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The Thermodynamics of Thinking: Is CBF Regulation Maintaining the Ratio [O 2]/[CO 2] in the Cells?

Richard B. Buxton

Department of Radiology and Center for Functional MRI, University of California, USA

In the mammalian brain, increased neural activity is accompanied by a large increase in cerebral blood flow (CBF), but a more modest increase in the cerebral metabolic rate of oxygen (CMRO 2), so that the oxygen extraction fraction (E) decreases with brain stimulation. This phenomenon lies at the heart of functional magnetic resonance imaging (fMRI) techniques used to map patterns of brain activity by detecting blood oxygenation level dependent (BOLD) changes in the magnetic resonance signal. Despite the fundamental importance of this physiological phenomenon for the interpretation of fMRI studies, the function served by the large CBF increase is poorly understood. In addition to the neural activation response, CBF also responds strongly to an increase in arterial carbon dioxide, a well-known physiological response that also decreases E, but whose function is unclear. Recent work modeling the transport of O 2 and CO 2 between blood and tissue suggests that these two CBF responses may be explained by a simple principle: preservation of the concentration ratio [O 2]/[CO 2] at the mitochondria. A thermodynamic homeostasis explanation is proposed for the importance of conserving this ratio.