The Significance and Limited Influence of Cerebrovascular Reactivity on Age and Sex Effects in Task- and Resting-State Brain Activity

Functional MRI (fMRI) measures the blood-oxygen-level dependent (BOLD) signals, which provide an indirect measure of neural activity mediated by neurovascular responses. Cerebrovascular reactivity affects both task-induced and resting-state BOLD activity and may confound inter-individual effects observed in BOLD-based measures, such as those related to aging and biological sex. To investigate this, we examined a large open-access fMRI dataset containing a breath-holding task, checkerboard task, and resting-state scans. We used the breath-holding task to measure cerebrovascular reactivity, used the checkerboard task to obtain task-based activations, and from the resting-state data, we quantified the resting-state amplitude of low-frequency fluctuations (ALFF), and resting-state regional homogeneity (ReHo). We hypothesized that cerebrovascular reactivity would be correlated with BOLD measures and that accounting for these correlations would result in better estimates of age and sex effects. Our analysis showed that cerebrovascular reactivity was correlated with checkerboard task activations in the visual cortex and with ALFF and ReHo in widespread fronto-parietal regions, as well as regions with large vessels. We also found significant age and sex effects in cerebrovascular reactivity, some of which overlapped with those observed in ALFF and ReHo scores. Finally, we demonstrated that correcting for the effects of cerebrovascular reactivity had very limited influence on the estimates of age and sex. Our results highlight the limitations of accounting for cerebrovascular reactivity with the current breath-holding task.