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Clinical profile impacts the replicability of multivariate brain-behavioural associations

Wang, M.; McPherson, B. C.; Misic, B.; Pestilli, F.; Greenwood, C. M.; Poline, J.-B.

2025-10-09 neuroscience
10.1101/2025.10.08.674881 bioRxiv
Show abstract

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 investigated how sample size and cohort composition influence the replicability of Canonical Correlation Analysis (CCA) results using the UK Biobank (N=40,514). We applied CCA to diffusion-weighted magnetic resonance imaging (dMRI) phenotypes and cognitive assessment test scores. We defined four participant cohorts based on clinical profile and found that, across all cohorts, sample sizes of {approx}500 were needed to obtain replicable canonical correlations and variable loadings. The most targeted cohort (comprising individuals with a history of psychoactive substance use) required 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.

Published in Communications Biology (predicted rank #1) · training set

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