Introduction: Replicability has become an increasing focus within the scientific communities with the ongoing "replication crisis." One area that appears to struggle with unreliable results is resting-state functional magnetic resonance imaging (rs-fMRI). Therefore, the current study aimed at improving the knowledge of endogenous factors that contribute to inter-individual variability. Methods: Arterial blood pressure (BP), body mass, hematocrit, and glycated hemoglobin were investigated as potential sources of between-subject variability in rs-fMRI, in healthy individuals. Whether changes in resting-state networks (rs-networks) could be attributed to variability in the blood-oxygen-level-dependent (BOLD)-signal, changes in neuronal activity, or both was of special interest. Within-subject parameters were estimated by utilizing dynamic-causal modeling, as it allows to make inferences on the estimated hemodynamic (BOLD-signal dynamics) and neuronal parameters (effective connectivity) separately. Results: The results of the analyses imply that BP and body mass can cause between-subject and between-group variability in the BOLD-signal and that all the included factors can affect the underlying connectivity. Discussion: Given the results of the current and previous studies, rs-fMRI results appear to be susceptible to a range of factors, which is likely to contribute to the low degree of replicability of these studies. Interestingly, the highest degree of variability seems to appear within the much-studied default mode network and its connections to other networks. Impact statement We believe that thanks to the evidence that we have collected by analyzing the well-controlled data of the Human Connectome Project with dynamic-causal modeling (DCM) and by focusing not only on the effective connectivity, which is the typical way of using DCM, but also by analyzing the underlying hemodynamic parameters, we were able to explore the underlying vascular dependencies in a much broader perspective. Our results challenge the premise for studying changes in the default mode network as a clinical marker of disease, and we add to the growing list of factors that contribute to resting-state network variability.
Keywords: BMI; blood pressure; dynamic-causal modelling; glycated hemoglobin; hematocrit; resting-state functional magnetic resonance imaging; resting-state network; resting-state variability.