The impact of study design choices on significance and generalizability of canonical correlation analysis in neuroimaging studies

This technical note describes the effects of different data reduction methods and sample sizes for neuroimaging studies in the context of canonical correlation analysis (CCA). CCA is a multivariate statistical technique which has gained increasing popularity in neuroimaging research in recent years. Here, we investigate the parcellation methods’ impact on elucidating neuroanatomical relationships (based on cortical thickness) with known risk factors related to Alzheimer’s disease risk using data from the UK Biobank. The cortical thickness values were parcellated using four common methods in neuroimaging (atlas-based parcellation, spectral clustering, principal component analysis, and independent component analysis) and results from CCA were compared. The results show that the choice of parcellation technique impacts the strength and significance of the correlation between the brain and behaviours. Principal component analysis and independent component analysis result in the strongest correlations. Additionally, we show that regardless of parcellation technique, smaller sample sizes of participants result in inflated correlation strength and significance. ### Competing Interest Statement The authors have declared no competing interest.