Biophysical basis of brain activity: implications for neuroimaging

In vivo C-13 magnetic resonance spectroscopy (MRS) studies of the brain have quantitatively assessed rates of glutamate-glutaminc cycle (V-eye) and glucose oxidation (CMRGle(ox)) by detecting C-13 label turnover from glucose to glutamate and glutamine. Contrary to expectations from in vitro and ex vivo studies, the in vivo C-13-MRS results demonstrate that glutamate recycling is a major metabolic pathway, inseparable from its actions of neurotransmission. Furthermore, both in the awake human and in the anesthetized rat brain, V-eye and CMRGle(ox) are stoichiometrically related, where more than two thirds of the energy from glucose oxidation supports events associated with glutamate neurotransmission. The high energy consumption of the brain measured at rest and its quantitative relation to neurotransmission reflects a sizeable activity level for the resting brain. The high activity of the non-stimulated brain, as measured by cerebral metabolic rate of oxygen use (CMRO2), establishes a new neurophysiological basis of cerebral function that leads to reinterpreting functional imaging data because the large baseline signal is commonly discarded in cognitive neuroscience paradigms. Changes in energy consumption (DeltaGWR(O2) %) can also be obtained from magnetic resonance imaging (MRI) experiments, using the blood oxygen level-dependent (BOLD) image contrast, provided that all the separate parameters contributing to the functional MRI (fMRI) signal are measured. The BOLD-derived DeltaCMR(O2) % when compared with alterations in neuronal spiking rate (Deltav %) during sensory, stimulation in the rat reveals a stoichiometric relationship, in good agreement with C-13-MRS results. Hence fMRI when calibrated so as to provide DeltaCMR(O2) % can provide high spatial resolution evaluation of neuronal activity. Our studies of quantitative measurements of changes in neuroenergetics and neurotransmission reveal that a stimulus does not provoke an arbitrary amount of activity in a localized region, rather a total level of activity is required where the increment is inversely related to the level of activity in the non-stimulated condition. These biophysical experiments have established relationships between energy consumption and neuronal activity that provide novel insights into the nature of brain function and the interpretation of fMRI data.