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.
Similar content being viewed by others
References
Roy C. and Sherrington C. (1890) On the regulation of the blood supply to the brain. J. Physiol. Lond. 11, 85–108.
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.
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.
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.
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.
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.
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.
Vanzetta I. and Grinvald A. (1999) Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging. Science 286, 1555–1558.
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.
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.
Logothetis N. K., Gugenberger H., Peled S., and Pauls J. (1999) Functional imaging of the monkey brain. Nature Neurosci. 2(6), 555–562.
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.
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.
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.
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.
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.
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.
de Curtis M. and Avanzini G. (2001) Interictal spikes in focal epileptogenesis. Prog. Neurobiol. 63, 541–567.
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.
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.
Ingvar M. (1986) Cerebral blood flow and metabolic rate during seizures: relationship to epileptic brain damage. Ann. NY Acad. Sci. 462, 207–223.
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.
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.
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.
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.
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.
Benar C.-G., Goross D. W., Wang, Y. et al. (2002) The BOLD response to interictal epileptiform discharges. NeuroImage 17, 1182–1192.
Hill D. K. and Keynes R. D. (1949) Opacity changes in stimulated nerve. J. Physiol. 108, 278–281.
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.
Bonhoeffer T. and Grinvald A. (1991) Iso-orientation domains in cat visual cortex are arranged in pinwheel-like patterns. Nature 353, 429–431.
Bonhoeffer T. and Grinvald A. (1996) The Methods, in Brain Mapping, Toga A. W. and Mazziota J. C., eds., 55–99, San Diego: Academic.
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.
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.
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.
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.
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.
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.
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.
Schwartz, T. H. (2003) Optical imaging of epileptiform events in visual cortex in response to patterned photic stimulation. Cereb. Cortex 13, 12, 1287–1298.
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.
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.
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.
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.
Bahar S., Suh M., and Schwartz T. H. (2006) Intrinsic optical signal imaging of neocortical seizures: the “epileptic dip”. Neuroreport 19(5), 499–503.
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.
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.
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.
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.
Van Paesschen W. (2004) Ictal SPECT. Epilepsia 45(S4), 35–40.
Haglund M. M. and Hochman D. W. (2004) Optical imaging of epileptiform activity in human neocortex Epilepsia 45(S4), 43–47.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Buxton R. B. (2001) The elusive initial dip. Neurolmage 13, 953–958.
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.
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.
Butovas S. and Schwarz C. (2003) Spatiotemporal effects of microstimulation in rat neocortex: a parametric study using multielectrode recordings. J. Neurophysiol. 90, 3024–3039.
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.
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.
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.
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.
Grinvald A., Frostig R. D., Lieke E., and Hildesheim R. (1988) Optical imaging of neuronal activity. Physiol. Rev. 68, 1285–1365.
Tsau Y., Guan L., and Wu J.-Y. (1998) Initiation of spontaneous epileptiform activity in the neocortical slice. J. Neurophysiol. 80, 978–982.
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.
Albowitz B., Kuhnt U., and Ehrenreich L. (1990) Optical recording of epileptiform voltage changes in the neocortical slice. Exp. Brain. Res. 81, 241–256.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Rights 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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/MN:33:3:181