Neurovascular reactivity increases across development in the visual and frontal pole 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 breath-hold activation is an important aspect to understand the neurovascular response in fMRI studies, it can be used to account for developmental differences in vascular response. This study examines how the vascular response changes over age in a longitudinal children breath-hold dataset from the Nathan Kline Institute (NKI) Rockland Sample (ages 6 to 18 years old at enrollment). A principal component analysis (PCA) approach was applied to derive brain activation from breath-hold data. To model both the longitudinal and cross-sectional effects of age on breath-hold activation, 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 activation in the frontal pole, medial visual, and lateral visual 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 vascular response increases across development in a brain network-specific manner and may also be nonlinear depending on the brain network. Therefore, fMRI studies investigating the developmental period should account for vascular changes which occur with age. ### Competing Interest Statement The authors have declared no competing interest.