objective: The imaging of brain activity with positron emission tomography (PET) and functional magnetic resonance imaging has assumed a central position in psychiatry. Functional imaging signals arise from changes in the neurophysiological parameters of glucose and oxygen consumption mediated by blood flow. Method: Recent in vivo C-13 nuclear magnetic resonance (NMR) neurochemical studies have established a quantitative coupling between the rates of glucose oxidation and glutamate neurotransmitter flux in rats and humans, thereby linking measured neurophysiological parameters to brain function. Results: These results show that in the awake, resting, and unstimulated slates, 70%-80% of brain energy consumption is devoted to the same glutamate/glutamine neurotransmitter signaling as are the small percentages stimulated by tasks. Furthermore, in anesthetized animals, in which unstimulated activity is reduced, the total signal rather than a particular increment is required for a response. Conclusions: On this basis, the total signal, as well as the difference in the signal, measures cortical neurotransmitter flux. The total signal in a region therefore contains valuable information about required brain activity Although signal change is often more easily measured, certain PET and C-13 NMR methods can quantify total regional signal activity and thereby provide another measure of neurotransmitter activity.