Sustained Poststimulus Elevation in Cerebral Oxygen Utilization after Vascular Recovery

The brain's response to functional activation is characterized by focal increases in cerebral blood flow. It is generally assumed that this hyperemia is a direct response to the energy demands of activation, the so-called flow-metabolism coupling. Here we report experimental evidence that increases in oxygen metabolism can occur after activation without increases in flow. When using multimodality functional MRI (fMRI) to study visual activation in human brain, we observed a postactivation period of about 30 seconds during which oxygen consumption remained elevated, while blood flow and volume had already returned to baseline levels. The finding of such a prolonged and complete dissociation of vascular response and energy metabolism during the poststimulus period indicates that increased metabolic demand needs not per se cause a concomitant increase in blood flow. The results also show that the postactivation undershoot after the positive blood-oxygen-level-dependent hemodynamic response in fMRI should be reinterpreted as a continued elevation of oxygen metabolism, rather than a delayed blood volume compliance.

[1]  W. Kuschinsky,et al.  Local chemical and neurogenic regulation of cerebral vascular resistance. , 1978, Physiological reviews.

[2]  Y. Ben‐Ari,et al.  Blood flow compensates oxygen demand in the vulnerable ca3 region of the hippocampus during kainate-induced seizures , 1984, Neuroscience.

[3]  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.

[4]  Richard S. J. Frackowiak,et al.  Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age. , 1990, Brain : a journal of neurology.

[5]  R. Turner,et al.  Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Donald S. Williams,et al.  Perfusion imaging , 1992, Magnetic resonance in medicine.

[7]  Ravi S. Menon,et al.  Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[8]  J. C. Smith,et al.  Microenvironment of respiratory neurons in the in vitro brainstem‐spinal cord of neonatal rats. , 1993, The Journal of physiology.

[9]  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.

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

[11]  M E Barish,et al.  Perturbation of intracellular calcium and hydrogen ion regulation in cultured mouse hippocampal neurons by reduction of the sodium ion concentration gradient , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  C. Iadecola,et al.  Nitric oxide and adenosine mediate vasodilation during functional activation in cerebellar cortex , 1994, Neuropharmacology.

[13]  E. Haacke,et al.  Theory of NMR signal behavior in magnetically inhomogeneous tissues: The static dephasing regime , 1994, Magnetic resonance in medicine.

[14]  A Villringer,et al.  Coupling of brain activity and cerebral blood flow: basis of functional neuroimaging. , 1995, Cerebrovascular and brain metabolism reviews.

[15]  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.

[16]  W. Powers,et al.  Effect of stepped hypoglycemia on regional cerebral blood flow response to physiological brain activation. , 1996, The American journal of physiology.

[17]  R. Macfarlane,et al.  Neurophysiological Basis of Cerebral Blood Flow Control: An Introduction , 1997 .

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

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

[20]  Risto A. Kauppinen,et al.  Quantitative assessment of blood flow, blood volume and blood oxygenation effects in functional magnetic resonance imaging , 1998, Nature Medicine.

[21]  B. Rosen,et al.  Evidence of a Cerebrovascular Postarteriole Windkessel with Delayed Compliance , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  Risto A. Kauppinen,et al.  Determination of Oxygen Extraction Ratios by Magnetic Resonance Imaging , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  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.

[24]  P. Boesiger,et al.  Transfer insensitive labeling technique (TILT): Application to multislice functional perfusion imaging , 1999, Journal of magnetic resonance imaging : JMRI.

[25]  U Dirnagl,et al.  Nitric oxide: a modulator, but not a mediator, of neurovascular coupling in rat somatosensory cortex. , 1999, The American journal of physiology.

[26]  A. Gjedde,et al.  Model of Blood–Brain Transfer of Oxygen Explains Nonlinear Flow-Metabolism Coupling During Stimulation of Visual Cortex , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[27]  S G Kim,et al.  Magnetic resonance studies of brain function and neurochemistry. , 2000, Annual review of biomedical engineering.

[28]  W. Kuschinsky,et al.  Regulation of Cerebral Blood Flow , 2000 .

[29]  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.

[30]  Xavier Golay,et al.  Measurement of tissue oxygen extraction ratios from venous blood T2: Increased precision and validation of principle , 2001, Magnetic resonance in medicine.

[31]  J. Detre,et al.  Temporal dynamics of the partial pressure of brain tissue oxygen during functional forepaw stimulation in rats , 2001, Neuroscience Letters.

[32]  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.

[33]  K Pettigrew,et al.  Regional differences in mechanisms of cerebral circulatory response to neuronal activation. , 2001, American journal of physiology. Heart and circulatory physiology.

[34]  N. Logothetis The neural basis of the blood-oxygen-level-dependent functional magnetic resonance imaging signal. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[35]  D. Attwell,et al.  The neural basis of functional brain imaging signals , 2002, Trends in Neurosciences.

[36]  A. Dale,et al.  Coupling of Total Hemoglobin Concentration, Oxygenation, and Neural Activity in Rat Somatosensory Cortex , 2003, Neuron.

[37]  M. C. Angulo,et al.  Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation , 2003, Nature Neuroscience.

[38]  X Golay,et al.  Comparison of the dependence of blood R2 and R  2* on oxygen saturation at 1.5 and 4.7 Tesla , 2003, Magnetic resonance in medicine.

[39]  J. Pekar,et al.  Functional magnetic resonance imaging based on changes in vascular space occupancy , 2003, Magnetic resonance in medicine.

[40]  R. Freeman,et al.  Single-Neuron Activity and Tissue Oxygenation in the Cerebral Cortex , 2003, Science.