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Applications of fMRI in translational medicine and clinical practice

Key Points

  • Functional MRI (fMRI) has had a major impact in cognitive neuroscience. It now has promising applications in clinical and translational medicine.

  • fMRI can assess changes in relative blood oxygenation accompanying increased blood flow in regions of the brain that are active while a task (for example, hand movement) is performed. The most well-established clinical application of fMRI is for presurgical mapping; this guides a neurosurgeon to spare brain tissue that, if injured, would cause new clinical deficits or limit good recovery.

  • In combination with simultaneously acquired electroencephalography (EEG), fMRI can image blood oxygenation state changes that accompany spontaneously generated changes in brain state in order to localize the source of seizure-inducing activity in epilepsy. The spatial definition of MRI allows this to be done at a much higher resolution than with EEG alone.

  • A frontier area for fMRI is in the identification of neurophysiologically based intermediate phenotypes in ways that can characterize even disorders that do not show structural changes in the brain. Recent applications suggest that functional intermediate phenotypes could better define heterogeneity in psychotic and affective disorders, and could be used to predict treatment outcomes.

  • In some instances, intermediate phenotypes that are heritable are endophenotypes. Because endophenotypes can be determined by smaller numbers of genes than conventional clinical phenotypes, in some cases plausible allelic associations have been identified with sample sizes smaller than those required in usual association studies.

  • By defining functional anatomy that is related to behavioural or perceptual states, fMRI can also help to directly understand the genesis of symptoms. For example, fMRI dissection of the subjective experience of pain into anatomically distinct activities of different functional systems provides a rationale for treatment approaches that are based on the modulation of different, interacting pathways.

  • Applications of fMRI as a pharmacodynamic (or pharmacokinetic) measure (pharmacological fMRI or phMRI) suggest that it might assume an important role in drug development. There are already several examples in which fMRI has been shown to be sensitive to change after a therapeutic intervention.

  • However, there remain practical problems that need to be resolved before fMRI can be used routinely. Signal changes are small, there are many confounds affecting the signal-to-noise ratio and the underlying physiological response itself is highly variable.

  • The promise of this new technique is substantial, but it is clear that the widespread introduction of clinical fMRI will demand new skills and working methods in clinical neuroradiology if this promise is to be delivered.


Functional MRI (fMRI) has had a major impact in cognitive neuroscience. fMRI now has a small but growing role in clinical neuroimaging, with initial applications to neurosurgical planning. Current clinical research has emphasized novel concepts for clinicians, such as the role of plasticity in recovery and the maintenance of brain functions in a broad range of diseases. There is a wider potential for clinical fMRI in applications ranging from presymptomatic diagnosis, through drug development and individualization of therapies, to understanding functional brain disorders. Realization of this potential will require changes in the way clinical neuroimaging services are planned and delivered.

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Figure 1: Applications of multimodal MRI to brain lesion characterization.
Figure 2: Integrated electroencephalography and fMRI for epilepsy.
Figure 3: Pharmacological functional MRI (phMRI) allows drug effects in the brain to be defined from their modulation of activity.
Figure 4: Monitoring of long-term brain activity changes with a chronic treatment intervention.


  1. 1

    Matthews, P. M. & Jezzard, P. Functional magnetic resonance imaging. J. Neurol. Neurosurg. Psychiatr. 75, 6–12 (2004).

    CAS  Google Scholar 

  2. 2

    Belliveau, J. W. et al. Magnetic resonance imaging mapping of brain function. Human visual cortex. Invest. Radiol. 27, S59–S65 (1992).

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3

    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). This seminal paper describes the theory and phenomenon of fMRI, supported by a compelling series of experiments. A methods paper that is almost unrivalled for completeness and clarity in this young field.

    Article  CAS  Google Scholar 

  4. 4

    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 

  5. 5

    Cabeza, R. & Nyberg, L. Imaging cognition II: an empirical review of 275 PET and fMRI studies. J. Cogn. Neurosci. 12, 1–47 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. 6

    Yousry, T. A. et al. Localization of the motor hand area to a knob on the precentral gyrus. A new landmark. Brain 120, 141–157 (1997).

    Article  PubMed  Google Scholar 

  7. 7

    Price, C. J. The anatomy of language: contributions from functional neuroimaging. J. Anat. 197, 335–359 (2000).

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8

    van Westen, D. et al. Fingersomatotopy in area 3b: an fMRI-study. BMC Neurosci. 5, 28 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9

    Uylings, H. B., Rajkowska, G., Sanz-Arigita, E., Amunts, K. & Zilles, K. Consequences of large interindividual variability for human brain atlases: converging macroscopical imaging and microscopical neuroanatomy. Anat. Embryol. (Berl) 210, 423–431 (2005).

    Article  CAS  Google Scholar 

  10. 10

    Haberg, A., Kvistad, K. A., Unsgard, G. & Haraldseth, O. Preoperative blood oxygen level-dependent functional magnetic resonance imaging in patients with primary brain tumors: clinical application and outcome. Neurosurgery 54, 902–914; discussion 914–915 (2004).

    Article  PubMed  Google Scholar 

  11. 11

    Lee, M. et al. The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis. Ann. Neurol. 47, 606–613 (2000). Provides evidence from patients with multiple sclerosis that adaptive plasticity acts as a general mechanism to limit expression of the disability caused by brain injury or disease, even in adults.

    Article  CAS  PubMed  Google Scholar 

  12. 12

    Adcock, J. E., Wise, R. G., Oxbury, J. M., Oxbury, S. M. & Matthews, P. M. Quantitative fMRI assessment of the differences in lateralization of language-related brain activation in patients with temporal lobe epilepsy. Neuroimage 18, 423–438 (2003).

    Article  CAS  PubMed  Google Scholar 

  13. 13

    Binder, J. R. et al. Determination of language dominance using functional MRI: a comparison with the Wada test. Neurology 46, 978–984 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. 14

    Rutten, G. J. et al. Toward functional neuronavigation: implementation of functional magnetic resonance imaging data in a surgical guidance system for intraoperative identification of motor and language cortices. Technical note and illustrative case. Neurosurg. Focus 15, E6 (2003).

    PubMed  PubMed Central  Google Scholar 

  15. 15

    Fischer, M. J., Scheler, G. & Stefan, H. Utilization of magnetoencephalography results to obtain favourable outcomes in epilepsy surgery. Brain 128, 153–157 (2005).

    Article  PubMed  Google Scholar 

  16. 16

    Gralla, J. et al. Image-guided removal of supratentorial cavernomas in critical brain areas: application of neuronavigation and intraoperative magnetic resonance imaging. Minim. Invasive. Neurosurg. 46, 72–77 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. 17

    Liegeois, F. et al. Language reorganization in children with early-onset lesions of the left hemisphere: an fMRI study. Brain 127, 1229–1236 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. 18

    Richardson, M. P. et al. Pre-operative verbal memory fMRI predicts post-operative memory decline after left temporal lobe resection. Brain 127, 2419–2426 (2004).

    Article  PubMed  Google Scholar 

  19. 19

    Ramnani, N., Behrens, T. E., Penny, W. & Matthews, P. M. New approaches for exploring anatomical and functional connectivity in the human brain. Biol. Psychiatry 56, 613–619 (2004).

    Article  PubMed  Google Scholar 

  20. 20

    Wilms, G., Demaerel, P. & Sunaert, S. Intra-axial brain tumours. Eur. Radiol. 15, 468–484 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. 21

    Devlin, J. T. et al. Reliable identification of the auditory thalamus using multi-modal structural analyses. Neuroimage 30, 1112–1120 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Behrens, T. E. et al. Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nature Neurosci. 6, 750–757 (2003).

    Article  CAS  PubMed  Google Scholar 

  23. 23

    Johansen-Berg, H. et al. Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex. Proc. Natl Acad. Sci. USA 101, 13335–13340 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. 24

    Hesselmann, V. et al. Intraoperative functional MRI as a new approach to monitor deep brain stimulation in Parkinson's disease. Eur. Radiol. 14, 686–690 (2004).

    Article  PubMed  Google Scholar 

  25. 25

    Georgi, J. C., Stippich, C., Tronnier, V. M. & Heiland, S. Active deep brain stimulation during MRI: a feasibility study. Magn. Reson. Med. 51, 380–388 (2004).

    Article  PubMed  Google Scholar 

  26. 26

    Brammer, M. J. in Functional MRI: An Introduction to Methods (eds Jezzard, P., Matthews, P. M. & Smith, S.) 243–250 (Oxford University Press, Oxford, 2001).

    Google Scholar 

  27. 27

    Tjandra, T. et al. Quantitative assessment of the reproducibility of functional activation measured with BOLD and MR perfusion imaging: implications for clinical trial design. Neuroimage 27, 393–401 (2005).

    Article  PubMed  Google Scholar 

  28. 28

    Johansen-Berg, H. et al. The role of ipsilateral premotor cortex in hand movement after stroke. Proc. Natl Acad. Sci. USA 99, 14518–14523 (2002). Illustrates, with the analysis of ipsilateral motor cortical activity in recovery after a motor stroke, the potential for transcranial magnetic stimulation to be used as a way of testing the functional significance of activity associated with a behaviour assessed by fMRI.

    Article  CAS  PubMed  Google Scholar 

  29. 29

    Schwarz, A. J. et al. Concurrent pharmacological MRI and in situ microdialysis of cocaine reveal a complex relationship between the central hemodynamic response and local dopamine concentration. Neuroimage 23, 296–304 (2004).

    Article  CAS  Google Scholar 

  30. 30

    Shulman, R. G., Rothman, D. L., Behar, K. L. & Hyder, F. Energetic basis of brain activity: implications for neuroimaging. Trends Neurosci. 27, 489–495 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. 31

    Gracco, V. L., Tremblay, P. & Pike, B. Imaging speech production using fMRI. Neuroimage 26, 294–301 (2005).

    Article  PubMed  Google Scholar 

  32. 32

    Hadjikhani, N. et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc. Natl Acad. Sci. USA 98, 4687–4692 (2001). An elegant demonstration of how spontaneous activity can be imaged in the brain, using fMRI to better define the relationship between neurophysiological changes and symptoms in migraine.

    Article  CAS  PubMed  Google Scholar 

  33. 33

    Cao, Y., Aurora, S. K., Nagesh, V., Patel, S. C. & Welch, K. M. Functional MRI-BOLD of brainstem structures during visually triggered migraine. Neurology 59, 72–78 (2002).

    Article  CAS  PubMed  Google Scholar 

  34. 34

    Lemieux, L. Electroencephalography-correlated functional MR imaging studies of epileptic activity. Neuroimaging Clin. N. Am. 14, 487–506 (2004).

    Article  PubMed  Google Scholar 

  35. 35

    Boor, S. et al. EEG-related functional MRI in benign childhood epilepsy with centrotemporal spikes. Epilepsia 44, 688–692 (2003).

    Article  PubMed  Google Scholar 

  36. 36

    Gotman, J. et al. Generalized epileptic discharges show thalamocortical activation and suspension of the default state of the brain. Proc. Natl Acad. Sci. USA 102, 15236–15240 (2005). This paper makes the compelling argument that central generators for primary generalized epilepsy are localized in the thalamus on the basis of combined EEG and fMRI studies: a striking example of the application of this new integration of technology for exciting new clinical neuroscience.

    Article  CAS  PubMed  Google Scholar 

  37. 37

    Lemieux, L., Allen, P. J., Franconi, F., Symms, M. R. & Fish, D. R. Recording of EEG during fMRI experiments: patient safety. Magn. Reson. Med. 38, 943–952 (1997).

    Article  CAS  PubMed  Google Scholar 

  38. 38

    Niazy, R. K., Beckmann, C. F., Iannetti, G. D., Brady, J. M. & Smith, S. M. Removal of FMRI environment artifacts from EEG data using optimal basis sets. Neuroimage 28, 720–737 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. 39

    Gottesman, I. I. & Gould, T. D. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 160, 636–645 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40

    Egan, M. F. et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc. Natl Acad. Sci. USA 98, 6917–6922 (2001). One of a series of papers illustrating how imaging can be used as an endophenotype for the characterization of genes that influence complex disease expression. The Weinberger laboratory has pioneered this approach for psychiatric disease.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 41

    Egan, M. F. et al. Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc. Natl Acad. Sci. USA 101, 12604–12609 (2004).

    Article  CAS  PubMed  Google Scholar 

  42. 42

    Fu, C. H. et al. Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Arch. Gen. Psychiatry 61, 877–889 (2004). One of the first studies to show how fMRI could be used to provide a short-term outcome measure that is potentially predictive of longer-term clinical treatment responses.

    Article  PubMed  Google Scholar 

  43. 43

    Kippenhan, J. S. et al. Genetic contributions to human gyrification: sulcal morphometry in Williams syndrome. J. Neurosci. 25, 7840–7846 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Thompson, P. M. et al. Abnormal cortical complexity and thickness profiles mapped in Williams syndrome. J. Neurosci. 25, 4146–4158 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Tomaiuolo, F. et al. Morphology and morphometry of the corpus callosum in Williams syndrome: a T1-weighted MRI study. Neuroreport 13, 2281–2284 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. 46

    Jones, W. et al. Cerebellar abnormalities in infants and toddlers with Williams syndrome. Dev. Med. Child. Neurol. 44, 688–694 (2002).

    Article  PubMed  Google Scholar 

  47. 47

    Meyer-Lindenberg, A. et al. Neural correlates of genetically abnormal social cognition in Williams syndrome. Nature Neurosci. 8, 991–993 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Meyer-Lindenberg, A. et al. Neural basis of genetically determined visuospatial construction deficit in Williams syndrome. Neuron 43, 623–631 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

    Honey, G. D. et al. Functional dysconnectivity in schizophrenia associated with attentional modulation of motor function. Brain 128, 2597–2611 (2005).

    Article  PubMed  Google Scholar 

  50. 50

    Honey, G. D. et al. The functional neuroanatomy of schizophrenic subsyndromes. Psychol. Med. 33, 1007–1018 (2003).

    Article  CAS  PubMed  Google Scholar 

  51. 51

    MacDonald, A. W. et al. Specificity of prefrontal dysfunction and context processing deficits to schizophrenia in never-medicated patients with first-episode psychosis. Am. J. Psychiatry 162, 475–484 (2005).

    Article  PubMed  Google Scholar 

  52. 52

    Barch, D. M., Sheline, Y. I., Csernansky, J. G. & Snyder, A. Z. Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression. Biol. Psychiatry 53, 376–384 (2003).

    Article  Google Scholar 

  53. 53

    Callicott, J. H. et al. Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am. J. Psychiatry 160, 709–719 (2003).

    Article  PubMed  Google Scholar 

  54. 54

    Whalley, H. C. et al. fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia. Brain 127, 478–490 (2004).

    Article  CAS  PubMed  Google Scholar 

  55. 55

    Morey, R. A. et al. Imaging frontostriatal function in ultra-high-risk, early, and chronic schizophrenia during executive processing. Arch. Gen. Psychiatry 62, 254–262 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56

    Whalley, H. C. et al. Functional disconnectivity in subjects at high genetic risk of schizophrenia. Brain 128, 2097–2108 (2005).

    Article  PubMed  Google Scholar 

  57. 57

    Whalley, H. C. et al. Functional Imaging as a Predictor of Schizophrenia. Biol. Psychiatry 7 Feb 2006 (doi:10.1016/j.biopsych.2005.11.013).

  58. 58

    Callicott, J. H. et al. Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc. Natl Acad. Sci. USA 102, 8627–8632 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. 59

    Hariri, A. R. et al. A susceptibility gene for affective disorders and the response of the human amygdala. Arch. Gen. Psychiatry 62, 146–152 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. 60

    Hariri, A. R. et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 297, 400–403 (2002).

    Article  CAS  Google Scholar 

  61. 61

    Pezawas, L. et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nature Neurosci. 8, 828–834 (2005). An unusually complete paper that integrates information from brain structure, function as determined by fMRI and genetics to test more fully a compelling hypothesis regarding the genesis of depression.

    Article  CAS  PubMed  Google Scholar 

  62. 62

    Heinz, A. et al. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nature Neurosci. 8, 20–21 (2005).

    Article  CAS  PubMed  Google Scholar 

  63. 63

    Smith, K. A. et al. Cerebellar responses during anticipation of noxious stimuli in subjects recovered from depression. Functional magnetic resonance imaging study. Br. J. Psychiatry 181, 411–415 (2002).

    Article  CAS  PubMed  Google Scholar 

  64. 64

    Baghai, T. C., Moller, H. J. & Rupprecht, R. Recent progress in pharmacological and non-pharmacological treatment options of major depression. Curr. Pharm. Des. 12, 503–515 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. 65

    Sheline, Y. I. et al. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol. Psychiatry 50, 651–658 (2001).

    Article  CAS  PubMed  Google Scholar 

  66. 66

    Canli, T. et al. Amygdala reactivity to emotional faces predicts improvement in major depression. Neuroreport 16, 1267–1270 (2005).

    Article  PubMed  Google Scholar 

  67. 67

    Killgore, W. D. & Yurgelun-Todd, D. A. Ventromedial prefrontal activity correlates with depressed mood in adolescent children. Neuroreport 17, 167–171 (2006).

    Article  PubMed  Google Scholar 

  68. 68

    Anand, A. et al. Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study. Neuropsychopharmacology 30, 1334–1344 (2005).

    Article  CAS  PubMed  Google Scholar 

  69. 69

    David, S. P. et al. Ventral striatum/nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers: a functional magnetic resonance imaging study. Biol. Psychiatry 58, 488–494 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  70. 70

    Myrick, H. et al. Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving. Neuropsychopharmacology 29, 393–402 (2004).

    Article  CAS  PubMed  Google Scholar 

  71. 71

    Reuter, J. et al. Pathological gambling is linked to reduced activation of the mesolimbic reward system. Nature Neurosci. 8, 147–148 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Paulus, M. P., Tapert, S. F. & Schuckit, M. A. Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse. Arch. Gen. Psychiatry 62, 761–768 (2005).

    Article  PubMed  Google Scholar 

  73. 73

    Kaufman, J. N., Ross, T. J., Stein, E. A. & Garavan, H. Cingulate hypoactivity in cocaine users during a GO-NOGO task as revealed by event-related functional magnetic resonance imaging. J. Neurosci. 23, 7839–7843 (2003).

    Article  CAS  PubMed  Google Scholar 

  74. 74

    Forman, S. D. et al. Opiate addicts lack error-dependent activation of rostral anterior cingulate. Biol. Psychiatry 55, 531–537 (2004).

    Article  CAS  PubMed  Google Scholar 

  75. 75

    Heinz, A. et al. Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. Am. J. Psychiatry 161, 1783–1789 (2004). A pioneering study relating variations in apparent striatal dopamine receptor density determined by PET with inter-individual differences in orbitofrontal cortex activity and alcohol craving among abstinent alcoholics.

    Article  PubMed  Google Scholar 

  76. 76

    Wexler, B. E. et al. Functional magnetic resonance imaging of cocaine craving. Am. J. Psychiatry 158, 86–95 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. 77

    Mattay, V. S. et al. Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc. Natl Acad. Sci. USA 100, 6186–6191 (2003).

    Article  CAS  PubMed  Google Scholar 

  78. 78

    Schweinsburg, A. D. et al. An FMRI study of response inhibition in youths with a family history of alcoholism. Ann. NY Acad. Sci. 1021, 391–394 (2004).

    Article  PubMed  Google Scholar 

  79. 79

    Ballmaier, M. & Schmidt, R. Conversion disorder revisited. Funct. Neurol. 20, 105–113 (2005).

    PubMed  PubMed Central  Google Scholar 

  80. 80

    Marshall, J. C., Halligan, P. W., Fink, G. R., Wade, D. T. & Frackowiak, R. S. The functional anatomy of a hysterical paralysis. Cognition 64, B1–B8 (1997).

    Article  CAS  PubMed  Google Scholar 

  81. 81

    Halligan, P. W., Bass, C. & Wade, D. T. New approaches to conversion hysteria. BMJ 320, 1488–1489 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. 82

    Mailis-Gagnon, A. et al. Altered central somatosensory processing in chronic pain patients with 'hysterical' anesthesia. Neurology 60, 1501–1507 (2003).

    Article  CAS  PubMed  Google Scholar 

  83. 83

    Spence, S. A., Crimlisk, H. L., Cope, H., Ron, M. A. & Grasby, P. M. Discrete neurophysiological correlates in prefrontal cortex during hysterical and feigned disorder of movement. Lancet 355, 1243–1244 (2000).

    Article  CAS  PubMed  Google Scholar 

  84. 84

    Werring, D. J., Weston, L., Bullmore, E. T., Plant, G. T. & Ron, M. A. Functional magnetic resonance imaging of the cerebral response to visual stimulation in medically unexplained visual loss. Psychol. Med. 34, 583–589 (2004).

    Article  CAS  PubMed  Google Scholar 

  85. 85

    Caesar, K., Thomsen, K. & Lauritzen, M. Dissociation of spikes, synaptic activity, and activity-dependent increments in rat cerebellar blood flow by tonic synaptic inhibition. Proc. Natl Acad. Sci. USA 100, 16000–16005 (2003).

    Article  CAS  Google Scholar 

  86. 86

    Bookheimer, S. Y. et al. Patterns of brain activation in people at risk for Alzheimer's disease. N. Engl. J. Med. 343, 450–456 (2000). An early fMRI clinical applications study suggesting that the initial phases of Alzheimer's disease might not be manifested clinically because of adaptive changes in brain functions in compensation. These changes could be used as a marker of risk in some high-risk populations.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. 87

    Reddy, H. et al. Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis. Brain 123, 2314–2320 (2000).

    Article  PubMed  Google Scholar 

  88. 88

    Rombouts, S. A. et al. Loss of frontal fMRI activation in early frontotemporal dementia compared to early AD. Neurology 60, 1904–1908 (2003).

    Article  CAS  PubMed  Google Scholar 

  89. 89

    Floyer-Lea, A. & Matthews, P. M. Changing brain networks for visuomotor control with increased movement automaticity. J. Neurophysiol. 92, 2405–2412 (2004).

    Article  CAS  PubMed  Google Scholar 

  90. 90

    Parry, A. M., Scott, R. B., Palace, J., Smith, S. & Matthews, P. M. Potentially adaptive functional changes in cognitive processing for patients with multiple sclerosis and their acute modulation by rivastigmine. Brain 126, 2750–2760 (2003).

    Article  PubMed  Google Scholar 

  91. 91

    Iaria, G., Petrides, M., Dagher, A., Pike, B. & Bohbot, V. D. Cognitive strategies dependent on the hippocampus and caudate nucleus in human navigation: variability and change with practice. J. Neurosci. 23, 5945–5952 (2003). Illustrates how important cognitive strategy is to the pattern of fMRI brain activation associated with a given task.

    Article  CAS  PubMed  Google Scholar 

  92. 92

    Vlieger, E. J., Lavini, C., Majoie, C. B. & den Heeten, G. J. Reproducibility of functional MR imaging results using two different MR systems. AJNR Am. J. Neuroradiol. 24, 652–657 (2003).

    PubMed  PubMed Central  Google Scholar 

  93. 93

    Maxim, V. et al. Fractional Gaussian noise, functional MRI and Alzheimer's disease. Neuroimage 25, 141–158 (2005).

    Article  PubMed  Google Scholar 

  94. 94

    Krings, T. et al. Functional MRI for presurgical planning: problems, artefacts, and solution strategies. J. Neurol. Neurosurg. Psychiatry 70, 749–760 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. 95

    Smith, S. M. et al. Variability in fMRI: a re-examination of inter-session differences. Hum. Brain Mapp. 24, 248–257 (2005).

    Article  Google Scholar 

  96. 96

    Ward, N. S. & Frackowiak, R. S. Age-related changes in the neural correlates of motor performance. Brain 126, 873–888 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. 97

    D'Esposito, M., Deouell, L. Y. & Gazzaley, A. Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nature Rev. Neurosci. 4, 863–872 (2003).

    Article  CAS  Google Scholar 

  98. 98

    Laurienti, P. J. et al. Relationship between caffeine-induced changes in resting cerebral perfusion and blood oxygenation level-dependent signal. AJNR Am. J. Neuroradiol. 24, 1607–1611 (2003).

    PubMed  PubMed Central  Google Scholar 

  99. 99

    Lawrence, N. S., Ross, T. J. & Stein, E. A. Cognitive mechanisms of nicotine on visual attention. Neuron 36, 539–548 (2002).

    Article  CAS  PubMed  Google Scholar 

  100. 100

    St Lawrence, K. S., Ye, F. Q., Lewis, B. K., Frank, J. A. & McLaughlin, A. C. Measuring the effects of indomethacin on changes in cerebral oxidative metabolism and cerebral blood flow during sensorimotor activation. Magn. Reson. Med. 50, 99–106 (2003).

    Article  CAS  PubMed  Google Scholar 

  101. 101

    Tracey, I. Nociceptive processing in the human brain. Curr. Opin. Neurobiol. 15, 478–487 (2005).

    Article  CAS  PubMed  Google Scholar 

  102. 102

    Gundel, H., O'Connor, M. F., Littrell, L., Fort, C. & Lane, R. D. Functional neuroanatomy of grief: an FMRI study. Am. J. Psychiatry 160, 1946–1953 (2003).

    Article  PubMed  Google Scholar 

  103. 103

    Saarela, M. V. et al. The compassionate brain: humans detect intensity of pain from another's face. Cereb. Cortex 22 Feb 2006 (doi:10.1093/cercor/bhj141).

  104. 104

    Borsook, D., Ploghaus, A. & Becerra, L. Utilizing brain imaging for analgesic drug development. Curr. Opin. Investig. Drugs 3, 1342–1347 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. 105

    Coghill, R. C., McHaffie, J. G. & Yen, Y. F. Neural correlates of interindividual differences in the subjective experience of pain. Proc. Natl Acad. Sci. USA 100, 8538–8542 (2003).

    Article  CAS  PubMed  Google Scholar 

  106. 106

    Wise, R. G. et al. Combining fMRI with a pharmacokinetic model to determine which brain areas activated by painful stimulation are specifically modulated by remifentanil. Neuroimage 16, 999–1014 (2002).

    Article  Google Scholar 

  107. 107

    Rogers, R., Wise, R. G., Painter, D. J., Longe, S. E. & Tracey, I. An investigation to dissociate the analgesic and anesthetic properties of ketamine using functional magnetic resonance imaging. Anesthesiology 100, 292–301 (2004).

    Article  CAS  PubMed  Google Scholar 

  108. 108

    Koeppe, C. et al. The influence of the 5-HT3 receptor antagonist tropisetron on pain in fibromyalgia: a functional magnetic resonance imaging pilot study. Scand. J. Rheumatol. Suppl., 24–27 (2004).

  109. 109

    Lieberman, M. D. et al. The neural correlates of placebo effects: a disruption account. Neuroimage 22, 447–455 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  110. 110

    Petrovic, P. et al. Placebo in emotional processing — induced expectations of anxiety relief activate a generalized modulatory network. Neuron 46, 957–969 (2005). Synthesizes hypotheses regarding the placebo effect in the immediate context of recent imaging studies and suggests that the functioning of reward and motivational systems might account for mechanisms of the placebo effect across different types of noxious stimulus.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. 111

    Wager, T. D. et al. Placebo-induced changes in FMRI in the anticipation and experience of pain. Science 303, 1162–1167 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. 112

    Henderson, L. A., Bandler, R., Gandevia, S. C. & Macefield, V. G. Distinct forebrain activity patterns during deep versus superficial pain. Pain 120, 286–296 (2006).

    Article  CAS  PubMed  Google Scholar 

  113. 113

    Singer, T. et al. Empathy for pain involves the affective but not sensory components of pain. Science 303, 1157–1162 (2004).

    Article  CAS  Google Scholar 

  114. 114

    Dierks, T. et al. Activation of Heschl's gyrus during auditory hallucinations. Neuron 22, 615–621 (1999).

    Article  CAS  PubMed  Google Scholar 

  115. 115

    Shergill, S. S. et al. Temporal course of auditory hallucinations. Br. J. Psychiatry 185, 516–517 (2004).

    Article  PubMed  Google Scholar 

  116. 116

    Shergill, S. S., Brammer, M. J., Williams, S. C., Murray, R. M. & McGuire, P. K. Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging. Arch. Gen. Psychiatry 57, 1033–1038 (2000).

    Article  CAS  PubMed  Google Scholar 

  117. 117

    Hunter, M. D. et al. A neural basis for the perception of voices in external auditory space. Brain 126, 161–169 (2003).

    Article  PubMed  Google Scholar 

  118. 118

    Jacobs, L. D. et al. Intramuscular interferon β-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N. Engl. J. Med. 343, 898–904 (2000).

    Article  CAS  PubMed  Google Scholar 

  119. 119

    Aylward, E. H. et al. Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington's disease. Mov. Disord. 15, 552–560 (2000).

    Article  CAS  PubMed  Google Scholar 

  120. 120

    den Heijer, T. et al. Use of hippocampal and amygdalar volumes on magnetic resonance imaging to predict dementia in cognitively intact elderly people. Arch. Gen. Psychiatry 63, 57–62 (2006).

    Article  PubMed  Google Scholar 

  121. 121

    Kim, J. S. et al. Functional MRI study of a serial reaction time task in Huntington's disease. Psychiatry Res. 131, 23–30 (2004).

    Article  PubMed  Google Scholar 

  122. 122

    Dickerson, B. C. et al. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65, 404–411 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. 123

    Chong, M. S. & Sahadevan, S. Preclinical Alzheimer's disease: diagnosis and prediction of progression. Lancet Neurol. 4, 576–579 (2005).

    Article  PubMed  Google Scholar 

  124. 124

    Honey, G. & Bullmore, E. Human pharmacological MRI. Trends Pharmacol. Sci. 25, 366–374 (2004).

    Article  CAS  Google Scholar 

  125. 125

    Stein, E. A. et al. Nicotine-induced limbic cortical activation in the human brain: a functional MRI study. Am. J. Psychiatry 155, 1009–1015 (1998).

    Article  CAS  Google Scholar 

  126. 126

    Vollm, B. A. et al. Methamphetamine activates reward circuitry in drug naive human subjects. Neuropsychopharmacology 29, 1715–1722 (2004).

    Article  CAS  Google Scholar 

  127. 127

    Gerdelat-Mas, A. et al. Chronic administration of selective serotonin reuptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects. Neuroimage 27, 314–322 (2005).

    Article  CAS  PubMed  Google Scholar 

  128. 128

    Pariente, J. et al. Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke. Ann. Neurol. 50, 718–729 (2001).

    Article  CAS  PubMed  Google Scholar 

  129. 129

    Goekoop, R. et al. Raloxifene exposure enhances brain activation during memory performance in healthy elderly males; its possible relevance to behavior. Neuroimage 25, 63–75 (2005).

    Article  CAS  PubMed  Google Scholar 

  130. 130

    Goekoop, R. et al. Challenging the cholinergic system in mild cognitive impairment: a pharmacological fMRI study. Neuroimage 23, 1450–1459 (2004).

    Article  PubMed  Google Scholar 

  131. 131

    Farahani, K., Slates, R., Shao, Y., Silverman, R. & Cherry, S. Contemporaneous positron emission tomography and MR imaging at 1.5 T. J. Magn. Reson. Imaging 9, 497–500 (1999).

    Article  CAS  PubMed  Google Scholar 

  132. 132

    Buxton, R. B., Uludag, K., Dubowitz, D. J. & Liu, T. T. Modeling the hemodynamic response to brain activation. Neuroimage 23, S220–S233 (2004).

    Article  PubMed  Google Scholar 

  133. 133

    Nahas, Z. et al. Augmenting atypical antipsychotics with a cognitive enhancer (donepezil) improves regional brain activity in schizophrenia patients: a pilot double-blind placebo controlled BOLD fMRI study. Neurocase 9, 274–282 (2003).

    Article  PubMed  Google Scholar 

  134. 134

    Rombouts, S. A., Barkhof, F., Van Meel, C. S. & Scheltens, P. Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 73, 665–671 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. 135

    Saykin, A. J. et al. Cholinergic enhancement of frontal lobe activity in mild cognitive impairment. Brain 127, 1574–1583 (2004).

    Article  PubMed  Google Scholar 

  136. 136

    Mattay, V. S. et al. Dopaminergic modulation of cortical function in patients with Parkinson's disease. Ann. Neurol. 51, 156–164 (2002).

    Article  CAS  PubMed  Google Scholar 

  137. 137

    Wilkinson, D. & Halligan, P. The relevance of behavioural measures for functional-imaging studies of cognition. Nature Rev. Neurosci. 5, 67–73 (2004).

    Article  CAS  Google Scholar 

  138. 138

    Matthews, P. M., Johansen-Berg, H. & Reddy, H. Non-invasive mapping of brain functions and brain recovery: applying lessons from cognitive neuroscience to neurorehabilitation. Restor. Neurol. Neurosci. 22, 245–260 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. 139

    Sadato, N. How the blind 'see' Braille: lessons from functional magnetic resonance imaging. Neuroscientist 11, 577–582 (2005).

    Article  PubMed  Google Scholar 

  140. 140

    Burton, H. et al. Adaptive changes in early and late blind: a fMRI study of Braille reading. J. Neurophysiol. 87, 589–607 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. 141

    Seitz, R. J. et al. Large-scale plasticity of the human motor cortex. Neuroreport 6, 742–744 (1995).

    Article  CAS  PubMed  Google Scholar 

  142. 142

    Calautti, C. & Baron, J. C. Functional neuroimaging studies of motor recovery after stroke in adults: a review. Stroke 34, 1553–1566 (2003).

    Article  PubMed  Google Scholar 

  143. 143

    Pantano, P. et al. Contribution of corticospinal tract damage to cortical motor reorganization after a single clinical attack of multiple sclerosis. Neuroimage 17, 1837–1843 (2002).

    Article  PubMed  Google Scholar 

  144. 144

    Reddy, H. et al. Relating axonal injury to functional recovery in MS. Neurology 54, 236–239 (2000).

    Article  CAS  PubMed  Google Scholar 

  145. 145

    Lee, M. A. et al. Axonal injury or loss in the internal capsule and motor impairment in multiple sclerosis. Arch. Neurol. 57, 65–70 (2000).

    Article  CAS  PubMed  Google Scholar 

  146. 146

    Rocca, M. A. et al. Evidence for widespread movement-associated functional MRI changes in patients with PPMS. Neurology 58, 866–872 (2002).

    Article  CAS  PubMed  Google Scholar 

  147. 147

    Luft, A. R. et al. Lesion location alters brain activation in chronically impaired stroke survivors. Neuroimage 21, 924–935 (2004).

    Article  PubMed  Google Scholar 

  148. 148

    Reddy, H. et al. Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability. Brain 125, 2646–2657 (2002).

    Article  CAS  PubMed  Google Scholar 

  149. 149

    Taub, E., Uswatte, G. & Elbert, T. New treatments in neurorehabilitation founded on basic research. Nature Rev. Neurosci. 3, 228–236 (2002).

    Article  CAS  Google Scholar 

  150. 150

    Ward, N. S. et al. Motor system activation after subcortical stroke depends on corticospinal system integrity. Brain 129, 809–819 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  151. 151

    Ward, N. S. & Cohen, L. G. Mechanisms underlying recovery of motor function after stroke. Arch. Neurol. 61, 1844–1848 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  152. 152

    Wade, D. T. Rehabilitation research — time for a change of focus. Lancet Neurol. 1, 209 (2002).

    Article  PubMed  Google Scholar 

  153. 153

    Johansen-Berg, H. et al. Correlation between motor improvements and altered fMRI activity after rehabilitative therapy. Brain 125, 2731–2742 (2002). An early demonstration of how fMRI can be used to relate functional changes in specific brain regions to behavioural improvements after neurorehabilitation post-stroke, with findings that suggest that motor learning and stroke recovery share some common mechanisms.

    Article  PubMed  Google Scholar 

  154. 154

    Luft, A. R. et al. Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial. JAMA 292, 1853–1861 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. 155

    Silani, G. et al. Brain abnormalities underlying altered activation in dyslexia: a voxel based morphometry study. Brain 128, 2453–2461 (2005).

    Article  CAS  PubMed  Google Scholar 

  156. 156

    Eckert, M. Neuroanatomical markers for dyslexia: a review of dyslexia structural imaging studies. Neuroscientist 10, 362–371 (2004).

    Article  PubMed  Google Scholar 

  157. 157

    Price, C. J. & Crinion, J. The latest on functional imaging studies of aphasic stroke. Curr. Opin. Neurol. 18, 429–434 (2005).

    Article  PubMed  Google Scholar 

  158. 158

    Turkeltaub, P. E., Gareau, L., Flowers, D. L., Zeffiro, T. A. & Eden, G. F. Development of neural mechanisms for reading. Nature Neurosci. 6, 767–773 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. 159

    Temple, E. et al. Neural deficits in children with dyslexia ameliorated by behavioral remediation: evidence from functional MRI. Proc. Natl Acad. Sci. USA 100, 2860–2865 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. 160

    Montague, P. R. et al. Hyperscanning: simultaneous fMRI during linked social interactions. Neuroimage 16, 1159–1164 (2002).

    Article  PubMed  Google Scholar 

  161. 161

    Franceschini, M. A. & Boas, D. A. Noninvasive measurement of neuronal activity with near-infrared optical imaging. Neuroimage 21, 372–386 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  162. 162

    Logothetis, N. K. The underpinnings of the BOLD functional magnetic resonance imaging signal. J. Neurosci. 23, 3963–3971 (2003).

    Article  CAS  PubMed  Google Scholar 

  163. 163

    Attwell, D. & Iadecola, C. The neural basis of functional brain imaging signals. Trends Neurosci. 25, 621–625 (2002).

    Article  CAS  Google Scholar 

  164. 164

    Magistretti, P. J. & Pellerin, L. Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. Philos. Trans. R. Soc. Lond. B Biol. Sci. 354, 1155–1163 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. 165

    Buerk, D. G., Ances, B. M., Greenberg, J. H. & Detre, J. A. Temporal dynamics of brain tissue nitric oxide during functional forepaw stimulation in rats. Neuroimage 18, 1–9 (2003).

    Article  Google Scholar 

  166. 166

    Thulborn, K. R., Waterton, J. C., Matthews, P. M. & Radda, G. K. Oxygenation dependence of the transverse relaxation time of water protons in whole blood at high field. Biochim. Biophys. Acta 714, 265–270 (1982).

    Article  CAS  PubMed  Google Scholar 

  167. 167

    Yang, Y., Gu, H. & Stein, E. A. Simultaneous MRI acquisition of blood volume, blood flow, and blood oxygenation information during brain activation. Magn. Reson. Med. 52, 1407–1417 (2004).

    Article  PubMed  Google Scholar 

  168. 168

    Schwindack, C. et al. Real-time functional magnetic resonance imaging (rt-fMRI) in patients with brain tumours: preliminary findings using motor and language paradigms. Br. J. Neurosurg. 19, 25–32 (2005).

    Article  CAS  PubMed  Google Scholar 

  169. 169

    Gasser, T. et al. Intraoperative functional MRI: implementation and preliminary experience. Neuroimage 26, 685–693 (2005).

    Article  PubMed  Google Scholar 

  170. 170

    Hoge, R. D. & Pike, G. B. Oxidative metabolism and the detection of neuronal activation via imaging. J. Chem. Neuroanat. 22, 43–52 (2001).

    Article  CAS  PubMed  Google Scholar 

  171. 171

    Hoge, R. D. et al. Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex. Proc. Natl Acad. Sci. USA 96, 9403–9408 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. 172

    Iannetti, G. D. et al. Simultaneous recording of laser-evoked brain potentials and continuous, high-field functional magnetic resonance imaging in humans. Neuroimage 28, 708–719 (2005).

    Article  CAS  PubMed  Google Scholar 

  173. 173

    Sibson, N. R. et al. MRI detection of early endothelial activation in brain inflammation. Magn. Reson. Med. 51, 248–252 (2004).

    Article  CAS  PubMed  Google Scholar 

  174. 174

    Biswal, B., Yetkin, F. Z., Haughton, V. M. & Hyde, J. S. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn. Reson. Med. 34, 537–541 (1995).

    Article  CAS  PubMed  Google Scholar 

  175. 175

    Raichle, M. E. et al. A default mode of brain function. Proc. Natl Acad. Sci. USA 98, 676–682 (2001).

    Article  CAS  Google Scholar 

  176. 176

    Lowe, M. J., Dzemidzic, M., Lurito, J. T., Mathews, V. P. & Phillips, M. D. Correlations in low-frequency BOLD fluctuations reflect cortico-cortical connections. Neuroimage 12, 582–587 (2000).

    Article  CAS  PubMed  Google Scholar 

  177. 177

    De Luca, M., Beckmann, C. F., De Stefano, N., Matthews, P. M. & Smith, S. M. fMRI resting state networks define distinct modes of long-distance interactions in the human brain. Neuroimage 29, 1359–1367 (2006).

    Article  CAS  PubMed  Google Scholar 

  178. 178

    Kiviniemi, V. et al. Slow vasomotor fluctuation in fMRI of anesthetized child brain. Magn. Reson. Med. 44, 373–378 (2000).

    Article  CAS  PubMed  Google Scholar 

  179. 179

    Wise, R. G., Ide, K., Poulin, M. J. & Tracey, I. Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal. Neuroimage 21, 1652–1664 (2004).

    Article  PubMed  Google Scholar 

  180. 180

    Leopold, D. A. & Logothetis, N. K. Spatial patterns of spontaneous local field activity in the monkey visual cortex. Rev. Neurosci. 14, 195–205 (2003).

    Article  PubMed  Google Scholar 

  181. 181

    Moosmann, M. et al. Correlates of alpha rhythm in functional magnetic resonance imaging and near infrared spectroscopy. Neuroimage 20, 145–158 (2003). An insightful series of experiments providing direct evidence that resting state networks observed with fMRI arise from low-frequency modulations of faster EEG activity. Particularly exciting is the suggestion that distinct resting state networks can be related to modulation of different frequencies of EEG activity.

    Article  PubMed  Google Scholar 

  182. 182

    Laufs, H. et al. EEG-correlated fMRI of human alpha activity. Neuroimage 19, 1463–1476 (2003).

    Article  CAS  PubMed  Google Scholar 

  183. 183

    Salvador, R. et al. Neurophysiological architecture of functional magnetic resonance images of human brain. Cereb. Cortex 15, 1332–1342 (2005).

    Article  PubMed  Google Scholar 

  184. 184

    Achard, S., Salvador, R., Whitcher, B., Suckling, J. & Bullmore, E. A resilient, low-frequency, small-world human brain functional network with highly connected association cortical hubs. J. Neurosci. 26, 63–72 (2006).

    Article  CAS  PubMed  Google Scholar 

  185. 185

    Greicius, M. D., Srivastava, G., Reiss, A. L. & Menon, V. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc. Natl Acad. Sci. USA 101, 4637–4642 (2004).

    Article  CAS  PubMed  Google Scholar 

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The authors are grateful to L. Lemieux, I. Tracey, H. Laufs, R. Wise and S. Sunaert for sharing images for figures. P.M.M. gratefully acknowledges the Medical Research Council and the Multiple Sclerosis Society of Great Britain and Northern Ireland for research support in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain.

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Correspondence to Paul M. Matthews.

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P.M.M. and E.T.B. are employees of GlaxoSmithKline.

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Alzheimer's disease

amyotrophic lateral sclerosis

Huntington's disease



Positron emission tomography

(PET). A technique that images the distribution of positron-emitting tracer isotopes (for example, 11C-choline) incorporated into compounds of interest by tomographical mapping that is based on photons emitted from positron collisions.

Functional MRI

(fMRI). An application of magnetic resonance to image physiological changes rather than structure. Use of blood-oxygen-level-dependent (BOLD) contrast is currently the most popular type.

Diffusion MRI

An application of magnetic resonance to image the moility (diffusion) of tissue water, an index of microstructure sensitive to many pathologies.

Functional neurosurgery

Neurosurgical procedures directed towards altering brain function through the ablation of tissue or implantation of stimulation electrodes.


A voxel is the three-dimensional (3D) equivalent of a pixel; a finite volume within 3D space. This corresponds to the smallest element measured in a 3D anatomical or functional brain image volume.

Transcranial magnetic stimulation

A method by which a single or series of brief magnetic pulses that are applied externally to the skull focally modulate brain function through the generation of intracortical electrical currents. Effects can be stimulatory or inhibitory depending on the approach.

Functional connectivity

A measure typically derived from the relative temporal correlation of brain regions in a physiological image that is interpreted to express the degree to which regions are functionally interacting.

Functional plasticity

Changes in the functional association of activity in a brain region, provoked by alterations of intrinsic brain function rather than by the context of the activities alone.

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Matthews, P., Honey, G. & Bullmore, E. Applications of fMRI in translational medicine and clinical practice. Nat Rev Neurosci 7, 732–744 (2006).

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