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Record W4411037189 · doi:10.1186/s13229-025-00667-z

Subgrouping autism and ADHD based on structural MRI population modelling centiles

2025· article· en· W4411037189 on OpenAlexafffund
Clara Pecci-Terroba, Meng‐Chuan Lai, Michael Lombardo, Bhismadev Chakrabarti, Amber Ruigrok, John Suckling, Evdokia Anagnostou, Jason P. Lerch, Margot J. Taylor, Rob Nicolson, Stelios Georgiades, Jennifer Crosbie, Russell Schachar, Elizabeth Kelley, Jessica Jones, Paul Arnold, Jakob Seidlitz, Aaron Alexander‐Bloch, Edward T. Bullmore, Simon Baron‐Cohen, Saashi A. Bedford, Richard A. I. Bethlehem

Bibliographic record

VenueMolecular Autism · 2025
Typearticle
Languageen
FieldNeuroscience
TopicAutism Spectrum Disorder Research
Canadian institutionsUniversity of CalgaryQueen's UniversityMcMaster UniversityHospital for Sick ChildrenUniversity of TorontoWestern UniversityHolland Bloorview Kids Rehabilitation HospitalCentre for Addiction and Mental Health
FundersNational Institute on Deafness and Other Communication DisordersNational Institute of Mental HealthNIHR Cambridge Biomedical Research CentreSimons Foundation Autism Research InitiativeBiotechnology and Biological Sciences Research CouncilMedical Research CouncilDirectorate for Biological SciencesAlberta InnovatesUniversity of TorontoAlberta Children's Hospital FoundationCanadian Institutes of Health ResearchNational Institute for Health and Care ResearchChildren's Hospital FoundationWellcome Trust
KeywordsAutismNeuropsychologyNeurologyNeuroimagingPsychologyMedicinePsychiatryCognition

Abstract

fetched live from OpenAlex

BACKGROUND: Autism and attention deficit hyperactivity disorder (ADHD) are two highly heterogeneous neurodevelopmental conditions with variable underlying neurobiology. Imaging studies have yielded varied results, and it is now clear that there is unlikely to be one characteristic neuroanatomical profile of either condition. Parsing this heterogeneity could allow us to identify more homogeneous subgroups, either within or across conditions, which may be more clinically informative. This has been a pivotal goal for neurodevelopmental research using both clinical and neuroanatomical features, though results thus far have again been inconsistent with regards to the number and characteristics of subgroups. METHODS: Here, we use population modelling to cluster a multi-site dataset based on global and regional centile scores of cortical thickness, surface area and grey matter volume. We use HYDRA, a novel semi-supervised machine learning algorithm which clusters based on differences to controls and compare its performance to a traditional clustering approach. RESULTS: We identified distinct subgroups within autism and ADHD, as well as across diagnosis, often with opposite neuroanatomical alterations relatively to controls. These subgroups were characterised by different combinations of increased or decreased patterns of morphometrics. We did not find significant clinical differences across subgroups. LIMITATIONS: Crucially, however, the number of subgroups and their membership differed vastly depending on chosen features and the algorithm used, highlighting the impact and importance of careful method selection. CONCLUSIONS: We highlight the importance of examining heterogeneity in autism and ADHD and demonstrate that population modelling is a useful tool to study subgrouping in autism and ADHD. We identified subgroups with distinct patterns of alterations relative to controls but note that these results rely heavily on the algorithm used and encourage detailed reporting of methods and features used in future studies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.729
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.021
GPT teacher head0.292
Teacher spread0.271 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2025
Admission routes2
Has abstractyes

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