Functional MRI of Multiple Sclerosis



Multiple sclerosis (MS) is the most common nontraumatic neurological disorder in young adults. Symptoms are variable and can affect motor, visual, somatosensory, cognitive, and other central nervous system (CNS) functions. The early stages of the disease are characterized by relapses and remissions of symptoms in 85% of patients. This may subsequently transition to a progressively worsening course in the later stages of the disease [1]. The aggressiveness of the disease course and time to transition are highly variable across patients. Some patients may experience a relatively benign course of the disease, while others ultimately become severely disabled. US Food and Drug Administration (FDA)-approved treatments are available that help decrease relapses and forestall the transition to progressive disease. Sympto­matic therapies are also available, but as yet the disease has no cure. The variable and progressive course translates into many significant and changing implications for patients and their families [1].


Multiple Sclerosis Optic Neuritis Retinal Nerve Fiber Layer Thickness Cognitive Reserve Clinically Isolate Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Joy JE, Johnston RB. Multiple sclerosis: current status and strategies for the future. Washington, DC: National Academy Press; 2001.Google Scholar
  2. 2.
    Murray TJ. Multiple sclerosis: the history of a disease. New York: Demos Medical Publishing; 2005.Google Scholar
  3. 3.
    Boomer J, Siatkowski R. Optic neuritis in children and adults. Semin Ophthalmol. 2003;18:174–80.PubMedGoogle Scholar
  4. 4.
    Rombouts SA, Lazeron RH, Scheltens P, et al. Visual activation patterns in patients with optic neuritis: an fMRI pilot study. Neurology. 1998;50:1896–9.PubMedGoogle Scholar
  5. 5.
    Gareau PJ, Gati JS, Menon RS, et al. Reduced visual evoked responses in multiple sclerosis patients with optic neuritis: comparison of functional magnetic resonance imaging and visual evoked potentials. Mult Scler. 1999;5:161–4.PubMedGoogle Scholar
  6. 6.
    Faro SH, Mohamed FB, Tracy JI, et al. Quantitative functional MR imaging of the visual cortex at 1.5 T as a function of luminance contrast in healthy volunteers and patients with multiple sclerosis. Am J Neuroradiol. 2002;23:59–65.PubMedGoogle Scholar
  7. 7.
    Werring DJ, Bullmore ET, Toosy AT, et al. Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation: a functional magnetic resonance imaging study. J Neurol Neurosurg Psychiatry. 2000;68:441–9.PubMedGoogle Scholar
  8. 8.
    Langkilde AR, Frederiksen JL, Rostrup E, Larsson HBW. Functional MRI of the visual cortex and visual testing in patients with previous optic neuritis. Eur J Neurol. 2002;9:277–86.PubMedGoogle Scholar
  9. 9.
    Levin N, Orlov T, Dotan S, Zohary E. Normal and abnormal fMRI activation patterns in the visual cortex after recovery from optic neuritis. Neuroimage. 2006;33:1161–8.PubMedGoogle Scholar
  10. 10.
    Russ MO, Cleff U, Lanfermann H, Schalnus R, Enzensberger W, Kleinschmidt A. Functional magnetic resonance imaging in acute unilateral optic neuritis. J Neuroimaging. 2002;12:339–50.PubMedGoogle Scholar
  11. 11.
    Toosy AT, Hickman SJ, Miszkiel KA, et al. Adaptive cortical plasticity in higher visual areas after acute optic neuritis. Ann Neurol. 2005;57:622–33.PubMedGoogle Scholar
  12. 12.
    Korsholm K, Madsen KH, Frederiksen JL, Skimminge A, Lund TE. Recovery from optic neuritis: an ROI-based analysis of LGN and visual cortical areas. Brain. 2007;130:1244–53.PubMedGoogle Scholar
  13. 13.
    Korsholm K, Madsen KH, Frederiksen JL, Rowe JB, Lund TE. Cortical neuroplasticity in patients recovering from acute optic neuritis. Neuroimage. 2008;42:836–44.PubMedGoogle Scholar
  14. 14.
    Toosy AT, Werring DJ, Bullmore ET, et al. Functional magnetic resonance imaging of the cortical response to photic stimulation in humans following optic neuritis recovery. Neurosci Lett. 2002;330:255–9.PubMedGoogle Scholar
  15. 15.
    Jenkins TM, Toosy AT, Ciccarelli O, et al. Neuroplasticity predicts outcome of optic neuritis independent of tissue damage. Ann Neurol. 2010;67:99–113.PubMedGoogle Scholar
  16. 16.
    Kolappan M, Henderson APD, Jenkins TM, et al. Assessing structure and function of the afferent visual pathway in multiple sclerosis and associated optic neuritis. J Neurol. 2009;256:305–19.PubMedGoogle Scholar
  17. 17.
    Reddy H, Narayanan S, Matthews PM, et al. Relating axonal injury to functional recovery in MS. Neurology. 2000;54:236–9.PubMedGoogle Scholar
  18. 18.
    Reddy H, Narayanan S, Arnoutelis R, et al. Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis. Brain. 2000;123:2314–20.PubMedGoogle Scholar
  19. 19.
    Pantano P, Iannetti GD, Caramia F, et al. Cortical motor reorganization after a single clinical attack of multiple sclerosis. Brain. 2002;125:1607–15.PubMedGoogle Scholar
  20. 20.
    Pantano P, Mainero C, Iannetti GD, et al. Contribution of corticospinal tract damage to cortical motor reorganization after a single clinical attack of multiple sclerosis. Neuroimage. 2002;17:1837–43.PubMedGoogle Scholar
  21. 21.
    Rocca MA, Falini A, Colombo B, Scotti G, Comi G, Filippi M. Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage. Ann Neurol. 2002;51:330–9.PubMedGoogle Scholar
  22. 22.
    Rocca MA, Mezzapesa DM, Falini A, et al. Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage. 2003;18:847–55.PubMedGoogle Scholar
  23. 23.
    Rocca MA, Gavazzi C, Mezzapesa DM, et al. A functional magnetic resonance imaging study of patients with secondary progressive multiple sclerosis. Neuroimage. 2003;19:1770–7.PubMedGoogle Scholar
  24. 24.
    Rocca MA, Pagani E, Ghezzi A, et al. Functional cortical changes in patients with multiple sclerosis and nonspecific findings on conventional magnetic resonance imaging scans of the brain. Neuroimage. 2003;19:826–36.PubMedGoogle Scholar
  25. 25.
    Rocca MA, Gallo A, Colombo B, et al. Pyramidal tract lesions and movement-associated cortical recruitment in patients with MS. Neuroimage. 2004;23:141–7.PubMedGoogle Scholar
  26. 26.
    Filippi M, Rocca MA, Falini A, et al. Correlations between structural CNS damage and functional MRI changes in primary progressive MS. Neuroimage. 2002;15:537–46.PubMedGoogle Scholar
  27. 27.
    Rocca M, Ceccarelli A, Rodegher M, et al. Preserved brain adaptive properties in patients with benign multiple sclerosis. Neurology. 2010;74:142–9.PubMedGoogle Scholar
  28. 28.
    Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. Neurology. 1996;46:907–11.PubMedGoogle Scholar
  29. 29.
    Mancini L, Ciccarelli O, Manfredonia F, et al. Short-term adaptation to a simple motor task: a physiological process preserved in multiple sclerosis. Neuroimage. 2009;45:500–11.PubMedGoogle Scholar
  30. 30.
    Rocca MA, Absinta M, Ghezzi A, Moiola L, Comi G, Filippi M. Is a preserved functional reserve a mechanism limiting clinical impairment in pediatric MS patients? Hum Brain Mapp. 2009;30:2844–51.PubMedGoogle Scholar
  31. 31.
    Rocca MA, Colombo B, Falini A, et al. Cortical adaptation in patients with MS: a cross-sectional functional MRI study of disease phenotypes. Lancet Neurol. 2005;4:618–26.PubMedGoogle Scholar
  32. 32.
    Wang J, Hier DB. Motor reorganization in multiple sclerosis. Neurol Res. 2007;29:3–8.PubMedGoogle Scholar
  33. 33.
    Lee M, Reddy H, Johansen-Berg H, et al. The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis. Ann Neurol. 2000;47:606–13.PubMedGoogle Scholar
  34. 34.
    Rocca MA, Pagani E, Absinta M, et al. Altered functional and structural connectivities in patients with MS: a 3-T study. Neurology. 2007;69:2136–45.PubMedGoogle Scholar
  35. 35.
    Rocca MA, Mezzapesa DM, Ghezzi A, et al. A widespread pattern of cortical activations in patients at presentation with clinically isolated symptoms is associated with evolution to definite multiple sclerosis. Am J Neuroradiol. 2005;26:1136–9.PubMedGoogle Scholar
  36. 36.
    Mezzapesa DM, Rocca MA, Rodegher M, Comi G, Filippi M. Functional cortical changes of the sensorimotor network are associated with clinical recovery in multiple sclerosis. Hum Brain Mapp. 2008;29:562–73.PubMedGoogle Scholar
  37. 37.
    Pantano P, Mainero C, Lenzi D, et al. A longitudinal fMRI study on motor activity in patients with multiple sclerosis. Brain. 2005;128:2146–53.PubMedGoogle Scholar
  38. 38.
    Filippi M, Rocca MA, Mezzapesa DM, et al. Simple and complex movement-associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Hum Brain Mapp. 2004;21:108–17.PubMedGoogle Scholar
  39. 39.
    Filippi M, Rocca MA, Mezzapesa DM, et al. A functional MRI study of cortical activations associated with object manipulation in patients with MS. Neuroimage. 2004;21:1147–54.PubMedGoogle Scholar
  40. 40.
    Ciccarelli O, Toosy AT, Marsden JF, et al. Functional response to active and passive ankle movements with clinical correlations in patients with primary progressive multiple sclerosis. J Neurol. 2006;253:882–91.PubMedGoogle Scholar
  41. 41.
    Pierno AC, Turella L, Grossi P, et al. Investigation of the neural correlates underlying action observation in multiple sclerosis patients. Exp Neurol. 2009;217:252–7.PubMedGoogle Scholar
  42. 42.
    Reddy H, Narayanan S, Woolrich M, et al. Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability. Brain. 2002;125:2646–57.PubMedGoogle Scholar
  43. 43.
    Rocca MA, Matthews PM, Caputo D, et al. Evidence for widespread movement-associated functional MRI changes in patients with PPMS. Neurology. 2002;58:866–72.PubMedGoogle Scholar
  44. 44.
    Rocca MA, Tortorella P, Ceccarelli A, et al. The “mirror-neuron system” in MS: a 3 tesla fMRI study. Neurology. 2008;70:255–62.PubMedGoogle Scholar
  45. 45.
    Thickbroom GW, Byrnes ML, Archer SA, Kermode AG, Mastaglia FL. Corticomotor organisation and motor function in multiple sclerosis. J Neurol. 2005;252:765–71.PubMedGoogle Scholar
  46. 46.
    Manson SC, Palace J, Frank JA, Matthews PM. Loss of interhemispheric inhibition in patients with multiple sclerosis is related to corpus callosum atrophy. Exp Brain Res. 2006;174:728–33.PubMedGoogle Scholar
  47. 47.
    Manson SC, Wegner C, Filippi M, et al. Impairment of movement-associated brain deactivation in multiple sclerosis: further evidence for a functional pathology of interhemispheric neuronal inhibition. Exp Brain Res. 2008;187:25–31.PubMedGoogle Scholar
  48. 48.
    Lenzi D, Conte A, Mainero C, et al. Effect of corpus callosum damage on ipsilateral motor activation in patients with multiple sclerosis: a functional and anatomical study. Hum Brain Mapp. 2007;28:636–44.PubMedGoogle Scholar
  49. 49.
    Saini S, DeStefano N, Smith S, et al. Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2004;75:840–6.PubMedGoogle Scholar
  50. 50.
    Lowe MJ, Phillips MD, Lurito JT, Mattson D, Dzemidzic M, Mathews VP. Multiple sclerosis: low-frequency temporal blood oxygen level-dependent fluctuations indicate reduced functional connectivity – initial results. Radiology. 2002;224:184–92.PubMedGoogle Scholar
  51. 51.
    Lowe MJ, Beall EB, Sakaie KE, et al. Resting state sensorimotor functional connectivity in multiple sclerosis inversely correlates with transcallosal motor pathway transverse diffusivity. Hum Brain Mapp. 2008;29:818–27.PubMedGoogle Scholar
  52. 52.
    Rocca MA, Absinta M, Moiola L, et al. Functional and structural connectivity of the motor network in pediatric and adult-onset relapsing-remitting multiple sclerosis. Radiology. 2010;254:541–50.PubMedGoogle Scholar
  53. 53.
    Bobholz JA, Rao SM. Cognitive dysfunction in multiple sclerosis: a review of recent developments. Curr Opin Neurol. 2003;16:283–8.PubMedGoogle Scholar
  54. 54.
    Genova H, Sumowski J, Chiaravalloti N, Voelbel G, Deluca J. Cognition in multiple sclerosis: a review of neuropsychological and fMRI research. Front Biosci. 2009;14:1730–44.PubMedGoogle Scholar
  55. 55.
    Bobholz JA, Rao SM, Lobeck L, et al. fMRI study of episodic memory in relapsing-remitting MS: correlation with T2 lesion volume. Neurology. 2006;67:1640–5.PubMedGoogle Scholar
  56. 56.
    Audoin B, Ibarrola D, Ranjeva J-P, et al. Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS. Hum Brain Mapp. 2003;20:51–8.PubMedGoogle Scholar
  57. 57.
    Audoin B, Au Duong MV, Ranjeva JP, et al. Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis. Hum Brain Mapp. 2005;24:216–28.PubMedGoogle Scholar
  58. 58.
    Ranjeva JP, Audoin B, Au Duong MV, et al. Structural and functional surrogates of cognitive impairment at the very early stage of multiple sclerosis. J Neurol Sci. 2006;245:161–7.PubMedGoogle Scholar
  59. 59.
    Chiaravalloti N, Hillary F, Ricker J, et al. Cerebral activation patterns during working memory performance in multiple sclerosis using fMRI. J Clin Exp Neuropsychol. 2005;27:33–54.PubMedGoogle Scholar
  60. 60.
    Forn C, Barros-Loscertales A, Escudero J, et al. Compensatory activations in patients with multiple sclerosis during preserved performance on the auditory N-back task. Hum Brain Mapp. 2007;28:424–30.PubMedGoogle Scholar
  61. 61.
    Forn C, Barros-Loscertales A, Escudero J, et al. Cortical reorganization during PASAT task in MS patients with preserved working memory functions. Neuroimage. 2006;31:686–91.PubMedGoogle Scholar
  62. 62.
    Genova HM, Hillary FG, Wylie G, Rypma B, Deluca J. Examination of processing speed deficits in multiple sclerosis using functional magnetic resonance imaging. J Int Neuropsychol Soc. 2009;15:383–93.PubMedGoogle Scholar
  63. 63.
    Gioia MC, Cerasa A, Liguori M, et al. Impact of individual cognitive profile on visuo-motor reorganization in relapsing-remitting multiple sclerosis. Brain Res. 2007;1167:71–9.PubMedGoogle Scholar
  64. 64.
    Cerasa A, Fera F, Gioia MC, et al. Adaptive cortical changes and the functional correlates of visuo-motor integration in relapsing-remitting multiple sclerosis. Brain Res Bull. 2006;69:597–605.PubMedGoogle Scholar
  65. 65.
    Hillary FG, Chiaravalloti ND, Ricker JH, et al. An investigation of working memory rehearsal in multiple sclerosis using fMRI. J Clin Exp Neuropsychol. 2003;25:965–78.PubMedGoogle Scholar
  66. 66.
    Lazeron RHC, Rombouts SARB, Scheltens P, Polman CH, Barkhof F. An fMRI study of planning-related brain activity in patients with moderately advanced multiple sclerosis. Mult Scler. 2004;10:549–55.PubMedGoogle Scholar
  67. 67.
    Li Y, Chiaravalloti ND, Hillary FG, et al. Differential cerebellar activation on functional magnetic resonance imaging during working memory performance in persons with multiple sclerosis. Arch Phys Med Rehabil. 2004;85:635–9.PubMedGoogle Scholar
  68. 68.
    Mainero C, Caramia F, Pozzilli C, et al. fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis. Neuroimage. 2004;21:858–67.PubMedGoogle Scholar
  69. 69.
    Morgen K, Sammer G, Courtney SM, et al. Distinct mechanisms of altered brain activation in patients with multiple sclerosis. Neuroimage. 2007;37:937–46.PubMedGoogle Scholar
  70. 70.
    Nebel K, Wiese H, Seyfarth J, et al. Activity of attention related structures in multiple sclerosis patients. Brain Res. 2007;1151:150–60.PubMedGoogle Scholar
  71. 71.
    Prakash RS, Erickson KI, Snook EM, Colcombe SJ, Motl RW, Kramer AF. Cortical recruitment during selective attention in multiple sclerosis: an fMRI investigation of individual differences. Neuropsychologia. 2008;46:2888–95.PubMedGoogle Scholar
  72. 72.
    Penner I-K, Rausch M, Kappos L, Opwis K, Radu EW. Analysis of impairment related functional architecture in MS patients during performance of different attention tasks. J Neurol. 2003;250:461–72.PubMedGoogle Scholar
  73. 73.
    Rachbauer D, Kronbichler M, Ropele S, Enzinger C, Fazekas F. Differences in cerebral activation patterns in idiopathic inflammatory demyelination using the paced visual serial addition task: an fMRI study. J Neurol Sci. 2006;244:11–6.PubMedGoogle Scholar
  74. 74.
    Rocca MA, Valsasina P, Ceccarelli A, et al. Structural and functional MRI correlates of Stroop control in benign MS. Hum Brain Mapp. 2009;30:276–90.PubMedGoogle Scholar
  75. 75.
    Smith AM, Walker LAS, Freedman MS, DeMeulemeester C, Hogan MJ, Cameron I. fMRI investigation of disinhibition in cognitively impaired patients with multiple sclerosis. J Neurol Sci. 2009;281:58–63.PubMedGoogle Scholar
  76. 76.
    Staffen W, Mair A, Zauner H, et al. Cognitive function and fMRI in patients with multiple sclerosis: evidence for compensatory cortical activation during an attention task. Brain. 2002;125:1275–82.PubMedGoogle Scholar
  77. 77.
    Rocca MA, Valsasina P, Absinta M, et al. Default-mode network dysfunction and cognitive impairment in progressive MS. Neurology. 2010;74:1252–9.PubMedGoogle Scholar
  78. 78.
    Sweet LH, Rao SM, Primeau M, Mayer AR, Cohen RA. Functional magnetic resonance imaging of working memory among multiple sclerosis patients. J Neuroimaging. 2004;14:150–7.PubMedGoogle Scholar
  79. 79.
    Sweet LH, Rao SM, Primeau M, Durgerian S, Cohen RA. Functional magnetic resonance imaging response to increased verbal working memory demands among patients with multiple sclerosis. Hum Brain Mapp. 2006;27:28–36.PubMedGoogle Scholar
  80. 80.
    Au Duong M, Boulanouar K, Audoin B, et al. Modulation of effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis. Neuroimage. 2005;24:533–8.PubMedGoogle Scholar
  81. 81.
    Au Duong MV, Audoin B, Boulanouar K, et al. Altered functional connectivity related to white matter changes inside the working memory network at the very early stage of MS. J Cereb Blood Flow Metab. 2005;25:1245–53.PubMedGoogle Scholar
  82. 82.
    Roosendaal SD, Hulst HE, Vrenken H, et al. Structural and functional hippocampal changes in multiple sclerosis patients with intact memory function. Radiology. 2010;255:595–604.PubMedGoogle Scholar
  83. 83.
    Bonzano L, Pardini M, Mancardi GL, Pizzorno M, Roccatagliata L. Structural connectivity influences brain activation during PVSAT in Multiple Sclerosis. Neuroimage. 2009;44:9–15.PubMedGoogle Scholar
  84. 84.
    Audoin B, Reuter F, Duong MVA, et al. Efficiency of cognitive control recruitment in the very early stage of multiple sclerosis: a one-year fMRI follow-up study. Mult Scler. 2008;14:786–92.PubMedGoogle Scholar
  85. 85.
    Meyn H, Kraemer M, de Greiff A, Diehl RR. Activation of working memory in patients at the earliest stage of multiple sclerosis – an fMRI study. Clin Neurol Neurosurg. 2010;112:490–5.PubMedGoogle Scholar
  86. 86.
    Bonnet MC, Allard M, Dilharreguy B, Deloire M, Petry KG, Brochet B. Cognitive compensation failure in multiple sclerosis. Neurology. 2010;75:1241–8.PubMedGoogle Scholar
  87. 87.
    Wishart H, Saykin A, McDonald B, et al. Brain activation patterns associated with working memory in relapsing-remitting MS. Neurology. 2004;62:234–8.PubMedGoogle Scholar
  88. 88.
    Cader S, Cifelli A, Abu-Omar Y, Palace J, Matthews PM. Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis. Brain. 2006;129:527–37.PubMedGoogle Scholar
  89. 89.
    Sumowski JF, Wylie GR, Deluca J, Chiaravalloti N. Intellectual enrichment is linked to cerebral efficiency in multiple sclerosis: functional magnetic resonance imaging evidence for cognitive reserve. Brain. 2010;133:362–74.PubMedGoogle Scholar
  90. 90.
    Audoin B, AuDuong MV, Malikova I, et al. Functional magnetic resonance imaging and cognition at the very early stage of MS. J Neurol Sci. 2006;245:87–91.PubMedGoogle Scholar
  91. 91.
    Mainero C, Pantano P, Caramia F, Pozzilli C. Brain reorganization during attention and memory tasks in multiple sclerosis: insights from functional MRI studies. J Neurol Sci. 2006;245:93–8.PubMedGoogle Scholar
  92. 92.
    Filippi M, Rocca MA. Functional MR imaging in multiple sclerosis. Neuroimaging Clin N Am. 2009;19:59–70.PubMedGoogle Scholar
  93. 93.
    Hillary FG. Neuroimaging of working memory dysfunction and the dilemna with brain reorganization hypotheses. J Int Neuropsychol Soc. 2008;14:526–34.PubMedGoogle Scholar
  94. 94.
    Caramia F, Tinelli E, Francis A, Pozzilli C. Cognitive deficits in multiple sclerosis: a review of functional MRI studies. Neurol Sci. 2010;31:S239–43.PubMedGoogle Scholar
  95. 95.
    Filippi M, Rocca MA, Colombo B, et al. Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis. Neuroimage. 2002;15:559–67.PubMedGoogle Scholar
  96. 96.
    Rocca MA, Gatti R, Agosta F, et al. Influence of task complexity during coordinated hand and foot movements in MS patients with and without fatigue. A kinematic and functional MRI study. J Neurol. 2009;256:470–82.PubMedGoogle Scholar
  97. 97.
    White AT, Lee JN, Light AR, Light KC. Brain activation in multiple sclerosis: a BOLD fMRI study of the effects of fatiguing hand exercise. Mult Scler. 2009;15:580–6.PubMedGoogle Scholar
  98. 98.
    Tartaglia MC, Narayanan S, Arnold DL. Mental fatigue alters the pattern and increases the volume of cerebral activation required for a motor task in multiple sclerosis patients with fatigue. Eur J Neurol. 2008;15:413–9.PubMedGoogle Scholar
  99. 99.
    Bryant D, Chiaravalloti ND, DeLuca J. Objective measurement of cognitive fatigue in multiple sclerosis. Rehabil Psychol. 2004;49:114–22.Google Scholar
  100. 100.
    DeLuca J, Genova HM, Hillary FG, Wylie G. Neural correlates of cognitive fatigue in multiple sclerosis using functional MRI. J Neurol Sci. 2008;270:28–39.PubMedGoogle Scholar
  101. 101.
    Filippi M, Rocca MA. Toward a definition of structural and functional MRI substrates of fatigue in multiple sclerosis. J Neurol Sci. 2007;263:1–2.PubMedGoogle Scholar
  102. 102.
    Tedeschi G, Dinacci D, Lavorgna L, et al. Correlation between fatigue and brain atrophy and lesion load in multiple sclerosis patients independent of disability. J Neurol Sci. 2007;263:15–9.PubMedGoogle Scholar
  103. 103.
    Passamonti L, Cerasa A, Liguori M, et al. Neurobiological mechanisms underlying emotional processing in relapsing-remitting multiple sclerosis. Brain. 2009;132:3380–91.PubMedGoogle Scholar
  104. 104.
    Valsasina P, Agosta F, Absinta M, Sala S, Caputo D, Filippi M. Cervical cord functional MRI changes in relapse-onset MS patients. J Neurol Neurosurg Psychiatry. 2010;81:405–8.PubMedGoogle Scholar
  105. 105.
    Agosta F, Valsasina P, Caputo D, Stroman PW, Filippi M. Tactile-associated recruitment of the cervical cord is altered in patients with multiple sclerosis. Neuroimage. 2008;39:1542–8.PubMedGoogle Scholar
  106. 106.
    Agosta F, Valsasina P, Rocca MA, et al. Evidence for enhanced functional activity of cervical cord in relapsing multiple sclerosis. Magn Reson Med. 2008;59:1035–42.PubMedGoogle Scholar
  107. 107.
    Mainero C, Inghilleri M, Pantano P, et al. Enhanced brain motor activity in patients with MS after a single dose of 3,4-diaminopyridine. Neurology. 2004;62:2044–50.PubMedGoogle Scholar
  108. 108.
    Parry A, Scott R, Palace J, Smith S, Matthews P. Potentially adaptive functional changes in cognitive processing for patients with multiple sclerosis and their acute modulation by rivastigmine. Brain. 2003;126:2750–60.PubMedGoogle Scholar
  109. 109.
    Cader S, Palace J, Matthews PM. Cholinergic agonism alters cognitive processing and enhances brain functional connectivity in patients with multiple sclerosis. J Psychopharmacol. 2009;23:686–96.PubMedGoogle Scholar
  110. 110.
    Rocca MA, Agosta F, Colombo B, et al. fMRI changes in relapsing-remitting multiple sclerosis patients complaining of fatigue after IFNbeta-1a injection. Hum Brain Mapp. 2007;28:373–82.PubMedGoogle Scholar
  111. 111.
    Rasova K, Krasensky J, Havrdova E, et al. Is it possible to actively and purposely make use of plasticity and adaptability in the neurorehabilitation treatment of multiple sclerosis patients? A pilot project. Clin Rehabil. 2005;19:170–81.PubMedGoogle Scholar
  112. 112.
    Morgen K, Kadom N, Sawaki L, et al. Training-dependent plasticity in patients with multiple sclerosis. Brain. 2004;127:2506–17.PubMedGoogle Scholar
  113. 113.
    Penner IK, Kappos L, Rausch M, Opwis K, Radu EW. Therapy-induced plasticity of cognitive functions in MS patients: insights from fMRI. J Physiol. 2006;99:455–62.Google Scholar
  114. 114.
    Penner IK, Kappos L. Retraining attention in MS. J Neurol Sci. 2006;245:147–51.PubMedGoogle Scholar
  115. 115.
    Penner I-K, Opwis K, Kappos L. Relation between functional brain imaging, cognitive impairment and cognitive rehabilitation in patients with multiple sclerosis. J Neurol. 2007;254 Suppl 2:53–7.Google Scholar
  116. 116.
    Prakash RS, Snook EM, Erickson KI, et al. Cardiorespiratory fitness: a predictor of cortical plasticity in multiple sclerosis. Neuroimage. 2007;34:1238–44.PubMedGoogle Scholar
  117. 117.
    Honey G, Bullmore E. Human pharmacological MRI. Trends Pharmacol Sci. 2004;25:366–74.PubMedGoogle Scholar
  118. 118.
    Cardinal KS, Wilson SM, Giesser BS, Drain AE, Sicotte NL. A longitudinal fMRI study of the paced auditory serial addition task. Mult Scler. 2008;14:465–71.PubMedGoogle Scholar
  119. 119.
    Rocca MA, Absinta M, Valsasina P, et al. Abnormal connectivity of the sensorimotor network in patients with MS: a multicenter fMRI study. Hum Brain Mapp. 2009;30:2412–25.PubMedGoogle Scholar
  120. 120.
    Wegner C, Filippi M, Korteweg T, et al. Relating functional changes during hand movement to clinical parameters in patients with multiple sclerosis in a multi-centre fMRI study. Eur J Neurol. 2008;15:113–22.PubMedGoogle Scholar
  121. 121.
    Bosnell R, Wegner C, Kincses ZT, et al. Reproducibility of fMRI in the clinical setting: implications for trial designs. Neuroimage. 2008;42:603–10.PubMedGoogle Scholar
  122. 122.
    Zivadinov R, Cox JL. Is functional MRI feasible for multi-center studies on multiple sclerosis? Eur J Neurol. 2008;15:109–10.PubMedGoogle Scholar
  123. 123.
    American Society of Functional Neuroradiology [online]. Accessed July 15, 2010.Google Scholar
  124. 124.
    Fox RJ. Picturing multiple sclerosis: conventional and diffusion tensor imaging. Semin Neurol. 2008;28:453–66.PubMedGoogle Scholar
  125. 125.
    Rovaris M, Agosta F, Pagani E, Filippi M. Diffusion tensor MR imaging. Neuroimaging Clin N Am. 2009;19:37–43.PubMedGoogle Scholar
  126. 126.
    Ozturk A, Smith SA, Gordon-Lipkin EM, et al. MRI of the corpus callosum in multiple sclerosis: association with disability. Mult Scler. 2010;16:166–77.PubMedGoogle Scholar
  127. 127.
    Feinstein A, O’Connor P, Akbar N, Moradzadeh L, Scott CJM, Lobaugh NJ. Diffusion tensor imaging abnormalities in depressed multiple sclerosis patients. Mult Scler. 2010;16:189–96.PubMedGoogle Scholar
  128. 128.
    Kirov II, Patil V, Babb JS, Rusinek H, Herbert J, Gonen O. MR spectroscopy indicates diffuse multiple sclerosis activity during remission. J Neurol Neurosurg Psychiatry. 2009;80:1330–6.PubMedGoogle Scholar
  129. 129.
    Bellmann-Strobl J, Stiepani H, Wuerfel J, et al. MR spectroscopy (MRS) and magnetisation transfer imaging (MTI), lesion load and clinical scores in early relapsing remitting multiple sclerosis: a combined cross-sectional and longitudinal study. Eur Radiol. 2009;19:2066–74.PubMedGoogle Scholar
  130. 130.
    Waters RJ, Nicoll JA. Genetic influences on outcome following acute neurological insults. Curr Opin Crit Care. 2005;11:105–10.PubMedGoogle Scholar
  131. 131.
    Wright AF. Neurogenetics II: complex disorders. J Neurol Neurosurg Psychiatry. 2005;76:623–31.PubMedGoogle Scholar
  132. 132.
    Chapman J, Sylantiev C, Nispeanu P, Korczyn AD. Preliminary observations on APOE E4 allele and progression of disability in multiple sclerosis. Arch Neurol. 1999;56:1484–7.PubMedGoogle Scholar
  133. 133.
    Chapman J, Vinokurov S, Achiron A, et al. APOE genotype is a major predictor of long-term progression of disability in MS. Neurology. 2001;56:312–6.PubMedGoogle Scholar
  134. 134.
    Oliveri RL, Cittadella R, Sibilia G, et al. APOE and risk of cognitive impairment in multiple sclerosis. Acta Neurol Scand. 1999;100:290–5.PubMedGoogle Scholar
  135. 135.
    Zakrzewska-Pniewska B, Styczynska M, Podlecka A, et al. Association of apolipoprotein E and myeloperoxidase genotypes to clinical course of familial and sporadic multiple sclerosis. Mult Scler. 2004;10:266–71.PubMedGoogle Scholar
  136. 136.
    Burwick RM, Ramsay PP, Haines JL, et al. APOE e variation in multiple sclerosis susceptibility and disease severity: some answers. Neurology. 2006;66:1373–83.PubMedGoogle Scholar
  137. 137.
    Pinholt M, Frederiksen J, Christiansen M. The association between apolipoprotein E and multiple sclerosis. Eur J Neurol. 2006;13:573–80.PubMedGoogle Scholar
  138. 138.
    De Stefano N, Bartolozzi ML, Nacmias B, et al. Influence of apolipoprotein E e4 genotype on brain tissue integrity in relapsing-remitting multiple sclerosis. Arch Neurol. 2004;61:536–40.PubMedGoogle Scholar
  139. 139.
    Enzinger C, Ropele S, Smith S, et al. Accelerated evolution of brain atrophy and “black holes” in MS patients with APOE e4. Ann Neurol. 2004;55:563–9.PubMedGoogle Scholar
  140. 140.
    Enzinger C, Ropele S, Strasser-Fuchs S, et al. Lower levels of N-acetylaspartate in multiple sclerosis patients with the apolipoprotein E e4 allele. Arch Neurol. 2003;60:65–70.PubMedGoogle Scholar
  141. 141.
    Cerasa A, Tongiorgi E, Fera F, et al. The effects of BDNF Val66Met polymorphism on brain function in controls and patients with multiple slerosis: an imaging genetic study. Behav Brain Res. 2010;207:377–86.PubMedGoogle Scholar
  142. 142.
    Lovblad KO, Anzalone N, Dorfler A, et al. MR imaging in multiple sclerosis: review and recommendations for current practice. Am J Neuroradiol. 2010;31:983–9.PubMedGoogle Scholar
  143. 143.
    Bakshi R, Thompson AJ, Rocca MA, et al. MRI in multiple sclerosis: current status and future prospects. Lancet Neurol. 2008;7:615–25.PubMedGoogle Scholar
  144. 144.
    Zipp F. A new window in multiple sclerosis pathology: non-conventional quantitative magnetic resonance imaging outcomes. J Neurol Sci. 2009;287:S24–9.PubMedGoogle Scholar
  145. 145.
    Buckle G. Functional magnetic resonance imaging and multiple sclerosis: the evidence for neuronal plasticity. J Neuroimaging. 2005;15:82S–93.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Brain Imaging Laboratory, Department of PsychiatryDartmouth Medical School, One Medical Center DriveLebanonUSA

Personalised recommendations