Archives of Physical Medicine and Rehabilitation
Volume 89, Issue 9 , Pages 1633-1641 , September 2008

Levodopa Improves Procedural Motor Learning in Chronic Stroke Patients

  • Nina Rösser, MA

      Affiliations

    • Department of Neurology, University of Münster, Münster, Germany
  • ,
  • Peter Heuschmann, MD, MPH

      Affiliations

    • Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
  • ,
  • Heike Wersching, MD

      Affiliations

    • Department of Neurology, University of Münster, Münster, Germany
  • ,
  • Caterina Breitenstein, PhD

      Affiliations

    • Department of Neurology, University of Münster, Münster, Germany
    • IMF Münster, University of Münster, Münster, Germany
  • ,
  • Stefan Knecht, MD

      Affiliations

    • Department of Neurology, University of Münster, Münster, Germany
  • ,
  • Agnes Flöel, MD

      Affiliations

    • Department of Neurology, University of Münster, Münster, Germany
    • IMF Münster, University of Münster, Münster, Germany
    • Corresponding Author InformationReprint requests to Agnes Flöel, MD, Dept of Neurology, University of Münster, Albert-Schweitzer-Str 33, 48149 Münster, Germany

References 

  1. Dennis MS, Burn JP, Sandercock PA, Bamford JM, Wade DT, Warlow CP. Long-term survival after first-ever stroke: the Oxfordshire Community Stroke Project. Stroke. 1993;24:796–800
  2. Ferrucci L, Bandinelli S, Guralnik JM, et al. Recovery of functional status after stroke (A postrehabilitation follow-up study). Stroke. 1993;24:200–205
  3. Rossini PM, Calautti C, Pauri F, Baron JC. Post-stroke plastic reorganisation in the adult brain. Lancet Neurol. 2003;2:493–502
  4. Chen R, Cohen LG, Hallett M. Nervous system reorganization following injury. Neuroscience. 2002;111:761–773
  5. Taub E, Uswatte G, Elbert T. New treatments in neurorehabilitation founded on basic research. Nat Rev Neurosci. 2002;3:228–236
  6. Cabeza R. Cognitive neuroscience of aging: contributions of functional neuroimaging. Scand J Psychol. 2001;42:277–286
  7. Li SC, Sikstrom S. Integrative neurocomputational perspectives on cognitive aging, neuromodulation, and representation. Neurosci Biobehav Rev. 2002;26:795–808
  8. Hedden T, Gabrieli JD. Insights into the ageing mind: a view from cognitive neuroscience. Nat Rev Neurosci. 2004;5:87–96
  9. Floel A, Hummel F, Breitenstein C, Knecht S, Cohen LG. Dopaminergic effects on encoding of a motor memory in chronic stroke. Neurology. 2005;65:472–474
  10. Bao S, Chan VT, Merzenich MM. Cortical remodelling induced by activity of ventral tegmental dopamine neurons. Nature. 2001;412:79–83
  11. Goerendt IK, Messa C, Lawrence AD, Grasby PM, Piccini P, Brooks DJ. Dopamine release during sequential finger movements in health and Parkinson's disease: a PET study. Brain. 2003;126(Pt 2):312–325
  12. Roelfsema PR, Engel AK, König P, Singer W. Visuomotor integration is associated with zero time-lag synchronization among cortical areas. Nature. 1997;385:157–161
  13. Stelmach GE, Worringham CJ, Strand EA. The programming and execution of movement sequences in Parkinson's disease. Int J Neurosci. 1987;36:55–65
  14. Carlsson A. Age-dependent changes in central dopaminergic and other monoaminergic systems. Adv Exp Med Biol. 1978;113:1–13
  15. Fearnley JM, Lees AJ. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain. 1991;114(Pt 5):2283–2301
  16. Volkow ND, Gur RC, Wang GJ, et al. Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatry. 1998;155:344–349
  17. Jay TM. Dopamine: a potential substrate for synaptic plasticity and memory mechanisms. Prog Neurobiol. 2003;69:375–390
  18. Wise RA. Dopamine, learning and motivation. Nat Rev Neurosci. 2004;5:483–494
  19. Scheidtmann K, Fries W, Müller F, Koenig E. Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study. Lancet. 2001;358:787–790
  20. Floel A, Breitenstein C, Hummel F, et al. Dopaminergic influences on formation of a motor memory. Ann Neurol. 2005;58:121–130
  21. Meintzschel F, Ziemann U. Modification of practice-dependent plasticity in human motor cortex by neuromodulators. Cereb Cortex. 2006;16:1106–1115
  22. Rosenbaum DA, Carlson RA, Gilmore RO. Acquisition of intellectual and perceptual-motor skills. Annu Rev Psychol. 2001;52:453–470
  23. Cohen NJ, Squire LR. Preserved learning and retention of pattern-analyzing skill in amnesia: dissociation of knowing how and knowing that. Science. 1980;210:207–210
  24. Sanes JN. Neocortical mechanisms in motor learning. Curr Opin Neurobiol. 2003;13:225–231
  25. Nissen MJ. Attentional requirements of learning: evidence from performance measures. Cogn Psychol. 1987;19:1–32
  26. Steinberg GK, Bell TE, Yenari MA. Dose escalation safety and tolerance study of the N-methyl-d-aspartate antagonist dextromethorphan in neurosurgery patients. J Neurosurg. 1996;84:860–866
  27. Howard JH, Howard DV. Age differences in implicit learning of higher order dependencies in serial patterns. Psychol Aging. 1997;12:634–656
  28. Berns GS, Cohen JD, Mintun MA. Brain regions responsive to novelty in the absence of awareness. Science. 1997;276:1272–1275
  29. Maquet P. Sleep on it!. Nat Neurosci. 2000;3:1235–1236
  30. Jimenez L, Mendez C, Cleeremans A. Comparing direct and indirect measures of sequence learning. J Exp Psychol Learn Mem Cogn. 1996;22:948–969
  31. Cleeremans A, McClelland JL. Learning the structure of event sequences. J Exp Psychol Gen. 1991;120:235–253
  32. Medical Research Council. Aids to examination of the peripheral nervous system. London: HMSO; 1976.
  33. Folstein MF, Robins LN, Helzer JE. The Mini-Mental State Examination. Arch Gen Psychiatry. 1983;40:812
  34. Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther. 1987;67:206–207
  35. Lincoln N, Leadbitter D. Assessment of motor function in stroke patients. Physiotherapy. 1979;65:48–51
  36. Knecht S, Breitenstein C, Bushuven S, et al. Levodopa: faster and better word learning in normal humans. Ann Neurol. 2004;56:20–26
  37. Goldberg LI. Dopamine-receptors and hypertension (Physiologic and pharmacologic implications). Am J Med. 1984;77:37–44
  38. Murphy MB, Elliott WJ. Dopamine and dopamine receptor agonists in cardiovascular therapy. Crit Care Med. 1990;18(1 Pt 2):S14–S18
  39. Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988;54:1063–1070
  40. Krohne HW, Egloff B, Kohlmann CW, Tausch A. Investigations with a German version of the positive and negative affect schedule (PANAS). Diagnostica. 1996;42:139–156
  41. Rascol O, Brefel-Courbon C, Payoux P, Ferreira J. The management of patients with early Parkinson's disease. Adv Neurol. 2003;91:203–211
  42. Werhahn KJ, Conforto AB, Kadom N, Hallett M, Cohen LG. Contribution of the ipsilateral motor cortex to recovery after chronic stroke. Ann Neurol. 2003;54:464–472
  43. Floel A, Nagorsen U, Werhahn KJ, et al. Influence of somatosensory input on motor function in patients with chronic stroke. Ann Neurol. 2004;56:206–212
  44. Baumer T, Dammann E, Bock F, Klöppel S, Siebner HR, Münchau A. Laterality of interhemispheric inhibition depends on handedness. Exp Brain Res. 2007;180:195–203
  45. Zemke AC, Heagerty PJ, Lee C, Cramer SC. Motor cortex organization after stroke is related to side of stroke and level of recovery. Stroke. 2003;34:e23–e28
  46. Karni A, Meyer G, Jezzard P, Adams MM, Turner R, Ungerleider LG. Functional MRI evidence for adult motor cortex plasticity during motor skill learning. Nature. 1995;377:155–158
  47. Muellbacher W, Ziemann U, Wissel J, et al. Early consolidation in human primary motor cortex. Nature. 2002;415:640–644
  48. Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993;361:31–39
  49. Hess G, Aizenman CD, Donoghue JP. Conditions for the induction of long-term potentiation in layer II/III horizontal connections of the rat motor cortex. J Neurophysiol. 1996;75:1765–1778
  50. Rioult-Pedotti MS, Friedman D, Hess G, Donoghue JP. Strengthening of horizontal cortical connections following skill learning. Nat Neurosci. 1998;1:230–234
  51. Rioult-Pedotti MS, Friedman D, Donoghue JP. Learning-induced LTP in neocortex. Science. 2000;290:533–536
  52. Bailey CH, Giustetto M, Huang YY, Hawkins RD, Kandel ER. Is heterosynaptic modulation essential for stabilizing Hebbian plasticity and memory?. Nat Rev Neurosci. 2000;1:11–20
  53. Wickens J, Kotter R. Cellular models of reinforcement. In:  Houk J editors. Models of information processing in the basal ganglia. Cambridge: MIT Pr; 1995;p. 187–214
  54. Bütefisch CM, Davis BC, Wise SP, et al. Mechanisms of use-dependent plasticity in the human motor cortex. Proc Natl Acad Sci U S A. 2000;97:3661–3665
  55. Bütefisch CM, Davis BC, Sawaki L, et al. Modulation of use-dependent plasticity by d-amphetamine. Ann Neurol. 2002;51:59–68
  56. Sawaki L, Cohen LG, Classen J, Davis BC, Bütefisch CM. Enhancement of use-dependent plasticity by D-amphetamine. Neurology. 2002;59:1262–1264
  57. Sawaki L, Werhahn KJ, Barco R, Kopylev L, Cohen LG. Effect of an alpha(1)-adrenergic blocker on plasticity elicited by motor training. Exp Brain Res. 2003;148:504–508
  58. Garris PA, Wightman RM. Different kinetics govern dopaminergic transmission in the amygdala, prefrontal cortex, and striatum: an in vivo voltammetric study. J Neurosci. 1994;14:442–450
  59. Otani S, Blond O, Desce JM, Crépel F. Dopamine facilitates long-term depression of glutamatergic transmission in rat prefrontal cortex. Neuroscience. 1998;85:669–676
  60. Smith R, Musleh W, Akopian G, Buckwalter G, Walsh JP. Regional differences in the expression of corticostriatal synaptic plasticity. Neuroscience. 2001;106:95–101
  61. Floel A, Garraux G, Xu B, et al. Levodopa increases memory encoding and dopamine release in the striatum in the elderly. Neurobiol Aging. 2008;29:267–279
  62. Murase N, Duque J, Mazzocchio R, Cohen LG. Influence of interhemispheric interactions on motor function in chronic stroke. Ann Neurol. 2004;55:400–409
  63. Mansur CG, Fregni F, Boggio PS, et al. A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients. Neurology. 2005;64:1802–1804
  64. Takeuchi N, Chuma T, Matsuo Y, Watanabe I, Ikoma K. Repetitive transcranial magnetic stimulation of contralesional primary motor cortex improves hand function after stroke. Stroke. 2005;36:2681–2686
  65. Grondin R, Zhang Z, Gerhardt GA, Gash DM. Dopaminergic therapy improves upper limb motor performance in aged rhesus monkeys. Ann Neurol. 2000;48:250–253
  66. Corwin JV, Kanter S, Watson RT, Heilman KM, Valenstein E, Hashimoto A. Apomorphine has a therapeutic effect on neglect produced by unilateral dorsomedial prefrontal cortex lesions in rats. Exp Neurol. 1986;94:683–698
  67. Sonde L, Lokk J. Effects of amphetamine and/or L-dopa and physiotherapy after stroke—a blinded randomized study. Acta Neurol Scand. 2007;115:55–59
  68. Hendricks HT, van Limbeek J, Geurts AC, Zwarts MJ. Motor recovery after stroke: a systematic review of the literature. Arch Phys Med Rehabil. 2002;83:1629–1637
  69. Kreisel SH, Bazner H, Hennerici MG. Pathophysiology of stroke rehabilitation: temporal aspects of neurofunctional recovery. Cerebrovasc Dis. 2006;21:6–17
  70. Scheidtmann K. Advances in adjuvant pharmacotherapy for motor rehabilitation: effects of levodopa. Restor Neurol Neurosci. 2004;22:393–398
  71. Martinsson L, Hardemark HG, Wahlgren NG. Amphetamines for improving stroke recovery: a systematic Cochrane review. Stroke. 2003;34:2766
  72. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971;9:97–113

 Supported by the Deutsche Forschungsgemeinschaft (grant no. FL 379-4/1), the Bundesministerium für Forschung und Bildung (grant no. 01GW0520), the Innovative Medizinische Forschung Münster (grant nos. FL110605, KN520301), and the Volkswagen Stiftung (grant no. Az I/80 708).

 No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated.

PII: S0003-9993(08)00434-6

doi: 10.1016/j.apmr.2008.02.030

Archives of Physical Medicine and Rehabilitation
Volume 89, Issue 9 , Pages 1633-1641 , September 2008