Longitudinal associations between white matter maturation and cognitive development across early childhood.

From birth to 5 years of age, brain structure matures and evolves alongside emerging cognitive and behavioral abilities. In relating concurrent cognitive functioning and measures of brain structure, a major challenge that has impeded prior investigation of their time-dynamic relationships is the sparse and irregular nature of most longitudinal neuroimaging data. We demonstrate how this problem can be addressed by applying functional concurrent regression models (FCRMs) to longitudinal cognitive and neuroimaging data. The application of FCRM in neuroimaging is illustrated with longitudinal neuroimaging and cognitive data acquired from a large cohort (n = 210) of healthy children, 2-48 months of age. Quantifying white matter myelination by using myelin water fraction (MWF) as imaging metric derived from MRI scans, application of this methodology reveals an early period (200-500 days) during which whole brain and regional white matter structure, as quantified by MWF, is positively associated with cognitive ability, while we found no such association for whole brain white matter volume. Adjusting for baseline covariates including socioeconomic status as measured by maternal education (SES-ME), infant feeding practice, gender, and birth weight further reveals an increasing association between SES-ME and cognitive development with child age. These results shed new light on the emerging patterns of brain and cognitive development, indicating that FCRM provides a useful tool for investigating these evolving relationships.