Skip to main content

Neuronal Basis of Non-Invasive Functional Imaging: From Microscopic Neurovascular Dynamics to BOLD fMRI

Part of the Advances in Neurobiology book series (NEUROBIOL,volume 4)

Abstract

With the growing recognition of the complexity of neurovascular coupling, research has focused on the “neurovascular unit”, a close association between neurons, astrocytes and blood vessels. A number of experimental tools have been developed for probing the neurovascular unit in animal models, providing the potential for a much deeper understanding of these fundamental physiological mechanisms. In this chapter, we review some of the available experimental and computational methods and present a multi-level conceptual framework for analyzing and interpreting a wide range of experimental measurements. We then discuss our working hypotheses regarding the regulation of blood flow and neurophysiological correlates of fMRI signals. Finally, we discuss how multimodal imaging, along with valid physiological models, can ultimately be used to obtain quantitative estimates of physiological parameters in health and disease and provide an outlook for the future directions in neurovascular research.

Keywords

  • Imaging
  • Neurovascular
  • Neurometabolic
  • CBF
  • CMRO2
  • LFP
  • CSD
  • MUA
  • fMRI
  • BOLD
  • Optical
  • Microscopy
  • Hemodynamic
  • Neurovascular unit
  • Extracellular potential
  • Forward modeling
  • Laminar population analysis

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-4614-1788-0_15
  • Chapter length: 68 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   219.00
Price excludes VAT (USA)
  • ISBN: 978-1-4614-1788-0
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   279.99
Price excludes VAT (USA)
Hardcover Book
USD   349.99
Price excludes VAT (USA)
Fig. 15.1
Fig. 15.2
Fig. 15.3
Fig. 15.4
Fig. 15.5
Fig. 15.6
Fig. 15.7
Fig. 15.8
Fig. 15.9
Fig. 15.10
Fig. 15.11
Fig. 15.12
Fig. 15.13
Fig. 15.14
Fig. 15.15
Fig. 15.16
Fig. 15.17
Fig. 15.18
Fig. 15.19
Fig. 15.20
Fig. 15.21
Fig. 15.22
Fig. 15.23
Fig. 15.24

References

  • Aguirre AD, Chen Y, Fujimoto JG, Ruvinskaya L, Devor A, Boas DA (2006) Depth-resolved imaging of functional activation in the rat cerebral cortex using optical coherence tomography. Opt Lett 31:3459–3461

    PubMed  CAS  Google Scholar 

  • Agulhon C, Petravicz J, McMullen AB, Sweger EJ, Minton SK, Taves SR, Casper KB, Fiacco TA, McCarthy KD (2008) What is the role of astrocyte calcium in neurophysiology? Neuron 59:932–946

    PubMed  CAS  Google Scholar 

  • Akkin T, Dave DP, Milner TE, Rylander HG (2004) Detection of neural activity using phase-sensitive optical low-coherence reflectometry. Opt Express 12:2377–2386

    PubMed  Google Scholar 

  • Alonso BD, Lowe AS, Dear JP, Lee KC, Williams SC, Finnerty GT (2008) Sensory inputs from whisking movements modify cortical whisker maps visualized with functional magnetic resonance imaging. Cereb Cortex 18(6):1314–1325

    Google Scholar 

  • Arai T, Nakao S, Mori K, Ishimori K, Morishima I, Miyazawa T, Fritz-Zieroth B (1990) Cerebral oxygen utilization analyzed by the use of oxygen-17 and its nuclear magnetic resonance. Biochem Biophys Res Commun 169:153–158

    PubMed  CAS  Google Scholar 

  • Arai T, Mori K, Nakao S, Watanabe K, Kito K, Aoki M, Mori H, Morikawa S, Inubushi T (1991) In vivo oxygen-17 nuclear magnetic resonance for the estimation of cerebral blood flow and oxygen consumption. Biochem Biophys Res Commun 179:954–961

    PubMed  CAS  Google Scholar 

  • Ayata C, Shin HK, Salomone S, Ozdemir-Gursoy Y, Boas DA, Dunn AK, Moskowitz MA (2004) Pronounced hypoperfusion during spreading depression in mouse cortex. J Cereb Blood Flow Metab 24:1172–1182

    PubMed  Google Scholar 

  • Baker BJ, Kosmidis EK, Vucinic D, Falk CX, Cohen LB, Djurisic M, Zecevic D (2005) Imaging brain activity with voltage- and calcium-sensitive dyes. Cell Mol Neurobiol 25:245–282

    PubMed  CAS  Google Scholar 

  • Barth DS, Di S (1991) Laminar excitability cycles in neocortex. J Neurophysiol 65:891–898

    PubMed  CAS  Google Scholar 

  • Barth DS, Di S, Baumgartner C (1989) Laminar cortical interactions during epileptic spikes studied with principal component analysis and physiological modeling. Brain Res 484:13–35

    PubMed  CAS  Google Scholar 

  • Barth DS, Baumgartner C, Di S (1990) Laminar interactions in rat motor cortex during cyclical excitability changes of the penicillin focus. Brain Res 508:105–117

    PubMed  CAS  Google Scholar 

  • Beierlein M, Gibson JR, Connors BW (2000) A network of electrically coupled interneurons drives synchronized inhibition in neocortex. Nat Neurosci 3:904–910

    PubMed  CAS  Google Scholar 

  • Beierlein M, Gibson JR, Connors BW (2003) Two dynamically distinct inhibitory networks in layer 4 of the neocortex. J Neurophysiol 90:2987–3000

    PubMed  Google Scholar 

  • Bizheva K, Unterhuber A, Hermann B, Povazay B, Sattmann H, Drexler W, Stingl A, Le T, Mei M, Holzwarth R, Reitsamer HA, Morgan JE, Cowey A (2004) Imaging ex vivo and in vitro brain morphology in animal models with ultrahigh resolution optical coherence tomography. J Biomed Opt 9:719–724

    PubMed  Google Scholar 

  • Blanco VM, Stern JE, Filosa JA (2008) Tone-dependent vascular responses to astrocyte-derived signals. Am J Physiol Heart Circ Physiol 294:H2855–H2863

    PubMed  CAS  Google Scholar 

  • Blomquist P, Devor A, Indahl UG, Ulbert I, Einevoll GT, Dale AM (2009) Estimation of thalamocortical and intracortical network models from joint thalamic single-electrode and cortical laminar-electrode recordings in the rat barrel system. PLoS Comput Biol 5:e1000328

    PubMed  Google Scholar 

  • Boas DA, Jones SR, Devor A, Huppert TJ, Dale AM (2008) A vascular anatomical network model of the spatio-temporal response to brain activation. Neuroimage 40:1116–1129

    PubMed  Google Scholar 

  • Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA (2002) Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 8:136–142

    PubMed  CAS  Google Scholar 

  • Bower JM, Beeman D (1998) The Book of GENESIS: Exploring Realistic Neural Models with the GEneral NEural SImulation System, 2nd edn. Springer, New York

    Google Scholar 

  • Boxerman JL, Hamberg LM, Rosen BR, Weisskoff RM (1995) MR contrast due to intravascular magnetic susceptibility perturbations. Magn Reson Med 34:555–566

    PubMed  CAS  Google Scholar 

  • Bressler D, Spotswood N, Whitney D (2007) Negative BOLD fMRI response in the visual cortex carries precise stimulus-specific information. PLoS One 2:e410

    PubMed  Google Scholar 

  • Briers JD (2001) Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. Physiol Meas 22:R35–R66

    PubMed  CAS  Google Scholar 

  • Brown GG, Perthen JE, Liu TT, Buxton RB (2007) A primer on functional magnetic resonance imaging. Neuropsychol Rev 17:107–125

    PubMed  Google Scholar 

  • Buxton RB (2005) Quantifying CBF with arterial spin labeling. J Magn Reson Imaging 22:723–726

    PubMed  Google Scholar 

  • Buxton RB, Wong EC, Frank LR (1998) Dynamics of blood flow and oxygenation changes during brain activation: the balloon model. Magn Reson Med 39:855–864

    PubMed  CAS  Google Scholar 

  • Buxton RB, Uludag K, Dubowitz DJ, Liu TT (2004) Modeling the hemodynamic response to brain activation. Neuroimage 23(Suppl 1):S220–S233

    PubMed  Google Scholar 

  • Buzsaki G (2004) Large-scale recording of neuronal ensembles. Nat Neurosci 7:446–451

    PubMed  CAS  Google Scholar 

  • Caesar K, Offenhauser N, Lauritzen M (2008) Gamma-aminobutyric acid modulates local brain oxygen consumption and blood flow in rat cerebellar cortex. J Cereb Blood Flow Metab 28:906–915

    PubMed  CAS  Google Scholar 

  • Carnevale NT, Hines ML (2006) The NEURON book. Cambridge University Press, Cambridge

    Google Scholar 

  • Cauli B, Tong XK, Rancillac A, Serluca N, Lambolez B, Rossier J, Hamel E (2004) Cortical GABA interneurons in neurovascular coupling: relays for subcortical vasoactive pathways. J Neurosci 24:8940–8949

    PubMed  CAS  Google Scholar 

  • Chaigneau E, Oheim M, Audinat E, Charpak S (2003) Two-photon imaging of capillary blood flow in olfactory bulb glomeruli. Proc Natl Acad Sci USA 100:13081–13086

    PubMed  CAS  Google Scholar 

  • Chaigneau E, Tiret P, Lecoq J, Ducros M, Knopfel T, Charpak S (2007) The relationship between blood flow and neuronal activity in the rodent olfactory bulb. J Neurosci 27:6452–6460

    PubMed  CAS  Google Scholar 

  • Chance B, Cohen P, Jobsis F, Schoener B (1962) Intracellular oxidation-reduction states in vivo. Science 137:499–508

    PubMed  CAS  Google Scholar 

  • Chen Y, Aguirre AD, Ruvinskaya L, Devor A, Boas DA, Fujimoto JG (2008) Optical coherence tomography (OCT) reveals depth-resolved dynamics during functional brain activation. J Neurosci Methods 178(1):162–173

    Google Scholar 

  • Cohen LB, Lesher S (1986) Optical monitoring of membrane potential: methods of multisite optical measurement. Soc Gen Physiol Ser 40:71–99

    PubMed  CAS  Google Scholar 

  • Cox SB, Woolsey TA, Rovainen CM (1993) Localized dynamic changes in cortical blood flow with whisker stimulation corresponds to matched vascular and neuronal architecture of rat barrels. J Cereb Blood Flow Metab 13:899–913

    PubMed  CAS  Google Scholar 

  • 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 4:863–872

    PubMed  Google Scholar 

  • Dale AM, Buckner RL (1997) Selective averaging of rapidly presented individual trails using fMRI. Hum Brain Mapp 5:329–340

    PubMed  CAS  Google Scholar 

  • Dale AM, Halgren E (2001) Spatiotemporal mapping of brain activity by integration of multiple imaging modalities. Curr Opin Neurobiol 11:202–208

    PubMed  CAS  Google Scholar 

  • Dale AM, Liu AK, Fischl BR, Buckner RL, Belliveau JW, Lewine JD, Halgren E (2000) Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity. Neuron 26:55–67

    PubMed  CAS  Google Scholar 

  • Davis TL, Kwong KK, Weisskoff RM, Rosen BR (1998) Calibrated functional MRI: mapping the dynamics of oxidative metabolism. Proc Natl Acad Sci USA 95:1834–1839

    PubMed  CAS  Google Scholar 

  • Deans MR, Gibson JR, Sellitto C, Connors BW, Paul DL (2001) Synchronous activity of inhibitory networks in neocortex requires electrical synapses containing connexin36. Neuron 31:477–485

    PubMed  CAS  Google Scholar 

  • Derdikman D, Hildesheim R, Ahissar E, Arieli A, Grinvald A (2003) Imaging spatiotemporal dynamics of surround inhibition in the barrels somatosensory cortex. J Neurosci 23:3100–3105

    PubMed  CAS  Google Scholar 

  • 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 39:353–359

    PubMed  CAS  Google Scholar 

  • Devor A, Sakadzic S, Yucel MA, Teng IC, Kasischke KA, Boas DA (2009) In vivo functional NADH imaging with single-cell resolution. In: Society for Neurosciences. Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online

    Google Scholar 

  • Devor A, Shih AY, Tsai PS, Blinder P, Tian P, Teng IC, Kleinfeld D (2008a) Two-photon laser scanning microscopy as a tool to study cortical vasodynamics under normal and ischemic conditions In: Roe AW (ed) Imaging the brain with optical methods. Springer http://www.springer.com/biomed/neuroscience/book/978-1-4419-0451-5

  • Devor A, Ulbert I, Dunn AK, Narayanan SN, Jones SR, Andermann ML, Boas DA, Dale AM (2005) Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity. Proc Natl Acad Sci USA 102:3822–3827

    PubMed  CAS  Google Scholar 

  • Devor A, Tian P, Nishimura N, Teng IC, Hillman EM, Narayanan SN, Ulbert I, Boas DA, Kleinfeld D, Dale AM (2007) Suppressed neuronal activity and concurrent arteriolar vasoconstriction may explain negative blood oxygenation level-dependent signal. J Neurosci 27:4452–4459

    PubMed  CAS  Google Scholar 

  • Devor A, Hillman EM, Tian P, Waeber C, Teng IC, Ruvinskaya L, Shalinsky MH, Zhu H, Haslinger RH, Narayanan SN, Ulbert I, Dunn AK, Lo EH, Rosen BR, Dale AM, Kleinfeld D, Boas DA (2008b) Stimulus-induced changes in blood flow and 2-deoxyglucose uptake dissociate in ipsilateral somatosensory cortex. J Neurosci 28:14347–14357

    PubMed  CAS  Google Scholar 

  • Di S, Baumgartner C, Barth DS (1990) Laminar analysis of extracellular field potentials in rat vibrissa/barrel cortex. J Neurophysiol 63:832–840

    PubMed  CAS  Google Scholar 

  • Draijer M, Hondebrink E, van Leeuwen T, Steenbergen W (2008) Review of laser speckle contrast techniques for visualizing tissue perfusion. Lasers Med Sci 24(4): 639–651

    Google Scholar 

  • Drexler W, Morgner U, Kartner FX, Pitris C, Boppart SA, Li XD, Ippen EP, Fujimoto JG (1999) In vivo ultrahigh-resolution optical coherence tomography. Opt Lett 24:1221–1223

    PubMed  CAS  Google Scholar 

  • Dunn AK, Bolay H, Moskowitz MA, Boas DA (2001) Dynamic imaging of cerebral blood flow using laser speckle. J Cereb Blood Flow Metab 21:195–201

    PubMed  CAS  Google Scholar 

  • 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 27:279–290

    PubMed  Google Scholar 

  • Dunn AK, Devor A, Bolay H, Andermann ML, Moskowitz MA, Dale AM, Boas DA (2003) Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation. Opt Lett 28:28–30

    PubMed  CAS  Google Scholar 

  • Dunphy I, Vinogradov SA, Wilson DF (2002) Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence. Anal Biochem 310:191–198

    PubMed  CAS  Google Scholar 

  • Ebner TJ, Chen G (1995) Use of voltage-sensitive dyes and optical recordings in the central nervous system. Prog Neurobiol 46:463–506

    PubMed  CAS  Google Scholar 

  • Einevoll GT, Pettersen KH, Devor A, Ulbert I, Halgren E, Dale AM (2007) Laminar population analysis: estimating firing rates and evoked synaptic activity from multielectrode recordings in rat barrel cortex. J Neurophysiol 97:2174–2190

    PubMed  Google Scholar 

  • Fang-Yen C, Chu MC, Seung HS, Dasari RR, Feld MS (2004) Noncontact measurement of nerve displacement during action potential with a dual-beam low-coherence interferometer. Opt Lett 29:2028–2030

    PubMed  Google Scholar 

  • Fang Q, Sakadzic S, Ruvinskaya L, Devor A, Dale AM, Boas DA (2008) Oxygen advection and ­diffusion in a three- dimensional vascular anatomical network. Opt Express 16:17530–17541

    PubMed  CAS  Google Scholar 

  • Faraci FM, Breese KR (1993) Nitric oxide mediates vasodilatation in response to activation of N-methyl-D-aspartate receptors in brain. Circ Res 72:476–480

    PubMed  CAS  Google Scholar 

  • Faraci FM, Heistad DD (1998) Regulation of the cerebral circulation: role of endothelium and potassium channels. Physiol Rev 78:53–97

    PubMed  CAS  Google Scholar 

  • Ferezou I, Bolea S, Petersen CC (2006) Visualizing the cortical representation of whisker touch: voltage-sensitive dye imaging in freely moving mice. Neuron 50:617–629

    PubMed  CAS  Google Scholar 

  • Fergus A, Lee KS (1997) GABAergic regulation of cerebral microvascular tone in the rat. J Cereb Blood Flow Metab 17:992–1003

    PubMed  CAS  Google Scholar 

  • Fiat D, Kang S (1992) Determination of the rate of cerebral oxygen consumption and regional cerebral blood flow by non-invasive 17O in vivo NMR spectroscopy and magnetic resonance imaging: Part 1. Theory and data analysis methods. Neurol Res 14:303–311

    PubMed  CAS  Google Scholar 

  • Fiat D, Kang S (1993) Determination of the rate of cerebral oxygen consumption and regional cerebral blood flow by non-invasive 17O in vivo NMR spectroscopy and magnetic resonance imaging. Part 2. Determination of CMRO2 for the rat by 17O NMR, and CMRO2, rCBF and the partition coefficient for the cat by 17O MRI. Neurol Res 15:7–22

    PubMed  CAS  Google Scholar 

  • Filosa JA, Bonev AD, Straub SV, Meredith AL, Wilkerson MK, Aldrich RW, Nelson MT (2006) Local potassium signaling couples neuronal activity to vasodilation in the brain. Nat Neurosci 9(11):1397–1403

    PubMed  CAS  Google Scholar 

  • Finikova OS, Lebedev AY, Aprelev A, Troxler T, Gao F, Garnacho C, Muro S, Hochstrasser RM, Vinogradov SA (2008) Oxygen microscopy by two-photon-excited phosphorescence. Chemphyschem 9:1673–1679

    PubMed  CAS  Google Scholar 

  • 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 83:1140–1144

    PubMed  CAS  Google Scholar 

  • Fox PT, Raichle ME, Mintun MA, Dence C (1988) Nonoxidative glucose consumption during focal physiologic neural activity. Science 241:462–464

    PubMed  CAS  Google Scholar 

  • Freeman JA, Nicholson C (1975) Experimental optimization of current source-density technique for anuran cerebellum. J Neurophysiol 38(2):369–82.

    PubMed  CAS  Google Scholar 

  • Friston KJ (2005) Models of brain function in neuroimaging. Annu Rev Psychol 56:57–87

    PubMed  Google Scholar 

  • Frostig RD, Lieke EE, Ts’o DY, Grinvald A (1990) Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. Proc Natl Acad Sci USA 87:6082–6086

    PubMed  CAS  Google Scholar 

  • Gobel W, Kampa BM, Helmchen F (2007) Imaging cellular network dynamics in three dimensions using fast 3D laser scanning. Nat Methods 4:73–79

    PubMed  Google Scholar 

  • Gordon GR, Choi HB, Rungta RL, Ellis-Davies GC, Macvicar BA (2008) Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456(7223):745–749

    PubMed  CAS  Google Scholar 

  • Grinvald A (1992) Optical imaging of architecture and function in the living brain sheds new light on cortical mechanisms underlying visual perception. Brain Topogr 5:71–75

    PubMed  CAS  Google Scholar 

  • Grinvald A, Hildesheim R (2004) VSDI: a new era in functional imaging of cortical dynamics. Nat Rev Neurosci 5:874–885

    PubMed  CAS  Google Scholar 

  • Grinvald A, Frostig RD, Lieke E, Hildesheim R (1988) Optical imaging of neuronal activity. Physiol Rev 68:1285–1366

    PubMed  CAS  Google Scholar 

  • Grinvald A, Lieke E, Frostig RD, Gilbert CD, Wiesel TN (1986) Functional architecture of cortex revealed by optical imaging of intrinsic signals. Nature 324:361–364

    PubMed  CAS  Google Scholar 

  • Grubb RL Jr, Raichle ME, Eichling JO, Ter-Pogossian MM (1974) The effects of changes in PaCO2 on cerebral blood volume, blood flow, and vascular mean transit time. Stroke 5:630–639

    PubMed  Google Scholar 

  • Guadagno JV, Calautti C, Baron JC (2003) Progress in imaging stroke: emerging clinical applications. Br Med Bull 65:145–157

    PubMed  CAS  Google Scholar 

  • Hämäläinen M, Hari R, Ilmoniemi R, Knuutila J, Lounasmaa O (1993) Magnetoencephalography theory, instrumentation, and applications to noninvasive studies of the working human brain. Rev Mod Phys 65:413–497

    Google Scholar 

  • Hamel E (2004) Cholinergic modulation of the cortical microvascular bed. Prog Brain Res 145:171–178

    PubMed  CAS  Google Scholar 

  • Hamel E (2006) Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol 100:1059–1064

    PubMed  Google Scholar 

  • Hillman EM, Boas DA, Dale AM, Dunn AK (2004) Laminar optical tomography: demonstration of millimeter-scale depth-resolved imaging in turbid media. Opt Lett 29:1650–1652

    PubMed  Google Scholar 

  • Hillman EM, Devor A, Bouchard MB, Dunn AK, Krauss GW, Skoch J, Bacskai BJ, Dale AM, Boas DA (2007) Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation. Neuroimage 35:89–104

    PubMed  Google Scholar 

  • Hodics T, Cohen LG (2005) Functional neuroimaging in motor recovery after stroke. Top Stroke Rehabil 12:15–21

    PubMed  Google Scholar 

  • Hu Y, Wilson GS (1997) A temporary local energy pool coupled to neuronal activity: fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzyme-based sensor. J Neurochem 69:1484–1490

    PubMed  CAS  Google Scholar 

  • Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA et al (1991) Optical coherence tomography. Science 254:1178–1181

    PubMed  CAS  Google Scholar 

  • Huber R, Adler DC, Srinivasan VJ, Fujimoto JG (2007) Fourier domain mode locking at 1050 nm for ultra-high-speed optical coherence tomography of the human retina at 236,000 axial scans per second. Opt Lett 32:2049–2051

    PubMed  CAS  Google Scholar 

  • Huchzermeyer C, Albus K, Gabriel HJ, Otahal J, Taubenberger N, Heinemann U, Kovacs R, Kann O (2008) Gamma oscillations and spontaneous network activity in the hippocampus are highly sensitive to decreases in pO2 and concomitant changes in mitochondrial redox state. J Neurosci 28:1153–1162

    PubMed  CAS  Google Scholar 

  • Huppert TJ, Allen MS, Diamond SG, Boas DA (2009) Estimating cerebral oxygen metabolism from fMRI with a dynamic multicompartment Windkessel model. Hum Brain Mapp 30: 1548–1567

    PubMed  Google Scholar 

  • Huppert TJ, Allen MS, Benav H, Jones PB, Boas DA (2007) A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation. J Cereb Blood Flow Metab 27:1262–1279

    PubMed  Google Scholar 

  • Iadecola C (2004) Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci 5:347–360

    PubMed  CAS  Google Scholar 

  • Iadecola C, Niwa K (2002) Nitric oxide. In: Edvinsson L, Krause DN (eds) Cerebral blood flow and metabolism, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, pp 295–310

    Google Scholar 

  • Iadecola C, Nedergaard M (2007) Glial regulation of the cerebral microvasculature. Nat Neurosci 10:1369–1376

    PubMed  CAS  Google Scholar 

  • Ido Y, Chang K, Williamson JR (2004) NADH augments blood flow in physiologically activated retina and visual cortex. Proc Natl Acad Sci USA 101:653–658

    PubMed  CAS  Google Scholar 

  • Iliff JJ, D’Ambrosio R, Ngai AC, Winn HR (2003) Adenosine receptors mediate glutamate-evoked arteriolar dilation in the rat cerebral cortex. Am J Physiol Heart Circ Physiol 284:H1631–H1637

    PubMed  CAS  Google Scholar 

  • Ito H, Ibaraki M, Kanno I, Fukuda H, Miura S (2005) Changes in the arterial fraction of human cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography. J Cereb Blood Flow Metab 25:852–857

    PubMed  Google Scholar 

  • Jackson J (1998) Classical electrodynamics. Wiley, Hoboken, NJ

    Google Scholar 

  • Jones M, Berwick J, Mayhew J (2002) Changes in blood flow, oxygenation, and volume following extended stimulation of rodent barrel cortex. Neuroimage 15:474–487

    PubMed  Google Scholar 

  • Jones M, Berwick J, Johnston D, Mayhew J (2001) Concurrent optical imaging spectroscopy and laser-Doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barrel cortex. Neuroimage 13:1002–1015

    PubMed  CAS  Google Scholar 

  • Jones M, Hewson-Stoate N, Martindale J, Redgrave P, Mayhew J (2004) Nonlinear coupling of neural activity and CBF in rodent barrel cortex. Neuroimage 22:956–965

    PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Kasischke KA, Lambert EM, Panepento B, Sun A, Gelbard HA, Burgess RW, Foster TH, Nedergaard M (2011) Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions. J Cereb Blood Flow Metab 31(1):68–81

    Google Scholar 

  • Kim T, Hendrich KS, Masamoto K, Kim SG (2007) Arterial versus total blood volume changes during neural activity-induced cerebral blood flow change: implication for BOLD fMRI. J Cereb Blood Flow Metab 27:1235–1247

    PubMed  Google Scholar 

  • Kleinfeld D, Griesbeck O (2005) From art to engineering? The rise of in vivo mammalian electrophysiology via genetically targeted labeling and nonlinear imaging. PLoS Biol 3:e355

    PubMed  Google Scholar 

  • Kleinfeld D, Mitra PP, Helmchen F, Denk W (1998) Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. Proc Natl Acad Sci USA 95:15741–15746

    PubMed  CAS  Google Scholar 

  • Kocharyan A, Fernandes P, Tong XK, Vaucher E, Hamel E (2008) Specific subtypes of cortical GABA interneurons contribute to the neurovascular coupling response to basal forebrain stimulation. J Cereb Blood Flow Metab 28:221–231

    PubMed  CAS  Google Scholar 

  • Koehler RC, Roman RJ, Harder DR (2009) Astrocytes and the regulation of cerebral blood flow. Trends Neurosci 32:160–169

    PubMed  CAS  Google Scholar 

  • Kohl M, Lindauer U, Royl G, Kuhl M, Gold L, Villringer A, Dirnagl U (2000) Physical model for the spectroscopic analysis of cortical intrinsic optical signals. Phys Med Biol 45:3749–3764

    PubMed  CAS  Google Scholar 

  • Koralek KA, Olavarria J, Killackey HP (1990) Areal and laminar organization of corticocortical projections in the rat somatosensory cortex. J Comp Neurol 299:133–150

    PubMed  CAS  Google Scholar 

  • Kudomi N, Watabe H, Hayashi T, Iida H (2007) Separation of input function for rapid measurement of quantitative CMRO2 and CBF in a single PET scan with a dual tracer administration method. Phys Med Biol 52:1893–1908

    PubMed  Google Scholar 

  • Kudomi N, Hayashi T, Watabe H, Teramoto N, Piao R, Ose T, Koshino K, Ohta Y, Iida H (2009) A physiologic model for recirculation water correction in CMRO2 assessment with 15O2 inhalation PET. J Cereb Blood Flow Metab 29:355–364

    PubMed  Google Scholar 

  • Lauritzen M (2005) Opinion: Reading vascular changes in brain imaging: is dendritic calcium the key? Nat Rev Neurosci 6:77–85

    PubMed  CAS  Google Scholar 

  • Lazebnik M, Marks DL, Potgieter K, Gillette R, Boppart SA (2003) Functional optical coherence tomography for detecting neural activity through scattering changes. Opt Lett 28: 1218–1220

    PubMed  Google Scholar 

  • Lee SP, Duong TQ, Yang G, Iadecola C, Kim SG (2001) Relative changes of cerebral arterial and venous blood volumes during increased cerebral blood flow: implications for BOLD fMRI. Magn Reson Med 45:791–800

    PubMed  CAS  Google Scholar 

  • Lefort S, Tomm C, Floyd Sarria JC, Petersen CC (2009) The excitatory neuronal network of the C2 barrel column in mouse primary somatosensory cortex. Neuron 61:301–316

    PubMed  CAS  Google Scholar 

  • Leitgeb RA, Schmetterer L, Drexler W, Fercher AF, Zawadzki RJ, Bajraszewski T (2003) Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography. Opt Express 11:3116–3121

    PubMed  Google Scholar 

  • Leontiev O, Buxton RB (2007) Reproducibility of BOLD, perfusion, and CMRO2 measurements with calibrated-BOLD fMRI. Neuroimage 35:175–184

    PubMed  Google Scholar 

  • Leontiev O, Dubowitz DJ, Buxton RB (2007) CBF/CMRO2 coupling measured with calibrated BOLD fMRI: sources of bias. Neuroimage 36:1110–1122

    PubMed  Google Scholar 

  • Leski S, Wojcik DK, Tereszczuk J, Swiejkowski DA, Kublik E, Wrobel A (2007) Inverse current-source density method in 3D: reconstruction fidelity, boundary effects, and influence of distant sources. Neuroinformatics 5:207–222

    PubMed  Google Scholar 

  • Lindauer U, Leithner C, Kaasch H, Rohrer B, Foddis M, Fuchtemeier M, Offenhauser N, Steinbrink J, Royl G, Kohl-Bareis M, Dirnagl U (2010) Neurovascular coupling in rat brain operates independent of hemoglobin deoxygenation. J Cereb Blood Flow Metab 30(4):757–768

    Google Scholar 

  • Liu X, Li C, Falck JR, Roman RJ, Harder DR, Koehler RC (2008) Interaction of nitric oxide, 20-HETE, and EETs during functional hyperemia in whisker barrel cortex. Am J Physiol Heart Circ Physiol 295:H619–H631

    PubMed  CAS  Google Scholar 

  • Logothetis NK (2002) The neural basis of the blood-oxygen-level-dependent functional magnetic resonance imaging signal. Philos Trans R Soc Lond B Biol Sci 357:1003–1037

    PubMed  Google Scholar 

  • Logothetis NK, Kayser C, Oeltermann A (2007) In vivo measurement of cortical impedance spectrum in monkeys: implications for signal propagation. Neuron 55:809–823

    PubMed  CAS  Google Scholar 

  • Lu H, Ge Y (2008) Quantitative evaluation of oxygenation in venous vessels using T2-Relaxation-Under-Spin-Tagging MRI. Magn Reson Med 60:357–363

    PubMed  Google Scholar 

  • Lu H, Zhao C, Ge Y, Lewis-Amezcua K (2008) Baseline blood oxygenation modulates response amplitude: physiologic basis for intersubject variations in functional MRI signals. Magn Reson Med 60:364–372

    PubMed  Google Scholar 

  • Magistretti PJ, Pellerin L, Rothman DL, Shulman RG (1999) Energy on demand. Science 283:496–497

    PubMed  CAS  Google Scholar 

  • Maheswari RU, Takaoka H, Kadono H, Homma R, Tanifuji M (2003) Novel functional imaging technique from brain surface with optical coherence tomography enabling visualization of depth resolved functional structure in vivo. J Neurosci Methods 124:83–92

    PubMed  Google Scholar 

  • Mainen ZF, Sejnowski TJ (1996) Influence of dendritic structure on firing pattern in model neocortical neurons. Nature 382:363–366

    PubMed  CAS  Google Scholar 

  • Malonek D, Grinvald A (1996) Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science 272:551–554

    PubMed  CAS  Google Scholar 

  • Mandeville JB, Marota JJ, Ayata C, Zaharchuk G, Moskowitz MA, Rosen BR, Weisskoff RM (1999) Evidence of a cerebrovascular postarteriole windkessel with delayed compliance. J Cereb Blood Flow Metab 19:679–689

    PubMed  CAS  Google Scholar 

  • Mann-Metzer P, Yarom Y (2000) Electrotonic coupling synchronizes interneuron activity in the cerebellar cortex. Prog Brain Res 124:115–122

    PubMed  CAS  Google Scholar 

  • Margrie TW, Meyer AH, Caputi A, Monyer H, Hasan MT, Schaefer AT, Denk W, Brecht M (2003) Targeted whole-cell recordings in the mammalian brain in vivo. Neuron 39:911–918

    PubMed  CAS  Google Scholar 

  • Mayhew J, Johnston D, Berwick J, Jones M, Coffey P, Zheng Y (2000) Spectroscopic analysis of neural activity in brain: increased oxygen consumption following activation of barrel cortex. Neuroimage 12:664–675

    PubMed  CAS  Google Scholar 

  • Metea MR, Newman EA (2006) Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling. J Neurosci 26:2862–2870

    PubMed  CAS  Google Scholar 

  • Mik EG, van Leeuwen TG, Raat NJ, Ince C (2004) Quantitative determination of localized tissue oxygen concentration in vivo by two-photon excitation phosphorescence lifetime measurements. J Appl Physiol 97:1962–1969

    PubMed  Google Scholar 

  • Miller RJ (1988) Calcium signalling in neurons. Trends Neurosci 11:415–419

    PubMed  CAS  Google Scholar 

  • Mintun MA, Raichle ME, Martin WR, Herscovitch P (1984) Brain oxygen utilization measured with O-15 radiotracers and positron emission tomography. J Nucl Med 25:177–187

    PubMed  CAS  Google Scholar 

  • Mintun MA, Vlassenko AG, Rundle MM, Raichle ME (2004) Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain. Proc Natl Acad Sci USA 101:659–664

    PubMed  CAS  Google Scholar 

  • Mitzdorf U (1985) Current source-density method and application in cat cerebral cortex: investigation of evoked potentials and EEG phenomena. Physiol Rev 65:37–100

    PubMed  CAS  Google Scholar 

  • Moore CI, Nelson SB (1998) Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J Neurophysiol 80:2882–2892

    PubMed  CAS  Google Scholar 

  • Mulligan SJ, MacVicar BA (2004) Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431:195–199

    PubMed  CAS  Google Scholar 

  • Narayan SM, Santori EM, Blood AJ, Burton JS, Toga AW (1994) Imaging optical reflectance in rodent barrel and forelimb sensory cortex. Neuroimage 1:181–190

    PubMed  CAS  Google Scholar 

  • Narayan SM, Esfahani P, Blood AJ, Sikkens L, Toga AW (1995) Functional increases in cerebral blood volume over somatosensory cortex. J Cereb Blood Flow Metab 15:754–765

    PubMed  CAS  Google Scholar 

  • Nemoto M, Sheth S, Guiou M, Pouratian N, Chen JW, Toga AW (2004) Functional signal- and paradigm-dependent linear relationships between synaptic activity and hemodynamic responses in rat somatosensory cortex. J Neurosci 24:3850–3861

    PubMed  CAS  Google Scholar 

  • Nemoto M, Nomura Y, Sato C, Tamura M, Houkin K, Koyanagi I, Abe H (1999) Analysis of optical signals evoked by peripheral nerve stimulation in rat somatosensory cortex: dynamic changes in hemoglobin concentration and oxygenation. J Cereb Blood Flow Metab 19:246–259

    PubMed  CAS  Google Scholar 

  • Nicholson C, Freeman JA (1975) Theory of current source-density analysis and determination of conductivity tensor for anuran cerebellum. J Neurophysiol 38:356–368

    PubMed  CAS  Google Scholar 

  • Nilsson M, Eriksson PS, Ronnback L, Hansson E (1993) GABA induces Ca2+ transients in astrocytes. Neuroscience 54:605–614

    PubMed  CAS  Google Scholar 

  • Nishimura N, Schaffer CB, Friedman B, Lyden PD, Kleinfeld D (2007) Penetrating arterioles are a bottleneck in the perfusion of neocortex. Proc Natl Acad Sci USA 104:365–370

    PubMed  CAS  Google Scholar 

  • Nishimura N, Schaffer CB, Friedman B, Tsai PS, Lyden PD, Kleinfeld D (2006) Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke. Nat Methods 3:99–108

    PubMed  CAS  Google Scholar 

  • Nunez PL, Srinivasan R (2006) Electric fields of the brain: the neurophysics of EEG. Oxford University Press, New York

    Google Scholar 

  • Obata T, Liu TT, Miller KL, Luh WM, Wong EC, Frank LR, Buxton RB (2004) Discrepancies between BOLD and flow dynamics in primary and supplementary motor areas: application of the balloon model to the interpretation of BOLD transients. Neuroimage 21:144–153

    PubMed  Google Scholar 

  • Ogawa S, Menon RS, Tank DW, Kim SG, Merkle H, Ellermann JM, Ugurbil K (1993) Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J 64:803–812

    PubMed  CAS  Google Scholar 

  • Ohata H, Cao S, Koehler RC (2006) Contribution of adenosine A2A and A2B receptors and heme oxygenase to AMPA-induced dilation of pial arterioles in rats. Am J Physiol Regul Integr Comp Physiol 291:R728–R735

    PubMed  CAS  Google Scholar 

  • Ou W, Nissila I, Radhakrishnan H, Boas DA, Hamalainen MS, Franceschini MA (2009) Study of neurovascular coupling in humans via simultaneous magnetoencephalography and diffuse optical imaging acquisition. Neuroimage 46:624–632

    PubMed  Google Scholar 

  • Peppiatt CM, Howarth C, Mobbs P, Attwell D (2006) Bidirectional control of CNS capillary diameter by pericytes. Nature 443:700–704

    PubMed  CAS  Google Scholar 

  • Pettersen KH, Einevoll GT (2008) Amplitude variability and extracellular low-pass filtering of neuronal spikes. Biophys J. 94(3):784–802.

    PubMed  CAS  Google Scholar 

  • Pettersen KH, Hagen E, Einevoll GT (2008) Estimation of population firing rates and current source densities from laminar electrode recordings. J Comput Neurosci 24:291–313

    PubMed  Google Scholar 

  • Pettersen KH, Linden H, Dale AM, Einevoll GT (2012) Extracellular spikes and CSD. In: Brette R, Destexhe A (eds) Handbook of neural activity measurement Cambridge University Press

    Google Scholar 

  • Pettersen KH, Devor A, Ulbert I, Dale AM, Einevoll GT (2006) Current-source density estimation based on inversion of electrostatic forward solution: effects of finite extent of neuronal activity and conductivity discontinuities. J Neurosci Methods 154:116–133

    PubMed  Google Scholar 

  • Petzold GC, Albeanu DF, Sato TF, Murthy VN (2008) Coupling of neural activity to blood flow in olfactory glomeruli is mediated by astrocytic pathways. Neuron 58:897–910

    PubMed  CAS  Google Scholar 

  • Phelps ME, Kuhl DE, Mazziota JC (1981) Metabolic mapping of the brain’s response to visual stimulation: studies in humans. Science 211:1445–1448

    PubMed  CAS  Google Scholar 

  • Pinto DJ, Brumberg JC, Simons DJ (2000) Circuit dynamics and coding strategies in rodent somatosensory cortex. J Neurophysiol 83:1158–1166

    PubMed  CAS  Google Scholar 

  • Polimeni JR, Granquist-Fraser D, Wood RJ, Schwartz EL (2005) Physical limits to spatial resolution of optical recording: clarifying the spatial structure of cortical hypercolumns. Proc Natl Acad Sci USA 102:4158–4163

    PubMed  CAS  Google Scholar 

  • Porter JT, McCarthy KD (1996) Hippocampal astrocytes in situ respond to glutamate released from synaptic terminals. J Neurosci 16:5073–5081

    PubMed  CAS  Google Scholar 

  • Raichle ME, Mintun MA (2006) Brain work and brain imaging. Annu Rev Neurosci 29:449–476

    PubMed  CAS  Google Scholar 

  • Rancillac A, Rossier J, Guille M, Tong XK, Geoffroy H, Amatore C, Arbault S, Hamel E, Cauli B (2006) Glutamatergic control of microvascular tone by distinct GABA neurons in the cerebellum. J Neurosci 26:6997–7006

    PubMed  CAS  Google Scholar 

  • Rappelsberger P, Pockberger H, Petsche H (1981) Current source density analysis: methods and application to simultaneously recorded field potentials of the rabbit’s visual cortex. Pflugers Arch 389:159–170

    PubMed  CAS  Google Scholar 

  • Ross WN (1989) Changes in intracellular calcium during neuron activity. Annu Rev Physiol 51:491–506

    PubMed  CAS  Google Scholar 

  • Rouach N, Koulakoff A, Abudara V, Willecke K, Giaume C (2008) Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322:1551–1555

    PubMed  CAS  Google Scholar 

  • Royl G, Fuchtemeier M, Leithner C, Megow D, Offenhauser N, Steinbrink J, Kohl-Bareis M, Dirnagl U, Lindauer U (2008) Hypothermia effects on neurovascular coupling and cerebral metabolic rate of oxygen. Neuroimage 40:1523–1532

    PubMed  Google Scholar 

  • Rubio R, Berne RM, Bockman EL, Curnish RR (1975) Relationship between adenosine concentration and oxygen supply in rat brain. Am J Physiol 228:1896–1902

    PubMed  CAS  Google Scholar 

  • Sakadzic S, Yuan S, Dilekoz E, Ruvinskaya S, Vinogradov SA, Ayata C, Boas DA (2009) Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression. Appl Opt 48:D169–D177

    PubMed  CAS  Google Scholar 

  • Schaffer CB, Friedman B, Nishimura N, Schroeder LF, Tsai PS, Ebner FF, Lyden PD, Kleinfeld D (2006) Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion. PLoS Biol 4:e22

    PubMed  Google Scholar 

  • Schmidt DM, George JS, Wood CC (1999) Bayesian inference applied to the electromagnetic inverse problem. Hum Brain Mapp 7:195–212

    PubMed  CAS  Google Scholar 

  • Schroeder CE, Lindsley RW, Specht C, Marcovici A, Smiley JF, Javitt DC (2001) Somatosensory input to auditory association cortex in the macaque monkey. J Neurophysiol 85:1322–1327

    PubMed  CAS  Google Scholar 

  • Schummers J, Yu H, Sur M (2008) Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320:1638–1643

    PubMed  CAS  Google Scholar 

  • 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 42:347–355

    PubMed  CAS  Google Scholar 

  • Shi Y, Liu X, Gebremedhin D, Falck JR, Harder DR, Koehler RC (2008) Interaction of mechanisms involving epoxyeicosatrienoic acids, adenosine receptors, and metabotropic glutamate receptors in neurovascular coupling in rat whisker barrel cortex. J Cereb Blood Flow Metab 28:111–125

    PubMed  CAS  Google Scholar 

  • Shmuel A, Augath M, Oeltermann A, Logothetis NK (2006) Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1. Nat Neurosci 9:569–577

    PubMed  CAS  Google Scholar 

  • Shoham D, Glaser DE, Arieli A, Kenet T, Wijnbergen C, Toledo Y, Hildesheim R, Grinvald A (1999) Imaging cortical dynamics at high spatial and temporal resolution with novel blue voltage-sensitive dyes. Neuron 24:791–802

    PubMed  CAS  Google Scholar 

  • Sicard KM, Duong TQ (2005) Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO2 in spontaneously breathing animals. Neuroimage 25:850–858

    PubMed  Google Scholar 

  • Simard M, Arcuino G, Takano T, Liu QS, Nedergaard M (2003) Signaling at the gliovascular interface. J Neurosci 23:9254–9262

    PubMed  CAS  Google Scholar 

  • Simons DJ (1978) Response properties of vibrissa units in rat SI somatosensory neocortex. J Neurophysiol 41:798–820

    PubMed  CAS  Google Scholar 

  • Simons DJ, Carvell GE (1989) Thalamocortical response transformation in the rat vibrissa/barrel system. J Neurophysiol 61:311–330

    PubMed  CAS  Google Scholar 

  • Smith AJ, Blumenfeld H, Behar KL, Rothman DL, Shulman RG, Hyder F (2002) Cerebral energetics and spiking frequency: the neurophysiological basis of fMRI. Proc Natl Acad Sci USA 99:10765–10770

    PubMed  CAS  Google Scholar 

  • Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14 C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916

    PubMed  CAS  Google Scholar 

  • Somogyvari Z, Zalanyi L, Ulbert I, Erdi P (2005) Model-based source localization of extracellular action potentials. J Neurosci Methods 147:126–137

    PubMed  CAS  Google Scholar 

  • Srinivasan VJ, Sakadzic S, Gorczynska I, Ruvinskaya S, Wu W, Fujimoto JG, Boas DA (2009) Depth-resolved microscopy of cortical hemodynamics with optical coherence tomography. Opt Lett 34:3086–3088

    PubMed  Google Scholar 

  • Srinivasan VJ, Sakadzić S, Gorczynska I, Ruvinskaya S, Wu W, Fujimoto JG, Boas DA (2010a) Quantitative cerebral blood flow with optical coherence tomography. Opt Express 18(3):2477–2494

    Google Scholar 

  • Srinivasan VJ, Jiang JY, Yaseen MA, Radhakrishnan H, Wu W, Barry S, Cable AE, Boas DA (2010b) Rapid volumetric angiography of cortical microvasculature with optical coherence tomography. Opt Lett 35:43–45

    PubMed  Google Scholar 

  • Stefanovic B, Hutchinson E, Yakovleva V, Schram V, Russell JT, Belluscio L, Koretsky AP, Silva AC (2008) Functional reactivity of cerebral capillaries. J Cereb Blood Flow Metab 28:961–972

    PubMed  Google Scholar 

  • Strangman G, Culver JP, Thompson JH, Boas DA (2002) A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation. Neuroimage 17:719–731

    PubMed  Google Scholar 

  • Straub SV, Nelson MT (2007) Astrocytic calcium signaling: the information currency coupling neuronal activity to the cerebral microcirculation. Trends Cardiovasc Med 17:183–190

    PubMed  CAS  Google Scholar 

  • Takano T, Tian GF, Peng W, Lou N, Libionka W, Han X, Nedergaard M (2006) Astrocyte-mediated control of cerebral blood flow. Nat Neurosci 9:260–267

    PubMed  CAS  Google Scholar 

  • Takano T, Tian GF, Peng W, Lou N, Lovatt D, Hansen AJ, Kasischke KA, Nedergaard M (2007) Cortical spreading depression causes and coincides with tissue hypoxia. Nat Neurosci 10:754–762

    PubMed  CAS  Google Scholar 

  • Takashima I, Kajiwara R, Iijima T (2001) Voltage-sensitive dye versus intrinsic signal optical imaging: comparison of optically determined functional maps from rat barrel cortex. Neuroreport 12:2889–2894

    PubMed  CAS  Google Scholar 

  • Teasell R, Bayona NA, Bitensky J (2005) Plasticity and reorganization of the brain post stroke. Top Stroke Rehabil 12:11–26

    PubMed  Google Scholar 

  • Thompson JK, Peterson MR, Freeman RD (2003) Single-neuron activity and tissue oxygenation in the cerebral cortex. Science 299:1070–1072

    PubMed  CAS  Google Scholar 

  • Thomson AM, Bannister AP (2003) Interlaminar connections in the neocortex. Cereb Cortex 13:5–14

    PubMed  Google Scholar 

  • Tian P, Teng IC, May LD, Kurz R, Lu K, Scadeng M, Hillman EM, De Crespigny AJ, D’Arceuil HE, Mandeville JB, Marota JJ, Rosen BR, Liu TT, Boas DA, Buxton RB, Dale AM, Devor A (2010) Cortical depth-specific microvascular dilation underlies laminar differences in blood oxygenation level-dependent functional MRI signal. Proc Natl Acad Sci USA 107(34):15246–15251

    Google Scholar 

  • Tsien RY (1981) A non-disruptive technique for loading calcium buffers and indicators into cells. Nature 290:527–528

    PubMed  CAS  Google Scholar 

  • Turner DA, Foster KA, Galeffi F, Somjen GG (2007) Differences in O2 availability resolve the apparent discrepancies in metabolic intrinsic optical signals in vivo and in vitro. Trends Neurosci 30:390–398

    PubMed  CAS  Google Scholar 

  • Ulbert I, Halgren E, Heit G, Karmos G (2001) Multiple microelectrode-recording system for human intracortical applications. J Neurosci Methods 106:69–79

    PubMed  CAS  Google Scholar 

  • Vakoc B, Yun S, de Boer J, Tearney G, Bouma B (2005) Phase-resolved optical frequency domain imaging. Opt Express 13:5483–5493

    PubMed  CAS  Google Scholar 

  • Vanzetta I, Grinvald A (1999) Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging. Science 286:1555–1558

    PubMed  CAS  Google Scholar 

  • Vanzetta I, Grinvald A (2001) Evidence and lack of evidence for the initial dip in the anesthetized rat: implications for human functional brain imaging. Neuroimage 13:959–967

    PubMed  CAS  Google Scholar 

  • Vanzetta I, Hildesheim R, Grinvald A (2005) Compartment-resolved imaging of activity-dependent dynamics of cortical blood volume and oximetry. J Neurosci 25:2233–2244

    PubMed  CAS  Google Scholar 

  • Villringer A, Chance B (1997) Non-invasive optical spectroscopy and imaging of human brain function. Trends Neurosci 20:435–442

    PubMed  CAS  Google Scholar 

  • Viswanathan A, Freeman RD (2007) Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity. Nat Neurosci 10:1308–1312

    PubMed  CAS  Google Scholar 

  • Wallace DJ, Zum Alten Borgloh SM, Astori S, Yang Y, Bausen M, Kugler S, Palmer AE, Tsien RY, Sprengel R, Kerr JN, Denk W, Hasan MT (2008) Single-spike detection in vitro and in vivo with a genetic Ca(2+) sensor. Nat Methods 5(9):797–804

    PubMed  CAS  Google Scholar 

  • Wang X, Lou N, Xu Q, Tian GF, Peng WG, Han X, Kang J, Takano T, Nedergaard M (2006) Astrocytic Ca(2+) signaling evoked by sensory stimulation in vivo. Nat Neurosci 9:816–823

    PubMed  CAS  Google Scholar 

  • White B, Pierce M, Nassif N, Cense B, Park B, Tearney G, Bouma B, Chen T, de Boer J (2003) In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography. Opt Express 11:3490–3497

    PubMed  Google Scholar 

  • White EL, DeAmicis RA (1977) Afferent and efferent projections of the region in mouse SmL cortex which contains the posteromedial barrel subfield. J Comp Neurol 175:455–482

    PubMed  CAS  Google Scholar 

  • 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 27:6268–6272

    PubMed  CAS  Google Scholar 

  • Wise SP, Jones EG (1976) The organization and postnatal development of the commissural projection of the rat somatic sensory cortex. J Comp Neurol 168:313–343

    PubMed  CAS  Google Scholar 

  • Wojtkowski M, Bajraszewski T, Targowski P, Kowalczyk A (2003) Real-time in vivo imaging by high-speed spectral optical coherence tomography. Opt Lett 28:1745–1747

    PubMed  CAS  Google Scholar 

  • Woolsey TA, Rovainen CM, Cox SB, Henegar MH, Liang GE, Liu D, Moskalenko YE, Sui J, Wei L (1996) Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain. Cereb Cortex 6:647–660

    PubMed  CAS  Google Scholar 

  • Xu F, Ge Y, Lu H (2009) Noninvasive quantification of whole-brain cerebral metabolic rate of oxygen (CMRO2) by MRI. Magn Reson Med 62:141–148

    PubMed  Google Scholar 

  • Yang SP, Krasney JA (1995) Cerebral blood flow and metabolic responses to sustained hypercapnia in awake sheep. J Cereb Blood Flow Metab 15:115–123

    PubMed  CAS  Google Scholar 

  • Yaseen MA, Srinivasan VJ, Sakadzic S, Wu W, Ruvinskaya S, Vinogradov SA, Boas DA (2009) Optical monitoring of oxygen tension in cortical microvessels with confocal microscopy. Opt Express 17:22341–22350

    PubMed  CAS  Google Scholar 

  • Yee SH, Lee K, Jerabek PA, Fox PT (2006) Quantitative measurement of oxygen metabolic rate in the rat brain using microPET imaging of briefly inhaled 15O-labelled oxygen gas. Nucl Med Commun 27:573–581

    PubMed  CAS  Google Scholar 

  • Zappe AC, Uludag K, Oeltermann A, Ugurbil K, Logothetis NK (2008) The influence of moderate hypercapnia on neural activity in the anesthetized nonhuman primate. Cereb Cortex 18: 2666–2673

    PubMed  CAS  Google Scholar 

  • Zhang N, Zhu XH, Lei H, Ugurbil K, Chen W (2004) Simplified methods for calculating cerebral metabolic rate of oxygen based on 17O magnetic resonance spectroscopic imaging measurement during a short 17O2 inhalation. J Cereb Blood Flow Metab 24:840–848

    PubMed  CAS  Google Scholar 

  • Zhu XH, Zhang N, Zhang Y, Zhang X, Ugurbil K, Chen W (2005) In vivo 17O NMR approaches for brain study at high field. NMR Biomed 18:83–103

    PubMed  CAS  Google Scholar 

  • Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann KA, Pozzan T, Carmignoto G (2003) Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 6:43–50

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like you to acknowledge Klas M. Pettersen, Henrik Linden, Ivan C. Teng and Peifang Tian for help with making some of the figures, and the financial support from the following NIH grants: R01NS051188, R01NS057198, R21EB009118 (to Anna Devor), R01EB000790 (to Anders M. Dale), R01NS057476 (to David A. Boas) and R01 NS036722 (to Richard R. Buxton) and Research Council of Norway (eVITA, FRIBIOMOL to Gaute T. Einevoll).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anna Devor Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Devor, A., Boas, D.A., Einevoll, G.T., Buxton, R.B., Dale, A.M. (2012). Neuronal Basis of Non-Invasive Functional Imaging: From Microscopic Neurovascular Dynamics to BOLD fMRI. In: Choi, IY., Gruetter, R. (eds) Neural Metabolism In Vivo. Advances in Neurobiology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1788-0_15

Download citation