva Loth and Lythgoe, {David J.} and Andre Marquand and Luke Mason and Murphy, {Declan G.M.} and Bethany Oakley and Barbara Ruggeri and C{\'a}ceres, {Antonia San Jos{\'e}} and Emily Simonoff and Julian Tillmann and Williams, {Steve C.R.}",

note = "Funding Information: The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement Nos. 115300 (for EU-AIMS) and 777394 (for AIMS-2-TRIALS). This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. DLF is supported by funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie Grant Agreement No. 101025785. 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{\textquoteright}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 Organization for Scientific Research VICI Grant No. 17854 (to CFB); Wellcome Trust Collaborative Award Grant No. 215573/Z/19/Z (to CFB); the Autism Research Trust (to SBC), and the NWO Gravitation Programme Language in Interaction (Grant 024.001.006). 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. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s13229-022-00529-y",

language = "English",

volume = "13",

journal = "Molecular Autism",

issn = "2040-2392",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Patterns of connectome variability in autism across five functional activation tasks

T2 - findings from the LEAP project

AU - the AIMS-2-TRIALS group

AU - Looden, Tristan

AU - Floris, Dorothea L.

AU - Llera, Alberto

AU - Chauvin, Roselyne J.

AU - Charman, Tony

AU - Banaschewski, Tobias

AU - Murphy, Declan

AU - Marquand, Andre F.

AU - Buitelaar, Jan K.

AU - Beckmann, Christian F.

AU - Ahmad, Jumana

AU - Ambrosino, Sara

AU - Auyeung, Bonnie

AU - Baron-Cohen, Simon

AU - Baumeister, Sarah

AU - Bölte, Sven

AU - Bourgeron, Thomas

AU - Bours, Carsten

AU - Brammer, Michael

AU - Brandeis, Daniel

AU - Brogna, Claudia

AU - de Bruijn, Yvette

AU - Chakrabarti, Bhismadev

AU - Cornelissen, Ineke

AU - Crawley, Daisy

AU - Acqua, Flavio Dell’

AU - Dumas, Guillaume

AU - Durston, Sarah

AU - Ecker, Christine

AU - Faulkner, Jessica

AU - Frouin, Vincent

AU - Garcés, Pilar

AU - Goyard, David

AU - Ham, Lindsay

AU - Hayward, Hannah

AU - Hipp, Joerg

AU - Holt, Rosemary

AU - Johnson, Mark H.

AU - Jones, Emily J.H.

AU - Loth, Eva

AU - Lythgoe, David J.

AU - Marquand, Andre

AU - Mason, Luke

AU - Murphy, Declan G.M.

AU - Oakley, Bethany

AU - Ruggeri, Barbara

AU - Cáceres, Antonia San José

AU - Simonoff, Emily

AU - Tillmann, Julian

AU - Williams, Steve C.R.

N1 - Funding Information: The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement Nos. 115300 (for EU-AIMS) and 777394 (for AIMS-2-TRIALS). This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. DLF is supported by funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 101025785. 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 Organization for Scientific Research VICI Grant No. 17854 (to CFB); Wellcome Trust Collaborative Award Grant No. 215573/Z/19/Z (to CFB); the Autism Research Trust (to SBC), and the NWO Gravitation Programme Language in Interaction (Grant 024.001.006). 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. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - Autism

KW - Canonical correlation analysis

KW - fMRI

KW - Functional connectivity

KW - Heterogeneity

KW - Normative modeling

UR - http://www.scopus.com/inward/record.url?scp=85144808761&partnerID=8YFLogxK

U2 - 10.1186/s13229-022-00529-y

DO - 10.1186/s13229-022-00529-y

M3 - Article

C2 - 36575450

AN - SCOPUS:85144808761

SN - 2040-2392

VL - 13

JO - Molecular Autism

JF - Molecular Autism

IS - 1

M1 - 53

ER -

Patterns of connectome variability in autism across five functional activation tasks: findings from the LEAP project

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this