Journal of Neural Transmission

, Volume 117, Issue 2, pp 207–216 | Cite as

1 Hz rTMS preconditioned by tDCS over the primary motor cortex in Parkinson’s disease: effects on bradykinesia of arm and hand

  • Ulrike Grüner
  • Carsten Eggers
  • Mitra Ameli
  • Anna-Sophia Sarfeld
  • Gereon R. Fink
  • Dennis Alexander Nowak
Movement Disorders - Original Article


To investigate whether a period of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over M1 preconditioned by tDCS improves bradykinesia of the upper limb in Parkinson’s disease (PD). Fifteen patients with PD performed index finger, hand tapping and horizontal pointing movements as well as reach-to-grasp movements with either hand before (baseline conditions) and after a period of 1 Hz rTMS preconditioned by (1) sham, (2) anodal or (3) cathodal tDCS over the primary motor cortex contralateral to the more affected body side. Movement kinematics was analysed using an ultrasound-based motion analyser at baseline, immediately after and 30 min after each stimulation session. Dopaminergic medication was continued. Compared to baseline, 1 Hz rTMS significantly increased the frequency of index finger and hand tapping as well as horizontal pointing movements performed with the contralateral hand. Movement frequency increased up to 40% over 30 min after cessation of the stimulation. Preconditioning with cathodal tDCS, but not with anodal tDCS, reduced the effectiveness of 1 Hz rTMS to improve tapping and pointing movements. There was no significant increase of movement frequencies of the ipsilateral hand induced by 1 Hz rTMS preconditioned by either tDCS session. Movement kinematics of reach-to-grasp movements were not significantly influenced by either stimulation session. In PD the beneficial effects of 1 Hz rTMS over the primary motor cortex on bradykinesia of simple finger, hand and pointing movements is reduced by preconditioning with cathodal tDCS, but not with anodal tDCS. Preconditioning with tDCS is a powerful tool to modulate the behavioural effect of 1 Hz rTMS over the primary motor cortex in PD.


Basal ganglia Neuromodulation Brain plasticity M1 



The study was supported by a stipend of the Deutsche Forschungsgemeinschaft (DFG NO737/4-1) to Dennis A. Nowak.

Conflict of interest statement

None of the authors has any financial disclosures regarding the present manuscript. The study was supported by a grant of the Deutsche Forschungsgemeinschaft (DFG) to Dennis A. Nowak (NO 737/4-1).


  1. Bäumer T, Pramstaller PP, Siebner HR, Schippling S, Hagenah J, Peller M, Gerloff C, Klein C, Münchau A (2007) Sensorimotor integration is abnormal in asymptomatic Parkin mutation carriers: a TMS study. Neurology 69:1976–1981CrossRefPubMedGoogle Scholar
  2. Bienenstock EL, Cooper LN, Munro PW (1982) Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J Neurosci 2:32–48PubMedGoogle Scholar
  3. Brooks DJ, Samuel M (2000) The effects of surgical treatment of Parkinson’s disease on brain function: PET findings. Neurology 55:S52–S59PubMedGoogle Scholar
  4. Buhmann C, Gorsler A, Baumer T, Hidding U, Demiralay C, Hinkelmann K, Weiler C, Siebner HR, Münchau A (2004) Abnormal excitability of premotor-motor connections in de novo Parkinson’s disease. Brain 127:2246–2732CrossRefGoogle Scholar
  5. Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG (1997) Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 48:1398–1403PubMedGoogle Scholar
  6. Crovitz HF, Zener K (1965) A group for assessing hand and eye dominance. Am J Psychol 75:271–276CrossRefGoogle Scholar
  7. De Frias CM, Dixon RA, Fisher N, Camicioli R (2007) Intraindividual variability in neurocognitive speed: a comparison of Parkinson’s disease and normal older adults. Neuropsychologia 45:2499–2507CrossRefPubMedGoogle Scholar
  8. Devanne H, Cohen LG, Kouchtir-Devanne N, Capaday C (2002) Integrated motor cortical control of task-related muscles during pointing in humans. J Neurophysiol 87:3006–3017PubMedGoogle Scholar
  9. Elahi B, Elahi B, Chen R (2009) Effect of transcranial magnetic stimulation on Parkinson motor function-systematic review of controlled clinical trials. Mov Disord 24:357–363CrossRefPubMedGoogle Scholar
  10. Fahn S, Elton RL, Members of the UPDRS Development Committee (1987) The Unified Parkinson’s disease Rating Scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M (eds) Recent developments in Parkinson’s disease, vol. 2. McMillan Healthcare Information, Florham Park, pp 153–163, 293–304Google Scholar
  11. Folstein MF, Folstein SE, McHugh PR (1975) Mini-Mental State (a practical method for grading the state of patients for the clinician). J Psychiatr Res 12:189–198CrossRefPubMedGoogle Scholar
  12. Fregni F, Boggio PS, Santos MC, Lima M, Vieira AL, Rigonatti SP, Silva MT, Barbosa ER, Nitsche MA, Pascual-Leone A (2006) Noninvasive cortical stimulation with transcranial direct current stimulation in Parkinson’s disease. Mov Disord 21:1693–1702CrossRefPubMedGoogle Scholar
  13. Ginanneschi F, Dominici F, Biasella A, Gelli F, Rossi A (2006) Changes in corticomotor excitability of forearm muscles in relation to static shoulder positions. Brain Res 1073:332–338CrossRefPubMedGoogle Scholar
  14. Helmich RC, Derikx LC, Bakker M, Scheeringa R, Bloem BR, Toni I (2009) Spatial remapping of cortico-striatal connectivity in Parkinson’s disease. Cereb Cortex [Epub ahead of print]Google Scholar
  15. Hermsdörfer J, Marquardt C, Wack S, Mai N (1999) Comparative analysis of diadochokinetic movements. J Electromyogr Kinesiol 9:283–295CrossRefPubMedGoogle Scholar
  16. Hoehn M, Yahr M (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442PubMedGoogle Scholar
  17. Jahanshahi M, Jenkins IH, Brown RG, Marsden CD, Passingham RE, Brooks DJ (1995) Self-initiated versus externally triggered movements. I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson’s disease subjects. Brain 118:913–933CrossRefPubMedGoogle Scholar
  18. Khedr EM, Farweez HM, Islam H (2003) Therapeutic effect of repetitive transcranial magnetic stimulation on motor function in Parkinson’s disease patients. Eur J Neurol 10:567–572CrossRefPubMedGoogle Scholar
  19. Krack P, Pollak P, Limousin P, Hoffmann D, Xie J, Benazzouz A (1998) Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson’s disease. Brain 121:141–147CrossRefGoogle Scholar
  20. Lefaucheur JP (2005) Motor cortex dysfunction revealed by cortical excitability studies in Parkinson’s disease: influence of antiparkinsonian treatment and cortical stimulation. Clin Neurophysiol 116:244–253CrossRefPubMedGoogle Scholar
  21. Lefaucheur JP, Drouot X, Von Raison F, Ménard-Lefaucheur I, Cesaro P, Nguyen JP (2004) Improvement of motor performance and modulation of cortical excitability by repetitive transcranial magnetic stimulation of the motor cortex in Parkinson’s disease. Clin Neurophysiol 115:2530–2541CrossRefPubMedGoogle Scholar
  22. Mally J, Stone TW (1999) Improvement in Parkinsonian symptoms after repetitive transcranial magnetic stimulation. J Neurol Sci 162:179–184CrossRefPubMedGoogle Scholar
  23. Mir P, Matsunaga K, Gilio F, Quinn NP, Siebner HR, Rothwell JC (2005) Dopaminergic drugs restore facilitatory premotor–motor interactions in Parkinson disease. Neurology 64:1906–1912CrossRefPubMedGoogle Scholar
  24. Morgante F, Espay AJ, Gunraj C, Lang AE, Chen R (2006) Motor cortex plasticity in Parkinson’s disease and levodopa-induced dyskinesias. Brain 129:1059–1069CrossRefPubMedGoogle Scholar
  25. Nowak DA (2008) The impact of stroke on the performance of grasping: usefulness of kinetic and kinematic motion analysis. Neurosci Biobehav Rev 32:1439–1450CrossRefPubMedGoogle Scholar
  26. Okabe S, Ugawa Y, Kanazawa I (2003) Effectiveness of rTMS on Parkinson’s Disease Study Group. 0.2-Hz repetitive transcranial magnetic stimulation has no add-on effects as compared to a realistic sham stimulation in Parkinson’s disease. Mov Disord 18:382–388CrossRefPubMedGoogle Scholar
  27. Palmer SJ, Ng B, Abugharbieh R, Eigenraam L, McKeown MJ (2009) Motor reserve and novel area recruitment: amplitude and spatial characteristics of compensation in Parkinson’s disease. Eur J Neurosci 29:2187–2196CrossRefPubMedGoogle Scholar
  28. Pascual-Leone A, Valls-Sole J, Wassermann EM, Hallett M (1994) Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain 117:847–858CrossRefPubMedGoogle Scholar
  29. Priori A (2003) Brain polarization in humans: a reappraisal of an old tool for prolonged non-invasive modulation of brain excitability. Clin Neurophysiol 114:589–595CrossRefPubMedGoogle Scholar
  30. Sabatini U, Boulanouar K, Fabre N, Martin F, Carel C, Colonnese C, Bozzao L, Berry I, Montastruc JL, Chollet F, Rascol O (2000) Cortical motor reorganization in a kinetic patients with Parkinson’s disease: a functional MRI study. Brain 123:394–403CrossRefPubMedGoogle Scholar
  31. Siebner HR, Rossmeier C, Mentschel C, Peinemann A, Conrad B (2000) Short-term motor improvement after sub-threshold 5-Hz repetitive transcranial magnetic stimulation of the primary motor hand area in Parkinson’s disease. J Neurol Sci 178:91–94CrossRefPubMedGoogle Scholar
  32. Siebner HR, Lang N, Rizzo V, Nitsche MA, Paulus W, Lemon RN, Rothwell JC (2004) Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J Neurosci 24:3379–3385CrossRefPubMedGoogle Scholar
  33. Soysal A, Sobe I, Atay T, Sen A, Arpaci B (2008) Effect of therapy on motor cortical excitability in Parkinson’s disease. Can J Neurol Sci 35:166–172PubMedGoogle Scholar
  34. Strafella AP, Paus T, Fraraccio M, Dagher A (2003) Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain 126:2609–2615CrossRefPubMedGoogle Scholar
  35. Strafella AP, Ko JH, Monchi O (2006) Therapeutic application of transcranial magnetic stimulation in Parkinson’s disease: the contribution of expectation. Neuroimage 31:1666–1672CrossRefPubMedGoogle Scholar
  36. Tergau F, Wassermann EM, Paulus W, Ziemann U (1999) Lack of clinical improvement in patients with Parkinson’s disease after low and high frequency repetitive transcranial magnetic stimulation. Electroencephalogr Clin Neurophysiol (Suppl) 51:281–288Google Scholar
  37. Ueki Y, Mima T, Kotb MA, Sawada H, Saiki H, Ikeda A, Begum T, Reza F, Nagamine T, Fukuyama H (2006) Altered plasticity of the human motor cortex in Parkinson’s disease. Ann Neurol 59:60–71CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ulrike Grüner
    • 1
  • Carsten Eggers
    • 1
  • Mitra Ameli
    • 1
  • Anna-Sophia Sarfeld
    • 1
  • Gereon R. Fink
    • 1
    • 2
  • Dennis Alexander Nowak
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of NeurologyUniversity of CologneCologneGermany
  2. 2.Institute of Neuroscience and Medicine (INM-3), Cognitive NeurologyResearch Centre JülichJülichGermany
  3. 3.Human Sensorimotor Control LaboratoryUniversity of MinnesotaMinneapolisUSA
  4. 4.Neurochirurgische und Neurologische FachklinikKlinik KipfenbergKipfenbergGermany

Personalised recommendations