Abstract
BACKGROUND: Fetal alcohol spectrum disorder (FASD) is associated with widespread neurocognitive deficits, including impairments in executive function, attention, and inhibitory control. However, understanding of the neural mechanisms underlying these deficits in young children 6-8 years of age remains limited. This study investigated functional connectivity (FC) alterations in key brain networks related to inhibitory control and executive function in children with FASD compared to typically developing controls (TDC). METHODS: Seed-based connectivity (SBC) analysis was conducted in 27 children with FASD and 30 TDC, focusing on the medial prefrontal cortex (MPFC) within the Default Mode Network (DMN) and Frontal Parietal Network (FPN). FC differences were assessed across resting-state conditions (eyes closed vs. eyes open) and correlated with Conners Continuous Performance Test (CPT). RESULTS: Children with FASD exhibited significantly reduced FC between MPFC and limbic regions, including the amygdala, hippocampus, and brainstem, suggesting impairments in emotion regulation and cognitive control. The FPN showed altered connectivity with the middle temporal gyrus and inferior lateral occipital cortex, regions crucial for higher order cognitive processing. Significant interactions between groups and resting-state condition were observed, with altered connectivity patterns in the MPFC and FPN suggesting sensory-motor and cognitive control disruptions. FC patterns in these networks were significantly correlated with CPT performance, including increased errors of omission and reaction time variability, indicating deficits in sustained attention and response inhibition. CONCLUSION: Our findings reveal early disruptions in FC within the DMN and FPN in young children with FASD, highlighting altered interactions between key brain regions implicated in inhibitory control and executive function. These neural alterations were associated with behavioral deficits in attention and cognitive control, suggesting that FC abnormalities may underlie core cognitive impairments in FASD. Findings underscore the importance of early identification and intervention strategies targeting neural network dysfunctions to improve cognitive outcomes in children with FASD.