Analysis of oxygen metabolism implies a neural origin for the negative BOLD response in human visual cortex

The sustained negative blood oxygenation level-dependent (BOLD) response in functional MRI is observed universally, but its interpretation is controversial. The origin of the negative response is of fundamental importance because it could provide a measurement of neural deactivation. However, a substantial component of the negative response may be due to a non-neural hemodynamic artifact. To distinguish these possibilities, we have measured evoked BOLD, cerebral blood flow (CBF), and oxygen metabolism responses to a fixed visual stimulus from two different baseline conditions. One is a normal resting baseline, and the other is a lower baseline induced by a sustained negative response. For both baseline conditions, CBF and oxygen metabolism responses reach the same peak amplitude. Consequently, evoked responses from the negative baseline are larger than those from the resting baseline. The larger metabolic response from negative baseline presumably reflects a greater neural response that is required to reach the same peak amplitude as that from resting baseline. Furthermore, the ratio of CBF to oxygen metabolism remains approximately the same from both baseline states (approximately 2:1). This tight coupling between hemodynamic and metabolic components implies that the magnitude of any hemodynamic artifact is inconsequential. We conclude that the negative response is a functionally significant index of neural deactivation in early visual cortex.

[1]  F. Hyder,et al.  Cerebral energetics and spiking frequency: The neurophysiological basis of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[2]  A. Angel,et al.  The effect of anaesthetic agents on primary cortical evoked responses. , 1973, British journal of anaesthesia.

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

[4]  Justin L. Gardner,et al.  Contrast Adaptation and Representation in Human Early Visual Cortex , 2005, Neuron.

[5]  C. Petersen,et al.  Correlating whisker behavior with membrane potential in barrel cortex of awake mice , 2006, Nature Neuroscience.

[6]  Martin Wiesmann,et al.  Eyes open and eyes closed as rest conditions: impact on brain activation patterns , 2004, NeuroImage.

[7]  Fahmeed Hyder,et al.  Energetic basis of brain activity: implications for neuroimaging , 2004, Trends in Neurosciences.

[8]  Fahmeed Hyder,et al.  Lamotrigine suppresses neurophysiological responses to somatosensory stimulation in the rodent , 2006, NeuroImage.

[9]  J. B. Levitt,et al.  Anatomical origins of the classical receptive field and modulatory surround field of single neurons in macaque visual cortical area V1. , 2002, Progress in brain research.

[10]  M. Ueki,et al.  Functional Activation of Cerebral Blood Flow and Metabolism before and after Global Ischemia of Rat Brain , 1988, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[11]  Dae-Shik Kim,et al.  Origin of Negative Blood Oxygenation Level—Dependent fMRI Signals , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[12]  M. Raichle,et al.  Searching for a baseline: Functional imaging and the resting human brain , 2001, Nature Reviews Neuroscience.

[13]  Thomas T. Liu,et al.  Coupling of cerebral blood flow and oxygen consumption during physiological activation and deactivation measured with fMRI , 2004, NeuroImage.

[14]  M D Ginsberg,et al.  Coupled forebrain increases of local cerebral glucose utilization and blood flow during physiologic stimulation of a somatosensory pathway in the rat , 1987, Neurology.

[15]  F. Hyder,et al.  Increased tricarboxylic acid cycle flux in rat brain during forepaw stimulation detected with 1H[13C]NMR. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Raichle Behind the scenes of functional brain imaging: a historical and physiological perspective. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Curio,et al.  Imperceptible Stimuli and Sensory Processing Impediment , 2003, Science.

[18]  Robert G. Shu lman Interview with Robert G. Shulman , 1996, Journal of Cognitive Neuroscience.

[19]  Sridhar S Kannurpatti,et al.  Negative Functional Response to Sensory Stimulation and its Origins , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  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.

[21]  Ralph D Freeman,et al.  Separate Spatial Scales Determine Neural Activity-Dependent Changes in Tissue Oxygen within Central Visual Pathways , 2005, The Journal of Neuroscience.

[22]  Fahmeed Hyder,et al.  Biophysical basis of brain activity: implications for neuroimaging , 2002, Quarterly Reviews of Biophysics.

[23]  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.

[24]  P. Lennie The Cost of Cortical Computation , 2003, Current Biology.

[25]  D. Heeger,et al.  Center-surround interactions in foveal and peripheral vision , 2000, Vision Research.

[26]  John Kostanoski Interview with Robert Granzow, MS, CFE , 2008 .

[27]  L. A. Geddes,et al.  Measurement of the Direct-Current (Faradic) Resistance of the Electrode-Electrolyte Interface for Commonly Used Electrode Materials , 2001, Annals of Biomedical Engineering.

[28]  Paul C Fletcher,et al.  Does the brain have a baseline? Why we should be resisting a rest. , 2007, NeuroImage.

[29]  M. Armstrong‐James,et al.  Spatiotemporal convergence and divergence in the rat S1 “Barrel” cortex , 1987, The Journal of comparative neurology.

[30]  Yasuomi Ouchi,et al.  Regulation of cerebral blood flow response to somatosensory stimulation through the cholinergic system: a positron emission tomography study in unanesthetized monkeys , 1997, Brain Research.

[31]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[32]  G. Bruce Pike,et al.  Hemodynamic and metabolic responses to neuronal inhibition , 2004, NeuroImage.

[33]  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.

[34]  J. Chapin,et al.  Laminar differences in sizes, shapes, and response profiles of cutaneous receptive fields in the rat SI cortex , 2004, Experimental Brain Research.

[35]  U. Mitzdorf Current source-density method and application in cat cerebral cortex: investigation of evoked potentials and EEG phenomena. , 1985, Physiological reviews.

[36]  R Weissleder,et al.  Cerebrovascular dynamics of autoregulation and hypoperfusion. An MRI study of CBF and changes in total and microvascular cerebral blood volume during hemorrhagic hypotension. , 1999, Stroke.

[37]  Y. Frégnac,et al.  The “silent” surround of V1 receptive fields: theory and experiments , 2003, Journal of Physiology-Paris.

[38]  M. Castro-Alamancos,et al.  Absence of Rapid Sensory Adaptation in Neocortex during Information Processing States , 2004, Neuron.

[39]  J. Chapin,et al.  Mapping the body representation in the SI cortex of anesthetized and awake rats , 1984, The Journal of comparative neurology.

[40]  Fahmeed Hyder,et al.  Neuroimaging With Calibrated fMRI , 2004, Stroke.

[41]  J. R. Baker,et al.  The intravascular contribution to fmri signal change: monte carlo modeling and diffusion‐weighted studies in vivo , 1995, Magnetic resonance in medicine.

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

[43]  I. Ohzawa,et al.  Asymmetric Suppression Outside the Classical Receptive Field of the Visual Cortex , 1999, The Journal of Neuroscience.

[44]  S. Laughlin Energy as a constraint on the coding and processing of sensory information , 2001, Current Opinion in Neurobiology.

[45]  Karl J. Friston Imaging neuroscience: principles or maps? , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[46]  R. Shulman,et al.  Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[47]  J. Fodor The Mind Doesn't Work That Way : The Scope and Limits of Computational Psychology , 2000 .

[48]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[49]  C. Petersen,et al.  Visualizing the Cortical Representation of Whisker Touch: Voltage-Sensitive Dye Imaging in Freely Moving Mice , 2006, Neuron.

[50]  A. Dale,et al.  Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[51]  F. Hyder,et al.  Toward absolute quantitation of bold functional MRI. , 1999, Advances in experimental medicine and biology.

[52]  T A Woolsey,et al.  Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain. , 1996, Cerebral cortex.

[53]  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.

[54]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[55]  A. Shmuel,et al.  Sustained Negative BOLD, Blood Flow and Oxygen Consumption Response and Its Coupling to the Positive Response in the Human Brain , 2002, Neuron.

[56]  J. Mayhew,et al.  Concurrent fMRI and optical measures for the investigation of the hemodynamic response function , 2005, Magnetic resonance in medicine.

[57]  F. Hyder,et al.  Stimulated changes in localized cerebral energy consumption under anesthesia. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[58]  T. Nagel The view from nowhere , 1987 .

[59]  D. Simons,et al.  Responses of barrel cortex neurons in awake rats and effects of urethane anesthesia , 2004, Experimental Brain Research.

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

[61]  Stephen V. David,et al.  Parametric reverse correlation reveals spatial linearity of retinotopic human V1 BOLD response , 2004, NeuroImage.

[62]  Albert Gjedde,et al.  Neuronal–Glial Glucose Oxidation and Glutamatergic–GABAergic Function , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[63]  R G Shulman,et al.  Interpreting functional imaging studies in terms of neurotransmitter cycling. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[64]  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.

[65]  N. Logothetis,et al.  Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1 , 2006, Nature Neuroscience.

[66]  F. Hyder,et al.  Total neuroenergetics support localized brain activity: Implications for the interpretation of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[67]  G. Crelier,et al.  Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: The deoxyhemoglobin dilution model , 1999, Magnetic resonance in medicine.

[68]  上木 雅人 Functional activation of cerebral blood flow and metabolism before and after global ischemia of rat brain , 1991 .

[69]  R G Shulman,et al.  Functional imaging studies: linking mind and basic neuroscience. , 2001, The American journal of psychiatry.

[70]  D. Heeger,et al.  Linear Systems Analysis of Functional Magnetic Resonance Imaging in Human V1 , 1996, The Journal of Neuroscience.

[71]  P. R. Bevington,et al.  Data Reduction and Error Analysis for the Physical Sciences , 1969 .

[72]  D L Rothman,et al.  High-Resolution CMRO2 Mapping in Rat Cortex: A Multiparametric Approach to Calibration of BOLD Image Contrast at 7 Tesla , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[73]  Donald J. Woodward,et al.  Differences in cutaneous sensory response properties of single somatosensory cortical neurons in awake and halothane anesthetized rats , 1981, Brain Research Bulletin.

[74]  G. Bonvento,et al.  Local Uncoupling of the Cerebrovascular and Metabolic Responses to Somatosensory Stimulation after Neuronal Nitric Oxide Synthase Inhibition , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[75]  R. Buxton,et al.  Implementation of quantitative perfusion imaging techniques for functional brain mapping using pulsed arterial spin labeling , 1997, NMR in biomedicine.

[76]  John E. W. Mayhew,et al.  Investigating neural–hemodynamic coupling and the hemodynamic response function in the awake rat , 2006, NeuroImage.

[77]  M. Ueki,et al.  Effect of alpha‐chloralose, halothane, pentobarbital and nitrous oxide anesthesia on metabolic coupling in somatosensory cortex of rat , 1992, Acta anaesthesiologica Scandinavica.