Developmental Coupling of Cerebral Blood Flow and fMRI Fluctuations in Youth

To support brain development during youth, the brain must balance energy delivery and consumption. Previous studies in adults have demonstrated high coupling between cerebral blood flow and brain function as measured using functional neuroimaging, but how this relationship evolves over adolescence is unknown. To address this gap, we studied a sample of 831 children and adolescents (478 females, ages 8-22) from the Philadelphia Neurodevelopmental Cohort who were scanned at 3T with both arterial spin-labeled (ASL) MRI and resting-state functional MRI (fMRI). Local coupling between cerebral blood flow (CBF, from ASL) and the amplitude of low frequency fluctuations (ALFF, from fMRI) was first quantified using locally weighted regressions on the cortical surface. We then used generalized additive models to evaluate how CBF-ALFF coupling was associated with age, sex, and executive function. Enrichment of effects within canonical functional networks was evaluated using spin-based permutation tests. Our analyses revealed tight CBF-ALFF coupling across the brain. Whole-brain CBF-ALFF coupling decreased with age, largely driven by coupling decreases in the inferior frontal cortex, precuneus, visual cortex, and temporoparietal cortex (pfdr<0.05). Furthermore, we found that females had stronger coupling in the frontoparietal network than males (pfdr<0.05) and that better executive function was associated with decreased coupling in the somatomotor network (pfdr<0.05). These results emphasize that CBF-ALFF coupling undergoes development in youth and is linked to individual differences in cognition. As such, this relationship may be a valuable marker of both normal brain development and abnormalities associated with neuropsychiatric illness in youth.