Brain-wide functional connectivity artifactually inflates throughout functional magnetic resonance imaging scans.

Functional magnetic resonance imaging (fMRI) is a central tool for investigating human brain function, organization and disease. Here, we show that fMRI-based estimates of functional brain connectivity artifactually inflate at spatially heterogeneous rates during resting-state and task-based scans. This produces false positive connection strength changes and spatial distortion of brain connectivity maps. We demonstrate that this artefact is driven by temporal inflation of the non-neuronal, systemic low-frequency oscillation (sLFO) blood flow signal during fMRI scanning and is not addressed by standard denoising procedures. We provide evidence that sLFO inflation reflects perturbations in cerebral blood flow by respiration and heart rate changes that accompany diminishing arousal during scanning, although the mechanisms of this pathway are uncertain. Finally, we show that adding a specialized sLFO denoising procedure to fMRI processing pipelines mitigates the artifactual inflation of functional connectivity, enhancing the validity and within-scan reliability of fMRI findings.