1932

Abstract

Functional magnetic resonance imaging (fMRI) provides a unique view of the working human mind. The blood-oxygen-level-dependent (BOLD) signal, detected in fMRI, reflects changes in deoxyhemoglobin driven by localized changes in brain blood flow and blood oxygenation, which are coupled to underlying neuronal activity by a process termed neurovascular coupling. Over the past 10 years, a range of cellular mechanisms, including astrocytes, pericytes, and interneurons, have been proposed to play a role in functional neurovascular coupling. However, the field remains conflicted over the relative importance of each process, while key spatiotemporal features of BOLD response remain unexplained. Here, we review current candidate neurovascular coupling mechanisms and propose that previously overlooked involvement of the vascular endothelium may provide a more complete picture of how blood flow is controlled in the brain. We also explore the possibility and consequences of conditions in which neurovascular coupling may be altered, including during postnatal development, pathological states, and aging, noting relevance to both stimulus-evoked and resting-state fMRI studies.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-neuro-071013-014111
2014-07-08
2024-06-18
Loading full text...

Full text loading...

/deliver/fulltext/neuro/37/1/annurev-neuro-071013-014111.html?itemId=/content/journals/10.1146/annurev-neuro-071013-014111&mimeType=html&fmt=ahah

Literature Cited

  1. Akerboom J, Chen T-W, Wardill TJ, Tian L, Marvin JS. et al. 2012. Optimization of a GCaMP calcium indicator for neural activity imaging. J. Neurosci. 32:13819–40 [Google Scholar]
  2. Ances BM, Buerk DG, Greenberg JH, Detre JA. 2001. Temporal dynamics of the partial pressure of brain tissue oxygen during functional forepaw stimulation in rats. Neurosci. Lett. 306:106–10 [Google Scholar]
  3. Andresen J, Shafi NI, Bryan RM Jr. 2006. Endothelial influences on cerebrovascular tone. J. Appl. Physiol. 100:318–27 [Google Scholar]
  4. Armulik A, Abramsson A, Betsholtz C. 2005. Endothelial/pericyte interactions. Circ. Res. 97:512–23 [Google Scholar]
  5. Arnerić SP, Honig MA, Milner TA, Greco S, Iadecola C, Reis DJ. 1988. Neuronal and endothelial sites of acetylcholine synthesis and release associated with microvessels in rat cerebral cortex: ultrastructural and neurochemical studies. Brain Res. 454:11–30 [Google Scholar]
  6. Attwell D, Buchan AM, Charpak S, Lauritzen M, MacVicar BA, Newman EA. 2010. Glial and neuronal control of brain blood flow. Nature 468:232–43 [Google Scholar]
  7. Attwell D, Iadecola C. 2002. The neural basis of functional brain imaging signals. Trends Neurosci. 25:621–25 [Google Scholar]
  8. Bagher P, Segal SS. 2011. Regulation of blood flow in the microcirculation: role of conducted vasodilation. Acta Physiol. 202:271–84 [Google Scholar]
  9. Bekar LK, Wei HS, Nedergaard M. 2012. The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand. J. Cereb. Blood Flow Metab. 32:2135–45 [Google Scholar]
  10. Berwick J, Johnston D, Jones M, Martindale J, Martin C. et al. 2008. Fine detail of neurovascular coupling revealed by spatiotemporal analysis of the hemodynamic response to single whisker stimulation in rat barrel cortex. J. Neurophysiol. 99:787–98 [Google Scholar]
  11. Blinder P, Tsai PS, Kaufhold JP, Knutsen PM, Suhl H, Kleinfeld D. 2013. The cortical angiome: an interconnected vascular network with noncolumnar patterns of blood flow. Nat. Neurosci. 16:889–97 [Google Scholar]
  12. Boorman L, Kennerley AJ, Johnston D, Jones M, Zheng Y. et al. 2010. Negative blood oxygen level dependence in the rat: a model for investigating the role of suppression in neurovascular coupling. J. Neurosci. 30:4285–94 [Google Scholar]
  13. Bouchard MB, Chen BR, Burgess SA, Hillman EMC. 2009. Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics. Opt. Express 17:15670–78 [Google Scholar]
  14. Boynton GM, Engel SA, Glover GH, Heeger DJ. 1996. Linear systems analysis of functional magnetic resonance imaging in human V1. J. Neurosci. 16:4207–21 [Google Scholar]
  15. Brown AM, Ransom BR. 2007. Astrocyte glycogen and brain energy metabolism. Glia 55:1263–71 [Google Scholar]
  16. Buxton RB. 2012. Dynamic models of BOLD contrast. NeuroImage 62:953–61 [Google Scholar]
  17. Buxton RB, Wong EC, Frank LR. 1998. Dynamics of blood flow and oxygenation changes during brain activation: the balloon model. Magn. Reson. Med. 39:855–64 [Google Scholar]
  18. Cardoso MMB, Sirotin YB, Lima B, Glushenkova E, Das A. 2012. The neuroimaging signal is a linear sum of neurally distinct stimulus- and task-related components. Nat. Neurosci. 15:1298–306 [Google Scholar]
  19. Cauli B, Hamel E. 2010. Revisiting the role of neurons in neurovascular coupling. Front. Neuroenerg. 2:9 [Google Scholar]
  20. Cauli B, Tong X-K, Rancillac A, Serluca N, Lambolez B. et al. 2004. Cortical GABA interneurons in neurovascular coupling: relays for subcortical vasoactive pathways. J. Neurosci. 24:8940–49 [Google Scholar]
  21. Chédotal A, Umbriaco D, Descarries L, Hartman BK, Hamel E. 1994. Light and electron microscopic immunocytochemical analysis of the neurovascular relationships of choline acetyltransferase and vasoactive intestinal polypeptide nerve terminals in the rat cerebral cortex. J. Comp. Neurol. 343:57–71 [Google Scholar]
  22. Chen BR, Bouchard MB, McCaslin AFH, Burgess SA, Hillman EMC. 2011. High-speed vascular dynamics of the hemodynamic response. NeuroImage 54:1021–30 [Google Scholar]
  23. Chen BR, Kozberg MG, Bouchard MB, Shaik MA, Hillman EMC. 2014. A critical role for the vascular endothelium in functional neurovascular coupling in the brain. J. Am. Heart Assoc. In press [Google Scholar]
  24. Chen LM, Friedman RM, Roe AW. 2005. Optical imaging of SI topography in anesthetized and awake squirrel monkeys. J. Neurosci. 25:7648–59 [Google Scholar]
  25. Culver JP, Siegel AM, Franceschini MA, Mandeville JB, Boas DA. 2005. Evidence that cerebral blood volume can provide brain activation maps with better spatial resolution than deoxygenated hemoglobin. NeuroImage 27:947–59 [Google Scholar]
  26. D'Esposito M, Deouell LY, Gazzaley A. 2003. Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nat. Rev. Neurosci. 4:863–72 [Google Scholar]
  27. Das A, Gilbert CD. 1997. Distortions of visuotopic map match orientation singularities in primary visual cortex. Nature 387:594–98 [Google Scholar]
  28. de Wit C, Griffith T. 2010. Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses. Pflügers Arch. - Eur. J. Physiol. 459:897–914 [Google Scholar]
  29. Devor A, Dunn AK, Andermann ML, Ulbert I, Boas DA, Dale AM. 2003. Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex. Neuron 39:353–59 [Google Scholar]
  30. Devor A, Hillman EMC, Tian P, Waeber C, Teng IC. et al. 2008. Stimulus-induced changes in blood flow and 2-deoxyglucose uptake dissociate in ipsilateral somatosensory cortex. J. Neurosci. 28:14347–57 [Google Scholar]
  31. Devor A, Sakadžić S, Saisan PA, Yaseen MA, Roussakis E. et al. 2011. “Overshoot” of O2 is required to maintain baseline tissue oxygenation at locations distal to blood vessels. J. Neurosci. 31:13676–81 [Google Scholar]
  32. Devor A, Tian P, Nishimura N, Teng IC, Hillman EMC. et al. 2007. Suppressed neuronal activity and concurrent arteriolar vasoconstriction may explain negative blood oxygenation level-dependent signal. J. Neurosci. 27:4452–59 [Google Scholar]
  33. Drew PJ, Shih AY, Kleinfeld D. 2011. Fluctuating and sensory-induced vasodynamics in rodent cortex extend arteriole capacity. Proc. Natl. Acad. Sci. USA 108:8473–78 [Google Scholar]
  34. Duling BR, Berne RM. 1970. Propagated vasodilation in the microcirculation of the hamster cheek pouch. Circ. Res. 26:163–70 [Google Scholar]
  35. Dunn AK, Devor A, Bolay H, Andermann M, Moskowitz M. et al. 2003. Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation. Opt. Lett. 28:28–30 [Google Scholar]
  36. Dunn AK, Devor A, Dale AM, Boas DA. 2005. Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex. NeuroImage 27:279–90 [Google Scholar]
  37. Eggebrecht AT, White BR, Ferradal SL, Chen C, Zhan Y. et al. 2012. A quantitative spatial comparison of high-density diffuse optical tomography and fMRI cortical mapping. NeuroImage 61:1120–28 [Google Scholar]
  38. Erinjeri JP, Woolsey TA. 2002. Spatial integration of vascular changes with neural activity in mouse cortex. J. Cereb. Blood Flow Metab. 22:353–60 [Google Scholar]
  39. Félétou M, Vanhoutte PM. 2004. EDHF: new therapeutic targets?. Pharmacol. Res. 49:565–80 [Google Scholar]
  40. Fernández-Klett F, Offenhauser N, Dirnagl U, Priller J, Lindauer U. 2010. Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain. Proc. Natl. Acad. Sci. USA 107:22290–95 [Google Scholar]
  41. Figueroa XF, Duling BR. 2009. Gap junctions in the control of vascular function. Antioxid. Redox Signal. 11:251–66 [Google Scholar]
  42. Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. 2005. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc. Natl. Acad. Sci. USA 102:279673–78 [Google Scholar]
  43. Fox PT, Raichle ME. 1986. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc. Natl. Acad. Sci. USA 83:1140–44 [Google Scholar]
  44. Fox PT, Raichle ME, Mintun MA, Dence C. 1988. Nonoxidative glucose consumption during focal physiologic neural activity. Science 241:462–64 [Google Scholar]
  45. Friedland RP, Iadecola C. 1991. Roy and Sherrington (1890): a centennial reexamination of “On the Regulation of the Blood-Supply of the Brain. Neurology 41:10–14 [Google Scholar]
  46. Friston KJ, Mechelli A, Turner R, Price CJ. 2000. Nonlinear responses in fMRI: the balloon model, Volterra kernels, and other hemodynamics. NeuroImage 12:466–77 [Google Scholar]
  47. Girouard H, Iadecola C. 2006. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J. Appl. Physiol. 100:328–35 [Google Scholar]
  48. Greicius MD, Srivastava G, Reiss AL, Menon V. 2004. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc. Natl. Acad. Sci. USA 101:4637–42 [Google Scholar]
  49. Hamilton NB, Attwell D, Hall CN. 2010. Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease. Front. Neuroenerg. 2:5 [Google Scholar]
  50. Harris S, Jones M, Zheng Y, Berwick J. 2010. Does neural input or processing play a greater role in the magnitude of neuroimaging signals?. Front. Neuroenerg. 2:15 [Google Scholar]
  51. Heeger DJ, Ress D. 2002. What does fMRI tell us about neuronal activity?. Nat. Rev. Neurosci. 3:142–51 [Google Scholar]
  52. Hertz L. 2004. The astrocyte-neuron lactate shuttle: a challenge of a challenge. J. Cereb. Blood Flow Metab. 24:1241–48 [Google Scholar]
  53. Hewson-Stoate N, Jones M, Martindale J, Berwick J, Mayhew J. 2005. Further nonlinearities in neurovascular coupling in rodent barrel cortex. NeuroImage 24:565–74 [Google Scholar]
  54. Hillman EMC. 2007. Optical brain imaging in-vivo: techniques and applications from animal to man. J. Biomed. Opt. 12:051402 [Google Scholar]
  55. Hillman EMC, Devor A, Bouchard M, Dunn AK, Krauss GW. et al. 2007. Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation. NeuroImage 35:89–104 [Google Scholar]
  56. Hirano Y, Stefanovic B, Silva AC. 2011. Spatiotemporal evolution of the functional magnetic resonance imaging response to ultrashort stimuli. J. Neurosci. 31:1440–47 [Google Scholar]
  57. Hotta H, Uchida S, Kagitani F, Maruyama N. 2011. Control of cerebral cortical blood flow by stimulation of basal forebrain cholinergic areas in mice. J. Physiol. Sci. 61:201–9 [Google Scholar]
  58. Hu X, Yacoub E. 2012. The story of the initial dip in fMRI. NeuroImage 62:1103–8 [Google Scholar]
  59. Kim J, Khan R, Thompson JK, Ress D. Hwan 2013. Model of the transient neurovascular response based on prompt arterial dilation. J. Cereb. Blood Flow Metab. 33:1429–39 [Google Scholar]
  60. Iadecola C, Yang G, Ebner TJ, Chen G. 1997. Local and propagated vascular responses evoked by focal synaptic activity in cerebellar cortex. J. Neurophysiol. 78:651–59 [Google Scholar]
  61. Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW. 2004. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305:99–103 [Google Scholar]
  62. Kennerley AJ, Harris S, Bruyns-Haylett M, Boorman L, Zheng Y. et al. 2012. Early and late stimulus-evoked cortical hemodynamic responses provide insight into the neurogenic nature of neurovascular coupling. J. Cereb. Blood Flow Metab. 32:468–80 [Google Scholar]
  63. Kocharyan A, Fernandes P, Tong X-K, Vaucher E, Hamel E. 2007. Specific subtypes of cortical GABA interneurons contribute to the neurovascular coupling response to basal forebrain stimulation. J. Cereb. Blood Flow Metab. 28:221–31 [Google Scholar]
  64. Kozberg MG, Chen BR, DeLeo SE, Bouchard MB, Hillman EMC. 2013. Resolving the transition from negative to positive blood oxygen level-dependent responses in the developing brain. Proc. Natl. Acad. Sci. USA 110:4380–85 [Google Scholar]
  65. Lecrux C, Toussay X, Kocharyan A, Fernandes P, Neupane S. et al. 2011. Pyramidal neurons are “neurogenic hubs” in the neurovascular coupling response to whisker stimulation. J. Neurosci. 31:9836–47 [Google Scholar]
  66. Li B, Freeman RD. 2010. Neurometabolic coupling in the lateral geniculate nucleus changes with extended age. J. Neurophysiol. 104:1414–25 [Google Scholar]
  67. Li P, Luo Q, Luo W, Chen S, Cheng H, Zeng S. 2003. Spatiotemporal characteristics of cerebral blood volume changes in rat somatosensory cortex evoked by sciatic nerve stimulation and obtained by optical imaging. J. Biomed. Opt. 8:629–35 [Google Scholar]
  68. Lind BL, Brazhe AR, Jessen SB, Tan FCC, Lauritzen MJ. 2013. Rapid stimulus-evoked astrocyte Ca2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo. Proc. Natl. Acad. Sci. USA 110(48):E4678–87 [Google Scholar]
  69. Lindauer U, Leithner C, Kaasch H, Rohrer B, Foddis M. et al. 2010. Neurovascular coupling in rat brain operates independent of hemoglobin deoxygenation. J. Cereb. Blood Flow Metab. 30:757–68 [Google Scholar]
  70. Lindauer U, Royl G, Leithner C, Kühl M, Gold L. et al. 2001. No evidence for early decrease in blood oxygenation in rat whisker cortex in response to functional activation. NeuroImage 13:988–1001 [Google Scholar]
  71. Logothetis NK. 2010. Neurovascular uncoupling: much ado about nothing. Front. Neuroenerg. 2:2 [Google Scholar]
  72. Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A. 2001. Neurophysiological investigation of the basis of the fMRI signal. Nature 412:150–57 [Google Scholar]
  73. Malonek D, Grinvald A. 1996. Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science 272:551–54 [Google Scholar]
  74. Mandeville JB, Marota JJA, Ayata C, Zaharchuk G, Moskowitz MA. et al. 1999. Evidence of a cerebrovascular postarteriole Windkessel with delayed compliance. J. Cereb. Blood Flow Metab. 19:679–89 [Google Scholar]
  75. Marrelli SP. 2001. Mechanisms of endothelial P2Y1- and P2Y2-mediated vasodilatation involve differential [Ca2+]i responses. Am. J. Physiol. - Heart Circ. Physiol. 281:H1759–66 [Google Scholar]
  76. Marrelli SP, Eckmann MS, Hunte MS. 2003. Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations. Am. J. Physiol. - Heart Circ. Physiol. 285:H1590–99 [Google Scholar]
  77. Martin C, Martindale J, Berwick J, Mayhew J. 2006. Investigating neural-hemodynamic coupling and the hemodynamic response function in the awake rat. NeuroImage 32:33–48 [Google Scholar]
  78. Martin C, Zheng Y, Sibson NR, Mayhew JEW, Berwick J. 2013. Complex spatiotemporal haemodynamic response following sensory stimulation in the awake rat. NeuroImage 66:1–8 [Google Scholar]
  79. Martindale J, Berwick J, Martin C, Kong Y, Zheng Y, Mayhew J. 2005. Long duration stimuli and nonlinearities in the neural-haemodynamic coupling. J. Cereb. Blood Flow Metab. 25:651–61 [Google Scholar]
  80. Martindale J, Mayhew J, Berwick J, Jones M, Martin C. et al. 2003. The hemodynamic impulse response to a single neural event. J. Cereb. Blood Flow Metab. 23:546–55 [Google Scholar]
  81. Mayhew J, Hu D, Zheng Y, Askew S, Hou Y. et al. 1998. An evaluation of linear model analysis techniques for processing images of microcirculation activity. NeuroImage 7:49–71 [Google Scholar]
  82. McCaslin AFH, Chen BR, Radosevich AJ, Cauli B, Hillman EMC. 2011. In-vivo 3D morphology of astrocyte-vasculature interactions in the somatosensory cortex: implications for neurovascular coupling. J. Cereb. Blood Flow Metab. 31:795–806 [Google Scholar]
  83. Mogi M, Horiuchi M. 2011. Neurovascular coupling in cognitive impairment associated with diabetes mellitus. Circ. J. 75:1042–48 [Google Scholar]
  84. Ngai AC, Winn HR. 2002. Pial arteriole dilation during somatosensory stimulation is not mediated by an increase in CSF metabolites. Am. J. Physiol. Heart Circ. Physiol. 282:H902–7 [Google Scholar]
  85. Nicolakakis N, Hamel E. 2011. Neurovascular function in Alzheimer's disease patients and experimental models. J. Cereb. Blood Flow Metab. 31:1354–70 [Google Scholar]
  86. Nielsen AN, Lauritzen M. 2001. Coupling and uncoupling of activity-dependent increases of neuronal activity and blood flow in rat somatosensory cortex. J. Physiol. 533:773–85 [Google Scholar]
  87. Nizar K, Uhlirova H, Tian P, Saisan PA, Cheng Q. et al. 2013. In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase. J. Neurosci. 33:8411–22 [Google Scholar]
  88. Ogawa S, Lee TM, Kay AR, Tank DW. 1990. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc. Natl. Acad. Sci. USA 87:9868–72 [Google Scholar]
  89. Parpaleix A, Houssen YG, Charpak S. 2013. Imaging local neuronal activity by monitoring PO2 transients in capillaries. Nat. Med. 19:241–46 [Google Scholar]
  90. Paulson OB, Hasselbalch SG, Rostrup E, Knudsen GM, Pelligrino D. 2009. Cerebral blood flow response to functional activation. J. Cereb. Blood Flow Metab. 30:2–14 [Google Scholar]
  91. Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M. et al. 2007. Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251–56 [Google Scholar]
  92. Pellerin L, Magistretti PJ. 1994. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. USA 91:10625–29 [Google Scholar]
  93. Peppiatt CM, Howarth C, Mobbs P, Attwell D. 2006. Bidirectional control of CNS capillary diameter by pericytes. Nature 443:700–4 [Google Scholar]
  94. Piché M, Uchida S, Hara S, Aikawa Y, Hotta H. 2010. Modulation of somatosensory-evoked cortical blood flow changes by GABAergic inhibition of the nucleus basalis of Meynert in urethane-anaesthetized rats. J. Physiol. 588:2163–71 [Google Scholar]
  95. Powers WJ, Hirsch IB, Cryer PE. 1996. Effect of stepped hypoglycemia on regional cerebral blood flow response to physiological brain activation. Am. J. Physiol. - Heart Circ. Physiol. 270:H554–59 [Google Scholar]
  96. Raichle ME. 1998. Behind the scenes of functional brain imaging: a historical and physiological perspective. Proc. Natl. Acad. Sci. USA 95:765–72 [Google Scholar]
  97. Rayshubskiy A, Wojtasiewicz TJ, Mikell CB, Bouchard MB, Timerman D. et al. 2013. Direct, intraoperative observation of ∼0.1 Hz hemodynamic oscillations in awake human cortex: implications for fMRI. NeuroImage 87:323–31 [Google Scholar]
  98. Rocca MA, Valsasina P, Absinta M, Riccitelli G, Rodegher ME. et al. 2010. Default-mode network dysfunction and cognitive impairment in progressive MS. Neurology 74:1252–59 [Google Scholar]
  99. Rosenblum WI. 1986. Endothelial dependent relaxation demonstrated in vivo in cerebral arterioles. Stroke 17:494–97 [Google Scholar]
  100. Roy CS, Sherrington CS. 1890. On the regulation of the blood-supply of the brain. J. Physiol. 11:85–108 [Google Scholar]
  101. Sakadzić S, Roussakis E, Yaseen MA, Mandeville ET, Srinivasan VJ. et al. 2010. Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue. Nat. Meth. 7:755–59 [Google Scholar]
  102. Sarelius I, Pohl U. 2010. Control of muscle blood flow during exercise: local factors and integrative mechanisms. Acta Physiol. 199:349–65 [Google Scholar]
  103. Sato A, Sato Y. 1995. Cholinergic neural regulation of regional cerebral blood flow. Alzheimer Dis. Assoc. Disord. 9:28–38 [Google Scholar]
  104. Schönfelder U, Hofer A, Paul M, Funk RHW. 1998. In situ observation of living pericytes in rat retinal capillaries. Microvasc. Res. 56:22–29 [Google Scholar]
  105. Schroeter ML, Cutini S, Wahl MM, Scheid R, Yves von Cramon D. 2007. Neurovascular coupling is impaired in cerebral microangiopathy—an event-related Stroop study. NeuroImage 34:26–34 [Google Scholar]
  106. Schummers J, Yu H, Sur M. 2008. Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320:1638–43 [Google Scholar]
  107. Schurr A. 2006. Lactate: the ultimate cerebral oxidative energy substrate?. J. Cereb. Blood Flow Metab. 26:142–52 [Google Scholar]
  108. Sheth SA, Nemoto M, Guiou M, Walker M, Pouratian N, Toga AW. 2004. Linear and nonlinear relationships between neuronal activity, oxygen metabolism, and hemodynamic responses. Neuron 42:347–55 [Google Scholar]
  109. Shibuki K, Hishida R, Murakami H, Kudoh M, Kawaguchi T. et al. 2003. Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence. J. Physiol. 549:919–27 [Google Scholar]
  110. Sirotin YB, Das A. 2009. Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity. Nature 457:475–79 [Google Scholar]
  111. Sirotin YB, Hillman EMC, Bordier C, Das A. 2009. Spatiotemporal precision and hemodynamic mechanism of optical point spreads in alert primates. Proc. Natl. Acad. Sci. USA 106:18390–95 [Google Scholar]
  112. Stefanovic B, Hutchinson E, Yakovleva V, Schram V, Russell JT. et al. 2007. Functional reactivity of cerebral capillaries. J. Cereb. Blood Flow Metab. 28:961–72 [Google Scholar]
  113. Sun W, McConnell E, Pare J-F, Xu Q, Chen M. et al. 2013. Glutamate-dependent neuroglial calcium signaling differs between young and adult brain. Science 339:197–200 [Google Scholar]
  114. Takano T, Tian G-F, Peng W, Lou N, Libionka W. et al. 2006. Astrocyte-mediated control of cerebral blood flow. Nat. Neurosci. 9:260–67 [Google Scholar]
  115. Takata N, Nagai T, Ozawa K, Oe Y, Mikoshiba K, Hirase H. 2013. Cerebral blood flow modulation by basal forebrain or whisker stimulation can occur independently of large cytosolic Ca2+ signaling in astrocytes. PLoS One 8:e66525 [Google Scholar]
  116. Tallini YN, Brekke JF, Shui B, Doran R, Hwang S-M. et al. 2007. Propagated endothelial Ca2+ waves and arteriolar dilation in vivo: measurements in Cx40BAC–GCaMP2 transgenic mice. Circ. Res. 101:1300–9 [Google Scholar]
  117. Tian P, Teng IC, May LD, Kurz R, Lu K. et al. 2010. Cortical depth-specific microvascular dilation underlies laminar differences in blood oxygenation level-dependent functional MRI signal. Proc. Natl. Acad. Sci. USA 107:15246–51 [Google Scholar]
  118. Tomita M. 2007. Blood flow control in the brain: possible biphasic mechanism of functional hyperemia. Asian Biomed 1:117–32 [Google Scholar]
  119. Turner R. 2002. How much cortex can a vein drain? Downstream dilution of activation-related cerebral blood oxygenation changes. NeuroImage 16:1062–67 [Google Scholar]
  120. Vanzetta I, Grinvald A. 1999. Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging. Science 286:1555–58 [Google Scholar]
  121. Vanzetta I, Hildesheim R, Grinvald A. 2005. Compartment-resolved imaging of activity-dependent dynamics of cortical blood volume and oximetry. J. Neurosci. 25:2233–44 [Google Scholar]
  122. Vaucher E, Hamel E. 1995. Cholinergic basal forebrain neurons project to cortical microvessels in the rat: electron microscopic study with anterogradely transported Phaseolus vulgaris leucoagglutinin and choline acetyltransferase immunocytochemistry. J. Neurosci. 15:7427–41 [Google Scholar]
  123. Villringer A, Them A, Lindauer U, Einhäupl K, Dirnagl U. 1994. Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study. Circ. Res. 75:55–62 [Google Scholar]
  124. Wang X, Lou N, Xu Q, Tian G, Peng WG. et al. 2006. Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo. Nat. Neurosci. 9:816–23 [Google Scholar]
  125. Winkler EA, Bell RD, Zlokovic BV. 2011. Central nervous system pericytes in health and disease. Nat. Neurosci. 14:1398–405 [Google Scholar]
  126. Winship IR, Plaa N, Murphy TH. 2007. Rapid astrocyte calcium signals correlate with neuronal activity and onset of the hemodynamic response in vivo. J. Neurosci. 27:6268–72 [Google Scholar]
  127. Winter P, Dora KA. 2007. Spreading dilatation to luminal perfusion of ATP and UTP in rat isolated small mesenteric arteries. J. Physiol. 582:335–47 [Google Scholar]
  128. Wolf T, Lindauer U, Villringer A, Dirnagl U. 1997. Excessive oxygen or glucose supply does not alter the blood flow response to somatosensory stimulation or spreading depression in rats. Brain Res. 761:290–99 [Google Scholar]
  129. Wölfle SE, Chaston DJ, Goto K, Sandow SL, Edwards FR, Hill CE. 2011. Non-linear relationship between hyperpolarisation and relaxation enables long distance propagation of vasodilatation. J. Physiol. 589:2607–23 [Google Scholar]
  130. Yablonskiy DA, Ackerman JJH, Raichle ME. 2000. Coupling between changes in human brain temperature and oxidative metabolism during prolonged visual stimulation. Proc. Natl. Acad. Sci. USA 97:7603–8 [Google Scholar]
  131. Yeşilyurt B, Uğurbil K, Uludağ K. 2008. Dynamics and nonlinearities of the BOLD response at very short stimulus durations. Magn. Reson. Imaging 26:853–62 [Google Scholar]
  132. You J, Johnson TD, Childres WF, Bryan RM Jr. 1997. Endothelial-mediated dilations of rat middle cerebral arteries by ATP and ADP. Am. J. Physiol. - Heart Circ. Physiol. 273:H1472–77 [Google Scholar]
  133. Zhang D, Raichle ME. 2010. Disease and the brain's dark energy. Nat. Rev. Neurol. 6:15–28 [Google Scholar]
  134. Zhao F, Wang P, Hendrich K, Ugurbil K, Kim S-G. 2006. Cortical layer-dependent BOLD and CBV responses measured by spin-echo and gradient-echo fMRI: insights into hemodynamic regulation. NeuroImage 30:1149–60 [Google Scholar]
/content/journals/10.1146/annurev-neuro-071013-014111
Loading
/content/journals/10.1146/annurev-neuro-071013-014111
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error