Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Functional imaging of the monkey brain

Nature Neuroscience volume 2, pages 555–562 (1999)Cite this article

Abstract

Functional magnetic resonance imaging (fMRI) has become an essential tool for studying human brain function. Here we describe the application of this technique to anesthetized monkeys. We present spatially resolved functional images of the monkey cortex based on blood oxygenation level dependent (BOLD) contrast. Checkerboard patterns or pictures of primates were used to study stimulus-induced activation of the visual cortex, in a 4.7-Tesla magnetic field, using optimized multi-slice, gradient-recalled, echo-planar imaging (EPI) sequences to image the entire brain. Under our anesthesia protocol, visual stimulation yielded robust, reproducible, focal activation of the lateral geniculate nucleus (LGN), the primary visual area (V1) and a number of extrastriate visual areas, including areas in the superior temporal sulcus. Similar responses were obtained in alert, behaving monkeys performing a discrimination task.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Activation maps and signal modulation.
Figure 2: Activation of LGN and visual cortex (p < 0.00000017).
Figure 3: Effects of stimulus position and size.
Figure 4: Faces and animal figures were compared with scrambled versions of the same images to examine activation of the temporal lobe.
Figure 5: Time course of the BOLD signal.
Figure 6: Optics and stimulus positioning.

Similar content being viewed by others

References

  1. Fox, P. T. et al. Mapping human visual cortex with positron emission tomography. Nature 323, 806–809 (1986).

    Article  CAS  Google Scholar 

  2. Fox, P. T. & Raichle, M. E. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc. Natl. Acad. Sci. USA 83, 1140–1144 (1986).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Frostig, R. D., Lieke, E. E., Ts'o, D. Y. & Grinvald, A. 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 (1990).

    Article  CAS  Google Scholar 

  5. Ogawa, S., Lee, T. M., Nayak, A. S. & Glynn, P. Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields. Magn. Reson. Med. 14, 68– 78 (1990).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Bandettini, P. A., Wong, E. C., Hinks, R. S., Tikofsky, R. S. & Hyde, J. S. Time course EPI of human brain function during task activation. Magn. Reson. Med. 25, 390–397 (1992).

    Article  CAS  Google Scholar 

  8. Kwong, K. K. et al. Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc. Natl. Acad. Sci. USA 89, 5675–5679 ( 1992).

    Article  CAS  Google Scholar 

  9. Menon, R. S. et al. Functional brain mapping using magnetic resonance imaging. Signal changes accompanying visual stimulation. Invest. Radiol. 27, S47–53 ( 1992).

    Article  Google Scholar 

  10. Ogawa, S. et al. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc. Natl. Acad. Sci. USA 89, 5951–5955 (1992).

    Article  CAS  Google Scholar 

  11. Courtney, S. M. & Ungerleider, L. G. What fMRI has taught us about human vision. Curr. Opin. Neurobiol. 7, 554–561 (1997).

    Article  CAS  Google Scholar 

  12. Posner, M. I. & Raichle, M. E. The neuroimaging of human brain function. Proc. Natl. Acad. Sci. USA 95, 763–764 (1998).

    Article  CAS  Google Scholar 

  13. Binder, J. R. Functional magnetic resonance imaging of language cortex. Int. J. Imaging Systems Technol. 6, 280– 294 (1995).

    Article  Google Scholar 

  14. Buckner, R. L. & Petersen, S. E. What does neuroimaging tell us about the role of prefrontal cortex in memory retrieval. Semin. Neurosci. 8, 47– 55 (1996).

    Article  Google Scholar 

  15. Kindermann, S. S., Karimi, A., Symonds, L., Brown, G. G. & Jeste, D. V. Review of functional magnetic resonance imaging in schizophrenia. Schizophrenia Res. 27, 143 –156 (1997).

    Article  CAS  Google Scholar 

  16. Bock, C. et al. Functional MRI of somatosensory activation in rat: effect of hypercapnic up-regulation on perfusion- and BOLD-imaging. Magn. Reson. Med. 39, 457–461 (1998).

    Article  CAS  Google Scholar 

  17. Yang, X., Hyder, F., & Shulman, R. G. Functional MRI BOLD signal coincides with electrical activity in the rat whisker barrels. Magn. Reson. Med. 38, 874–877 (1997).

    Article  CAS  Google Scholar 

  18. Gyngell, M. L., Bock, C., Schmitz, B., Hoehn-Berlage, M. & Hossmann, K. A. Variation of functional MRI signal in response to frequency of somatosensory stimulation in alpha-chloralose anesthetized rats. Magn. Reson. Med. 36, 13– 15 (1996).

    Article  CAS  Google Scholar 

  19. Huang, W. et al. Magnetic resonance imaging (MRI) detection of the murine brain response to light-temporal differentiation and negative functional MRI changes. Proc. Natl. Acad. Sci. USA 93, 6037–6042 (1996).

    Article  CAS  Google Scholar 

  20. Yang, X., Hyder, F. & Shulman, R. G. Activation of single whisker barrel in rat brain localized by functional magnetic resonance imaging. Proc. Natl. Acad. Sci. USA 93, 475–478 (1996).

    Article  CAS  Google Scholar 

  21. Jezzard, P., Rauschecker, J. P. & Malonek, D. An in vivo model for functional MRI in cat visual cortex. Magn. Reson. Med. 38, 699– 705 (1997).

    Article  CAS  Google Scholar 

  22. Dubowitz, D. J. et al. Functional magnetic-resonance-imaging in macaque cortex. Neuroreport 9, 2213–2218 (1998).

    Article  CAS  Google Scholar 

  23. Stefanacci, L. et al. FMRI of monkey visual-cortex. Neuron 20, 1051–1057 (1998).

    Article  CAS  Google Scholar 

  24. Frahm, J., Merboldt, K. D. & Hanicke, W. Functional MRI of human brain activation at high spatial resolution. Magn. Reson. Med. 29, 139– 144 (1993).

    Article  CAS  Google Scholar 

  25. Menon, R. S., Ogawa, S., Strupp, J. P. & Ugurbil, K. Ocular dominance in human V1 demonstrated by functional magnetic resonance imaging. J. Neurophysiol. 77, 2780–2787 (1997).

    Article  CAS  Google Scholar 

  26. Turner, R. et al. Functional mapping of the human visual cortex at 4 and 1.5 tesla using deoxygenation contrast EPI. Magn. Reson. Med. 29, 277–279 (1993).

    Article  CAS  Google Scholar 

  27. Ugurbil, K. et al. Imaging at high magnetic fields: initial experiences at 4 T. Magn. Reson. Q. 9, 259– 277 (1993).

    CAS  PubMed  Google Scholar 

  28. Bandettini, P. A., Jesmanowicz, A., Wong, E. C. & Hyde, J. S. Processing strategies for time-course data sets in functional MRI of the human brain. Magn. Reson. Med. 30, 161– 173 (1993).

    Article  CAS  Google Scholar 

  29. Woods, R. P., Grafton, S. T., Watson, J. D., Sicotte, N. L. & Mazziotta, J. C. Automated image registration: II. Intersubject validation of linear and nonlinear models. J. Comput. Assist. Tomogr. 22, 153–165 (1998).

    Article  CAS  Google Scholar 

  30. Woods, R. P., Grafton, S. T., Holmes, C. J., Cherry, S. R. & Mazziotta, J. C. Automated image registration: I. General methods and intrasubject, intramodality validation. J. Comput. Assist. Tomogr. 22, 139– 152 (1998).

    Article  CAS  Google Scholar 

  31. Sereno, M. I. et al. Borders of multiple visual areas in humans revealed by functional magnetic resonance imaging. Science 268, 889–894 (1995).

    Article  CAS  Google Scholar 

  32. Deyoe, E. A., Bandettini, P., Neitz, J., Miller, D. & Winans, P. Functional magnetic resonance imaging (FMRI) of the human brain. J. Neurosci. Methods 54, 171–187 (1994).

    Article  CAS  Google Scholar 

  33. Engel, S. A., Glover, G. H. & Wandell, B. A. Retinotopic organization in human visual cortex and the spatial precision of functional MRI. Cereb. Cortex 7, 181–192 (1997).

    Article  CAS  Google Scholar 

  34. Logothetis, N. K. & Sheinberg, D. L. Visual object recognition. Annu. Rev. Neurosci. 19, 577 –621 (1996).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  36. Hu, X., Le, T. H. & Ugurbil, K. Evaluation of the early response in fMRI in individual subjects using short stimulus duration. Magn. Reson. Med. 37, 877–884 (1997).

    Article  CAS  Google Scholar 

  37. Menon, R. S. et al. BOLD based functional MRI at 4 Tesla includes a capillary bed contribution: echo-planar imaging correlates with previous optical imaging using intrinsic signals. Magn. Reson. Med. 33, 453–459 (1995).

    Article  CAS  Google Scholar 

  38. Cryer, P. E. Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system. N. Engl. J. Med. 303, 436– 444 (1980).

    Article  CAS  Google Scholar 

  39. Hochmann, J. & Kellerhals, H. Proton NMR on deoxyhaemoglobin. Use of a modified DEFT technique. J. Magn. Reson. 38 , 23–39 (1980).

    CAS  Google Scholar 

  40. Lee, J. H. et al. High contrast and fast three-dimensional magnetic resonance imaging at high fields. Magn. Reson. Med. 34, 308–312 (1995).

    Article  CAS  Google Scholar 

  41. Haase, A., Frahm, J., Matthaei, D., Hanicke, W. & Merboldt, K.-D. FLASH imaging. Rapid NMR imaging using low flip-angle pulses. J. Magn. Reson. 67, 258– 266 (1986).

    CAS  Google Scholar 

  42. Mansfield, P. Multi-planar image formation using NMR spin echoes. J. Phys. C 10, L55–58 ( 1977).

    Article  CAS  Google Scholar 

  43. Donoho, D. L. & Johnstone, I. M. Adapting to unknown smoothness via wavelet shrinkage. J. Am. Stat. Assoc. 90, 1200–1224 (1995).

    Article  Google Scholar 

  44. Worsley, K. J. & Friston, K. J. Analysis of fMRI time-series revisited - again. Neuroimage 2, 173–181 (1995).

    Article  CAS  Google Scholar 

  45. Worsley, K. J., Evans, A. C., Marrett, S. & Neelin, P. A three-dimensional statistical analysis for CBF activation studies in human brain. J. Cereb. Blood Flow Metab. 12, 900 –918 (1992).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Torsten Trinath for laboratory assistance, Albert Vaeth and Mark Augath for help in running the MR scanner, D. Cory of MIT for advice in the initial phase of the project and Bernd Gewiese, Martin Ilg and Wolfgang Kreibich of Bruker Medical Inc. for help with technical issues. We are indebted to C. Hoffman, K. Stahl, S. Weber and A. Dietz for design and fine-mechanical work and to Klaus Lamberty for the hand drawings. Finally we thank R. Turner, P. Tse, M. Sereno and D. Blaurock for comments on the manuscript and K. Unertl for enabling the collaboration with the Department of Anesthesiology, University of Tuebingen School of Medicine.

Author information

Authors and Affiliations

  1. Max Planck Institute for Biological Cybernetics, Spemannstr. 38, Tübingen, 72076, Germany

    Nikos K. Logothetis, Sharon Peled & Jon Pauls

  2. Department of Anesthesiology, University Hospital Eberhard-Karls-University, Tübingen, 72076, Germany

    Heinz Guggenberger

Authors
  1. Nikos K. Logothetis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heinz Guggenberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharon Peled
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jon Pauls
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nikos K. Logothetis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Logothetis, N., Guggenberger, H., Peled, S. et al. Functional imaging of the monkey brain. Nat Neurosci 2, 555–562 (1999). https://doi.org/10.1038/9210

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/9210

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing