Cerebrovascular reactivity increases across development in multiple networks as revealed by a breath-holding task: a longitudinal fMRI study

Functional magnetic resonance imaging (fMRI) has been widely used to understand the neurodevelopmental changes that occur in cognition and behavior across childhood. The blood-oxygen-level-dependent (BOLD) signal obtained from fMRI is understood to be comprised of both neuronal and vascular information. However, it is unclear whether the vascular response is altered across age in studies investigating development in children. Since the breath-hold task is commonly used to understand cerebrovascular reactivity in fMRI studies, it can be used to account for developmental differences in vascular response. This study examines how the cerebrovascular response changes over age in a longitudinal children's breath-hold dataset from the Nathan Kline Institute (NKI) Rockland Sample (ages 6 to 18 years old at enrollment). A general linear model (GLM) approach was applied to derive cerebrovascular reactivity from breath-hold data. To model both the longitudinal and cross-sectional effects of age on breath-hold response, we used mixed effects modeling with the following terms: linear, quadratic, logarithmic, and quadratic-logarithmic, to find the best-fitting model. We observed increased breath-hold BOLD signal in multiple networks across age, in which linear and logarithmic mixed effects models provided the best fit with the lowest Akaike Information Criterion (AIC) scores. This shows that the cerebrovascular response increases across development in a brain network-specific manner. Therefore, fMRI studies investigating the developmental period should account for cerebrovascular changes which occur with age.