RT Journal Article SR Electronic T1 Developmental coupling of cerebral blood flow and fMRI fluctuations in youth JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.07.28.454179 DO 10.1101/2021.07.28.454179 A1 Erica B. Baller A1 Alessandra M. Valcarcel A1 Azeez Adebimpe A1 Aaron Alexander-Bloch A1 Zaixu Cui A1 Ruben C. Gur A1 Raquel E. Gur A1 Bart L. Larsen A1 Kristin A. Linn A1 Carly M. O’Donnell A1 Adam R. Pines A1 Armin Raznahan A1 David. R. Roalf A1 Valerie J. Sydnor A1 Tinashe M. Tapera A1 M. Dylan Tisdall A1 Simon Vandekar A1 Cedric H. Xia A1 John A. Detre A1 Russell T. Shinohara A1 Theodore D. Satterthwaite YR 2021 UL http://biorxiv.org/content/early/2021/07/29/2021.07.28.454179.abstract AB 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). Females had stronger coupling in the frontoparietal network than males (pfdr <0.05). Better executive function was associated with decreased coupling in the somatomotor network (pfdr <0.05). Overall, we found that CBF-ALFF coupling evolves in development, differs by sex, and is associated with individual differences in executive function. Future studies will investigate relationships between maturational changes in CBF-ALFF coupling and the presence of psychiatric symptoms in youth.SIGNIFICANCE The functions of the human brain are metabolically expensive and reliant on coupling between cerebral blood flow and neural activity. Previous neuroimaging studies in adults demonstrate tight physiology-function coupling, but how this coupling evolves over development is unknown. Here, we examine the relationship between blood flow as measured by arterial spin labeling and the amplitude of low frequency fluctuations from resting-state magnetic resonance imaging across a large sample of youth. We demonstrate regionally specific changes in coupling over age and show that variations in coupling are related to biological sex and executive function. Our results highlight the importance of CBF-ALFF coupling throughout development; we discuss its potential as a future target for the study of neuropsychiatric diseases.Competing Interest StatementThe authors have declared no competing interest.