Integration between breathing and brain blood flow

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The most important task for the circulatory system is to maintain blood flow to the brain. Stable brain blood flow is crucial to help regulate breathing, especially during exercise which provides the greatest single stress on the human body. Although the physiological mechanisms involved in this relationship are largely unknown, breathing-induced changes in carbon dioxide and brain blood flow are tightly linked. Recently, however, we have demonstrated that brain blood flow increases during exercise and, importantly, plays a critical role in regulating breathing. These findings, as well as the technological evolutions in studying human brain hemodynamics, has ignited interest in studying regulatory mechanisms of brain blood flow at rest and during exercise. Interestingly, marked increases in ventilation as well as the development of abnormal periodic breathing commonly occur when healthy humans ascend to high altitude. Although the mechanisms are largely unknown, our preliminary data indicate that alterations in brain blood flow may underpin the condition. By combining sophisticated gold-standard brain imaging techniques at rest and during exercise, with and without pharmacological intervention, this program of research aims to examine: 1) the mechanisms by which brain blood flow influences the breathing at rest and during exercise; 2) the extent to which these control mechanisms are altered during exposure to high altitude; and 3) how long term exposure to high altitude may lead to biological adaptations to the mechanisms that regulate blood flow and breathing. The latter aim will be explored in the Nepalese Sherpa, a population born and bred at high altitude over many generations. Addressing the novel aims outlined in this proposal will provide new information about brain blood flow during stress (e.g., exercise) and adaptation to such stress (e.g., at high altitude). Importantly, these studies will broaden understanding of the fundamental mechanisms governing both brain blood flow and breathing control.