The effects of respiratory CO2 fluctuations in the resting-state BOLD signal differ between eyes open and eyes closed

Resting fluctuations in arterial CO2 (a cerebral vasodilator) are believed to be an important source of low-frequency blood oxygenation level dependent (BOLD) signal fluctuations. In this study we focus on the two commonly used resting-states in functional magnetic resonance imaging experiments, eyes open and eyes closed, and quantify the degree to which measured spontaneous fluctuations in the partial pressure of end-tidal CO2 (Petco2) relate to BOLD signal time series. A significantly longer latency of BOLD signal changes following Petco2 fluctuations was found in the eyes closed condition compared to with eyes open, which may reveal different intrinsic vascular response delays in CO2 reactivity or an alteration in the net BOLD signal arising from Petco2 fluctuations and altered neural activity with eyes closed. By allowing a spatially varying time delay for the compensation of this temporal difference, a more spatially consistent CO2 correlation map can be obtained. Finally, Granger-causality analysis demonstrated a “causal” relationship between Petco2 and BOLD. The identified dominant Petco2→BOLD directional coupling supports the notion that Petco2 fluctuations are indeed a cause of resting BOLD variance in the majority of subjects.