Neuroimaging and Cognitive Function in Multiple Sclerosis

  • Lawrence H. Sweet
  • Susan D. Vandermorris


Multiple Sclerosis (MS) is a degenerative disease of uncertain etiology which affects the central nervous system. It is the most common nontraumatic disabling neurological disorder among adults under 60 years of age (Rao, Neurobehavioral Aspects of Multiple Sclerosis, 1990), with approximately 12,000 individuals receiving a diagnosis of MS in the United States each year (Alonso and Hernan, Neurology 71(2):129–135, 2008). MS affects women more frequently than men (1.7:1; Baum and Rothschild, Ann Neurol 10(5):420–428, 1981), and the risk for MS increases the farther one lives from the equator (Ebers and Sadovnick, Multiple Sclerosis, 1998)


Multiple Sclerosis Single Photon Emission Compute Tomography Multiple Sclerosis Patient Diffusion Tensor Imaging Functional Magnetic Resonance Imaging 
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.
    Alonso A, Hernan MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology. 2008;71(2):129–135.PubMedCrossRefGoogle Scholar
  2. 2.
    Amato MP, Bartolozzi ML, Zipoli V, et al. Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment. Neurology. 2004;63(1):89–93.PubMedGoogle Scholar
  3. 3.
    Amato MP, Zipoli V, Portaccio E. Cognitive changes in ­multiple sclerosis. Expert Rev Neurother. 2008;8(10):1585–1596.PubMedCrossRefGoogle Scholar
  4. 4.
    APA. Diagnostic and Statistical Manual – IV. Washington, DC: American Psychiatric Association; 1994.Google Scholar
  5. 5.
    Arnett P, Rao SM, Bernardin L, Grafman J, Yetkin F, Lobeck L. Relationship between frontal lobe lesion and Wisconsin card sorting test performance in patients with MS. Neurology. 1994;44:420–425.PubMedGoogle Scholar
  6. 6.
    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(10):1245–1253.PubMedCrossRefGoogle Scholar
  7. 7.
    Au Duong MV, 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(2):533–538.PubMedCrossRefGoogle Scholar
  8. 8.
    Audoin B, Ibarrola D, Au Duong MV, et al. Functional MRI study of PASAT in normal subjects. Magma. 2005;18(2):96–102.PubMedCrossRefGoogle Scholar
  9. 9.
    Audoin B, Ibarrola D, Ranjeva JP, et al. Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS. Hum Brain Mapp. 2003;20(2):51–58.PubMedCrossRefGoogle Scholar
  10. 10.
    Bakshi R, Benedict RH, Bermel RA, Jacobs L. Regional brain atrophy is associated with physical disability in multiple sclerosis: semiquantitative magnetic resonance imaging and relationship to clinical findings. J Neuroimaging. 2001;11(2):129–136.PubMedCrossRefGoogle Scholar
  11. 11.
    Baum HM, Rothschild BB. The incidence and prevalence of reported multiple sclerosis. Ann Neurol. 1981;10(5):420–428.PubMedCrossRefGoogle Scholar
  12. 12.
    Baumhefner RW, Tourtellotte WW, Syndulko K, et al. Quantitative multiple sclerosis plaque assessment with magnetic resonance imaging. Its correlation with clinical parameters, evoked potentials, and intra-blood–brain barrier IgG synthesis. Arch Neurol. 1990;47(1):19–26.PubMedGoogle Scholar
  13. 13.
    Beatty WW, Goodkin DE, Monson N, Beatty PA. Cognitive disturbances in patients with relapsing remitting multiple sclerosis. Arch Neurol. 1989;46:1113.PubMedGoogle Scholar
  14. 14.
    Benedict RH, Bruce JM, Dwyer MG, et al. Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol. 2006;63(9):1301–1306.PubMedCrossRefGoogle Scholar
  15. 15.
    Benedict RH, Carone DA, Bakshi R. Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis. J Neuroimaging. 2004;14(3 suppl):36S–45S.PubMedCrossRefGoogle Scholar
  16. 16.
    Benedict RH, Fischer JS, Archibald CJ, et al. Minimal neuropsychological assessment of MS patients: a consensus approach. Clin Neuropsychol. 2002;16(3):381–397.PubMedGoogle Scholar
  17. 17.
    Berg D, Maurer M, Warmuth-Metz M, Rieckmann P, Becker G. The correlation between ventricular diameter measured by transcranial sonography and clinical disability and cognitive dysfunction in patients with multiple sclerosis. Arch Neurol. 2000;57(9):1289–1292.PubMedCrossRefGoogle Scholar
  18. 18.
    Bermel RA, Bakshi R, Tjoa C, Puli SR, Jacobs L. Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis. Arch Neurol. 2002;59:275.PubMedCrossRefGoogle Scholar
  19. 19.
    Blinkenberg M, Rune K, Jensen CV, et al. Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS. Neurology. 2000;54(3):558–564.PubMedGoogle Scholar
  20. 20.
    Bobholz JA, Rao SM. Cognitive dysfunction in multiple sclerosis: a review of recent developments. Curr Opin Neurol. 2003;16(3):283–288.PubMedCrossRefGoogle Scholar
  21. 21.
    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(9):1640–1645.PubMedCrossRefGoogle Scholar
  22. 22.
    Bonzano L, Pardini M, Mancardi GL, Pizzorno M, Roccatagliata L. Structural connectivity influences brain activation during PVSAT in multiple sclerosis. Neuroimage. 2009;44(1):9–15.PubMedCrossRefGoogle Scholar
  23. 23.
    Brassington JC, Marsh NV. Neuropsychological aspects of multiple sclerosis. Neuropsychol Rev. 1998;8(2):43–77.PubMedCrossRefGoogle Scholar
  24. 24.
    Brooks DJ, Leenders KL, Head G, Marshall J, Legg NJ, Jones T. Studies on regional cerebral oxygen utilisation and cognitive function in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1984;47(11):1182–1191.PubMedCrossRefGoogle Scholar
  25. 25.
    Brownell B, Hughes JT. The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1962;25:315.PubMedCrossRefGoogle Scholar
  26. 26.
    Bush G, Whalen PJ, Rosen BR, Jenike MA, McInerney SC, Rauch SL. The counting Stroop: an interference task specialized for functional neuroimaging–validation study with functional MRI. Hum Brain Mapp. 1998;6(4):270–282.PubMedCrossRefGoogle Scholar
  27. 27.
    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(pt 2):527–537.PubMedGoogle Scholar
  28. 28.
    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(1):33–54.PubMedCrossRefGoogle Scholar
  29. 29.
    Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol. 2008;7(12):1139–1151.PubMedCrossRefGoogle Scholar
  30. 30.
    Christodoulou C, Krupp LB, Liang Z, et al. Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients. Neurology. 2003;60(11):1793–1798.PubMedGoogle Scholar
  31. 31.
    Chwastiak L, Ehde DM, Gibbons LE, Sullivan M, Bowen JD, Kraft GH. Depressive symptoms and severity of illness in multiple sclerosis: epidemiologic study of a large community sample. Am J Psychiatry. 2002;159(11):1862–1868.PubMedCrossRefGoogle Scholar
  32. 32.
    Comi G, Filippi M, Martinelli V, et al. Brain magnetic resonance imaging correlates of cognitive impairment in multiple sclerosis. J Neurol Sci. 1993;115(suppl):S66–73.PubMedCrossRefGoogle Scholar
  33. 33.
    Cutter GR, Baier ML, Rudick RA, et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain. 1999;122(pt 5):871–882.PubMedCrossRefGoogle Scholar
  34. 34.
    de Groot V, Beckerman H, Twisk JW, et al. Vitality, perceived social support and disease activity determine the performance of social roles in recently diagnosed multiple sclerosis: a longitudinal analysis. J Rehabil Med. 2008;40(2):151–157.PubMedCrossRefGoogle Scholar
  35. 35.
    Ebers GC, Sadovnick AD. Epidemiology. In: Paty DW, Ebers GC, eds. Multiple Sclerosis. Philadelphia, PA: FA Davis Co; 1998:5–28.Google Scholar
  36. 36.
    Filippi M, Tortorella C, Rovaris M, et al. Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2000;68(2):157–161.PubMedCrossRefGoogle Scholar
  37. 37.
    Foong J, Rozewicz L, Quaghebeur G, et al. Executive function in multiple sclerosis. The role of frontal lobe pathology. Brain. 1997;120(1):15–26.PubMedCrossRefGoogle Scholar
  38. 38.
    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(2):686–691.PubMedCrossRefGoogle Scholar
  39. 39.
    Forn C, Barros-Loscertales A, Escudero JN, et al. Compensatory activations in patients with multiple sclerosis during preserved performance on the auditory N-back task. Hum Brain Mapp. 2007;28(5):424–430.PubMedCrossRefGoogle Scholar
  40. 40.
    Franklin GM, Heaton RK, Nelson LM, Filley CM, Seibert C. Correlation of neuropsychological and MRI findings in chronic/progressive multiple sclerosis. Neurology. 1988;38(12):1826–1829.PubMedGoogle Scholar
  41. 41.
    Gronwall DM. Paced auditory serial-addition task: a measure of recovery from concussion. Percept Mot Skills. 1977;44(2):367–373.PubMedGoogle Scholar
  42. 42.
    Haacke EM, Makki M, Ge Y, et al. Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging. J Magn Reson Imaging. 2009;29(3):537–544.PubMedCrossRefGoogle Scholar
  43. 43.
    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(7):965–978.PubMedCrossRefGoogle Scholar
  44. 44.
    Hohol MJ, Guttmann CRG, Orav J, et al. Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis. Arch Neurol. 1997;54(8):1018–1025.PubMedGoogle Scholar
  45. 45.
    Houtchens MK, Benedict RH, Killiany R, et al. Thalamic atrophy and cognition in multiple sclerosis. Neurology. 2007;69(12):1213–1223.PubMedCrossRefGoogle Scholar
  46. 46.
    Huber SJ, Bornstein RA, Rammohan KW, Christy JA. Magnetic resonance imaging correlates of executive function impairments in multiple sclerosis. Neuropsychiatry Neuropsychol Behav Neurol. 1992;5(1):33–36.Google Scholar
  47. 47.
    Huber SJ, Bornstein RA, Rammohan KW, Christy JA. Magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis. J Neuropsychiatry Clin Neurosci. 1992;4(2):152–158.PubMedGoogle Scholar
  48. 48.
    Huber SJ, Paulson GW, Shuttleworth EC, et al. Magnetic resonance imaging correlates of dementia in multiple sclerosis. Arch Neurol. 1987;44(7):732–736.PubMedGoogle Scholar
  49. 49.
    Inglese M, Adhya S, Johnson G, et al. Perfusion magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis. J Cereb Blood Flow Metab. 2008;28(1):164–171.PubMedCrossRefGoogle Scholar
  50. 50.
    Janardhan V, Bakshi R. Quality of life and its relationship to brain lesions and atrophy on magnetic resonance images in 60 patients with multiple sclerosis. Arch Neurol. 2000;57(10):1485–1491.PubMedCrossRefGoogle Scholar
  51. 51.
    Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289(23):3095–3105.PubMedCrossRefGoogle Scholar
  52. 52.
    Lazeron RH, Boringa JB, Schouten M, et al. Brain atrophy and lesion load as explaining parameters for cognitive impairment in multiple sclerosis. Mult Scler. 2005;11(5):524–531.PubMedCrossRefGoogle Scholar
  53. 53.
    Lazeron RH, Rombouts SA, 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(5):549–555.PubMedCrossRefGoogle Scholar
  54. 54.
    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(4):635–639.PubMedCrossRefGoogle Scholar
  55. 55.
    Lycke J, Wikkelso C, Bergh AC, Jacobsson L, Andersen O. Regional cerebral blood flow in multiple sclerosis measured by single photon emission tomography with technetium-99m hexamethylpropyleneamine oxime. Eur Neurol. 1993;33(2):163–167.PubMedCrossRefGoogle Scholar
  56. 56.
    Mainero C, Caramia F, Pozzilli C, et al. fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis. Neuroimage. 2004;21(3):858–867.PubMedCrossRefGoogle Scholar
  57. 57.
    Mathiesen HK, Jonsson A, Tscherning T, et al. Correlation of global N-acetyl aspartate with cognitive impairment in multiple sclerosis. Arch Neurol. 2006;63(4):533–536.PubMedCrossRefGoogle Scholar
  58. 58.
    McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121–127.PubMedCrossRefGoogle Scholar
  59. 59.
    Minden SL, Schiffer RB. Affective disorders in multiple sclerosis. Review and recommendations for clinical research. Arch Neurol. 1990;47(1):98–104.PubMedGoogle Scholar
  60. 60.
    Moller A, Wiedemann G, Rohde U, Backmund H, Sonntag A. Correlates of cognitive impairment and depressive mood disorder in multiple sclerosis. Acta Psychiatr Scand. 1994;89(2):117–121.PubMedCrossRefGoogle Scholar
  61. 61.
    Morgen K, Sammer G, Courtney SM, et al. Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing-remitting MS. Neuroimage. 2006;30(3):891–898.PubMedCrossRefGoogle Scholar
  62. 62.
    Morgen K, Sammer G, Courtney SM, et al. Distinct mechanisms of altered brain activation in patients with multiple sclerosis. Neuroimage. 2007;37(3):937–946.PubMedCrossRefGoogle Scholar
  63. 63.
    Mowry EM, Beheshtian A, Waubant E, et al. Quality of life in multiple sclerosis is associated with lesion burden and brain volume measures. Neurology. 2009;72(20):1760–1765.PubMedCrossRefGoogle Scholar
  64. 64.
    Nebel K, Wiese H, Seyfarth J, et al. Activity of attention related structures in multiple sclerosis patients. Brain Res. 2007;1151:150–160.PubMedCrossRefGoogle Scholar
  65. 65.
    Owen AM, McMillan KM, Laird AR, Bullmore E. N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum Brain Mapp. 2005;25(1):46–59.PubMedCrossRefGoogle Scholar
  66. 66.
    Pan JW, Krupp LB, Elkins LE, Coyle PK. Cognitive dysfunction lateralizes with NAA in multiple sclerosis. Appl Neuropsychol. 2001;8(3):155–160.PubMedCrossRefGoogle Scholar
  67. 67.
    Parmenter BA, Zivadinov R, Kerenyi L, et al. Validity of the Wisconsin Card Sorting and Delis–Kaplan Executive Function System (DKEFS) Sorting Tests in multiple sclerosis. J Clin Exp Neuropsychol. 2007;29(2):215–223.PubMedCrossRefGoogle Scholar
  68. 68.
    Parry AM, Scott RB, Palace J, Smith S, Matthews PM. Potentially adaptive functional changes in cognitive processing for patients with multiple sclerosis and their acute modulation by rivastigmine. Brain. 2003;126(12):2750–2760.PubMedCrossRefGoogle Scholar
  69. 69.
    Paulesu E, Perani D, Fazio F, et al. Functional basis of memory impairment in multiple sclerosis: a [18F]FDG PET study. Neuroimage. 1996;4(2):87–96.PubMedCrossRefGoogle Scholar
  70. 70.
    Pelletier J, Suchet L, Witjas T, et al. A longitudinal study of callosal atrophy and interhemispheric dysfunction in relapsing-remitting multiple sclerosis. Arch Neurol. 2001;58(1):105–111.PubMedCrossRefGoogle Scholar
  71. 71.
    Penner IK, 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(4):461–472.PubMedCrossRefGoogle Scholar
  72. 72.
    Piras MR, Magnano I, Canu ED, et al. Longitudinal study of cognitive dysfunction in multiple sclerosis: neuropsychological, neuroradiological, and neurophysiological findings. J Neurol Neurosurg Psychiatry. 2003;74(7):878–885.PubMedCrossRefGoogle Scholar
  73. 73.
    Portaccio E, Amato MP, Bartolozzi ML, et al. Neocortical volume decrease in relapsing-remitting multiple sclerosis with mild cognitive impairment. J Neurol Sci. 2006;245(1–2):195–199.PubMedCrossRefGoogle Scholar
  74. 74.
    Poser CM, Brinar VV. Diagnostic criteria for multiple sclerosis: an historical review. Clin Neurol Neurosurg. 2004;106(3):147–158.PubMedCrossRefGoogle Scholar
  75. 75.
    Pozzilli C, Passafiume D, Bernardi S, et al. SPECT, MRI and cognitive functions in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1991;54(2):110–115.PubMedCrossRefGoogle Scholar
  76. 76.
    Prinster A, Quarantelli M, Orefice G, et al. Grey matter loss in relapsing-remitting multiple sclerosis: a voxel-based morphometry study. Neuroimage. 2006;29(3):859–867.PubMedCrossRefGoogle Scholar
  77. 77.
    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(1–2):11–16.PubMedCrossRefGoogle Scholar
  78. 78.
    Rao SM. Neuropsychological studies in chronic progressive multiple sclerosis. Ann N Y Acad Sci. 1984;436:495–497.CrossRefGoogle Scholar
  79. 79.
    Rao SM. Neurobehavioral Aspects of Multiple Sclerosis. New York: Oxford University Press; 1990.Google Scholar
  80. 80.
    Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology. 1991;41(5):685–691.PubMedGoogle Scholar
  81. 81.
    Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology. 1991;41(5):692–696.PubMedGoogle Scholar
  82. 82.
    Rao SM, Leo GJ, Haughton VM, St Aubin-Faubert P, Bernardin L. Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis. Neurology. 1989;39(1):161–166.PubMedGoogle Scholar
  83. 83.
    Roca M, Torralva T, Meli F, et al. Cognitive deficits in multiple sclerosis correlate with changes in fronto-subcortical tracts. Mult Scler. 2008;14(3):364–369.PubMedCrossRefGoogle Scholar
  84. 84.
    Roelcke U, Kappos L, Lechner-Scott J, et al. Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study. Neurology. 1997;48(6):1566–1571.PubMedGoogle Scholar
  85. 85.
    Ron MA. Multiple sclerosis: psychiatric and psychometric abnormalities. J Psychosom Res. 1986;30(1):3–11.PubMedCrossRefGoogle Scholar
  86. 86.
    Rovaris M, Filippi M, Falautano M, et al. Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis. Neurology. 1998;50(6):1601–1608.PubMedGoogle Scholar
  87. 87.
    Rovaris M, Filippi M, Minicucci L, et al. Cortical/subcortical disease burden and cognitive impairment in patients with multiple sclerosis. AJNR Am J Neuroradiol. 2000;21(2):402–408.PubMedGoogle Scholar
  88. 88.
    Rovaris M, Iannucci G, Falautano M, et al. Cognitive dysfunction in patients with mildly disabling relapsing-remitting multiple sclerosis: an exploratory study with diffusion tensor MR imaging. J Neurol Sci. 2002;195(2):103–109.PubMedCrossRefGoogle Scholar
  89. 89.
    Ryan L, Clark C, Klonoff H, Li D, Paty D. Patterns of cognitive impairment in relapsing-remitting multiple sclerosis and their relationship to neuropathy on MRI. Neuropsychology. 1996;10:176–193.CrossRefGoogle Scholar
  90. 90.
    Sailer M, Fischl B, Salat D, et al. Focal thinning of the cerebral cortex in multiple sclerosis. Brain. 2003;126(8):1734–1744.PubMedCrossRefGoogle Scholar
  91. 91.
    Sanfilipo MP, Benedict RH, Weinstock-Guttman B, Bakshi R. Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology. 2006;66(5):685–692.PubMedCrossRefGoogle Scholar
  92. 92.
    Shallice T. Specific impairments of planning. Philos Trans R Soc Lond B Biol Sci. 1982;298(1089):199–209.PubMedCrossRefGoogle Scholar
  93. 93.
    Sperling RA, Guttmann CR, Hohol MJ, et al. Regional magnetic resonance imaging lesion burden and cognitive function in multiple sclerosis: a longitudinal study. Arch Neurol. 2001;58(1):115–121.PubMedCrossRefGoogle Scholar
  94. 94.
    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(6):1275–1282.PubMedCrossRefGoogle Scholar
  95. 95.
    Staffen W, Zauner H, Mair A, et al. Magnetic resonance spectroscopy of memory and frontal brain region in early multiple sclerosis. J Neuropsychiatry Clin Neurosci. 2005;17(3):357–363.PubMedGoogle Scholar
  96. 96.
    Summers M, Swanton J, Fernando K, et al. Cognitive impairment in multiple sclerosis can be predicted by imaging early in the disease. J Neurol Neurosurg Psychiatry. 2008;79(8):955–958.PubMedCrossRefGoogle Scholar
  97. 97.
    Sun X, Tanaka M, Kondo S, Okamoto K, Hirai S. Clinical significance of reduced cerebral metabolism in multiple sclerosis: a combined PET and MRI study. Ann Nucl Med. 1998;12(2):89–94.PubMedCrossRefGoogle Scholar
  98. 98.
    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(1):28–36.PubMedCrossRefGoogle Scholar
  99. 99.
    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(2):150–157.PubMedGoogle Scholar
  100. 100.
    Swirsky-Sacchetti T, Mitchell DR, Seward J, et al. Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis. Neurology. 1992;42(7):1291–1295.PubMedGoogle Scholar
  101. 101.
    Tekok-Kilic A, Benedict RH, Zivadinov R. Update on the relationships between neuropsychological dysfunction and structural MRI in multiple sclerosis. Expert Rev Neurother. 2006;6(3):323–331.PubMedCrossRefGoogle Scholar
  102. 102.
    Tsolaki M, Drevelegas A, Karachristianou S, Kapinas K. Correlation of dementia, neuropsychological and MRI findings in multiple sclerosis. Dementia. 1994;5(1):48–52.PubMedGoogle Scholar
  103. 103.
    Valsasina P, Benedetti B, Rovaris M, Sormani MP, Comi G, Filippi M. Evidence for progressive gray matter loss in patients with relapsing-remitting MS. Neurology. 2005;65(7):1126–1128.PubMedCrossRefGoogle Scholar
  104. 104.
    Wishart HA, Saykin AJ, McDonald BC, et al. Brain activation patterns associated with working memory in relapsing-remitting MS. Neurology. 2004;62(2):234–238.PubMedGoogle Scholar
  105. 105.
    Zivadinov R, De Masi R, Nasuelli D, et al. MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis. Neuroradiology. 2001;43(4):272–278.PubMedCrossRefGoogle Scholar
  106. 106.
    Zivadinov R, Sepcic J, Nasuelli D, et al. A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2001;70(6):773–780.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Psychiatry and Human BehaviorWarren Alpert Medical School of Brown UniversityProvidenceUSA

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