, Volume 78, Issue 2, pp 308–321 | Cite as

An Introduction to Normalization and Calibration Methods in Functional MRI

  • Thomas T. LiuEmail author
  • Gary H. Glover
  • Bryon A. Mueller
  • Douglas N. Greve
  • Gregory G. Brown


In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes in the baseline neurovascular state can result in significant modulations of the BOLD signal that are independent of changes in neural activity. This paper introduces some of the normalization and calibration methods that have been proposed for making the BOLD signal a more accurate reflection of underlying brain activity for human fMRI studies.

Key words

functional MRI arterial spin labeling cerebral blood flow quantitative fMRI calibrated fMRI hypercapnia 



We acknowledge funding support by the NIH National Center for Research Resources for the FBIRN consortium (Grant U24-RR021992) as well as individual grants to coinvestigators: P41-RR009784 (GHG), R01NS051661, and R01MH084796 (TTL).


  1. Aguirre, G.K., Zarahn, E., & D’Esposito, M. (1998). The variability of human, BOLD hemodynamic responses. NeuroImage, 8, 360–369. CrossRefPubMedGoogle Scholar
  2. Ances, B., Leontiev, O., Perthen, J.E., Liang, C., Lansing, A.E., & Buxton, R.B. (2008). Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: implications for BOLD-fMRI. NeuroImage, 39(4), 1510–1521. doi: 10.1016/j.neuroimage.2007.11.015. CrossRefPubMedGoogle Scholar
  3. Ances, B., Vaida, F., Ellis, R., & Buxton, R. (2011). Test-retest stability of calibrated BOLD-fMRI in HIV− and HIV+ subjects. NeuroImage, 54(3), 2156–2162. doi: 10.1016/j.neuroimage.2010.09.081. CrossRefPubMedGoogle Scholar
  4. Ances, B.M., Liang, C.L., Leontiev, O., Perthen, J.E., Fleisher, A.S., Lansing, A.E., et al. (2008). Effects of aging on cerebral blood flow, oxygen metabolism, and blood oxygenation level dependent responses to visual stimulation. Human Brain Mapping. doi: 10.1002/hbm.20574. Google Scholar
  5. Asghar, M.S., Hansen, A.E., Pedersen, S., Larsson, H.B.W., & Ashina, M. (2011). Pharmacological modulation of the BOLD response: a study of acetazolamide and glyceryl trinitrate in humans. Journal of Magnetic Resonance Imaging, 34(4), 921–927. doi: 10.1002/jmri.22659. CrossRefPubMedGoogle Scholar
  6. Bandettini, P.A., & Wong, E.C. (1997). A hypercapnia-based normalization method for improved spatial localization of human brain activation with fMRI. NMR in Biomedicine, 10(4–5), 197–203. CrossRefPubMedGoogle Scholar
  7. Behzadi, Y., & Liu, T.T. (2005). An arteriolar compliance model of the cerebral blood flow response to neural stimulus. NeuroImage, 25(4), 1100–1111. CrossRefPubMedGoogle Scholar
  8. Birn, R.M., Diamond, J.B., Smith, M.A., & Bandettini, P.A. (2006). Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI. NeuroImage, 31(4), 1536–1548. CrossRefPubMedGoogle Scholar
  9. Birn, R.M., Saad, Z.S., & Bandettini, P.A. (2001). Spatial heterogeneity of the nonlinear dynamics in the FMRI BOLD response. NeuroImage, 14, 817–826. CrossRefPubMedGoogle Scholar
  10. Biswal, B.B., Kannurpatti, S.S., & Rypma, B. (2007). Hemodynamic scaling of fMRI-BOLD signal: validation of low-frequency spectral amplitude as a scalability factor. Magnetic Resonance Imaging, 25(10), 1358–1369. CrossRefPubMedGoogle Scholar
  11. Bolar, D.S., Sorensen, A.G., Rosen, B.R., & Adalsteinsson, E. (2009). Feasibility of QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption (QUIXOTIC) to assess functional changes in venous oxygen saturation during visual stimulus. Paper presented at the 17th ISMRM scientific meeting, Honolulu. Google Scholar
  12. Boxerman, J.L., Bandettini, P.A., Kwong, K.K., Baker, J.R., Davis, T.L., Rosen, B.R., et al. (1995). The intravascular contribution to fMRI signal change: Monte Carlo modeling and diffusion-weighted studies in vivo. Magnetic Resonance in Medicine, 34, 4–10. CrossRefPubMedGoogle Scholar
  13. Boynton, G.M., Engel, S.A., Glover, G.H., & Heeger, D.J. (1996). Linear systems analysis of functional magnetic resonance imaging in human V1. The Journal of Neuroscience, 16, 4207–4221. PubMedGoogle Scholar
  14. Brown, G.G., Zorrilla, L.T.E., Gerogy, B., Kindermann, S.S., Wong, E.C., & Buxton, R.B. (2003). BOLD and perfusion response to finger-thumb apposition after acetazolamide administration: differential relationship to global perfusion. Journal of Cerebral Blood Flow and Metabolism, 23, 829–837. PubMedGoogle Scholar
  15. Bruhn, H., Kleinschmidt, A., Boecker, H., Merboldt, K.D., Hänicke, W., & Frahm, J. (1994). The effect of acetazolamide on regional cerebral blood oxygenation at rest and under stimulation as assessed by MRI. Journal of Cerebral Blood Flow and Metabolism, 14(5), 742–748. doi: 10.1038/jcbfm.1994.95. CrossRefPubMedGoogle Scholar
  16. Buxton, R.B., Uludag, K., Dubowitz, D.J., & Liu, T.T. (2004). Modeling the hemodynamic response to brain activation. NeuroImage, 23(Suppl 1), S220–S233. CrossRefPubMedGoogle Scholar
  17. Carusone, L.M., Srinivasan, J., Gitelman, D.R., Mesulam, M.M., & Parrish, T.B. (2002). Hemodynamic response changes in cerebrovascular disease: implications for functional MR imaging. American Journal of Neuroradiology, 23(7), 1222–1228. PubMedGoogle Scholar
  18. Chen, J.J., & Pike, G.B. (2009). BOLD-specific cerebral blood volume and blood flow changes during neuronal activation in humans. NMR in Biomedicine, 22(10), 1054–1062. doi: 10.1002/nbm.1411. PubMedGoogle Scholar
  19. Chen, J.J., & Pike, G.B. (2010a). Global cerebral oxidative metabolism during hypercapnia and hypocapnia in humans: implications for BOLD fMRI. Journal of Cerebral Blood Flow and Metabolism. doi: 10.1038/jcbfm.2010.42. Google Scholar
  20. Chen, J.J., & Pike, G.B. (2010b). MRI measurement of the BOLD-specific flow-volume relationship during hypercapnia and hypocapnia in humans. NeuroImage, 53(2), 383–391. doi: 10.1016/j.neuroimage.2010.07.003. CrossRefPubMedGoogle Scholar
  21. Chen, Y., & Parrish, T.B. (2009). Caffeine’s effects on cerebrovascular reactivity and coupling between cerebral blood flow and oxygen metabolism. NeuroImage, 44(3), 647–652. doi: 10.1016/j.neuroimage.2008.09.057. CrossRefPubMedGoogle Scholar
  22. Chiarelli, P.A., Bulte, D.P., Gallichan, D., Piechnik, S.K., Wise, R., & Jezzard, P. (2007). Flow-metabolism coupling in human visual, motor, and supplementary motor areas assessed by magnetic resonance imaging. Magnetic Resonance in Medicine, 57(3), 538–547. doi: 10.1002/mrm.21171. CrossRefPubMedGoogle Scholar
  23. Cohen, E.R., Rostrup, E., Sidaros, K., Lund, T.E., Paulson, O.B., Ugurbil, K., et al. (2004). Hypercapnic normalization of BOLD fMRI: comparison across field strengths and pulse sequences. NeuroImage, 23(2), 613–624. CrossRefPubMedGoogle Scholar
  24. Cohen, E.R., Ugurbil, K., & Kim, S.G. (2002). Effect of basal conditions on the magnitude and dynamics of the blood oxygenation level-dependent fMRI response. Journal of Cerebral Blood Flow and Metabolism, 22(9), 1042–1053. PubMedGoogle Scholar
  25. D’Esposito, M., Deouell, L.Y., & Gazzaley, A. (2003). Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nature Reviews. Neuroscience, 4(11), 863–872. CrossRefPubMedGoogle Scholar
  26. Davis, T.L., Kwong, K.K., Weisskoff, R.M., & Rosen, B.R. (1998). Calibrated functional MRI: mapping the dynamics of oxidative metabolism. Proceedings of the National Academy of Sciences of the United States of America, 95, 1834–1839. CrossRefPubMedGoogle Scholar
  27. de Zwart, J.A., van Gelderen, P., Jansma, J.M., Fukunaga, M., Bianciardi, M., & Duyn, J.H. (2009). Hemodynamic nonlinearities affect BOLD fMRI response timing and amplitude. NeuroImage, 47(4), 1649–1658. doi: 10.1016/j.neuroimage.2009.06.001. CrossRefPubMedGoogle Scholar
  28. Detre, J.A., Rao, H., Wang, D.J.J., Chen, Y.F., & Wang, Z. (2012). Applications of arterial spin labeled MRI in the brain. Journal of Magnetic Resonance Imaging. doi: 10.1002/jmri.23581. PubMedGoogle Scholar
  29. Detre, J.A., Wang, J., Wang, Z., & Rao, H. (2009). Arterial spin-labeled perfusion MRI in basic and clinical neuroscience. Current Opinion in Neurology, 22(4), 348–355. doi: 10.1097/WCO.0b013e32832d9505. CrossRefPubMedGoogle Scholar
  30. Devor, A., Dunn, A.K., Andermann, M.L., Ulbert, I., Boas, D.A., & Dale, A.M. (2003). Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex. Neuron, 39(2), 353–359. CrossRefPubMedGoogle Scholar
  31. Formaggio, E., Storti, S., Avesani, M., Cerini, R., Milanese, F., Gasparini, A., et al. (2008). EEG and FMRI coregistration to investigate the cortical oscillatory activities during finger movement. Brain Topography, 21(2), 100–111. doi: 10.1007/s10548-008-0058-1. CrossRefPubMedGoogle Scholar
  32. Friston, K.J., Josephs, O., Rees, G., & Turner, R. (1998). Nonlinear event-related responses in fMRI. Magnetic Resonance in Medicine, 39, 41–52. CrossRefPubMedGoogle Scholar
  33. Griffeth, V.E.M., & Buxton, R.B. (2011). A theoretical framework for estimating cerebral oxygen metabolism changes using the calibrated-BOLD method: modeling the effects of blood volume distribution, hematocrit, oxygen extraction fraction, and tissue signal properties on the BOLD signal. NeuroImage, 58(1), 198–212. doi: 10.1016/j.neuroimage.2011.05.077. CrossRefPubMedGoogle Scholar
  34. Handwerker, D.A., Gazzaley, A., Inglis, B.A., & D’Esposito, M. (2007). Reducing vascular variability of fMRI data across aging populations using a breathholding task. Human Brain Mapping, 28(9), 846–859. doi: 10.1002/hbm.20307. CrossRefPubMedGoogle Scholar
  35. Handwerker, D.A., Ollinger, J.M., & D’Esposito, M. (2004). Variation of BOLD hemodynamic responses across subjects and brain regions and their effects on statistical analyses. NeuroImage, 21(4), 1639–1651. CrossRefPubMedGoogle Scholar
  36. Hewson-Stoate, N., Jones, M., Martindale, J., Berwick, J., & Mayhew, J. (2005). Further nonlinearities in neurovascular coupling in rodent barrel cortex. NeuroImage, 24(2), 565–574. doi: 10.1016/j.neuroimage.2004.08.040. CrossRefPubMedGoogle Scholar
  37. Hoge, R.D., Atkinson, J., Gill, B., Crelier, G.R., Marrett, S., & Pike, G.B. (1999a). Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: the deoxyhemoglobin dilution model. Magnetic Resonance in Medicine, 42(5), 849–863. CrossRefPubMedGoogle Scholar
  38. Hoge, R.D., Atkinson, J., Gill, B., Crelier, G.R., Marrett, S., & Pike, G.B. (1999b). Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex. Proceedings of the National Academy of Sciences of the United States of America, 96(16), 9403–9408. CrossRefPubMedGoogle Scholar
  39. Huttunen, J.K., Gröhn, O., & Penttonen, M. (2008). Coupling between simultaneously recorded BOLD response and neuronal activity in the rat somatosensory cortex. NeuroImage, 39(2), 775–785. doi: 10.1016/j.neuroimage.2007.06.042. CrossRefPubMedGoogle Scholar
  40. Hyder, F. (2004). Neuroimaging with calibrated FMRI. Stroke, 35(11 Suppl 1), 2635–2641. CrossRefPubMedGoogle Scholar
  41. Hyder, F., Rothman, D.L., & Shulman, R.G. (2002). Total neuroenergetics support localized brain activity: implications for the interpretation of fMRI. Proceedings of the National Academy of Sciences of the United States of America, 99(16), 10771–10776. doi: 10.1073/pnas.132272299. CrossRefPubMedGoogle Scholar
  42. Iannetti, G., & Wise, R. (2007). BOLD functional MRI in disease and pharmacological studies: room for improvement? Magnetic Resonance Imaging, 25(6), 978–988. doi: 10.1016/j.mri.2007.03.018. CrossRefPubMedGoogle Scholar
  43. Jain, V., Langham, M.C., Floyd, T.F., Jain, G., Magland, J.F., & Wehrli, F.W. (2011). Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapnia. Journal of Cerebral Blood Flow and Metabolism. doi: 10.1038/jcbfm.2011.34. Google Scholar
  44. Jones, M., Berwick, J., Hewson-Stoate, N., Gias, C., & Mayhew, J. (2005). The effect of hypercapnia on the neural and hemodynamic responses to somatosensory stimulation. NeuroImage, 27(3), 609–623. doi: 10.1016/j.neuroimage.2005.04.036. CrossRefPubMedGoogle Scholar
  45. Kannurpatti, S.S., & Biswal, B.B. (2008). Detection and scaling of task-induced fMRI-BOLD response using resting state fluctuations. NeuroImage, 40(4), 1567–1574. doi: 10.1016/j.neuroimage.2007.09.040. CrossRefPubMedGoogle Scholar
  46. Kida, I., Rothman, D.L., & Hyder, F. (2007). Dynamics of changes in blood flow, volume, and oxygenation: implications for dynamic functional magnetic resonance imaging calibration. Journal of Cerebral Blood Flow and Metabolism, 27(4), 690–696. doi: 10.1038/sj.jcbfm.9600409. PubMedGoogle Scholar
  47. Kim, T., Hendrich, K.S., Masamoto, K., & Kim, S.-G. (2007). Arterial versus total blood volume changes during neural activity-induced cerebral blood flow change: implication for BOLD fMRI. Journal of Cerebral Blood Flow and Metabolism, 27(6), 1235–1247. doi: 10.1038/sj.jcbfm.9600429. CrossRefPubMedGoogle Scholar
  48. Koch, S.P., Koendgen, S., Bourayou, R., Steinbrink, J., & Obrig, H. (2008). Individual alpha-frequency correlates with amplitude of visual evoked potential and hemodynamic response. NeuroImage, 41(2), 233–242. doi: 10.1016/j.neuroimage.2008.02.018. CrossRefPubMedGoogle Scholar
  49. Leuchter, A.F., Uijtdehaage, S.H., Cook, I.A., O’Hara, R., & Mandelkern, M. (1999). Relationship between brain electrical activity and cortical perfusion in normal subjects. Psychiatry Research, 90(2), 125–140. CrossRefPubMedGoogle Scholar
  50. Li, T.Q., Haefelin, T.N., Chan, B., Kastrup, A., Jonsson, T., Glover, G.H., et al. (2000). Assessment of hemodynamic response during focal neural activity in human using bolus tracking, arterial spin labeling and BOLD techniques. NeuroImage, 12(4), 442–451. doi: 10.1006/nimg.2000.0634. CrossRefPubMedGoogle Scholar
  51. Liau, J., & Liu, T.T. (2009). Inter-subject variability in hypercapnic normalization of the BOLD fMRI response. NeuroImage, 45(2), 420–430. doi: 10.1016/j.neuroimage.2008.11.032. CrossRefPubMedGoogle Scholar
  52. Liu, T.T., & Brown, G.G. (2007). Measurement of cerebral perfusion with arterial spin labeling: Part 1. Methods. Journal of the International Neuropsychological Society, 13(3), 517–525. doi: 10.1017/S1355617707070646. CrossRefPubMedGoogle Scholar
  53. Liu, T.T., & Liau, J. (2010). Caffeine increases the linearity of the visual BOLD response. NeuroImage, 49(3), 2311–2317. doi: 10.1016/j.neuroimage.2009.10.040. CrossRefPubMedGoogle Scholar
  54. Liu, T.T., & Wong, E.C. (2005). A signal processing model for arterial spin labeling functional MRI. NeuroImage, 24(1), 207–215. CrossRefPubMedGoogle Scholar
  55. Lu, H., & Ge, Y. (2008). Quantitative evaluation of oxygenation in venous vessels using T2-Relaxation-Under-Spin-Tagging MRI. Magnetic Resonance in Medicine, 60(2), 357–363. doi: 10.1002/mrm.21627. CrossRefPubMedGoogle Scholar
  56. Lu, H., Yezhuvath, U.S., & Xiao, G. (2010). Improving fMRI sensitivity by normalization of basal physiologic state. Human Brain Mapping, 31(1), 80–87. doi: 10.1002/hbm.20846. PubMedGoogle Scholar
  57. Lu, H., Zhao, C., Ge, Y., & Lewis-Amezcua, K. (2008). Baseline blood oxygenation modulates response amplitude: physiologic basis for intersubject variations in functional MRI signals. Magnetic Resonance in Medicine, 60(2), 364–372. doi: 10.1002/mrm.21686. CrossRefPubMedGoogle Scholar
  58. Maandag, N.J., Coman, D., Sanganahalli, B.G., Herman, P., Smith, A.J., Blumenfeld, H., et al. (2007). Energetics of neuronal signaling and fMRI activity. Proceedings of the National Academy of Sciences of the United States of America, 104(51), 20546–20551. doi: 10.1073/pnas.0709515104. CrossRefPubMedGoogle Scholar
  59. Meltzer, J., Negishi, M., Mayes, L.C., & Constable, R.T. (2007). Individual differences in EEG theta and alpha dynamics during working memory correlate with fMRI responses across subjects. Clinical Neurophysiology, 118(11), 2419–2436. doi: 10.1016/j.clinph.2007.07.023. CrossRefPubMedGoogle Scholar
  60. Nangini, C., Hlushchuk, Y., & Hari, R. (2009). Predicting stimulus-rate sensitivity of human somatosensory fMRI signals with MEG. Human Brain Mapping, 30(6), 1824–1832. doi: 10.1002/hbm.20787. CrossRefPubMedGoogle Scholar
  61. Oakes, T.R., Pizzagalli, D.A., Hendrick, A.M., Horras, K.A., Larson, C.L., Abercrombie, H.C., et al. (2004). Functional coupling of simultaneous electrical and metabolic activity in the human brain. Human Brain Mapping, 21(4), 257–270. doi: 10.1002/hbm.20004. CrossRefPubMedGoogle Scholar
  62. Ogawa, S., Menon, R.S., Tank, D.W., Kim, S.-G., Merkle, H., Ellerman, J.M., et al. (1993). Functional brain mapping by blood oxygenation level—dependent contrast magnetic resonance imaging: a comparison of signal characteristics with a biophysical model. Biophysical Journal, 64, 803–812. CrossRefPubMedGoogle Scholar
  63. Ou, W., Golland, P., & Hämäläinen, M. (2007). Sources of variability in MEG. In Medical image computing and computer-assisted intervention: MICCAI International Conference on Medical Image Computing and Computer-Assisted Intervention, 10(Pt 2) (pp. 751–759). Google Scholar
  64. Perthen, J.E., Lansing, A.E., Liau, J., Liu, T.T., & Buxton, R.B. (2008). Caffeine-induced uncoupling of cerebral blood flow and oxygen metabolism: a calibrated BOLD fMRI study. NeuroImage, 40(1), 237–247. CrossRefPubMedGoogle Scholar
  65. Pigeau, R.A., & Frame, A.M. (1992). Steady-state visual evoked responses in high and low alpha subjects. Electroencephalography and Clinical Neurophysiology, 84(2), 101–109. CrossRefPubMedGoogle Scholar
  66. Polich, J. (1997). On the relationship between EEG and P300: individual differences, aging, and ultradian rhythms. International Journal of Psychophysiology, 26(1–3), 299–317. CrossRefPubMedGoogle Scholar
  67. Restom, K., Bangen, K.J., Bondi, M.W., Perthen, J.E., & Liu, T.T. (2007). Cerebral blood flow and BOLD responses to a memory encoding task: a comparison between healthy young and elderly adults. NeuroImage, 37(2), 430–439. CrossRefPubMedGoogle Scholar
  68. Restom, K., Behzadi, Y., & Liu, T.T. (2006). Physiological noise reduction for arterial spin labeling functional MRI. NeuroImage, 31(3), 1104–1115. CrossRefPubMedGoogle Scholar
  69. Restom, K., Perthen, J.E., & Liu, T.T. (2008). Calibrated fMRI in the medial temporal lobe during a memory-encoding task. NeuroImage, 40(4), 1495–1502. CrossRefPubMedGoogle Scholar
  70. Sheth, S.A., Nemoto, M., Guiou, M., Walker, M., Pouratian, N., & Toga, A.W. (2004). Linear and nonlinear relationships between neuronal activity, oxygen metabolism, and hemodynamic responses. Neuron, 42(2), 347–355. CrossRefPubMedGoogle Scholar
  71. Sicard, K., & Duong, T. (2005). Effects of hypoxia, hyperoxia, and hypercapnia on baseline and stimulus-evoked BOLD, CBF, and CMRO in spontaneously breathing animals. NeuroImage, 25(3), 850–858. doi: 10.1016/j.neuroimage.2004.12.010. CrossRefPubMedGoogle Scholar
  72. Smith, A.J., Blumenfeld, H., Behar, K.L., Rothman, D.L., Shulman, R.G., & Hyder, F. (2002). Cerebral energetics and spiking frequency: the neurophysiological basis of fMRI. Proceedings of the National Academy of Sciences of the United States of America, 99(16), 10765–10770. doi: 10.1073/pnas.132272199. CrossRefPubMedGoogle Scholar
  73. St Lawrence, K.S., Ye, F.Q., Lewis, B.K., Frank, J.A., & McLaughlin, A.C. (2003). Measuring the effects of indomethacin on changes in cerebral oxidative metabolism and cerebral blood flow during sensorimotor activation. Magnetic Resonance in Medicine, 50(1), 99–106. CrossRefGoogle Scholar
  74. Stefanovic, B., Warnking, J.M., Kobayashi, E., Bagshaw, A.P., Hawco, C., Dubeau, F., et al. (2005). Hemodynamic and metabolic responses to activation, deactivation and epileptic discharges. NeuroImage, 28(1), 205–215. CrossRefPubMedGoogle Scholar
  75. Thomason, M.E., Foland, L.C., & Glover, G.H. (2007). Calibration of BOLD fMRI using breath holding reduces group variance during a cognitive task. Human Brain Mapping, 28(1), 59–68. CrossRefPubMedGoogle Scholar
  76. Thomason, M.E., & Glover, G.H. (2008). Controlled inspiration depth reduces variance in breath-holding-induced BOLD signal. NeuroImage, 39(1), 206–214. doi: 10.1016/j.neuroimage.2007.08.014. CrossRefPubMedGoogle Scholar
  77. Tobimatsu, S., Tomoda, H., & Kato, M. (1996). Normal variability of the amplitude and phase of steady-state VEPs. Electroencephalography and Clinical Neurophysiology, 100(3), 171–176. CrossRefPubMedGoogle Scholar
  78. Vasquez, A.L., & Noll, D.C. (1998). Nonlinear aspects of the BOLD response in functional MRI. NeuroImage, 7, 108–118. CrossRefGoogle Scholar
  79. Wager, T.D., Vazquez, A., Hernandez, L., & Noll, D.C. (2005). Accounting for nonlinear BOLD effects in fMRI: parameter estimates and a model for prediction in rapid event-related studies. NeuroImage, 25(1), 206–218. CrossRefPubMedGoogle Scholar
  80. Wise, R.G., Ide, K., Poulin, M.J., & Tracey, I. (2004). Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal. NeuroImage, 21(4), 1652–1664. CrossRefPubMedGoogle Scholar
  81. Xu, F., Uh, J., Brier, M.R., Hart, J., Yezhuvath, U.S., Gu, H., et al. (2011). The influence of carbon dioxide on brain activity and metabolism in conscious humans. Journal of Cerebral Blood Flow and Metabolism, 31(1), 58–67. doi: 10.1038/jcbfm.2010.153. CrossRefPubMedGoogle Scholar
  82. Zappe, A.C., Uludağ, K., Oeltermann, A., Uğurbil, K., & Logothetis, N.K. (2008). The influence of moderate hypercapnia on neural activity in the anesthetized nonhuman primate. Cerebral Cortex, 18(11), 2666–2673. doi: 10.1093/cercor/bhn023. CrossRefPubMedGoogle Scholar

Copyright information

© The Psychometric Society 2012

Authors and Affiliations

  • Thomas T. Liu
    • 1
    Email author
  • Gary H. Glover
    • 2
  • Bryon A. Mueller
    • 3
  • Douglas N. Greve
    • 4
  • Gregory G. Brown
    • 5
  1. 1.Center for Functional MRIUniversity of California San DiegoLa JollaUSA
  2. 2.Department of RadiologyStanford UniversityStanfordUSA
  3. 3.Department of Psychiatry, CMRRUniversity of MinnesotaMinneapolisUSA
  4. 4.Department of Radiology, Martinos Center for Biomedical ImagingMassachusetts General HospitalCharlestownUSA
  5. 5.VA San Diego Healthcare System, Psychology Service (116B) and Department of PsychiatryUniversity of California San DiegoSan DiegoUSA

Personalised recommendations