Abstract
Parkinson’s disease (PD) has wide-ranging clinical features, and repetitive transcranial magnetic stimulation (rTMS) therapy has been tried for many aspects of PD. Underlying mechanism of rTMS therapy in PD remains unclear, but several possibilities are proposed such as endogenous dopamine release or restoration of neural plasticity or network activity. Motor symptoms are a cardinal feature of PD, for which evidence suggested moderate efficacy of rTMS. High-frequency (HF) rTMS over the M1 including less focal stimulation (e.g., leg and bilateral hand M1 rTMS) or over the DLPFC, and low-frequency (LF) rTMS over the SMA were most favorable. Long-term administration of levodopa, a major agent for medical therapy of PD, can induce a motor complication called levodopa-induced dyskinesia (LID). Several types of rTMS were reported to be effective for the LID. rTMS has also been tried for non-pharmacological treatment of non-motor symptoms of PD including depression. A “weak recommendation” in favor of HF rTMS of the left DLPFC can be given for the treatment of depressive symptoms associated with PD. These are examples of growing application of rTMS therapy to PD for symptoms other than the classical motor symptoms. As such, rTMS has a potential to become an important adjunctive treatment for PD. Well-designed large clinical trials are needed to establish its utility in the clinical settings.
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References
Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381
Bashir S, Perez JM, Horvath JC et al (2014) Differential effects of motor cortical excitability and plasticity in young and old individuals: a Transcranial Magnetic Stimulation (TMS) study. Front Aging Neurosci 6:111
Bäumer T, Hidding U, Hamel W et al (2009) Effects of DBS, premotor rTMS, and levodopa on motor function and silent period in advanced Parkinson’s disease. Mov Disord 24:672–676
Benninger DH, Berman BD, Houdayer E et al (2011) Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease. Neurology 76:601–609
Benninger DH, Iseki K, Kranick S, Luckenbaugh DA, Houdayer E, Hallett M (2012) Controlled Study of 50-Hz Repetitive Transcranial Magnetic Stimulation for the Treatment of Parkinson Disease. Neurorehabil Neural Repair 26:1096–1105
Ben-Shachar D, Belmaker RH, Grisaru N, Klein E (1997) Transcranial magnetic stimulation induces alterations in brain monoamines. J Neural Transm 104:191–197
Boggio PS, Fregni F, Bermpohl F et al (2005) Effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson’s disease and concurrent depression. Mov Disord 20:1178–1184
Boylan LS, Pullman SL, Lisanby SH, Spicknall KE, Sackeim HA (2001) Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson’s disease. Clin Neurophysiol 112:259–264
Brusa L, Versace V, Koch G, Iani C, Stanzione P, Bernardi G, Centonze D (2006) Low frequency rTMS of the SMA transiently ameliorates peak-dose LID in Parkinson’s disease. Clin Neurophysiol 117:1917–1921
Buhmann C, Glauche V, Stürenburg HJ, Oechsner M, Weiller C, Büchel C (2003) Pharmacologically modulated fMRI – cortical responsiveness to levodopa in drug-naive hemiparkinsonian patients. Brain 126:451–461
Buhmann C, Gorsler A, Bäumer T et al (2004) Abnormal excitability of premotor–motor connections in de novo Parkinson’s disease. Brain 127:2732–2746
Cardoso EF, Fregni F, Martins Maia F et al (2008) rTMS treatment for depression in Parkinson’s disease increases BOLD responses in the left prefrontal cortex. Int J Neuropsychopharmacol 11:173–183
Catalan MJ, Ishii K, Honda M, Samii A, Hallett M (1999) A PET study of sequential finger movements of varying length in patients with Parkinson’s disease. Brain 122:483–495
Chaudhuri KR, Martinez-Martin P, Schapira AH et al (2006) International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord 21:916–923
Chaudhuri KR, Prieto-Jurcynska C, Naidu Y et al (2010) The nondeclaration of nonmotor symptoms of Parkinson’s disease to health care professionals: an international study using the nonmotor symptoms questionnaire. Mov Disord 25:697–701
Chen R, Classen J, Gerloff C et al (1997) Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 48:1398–1403
Degardin A, Devos D, Defebvre L et al (2012) Effect of intermittent theta-burst stimulation on akinesia and sensorimotor integration in patients with Parkinson’s disease. Eur J Neurosci 36:2669–2678
del Olmo MF, Bello O, Cudeiro J (2007) Transcranial magnetic stimulation over dorsolateral prefrontal cortex in Parkinson’s disease. Clin Neurophysiol 118:131–139
DeLong MR, Wichmann T (2007) Circuits and circuit disorders of the basal ganglia. Arch Neurol 64:20–24
Dias AE, Barbosa ER, Coracini K, Maia F, Marcolin MA, Fregni F (2006) Effects of repetitive transcranial magnetic stimulation on voice and speech in Parkinson’s disease. Acta Neurol Scand 113:92–99
Drouot X, Oshino S, Jarraya B et al (2004) Functional recovery in a primate model of Parkinson’s disease following motor cortex stimulation. Neuron 44:769–778
Eckert T, Peschel T, Heinze HJ, Rotte M (2006) Increased pre-SMA activation in early PD patients during simple self-initiated hand movements. J Neurol 253:199–207
Eggers C, Fink GR, Nowak DA (2010) Theta burst stimulation over the primary motor cortex does not induce cortical plasticity in Parkinson’s disease. J Neurol 257:1669–1674
Elahi B, Chen R (2009) Effect of transcranial magnetic stimulation on Parkinson motor function – systematic review of controlled clinical trials. Mov Disord 24:357–363
Epstein CM, Evatt ML, Funk A et al (2007) An open study of repetitive transcranial magnetic stimulation in treatment-resistant depression with Parkinson’s disease. Clin Neurophysiol 118:2189–2194
Fabbrini G, Brotchie JM, Grandas F, Nomoto M, Goetz CG (2007) Levodopa-induced dyskinesias. Mov Disord 22:1379–1389
Fahn S, Elton R, Members of the UPDRS Development Committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M (eds) Recent developments in Parkinson’s disease, vol 2. Macmillan Health Care Information, Florham Park, pp 153–164
Fathi D, Ueki Y, Mima T et al (2010) Effects of aging on the human motor cortical plasticity studied by paired associative stimulation. Clin Neurophysiol 121:90–93
Filipović SR, Rothwell JC, van de Warrenburg BP, Bhatia K (2009) Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson’s disease. Mov Disord 24:246–253
Filipović SR, Rothwell JC, Bhatia K (2010) Low-frequency repetitive transcranial magnetic stimulation and off-phase motor symptoms in Parkinson’s disease. J Neurol Sci 291:1–4
Fregni F, Santos CM, Myczkowski ML et al (2004) Repetitive transcranial magnetic stimulation is as effective as fluoxetine in the treatment of depression in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 75:1171–1174
Fregni F, Simon DK, Wu A, Pascual-Leone A (2005) Non-invasive brain stimulation for Parkinson’s disease: a systematic review and meta-analysis of the literature. J Neurol Neurosurg Psychiatry 76:1614–1623
Gerloff C, Corwell B, Chen R, Hallett M, Cohen LG (1997) Stimulation over the human supplementary motor area interferes with the organization of future elements in complex motor sequences. Brain 120:1587–1602
Gibb WR, Lees AJ (1988) The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 51:745–752
González-García N, Armony J, Soto J, Trejo D, Alegría M, Drucker-Colín R (2011) Effects of rTMS on Parkinson’s disease: a longitudinal fMRI study. J Neurol 258:1268–1280
Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K (2009) Optical deconstruction of parkinsonian neural circuitry. Science 324:354–359
Guyatt GH, Oxman AD, Kunz R et al (2008) GRADE: going from evidence to recommendations. BMJ 336:1049–1051
Hamada M, Ugawa Y, Tsuji S (2008) High-frequency rTMS over the supplementary motor area for treatment of Parkinson’s disease. Mov Disord 23:1524–1531
Hamada M, Ugawa Y, Tsuji S (2009) High-frequency rTMS over the supplementary motor area improves bradykinesia in Parkinson’s disease: subanalysis of double-blind sham-controlled study. J Neurol Sci 287:143–146
Hamada M, Murase N, Hasan A, Balaratnam M, Rothwell JC (2013) The role of interneuron networks in driving human motor cortical plasticity. Cereb Cortex 23:1593–1605
Haslinger B, Erhard P, Kämpfe N et al (2001) Event-related functional magnetic resonance imaging in Parkinson’s disease before and after levodopa. Brain 124:558–570
Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC (2005) Theta burst stimulation of the human motor cortex. Neuron 45:201–206
Huang Y-Z, Rothwell JC, Lu C-S, Chuang W-L, Chen R-S (2011) Abnormal bidirectional plasticity-like effects in Parkinson’s disease. Brain 134:2312–2320
Jenkins IH, Fernandez W, Playford ED et al (1992) Impaired activation of the supplementary motor area in Parkinson’s disease is reversed when akinesia is treated with apomorphine. Ann Neurol 32:749–757
Kanno M, Matsumoto M, Togashi H, Yoshioka M, Mano Y (2004) Effects of acute repetitive transcranial magnetic stimulation on dopamine release in the rat dorsolateral striatum. J Neurol Sci 217:73–81
Keck ME, Welt T, Müller MB et al (2002) Repetitive transcranial magnetic stimulation increases the release of dopamine in the mesolimbic and mesostriatal system. Neuropharmacology 43:101–109
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 10:567–572
Khedr EM, Rothwell JC, Shawky OA, Ahmed MA, Hamdy A (2006) Effect of daily repetitive transcranial magnetic stimulation on motor performance in Parkinson’s disease. Mov Disord 21:2201–2205
Khedr EM, Rothwell JC, Shawky OA, Ahmed MA, Foly KN, Hamdy A (2007) Dopamine levels after repetitive transcranial magnetic stimulation of motor cortex in patients with Parkinson’s disease: Preliminary results. Mov Disord 22:1046–1050
Kishore A, Joseph T, Velayudhan B, Popa T, Meunier S (2012a) Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex (M1) in de novo Parkinson’s disease. Clin Neurophysiol 123:822–828
Kishore A, Popa T, Velayudhan B, Joseph T, Balachandran A, Meunier S (2012b) Acute dopamine boost has a negative effect on plasticity of the primary motor cortex in advanced Parkinson’s disease. Brain 135:2074–2088
Koch G (2013) Do studies on cortical plasticity provide a rationale for using non invasive brain stimulation as a treatment for Parkinson’s disease patients? Front Neurol 4:180
Koch G, Brusa L, Caltagirone C et al (2005) rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease. Neurology 65:623–625
Koch G, Brusa L, Carrillo F et al (2009) Cerebellar magnetic stimulation decreases levodopa-induced dyskinesias in Parkinson disease. Neurology 73:113–119
Lee JY, Kim SH, Ko AR et al (2013) Therapeutic effects of repetitive transcranial magnetic stimulation in an animal model of Parkinson’s disease. Brain Res 1537:290–302
Lefaucheur JP, Drouot X, Von Raison F, Menard-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 115:2530–2541
Mally J, Stone TW (1999) Therapeutic and “dose-dependent” effect of repetitive microelectroshock induced by transcranial magnetic stimulation in Parkinson’s disease. J Neurosci Res 57:935–940
Miocinovic S, Somayajula S, Chitnis S, Vitek JL (2013) History, applications, and mechanisms of deep brain stimulation. JAMA Neurol 70:163–171
Mir P, Matsunaga K, Gilio F, Quinn NP, Siebner HR, Rothwell JC (2005) Dopaminergic drugs restore facilitatory premotor-motor interactions in Parkinson disease. Neurology 64:1906–1912
Monte-Silva K, Liebetanz D, Grundey J, Paulus W, Nitsche MA (2010) Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity. J Physiol 588:3415–3424
Morgante F, Espay AJ, Gunraj C, Lang AE, Chen R (2006) Motor cortex plasticity in Parkinson’s disease and levodopa-induced dyskinesias. Brain 129:1059–1069
Müller-Dahlhaus JF, Orekhov Y, Liu Y, Ziemann U (2008) Interindividual variability and age-dependency of motor cortical plasticity induced by paired associative stimulation. Exp Brain Res 187:467–475
Mure H, Tang CC, Argyelan M et al (2012) Improved sequence learning with subthalamic nucleus deep brain stimulation: evidence for treatment-specific network modulation. J Neurosci 32:2804–2813
Ohnishi T, Hayashi T, Okabe S et al (2004) Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex: an [11C]raclopride positron emission tomography study in anesthetized macaque monkeys. Biol Psychiatry 55:484–489
Okabe S, Ugawa Y, Kanazawa I (2003) 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 18:382–388
Padberg F, George MS (2009) Repetitive transcranial magnetic stimulation of the prefrontal cortex in depression. Exp Neurol 219:2–13
Pal E, Nagy F, Aschermann Z, Balazs E, Kovacs N (2010) The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson’s disease: a randomized, double-blind, placebo-controlled study. Mov Disord 25:2311–2317
Pascual-Leone A, Valls-Sole J, Brasil-Neto JP, Cammarota A, Grafman J, Hallett M (1994a) Akinesia in Parkinson’s disease. II Effects of subthreshold repetitive transcranial motor cortex stimulation. Neurology 44:892–898
Pascual-Leone A, Valls-Sole J, Wassermann EM, Hallett M (1994b) Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain 117:847–858
Peinemann A, Reimer B, Loer C, Quartarone A, Munchau A, Conrad B, Siebner HR (2004) Long-lasting increase in corticospinal excitability after 1800 pulses of subthreshold 5 Hz repetitive TMS to the primary motor cortex. Clin Neurophysiol 115:1519–1526
Picconi B, Centonze D, Hakansson K et al (2003) Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia. Nat Neurosci 6:501–506
Playford ED, Jenkins IH, Passingham RE, Nutt J, Frackowiak RS, Brooks DJ (1992) Impaired mesial frontal and putamen activation in Parkinson’s disease: a positron emission tomography study. Ann Neurol 32:151–161
Rascol O, Sabatini U, Chollet F et al (1992) Supplementary and primary sensory motor area activity in Parkinson’s disease. Regional cerebral blood flow changes during finger movements and effects of apomorphine. Arch Neurol 49:144–148
Rascol O, Sabatini U, Brefel C et al (1998) Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia. Brain 121:527–533
Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE (2000) A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. 056 Study Group. N Engl J Med 342:1484–1491
Romero JR, Anschel D, Sparing R, Gangitano M, Pascual-Leone A (2002) Subthreshold low frequency repetitive transcranial magnetic stimulation selectively decreases facilitation in the motor cortex. Clin Neurophysiol 113:101–107
Rossi S, Hallett M, Rossini PM, Pascual-Leone A (2009) Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 120:2008–2039
Rothkegel H, Sommer M, Rammsayer T, Trenkwalder C, Paulus W (2009) Training effects outweigh effects of single-session conventional rTMS and theta burst stimulation in PD patients. Neurorehabil Neural Repair 23:373–381
Sabatini U, Boulanouar K, Fabre N et al (2000) Cortical motor reorganization in akinetic patients with Parkinson’s disease: a functional MRI study. Brain 123:394–403
Samuel M, Ceballos-Baumann AO, Blin J et al (1997) Evidence for lateral premotor and parietal overactivity in Parkinson’s disease during sequential and bimanual movements. A PET study. Brain 120:963–976
Sayin S, Cakmur R, Yener GG, Yaka E, Ugurel B, Uzunel F (2014) Low-frequency repetitive transcranial magnetic stimulation for dyskinesia and motor performance in Parkinson’s disease. J Clin Neurosci 21:1373–1376
Shirota Y, Ohtsu H, Hamada M, Enomoto H, Ugawa Y (2013) Supplementary motor area stimulation for Parkinson disease: a randomized controlled study. Neurology 80:1400–1405
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 178:91–94
Sommer M, Kamm T, Tergau F, Ulm G, Paulus W (2002) Repetitive paired-pulse transcranial magnetic stimulation affects corticospinal excitability and finger tapping in Parkinson’s disease. Clin Neurophysiol 113:944–950
Spagnolo F, Volonté MA, Fichera M et al (2014) Excitatory deep repetitive transcranial magnetic stimulation with H-coil as add-on treatment of motor symptoms in Parkinson’s disease: an open label, pilot study. Brain Stimul 7:297–300
Strafella AP, Paus T, Fraraccio M, Dagher A (2003) Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain 126:2609–2615
Strafella AP, Ko JH, Grant J, Fraraccio M, Monchi O (2005) Corticostriatal functional interactions in Parkinson’s disease: a rTMS/[11C]raclopride PET study. Eur J Neurosci 22:2946–2952
Suppa A, Marsili L, Belvisi D et al (2011) Lack of LTP-like plasticity in primary motor cortex in Parkinson’s disease. Exp Neurol 227:296–301
Tessa C, Lucetti C, Diciotti S et al (2010) Decreased and increased cortical activation coexist in de novo Parkinson’s disease. Exp Neurol 224:299–306
Thirugnanasambandam N, Grundey J, Paulus W, Nitsche MA (2011) Dose-dependent nonlinear effect of l-DOPA on paired associative stimulation-induced neuroplasticity in humans. J Neurosci 31:5294–5299
VonLoh M, Chen R, Kluger B (2013) Safety of transcranial magnetic stimulation in Parkinson’s disease: a review of the literature. Parkinsonism Relat Disord 19:573–585
Wagle-Shukla A, Angel MJ, Zadikoff C, Enjati M, Gunraj C, Lang AE, Chen R (2007) Low-frequency repetitive transcranial magnetic stimulation for treatment of levodopa-induced dyskinesias. Neurology 68:704–705
Yang X, Song L, Liu Z (2010) The effect of repetitive transcranial magnetic stimulation on a model rat of Parkinson’s disease. Neuroreport 21:268–272
Yu H, Sternad D, Corcos DM, Vaillancourt DE (2007) Role of hyperactive cerebellum and motor cortex in Parkinson’s disease. Neuroimage 35:222–233
Zafar N, Paulus W, Sommer M (2008) Comparative assessment of best conventional with best theta burst repetitive transcranial magnetic stimulation protocols on human motor cortex excitability. Clin Neurophysiol 119:1393–1399
Zesiewicz TA, Sullivan KL, Arnulf I et al (2010) Practice parameter: treatment of nonmotor symptoms of Parkinson disease. Neurology 74:924–931
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Shirota, Y., Hamada, M., Ugawa, Y. (2016). Clinical Applications of rTMS in Parkinson’s Disease. In: Platz, T. (eds) Therapeutic rTMS in Neurology. Springer, Cham. https://doi.org/10.1007/978-3-319-25721-1_9
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