Near-Infrared Spectroscopy in Functional Activation Studies

Can NIRS Demonstrate Cortical Activation?
  • Hellmuth Obrig
  • Arno Villringer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 413)


Near infrared spectroscopy (NIRS) has recently been used in functional activation studies as a non-invasive tool to monitor changes in cerebral oxygenation in human adults1–6. If NIRS is to establish its place in functional brain research it must be proven that the changes monitored reflect the activation state of the cortex in response to a stimulus. This article gives an overview of the studies performed. On the basis of the reported findings and results from two studies by our own group7,8 a description of the typical NIRS response pattern over an activated cortical area is attempted.


Cerebral Blood Volume Probe Position Cerebral Oxygenation Near Infrared Spectroscopy Grand Average 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    B. Chance, Z. Zhuang, C. UnAh, C. Alter, and L. Lipton, Cognition-activated low-frequency modulation of light absorption in human brain, Proc. Natl. Acad. Sci. U. S. A. 90:3770–3774 (1993).ADSCrossRefGoogle Scholar
  2. 2.
    G. Gratton, P.M. Corballis, E. Cho, M. Fabiani, and D.C. Hood, Shades of gray matter:noninvasive optical images of human brain responses during visual stimulation. Psychophysiology 32:505–509 (1995).CrossRefGoogle Scholar
  3. 3.
    G. Gratton, M. Fabiani, D. Friedman, M.A. Franceschini, S. Fantini, P. Corballis, and E. Gratton, Rapid changes of optical parameters in the human brain during a tapping task. Journal of Cognitive Neuroscience 7:4:446–456(1995).CrossRefGoogle Scholar
  4. 4.
    Y. Hoshi and M. Tamura, Detection of dynamic changes in cerebral oxygenation coupled to neuronal function during mental work in man, Neurosci. Lett. 150:5–8 (1993).CrossRefGoogle Scholar
  5. 5.
    J.H. Meek, C.E. Elwell, M.J. Khan, J. Romaya, J.S. Wyatt, D.T. Delpy, and S. Zeki, Regional changes in cerebral haemodynamics as a result of a visual stimulus measured by near infrared spectroscopy, Proc. R. Soc. Lond. B 261:351–356 (1995).ADSCrossRefGoogle Scholar
  6. 6.
    A. Villringer, J. Planck, C. Hock, L. Schleinkofer, and U. Dirnagl, Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults, Neurosci. Lett. 154:101–104(1993).CrossRefGoogle Scholar
  7. 7.
    H. Obrig, T. Wolf, C. Doge, J. Junge-Hülsing, U. Dirnagl, and A. Villringer, Adv. Exp. Med. Biol. (1995).(in press).Google Scholar
  8. 8.
    H. Obrig, C. Hirth, J.G. Junge-Hülsing, C. Doge, T. Wolf, A. Villringer, and U. Dirnagl, Cerebral oxygenation changes in response to motor stimulation, Journal of Applied Physiology (submitted).Google Scholar
  9. 9.
    F.F. Jobsis, Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters, Science 198:1264–1267 (1977).ADSCrossRefGoogle Scholar
  10. 10.
    M. Cope and D.T. Delpy, System for long-term measurement of cerebral blood and tissue oxygenation on newborn infants by near infra-red transillumination, Med. Biol. Eng. Comput. 26:289–294 (1988).CrossRefGoogle Scholar
  11. 11.
    M. Tamura, O. Hazeki, S. Nioka, and B. Chance, In vivo study of tissue oxygen metabolism using optical and nuclear magnetic resonance spectroscopies, Annu. Rev. Physiol. 51:813–834 (1989).CrossRefGoogle Scholar
  12. 12.
    J.S. Wyatt, M. Cope, D.T. Delpy, S. Wray, and E.O. Reynolds, Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry, Lancet 2:1063–1066 (1986).CrossRefGoogle Scholar
  13. 13.
    D.T. Delpy, M. Cope, P. van der Zee, S. Arridge, S. Wray, and J. Wyatt, Estimation of optical pathlength through tissue from direct time of flight measurement, Phys. Med. Biol. 33:1433–1442 (1988).CrossRefGoogle Scholar
  14. 14.
    P. van der Zee and D.T. Delpy, Simulation of the point spread function for light in tissue by a Monte Carlo method, Adv. Exp. Med Biol. 215:179–191 (1987).CrossRefGoogle Scholar
  15. 15.
    B. Chance, J.S. Leigh, H. Miyake, D.S. Smith, S. Nioka, R. Greenfeld, M. Finander, K. Kaufmann, W. Levy, M. Young, and et al, Comparison of time-resolved and-unresolved measurements of deoxyhemoglobin in brain, Proc. Natl. Acad. Sci. U. S A. 85:4971–4975 (1988).ADSCrossRefGoogle Scholar
  16. 16.
    P. van der Zee, M. Cope, S.R. Arridge, M. Essenpreis, L.A. Potter, A.D. Edwards, J.S. Wyatt, D.C. McCormick, S.C. Roth, E.O. Reynolds, and et al, Experimentally measured optical pathlengths for the adult head, calf and forearm and the head of the newborn infant as a function of inter optode spacing, Adv. Exp. Med. Biol. 316:143–153(1992).CrossRefGoogle Scholar
  17. 17.
    Y. Hoshi and M. Tamura, Dynamic multichannel near-infrared optical imaging of human brain activity, J. Appl. Physiol. 75:1842–1846 (1993).Google Scholar
  18. 18.
    Y. Hoshi, H. Onoe, Y. Watanabe, J. Andersson, M. Bergstrom, A. Lilja, B. Langstrom, and M. Tamura, Non-synchronous behavior of neuronal activity, oxidative metabolism and blood supply during mental tasks in man, Neurosci. Lett. 172:129–133 (1994).CrossRefGoogle Scholar
  19. 19.
    F. Okada, Y. Tokumitsu, Y. Hoshi, and M. Tamura, Gender-and handedness-related differences of forebrain oxygenation and hemodynamics, Brain Res. 601:337–342 (1993).CrossRefGoogle Scholar
  20. 20.
    F. Okada, Y. Tokumitsu, Y. Hoshi, and M. Tamura, Impaired interhemispheric integration in brain oxygenation and hemodynamics in schizophrenia, Eur. Arch. Psychiatry Clin. Neurosci. 244:17–25 (1994).CrossRefGoogle Scholar
  21. 21.
    F. Okada, Y. Tokumitsu, N. TAKAHASHI, Y. Hoshi, and M. Tamura, Region-dependent asymmetrical or symmetrical variations in the oxygenation and hemodynamics of the brain due to different mental stimuli, Brain Res. Cogn. Brain Res. 2:215–219 (1995).CrossRefGoogle Scholar
  22. 22.
    C.E. Cooper, S.J. Matcher, J.S. Wyatt, M. Cope, G.C. Brown, E.M. Nemoto, and D.T. Delpy, Near-infrared spectroscopy of the brain: relevance to cytochrome oxidase bioenergetics, Biochem. Soc. Trans. 22:974–980 (1994).Google Scholar
  23. 23.
    M.E. Raichle, W.R. Martin, P. Herscovitch, M.A. Mintun, and J. Markham, Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation, J. Nucl. Med. 24:790–798 (1983).Google Scholar
  24. 24.
    A. Villringer and U. Dirnagl, Coupling of brain activity and cerebral blood flow — basis of functional neuroimaging, Cerebrovasc. Brain Metab. Rev. (1996).Google Scholar
  25. 25.
    P.T. Fox and M.E. Raichle, Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects, Proc. Natl. Acad. Sci. U. S. A. 83:1140–1144 (1986).ADSCrossRefGoogle Scholar
  26. 26.
    P.T. Fox, M.E. Raichle, M.A. Mintun, and C. Dence, Nonoxidative glucose consumption during focal physiologic neural activity, Science 241:462–464 (1988).ADSCrossRefGoogle Scholar
  27. 27.
    K. Villringer, A. Villringer, S. Minoshima, S. Ziegler, M. Herz, S. Schuh-Hofer, H. Obrig, C. Hock, U. Dirnagl, and M. Schwaiger, Frontal brain activation in humans: a combined near infrared spectroscopy and positron emission tomography study. Soc. Neurosci. Abst. 20, 1:355:(1994).Google Scholar
  28. 28.
    O. Pryds, G. Greisen, and B. Friis Hansen, Acta Paediatr. Scand. 77:632–637 (1988).CrossRefGoogle Scholar
  29. 29.
    G.I. Mchedlishvili, Arterial behaviour and blood circulation in the brain., Plenum Press, New York, pp. 274–291 (1986).Google Scholar
  30. 30.
    K.K. Kwong, J.W. Belliveau, D.A. Chesler, I.E. Goldberg, R.M. Weisskoff, B.P. Poncelet, D.N. Kennedy, B.E. Hoppel, M.S. Cohen, R. Turner, and et al, Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation, Proc. Natl. Acad. Sci. U. S. A. 89:5675–5679 (1992).ADSCrossRefGoogle Scholar
  31. 31.
    S. Ogawa, T.M. Lee, A.R. Kay, and D.W. Tank, Brain magnetic resonance imaging with contrast dependent on blood oxygenation, Proc. Natl. Acad. Sci. U. S. A. 87:9868–9872 (1990).ADSCrossRefGoogle Scholar
  32. 32.
    J. Frahm, H. Bruhn, K.D. Merboldt, and W. Hanicke, Dynamic MR imaging of human brain oxygenation during rest and photic stimulation, J. Magn. Reson. Imaging 2:501–505 (1992).CrossRefGoogle Scholar
  33. 33.
    P.A. Bandettini, E.C. Wong, R.S. Hinks, R.S. Tikofsky, and J.S. Hyde, Time course EPI of human brain function during task activation, Magn. Reson. Med. 25:390–397 (1992).CrossRefGoogle Scholar
  34. 34.
    S.G. Kim, J. Ashe, A.P. Georgopoulos, H. Merkle, J.M. Ellermann, R.S. Menon, S. Ogawa, and K. Ugurbil, Functional imaging of human motor cortex at high magnetic field, J. Neumphysiol. 69:297–302 (1993).Google Scholar
  35. 35.
    R. Kawashima, K. Yamada, S. Kinomura, T. Yamaguchi, H. Matsui, S. Yoshioka, and H. Fukuda, Regional cerebral blood flow changes of cortical motor areas and prefrontal areas in humans related to ipsilateral and contralateral hand movement, Brain Res. 623:33–40 (1993).CrossRefGoogle Scholar
  36. 36.
    A. Kleinschmidt, H. Obrig, M. Requardt, K.D. Merboldt, U. Dirnagl, A. Villringer, and J. Frahm, Simultaneous recording of cerebral blood oxygenation changes during human brain activation by MRI and near-infrared spectroscopy. J. Cereb. Blood Flow Metab. (1996).Google Scholar
  37. 37.
    U. Lindauer, A. Villringer, and U. Dirnagl, Characterization of CBF response to somatosensory stimulation: model and influence of anesthetics, Am. J. Physiol. 264:H1223–8 (1993).Google Scholar
  38. 38.
    K.J. Friston, CD. Frith, P.F. Liddle, R.J. Dolan, A.A. Lammertsma, and R.S. Frackowiak, The relationship between global and local changes in PET scans, J. Cereb. Blood Flow Metab. 10:458–466 (1990).CrossRefGoogle Scholar
  39. 39.
    J. Frahm, K.D. Merboldt, W. Hanicke, A. Kleinschmidt, and H. Boecker, Brain or vein-oxygenation or flow? On signal physiology in functional MRI of human brain activation, NMR. Biomed. 7:45–53 (1994).CrossRefGoogle Scholar
  40. 40.
    A. Maki, Y. Yamashita, Y. Ito, E. Watanabe, Y. Mayanagi, and H. Koizumi, Spatial and temporal analysis of human motor activity using noninvasive NIR topography. Am. Assoc. Phys. Med. 22:12:1997–2005 (1995).Google Scholar
  41. 41.
    M. Tamura, M. Ishiki, H. Tachibana, Y. Kubo, and T. Tamura, Non-invasive monitoring of tissue oxygen metabolism by NIR laser spectrophotometry. Jpn. J. Artif. Organs 18:1573–1580 (1989).Google Scholar
  42. 42.
    S.J. Matcher, C.E. Elwell, C.E. Cooper, M. Cope, and D.T. Delpy, Performance comparison of several published tissue near-infrared spectroscopy algorithms. Anal. Biochem. 227:54–68 (1995).CrossRefGoogle Scholar
  43. 43.
    T. Kato, A. Kamei, S. Takashima, and T. Ozaki, Human visual cortical function during photic stimulation monitoring by means of near-infrared spectroscopy, J. Cereb. Blood Flow Metab. 13:516–520 (1993).CrossRefGoogle Scholar
  44. 44.
    C. Hock, F. Müllerspahn, S. Schuhhofer, M. Hofmann, U. Dirnagl, and A. Villringer, Age dependency of changes in cerebral hemoglobin oxygenation during brain activation: a near infrared spectroscopy study, J. Cereb. Blood Flow Metab. 15:1103–1108. (1995).CrossRefGoogle Scholar
  45. 45.
    Y. Shinohara, S. Takagi, N. Shinohara, F. Kawaguchi, Y. Itoh, Y. Yamashita, and A. Maki, Optical CT imaging of hemoglobin oxygen-saturation using dual-wave length time gate technique, Adv. Exp. Med. Biol. 333:43–46(1993).CrossRefGoogle Scholar
  46. 46.
    H. Steinmetz, G. Fürst, and B.U. Meyer, Craniocerebral topography within the international 10–20 system, Electroencephalogr. Clin. Neurophysiol. 72:499–506 (1989).Google Scholar
  47. 47.
    P. van der Zee, S.R. Arridge, M. Cope, and D.T. Delpy, The effect of optode positioning on optical path-length in near infrared spectroscopy of brain, Adv. Exp. Med. Biol. 277:79–84 (1990).CrossRefGoogle Scholar
  48. 48.
    Y. Hoshi, S. Mizukami, and M. Tamura, Dynamic features of hemodynamic and metabolic changes in the human brain during all-night sleep as revealed by near-infrared spectroscopy, Brain Res. 652:257–262 (1994).CrossRefGoogle Scholar
  49. 49.
    C. Hock, K. Villringer, F. Müller-Spahn, M. HOFMANN, S. Schuh-Hofer, H. Heekeren, U. Dirnagl, and A. Villringer, Near infrared spectroscopy in the diagnosis of Alzheimer’s disease., Annals of the New York Acadamy of Science (1996).Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Hellmuth Obrig
    • 1
  • Arno Villringer
    • 1
  1. 1.Neurologische Universitätsklinik, Charité BerlinHumboldt-UniversityBerlinGermany

Personalised recommendations