We investigated the relationship between neuronal activity, oxygen metabolism, and hemodynamic responses in rat somatosensory cortex with simultaneous optical intrinsic signal imaging and spectroscopy, laser Doppler flowmetry, and local field potential recordings. Changes in cerebral oxygen consumption increased linearly with synaptic activity but with a threshold effect consistent with the existence of a tissue oxygen buffer. Modeling analysis demonstrated that the coupling between neuronal activity and hemodynamic response magnitude may appear linear over a narrow range but incorporates nonlinear effects that are better described by a threshold or power law relationship. These results indicate that caution is required in the interpretation of perfusion-based indicators of brain activity, such as functional magnetic resonance imaging (fMRI), and may help to refine quantitative models of neurovascular coupling.