Cortical alterations associated with executive function deficits in youth with a congenital heart defect
Authors: Abboud Fatme , Easson Kaitlyn , Ehrler Melanie , Ziolkowski Justine , Rohlicek Charles V. , Latal Bea , Saint-Martin Christine , Gilbert Guillaume , Greutmann Matthias , Devenyi Gabriel A. , Tuura Ruth O’Gorman , Chakravarty M. Mallar , Brossard-Racine Marie 
Published: October 2024

Abstract
Adolescents and young adults born with a complex congenital heart defect (CHD) are at risk for executive function (ExF) impairments, which contribute to the psychological and everyday burden of CHD. Cortical dysmaturation has been well described in fetuses and neonates with CHD and early evidence suggests that cortical alterations in thickness, surface area, and gyrification index are non-transient and can be observed in adolescents with CHD. However, cortical alterations have yet to be correlated with ExF deficits in youth with CHD. This study aims to use a data-driven approach to identify the most important cortical features associated with ExF deficits in adolescents and young adults with CHD. To do so, we combined two comparable datasets acquired at the Research Institute of the McGill University Health Centre and the University Children’s Hospital Zurich, each including both youth with CHD and healthy controls. For each participant, a high-resolution T1-weighted magnetic resonance image, a self-reported ExF assessment (the Behaviour Rating Inventory of Executive Function – Adult Scale), and their clinical and demographic characteristics were available. Corticometric Iterative Vertex-Based Estimation of Thickness (CIVET) was used to extract cortical thickness, cortical surface area, and local gyrification index measures. Using orthogonal projective non-negative matrix factorization (OPNMF), we identified non-overlapping spatial components that integrate cortical thickness, cortical surface area, and local gyrification index and capture structural covariance across these features. Behavioral partial least squares correlation (bPLS) analysis was then used to compute correlations between the individual variability in the OPNMF covariance patterns and ExF outcomes for each subject. A total of 56 youth with CHD who underwent cardiopulmonary bypass surgery before 3 years of age and 56 age- and sex-matched healthy controls were included in our analyses. Cortical grey matter volume, cortical thickness, and cortical surface area were found to be significantly reduced in CHD patients compared to controls. OPNMF identified 12 stable cortex-wide components summarizing the inter-subject variability in cortical thickness, cortical surface area, and local gyrification index. bPLS revealed two significant latent variables (LV) accounting for a total of 82.8% of the variance in the sample, each describing distinct patterns between the brain and cognitive data. LV1 summarized a pattern of belonging to the CHD group, worse scores on most Behaviour Rating Inventory of Executive Function – Adult Scale (BRIEF-A) scales, younger age at MRI, and female sex. This pattern was associated with increased cortical thickness, local gyrification index, and decreased cortical surface area in several OPNMF components. Finally, we identified a positive relationship between the LV1 brain-behavior pattern and total aortic cross-clamp time in the CHD group, indicating that longer aortic cross-clamp time was associated with worse neuropsychological outcomes. In this study, we uncover novel multivariate relationships between ExF and alterations in cortical thickness, surface area, and local gyrification index in adolescents and young adults with CHD using a data-driven approach. Although our findings highlight the important role played by the cortex in higher-order cognitive processes, future studies are needed to elucidate the individual contribution of individual and clinical attributes into the deficits observed in this population.