Mapping the end-tidal CO2 response function in the resting-state BOLD fMRI signal: spatial specificity, test-retest reliability and effect of fMRI sampling rate.

The blood oxygenation level dependent (BOLD) signal measures brain function indirectly through physiological processes and hence is susceptible to global physiological changes. Specifically, fluctuations in end-tidal CO2 (PETCO2), in addition to cardiac rate variation (CRV), and respiratory volume per time (RVT) variations, have been known to confound the resting-state fMRI (rs-fMRI) signal. Previous studies addressed the resting-state fMRI response function to CRV and RVT, but no attempt has been made to directly estimate the voxel-wise response function to PETCO2. Moreover, the potential interactions among PETCO2, CRV, and RVT necessitate their simultaneous inclusion in a multi-regression model to estimate the PETCO2 response. In this study, we use such a model to estimate the voxel-wise PETCO2 response functions directly from rs-fMRI data of nine healthy subjects. We also characterized the effect of sampling rate (TR=2seconds vs. 323ms) on the temporal and spatial variability of the PETCO2 response function in addition to that of CRV and RVT. In addition, we assess the test-retest reproducibility of the response functions to PETCO2, CRV and RVT. We found that despite overlaps across their spatial patterns, PETCO2 explains a unique portion of the rs-fMRI signal variance compared to RVT and CRV. We also found the shapes of the estimated responses are very similar between long- and short-TR data, although responses estimated from short-TR data have higher reproducibility. Crown