Background: Voluntary breath-holding (BH) is regulated by central neural control and respiratory centers in the brainstem. Volitional BH results in general hypoxemia and hypercapnia and triggers the response of the central respiratory centers to restore breathing. To decipher the mechanisms behind the fMRI-BOLD response to volitional apnea, a pilot study was carried out in healthy volunteers.
Methods: In 21 healthy human subjects (mean age ± SD, 32.8 ± 9.9 years old), fMRI was used to determine, at both the individual and group levels, the physiological neural response to expiratory and inspiratory voluntary apneas, within respiratory control centers in the brain and brainstem. Physiological measurements (pulse oximetry, thoracic movement, end-tidal CO2 and O2) were concomitantly acquired. The resulting data were included in a general linear model, with and without a specific mask for the brainstem. Regions of interest (ROIs) were also created and integrated within the masks. The mean β value of each ROI was extracted and compared during the expiratory BH, inspiratory BH and baseline.
Results: BOLD signal change in the brainstem was observed in 18 out of 21 subjects. Activation in the main subcortical/cortical and brainstem structures related to respiratory control, potentially covering the midbrain, pons and medulla oblongata, were identified during expiratory BHs and inspiratory BHs. However, signal within the medulla oblongata, covering the ventral respiratory group (VRG), dorsal respiratory group (DRG) and the raphe nuclei was only observed during expiratory BHs (the group analysis). In the individual subject analysis, brainstem activations were similar during expiratory BHs (71,4% of subjects) and inspiratory BHs (76,2% of subject). The percentage of subjects that activated the PRG, VRG and DRG during both types of BHs represented, respectively, 58,8%, 20% and 30% of the subjects. When using predefined ROIs, the only significant differences in percentage BOLD change between the task and the baseline were over the PRG, bilateral thalamic nuclei (ANT, VPL, VL), dorsal and median raphe. BOLD signal variation in the right ANT and the left VL thalamic nuclei was significantly higher for the inspiratory apneas compared to expiratory apneas. The left DRG and the right NA presented significant variation only during expiratory BHs and the dorsal raphe during inspiratory BHs.
Conclusion: The ability to image brainstem respiratory centers and cortical areas involved in respiratory regulation in healthy subjects, on an individual basis, is an important step toward understanding pathologies that may affect the control of respiration.