Do aggregate, multimodal structural neuroimaging measures replicate regional developmental differences observed in highly cited cellular histological studies?. (April 2022) - Hagler, Donald J.
Abstract: Influential investigations of postmortem human brain tissue showed regional differences in tissue properties at early phases of development, such as between prefrontal and primary sensory cortical regions. Large-scale neuroimaging studies enable characterization of age-related trajectories with much denser sampling of cortical regions, assessment ages, and demographic variables than postmortem tissue analyses, but no single imaging measure perfectly captures what is measured with histology. Using publicly available data from the Pediatric Imaging, Neurocognition, and Genetics (PING) study, including 951 participants with ages ranging from 3 to 21 years, we characterized cortical regional variability in developmental trajectories of multimodal brain imaging measures. Multivariate analyses integrated morphometric and microstructural cortical surface measures. To replicate foundational histological work showing delayed synapse elimination in middle frontal gyrus relative to primary sensory areas, we tested whether developmental trajectories differ between prefrontal and visual or auditory cortex. We extended this to a whole-cortex analysis of interregional differences, producing cortical parcellations with maximally different developmental trajectories. Consistent with the general conclusions of postmortem analyses, our imaging results suggest that prefrontal regions show a protracted period of greater developmental change; however, they also illustrate the challenges of drawing conclusions about the relative maturational phases of different brain regions. Highlights: Multimodal, multivariate, nonlinear modeling, integrating morphometric and microstructural measures. Tested regional developmental differences previously found in highly influential cellular histological studies. Produced cortical parcellations with maximally different, multimodal, developmental trajectories. Findings converge with evidence from histological studies showing delayed prefrontal cortical development. Interregional differences vary by measure and illustrate complexities of defining which regions mature first.