The coupling controversy.

Functional magnetic resonance imaging (fMRI) relies on the well-known phenomenon of coupling between neuronal activity and brain blood flow. For nearly a century, the presumption was that hemodynamics were coupled to neuronal activity via energy demand and oxidative metabolism. Early (15)O positron-emission tomographic (PET) studies challenged this theory, demonstrating a physiological "uncoupling" between brain blood flow and oxygen metabolism. These PET observations played a pivotal role in guiding the development of fMRI, by demonstrating which physiological parameters were most closely coupled to neuronal activity and by presaging the BOLD-contrast effect. Subsequent PET studies were crucial for constraining theories concerning the physiological mechanisms underlying hemodynamic/neuronal coupling and, thereby, guiding the development of models for quantification of oxygen metabolic rate %∆ from fMRI. A first-person account of the PET "coupling" studies and their influence on the development of fMRI is provided.