Abstract Introduction Canonical Correlation Analysis (CCA) and Partial Least Squares Correlation (PLS) detect associations between two data matrices based on computing a linear combination between the two matrices (called latent variables; LVs). These LVs maximize correlation (CCA) and covariance (PLS). These different maximization criteria may render one approach more stable and reproducible than the other when working with brain and behavioural data at the population-level. This study compared the LVs which emerged from CCA and PLS analyses of brain-behaviour relationships from the Adolescent Brain Cognitive Development (ABCD) dataset and examined their stability and reproducibility. Methods Structural T1-weighted imaging and behavioural data were accessed from the baseline Adolescent Brain Cognitive Development dataset ( N &gt; 9000, ages = 9-11 years). The brain matrix consisted of cortical thickness estimates in different cortical regions. The behavioural matrix consisted of 11 subscale scores from the parent-reported Child Behavioral Checklist (CBCL) or 7 cognitive performance measures from the NIH Toolbox. CCA and PLS models were separately applied to the brain-CBCL analysis and brain-cognition analysis. A permutation test was used to assess whether identified LVs were statistically significant. A series of resampling statistical methods were used to assess stability and reproducibility of the LVs. Results When examining the relationship between cortical thickness and CBCL scores, the first LV was found to be significant across both CCA and PLS models (singular value: CCA = .13, PLS = .39, p &lt; .001). LV 1 from the CCA model found that covariation of CBCL scores was linked to covariation of cortical thickness. LV 1 from the PLS model identified decreased cortical thickness linked to lower CBCL scores. There was limited evidence of stability or reproducibility of LV 1 for both CCA and PLS. When examining the relationship between cortical thickness and cognitive performance, there were 6 significant LVs for both CCA and PLS ( p &lt; .01). The first LV showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, p &lt; .001). Conclusion CCA and PLS identify different brain-behaviour relationships with limited stability and reproducibility when examining the relationship between cortical thickness and parent-reported behavioural measures. However, both methods identified relatively similar brain-behaviour relationships that were stable and reproducible when examining the relationship between cortical thickness and cognitive performance. The results of the current study suggest that stability and reproducibility of brain-behaviour relationships identified by CCA and PLS are influenced by characteristics of the analyzed sample and the included behavioural measurements when applied to a large pediatric dataset.

Comparing the stability and reproducibility of brain-behaviour relationships found using Canonical Correlation Analysis and Partial Least Squares within the ABCD Sample