Replicability of multivariate brain-behaviour associations depends on clinical profile
Recent work suggests that thousands of individuals are required in multivariate brain-behaviour analyses to obtain consistently replicable results. Some believe, however, that smaller sample sizes may be sufficient if specific subpopulations are targeted. We investigate how sample size and cohort composition influence the replicability of Canonical Correlation Analysis (CCA) results using the UK Biobank (N = 40,514). We apply CCA to diffusion-weighted magnetic resonance imaging (dMRI) phenotypes and cognitive assessment test scores. We define four participant cohorts based on clinical profile and find that, across all cohorts, sample sizes of ≈500 are needed to obtain replicable canonical correlations and variable loadings. The most targeted cohort (comprising individuals with a history of psychoactive substance use) requires much fewer samples to achieve similar or greater correlations than the other cohorts. Our findings support the idea that moderate sample sizes from targeted cohorts can be sufficient for obtaining replicable brain-behaviour associations.
Authors
- Celia M.T. Greenwood (ORCID: https://orcid.org/0000-0002-2427-5696)
- Michelle Wang (ORCID: https://orcid.org/0000-0002-3432-6899)
- Brent McPherson (ORCID: https://orcid.org/0000-0001-8378-8136)
- Bratislav Mišić (ORCID: https://orcid.org/0000-0003-0307-2862)
- Jean‐Baptiste Poline (ORCID: https://orcid.org/0000-0002-9794-749X)
- Franco Pestilli (ORCID: https://orcid.org/0000-0002-2469-0494)
Institutions
- Montreal Neurological Institute and Hospital (CA)
- Jewish General Hospital (CA)
- McGill University (CA)
- The University of Texas at Austin (US)
Publication Details
- Journal
- Communications Biology
- Published
- 2026-06-25
- DOI
- https://doi.org/10.1038/s42003-026-10364-z
- Primary Topic
- Functional Brain Connectivity Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Michael J. Fox Foundation for Parkinson's Research
- Wellcome
- Amazon Web Services
- McGill University
- Fondation Brain Canada
- Canadian Bee Research Fund
- Ministère de l'Économie, de l’Innovation et des Exportations du Québec
- Government of Canada
- Canada First Research Excellence Fund
- Alliance de recherche numérique du Canada
- National Institutes of Health
- Health Canada
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé
- Fonds de recherche du Québec – Nature et technologies
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- National Institute of Biomedical Imaging and Bioengineering