Localization of activity-dependent changes in blood volume to submillimeter-scale functional domains in cat visual cortex.

We have examined whether blood volume changes induced by neural activation are controlled precisely enough for us to visualize the submillimeter-scale functional structure in anesthetized and awake cat visual cortex. To activate the submillimeter-scale functional structures such as iso-orientation domains in the cortex, visual stimuli (gratings) were presented to the cats. Two methods were used to examine the spatial precision of blood volume changes including changes in total hemoglobin content and changes in plasma volume: (i) intrinsic signal imaging at the wavelength of hemoglobin's isosbestic point (569 nm) and (ii) imaging of absorption changes of an intravenously injected dye. Both measurements showed that the visual stimuli elicited stimulus-nonspecific and stimulus-specific blood volume changes in the cortex. The former was not spatially localized, while the latter was confined to iso-orientation domains. From the measurement of spatial separation of the iso-orientation domains, we estimated the spatial resolution of stimulus-specific blood volume changes to be as high as 0.6 mm. The changes in stimulus-nonspecific and -specific blood volume were not linearly correlated. These results suggest the existence of fine blood volume control mechanisms in the capillary bed in addition to global control mechanisms in arteries.

[1]  C Sato,et al.  Analysis of Optical Signals Evoked by Peripheral Nerve Stimulation in Rat Somatosensory Cortex: Dynamic Changes in Hemoglobin Concentration and Oxygenation , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  L. Cohen,et al.  Optical monitoring of activity from many areas of the in vitro and in vivo salamander olfactory bulb: a new method for studying functional organization in the vertebrate central nervous system , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[4]  H. Kadono,et al.  Novel functional imaging technique from brain surface with optical coherence tomography enabling visualization of depth resolved functional structure in vivo , 2003, Journal of Neuroscience Methods.

[5]  M. Nemoto,et al.  Optical imaging and measuring of local hemoglobin concentration and oxygenation changes during somatosensory stimulation in rat cerebral cortex. , 1997, Advances in experimental medicine and biology.

[6]  B. MacVicar,et al.  Imaging of synaptically evoked intrinsic optical signals in hippocampal slices , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  A. Toga,et al.  Functional Increases in Cerebral Blood Volume over Somatosensory Cortex , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[8]  T. Maeda,et al.  Microangioarchitecture of Rat Parietal Cortex With Special Reference to Vascular “Sphincters’: Scanning Electron Microscopic and Dark Field Microscopic Study , 1981, Stroke.

[9]  P. C. Murphy,et al.  Cerebral Cortex , 2017, Cerebral Cortex.

[10]  A Villringer,et al.  Characterization of CBF response to somatosensory stimulation: model and influence of anesthetics. , 1993, The American journal of physiology.

[11]  A W Toga,et al.  Refractory periods observed by intrinsic signal and fluorescent dye imaging. , 1998, Journal of neurophysiology.

[12]  A. Grinvald,et al.  Optical Imaging of the Layout of Functional Domains in Area 17 and Across the Area 17/18 Border in Cat Visual Cortex , 1995, The European journal of neuroscience.

[13]  O. Paulson,et al.  Capillary circulation in the brain. , 1992, Cerebrovascular and brain metabolism reviews.

[14]  Katsushige Sato,et al.  Optical illustration of glutamate‐induced cell swelling coupled with membrane depolarization in embryonic brain stem slices , 1997, Neuroreport.

[15]  N. Harel,et al.  Blood capillary distribution correlates with hemodynamic-based functional imaging in cerebral cortex. , 2002, Cerebral cortex.

[16]  A. Ngai,et al.  Simultaneous Measurements of Pial Arteriolar Diameter and Laser-Doppler Flow during Somatosensory Stimulation , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  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.

[18]  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.

[19]  A Grinvald,et al.  Optical imaging reveals the functional architecture of neurons processing shape and motion in owl monkey area MT , 1994, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[20]  Y. Yamane,et al.  Complex objects are represented in macaque inferotemporal cortex by the combination of feature columns , 2001, Nature Neuroscience.

[21]  T. Wiesel,et al.  Functional architecture of cortex revealed by optical imaging of intrinsic signals , 1986, Nature.

[22]  I A Silver,et al.  Cellular microenvironment in relation to local blood flow. , 1978, Ciba Foundation symposium.

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

[24]  T. Ebner,et al.  Local and propagated vascular responses evoked by focal synaptic activity in cerebellar cortex. , 1997, Journal of neurophysiology.

[25]  Dae-Shik Kim,et al.  Localized cerebral blood flow response at submillimeter columnar resolution , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  G. Pawlik,et al.  Quantitative capillary topography and blood flow in the cerebral cortex of cats: an in vivo microscopic study , 1981, Brain Research.

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

[28]  R. Keynes,et al.  Changes in light scattering associated with the action potential in crab nerves , 1971, The Journal of physiology.

[29]  N. Akgören,et al.  Functional recruitment of red blood cells to rat brain microcirculation accompanying increased neuronal activity in cerebellar cortex. , 1999, Neuroreport.

[30]  N. Morel,et al.  Pericyte physiology , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[31]  Amiram Grinvald,et al.  Iso-orientation domains in cat visual cortex are arranged in pinwheel-like patterns , 1991, Nature.

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

[33]  Dewen Hu,et al.  An Evaluation of Linear Model Analysis Techniques for Processing Images of Microcirculation Activity , 1998, NeuroImage.

[34]  A. Grinvald,et al.  The layout of iso-orientation domains in area 18 of cat visual cortex: optical imaging reveals a pinwheel-like organization , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  G. Ghose,et al.  Form processing modules in primate area V4. , 1997, Journal of neurophysiology.

[36]  J. Ricardo Alcala,et al.  Light transmittance as an index of cell volume in hippocampal slices: optical differences of interfaced and submerged positions , 1995, Brain Research.

[37]  Keiji Tanaka,et al.  Optical Imaging of Functional Organization in the Monkey Inferotemporal Cortex , 1996, Science.

[38]  A Grinvald,et al.  Long-Term Optical Imaging and Spectroscopy Reveal Mechanisms Underlying the Intrinsic Signal and Stability of Cortical Maps in V1 of Behaving Monkeys , 2000, The Journal of Neuroscience.

[39]  Dae-Shik Kim,et al.  High-resolution mapping of iso-orientation columns by fMRI , 2000, Nature Neuroscience.

[40]  K. Holthoff,et al.  Intrinsic optical signals in rat neocortical slices measured with near- infrared dark-field microscopy reveal changes in extracellular space , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  D. Ts'o,et al.  Visual topography in primate V2: multiple representation across functional stripes , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  M Tomita,et al.  Effects of hemolysis, hematocrit, RBC swelling, and flow rate on light scattering by blood in a 0.26 cm ID transparent tube. , 1983, Biorheology.

[43]  H. Scheich,et al.  New Insights into the Hemodynamic Blood Oxygenation Level-Dependent Response through Combination of Functional Magnetic Resonance Imaging and Optical Recording in Gerbil Barrel Cortex , 2000, The Journal of Neuroscience.

[44]  A. Ngai,et al.  Effect of sciatic nerve stimulation on pial arterioles in rats. , 1988, The American journal of physiology.

[45]  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.

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

[47]  Keiji Tanaka,et al.  Functional architecture in monkey inferotemporal cortex revealed by in vivo optical imaging , 1998, Neuroscience Research.

[48]  R. Andrew,et al.  Potential sources of intrinsic optical signals imaged in live brain slices. , 1999, Methods.

[49]  A. Grinvald,et al.  A tandem-lens epifluorescence macroscope: Hundred-fold brightness advantage for wide-field imaging , 1991, Journal of Neuroscience Methods.

[50]  K. Sato,et al.  GABA-Induced intrinsic light-scattering changes associated with voltage-sensitive dye signals in embryonic brain stem slices: coupling of depolarization and cell shrinkage. , 1998, Journal of neurophysiology.

[51]  Ying Zheng,et al.  Spectroscopic Analysis of Changes in Remitted Illumination: The Response to Increased Neural Activity in Brain , 1999, NeuroImage.

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

[53]  A. Villringer,et al.  Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study. , 1994, Circulation research.

[54]  D. Ts'o,et al.  Functional organization of primate visual cortex revealed by high resolution optical imaging. , 1990, Science.

[55]  A. Grinvald,et al.  Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[56]  H. Gainer,et al.  Large and rapid changes in light scattering accompany secretion by nerve terminals in the mammalian neurohypophysis , 1985, The Journal of general physiology.