Vascular origins of low‐frequency oscillations in the cerebrospinal fluid signal in resting‐state fMRI: Interpretation using photoplethysmography

In vivo mapping of cerebrovascular oscillations in the 0.05–0.15 Hz remains difficult. Oscillations in the cerebrospinal fluid (CSF) represent a possible avenue for noninvasively tracking these oscillations using resting‐state functional MRI (rs‐fMRI), and have been used to correct for vascular oscillations in rs‐fMRI functional connectivity. However, the relationship between low‐frequency CSF and vascular oscillations remains unclear. In this study, we investigate this relationship using fast simultaneous rs‐fMRI and photoplethysmogram (PPG), examining the 0.1 Hz PPG signal, heart‐rate variability (HRV), pulse‐intensity ratio (PIR), and the second derivative of the PPG (SDPPG). The main findings of this study are: (a) signals in different CSF regions are not equivalent in their associations with vascular and tissue rs‐fMRI signals; (b) the PPG signal is maximally coherent with the arterial and CSF signals at the cardiac frequency, but coherent with brain tissue at ~0.2 Hz; (c) PIR is maximally coherent with the CSF signal near 0.03 Hz; and (d) PPG‐related vascular oscillations only contribute to ~15% of the CSF (and arterial) signal in rs‐fMRI. These findings caution against averaging all CSF regions when extracting physiological nuisance regressors in rs‐fMRI applications, and indicate the drivers of the CSF signal are more than simply cardiac. Our study is an initial attempt at the refinement and standardization of how the CSF signal in rs‐fMRI can be used and interpreted. It also paves the way for using rs‐fMRI in the CSF as a potential tool for tracking cerebrovascular health through, for instance, the potential relationship between PIR and the CSF signal.