BACKGROUND AND PURPOSE: The relationship between the local blood oxygen level-dependent (BOLD) signals caused by neural stimulation (fBOLD) and the global BOLD signals induced by hypercapnia (hBOLD) has not been fully investigated. In this study, we examine whether fBOLD is modulated by hBOLD signals, by means of experiments using a relatively wide range of inhaled carbon dioxide (CO2) for a long duration of 5 minutes. MATERIALS AND METHODS: Ten healthy volunteers were recruited, each undergoing 6 separate experiments by inhaling gas mixtures with different fractions of CO2 (room air, 3%-7%). Each experiment contained 3 phases, prehypercapnic, hypercapnic, and posthypercapnic, during which boxcar visual stimulus was given. The local fBOLD signals were measured from areas showing activation patterns highly correlated with the visual stimulus paradigm, whereas the global hBOLD signals were measured from areas showing no visual activations. Percentage changes in fBOLD during transient-state hypercapnia and steady-state hypercapnia were both investigated in response to varying degrees of hypercapnic perturbations. RESULTS: The hBOLD signals increased with increase of inhaled CO2 fractions. The duration for the hBOLD signals to reach steady state prolonged with increase of inhaled CO2 fractions. Normalized fBOLD ratio was inversely related to the inhaled CO2 during steady-state hypercapnia but showed positive association with hBOLD during transient-state hypercapnia. CONCLUSION: Our study concludes that the steady-state fBOLD signal intensity is dependent on and inversely related to the hBOLD signals. Previous reports documenting independent and additive relationships between hBOLD and fBOLD may likely be due to transient-state observations.
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