Modeling of regional dynamic CO2 reactivity in respiratory related brain areas using BOLD fMRI

The cerebrovascular bed is very sensitive to CO₂ changes, particularly the areas responsible for generation and control of respiratory rhythm. We have used BOLD functional magnetic resonance imaging (fMRI) and externally induced CO₂ challenges that stimulate respiration, to identify respiratory areas in-vivo in humans and to quantify the dynamic effects of CO₂ on the BOLD fMRI signal (dynamic CO₂ reactivity). We sought to identify regional differences in dynamic reactivity within the brainstem and other respiratory related areas (thalamus) by using linear impulse response (IR) and nonlinear Volterra models, as well as experimental measurements obtained during spontaneous breathing and larger externally induced step CO₂ changes (end-tidal forcing). The results revealed areas in the brainstem and thalamus that responded strongly to the external CO₂ stimuli, which correspond to respiratory nuclei identified in recent rodent studies, as well as pronounced regional differences in CO₂ reactivity.