The maturation of regional brain volumes from birth to preadolescence is a critical developmental process that underlies emerging brain structural connectivity and function. Regulated by genes and environment, the coordinated growth of different brain regions plays an important role in cognitive development. Current knowledge about structural network evolution is limited, partly due to the sparse and irregular nature of most longitudinal neuroimaging data. In particular, it is unknown how factors such as mother’s education or sex of the child impact the structural network evolution. To address this issue, we propose a method to construct evolving structural networks and study how the evolving connections among brain regions as reflected at the network level are related to maternal education and biological sex of the child and also how they are associated with cognitive development. Our methodology is based on applying local Fréchet regression to longitudinal neuroimaging data acquired from the RESONANCE cohort, a cohort of healthy children (245 females and 309 males) ranging in age from 9 weeks to 10 years. Our findings reveal that sustained highly coordinated volume growth across brain regions is associated with lower maternal education and lower cognitive development. This suggests that higher neurocognitive performance levels in children are associated with increased variability of regional growth patterns as children age.

For all MR image acquisition, children under 4 years of age were scanned during natural and non-sedated sleep and older children were imaged whilst watching a movie or other video. Our imaging protocol included relaxometry, multi-shell diffusion, resting-state connectivity, and magnetic resonance spectroscopy acquisitions in addition to the anatomical data. As a result, depending on child compliance (sleeping and/or motion), high-quality anatomical data were not collected or available for every child at every scan time-point. Following data acquisition, scans were inspected to ensure there were no motion-related artifacts and image blurring and ghosting. T1-weighted anatomical data were acquired on a 3T Siemens Trio scanner with a 12-channel head RF array. T1-weighted magnetization-prepared rapid acquisition gradient echo anatomical data were acquired with an isotropic voxel volume of 1.2×1.2×1.2 mm³, resampled to 0.9×0.9×0.9 mm³. Sequence-specific parameters were: TE = 6.9 ms; TR = 16 ms; inversion preparation time = 950 ms; flip angle = 15 degrees; BW = 450 Hz/Pixel. The acquisition matrix and field of view were varied according to child head size in order to maintain a constant voxel volume and spatial resolution across all ages. Using a multistep registration procedure, a series of age-specific anatomical T1-weighted templates were created corresponding to 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 60, 72, 84, 96 and 108-month ages. At least 10 boys and 10 girls were included in each template. An overall study template was then created from these age templates, which was aligned to the MNI152 template. Each child’s anatomical T1-weighted image was transformed into MNI space by first aligning to their age-appropriate template and then applying the pre-computed transformation to MNI space, with the calculated individual forward and reverse transformations saved and used for the volumetric analysis described below. All template creation and image alignment were performed using a 3D nonlinear approach with cross-correlation and mutual information cost functions. We then applied the Desikan-Killiany-Tourville (DKT) cortical labeling protocol, FreeSurfer's wmparc and aseg non-cortical (plus white matter) labels through Mindboggle, resulting in volumetric output from 96 brain regions. Five regions with very small volumes were excluded: left inferior lateral ventricle, left vessel, right inferior lateral ventricle, left basal forebrain, and right basal forebrain.