Skip to main content
SpringerLink
Log in

Imaging resting state brain function in multiple sclerosis

  • Review
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

In multiple sclerosis (MS), physical and cognitive deficits not only reflect structural damage, but also functional imbalance in and between brain networks. Resting-state functional magnetic resonance imaging (fMRI) allows one to investigate intrinsic, synchronized brain activity across the whole brain, and to measure the degree of functional correlation between different cortical regions. This review describes the major findings obtained in MS patients at different clinical stages using resting state fMRI, and discusses how the use of fMRI techniques may improve our ability to identify novel biomarkers useful in the context of the diagnostic work-up, establishing prognosis and monitoring treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Agosta F, Canu E, Valsasina P, Riva N, Prelle A, Comi G, Filippi M (2012) Divergent brain network connectivity in amyotrophic lateral sclerosis. Neurobiol Aging (in press)

  2. Agosta F, Pievani M, Geroldi C, Copetti M, Frisoni GB, Filippi M (2011) Resting state fMRI in Alzheimer’s disease: beyond the default mode network. Neurobiol Aging 33:1564–1578

    Article  PubMed  Google Scholar 

  3. Agosta F, Valsasina P, Absinta M, Riva N, Sala S, Prelle A, Copetti M, Comola M, Comi G, Filippi M (2011) Sensorimotor functional connectivity changes in amyotrophic lateral sclerosis. Cereb Cortex 21:2291–2298

    Article  PubMed  CAS  Google Scholar 

  4. Audoin B, Au Duong MV, Ranjeva JP, Ibarrola D, Malikova I, Confort-Gouny S, Soulier E, Viout P, Ali-Cherif A, Pelletier J, Cozzone PJ (2005) 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 24:216–228

    Article  PubMed  Google Scholar 

  5. Barkhof F (2002) The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol 15:239–245

    Article  PubMed  Google Scholar 

  6. Bassett DS, Nelson BG, Mueller BA, Camchong J, Lim KO (2012) Altered resting state complexity in schizophrenia. Neuroimage 59:2196–2207

    Article  PubMed  Google Scholar 

  7. Bonavita S, Gallo A, Sacco R, Corte MD, Bisecco A, Docimo R, Lavorgna L, Corbo D, Costanzo AD, Tortora F, Cirillo M, Esposito F, Tedeschi G (2011) Distributed changes in default-mode resting-state connectivity in multiple sclerosis. Mult Scler 17:411–422

    Article  PubMed  Google Scholar 

  8. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38

    Article  PubMed  Google Scholar 

  9. Cader S, Cifelli A, Abu-Omar Y, Palace J, Matthews PM (2006) Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis. Brain 129:527–537

    Article  PubMed  Google Scholar 

  10. Cerasa A, Fera F, Gioia MC, Liguori M, Passamonti L, Nicoletti G, Vercillo L, Paolillo A, Clodomiro A, Valentino P, Quattrone A (2006) Adaptive cortical changes and the functional correlates of visuo-motor integration in relapsing-remitting multiple sclerosis. Brain Res Bull 69:597–605

    Article  PubMed  Google Scholar 

  11. Cole DM, Smith SM, Beckmann CF (2010) Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Front Syst Neurosci 4:8

    PubMed  Google Scholar 

  12. Damoiseaux JS, Beckmann CF, Arigita EJ, Barkhof F, Scheltens P, Stam CJ, Smith SM, Rombouts SA (2008) Reduced resting-state brain activity in the “default network” in normal aging. Cereb Cortex 18:1856–1864

    Article  PubMed  CAS  Google Scholar 

  13. Douaud G, Filippini N, Knight S, Talbot K, Turner MR (2011) Integration of structural and functional magnetic resonance imaging in amyotrophic lateral sclerosis. Brain 134:3470–3479

    Article  PubMed  Google Scholar 

  14. Faivre A, Rico A, Zaaraoui W, Crespy L, Reuter F, Wybrecht D, Soulier E, Malikova I, Confort-Gouny S, Cozzone PJ, Pelletier J, Ranjeva JP, Audoin B (2012) Assessing brain connectivity at rest is clinically relevant in early multiple sclerosis. Mult Scler 18(9):1251–1258

    Article  PubMed  Google Scholar 

  15. Filippi M, Agosta F (2010) Imaging biomarkers in multiple sclerosis. J Magn Reson Imaging 31:770–788

    Article  PubMed  CAS  Google Scholar 

  16. Filippi M, Riccitelli G, Mattioli F, Capra R, Stampatori C, Pagani E, Valsasina P, Copetti M, Falini A, Comi G, Rocca MA (2012) Multiple sclerosis: effects of cognitive rehabilitation on structural and functional MR imaging measures–an explorative study. Radiology 262:932–940

    Article  PubMed  Google Scholar 

  17. Filippi M, Rocca MA (2009) Functional MR imaging in multiple sclerosis. Neuroimaging Clin N Am 19:59–70

    Article  PubMed  Google Scholar 

  18. Filippi M, Rocca MA, De Stefano N, Enzinger C, Fisher E, Horsfield MA, Inglese M, Pelletier D, Comi G (2012) Magnetic resonance techniques in multiple sclerosis: the present and the future. Arch Neurol 68:1514–1520

    Article  Google Scholar 

  19. Fox MD, Greicius M (2010) Clinical applications of resting state functional connectivity. Front Syst Neurosci 4:19

    PubMed  Google Scholar 

  20. Fox MD, Raichle ME (2007) Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci 8:700–711

    Article  PubMed  CAS  Google Scholar 

  21. Greicius MD, Flores BH, Menon V, Glover GH, Solvason HB, Kenna H, Reiss AL, Schatzberg AF (2007) Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry 62:429–437

    Article  PubMed  Google Scholar 

  22. Greicius MD, Srivastava G, Reiss AL, Menon V (2004) Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci USA 101:4637–4642

    Article  PubMed  CAS  Google Scholar 

  23. Hawellek DJ, Hipp JF, Lewis CM, Corbetta M, Engel AK (2011) Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis. Proc Natl Acad Sci USA 108:19066–19071

    Article  PubMed  CAS  Google Scholar 

  24. Leavitt VM, Wylie GR, Girgis PA, Deluca J, Chiaravalloti ND (2012) Increased functional connectivity within memory networks following memory rehabilitation in multiple sclerosis. Brain Imaging Behav (in press)

  25. Levin N, Orlov T, Dotan S, Zohary E (2006) Normal and abnormal fMRI activation patterns in the visual cortex after recovery from optic neuritis. Neuroimage 33:1161–1168

    Article  PubMed  Google Scholar 

  26. Logothetis NK (2008) What we can do and what we cannot do with fMRI. Nature 453:869–878

    Article  PubMed  CAS  Google Scholar 

  27. Loitfelder M, Fazekas F, Petrovic K, Fuchs S, Ropele S, Wallner-Blazek M, Jehna M, Aspeck E, Khalil M, Schmidt R, Neuper C, Enzinger C (2011) Reorganization in cognitive networks with progression of multiple sclerosis: insights from fMRI. Neurology 76:526–533

    Article  PubMed  CAS  Google Scholar 

  28. Loitfelder M, Filippi M, Rocca M, Valsasina P, Ropele S, Jehna M, Fuchs S, Schmidt R, Neuper C, Fazekas F, Enzinger C (2012) Abnormalities of resting state functional connectivity are related to sustained attention deficits in MS. PLoS ONE 7:e42862

    Article  PubMed  CAS  Google Scholar 

  29. Mainero C, Caramia F, Pozzilli C, Pisani A, Pestalozza I, Borriello G, Bozzao L, Pantano P (2004) fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis. Neuroimage 21:858–867

    Article  PubMed  Google Scholar 

  30. Mainero C, Pantano P, Caramia F, Pozzilli C (2006) Brain reorganization during attention and memory tasks in multiple sclerosis: insights from functional MRI studies. J Neurol Sci 245:93–98

    Article  PubMed  Google Scholar 

  31. Pantano P, Mainero C, Iannetti GD, Caramia F, Di Legge S, Piattella MC, Pozzilli C, Bozzao L, Lenzi GL (2002) Contribution of corticospinal tract damage to cortical motor reorganization after a single clinical attack of multiple sclerosis. Neuroimage 17:1837–1843

    Article  PubMed  Google Scholar 

  32. Parisi L, Rocca MA, Valsasina P, Panicari L, Mattioli F, Filippi M (2012) Cognitive rehabilitation correlates with the functional connectivity of the anterior cingulate cortex in patients with multiple sclerosis. Brain Imaging Behav 158(4):882–887

    Google Scholar 

  33. Petrella JR, Sheldon FC, Prince SE, Calhoun VD, Doraiswamy PM (2011) Default mode network connectivity in stable vs progressive mild cognitive impairment. Neurology 76:511–517

    Article  PubMed  CAS  Google Scholar 

  34. Qi Z, Wu X, Wang Z, Zhang N, Dong H, Yao L, Li K (2010) Impairment and compensation coexist in amnestic MCI default mode network. Neuroimage 50:48–55

    Article  PubMed  Google Scholar 

  35. Raichle ME (2009) A brief history of human brain mapping. Trends Neurosci 32:118–126

    Article  PubMed  CAS  Google Scholar 

  36. Raichle ME, Snyder AZ (2007) A default mode of brain function: a brief history of an evolving idea. Neuroimage 37:1083–1090

    Article  PubMed  Google Scholar 

  37. Reddy H, Narayanan S, Arnoutelis R, Jenkinson M, Antel J, Matthews PM, Arnold DL (2000) Evidence for adaptive functional changes in the cerebral cortex with axonal injury from multiple sclerosis. Brain 123(Pt 11):2314–2320

    Article  PubMed  Google Scholar 

  38. Reddy H, Narayanan S, Matthews PM, Hoge RD, Pike GB, Duquette P, Antel J, Arnold DL (2000) Relating axonal injury to functional recovery in MS. Neurology 54:236–239

    Article  PubMed  CAS  Google Scholar 

  39. Richiardi J, Gschwind M, Simioni S, Annoni JM, Greco B, Hagmann P, Schluep M, Vuilleumier P, Van De Ville D (2012) Classifying minimally disabled multiple sclerosis patients from resting state functional connectivity. Neuroimage 62:2021–2033

    Article  PubMed  Google Scholar 

  40. Rocca MA, Colombo B, Falini A, Ghezzi A, Martinelli V, Scotti G, Comi G, Filippi M (2005) Cortical adaptation in patients with MS: a cross-sectional functional MRI study of disease phenotypes. Lancet Neurol 4:618–626

    Article  PubMed  Google Scholar 

  41. Rocca MA, Falini A, Colombo B, Scotti G, Comi G, Filippi M (2002) Adaptive functional changes in the cerebral cortex of patients with nondisabling multiple sclerosis correlate with the extent of brain structural damage. Ann Neurol 51:330–339

    Article  PubMed  Google Scholar 

  42. Rocca MA, Gavazzi C, Mezzapesa DM, Falini A, Colombo B, Mascalchi M, Scotti G, Comi G, Filippi M (2003) A functional magnetic resonance imaging study of patients with secondary progressive multiple sclerosis. Neuroimage 19:1770–1777

    Article  PubMed  Google Scholar 

  43. Rocca MA, Pagani E, Absinta M, Valsasina P, Falini A, Scotti G, Comi G, Filippi M (2007) Altered functional and structural connectivities in patients with MS: a 3-T study. Neurology 69:2136–2145

    Article  PubMed  CAS  Google Scholar 

  44. Rocca MA, Valsasina P, Absinta M, Riccitelli G, Rodegher ME, Misci P, Rossi P, Falini A, Comi G, Filippi M (2010) Default-mode network dysfunction and cognitive impairment in progressive MS. Neurology 74:1252–1259

    Article  PubMed  CAS  Google Scholar 

  45. Rocca MA, Valsasina P, Martinelli V, Misci P, Falini A, Comi G, Filippi M (2012) Large-scale neuronal network dysfunction in relapsing-remitting multiple sclerosis. Neurology (in press)

  46. Roosendaal SD, Schoonheim MM, Hulst HE, Sanz-Arigita EJ, Smith SM, Geurts JJ, Barkhof F (2010) Resting state networks change in clinically isolated syndrome. Brain 133:1612–1621

    Article  PubMed  Google Scholar 

  47. Smith SM, Fox PT, Miller KL, Glahn DC, Fox PM, Mackay CE, Filippini N, Watkins KE, Toro R, Laird AR, Beckmann CF (2009) Correspondence of the brain’s functional architecture during activation and rest. Proc Natl Acad Sci U S A 106:13040–13045

    Article  PubMed  CAS  Google Scholar 

  48. Sumowski JF, Wylie GR, Deluca J, Chiaravalloti N (2010) Intellectual enrichment is linked to cerebral efficiency in multiple sclerosis: functional magnetic resonance imaging evidence for cognitive reserve. Brain 133:362–374

    Article  PubMed  Google Scholar 

  49. Tessitore A, Amboni M, Esposito F, Russo A, Picillo M, Marcuccio L, Pellecchia MT, Vitale C, Cirillo M, Tedeschi G, Barone P (2012) Resting-state brain connectivity in patients with Parkinson’s disease and freezing of gait. Parkinsonism Relat Disord 18:781–787

    Article  PubMed  Google Scholar 

  50. Whitwell JL, Avula R, Master A, Vemuri P, Senjem ML, Jones DT, Jack CR Jr, Josephs KA (2011) Disrupted thalamocortical connectivity in PSP: a resting-state fMRI, DTI, and VBM study. Parkinsonism Relat Disord 17:599–605

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

The Authors declare that they have no conflict of interest related to the publication of this manuscript.

Author information

Authors and Affiliations

  1. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, via Olgettina 60, 20132, Milan, Italy

    Massimo Filippi, Federica Agosta, Edoardo G. Spinelli & Maria Assunta Rocca

Authors
  1. Massimo Filippi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Federica Agosta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edoardo G. Spinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Assunta Rocca
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Massimo Filippi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Filippi, M., Agosta, F., Spinelli, E.G. et al. Imaging resting state brain function in multiple sclerosis. J Neurol 260, 1709–1713 (2013). https://doi.org/10.1007/s00415-012-6695-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-012-6695-z

Keywords

Search

Navigation