Abstract
Patients with multiple sclerosis (MS) activate a more diffuse cortical network than do healthy subjects when they perform motor tasks. This brain functional reorganisation might contribute to the limiting of disability, but it is unclear whether there is a loss of regional activation in more advanced disease. The aim of this study was to assess whether functional reorganisation diminishes in more disabled patients with primary progressive (PP) MS. The differences in the fMRI response to active and passive movements of the dominant ankle of 13 patients and 16 controls were assessed. The relationships between functional activation and disability and brain lesion load and atrophy were investigated.
Patients showed greater fMRI activation than controls with passive movements in the superior temporal gyrus, rolandic operculum, and putamen. The fMRI response to active and passive movements in the ipsilateral inferior frontal gyrus was lower in patients with greater disability and greater brain T2 lesion load, respectively. Furthermore, the fMRI activation with active movements in the contralateral cerebellum was lower in patients with worse mobility.
The increased activity with passive movements in regions that participate in sensori–motor integration, such as the putamen, reflects true functional reorganisation, since passive movements induce brain activation through sensory afferents only. The inverse correlation between the fMRI response in regions that are associated with motor control, and clinical or MRI measures of disease progression, suggests that there is a loss of distributed activation in more disabled patients. This may inform future treatment strategies.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Filippi M, Rocca MA (2003) Disturbed function and plasticity in multiple sclerosis as gleaned from functional magnetic resonance imaging. Curr Opin Neurol 16:275–282
Audoin B, Ibarrola D, Ranjeva JP, Confort– Gouny S, Malikova I, Ali–Cherif A, Pelletier J, Cozzone P (2003) Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS. Hum Brain Mapp 20:51–58
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
Lee M, Reddy H, Johansen–Berg H, Pendlebury S, Jenkinson M, Smith S, Palace J, Matthews PM (2000) The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis. Ann Neurol 47:606–613
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 123:2314–2320
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
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
Filippi M, Rocca MA, Falini A, Caputo D, Ghezzi A, Colombo B, Scotti G, Comi G (2002) Correlations between structural CNS damage and functional MRI changes in primary progressive MS. Neuroimage 15:537–546
Thompson AJ, Montalban X, Barkhof F, Brochet B, Filippi M, Miller DH, Polman CH, Stevenson VL, McDonald WI (2000) Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol 47:831–835
Thompson AJ, Kermode AG, Wicks D, MacManus DG, Kendall BE, Kingsley DP, McDonald WI (1991) Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol 29:53–62
Wolinsky JS (2003) The diagnosis of primary progressive multiple sclerosis. J Neurol Sci 206:145–152
Reddy H, Narayanan S, Woolrich M, Mitsumori T, Lapierre Y, Arnold DL, Matthews PM (2002) Functional brain reorganization for hand movement in patients with multiple sclerosis: defining distinct effects of injury and disability. Brain 125:2646–2657
Penfield W, Rasmusseun T (1950) The cerebral cortex of man. New York: Macmillan
Dobkin BH, Firestine A, West M, Saremi K, Woods R (2004) Ankle dorsiflexion as an fMRI paradigm to assay motor control for walking during rehabilitation. Neuroimage 23:370–381
Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452
Schwid SR, Goodman AD, Mattson DH, Mihai C, Donohoe KM, Petrie MD, Scheid EA, Dudman JT, McDermott MP (1997) The measurement of ambulatory impairment in multiple sclerosis. Neurology 49:1419–1424
Bohannon RW, Smith MB (1987) Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 67:206–207
Raczkowski D, Kalat JW, Nebes R (1974) Reliability and validity of some handedness questionnaire items. Neuropsychologia 12:43–47
Friston KJ, Holmes AP, Worsley KJ, Poline JB, Frith CD, Frackowiak RSJ (1995) Statistical parametric maps in functional imaging: A general linear approach. Hum Brain Mapp 2:189–210
Worsley KJ, Friston KJ (1995) Analysis of fMRI time–series revisited – again. Neuroimage 2:173–181
Friston KJ, Holmes AP, Worsley KJ (1999) How many subjects constitute a study? Neuroimage 10:1–5
Worsley KJ, Marrett S, Neelin P, Vandal AC, Friston KJ, Evans AC (1996) A unified statistical approach for determining significant signals in images of cerebral activation. Hum Brain Mapp 4:58–73
Sahyoun C, Floyer–Lea A, Johansen– Berg H, Matthews PM (2004) Towards an understanding of gait control: brain activation during the anticipation, preparation and execution of foot movements. Neuroimage 21:568–575
Rocca MA, Matthews PM, Caputo D, Ghezzi A, Falini A, Scotti G, Comi G, Filippi M (2002) Evidence for widespread movement–associated functional MRI changes in patients with PPMS. Neurology 58:866–872
Rorden C, Brett M (2000) Stereotaxic display of brain lesions. Behav Neurol 12:191–200
Plummer DL (1992) Dispimage: a display and analysis tool for medical images. Rev Neuroradiol 5:489–495
Chard DT, Parker GJ, Griffin CM, Thompson AJ, Miller DH (2002) The reproducibility and sensitivity of brain tissue volume measurements derived from an SPM–based segmentation methodology. J Magn Reson Imaging 15:259–267
Rocca MA, Pagani E, Ghezzi A, Falini A, Zaffaroni M, Colombo B, Scotti G, Comi G, Filippi M (2003) Functional cortical changes in patients with multiple sclerosis and nonspecific findings on conventional magnetic resonance imaging scans of the brain. Neuroimage 19:826–836
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
Filippi M, Rocca MA, Mezzapesa DM, Ghezzi A, Falini A, Martinelli V, Scotti G, Comi G (2004) Simple and complex movement–associated functional MRI changes in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Hum Brain Mapp 21:108–117
Yeterian EH, Pandya DN (1998) Corticostriatal connections of the superior temporal region in rhesus monkeys. J Comp Neurol 399:384–402
Ward NS, Frackowiak RS (2003) Agerelated changes in the neural correlates of motor performance. Brain 126:873–888
Weiller C, Juptner M, Fellows S, Rijntjes M, Leonhardt G, Kiebel S, Muller S, Diener HC, Thilmann AF (1996) Brain representation of active and passive movements. Neuroimage 4:105–110
Gerardin E, Lehericy S, Pochon JB, Tezenas du MS, Mangin JF, Poupon F, Agid Y, Le Bihan D, Marsault C (2003) Foot, hand, face and eye representation in the human striatum. Cereb Cortex 13:162–169
Ciccarelli O, Toosy AT, Marsden JF, Wheeler–Kingshott CM, Sahyoun C, Matthews PM, Miller DH, Thompson AJ (2005) Identifying brain regions for integrative sensorimotor processing with ankle movements. Exp Brain Res 166:31–42
Abbruzzese G, Berardelli A (2003) Sensorimotor integration in movement disorders. Mov Disord 18:231–240
Rizzolatti G, Luppino G (2001) The cortical motor system. Neuron 31:889–901
Filippi M, Rocca MA, Mezzapesa DM, Falini A, Colombo B, Scotti G, Comi G (2004) A functional MRI study of cortical activations associated with object manipulation in patients with MS. Neuroimage 21:1147–1154
Rocca MA, Mezzapesa DM, Falini A, Ghezzi A, Martinelli V, Scotti G, Comi G, Filippi M (2003) Evidence for axonal pathology and adaptive cortical reorganization in patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis. Neuroimage 18:847–855
Okabe S, Hanajima R, Ohnishi T, Nishikawa M, Imabayashi E, Takano H, Kawachi T, Matsuda H, Shiio Y, Iwata NK, Furubayashi T, Terao Y, Ugawa Y (2003) Functional connectivity revealed by single–photon emission computed tomography (SPECT) during repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. Clin Neurophysiol 114:450–457
Pantano P, Mainero C, Lenzi D, Caramia F, Iannetti GD, Piattella MC, Pestalozza I, Di Legge S, Bozzao L, Pozzilli C (2005) A longitudinal fMRI study on motor activity in patients with multiple sclerosis. Brain 128:2146–2153
Filippi M, Rocca MA (2004) Cortical reorganisation in patients with MS. J Neurol Neurosurg Psychiatry 75:1087–1089
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
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ciccarelli, O., Toosy, A.T., Marsden, J.F. et al. Functional response to active and passive ankle movements with clinical correlations in patients with primary progressive multiple sclerosis. J Neurol 253, 882–891 (2006). https://doi.org/10.1007/s00415-006-0125-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-006-0125-z