Probing Autism and ADHD subtypes using cortical signatures of the T1w/T2w-ratio and morphometry

Linn B. Norbom; Bilal Syed; Rikka Kjelkenes; Jaroslav Rokicki; Antoine Beauchamp; Stener Nerland; Azadeh Kushki; Evdokia Anagnostou; Paul Arnold; Jennifer Crosbie; Elizabeth Kelley; Robert Nicolson; Russell Schachar; Margot J. Taylor; Lars T. Westlye; Christian K. Tamnes; Jason P. Lerch

NeuroImage: Clinical (Jan 2025)

Probing Autism and ADHD subtypes using cortical signatures of the T1w/T2w-ratio and morphometry

Linn B. Norbom,
Bilal Syed,
Rikka Kjelkenes,
Jaroslav Rokicki,
Antoine Beauchamp,
Stener Nerland,
Azadeh Kushki,
Evdokia Anagnostou,
Paul Arnold,
Jennifer Crosbie,
Elizabeth Kelley,
Robert Nicolson,
Russell Schachar,
Margot J. Taylor,
Lars T. Westlye,
Christian K. Tamnes,
Jason P. Lerch

Affiliations

Linn B. Norbom: PROMENTA Research Center, Department of Psychology, University of Oslo, Norway; Corresponding author.
Bilal Syed: The Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada
Rikka Kjelkenes: Department of Psychology, University of Oslo, Norway; Section for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
Jaroslav Rokicki: Centre of Research and Education in Forensic Psychiatry, Oslo University Hospital, Oslo, Norway
Antoine Beauchamp: The Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Psychiatry, Western University, London, Canada
Stener Nerland: Division of Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway
Azadeh Kushki: Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Canada; University of Toronto, Institute of Biomedical Engineering, Toronto, Canada
Evdokia Anagnostou: Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Canada
Paul Arnold: Hotchkiss Brain Institute, Departments of Psychiatry & Medical Genetics, University of Calgary, Calgary, Canada
Jennifer Crosbie: Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada
Elizabeth Kelley: Department of Psychology and Centre for Neuroscience Studies, Queen’s University, Kingston, Canada
Robert Nicolson: Department of Psychiatry, Western University, London, Canada
Russell Schachar: Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada
Margot J. Taylor: Diagnostic & Interventional Radiology, The Hospital for Sick Children, Toronto, Canada; Department of Medical Imaging, University of Toronto, Toronto, Canada
Lars T. Westlye: Department of Psychology, University of Oslo, Norway; Section for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; K.G Jebsen Center for Neurodevelopmental Disorders, University of Oslo, Norway
Christian K. Tamnes: PROMENTA Research Center, Department of Psychology, University of Oslo, Norway; Division of Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway
Jason P. Lerch: The Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Canada; Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

Journal volume & issue: Vol. 45
p. 103736

Abstract

Read online

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental conditions that share genetic etiology and frequently co-occur. Given this comorbidity and well-established clinical heterogeneity, identifying individuals with similar brain signatures may be valuable for predicting clinical outcomes and tailoring treatment strategies. Cortical myelination is a prominent developmental process, and its disruption is a candidate mechanism for both disorders. Yet, no studies have attempted to identify subtypes using T1w/T2w-ratio, a magnetic resonance imaging (MRI) based proxy for intracortical myelin. Moreover, cortical variability arises from numerous biological pathways, and multimodal approaches can integrate cortical metrics into a single network. We analyzed data from 310 individuals aged 2.6–23.6 years, obtained from the Province of Ontario Neurodevelopmental (POND) Network consisting of individuals diagnosed with ASD (n = 136), ADHD (n = 100), and typically developing (TD) individuals (n = 74). We first tested for differences in T1w/T2w-ratio between diagnostic categories and controls. We then performed unimodal (T1w/T2w-ratio) and multimodal (T1w/T2w-ratio, cortical thickness, and surface area) spectral clustering to identify diagnostic-blind subgroups. Linear models revealed no statistically significant case-control differences in T1w/T2w-ratio. Unimodal clustering mostly isolated single individual- or minority clusters, driven by image quality and intensity outliers. Multimodal clustering suggested three distinct subgroups, which transcended diagnostic boundaries, showing separate cortical patterns but similar clinical and cognitive profiles. T1w/T2w-ratio features were the most relevant for demarcation, followed by surface area. While our analysis revealed no significant case-control differences, multimodal clustering incorporating the T1w/T2w-ratio among cortical features holds promise for identifying biologically similar subsets of individuals with neurodevelopmental conditions.

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

About the journal

Abstract

Keywords