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White matter microstructure is differently associated with executive functioning in youth born with congenital heart
Kaitlyn Easson1,2, May Khairy3, Charles V Rohlicek4
1Advances in Brain & Child Development (ABCD) Research Laboratory, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Insights
White matter alterations in youth with congenital heart disease (CHD) or born preterm impact executive functions differently. Lower myelination and axon density in association bundles correlate with specific executive function deficits in these populations.
Area of Science:
- Neuroscience
- Developmental Psychology
- Pediatric Cardiology
Background:
- Executive function deficits and psychological challenges are prevalent in youth with congenital heart disease (CHD) or born preterm.
- Association white matter tracts are crucial for cognitive and emotional regulation, and their microstructural integrity is vital for neuropsychological health.
Purpose of the Study:
- To investigate the relationship between myelination, axon density, and orientation within association white matter bundles and executive functioning, psychosocial well-being, and resilience in youth with CHD or born preterm.
- To identify specific white matter microstructural alterations associated with executive function deficits in these at-risk youth populations.
Main Methods:
- Utilized advanced neuroimaging techniques (diffusion imaging and T1/T2 relaxometry) to quantify white matter microstructure (myelin water fraction, neurite density index, orientation dispersion index) in association bundles.
- Assessed executive functioning, psychosocial well-being, and resilience using self-report measures in a cohort of youth with CHD, preterm-born youth, and healthy controls.
- Employed linear regression and mediation analyses to explore associations between white matter metrics and neuropsychological outcomes.
Main Results:
- In the CHD group, reduced myelination (lower myelin water fraction) in specific bundles was linked to poorer working memory and self-monitoring, with mediation observed for self-monitoring deficits.
- In the preterm group, decreased axon density (lower neurite density index) correlated with impaired emotional control, and reduced myelination in the superior longitudinal fasciculus III mediated planning/organizing deficits.
- No significant associations were found between white matter microstructure and psychosocial well-being or resilience in either group.
Conclusions:
- Microstructural differences in association white matter bundles, specifically altered myelination and axon density, exhibit distinct associations with executive functioning in youth with CHD and those born preterm.
- These findings highlight the differential impact of white matter alterations on cognitive development in these vulnerable pediatric populations.
- Further research is warranted to explore the interplay of neurobiological, social, and environmental factors influencing white matter microstructure and neuropsychological outcomes.
Introduction:
Executive function deficits and adverse psychological outcomes are common in youth with congenital heart disease (CHD) or born preterm. Association white matter bundles play a critical role in higher order cognitive and emotional functions and alterations to their microstructural organization may result in adverse neuropsychological functioning. This study aimed to examine the relationship of myelination and axon density and orientation alterations within association bundles with executive functioning, psychosocial well-being, and resilience in youth with CHD or born preterm.
Methods:
Youth aged 16 to 26 years born with complex CHD or preterm at ≤33 weeks of gestational age and healthy controls completed a brain MRI and self-report assessments of executive functioning, psychosocial well-being, and resilience. Multicomponent driven equilibrium single-pulse observation of T1 and T2 and neurite orientation dispersion and density imaging were used to calculate average myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index values for eight bilateral association bundles. The relationships of bundle-average metrics with neuropsychological outcomes were explored with linear regression and mediation analyses.
Results:
In the CHD group, lower MWF in several bundles was associated with poorer working memory and behavioral self-monitoring and mediated self-monitoring deficits relative to controls. In the preterm group, lower NDI in several bundles was associated with poorer emotional control and lower MWF in the left superior longitudinal fasciculus III mediated planning/organizing deficits relative to controls. No significant relationships were observed for psychosocial well-being or resilience.
Conclusion:
The findings of this study suggest that microstructural alterations to association bundles, including lower myelination and axon density, have different relationships with executive functioning in youth with CHD and youth born preterm. Future studies should aim to characterize other neurobiological, social, and environmental influences that may interact with white matter microstructure and neuropsychological functioning in these at-risk individuals.
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