Resting-State Functional Brain Connectivity and Neurodevelopmental Profiles in 3-Year-Olds with Congenital Heart Disease

Abstract

Background/Objectives: Congenital heart disease (CHD) is associated with altered brain development and an increased risk of neurodevelopmental difficulties, particularly in more severe forms of the condition. Although alterations in functional brain connectivity have been reported before and after the first corrective surgery in early infancy, as well as in adulthood, little is known about their presentation in early childhood and their association with neurodevelopmental outcomes. This study aimed to characterize resting-state functional connectivity in 3-year-old children with moderate-to-severe CHD and to examine its associations with neurodevelopmental outcomes, including cognitive, language, and motor abilities. Methods: Twenty-five 3-year-old children with moderate-to-severe CHD and 28 age-matched healthy controls completed resting-state functional near-infrared spectroscopy (fNIRS) analysis and a standardized neurodevelopmental assessment. Connectivity was compared across networks using a repeated-measures analysis of covariance (ANCOVA), then within each network separately, controlling for maternal socioeconomic status and with sex as a factor. Associations with neurodevelopmental measures were examined using hierarchical linear regressions adjusted for group, sex, and socioeconomic status, with connectivity-by-group interactions tested. Results: Children with moderate-to-severe CHD showed lower resting-state functional connectivity than controls specifically within the right fronto-temporal network, with no group differences in the four remaining networks, as well as poorer language performance. Greater inter-hemispheric functional connectivity was associated with fewer executive function difficulties and better overall motor performance across participants, and greater frontal connectivity with better motor coordination, with no significant differences in these associations between groups. Conclusions: Preschool-aged children with CHD show regionally circumscribed alterations in functional connectivity and language vulnerabilities, while the associations between connectivity and executive and motor functioning appear to extend across both CHD and typically developing children.