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Biophysical basis of brain activity: implications for neuroimaging

2002; Cambridge University Press; Volume: 35; Issue: 3 Linguagem: Inglês

10.1017/s0033583502003803

1469-8994

Robert G. Shulman, Fahmeed Hyder, Douglas L. Rothman,

Neuroscience and Neuropharmacology Research

1. Summary 288 2. Introduction 288 3. Relationship between neuroenergetics and neurotransmitter flux 294 4. A model of coupling between neuroenergetics and neurotransmission 296 5. Relationship between neuroenergetics and neural spiking frequency 297 6. Comparison with previous electrophysiological and fMRI measurements 298 7. Contributions of non-oxidative energetics to a primarily oxidative brain 299 8. Possible explanation for non-oxidative energetics contributions 300 9. A model of total neuronal activity to support cerebral function 302 10. Implications for interpretation of fMRI studies 305 11. The restless brain 306 12. Acknowledgements 310 13. Appendix A. CMR O 2 by 13 C-MRS 310 14. Appendix B. V cyc and test of model 313 15. Appendix C. CMR O 2 by calibrated BOLD 316 16. Appendix D. Comparison of spiking activity of a neuronal ensemble with CMR O 2 318 17. References 320 In vivo 13 C magnetic resonance spectroscopy (MRS) studies of the brain have quantitatively assessed rates of glutamate–glutamine cycle ( V cyc ) and glucose oxidation (CMR Glc(ox) ) by detecting 13 C label turnover from glucose to glutamate and glutamine. Contrary to expectations from in vitro and ex vivo studies, the in vivo 13 C-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 cyc and CMR Glc(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 (CMRO 2 ), 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 (ΔCMRO 2 %) 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 ΔCMRO 2 % when compared with alterations in neuronal spiking rate (Δν%) during sensory stimulation in the rat reveals a stoichiometric relationship, in good agreement with 13 C-MRS results. Hence fMRI when calibrated so as to provide ΔCMRO 2 % 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.