Are the Local Blood Oxygen Level–Dependent (BOLD) Signals Caused by Neural Stimulation Response Dependent on Global BOLD Signals Induced by Hypercapnia in the Functional MR Imaging Experiment? Experiments of Long-Duration Hypercapnia and Multilevel Carbon Dioxide Concentration

Signal intensity variations during a single experiment for the illustration of data analysis, with the subject breathing a gas mixture containing 5% CO₂. A, Signal intensity of the activated visual cortex consists of both fBOLD and hBOLD components. For the prehypercapnic and posthypercapnic phases, the signals corresponding to the 2 visual stimulation blocks (2 OFF and 2 ON, as indicated in the figure) are used for fBOLD signal intensity analysis. For the hypercapnic phase, the signals of the first OFF-ON cycle and 2 OFF-ON cycles at the end are used to reflect the transient-state response and the steady-state response, respectively. The fBOLD signal intensity change in each phase is calculated by the difference between the average of 2 ON-state signals and the average of 2 OFF-state signals. Only 1 OFF-ON cycle is chosen for transient-state hypercapnia analysis to minimize the influence from hBOLD-induced baseline changes. B, Signal intensity of the brain area near the visual cortex but without showing fBOLD activations consists of the hBOLD component only. The hBOLD signal intensity change is computed as the difference between the average of the last 25 scans in the hypercapnic phase and the average of the last 50 scans.

The mean percentage changes of BOLD signals as a function of time for the 6 subjects included in this study. Only 4 curves (room air, 3%, 5%, 7%) are shown for better visualization clarity. A, The signal intensity (SI) response shows the ON-OFF fBOLD pattern in response to the visual stimulation, superimposed on hBOLD changes from hypercapnia. Note the gradual decrease of fBOLD amplitude from early to late hypercapnia that is particularly prominent at high concentrations of CO₂ inhalation. Furthermore, steady-state fBOLD signals are seen to decrease with increasing CO₂ concentration. Posthypercapnic fBOLD amplitude returns to a level similar to the prehypercapnic phase. Min indicates minutes. B, The hBOLD signal intensity changes positively correlate with the inhaled CO₂ concentrations. In addition, the time duration to reach steady-state hBOLD level seems to increase with higher hypercapnic perturbations.

Steady-state hBOLD signal intensity changes plotted versus CO₂ concentration. There is a tendency for the hBOLD signal intensity change to be positively correlated with the concentration of inhaled CO₂.