Skip to content
Frontiers
Search

Neuroscience

Frontiers in Neuroenergetics ·

Volume 2 - 2010 | https://doi.org/10.3389/fnene.2010.00017

Functional Neuroimaging: A Physiological Perspective

  • Ai-Ling Lin1,2*corresponding author
  • Jia-Hong Gao3
  • Timonthy Q. Duong1,4,5,6,7
  • Peter T. Fox1,2,4,6,7
  1. 11 Research Imaging Institute, University of Texas Health Science Center San Antonio, TX, USA
  2. 22 Department of Psychiatry, University of Texas Health Science Center San Antonio, TX, USA
  3. 33 Department of Psychiatry and Behavioral Neuroscience, and Brain Research Imaging Center, University of Chicago Chicago, IL, USA
  4. 44 Department of Physiology, University of Texas Health Science Center San Antonio, TX, USA
  5. 55 Department of Ophthalmology, University of Texas Health Science Center San Antonio, TX, USA
  6. 66 South Texas Veterans Health Care System, Department of Veterans Affairs San Antonio, TX, USA
  7. 77 Department of Radiology, University of Texas Health Science Center San Antonio, TX, USA
Article metrics0 viewsView details
PDFCiteMetrics

Abstract

Metabolic physiology and functional neuroimaging have played important and complementary roles over the past two decades. In particular, investigations of the mechanisms underlying functional neuroimaging signals have produced fundamental new insights into hemodynamic and metabolic regulation. However, controversies were also raised as regards the metabolic pathways (oxidative vs. non-oxidative) for meeting the energy demand and driving the increases in cerebral blood flow (CBF) during brain activation. In a recent study, with the concurrent functional MRI-MRS measurements, we found that task-evoked energy demand was predominately met through oxidative metabolism (approximately 98%), despite a small increase in cerebral metabolic rate of oxygen (12–17%). In addition, the task-induced increases in CBF were most likely mediated by anaerobic glycolysis rather than oxygen demand. These observations and others from functional neuroimaging support the activation-induced neuron-astrocyte interactions portrayed by the astrocyte-neuron lactate shuttle model. The concurrent developments of neuroimaging methods and metabolic physiology will also pave the way for the future investigation of cerebral hemodynamics and metabolism in disease states.

Keywords

References

  1. Brand M. D. (2005). The efficiency and plasticity of mitochondrial energy transduction. Biochem. Soc. Trans. 33, 897 – 904. doi:10.1042/BST20050897
  2. Buxton R. B., Wong E. C., Frank L. R. (1998). Dynamics of blood flow and oxygen metabolism during brain activation: the balloon model. Magn. Reson. Med. 39, 855 – 864. doi:10.1002/mrm.1910390602
  3. Fox P. T., Raichle M. E. (1986). Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc. Natl. Acad. Sci. U.S.A. 83, 1140 – 1144. doi:10.1073/pnas.83.4.1140
  4. Fox P. T., Raichle M. E., Mintun M. A., Dence C. (1988). Nonoxidative glucose consumption during focal physiologic neural activity. Science 241, 462 – 464. doi:10.1126/science.3260686
  5. Frackowiak R. S., Lenzi G. L., Jones T., Heather J. D. (1980). Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure, and normal values. J. Comput. Assist. Tomogr. 4, 727 – 736. doi:10.1097/00004728-198012000-00001
  6. Frahm J., Kruger G., Merboldt K. D., Kleinschmidt A. (1996). Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal brain activation in man. Magn. Reson. Med. 35, 143 – 148. doi:10.1002/mrm.1910350202
  7. Fulton J. (1928). Observation upon the vascularity of the human occipital lobe during visual activity. Brain 51, 310 – 320. doi:10.1093/brain/51.3.310
  8. Gjedde A. (1997). “The relation between brain function and cerebral blood flow and metabolism,” in Cerebrovascular Disease, eds Bajter H., Caplan L. (Philadelphia, PA: Lippincott-Raven Publishers), 23 – 40.
  9. Gjedde A., Marrett S. (2001). Glycolysis in neurons, not astrocytes, delays oxidative metabolism of human visual cortex during sustained checkerboard stimulation in vivo. J. Cereb. Blood Flow Metab. 21, 1384 – 1392. doi:10.1097/00004647-200112000-00002
  10. Hoge R. D., Atkinson J., Gill B., Crelier G. R., Marrett S., Pike G. B. (1999). Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: the deoxyhemoglobin dilution model. Magn. Reson. Med. 42, 849 – 863. doi:10.1002/(SICI)1522-2594(199911)42:5<849::AID-MRM4>3.0.CO;2-Z
  11. Hyder F., Patel A. B., Gjedde A., Rothman D. L., Behar K. L., Shulman R. G. (2006). Neuronal-glial glucose oxidation and glutamatergic-GABAergic function. J. Cereb. Blood Flow Metab. 26, 865 – 877. doi:10.1038/sj.jcbfm.9600263
  12. Jenkins B. G., Koroshetz W. J., Beal M. F., Rosen B. R. (1993). Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. Neurology 43, 2689 – 2695.
  13. Kasischke K. A., Vishwasrao H. D., Fisher P. J., Zipfel W. R., Webb W. W. (2004). Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305, 99 – 103. doi:10.1126/science.1096485
  14. Kety S. S., Schmidt C. F. (1948). The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J. Clin. Invest. 27, 484 – 492. doi:10.1172/JCI101995
  15. Koroshetz W. J., Jenkins B. G., Rosen B. R., Beal M. F. (1997). Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann. Neurol. 41, 160 – 165. doi:10.1002/ana.410410206
  16. Kwong K. K., Belliveau J. W., Chesler D. A., Goldberg I. E., Weisskoff R. M., Poncelet B. P., Kennedy D. N., Hoppel B. E., Cohen M. S., Turner R., Cheng H. M., Brady T. J., Rosen B. R. (1992). Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc. Natl. Acad. Sci. U.S.A. 89, 5675 – 5679. doi:10.1073/pnas.89.12.5675
  17. Landau W. M., Freygang W. H. J., Roland L. P., Sokoloff L., Kety S. S. (1955). The local circulation of the living brain: values in the unanesthetized and anesthetized cat. Trans. Am. Neurol. Assoc. 80, 125 – 129.
  18. Lin A.-L., Fox P. T., Hardies J., Duong T. Q., Gao J.-H. (2010). Nonlinear coupling between cerebral blood flow, oxygen consumption, and ATP production in human visual cortex. Proc. Natl. Acad. Sci. U.S.A. 107, 8446 – 8451. doi:10.1073/pnas.0909711107
  19. Lin A.-L., Fox P. T., Yang Y., Lu H., Tan L.-H., Gao J.-H. (2009). Time-dependent correlation of cerebral blood flow with oxygen metabolism in activated human visual cortex as measured by fMRI. Neuroimage 44, 16 – 22. doi:10.1016/j.neuroimage.2008.08.029
  20. Lin A.-L., Fox P. T., Yang Y., Lu H., Tan L.-H., Gao J.-H. (2008). Evaluation of MRI models in the measurement of CMRO2 and its relationship with CBF. Magn. Reson. Med. 60, 380 – 389. doi:10.1002/mrm.21655
  21. Lu H., Golay X., Pekar J. J., Van Zijl P. C. (2004). Sustained poststimulus elevation in cerebral oxygen utilization after vascular recovery. J. Cereb. Blood Flow Metab. 24, 764 – 770. doi:10.1097/01.WCB.0000124322.60992.5C
  22. Malonek D., Grinvald A. (1996). Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science 272, 551 – 554. doi:10.1126/science.272.5261.551
  23. Mandeville J. B., Marota J. J., Ayata C., Zaharchuk G., Moskowitz M. A., Rosen B. R., Weisskoff R. M. (1999). Evidence of a cerebrovascular postarteriole windkessel with delayed compliance. J. Cereb. Blood Flow Metab. 19, 679 – 689. doi:10.1097/00004647-199906000-00012
  24. Menon R. S., Ogawa S., Hu X., Strupp J. P., Anderson P., Ugurbil K. (1995). BOLD based functional MRI at 4 Tesla includes a capillary bed contribution: echo-planar imaging correlates with previous optical imaging using intrinsic signals. Magn. Reson. Med. 33, 453 – 459. doi:10.1002/mrm.1910330323
  25. Mintun M. A., Raichle M. E., Martin W. R., Herscovitch P. (1984). Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. J. Nucl. Med. 25, 177 – 187.
  26. Mintun M. A., Vlassenko A. G., Rundle M. M., Raichle M. E. (2004). Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain. Proc. Natl. Acad. Sci. U.S.A. 101, 659 – 664. doi:10.1073/pnas.0307457100
  27. Mintun M. A., Vlassenko A. G., Shulman G. L., Snyder A. Z. (2002). Time-related increase of oxygen utilization in continuously activated human visual cortex. Neuroimage 16, 531 – 537. doi:10.1006/nimg.2002.1114
  28. Mosso A. (1881). Ueber den Kreislauf des Blutes im menschlichen Gehirn. Leipzig: Verlag von Veit.
  29. Ogawa S., Tank D. W., Menon R., Ellermann J. M., Kim S. G., Merkle H., Ugurbil K. (1992). Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc. Natl. Acad. Sci. U.S.A. 89, 5951 – 5955. doi:10.1073/pnas.89.13.5951
  30. Pellerin L., Magistretti P. J. (1994). Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. U.S.A. 91, 10625 – 10629. doi:10.1073/pnas.91.22.10625
  31. Phelps M. E., Mazziotta J. C. (1985). Positron emission tomography: human brain function and biochemistry. Science 228, 799 – 809. doi:10.1126/science.2860723
  32. Posner M. I., Raichle M. E. (1994). Images of Mind. New York: Scientific American Library.
  33. Powers W. J., Videen T. O., Markham J., McGee-Minnich L., Antenor-Dorsey J. V., Hershey T., Perlmutter J. S. (2007). Selective defect of in vivo glycolysis in early huntington's disease striatum. Proc. Natl. Acad. Sci. U.S.A. 104, 2945 – 2949. doi:10.1073/pnas.0609833104
  34. Prichard J., Rothman D., Novotny E., Petroff O., Kuwabara T., Avison M., Howseman A., Hanstock C., Shulman R. (1991). Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation. Proc. Natl. Acad. Sci. U.S.A. 88, 5829 – 5831. doi:10.1073/pnas.88.13.5829
  35. Raichle M. E., Martin W. R., Herscovitch P., Mintun M. A., Markham J. (1983). Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. J. Nucl. Med. 24, 790 – 798.
  36. Reivich M., Kuhl D., Wolf A., Greenberg J., Phelps M., Ido T., Casella V., Fowler J., Hoffman E., Alavi A., Som P., Sokoloff L. (1979). The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ. Res. 44, 127 – 137.
  37. Richardson R. B. (2009). Ionizing radiation and aging: rejuvenating an old idea. Aging 1, 887 – 902.
  38. Roy C. S., Sherrington C. S. (1890). On the regulation of the blood-supply of the brain. J. Physiol. (Lond.) 11, 85 – 108.
  39. Schmidt C. F., Kety S. S. (1947). Recent studies of cerebral blood flow and cerebral metabolism in man. Trans. Assoc. Am. Physicians 60, 52 – 58.
  40. Schummers J., Yu H., Sur M. (2008). Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320, 1638 – 1643. doi:10.1126/science.1156120
  41. Siesjo B. (1978). Brain Energy Metabolism. New York: Wiley, 101 – 110.
  42. Sokoloff L., Reivich M., Kennedy C., Des Rosiers M. H., Patlak C. S., Pettigrew K. D., Sakurada O., Shinohara M. (1977). The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28, 897 – 916. doi:10.1111/j.1471-4159.1977.tb10649.x
  43. Spilman P., Podlutskaya N., Hart M. J., Debnath J., Gorostiza O., Bredesen D., Richardson A., Strong R., Galvan V. (2010). Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS ONE 5, e9979. doi:10.1371/journal.pone.0009979
  44. Vafaee M. S., Gjedde A. (2000). Model of blood-brain transfer of oxygen explains nonlinear flow-metabolism coupling during stimulation of visual cortex. J. Cereb. Blood Flow Metab. 20, 747 – 754. doi:10.1097/00004647-200004000-00012
  45. Van Remmen H., Guo Z., Richardson A. (2001). The anti-ageing action of dietary restriction. Novartis Found. Symp. 235, 221 – 230. doi:10.1002/0470868694.ch18
  46. Vlassenko A. G., Rundle M. M., Raichle M. E., Mintun M. A. (2006). Regulation of blood flow in activated human brain by cytosolic NADH/NAD + ratio. Proc. Natl. Acad. Sci. U.S.A. 103, 1964 – 1969. doi:10.1073/pnas.0510632103

Citation

Lin, A., et al. (2010). Functional Neuroimaging: A Physiological Perspective. Frontiers in Neuroenergetics, Volume 2. https://doi.org/
Received
Accepted
Published
Volume
2 - 2010

Copyright

Copyright © 2010 Lin, Gao, Duong and Fox.

License: http://www.frontiersin.org/licenseagreement

*Correspondence: Ai-Ling Lin

Article metrics

Views
0
Downloads
0
Citations
0
Shares
0

Related articles

NeuroscienceInduction of ischemic stroke in awake freely moving mice reveals that isoflurane anesthesia can mask the benefits of a neuroprotection therapyAngela Seto, Stephanie Taylor, Dustin Trudeau, Ian Swan, Jay Leung, Patrick Reeson, Kerry R. Delaney, Craig E. BrownNeuroscienceImpaired cortical mitochondrial function following TBI precedes behavioral changesWilliam D. Watson, John E. Buonora, Angela M. Yarnell, Jessica J. Lucky, Michaela I. D’Acchille, David C. McMullen, Andrew G. Boston, Andrew V. Kuczmarski, William S. Kean, Ajay Verma, Neil E. Grunberg, Jeffrey T. ColeNeuroscienceFDG-PET imaging in mild traumatic brain injury: a critical reviewKimberly R. Byrnes, Colin M. Wilson, Fiona Brabazon, Ramona von Leden, Jennifer S. Jurgens, Terrence R. Oakes, Reed G. Selwyn