Dynamic Brain-Body Coupling of Breath-by-Breath O₂-CO₂Exchange Ratio with Resting State Cerebral Hemodynamic Fluctuations

Abstract

Running headline: Dynamic brain-body coupling between resting state hemodynamics and O 2 -CO 2 exchange ratio 2 ABSTRACT The origin of low frequency cerebral hemodynamic fluctuations (CHF) in resting state remains unknown. Here we studied the contribution of respiratory gas exchange (RGE) metrics to CHF during spontaneous breathing. RGE metrics include the breath-by-breath changes of partial pressure of oxygen (ΔPO 2 ) and carbon dioxide (ΔPCO 2 ) between end inspiration and end expiration, and their ratio breath-by-breath O 2 -CO 2 exchange ratio (bER). We used transcranial Doppler sonography to evaluate CHF changes during spontaneous breathing by measuring the cerebral blood flow velocity (CBFv) in the middle cerebral arteries. The regional CHF changes during spontaneous breathing were mapped with blood oxygenation level dependent (BOLD) signal changes using functional magnetic resonance imaging (fMRI) technique. We found that prominent oscillations with periods of 0.5 to 2 minutes characterized Δ PO 2 , Δ PCO 2 and bER.The oscillations of bER were coherent with CHF during spontaneous breathing at the frequency range of 0.008-0.03Hz which is consistent with the low frequency resting state CHF. CHF had strong correlation with bER, followed by Δ PO 2 and then by Δ PCO 2 . Brain regions with the strongest bER-CHF coupling overlapped with many areas of default mode network. Although the physiological mechanisms underlying the strong correlation between bER and CHF are not completely understood, our findings suggest the contribution of bER to low frequency resting state CHF. It also provides a novel insight of brain-body interaction via CHF and oscillations of RGE metrics. 3 KEYWORDS Resting State Blood oxygenation level dependent Functional magnetic resonance imaging Breath-by-breath O 2 -CO 2 exchange ratio Cerebral blood flow velocity Transcranial Doppler sonography 1 0