The physiology and metabolism of neuronal activation: in vivo studies by NMR and other methods.

In this article, a review is made of the current knowledge concerning the physiology and metabolism of neuronal activity, as provided by the application of NMR approaches in vivo. The evidence furnished by other functional spectroscopic and imaging techniques, such as PET and optical methods, are also discussed. In spite of considerable amounts of studies presented in the literature, several controversies concerning the mechanisms underlying brain function still remain, mainly due to the difficult assessment of the single vascular and metabolic dynamics which generally influence the functional signals. In this framework, methodological and technical improvements are required to provide new and reliable experimental elements, which can support or eventually modify the current models of activation.

[1]  L. Sokoloff,et al.  Cerebral Oxygen/Glucose Ratio is Low during Sensory Stimulation and Rises above Normal during Recovery: Excess Glucose Consumption during Stimulation is Not Accounted for by Lactate Efflux from or Accumulation in Brain Tissue , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  G L Shulman,et al.  Blood flow and oxygen delivery to human brain during functional activity: Theoretical modeling and experimental data , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Ying Zheng,et al.  Increased Oxygen Consumption Following Activation of Brain: Theoretical Footnotes Using Spectroscopic Data from Barrel Cortex , 2001, NeuroImage.

[4]  A. Villringer,et al.  No Evidence for Early Decrease in Blood Oxygenation in Rat Whisker Cortex in Response to Functional Activation , 2001, NeuroImage.

[5]  Alan C. Evans,et al.  Cerebral blood flow and metabolism during nonspecific bilateral visual stimulation in normal subjects , 1993 .

[6]  J. Chatham,et al.  Lactic acid and protein interactions: implications for the NMR visibility of lactate in biological systems. , 1999, Biochimica et biophysica acta.

[7]  G Krueger,et al.  Dynamic NMR studies of perfusion and oxidative metabolism during focal brain activation. , 1997, Advances in experimental medicine and biology.

[8]  R. J. Seitz,et al.  Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study , 1992, Acta neurologica Scandinavica.

[9]  J. Mayhew,et al.  Spectroscopic Analysis of Neural Activity in Brain: Increased Oxygen Consumption Following Activation of Barrel Cortex , 2000, NeuroImage.

[10]  S. Stone-Elander,et al.  Regional cerebral oxidative and total glucose consumption during rest and activation studied with positron emission tomography. , 1994, Acta physiologica Scandinavica.

[11]  R. Buxton,et al.  Dynamics of blood flow and oxygenation changes during brain activation: The balloon model , 1998, Magnetic resonance in medicine.

[12]  G. Crelier,et al.  Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  R. Goebel,et al.  Exploring brain function with magnetic resonance imaging. , 1999, European journal of radiology.

[14]  G. Glover,et al.  Assessment of cerebral oxidative metabolism with breath holding and fMRI , 1999, Magnetic resonance in medicine.

[15]  Kamil Ugurbil,et al.  Development of 17O NMR approach for fast imaging of cerebral metabolic rate of oxygen in rat brain at high field , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[16]  R G Shulman,et al.  A model for the regulation of cerebral oxygen delivery. , 1998, Journal of applied physiology.

[17]  Anand Rangarajan,et al.  Oxidative Glucose Metabolism in Rat Brain during Single Forepaw Stimulation: A Spatially Localized 1H[13C] Nuclear Magnetic Resonance Study , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  A. Kleinschmidt,et al.  Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal brain activation in man , 1996, Magnetic resonance in medicine.

[19]  E Yacoub,et al.  Detection of the early negative response in fMRI at 1.5 Tesla , 1999, Magnetic resonance in medicine.

[20]  M. Mintun,et al.  Nonoxidative glucose consumption during focal physiologic neural activity. , 1988, Science.

[21]  S. Ogawa,et al.  BOLD Based Functional MRI at 4 Tesla Includes a Capillary Bed Contribution: Echo‐Planar Imaging Correlates with Previous Optical Imaging Using Intrinsic Signals , 1995, Magnetic resonance in medicine.

[22]  I. Macdonald,et al.  Measurement of human tricarboxylic acid cycle rates during visual activation by 13C magnetic resonance spectroscopy , 2001, Journal of neuroscience research.

[23]  P E Roland,et al.  Does mental activity change the oxidative metabolism of the brain? , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  T. Yuasa,et al.  Lactate rise in the basal ganglia accompanying finger movements: a localized1H-MRS study , 1995, Brain Research.

[25]  J. Mayhew,et al.  Concurrent Optical Imaging Spectroscopy and Laser-Doppler Flowmetry: The Relationship between Blood Flow, Oxygenation, and Volume in Rodent Barrel Cortex , 2001, NeuroImage.

[26]  P. Magistretti,et al.  Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[27]  X. Hu,et al.  Evaluation of the early response in fMRI in individual subjects using short stimulus duration , 1997, Magnetic resonance in medicine.

[28]  M. Mintun,et al.  Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. , 1984, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[29]  N. Lassen,et al.  Persistent Resetting of the Cerebral Oxygen/Glucose Uptake Ratio by Brain Activation: Evidence Obtained with the Kety—Schmidt Technique , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  B. Rosen,et al.  MRI measurement of the temporal evolution of relative CMRO2 during rat forepaw stimulation , 1999, Magnetic resonance in medicine.

[31]  Gary H. Glover,et al.  Changes of Cerebral Blood Flow, Oxygenation, and Oxidative Metabolism during Graded Motor Activation , 2002, NeuroImage.

[32]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Karl J. Friston,et al.  Nonlinear Responses in fMRI: The Balloon Model, Volterra Kernels, and Other Hemodynamics , 2000, NeuroImage.

[34]  D. Ts'o,et al.  Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[35]  S. Laughlin,et al.  An Energy Budget for Signaling in the Grey Matter of the Brain , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[36]  A. Grinvald,et al.  Interactions Between Electrical Activity and Cortical Microcirculation Revealed by Imaging Spectroscopy: Implications for Functional Brain Mapping , 1996, Science.

[37]  R. Edelman,et al.  Magnetic resonance imaging (2) , 1993, The New England journal of medicine.

[38]  Gary H. Glover,et al.  Assessment of Hemodynamic Response during Focal Neural Activity in Human Using Bolus Tracking, Arterial Spin Labeling and BOLD Techniques , 2000, NeuroImage.

[39]  Seong-Gi Kim,et al.  Early Temporal Characteristics of Cerebral Blood Flow and Deoxyhemoglobin Changes during Somatosensory Stimulation , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[40]  G M Hathout,et al.  The early response in fMRI: A modeling approach , 1999, Magnetic resonance in medicine.

[41]  S. Ogawa Brain magnetic resonance imaging with contrast-dependent oxygenation , 1990 .

[42]  F. Di Salle,et al.  Issues concerning the construction of a metabolic model for neuronal activation , 2003, Journal of neuroscience research.

[43]  B. Rosen,et al.  Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation , 1998, Magnetic resonance in medicine.

[44]  M. Raichle,et al.  The Effects of Changes in PaCO2 Cerebral Blood Volume, Blood Flow, and Vascular Mean Transit Time , 1974, Stroke.

[45]  L. Fellows,et al.  Rapid changes in extracellular glucose levels and blood flow in the striatum of the freely moving rat , 1993, Brain Research.

[46]  Rolf Gruetter,et al.  Localized 13C NMR Spectroscopy in the Human Brain of Amino Acid Labeling from d‐[1‐13C]Glucose , 1994, Journal of neurochemistry.

[47]  M. Raichle,et al.  Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[48]  B. Siesjö,et al.  Brain energy metabolism , 1978 .

[49]  J. Hennig,et al.  Observation of a fast response in functional MR , 1994, Magnetic resonance in medicine.

[50]  L. Fellows,et al.  Physiological Stimulation Increases Nonoxidative Glucose Metabolism in the Brain of the Freely Moving Rat , 1993, Journal of neurochemistry.

[51]  D Shedid,et al.  MRS Metabolic Markers of Seizures and Seizure‐Induced Neuronal Damage , 1998, Epilepsia.

[52]  C. Schwarzbauer,et al.  Investigating the dependence of BOLD contrast on oxidative metabolism , 1999, Magnetic resonance in medicine.

[53]  R. Buxton,et al.  A Model for the Coupling between Cerebral Blood Flow and Oxygen Metabolism during Neural Stimulation , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[54]  A. Villringer,et al.  Non-invasive optical spectroscopy and imaging of human brain function , 1997, Trends in Neurosciences.

[55]  T. L. Davis,et al.  Calibrated functional MRI: mapping the dynamics of oxidative metabolism. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[56]  Egill Rostrup,et al.  Determination of relative CMRO2 from CBF and BOLD changes: Significant increase of oxygen consumption rate during visual stimulation , 1999, Magnetic resonance in medicine.

[57]  G. Aeppli,et al.  Proceedings of the International School of Physics Enrico Fermi , 1994 .

[58]  R. Buxton The Elusive Initial Dip , 2001, NeuroImage.

[59]  Seong-Gi Kim,et al.  In vivo MR measurements of regional arterial and venous blood volume fractions in intact rat brain , 2000, Magnetic resonance in medicine.

[60]  G. Fein,et al.  Effect of Photic Stimulation on Human Visual Cortex Lactate and Phosphates Using 1H and 31P Magnetic Resonance Spectroscopy , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[61]  A. Song,et al.  Diffusion weighted fMRI at 1.5 T , 1996, Magnetic resonance in medicine.

[62]  Robert Costalat,et al.  A Model of the Coupling between Brain Electrical Activity, Metabolism, and Hemodynamics: Application to the Interpretation of Functional Neuroimaging , 2002, NeuroImage.

[63]  Jens Frahm,et al.  Decrease of glucose in the human visual cortex during photic stimulation , 1992, Magnetic resonance in medicine.

[64]  B. Rosen,et al.  Investigation of the early response to rat forepaw stimulation , 1999, Magnetic resonance in medicine.

[65]  Alan C. Evans,et al.  Increased oxygen consumption in human visual cortex: response to visual stimulation , 1998, Acta neurologica Scandinavica.

[66]  Xiaolian Gao,et al.  A method for measuring cerebral glucose metabolism in vivo by 13C‐NMR spectroscopy , 2002, Magnetic resonance in medicine.

[67]  F. Hyder,et al.  Quantitative functional imaging of the brain: towards mapping neuronal activity by BOLD fMRI , 2001, NMR in biomedicine.

[68]  A. Villringer,et al.  Near infrared spectroscopy (NIRS): A new tool to study hemodynamic changes during activation of brain function in human adults , 1993, Neuroscience Letters.

[69]  Seong-Gi Kim,et al.  Relative changes of cerebral arterial and venous blood volumes during increased cerebral blood flow: Implications for BOLD fMRI , 2001, Magnetic resonance in medicine.

[70]  J. Korf,et al.  Extracellular Lactic Acid as an Indicator of Brain Metabolism: Continuous On-Line Measurement in Conscious, Freely Moving Rats with Intrastriatal Dialysis , 1988, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[71]  F. Luo,et al.  Transient relationships among BOLD, CBV, and CBF changes in rat brain as detected by functional MRI , 2002, Magnetic resonance in medicine.

[72]  R G Shulman,et al.  Localized 1H NMR measurement of glucose consumption in the human brain during visual stimulation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[73]  A. Villringer,et al.  Cerebral oxygenation changes in response to motor stimulation. , 1996, Journal of applied physiology.

[74]  G. Krüger,et al.  Temporal characteristics of oxygenation‐sensitive MRI responses to visual activation in humans , 1998, Magnetic resonance in medicine.

[75]  Weili Lin,et al.  Cerebral venous and arterial blood volumes can be estimated separately in humans using magnetic resonance imaging , 2002, Magnetic resonance in medicine.

[76]  R. Shulman,et al.  Lactate rise detected by 1H NMR in human visual cortex during physiologic stimulation. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[77]  M. Bianciardi,et al.  The aerobic brain: lactate decrease at the onset of neural activity , 2003, Neuroscience.

[78]  S G Kim,et al.  Perfusion imaging by a flow‐sensitive alternating inversion recovery (Fair) technique: Application to functional brain imaging , 1997, Magnetic resonance in medicine.

[79]  G. Dienel,et al.  Glucose and lactate metabolism during brain activation , 2001, Journal of neuroscience research.

[80]  Seong‐gi Kim Cmrr,et al.  Comparison of blood oxygenattion and cerebral blood flow effect in fMRI: Estimation of relative oxygen consumption change , 1997, Magnetic resonance in medicine.

[81]  K. Uğurbil,et al.  Study of tricarboxylic acid cycle flux changes in human visual cortex during hemifield visual stimulation using 1H‐{13C} MRS and fMRI , 2001, Magnetic resonance in medicine.

[82]  J. Toole,et al.  Headache and Transient Ischemic Attacks , 1974, Stroke.

[83]  A. Grinvald,et al.  Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging. , 1999, Science.

[84]  Ravi S. Menon,et al.  Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. , 1993, Biophysical journal.

[85]  E Yacoub,et al.  Detection of the early decrease in fMRI signal in the motor area , 2001, Magnetic resonance in medicine.

[86]  R. Gruetter,et al.  Simultaneous Determination of the Rates of the TCA Cycle, Glucose Utilization, α-Ketoglutarate/Glutamate Exchange, and Glutamine Synthesis in Human Brain by NMR , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.