Transient arousal modulations are responsible for resting-state functional connectivity changes associated with head motion

Correlations of resting-state functional magnetic resonance imaging (rsfMRI) signals are being widely used for assessing functional connectivity of healthy and diseased brains. However, an association was recently observed between rsfMRI connectivity modulations and head motion and regarded as a causal relationship, which has raised serious concerns about the validity of many rsfMRI findings. Here, we studied the origin of this rsfMRI-motion association and its relationship to arousal modulations. By using a template-matching method to locate arousal-related fMRI changes, we showed that the effects of high motion time points on rsfMRI connectivity are due to their significant overlap with arousal-affected time points. The finding suggests that the association between rsfMRI connectivity and head motion arises from their co-modulations at transient arousal modulations, and this information is critical not only for proper interpretation of motion-associated rsfMRI connectivity changes but also for controlling the potential confounding effects of arousal modulation on rsMRI metrics.