Dorothea L Floris1, Thomas Wolfers2, Mariam Zabihi3, Nathalie E Holz4, Marcel P Zwiers5, Tony Charman6, Julian Tillmann7, Christine Ecker8, Flavio Dell'Acqua9, Tobias Banaschewski4, Carolin Moessnang10, Simon Baron-Cohen11, Rosemary Holt11, Sarah Durston12, Eva Loth9, Declan G M Murphy9, Andre Marquand13, Jan K Buitelaar14, Christian F Beckmann15. 1. Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands; Department for Cognitive Neuroscience, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands. Electronic address: d.floris@donders.ru.nl. 2. Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands; Department of Psychology, University of Oslo, Norway; Norwegian Center for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, University of Oslo Hospital and Oslo University Hospital, Oslo, Norway. 3. Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands; Department for Cognitive Neuroscience, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands. 4. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. 5. Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands. 6. Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom. 7. Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom; Department of Applied Psychology: Health, Development, Enhancement, and Intervention, University of Vienna, Vienna, Austria. 8. Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, University Hospital Frankfurt am Main, Goethe University, Frankfurt, Germany; Department of Psychology, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom. 9. Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom. 10. Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. 11. Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom. 12. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. 13. Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands; Department for Cognitive Neuroscience, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands; Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, United Kingdom. 14. Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands; Department for Cognitive Neuroscience, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands; Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands. 15. Donders Institute for Brain, Cognition, and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands; Department for Cognitive Neuroscience, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands; Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom.
Abstract
BACKGROUND: Autism spectrum disorder ("autism") is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, but its potential as a neural stratification marker has not been widely examined. METHODS: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS (European Autism Interventions-A Multicentre Study for Developing New Medications) Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical control subjects as well as a replication dataset from ABIDE (Autism Brain Imaging Data Exchange) (513 individuals with autism, 691 neurotypical subjects) using a promising approach that moves beyond mean group comparisons. We derived gray matter voxelwise laterality values for each subject and modeled individual deviations from the normative pattern of brain laterality across age using normative modeling. RESULTS: Individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language, motor, and visuospatial regions, associated with symptom severity. Language delay explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged, with individuals with autism with language delay showing more pronounced rightward deviations than individuals with autism without language delay. CONCLUSIONS: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism and indicate that atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
BACKGROUND:Autism spectrum disorder ("autism") is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, but its potential as a neural stratification marker has not been widely examined. METHODS: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS (European Autism Interventions-A Multicentre Study for Developing New Medications) Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical control subjects as well as a replication dataset from ABIDE (Autism Brain Imaging Data Exchange) (513 individuals with autism, 691 neurotypical subjects) using a promising approach that moves beyond mean group comparisons. We derived gray matter voxelwise laterality values for each subject and modeled individual deviations from the normative pattern of brain laterality across age using normative modeling. RESULTS: Individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language, motor, and visuospatial regions, associated with symptom severity. Language delay explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged, with individuals with autism with language delay showing more pronounced rightward deviations than individuals with autism without language delay. CONCLUSIONS: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism and indicate that atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
Authors: Henricus G Ruhe; Christian F Beckmann; Andre F Marquand; Saige Rutherford; Seyed Mostafa Kia; Thomas Wolfers; Charlotte Fraza; Mariam Zabihi; Richard Dinga; Pierre Berthet; Amanda Worker; Serena Verdi Journal: Nat Protoc Date: 2022-06-01 Impact factor: 17.021
Authors: Dorothea L Floris; José O A Filho; Meng-Chuan Lai; Steve Giavasis; Marianne Oldehinkel; Maarten Mennes; Tony Charman; Julian Tillmann; Guillaume Dumas; Christine Ecker; Flavio Dell'Acqua; Tobias Banaschewski; Carolin Moessnang; Simon Baron-Cohen; Sarah Durston; Eva Loth; Declan G M Murphy; Jan K Buitelaar; Christian F Beckmann; Michael P Milham; Adriana Di Martino Journal: Mol Autism Date: 2021-03-01 Impact factor: 6.476
Authors: Giordano D'Urso; Elena Toscano; Veronica Sanges; Anne Sauvaget; Christine E Sheffer; Maria Pia Riccio; Roberta Ferrucci; Felice Iasevoli; Alberto Priori; Carmela Bravaccio; Andrea de Bartolomeis Journal: J Clin Med Date: 2021-12-28 Impact factor: 4.241
Authors: Patrick Friedrich; Kaustubh R Patil; Lisa N Mochalski; Xuan Li; Julia A Camilleri; Jean-Philippe Kröll; Lisa Wiersch; Simon B Eickhoff; Susanne Weis Journal: Brain Struct Funct Date: 2021-12-09 Impact factor: 3.270
Authors: Zhiqiang Sha; Dick Schijven; Amaia Carrion-Castillo; Marc Joliot; Bernard Mazoyer; Simon E Fisher; Fabrice Crivello; Clyde Francks Journal: Nat Hum Behav Date: 2021-03-15