Very Preterm Birth and Cortical Expansion in Early Life

From infancy to adulthood, the human cortex expands three-fold, with consequences for cognition and behavior. While preclinical and histological research suggests that cortical expansion is driven by underlying microstructural processes including dendritic arborization and synaptogenesis, it remains poorly understood whether patterns of expansion reflect underlying changes in cortical microstructure in human samples. Importantly, this key developmental process of cortical expansion may have clinical implications, as surface area (the end result of expansion) has been linked to both cognitive and psychiatric outcomes in numerous clinical populations. Thus, work exploring the biological underpinnings and functional consequences of cortical expansion in early childhood is critically important. Children born very preterm (VPT; prior to 32 weeks gestation) are a population of specific interest, as they experience increased rates of aberrant brain development as well as comorbid ADHD, autism, and anxiety and impairments in executive functioning (EF) in childhood. Further still, previous work has shown that over the first decade of life, they experience altered expansion in association cortices known to be important for cognitive and psychiatric functioning. However, it remains unclear if these alterations in cortical expansion relate to changes in cortical microstructure and if these patterns of altered expansion underlie the increased rates of EF and psychiatric difficulties common in VPT children. The current proposal will leverage ten years of unique existing data from a highly valuable, prospective, longitudinal cohort of 52 VPT and 41 full-term (FT) children (currently being studied through R37 MH113570) to address these gaps. It is hypothesized that decreased cortical expansion in association cortices will predict greater EF and psychiatric impairments at age 10 years, and that these patterns of expansion will be predicted by cortical microstructure differences already visible in infancy. To test this, in Aim 1, the applicant will innovatively analyze both longitudinal diffusion and structural imaging data to define the relationship between spatial patterns of cortical microstructure and patterns of cortical expansion in VPT and FT children. In Aim 2, the applicant will determine how individual differences in cortical expansion relate to EF and psychiatric functioning at age 10 years in the same sample. By identifying brain-based risk factors for cognitive and psychiatric impairments, this work will expand our understanding of how the brain develops and could facilitate the creation of more targeted, early treatments for at-risk children. Importantly, this proposed project will allow the applicant to develop her skills in diffusion neuroimaging, longitudinal data analysis, scientific communication, and child psychiatry under the highly valuable mentorship of Drs. Cynthia Rogers and Chris Smyser at Washington University. This will provide the candidate with a strong foundation as she pursues her ultimate goal of becoming an academic child psychiatrist who studies how early interventions support brain development and improve psychiatric functioning in children. Project Number: 1F30HD119918-01 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Lisa Gorham | Institution: WASHINGTON UNIVERSITY, SAINT LOUIS, MO | Award Amount: $36,673 | Activity Code: F30 | Study Section: Special Emphasis Panel[ZRG1 F01A-S (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1F30HD11991801