Skip to main content
Log in

Neurovascular coupling and oximetry during epileptic events

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Epilepsy is an abnormal brain state in which a large population of neurons is synchronously active, causing an enormous increase in metabolic demand. Recent investigations using high-resolution imaging techniques, such as optical recording of intrinsic signals and voltagesensitive dyes, as well as measurements with oxygen-sensitive electrodes have elucidated the spatiotemporal relationship between neuronal activity, cerebral blood volume, and oximetry in vivo. A focal decrease in tissue oxygenation and a focal increase in deoxygenated hemoglobin occurs following both interictal and ictal events. This “epileptic dip” in oxygenation can persist for the duration of an ictal event, suggesting that cerebral blood flow is inadequate to meet metabolic demand. A rapid focal increase in cerebral blood flow and cerebral blood volume also accompanies epileptic events; however, this increase in perfusion soon (>2 s) spreads to a larger area of the cortex than the excitatory change in membrane potential. Investigations in humans during neurosurgical operations have confirmed the laboratory data derived from animal studies. These data not only have clinical implications for the interpretation of noninvasive imaging studies such as positron emission tomography, single-photon emission tomography, and functional magnetic resonance imaging but also provide a mechanism for the cognitive decline in patients with chronic epilepsy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Roy C. and Sherrington C. (1890) On the regulation of the blood supply to the brain. J. Physiol. Lond. 11, 85–108.

    PubMed  CAS  Google Scholar 

  2. Fox P. T., Raichle M. E., Mintun M. A., and Dence C. (1988) Monoxidative glucose consumption during focal physiologic neural activity. Science 241, 462–464.

    Article  PubMed  CAS  Google Scholar 

  3. Ogawa, S., Lee T. M., Kay, A. R., and Tank D. W. (1990) Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc. Natl. Acad. Sci. USA 87, 9868–9872.

    Article  PubMed  CAS  Google Scholar 

  4. Frostig R. D., Lieke E. E., Ts'o D. Y., and 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.

    Article  PubMed  CAS  Google Scholar 

  5. Sheth S. A., Nemoto M., Guiuo M., Walker M., Pouratian N., and Toga A. W. (2003) Evaluation of coupling between optical intrinsic signals and neuronal activity in rat somatosensory cortex. Neurolmage 19, 884–894.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Mayhew J. E. W., Zheng Y., Hou Y., et al. (1999) Spectroscopic analysis of changes in remited illumination: the response to increased neural activity in brain. NeuroImage 10, 304–326.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Thompson, J. K., Peterson M. R., and Freeman R. D. (2003) Single-neuron activity and tissue oxygenation in the cerebral cortex. Science 299, 1070–1072.

    Article  PubMed  CAS  Google Scholar 

  10. Ances B. M., Buerk D. G., Greenberg J. H., and Detre J. A. (2001) Temporal dynamics of the partial pressure of brain tissue oxygen during functional forepaw stimulation in rats. Neurosci. Lett. 306, 106–110.

    Article  PubMed  CAS  Google Scholar 

  11. Logothetis N. K., Gugenberger H., Peled S., and Pauls J. (1999) Functional imaging of the monkey brain. Nature Neurosci. 2(6), 555–562.

    Article  PubMed  CAS  Google Scholar 

  12. Kim D.-S., Duong T. Q., and Kim S.-G. (2000) High-resolution mapping of iso-orientation columns by fMRI. Nature Neurosci. 3(2), 164–169.

    Article  PubMed  CAS  Google Scholar 

  13. Sheth S. A., Nemoto M., Guiou G., Walker M., Pouratian N., and Toga A. W. (2004) Linear and nonlinear relationships between neuronal actiity, oxygen metabolism, and hemodynamic response. Neuron 42, 347–355.

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Lindauer U., Royl G., Leithner C., et al. (2001) No evidence for early decrease in blood oxygenation in rat whisker cortex in response to functional activation. Neurolmage 13, 988–1001.

    Article  CAS  Google Scholar 

  16. Folbergrova, J., Ingvar M., and Siesjo B. K. (1981) Metabolic changes in cerebral cortex, hippocampus, and cerebellum during sustained bicuculline-induced seizures. J. Neurochem. 37, 1228–1238.

    Article  PubMed  CAS  Google Scholar 

  17. Bragin A., Mody I., Wilson C. L., and Engel J. J. (2002) Local generation of fast ripples in epileptic brain. J. Neurosci. 22, 5, 2012–2021.

    PubMed  CAS  Google Scholar 

  18. de Curtis M. and Avanzini G. (2001) Interictal spikes in focal epileptogenesis. Prog. Neurobiol. 63, 541–567.

    Article  PubMed  Google Scholar 

  19. Pereira de Vasconcelos A., Ferrandon A., and Nehlig A. (2002) Local cerebral blood flow during lithium-pilocarpine seizures in the developing and adult rat: role of coupling between blood flow and metabolism in the genesis of neuronal damage. J. Cereb. Blood Flow Metab. 22, 196–205.

    Article  PubMed  CAS  Google Scholar 

  20. Andre, V., Henry D., and Nehlig A. (2002) Dynamic variations of local cerebral blood flow in maximal electroshock seizures in the rat. Epilepsia 43, 1120–1128.

    Article  PubMed  Google Scholar 

  21. Ingvar M. (1986) Cerebral blood flow and metabolic rate during seizures: relationship to epileptic brain damage. Ann. NY Acad. Sci. 462, 207–223.

    Article  PubMed  Google Scholar 

  22. Tanaka S., Sako K., Tanaka T., Nishihara I., and Yonemasu Y. (1990) Uncoupling of local blood flow and metabolism in the hippocampal CA3 kainic acid-induced limbic seizure status. Neuroscience 36, 339–348.

    Article  PubMed  CAS  Google Scholar 

  23. Kreisman, N. R., Magee J. C., and Brizzee B. L. (1991) Relative hypoperfusion in rat cerebral cortex during recurrent seizures. J. Cereb. Blood Flow Metab. 11, 77–87.

    PubMed  CAS  Google Scholar 

  24. Tenney J. R., Duong T. Q., King J. A., and Ferris C. F. (2004) PMRI of brain activation in genetic rat model of absence seizures. Epilepsia 45, 6, 576–582.

    Article  PubMed  Google Scholar 

  25. Nersesyan H., Hydeer F. Rothman D. L., and Blumenfeld H. (2004) Dynamic fMRI and EEG recording during Spike-Wave seizures and generalized tonic-clonic seizures in WAG/Rij rats. J. Cereb. Blood Flow Metab. 24, 589–599.

    Article  PubMed  Google Scholar 

  26. Lemieux L., Krakow K., and RFish D. R. (2001) Comparison of spike-triggered functional MRI BOLD activation and EEG dipole model localization. NeuroImage 17, 1097–1104.

    Article  Google Scholar 

  27. Benar C.-G., Goross D. W., Wang, Y. et al. (2002) The BOLD response to interictal epileptiform discharges. NeuroImage 17, 1182–1192.

    Article  PubMed  Google Scholar 

  28. Hill D. K. and Keynes R. D. (1949) Opacity changes in stimulated nerve. J. Physiol. 108, 278–281.

    PubMed  CAS  Google Scholar 

  29. Schwartz T. H., Chen L.-M., Friedman R. M., Spencer D. D., and Roe A. W. (2004) High resolution intraoperative optical imaging of human face cortical topography: a case study. NeuroReport 15, 9, 1527–1531.

    Article  PubMed  Google Scholar 

  30. Bonhoeffer T. and Grinvald A. (1991) Iso-orientation domains in cat visual cortex are arranged in pinwheel-like patterns. Nature 353, 429–431.

    Article  PubMed  CAS  Google Scholar 

  31. Bonhoeffer T. and Grinvald A. (1996) The Methods, in Brain Mapping, Toga A. W. and Mazziota J. C., eds., 55–99, San Diego: Academic.

    Google Scholar 

  32. Mayhew J. E. W., Johnston D., Berwixk J., Jones M., Cofey P. and Zheng Y. (2000) Spectroscopic analysis of neural activity in brain: increased oxygen consumption following activation of barrel cortex. NeuroImage 12, 664–675.

    Article  PubMed  CAS  Google Scholar 

  33. Nemoto M., Sheth S., Guiou M., Pouratian N., Chen, J. W. Y., and Toga A. W. (2004) Functional signal- and paradigm-dependent linear relationships between synaptic activity and hemodynamic responses in rat somatosensory cortex. J. Neurosci. 24, 15, 3850–3861.

    Article  PubMed  CAS  Google Scholar 

  34. Sato C., Nemoto M., and Tamura M. (2002) Reassessment of activity-related optical signals in somatosensory cortex by an algorith with wavelength-dependent path length. Jpn. J. Physiol. 52, 301–312.

    Article  PubMed  CAS  Google Scholar 

  35. Hochman D. W., Baraban S. C., Owens J. W. M., and Schwartzkroin P. A. (1995) Dissociation of synchronization and excitability in furosemide blockade of epileptiform activity. Science 270, 99–102.

    Article  PubMed  CAS  Google Scholar 

  36. Federico P., Borg S. G., Salkauskus A. G., and MacVicar B. A. (1994) Mapping patterns of neuronal activity and seizure propagation in the isolated whole brain of the guinea-pig. Neuroscience 58, 3, 461–480.

    Article  PubMed  CAS  Google Scholar 

  37. Chen J. W. Y., O'Farrell A. M., and Toga A. W. (2000) Optical intrinsic signal imaging in a rodent seizure model. Neurology 55, 312–315.

    PubMed  CAS  Google Scholar 

  38. Schwartz T. H. and Bonhoeffer T. (2001) In vivo optical mapping of epileptic foci and surround inhibition in ferret cerebral cortex. Nature Med. 7(9), 1063–1067.

    Article  PubMed  CAS  Google Scholar 

  39. Schwartz, T. H. (2003) Optical imaging of epileptiform events in visual cortex in response to patterned photic stimulation. Cereb. Cortex 13, 12, 1287–1298.

    Article  PubMed  Google Scholar 

  40. Schwartz T. H. (2005) The application of optical recording of intrinsic signal to simultaneously acquire functional, pathological and localizing information and its potential role in neurosurgery. Stereotac. Funct Neurosurg. 83, 36–44.

    Article  Google Scholar 

  41. Haglund M. M., Oiemann G. A., and Hochman D. W. (1992) Optical imaging of epileptiform and functional activity in human cerebral cortex. Nature 358(6388) 668–671.

    Article  PubMed  CAS  Google Scholar 

  42. Suh M., Bahar S., Mehta A. D., and Schwartz T. H. (2005) Temporal dependence in uncoupling of blood volume and oxygenation during interictal epileptiform events in rat neocortex. J. Neurosci. 25, 1, 68–77.

    Article  PubMed  CAS  Google Scholar 

  43. Bahar S., Suh M., Mehta A. D., and Schwartz T. H. (2005) In Bioimaging in Neurodegeneration, Broderick P. A., Rahni D. N., and Kolodny E. H., eds. Totowa, NJ: Humana Press, pp. 149–175.

    Google Scholar 

  44. Bahar S., Suh M., and Schwartz T. H. (2006) Intrinsic optical signal imaging of neocortical seizures: the “epileptic dip”. Neuroreport 19(5), 499–503.

    Article  Google Scholar 

  45. Zhao M., Ma H., Suh M., and Schwartz T. H. (2005) Decrease in brain tissue oxygenation in spite of an increase in cerebral blood flow during acute focal 4-aminopyridine seizures in rat neocortex. Abstract for Society of Neuroscience Annual Conference, November 12–16.

  46. Sheth S. A., Nemoto M., Guiou G., et al. (2004) Columnar Specificity of microvascular oxygenation and volume responses: Implications for functional brain mapping. J. Neurosci. 24(3), 634–641.

    Article  PubMed  CAS  Google Scholar 

  47. Vanzetta I., Slovin H., Omer D. B., and Grinvald A. (2004) Columnar resolution of blood volume and oximetry functional maps in the behaving monkey: Implications for fMRI. Neuron 42, 843–854.

    Article  PubMed  CAS  Google Scholar 

  48. Vanzetta I., Hildesheim R., and Grinvald A. (2005) Compartment-resolved imaging of activity dependent dynamics of cortical blood volume and oximetry. J. Neurosci. 25 (9), 2233–2244.

    Article  PubMed  CAS  Google Scholar 

  49. Van Paesschen W. (2004) Ictal SPECT. Epilepsia 45(S4), 35–40.

    Article  PubMed  Google Scholar 

  50. Haglund M. M. and Hochman D. W. (2004) Optical imaging of epileptiform activity in human neocortex Epilepsia 45(S4), 43–47.

    Article  PubMed  Google Scholar 

  51. Tenney J. R., Duong T. Q., King J. A., and Ferris C. F. (2003) Corticothalamic modulation during absence seizures in rats: a functional MRI assessment. Epilepsia 44, 1133–1140.

    Article  PubMed  Google Scholar 

  52. Handforth A., Finch D. M., Peters R., Tan A. M., and Treiman D. M. (1994) Interictal spiking increases 2deoxy[14C]glucose uptake and c-fos-like reactivity. Ann. Neurol. 35, 724–731.

    Article  PubMed  CAS  Google Scholar 

  53. Hagemann G., Bruehl C., Lutzenburg M., and Wite O. W. (1998) Brain hypometabolism in a rat model of chronic focal epilepsy in rat neocortex. Epilepsia 39(4), 339–346.

    Article  PubMed  CAS  Google Scholar 

  54. Pouratian N., Sheth S. A., Martin N. A., and Toga A. W. (2003) Shedding light on brain mapping: advances in human optical imaging. Trends Neurosci. 26(5), 277–282.

    Article  PubMed  CAS  Google Scholar 

  55. Schwartz T. H., Chen, L. M., Friedman R. M., Spencer D. D., and Roe A. W. (2005) Intraoperative optical imaging of human face cortical topography: a case study. NeuroReport 15(9), 1527–1531.

    Article  Google Scholar 

  56. Cannestra A. F., Black K. L., Martin N. A., et al. (1998) Topographical and temporal specificity of human intraoperative optical intrinsic signals. NeuroReport 9, 2557–2563.

    Article  PubMed  CAS  Google Scholar 

  57. Cannestra A. F., Pouratian N., Bookheimer S. Y., Martin N. A., Becker D. P., and Toga A. W. (2001) Temporal spatial differences observed by functional MRI and human intraoperative optical imaging. Cerebral Cortex 11, 773–782.

    Article  PubMed  CAS  Google Scholar 

  58. Sato K. et al. (2002) Intraoperative intrinsic signal imaging of neuronal activity from subdivisions of the human primary somatosensory cortex. Cerebral Cortex 12, 269–280.

    Article  PubMed  Google Scholar 

  59. Shoham D. and Grinvald A. (2001) The cortical representation of the hand in macaque and human area S-1: high resolution optical imaging. J. Neurosci. 21, 17, 6820–6835.

    PubMed  CAS  Google Scholar 

  60. Suh M., Bahar S., Mehta, A. D. and Schwartz T. H. (2006) Blood volume and hemoglobin oxygenation response following electrical stimulation of human cortex. Neuroimage, in press.

  61. Suh M., Bahar S., Mehta A. D., et al. (2005) Optical imaging of intrinsic signal during stimulus-induced afterdischarge in the human cortex. Soc. Neurosci. Abs.

  62. Lindauer U., Gethman J., Kuhl M., Kohl-Bareis M., Villringer A., and Dirnagl U. (2003) Neuronal activity-induced changes of local cerebral microvascular blood oxygenation in the rat: effect of systemic hyperoxia or hypoxia. Brain Res. 975, 135–140.

    Article  PubMed  CAS  Google Scholar 

  63. Buxton R. B. (2001) The elusive initial dip. Neurolmage 13, 953–958.

    Article  CAS  Google Scholar 

  64. Buxton R. B., Wong E. C., and Frank L. R. (1998) Dynamics of blood flow and oxygenation changes during brain activation: the balloon model. Magn. Res. Med. 39, 855–864.

    Article  CAS  Google Scholar 

  65. Jones M., Berwick J., Johnston D., and Mayhew J. E. W. (2001) Concurrent optical imaging spectroscopy and laser-doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barell cortex. NeuroImage 13, 1002–1015.

    Article  PubMed  CAS  Google Scholar 

  66. Butovas S. and Schwarz C. (2003) Spatiotemporal effects of microstimulation in rat neocortex: a parametric study using multielectrode recordings. J. Neurophysiol. 90, 3024–3039.

    Article  PubMed  Google Scholar 

  67. Sutor B., Hablitz J. J., Rucker F., and Bruggencate G. (1994) Spread of epileptiform activity in the immature rat neocortex studied with voltage-sensitive dyes and laser scanning microscopy. J. Neurophys. 4, 1756–1768.

    Google Scholar 

  68. Das A. and Gilbert C. D. (1995) Long-range horizontal connections and their role in cortical reorganization revealed by optical recording of cat primary visual cortex. Nature 375, 780–784.

    Article  PubMed  CAS  Google Scholar 

  69. Takashima I., Kajiwara R., and Iijima T. (2001) Voltage-sensitive dye versus intrinsic signal optical imaging: comparison of optically determined functional maps from rat barrel cortex. Neuroreport 12, 13, 2889–2894.

    Article  PubMed  CAS  Google Scholar 

  70. Logothetis N. K., Pauls J., Augath M., Trinath T., and Oeltermann A. (2001) Neurophysiological investigation of the basis of the MRI signal. Nature 412, 150–157.

    Article  PubMed  CAS  Google Scholar 

  71. Grinvald A., Frostig R. D., Lieke E., and Hildesheim R. (1988) Optical imaging of neuronal activity. Physiol. Rev. 68, 1285–1365.

    PubMed  CAS  Google Scholar 

  72. Tsau Y., Guan L., and Wu J.-Y. (1998) Initiation of spontaneous epileptiform activity in the neocortical slice. J. Neurophysiol. 80, 978–982.

    PubMed  CAS  Google Scholar 

  73. Albowitz B. and Kuhnt U. (1995) Epileptiform activity in the guinea-pig neocortical slice spreads preferentially along supragranular layers-recordings with voltage-sensitive dyes. Europ. J. Neurosci. 7, 1273–1284.

    Article  CAS  Google Scholar 

  74. Albowitz B., Kuhnt U., and Ehrenreich L. (1990) Optical recording of epileptiform voltage changes in the neocortical slice. Exp. Brain. Res. 81, 241–256.

    Article  PubMed  CAS  Google Scholar 

  75. Yuste R. M., Simons D. J., and Woolsey T. A. (1997) The neocortical local circuit—a research workshop held in Sde-Boker Israel, May 4–8, 1997. Somatosens Mot Res. 14(3), 213–221.

    Article  PubMed  CAS  Google Scholar 

  76. Tsau Y., Guan L., and Wu J.-Y. (1999) Epileptiform activity can be initiated in various neocortical layers: an optical imaging study. J. Neurophysiol. 82, 1965–1973.

    PubMed  CAS  Google Scholar 

  77. London, J. A., Cohen L. B., and Wu J.-Y. (1989) Optical recordings of the cortical response to whisker stimulation before and after the addition of an epileptic agent. J. Neurosci. 9(6), 2182–2190.

    PubMed  CAS  Google Scholar 

  78. Ma H., Wu C. H., and Wu JY. (2004) Initiation of spontaneous epileptiform events in the rat neocortex in vivo. J Neurophysiol. 91(2) 934–945.

    Article  PubMed  Google Scholar 

  79. Ma H., Zhao M. Shariff S., Wong K. Suh M., and Schwartz T. H. (2005) The Spatial Correlation between Neuronal Activity and Intrinsic Optical Signals during Interictal Spikes in Rat Neocortex. Soc. Neurosci. Ann. Conf.

  80. McKhann G. M. 2nd, Schoenfeld-McNeill J., Born D. E., Haglund M. M., and Ojemann G. A. (2000) Intraoperative hippocampal electrocorticography to predict the extent of hippocampal resection in temporal lobe epilepsy surgery. J Neurosurg. 93(1), 44–52.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Minah Suh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Suh, M., Ma, H., Zhao, M. et al. Neurovascular coupling and oximetry during epileptic events. Mol Neurobiol 33, 181–197 (2006). https://doi.org/10.1385/MN:33:3:181

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/MN:33:3:181

Index Entries

Navigation