Vigilance and wakefulness modulate estimates of functional connectivity, and, if unaccounted for, they can become a substantial confound in resting-state fMRI. Unfortunately, wakefulness is rarely monitored due to the need for additional concurrent recordings (e.g., eye tracking, EEG). Recent work has shown that strong fluctuations around 0.05Hz, hypothesized to be CSF inflow, appear in the fourth ventricle (FV) when subjects fall asleep. The analysis of these fluctuations could provide an easy way to evaluate wakefulness in fMRI-only data. Here we evaluate this possibility using the 7T resting-state sample from the Human Connectome Project. Our results confirm the presence of those fluctuations in the HCP sample despite this data having relatively small inflow weighting. Moreover, we show that fluctuations of a similar frequency appear in large portions of grey matter with different temporal delays, and that they can substantially influence estimates of functional connectivity. Finally, we demonstrate that the temporal evolution of this signal cannot only help us reproduce previously reported overall sleep patterns in resting-state data, but also predict individual periods of eye closure with 70% accuracy, matching predictions attainable using the amplitude of the global signal (a common fMRI marker of arousal). In summary, our results demonstrate the ubiquitous presence of this signal in a large, publicly available, fMRI sample, its value as a marker of arousal in absence of a better metric, its relationship to the global signal, and its potential nuisance effects on functional connectivity estimates when ignored.
Investigating neural primacy in Major Depressive Disorder: multivariate Granger causality analysis of resting-state fMRI time-series data
