The coupling of BOLD signal variability and degree centrality underlies cognitive functions and psychiatric diseases.

Brain signal variability has been consistently linked to functional integration; however, whether this coupling is associated with cognitive functions and/or psychiatric diseases has not been clarified. Using multiple multimodality datasets, including resting-state functional magnetic resonance imaging (rsfMRI) data from the Human Connectome Project (HCP: N = 927) and a Beijing sample (N = 416) and cerebral blood flow (CBF) and rsfMRI data from a Hangzhou sample (N = 29), we found that, compared with the existing variability measure (i.e., SDBOLD), the mean-scaled (standardized) fractional standard deviation of the BOLD signal (mfSDBOLD) maintained very high test-retest reliability, showed greater cross-site reliability and was less affected by head motion. We also found strong reproducible couplings between the mfSDBOLD and functional integration measured by the degree centrality (DC), both cross-voxel and cross-subject, which were robust to scanning and preprocessing parameters. Moreover, both mfSDBOLD and DC were correlated with CBF, suggesting a common physiological basis for both measures. Critically, the degree of coupling between mfSDBOLD and long-range DC was positively correlated with individuals' cognitive total composite scores. Brain regions with greater mismatches between mfSDBOLD and long-range DC were more vulnerable to brain diseases. Our results suggest that BOLD signal variability could serve as a meaningful index of local function that underlies functional integration in the human brain and that a strong coupling between BOLD signal variability and functional integration may serve as a hallmark of balanced brain networks that are associated with optimal brain functions.