Central Neural Substrates of Cardiorespiratory Control During Slow Breathing and Hypoxic Challenge

F1 Central Neural Substrates of Cardiorespiratory Control During Slow Breathing and Hypoxic Challenge Alessia Nicotra, MD; Hugo Critchley, MD; Patrizia Chiesa, MD; Yoko Nagai, MD; Marcus Gray, MD; Ludovico Minati, MD; Luciano Bernardi, MD Controlled slow breathing (at 6/min) can have beneficial effects on cardiovascular function, including responses to hypoxia. We tested neural substrates of cardiorespiratory control in 20 healthy subjects (F=8; age = 35 ± 10 yrs) during paced (slow and normal rate) and unpaced spontaneous breathing of normoxic and hypoxic (13% inspired O2) air using functional magnetic resonance imaging. Cardiovascular and respiratory measures were acquired synchronously. Peripherally, slow breathing was associated with increased tidal ventilatory volume; hypoxia suppressed heart rate variability and increased heart rate. Centrally, slow breathing activated dorsal pons, cerebellum, periaqueductal grey matter, hypothalamus, thalamus, lateral and anterior insular cortices. Blocks of hypoxia induced activation of mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was shown in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Our study outlines slow breathing effects on central and cardiovascular responses to hypoxic challenge. The findings show involvement of discrete brainstem nuclei to cardiorespiratory coupling and corticostriatal circuitry during physiological responses accompanying breathing regulation in hypoxic challenge.