Control of breathing and volitional respiratory rhythm in humans

When breathing frequency (f) is imperceptibly increased during a volitionally paced respiratory rhythm imposed by an auditory signal, tidal volume (VT) decreases such that minute ventilation (V̇E) rises according to f-induced dead-space ventilation changes (18). As a result, significant change in alveolar ventilation and PCO₂ are prevented as f varies. The present study was performed to determine what regulatory properties are retained by the respiratory control system, wherein the spontaneous automatic rhythmic activity is replaced by a volitionally paced rhythm. Six volunteers were asked to trigger each breath cycle on hearing a brief auditory signal. The time interval between subsequent auditory signals was imperceptibly changed for 10-15 min, during 1) air breathing (condition 1), 2) the addition of a 300 ml of instrumental dead space (condition 2), 3) an increase in the inspired level of CO₂ (condition 3), and 4) light exercise (condition 4). We found that as f was slowly increased the elaborated VT decreased in accordance to the background level of CO₂ and metabolic rate. Indeed, for any given breath duration, VT was shifted upward in condition 2 vs. 1, whereas the slope of VT changes according to the volitionally rhythm was much steeper in conditions 3 and 4 vs. 1. The resulting changes in V̇E offset any f-induced changes in dead-space ventilation in all conditions. We conclude that there is an inherent, fundamental mechanism that elaborates VT based on f when imposed by the premotor cortex in humans. The chemoreflex and exercise drive to breath interacts with this cortically mediated rhythm maintaining alveolar rather than V̇E constant as f changes. The implications of our findings are discussed in the context of our current understanding of the central generation of breathing rhythm.