• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of transbhomepageaboutsubmitalertseditorial board
Philos Trans R Soc Lond B Biol Sci. Jul 29, 1999; 354(1387): 1179–1194.
PMCID: PMC1692627

Functional magnetic resonance imaging: imaging techniques and contrast mechanisms.


Functional magnetic resonance imaging (fMRI) is a widely used technique for generating images or maps of human brain activity. The applications of the technique are widespread in cognitive neuroscience and it is hoped they will eventually extend into clinical practice. The activation signal measured with fMRI is predicated on indirectly measuring changes in the concentration of deoxyhaemoglobin which arise from an increase in blood oxygenation in the vicinity of neuronal firing. The exact mechanisms of this blood oxygenation level dependent (BOLD) contrast are highly complex. The signal measured is dependent on both the underlying physiological events and the imaging physics. BOLD contrast, although sensitive, is not a quantifiable measure of neuronal activity. A number of different imaging techniques and parameters can be used for fMRI, the choice of which depends on the particular requirements of each functional imaging experiment. The high-speed MRI technique, echo-planar imaging provides the basis for most fMRI experiments. The problems inherent to this method and the ways in which these may be overcome are particularly important in the move towards performing functional studies on higher field MRI systems. Future developments in techniques and hardware are also likely to enhance the measurement of brain activity using MRI.

Full Text

The Full Text of this article is available as a PDF (645K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Albert MS, Cates GD, Driehuys B, Happer W, Saam B, Springer CS, Jr, Wishnia A. Biological magnetic resonance imaging using laser-polarized 129Xe. Nature. 1994 Jul 21;370(6486):199–201. [PubMed]
  • Allen PJ, Polizzi G, Krakow K, Fish DR, Lemieux L. Identification of EEG events in the MR scanner: the problem of pulse artifact and a method for its subtraction. Neuroimage. 1998 Oct;8(3):229–239. [PubMed]
  • Ashe J, Ugurbil K. Functional imaging of the motor system. Curr Opin Neurobiol. 1994 Dec;4(6):832–839. [PubMed]
  • Bandettini PA, Wong EC, Hinks RS, Tikofsky RS, Hyde JS. Time course EPI of human brain function during task activation. Magn Reson Med. 1992 Jun;25(2):390–397. [PubMed]
  • Bandettini PA, Kwong KK, Davis TL, Tootell RB, Wong EC, Fox PT, Belliveau JW, Weisskoff RM, Rosen BR. Characterization of cerebral blood oxygenation and flow changes during prolonged brain activation. Hum Brain Mapp. 1997;5(2):93–109. [PubMed]
  • Bandettini PA, Jesmanowicz A, Van Kylen J, Birn RM, Hyde JS. Functional MRI of brain activation induced by scanner acoustic noise. Magn Reson Med. 1998 Mar;39(3):410–416. [PubMed]
  • Belliveau JW, Kennedy DN, Jr, McKinstry RC, Buchbinder BR, Weisskoff RM, Cohen MS, Vevea JM, Brady TJ, Rosen BR. Functional mapping of the human visual cortex by magnetic resonance imaging. Science. 1991 Nov 1;254(5032):716–719. [PubMed]
  • Binder JR. Neuroanatomy of language processing studied with functional MRI. Clin Neurosci. 1997;4(2):87–94. [PubMed]
  • Birn RM, Bandettini PA, Cox RW, Jesmanowicz A, Shaker R. Magnetic field changes in the human brain due to swallowing or speaking. Magn Reson Med. 1998 Jul;40(1):55–60. [PubMed]
  • Bohning DE, Shastri A, Nahas Z, Lorberbaum JP, Andersen SW, Dannels WR, Haxthausen EU, Vincent DJ, George MS. Echoplanar BOLD fMRI of brain activation induced by concurrent transcranial magnetic stimulation. Invest Radiol. 1998 Jun;33(6):336–340. [PubMed]
  • Buxton RB, Frank LR. A model for the coupling between cerebral blood flow and oxygen metabolism during neural stimulation. J Cereb Blood Flow Metab. 1997 Jan;17(1):64–72. [PubMed]
  • Buxton RB, Wong EC, Frank LR. Dynamics of blood flow and oxygenation changes during brain activation: the balloon model. Magn Reson Med. 1998 Jun;39(6):855–864. [PubMed]
  • Chen W, Zhu XH, Kato T, Andersen P, Ugurbil K. Spatial and temporal differentiation of fMRI BOLD response in primary visual cortex of human brain during sustained visual simulation. Magn Reson Med. 1998 Apr;39(4):520–527. [PubMed]
  • Davis KD, Taylor SJ, Crawley AP, Wood ML, Mikulis DJ. Functional MRI of pain- and attention-related activations in the human cingulate cortex. J Neurophysiol. 1997 Jun;77(6):3370–3380. [PubMed]
  • Davis TL, Kwong KK, Weisskoff RM, Rosen BR. Calibrated functional MRI: mapping the dynamics of oxidative metabolism. Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1834–1839. [PMC free article] [PubMed]
  • Dymond RC, Norris DG. Mechanism and echo time dependence of the fast response in fMR. Magn Reson Med. 1997 Jul;38(1):1–6. [PubMed]
  • Edelman RR, Siewert B, Adamis M, Gaa J, Laub G, Wielopolski P. Signal targeting with alternating radiofrequency (STAR) sequences: application to MR angiography. Magn Reson Med. 1994 Feb;31(2):233–238. [PubMed]
  • Eden GF, Joseph JE, Brown HE, Brown CP, Zeffiro TA. Utilizing hemodynamic delay and dispersion to detect fMRI signal change without auditory interference: the behavior interleaved gradients technique. Magn Reson Med. 1999 Jan;41(1):13–20. [PubMed]
  • Fisel CR, Ackerman JL, Buxton RB, Garrido L, Belliveau JW, Rosen BR, Brady TJ. MR contrast due to microscopically heterogeneous magnetic susceptibility: numerical simulations and applications to cerebral physiology. Magn Reson Med. 1991 Feb;17(2):336–347. [PubMed]
  • Fletcher PC, Frith CD, Rugg MD. The functional neuroanatomy of episodic memory. Trends Neurosci. 1997 May;20(5):213–218. [PubMed]
  • Fox PT, Raichle ME. Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1140–1144. [PMC free article] [PubMed]
  • Fox PT, Raichle ME, Mintun MA, Dence C. Nonoxidative glucose consumption during focal physiologic neural activity. Science. 1988 Jul 22;241(4864):462–464. [PubMed]
  • Frahm J, Merboldt KD, Hänicke W. Functional MRI of human brain activation at high spatial resolution. Magn Reson Med. 1993 Jan;29(1):139–144. [PubMed]
  • Frahm J, Merboldt KD, Hänicke W, Kleinschmidt A, Boecker H. Brain or vein--oxygenation or flow? On signal physiology in functional MRI of human brain activation. NMR Biomed. 1994 Mar;7(1-2):45–53. [PubMed]
  • Frahm J, Krüger G, Merboldt KD, Kleinschmidt A. Dynamic uncoupling and recoupling of perfusion and oxidative metabolism during focal brain activation in man. Magn Reson Med. 1996 Feb;35(2):143–148. [PubMed]
  • Fransson P, Krüger G, Merboldt KD, Frahm J. Temporal characteristics of oxygenation-sensitive MRI responses to visual activation in humans. Magn Reson Med. 1998 Jun;39(6):912–919. [PubMed]
  • Friston KJ, Williams S, Howard R, Frackowiak RS, Turner R. Movement-related effects in fMRI time-series. Magn Reson Med. 1996 Mar;35(3):346–355. [PubMed]
  • Friston KJ, Josephs O, Rees G, Turner R. Nonlinear event-related responses in fMRI. Magn Reson Med. 1998 Jan;39(1):41–52. [PubMed]
  • Friston KJ, Fletcher P, Josephs O, Holmes A, Rugg MD, Turner R. Event-related fMRI: characterizing differential responses. Neuroimage. 1998 Jan;7(1):30–40. [PubMed]
  • Gati JS, Menon RS, Ugurbil K, Rutt BK. Experimental determination of the BOLD field strength dependence in vessels and tissue. Magn Reson Med. 1997 Aug;38(2):296–302. [PubMed]
  • Glover GH, Lai S. Self-navigated spiral fMRI: interleaved versus single-shot. Magn Reson Med. 1998 Mar;39(3):361–368. [PubMed]
  • Haacke EM, Hopkins A, Lai S, Buckley P, Friedman L, Meltzer H, Hedera P, Friedland R, Klein S, Thompson L, et al. 2D and 3D high resolution gradient echo functional imaging of the brain: venous contributions to signal in motor cortex studies. NMR Biomed. 1994 Mar;7(1-2):54–62. [PubMed]
  • Hajnal JV, Bydder GM, Young IR. fMRI: does correlation imply activation? NMR Biomed. 1995 May;8(3):97–100. [PubMed]
  • Harvey PR, Mansfield P. Echo-volumar imaging (EVI) at 0.5 T: first whole-body volunteer studies. Magn Reson Med. 1996 Jan;35(1):80–88. [PubMed]
  • Howseman AM, Porter DA, Hutton C, Josephs O, Turner R. Blood oxygenation level dependent signal time courses during prolonged visual stimulation. Magn Reson Imaging. 1998;16(1):1–11. [PubMed]
  • Howseman AM, Grootoonk S, Porter DA, Ramdeen J, Holmes AP, Turner R. The effect of slice order and thickness on fMRI activation data using multislice echo-planar imaging. Neuroimage. 1999 Apr;9(4):363–376. [PubMed]
  • Hu X, Le TH. Artifact reduction in EPI with phase-encoded reference scan. Magn Reson Med. 1996 Jul;36(1):166–171. [PubMed]
  • Hu X, Le TH, Uğurbil K. Evaluation of the early response in fMRI in individual subjects using short stimulus duration. Magn Reson Med. 1997 Jun;37(6):877–884. [PubMed]
  • Ives JR, Warach S, Schmitt F, Edelman RR, Schomer DL. Monitoring the patient's EEG during echo planar MRI. Electroencephalogr Clin Neurophysiol. 1993 Dec;87(6):417–420. [PubMed]
  • Jackson GD, Connelly A, Cross JH, Gordon I, Gadian DG. Functional magnetic resonance imaging of focal seizures. Neurology. 1994 May;44(5):850–856. [PubMed]
  • Jakob PM, Schlaug G, Griswold M, Lovblad KO, Thomas R, Ives JR, Matheson JK, Edelman RR. Functional burst imaging. Magn Reson Med. 1998 Oct;40(4):614–621. [PubMed]
  • Janz C, Speck O, Hennig J. Time-resolved measurements of brain activation after a short visual stimulus: new results on the physiological mechanisms of the cortical response. NMR Biomed. 1997 Jun-Aug;10(4-5):222–229. [PubMed]
  • Jesmanowicz A, Bandettini PA, Hyde JS. Single-shot half k-space high-resolution gradient-recalled EPI for fMRI at 3 Tesla. Magn Reson Med. 1998 Nov;40(5):754–762. [PubMed]
  • Jezzard P, Balaban RS. Correction for geometric distortion in echo planar images from B0 field variations. Magn Reson Med. 1995 Jul;34(1):65–73. [PubMed]
  • Jueptner M, Weiller C. Review: does measurement of regional cerebral blood flow reflect synaptic activity? Implications for PET and fMRI. Neuroimage. 1995 Jun;2(2):148–156. [PubMed]
  • Kim SG, Hendrich K, Hu X, Merkle H, Uğurbil K. Potential pitfalls of functional MRI using conventional gradient-recalled echo techniques. NMR Biomed. 1994 Mar;7(1-2):69–74. [PubMed]
  • Kim SG, Hu X, Adriany G, Uğurbil K. Fast interleaved echo-planar imaging with navigator: high resolution anatomic and functional images at 4 Tesla. Magn Reson Med. 1996 Jun;35(6):895–902. [PubMed]
  • Kim SG, Richter W, Uğurbil K. Limitations of temporal resolution in functional MRI. Magn Reson Med. 1997 Apr;37(4):631–636. [PubMed]
  • Krüger G, Kleinschmidt A, Frahm J. Dynamic MRI sensitized to cerebral blood oxygenation and flow during sustained activation of human visual cortex. Magn Reson Med. 1996 Jun;35(6):797–800. [PubMed]
  • Lai S, Glover GH. Three-dimensional spiral fMRI technique: a comparison with 2D spiral acquisition. Magn Reson Med. 1998 Jan;39(1):68–78. [PubMed]
  • Lai S, Hopkins AL, Haacke EM, Li D, Wasserman BA, Buckley P, Friedman L, Meltzer H, Hedera P, Friedland R. Identification of vascular structures as a major source of signal contrast in high resolution 2D and 3D functional activation imaging of the motor cortex at 1.5T: preliminary results. Magn Reson Med. 1993 Sep;30(3):387–392. [PubMed]
  • Lee AT, Glover GH, Meyer CH. Discrimination of large venous vessels in time-course spiral blood-oxygen-level-dependent magnetic-resonance functional neuroimaging. Magn Reson Med. 1995 Jun;33(6):745–754. [PubMed]
  • Lemieux L, Allen PJ, Franconi F, Symms MR, Fish DR. Recording of EEG during fMRI experiments: patient safety. Magn Reson Med. 1997 Dec;38(6):943–952. [PubMed]
  • Malonek D, Grinvald A. Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science. 1996 Apr 26;272(5261):551–554. [PubMed]
  • Menon RS, Ogawa S, Tank DW, Uğurbil K. Tesla gradient recalled echo characteristics of photic stimulation-induced signal changes in the human primary visual cortex. Magn Reson Med. 1993 Sep;30(3):380–386. [PubMed]
  • Menon RS, Ogawa S, Hu X, Strupp JP, Anderson P, Uğurbil K. 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. 1995 Mar;33(3):453–459. [PubMed]
  • Noll DC, Genovese CR, Nystrom LE, Vazquez AL, Forman SD, Eddy WF, Cohen JD. Estimating test-retest reliability in functional MR imaging. II: Application to motor and cognitive activation studies. Magn Reson Med. 1997 Sep;38(3):508–517. [PubMed]
  • Ogawa S, Lee TM, Kay AR, Tank DW. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9868–9872. [PMC free article] [PubMed]
  • Ogawa S, Tank DW, Menon R, Ellermann JM, Kim SG, Merkle H, Ugurbil K. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5951–5955. [PMC free article] [PubMed]
  • Ogawa S, Menon RS, Tank DW, Kim SG, Merkle H, Ellermann JM, Ugurbil K. Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. Biophys J. 1993 Mar;64(3):803–812. [PMC free article] [PubMed]
  • Phillips ML, Young AW, Senior C, Brammer M, Andrew C, Calder AJ, Bullmore ET, Perrett DI, Rowland D, Williams SC, et al. A specific neural substrate for perceiving facial expressions of disgust. Nature. 1997 Oct 2;389(6650):495–498. [PubMed]
  • Ramsey NF, van den Brink JS, van Muiswinkel AM, Folkers PJ, Moonen CT, Jansma JM, Kahn RS. Phase navigator correction in 3D fMRI improves detection of brain activation: quantitative assessment with a graded motor activation procedure. Neuroimage. 1998 Oct;8(3):240–248. [PubMed]
  • Reber PJ, Wong EC, Buxton RB, Frank LR. Correction of off resonance-related distortion in echo-planar imaging using EPI-based field maps. Magn Reson Med. 1998 Feb;39(2):328–330. [PubMed]
  • Rees G, Howseman A, Josephs O, Frith CD, Friston KJ, Frackowiak RS, Turner R. Characterizing the relationship between BOLD contrast and regional cerebral blood flow measurements by varying the stimulus presentation rate. Neuroimage. 1997 Nov;6(4):270–278. [PubMed]
  • Robitaille PM, Abduljalil AM, Kangarlu A, Zhang X, Yu Y, Burgess R, Bair S, Noa P, Yang L, Zhu H, et al. Human magnetic resonance imaging at 8 T. NMR Biomed. 1998 Oct;11(6):263–265. [PubMed]
  • Rosen BR, Buckner RL, Dale AM. Event-related functional MRI: past, present, and future. Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):773–780. [PMC free article] [PubMed]
  • Schneider F, Grodd W, Weiss U, Klose U, Mayer KR, Nägele T, Gur RC. Functional MRI reveals left amygdala activation during emotion. Psychiatry Res. 1997 Dec 30;76(2-3):75–82. [PubMed]
  • Shulman RG, Rothman DL. Interpreting functional imaging studies in terms of neurotransmitter cycling. Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11993–11998. [PMC free article] [PubMed]
  • Shulman RG, Blamire AM, Rothman DL, McCarthy G. Nuclear magnetic resonance imaging and spectroscopy of human brain function. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3127–3133. [PMC free article] [PubMed]
  • Song AW, Wong EC, Tan SG, Hyde JS. Diffusion weighted fMRI at 1.5 T. Magn Reson Med. 1996 Feb;35(2):155–158. [PubMed]
  • Stables LA, Kennan RP, Gore JC. Asymmetric spin-echo imaging of magnetically inhomogeneous systems: theory, experiment, and numerical studies. Magn Reson Med. 1998 Sep;40(3):432–442. [PubMed]
  • Teo PC, Sapiro G, Wandell BA. Creating connected representations of cortical gray matter for functional MRI visualization. IEEE Trans Med Imaging. 1997 Dec;16(6):852–863. [PubMed]
  • Thulborn KR, Chang SY, Shen GX, Voyvodic JT. High-resolution echo-planar fMRI of human visual cortex at 3.0 tesla. NMR Biomed. 1997 Jun-Aug;10(4-5):183–190. [PubMed]
  • Turner R, Le Bihan D, Moonen CT, Despres D, Frank J. Echo-planar time course MRI of cat brain oxygenation changes. Magn Reson Med. 1991 Nov;22(1):159–166. [PubMed]
  • Turner R, Jezzard P, Wen H, Kwong KK, Le Bihan D, Zeffiro T, Balaban RS. Functional mapping of the human visual cortex at 4 and 1.5 tesla using deoxygenation contrast EPI. Magn Reson Med. 1993 Feb;29(2):277–279. [PubMed]
  • Weisskoff RM, Zuo CS, Boxerman JL, Rosen BR. Microscopic susceptibility variation and transverse relaxation: theory and experiment. Magn Reson Med. 1994 Jun;31(6):601–610. [PubMed]
  • Yang QX, Dardzinski BJ, Li S, Eslinger PJ, Smith MB. Multi-gradient echo with susceptibility inhomogeneity compensation (MGESIC): demonstration of fMRI in the olfactory cortex at 3.0 T. Magn Reson Med. 1997 Mar;37(3):331–335. [PubMed]
  • Yang X, Hyder F, Shulman RG. Functional MRI BOLD signal coincides with electrical activity in the rat whisker barrels. Magn Reson Med. 1997 Dec;38(6):874–877. [PubMed]
  • Yang Y, Glover GH, van Gelderen P, Mattay VS, Santha AK, Sexton RH, Ramsey NF, Moonen CT, Weinberger DR, Frank JA, et al. Fast 3D functional magnetic resonance imaging at 1.5 T with spiral acquisition. Magn Reson Med. 1996 Oct;36(4):620–626. [PubMed]
  • Yang Y, Frank JA, Hou L, Ye FQ, McLaughlin AC, Duyn JH. Multislice imaging of quantitative cerebral perfusion with pulsed arterial spin labeling. Magn Reson Med. 1998 May;39(5):825–832. [PubMed]
  • Yang Y, Glover GH, van Gelderen P, Patel AC, Mattay VS, Frank JA, Duyn JH. A comparison of fast MR scan techniques for cerebral activation studies at 1.5 tesla. Magn Reson Med. 1998 Jan;39(1):61–67. [PubMed]
  • Zhong J, Kennan RP, Fulbright RK, Gore JC. Quantification of intravascular and extravascular contributions to BOLD effects induced by alteration in oxygenation or intravascular contrast agents. Magn Reson Med. 1998 Oct;40(4):526–536. [PubMed]
  • Zhu XH, Kim SG, Andersen P, Ogawa S, Uğurbil K, Chen W. Simultaneous oxygenation and perfusion imaging study of functional activity in primary visual cortex at different visual stimulation frequency: quantitative correlation between BOLD and CBF changes. Magn Reson Med. 1998 Nov;40(5):703–711. [PubMed]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...