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 (Pet_co2) relate to BOLD signal time series. A significantly longer latency of BOLD signal changes following Pet_co2 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 Pet_co2 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 Pet_co2 and BOLD. The identified dominant Pet_co2→BOLD directional coupling supports the notion that Pet_co2 fluctuations are indeed a cause of resting BOLD variance in the majority of subjects.