Developmental coupling of cerebral blood flow and fMRI fluctuations in youth

Abstract

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.

Voxel-wise Intermodal Coupling Analysis of Two or More Modalities using Local Covariance Decomposition

“…This suggests that in neurodevelopment, there is change in not only blood flow, resting state fluctuations, and local connectivity individually, but also in the strength of interaction among these features. These findings are consistent with and fortify the literature demonstrating the importance of frontoparietal and default networks as regions for change in neurodevelopment (Baller et al, 2021;Chai et al, 2017;Fair et al, 2008;Lin et al, 2019). Outside of neurodevelopment, our findings are consistent with previous work showing that coupling between CBF and functional connectivity strength is stronger in frontoparietal and default networks than regions outside these networks (Tak et al, 2015).…”

“…In the cortex, the rarity of coupling-sex associations suggests that this coupling may not play a role in explaining cortical sexbased differences or that this relationship is more complex than our analyses could uncover. These cortical findings are of interest when compared to previous work showing a high proportion of the cortex had significant associations between sex and CBF-ALFF coupling (Baller et al, 2021). Together, these studies demonstrate that three-modality coupling identifies unique relationships when compared to two-modality coupling.…”

“…On the sub-regional local scale, studies from our group on coupling between cortical thickness and sulcal depth have suggested the cortical sheet is generally thinner in sulcal locations than in gyral locations and that this relationship was more spatially heterogeneous than previously described (Vandekar et al, 2016). A separate study exploring local IMCo between CBF and resting-state amplitude of low-frequency fluctuations (ALFF) showed that age-related declines in this measure of neurovascular coupling were most pronounced during mid-adolescence and were enriched in the dorsal attention network (Baller et al, 2021). There were also differences in CBF-ALFF coupling between males and females which were enriched in the frontoparietal network.…”

“…Image processing of T1-weighted structural images, pcASL scans, and rfMRI scans have been previously described (Baller et al, 2021;Gur et al, 2020). They are summarized here in brief.…”

“…There is increased availability of multi-modality neuroimaging data on individual subjects, with each modality containing unique information about brain structure or function. Such data allow us to explore patterns in individual modalities as well as patterns in the relationships between modalities, which we call intermodal coupling (IMCo), at global, regional, or local resolutions (Baller et al, 2021;Gu et al, 2021;Honey et al, 2009;Shokri-Kojori et al, 2019;Tak et al, 2015;Uddin, 2013;Valcarcel et al, 2018aValcarcel et al, , 2018bVandekar et al, 2016). The progress made by these IMCo studies have transformed our understanding of the brain, and it suggests that advancements in the methodology for studying IMCo have the potential to further enable such insights.…”