Cornea, E. | Search bioRxiv

bioRxiv2025

Impacts of perinatal factors on white matter outcome at 8 to 10 years by diffusion tensor imaging

BackgroundWhile perinatal factors are known to influence brain development, their long-term impact on white matter microstructure remains incompletely understood. Previous studies using tract-based spatial statistics (TBSS) have shown limited associations between neonatal measures and later white matter development. MethodsWe investigated associations between perinatal factors (birth weight [BW], gestational age [GA], and head circumference [HC]) and white matter microstructure in 117 children aged 8-10 years from the UNC Early Brain Development Study cohort. Diffusion tensor imaging (DTI) data were analyzed using a fiber tract-based framework examining 54 major white matter tracts. Statistical analysis was performed using a functional analysis of fiber tract profiles. ResultsGA and BW showed widespread significant associations with white matter microstructure (38 and 36 out of 54 tracts, respectively), while HC showed limited associations (3 out of 54 tracts). Post-hoc univariate analysis revealed stronger associations with axial diffusivity (AD) compared to radial diffusivity (RD) or fractional anisotropy (FA). AD associations with BW, GA, and HC were found in 30, 31, and 8 tracts, respectively. ConclusionsUsing a fiber tract-based analysis approach, we demonstrated that GA and BW are strongly predictive of white matter organization at school age, while HC showed limited predictive power. The predominant associations with AD suggest these perinatal factors primarily influence axonal organization rather than myelination. These findings enhance our understanding of how early life factors impact long-term brain development.

neuroscience↗

bioRxiv2024

Sex differences in brain-behavior relationships in the first two years of life

BackgroundEvidence for sex differences in cognition in childhood is established, but less is known about the underlying neural mechanisms for these differences. Recent findings suggest the existence of brain-behavior relationship heterogeneities during infancy; however, it remains unclear whether sex underlies these heterogeneities during this critical period when sex-related behavioral differences arise. MethodsA sample of 316 infants was included with resting-state functional magnetic resonance imaging scans at neonate (3 weeks), 1, and 2 years of age. We used multiple linear regression to test interactions between sex and resting-state functional connectivity on behavioral scores of working memory, inhibitory self-control, intelligence, and anxiety collected at 4 years of age. ResultsWe found six age-specific, intra-hemispheric connections showing significant and robust sex differences in functional connectivity-behavior relationships. All connections are either with the prefrontal cortex or the temporal pole, which has direct anatomical pathways to the prefrontal cortex. Sex differences in functional connectivity only emerge when associated with behavior, and not in functional connectivity alone. Furthermore, at neonate and 2 years of age, these age-specific connections displayed greater connectivity in males and lower connectivity in females in association with better behavioral scores. ConclusionsTaken together, we critically capture robust and conserved brain mechanisms that are distinct to sex and are defined by their relationship to behavioral outcomes. Our results establish brain-behavior mechanisms as an important feature in the search for sex differences during development. Plain language summaryEarly childhood differences exist in mental processes and behavior between males and females. The brain-basis for these sex differences may arise in infancy. Indeed, small brain differences in infancy may contribute to major changes in cognitive ability throughout childhood. However, few studies have examined sex differences in brain functionality in infancy and their relationship to future behaviors in early childhood. In this study, we aimed to study this relationship by using sex differences in brain functional measures in neonate, 1, and 2-year-olds and 4-year behavioral outcomes. We identified six functional connections with robust brain-behavior sex differences. These connections were unique to frontal brain regions. Also, these connections were not specific to the brain and were only evident when associated with future behavior. In brief, our analysis shows distinct age-specific brain-behavior relationships in males and females in early childhood. This is helpful for a better understanding of brain-based prediction of behavior and informed intervention of future disorders and disabilities characterized by a sex bias. HighlightsO_LIMultiple linear regression was used to test the interaction between sex and early childhood resting-state functional connectivity on future behavioral scores C_LIO_LISix age-specific, intra-hemispheric functional connections displayed sex differences C_LIO_LIMost connections exist within prefrontal regions (with one connection in the temporal pole) C_LIO_LIFunctional connections are specific to brain-behavior relationships and not in brain connectivity alone C_LIO_LISex differences in brain-behavior relationships are robust at smaller sample sizes C_LI

neuroscience↗