title: Motor cortical plasticity in Parkinson's disease.
abstract: In Parkinson's disease (PD), there are alterations of the basal ganglia (BG) thalamocortical networks, primarily due to degeneration of nigrostriatal dopaminergic neurons. These changes in subcortical networks lead to plastic changes in primary motor cortex (M1), which mediates cortical motor output and is a potential target for treatment of PD. Studies investigating the motor cortical plasticity using non-invasive transcranial magnetic stimulation (TMS) have found altered plasticity in PD, but there are inconsistencies among these studies. This is likely because plasticity depends on many factors such as the extent of dopaminergic loss and disease severity, response to dopaminergic replacement therapies, development of l-DOPA-induced dyskinesias (LID), the plasticity protocol used, medication, and stimulation status in patients treated with deep brain stimulation (DBS). The influences of LID and DBS on BG and M1 plasticity have been explored in animal models and in PD patients. In addition, many other factors such age, genetic factors (e.g., brain derived neurotropic factor and other neurotransmitters or receptors polymorphism), emotional state, time of the day, physical fitness have been documented to play role in the extent of plasticity induced by TMS in human studies. In this review, we summarize the studies that investigated M1 plasticity in PD and demonstrate how these afore-mentioned factors affect motor cortical plasticity in PD. We conclude that it is important to consider the clinical, demographic, and technical factors that influence various plasticity protocols while developing these protocols as diagnostic or prognostic tools in PD. We also discuss how the modulation of cortical excitability and the plasticity with these non-invasive brain stimulation techniques facilitate the understanding of the pathophysiology of PD and help design potential therapeutic possibilities in this disorder.
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto , Toronto, ON , Canada ; Division of Brain, Imaging and Behavior - Systems Neuroscience, Toronto Western Research Institute , Toronto, ON , Canada.
authors.forename: Kaviraja
authors.initials: K
authors.lastname: Udupa
authors.forename: Robert
authors.initials: R
authors.lastname: Chen
keywords: M1 plasticity; Parkinson’s disease; paired associative stimulation; repetitive transcranial magnetic stimulation; theta burst stimulation; transcranial direct current stimulation; transcranial magnetic stimulation
references.citation: Ir J Med Sci. 2011 Dec;180(4):873-80
references.pmid: 21660652
references.citation: J Physiol. 2010 Jul 1;588(Pt 13):2291-304
references.pmid: 20478978
references.citation: Cereb Cortex. 2013 Jul;23(7):1593-605
references.pmid: 22661405
references.citation: J Neurol Neurosurg Psychiatry. 2005 Dec;76(12):1614-23
references.pmid: 16291882
references.citation: J Neurosci. 1997 Jun 15;17(12):4536-44
references.pmid: 9169514
references.citation: Motor Control. 2009 Oct;13(4):442-53
references.pmid: 20014649
references.citation: Muscle Nerve. 2000 Oct;23(10):1594-7
references.pmid: 11003798
references.citation: Neuron. 2004 Sep 30;44(1):5-21
references.pmid: 15450156
references.citation: Cereb Cortex. 2003 Nov;13(11):1251-6
references.pmid: 14576216
references.citation: J Neurol. 2010 Oct;257(10):1669-74
references.pmid: 20496035
references.citation: J Neurosci. 2009 May 13;29(19):6124-31
references.pmid: 19439590
references.citation: Nature. 2005 Mar 10;434(7030):221-5
references.pmid: 15759002
references.citation: Arch Neurol. 2003 Oct;60(10):1365-8
references.pmid: 14568805
references.citation: J Neurochem. 2003 May;85(4):935-43
references.pmid: 12716425
references.citation: Brain. 2003 Aug;126(Pt 8):1883-94
references.pmid: 12805105
references.citation: Brain. 2011 Feb;134(Pt 2):375-87
references.pmid: 21183486
references.citation: Neuroscience. 2012 Jul 26;215:31-41
references.pmid: 22537846
references.citation: Clin Neurophysiol. 2011 Oct;122(10):2044-8
references.pmid: 21536493
references.citation: Brain. 2000 Feb;123 ( Pt 2):394-403
references.pmid: 10648446
references.citation: Mov Disord. 2007 May 15;22(7):1046-50
references.pmid: 17575584
references.citation: Neuroscience. 2003;117(4):931-8
references.pmid: 12654344
references.citation: Parkinsonism Relat Disord. 2011 May;17(4):297-8
references.pmid: 21316290
references.citation: Ann N Y Acad Sci. 2003 Nov;1003:226-40
references.pmid: 14684449
references.citation: Neurology. 2012 May 1;78(18):1441-8
references.pmid: 22517098
references.citation: Neurology. 2009 Jul 14;73(2):113-9
references.pmid: 19597133
references.citation: Ann Neurol. 2006 Jan;59(1):60-71
references.pmid: 16240372
references.citation: Neurosci Res. 2002 Jun;43(2):111-7
references.pmid: 12067746
references.citation: Mov Disord. 2010 Apr 15;25(5):560-9
references.pmid: 20131394
references.citation: Brain. 2004 Dec;127(Pt 12):2732-46
references.pmid: 15509619
references.citation: Clin Neurophysiol. 2012 Nov;123(11):2220-6
references.pmid: 22608487
references.citation: Neurosci Lett. 1992 Aug 3;142(1):95-9
references.pmid: 1357611
references.citation: Clin Neurophysiol. 2004 Nov;115(11):2530-41
references.pmid: 15465443
references.citation: Brain. 2012 Jul;135(Pt 7):2074-88
references.pmid: 22609619
references.citation: Neurobiol Aging. 2003 Mar-Apr;24(2):197-211
references.pmid: 12498954
references.citation: Brain. 2000 Nov;123 ( Pt 11):2297-305
references.pmid: 11050029
references.citation: Amino Acids. 2002;23(1-3):133-9
references.pmid: 12373527
references.citation: Science. 2009 Apr 17;324(5925):354-9
references.pmid: 19299587
references.citation: Clin Neurophysiol. 2012 Apr;123(4):822-8
references.pmid: 21945457
references.citation: J Neurosci. 2005 Dec 7;25(49):11279-87
references.pmid: 16339023
references.citation: Cereb Cortex. 2014 Aug;24(8):2055-67
references.pmid: 23535177
references.citation: J Neurosci. 2006 Oct 11;26(41):10420-9
references.pmid: 17035526
references.citation: Clin Neurophysiol. 2005 Sep;116(9):2099-109
references.pmid: 16043397
references.citation: J Neurol. 2000 Sep;247 Suppl 5:V1-15
references.pmid: 11081799
references.citation: Cereb Cortex. 2010 Sep;20(9):2224-33
references.pmid: 20051362
references.citation: Trends Pharmacol Sci. 2005 Aug;26(8):391-7
references.pmid: 16009432
references.citation: Mov Disord. 2006 Mar;21(3):325-31
references.pmid: 16211618
references.citation: J Neurol Neurosurg Psychiatry. 2010 Oct;81(10):1105-11
references.pmid: 20870863
references.citation: Mov Disord. 2003 Mar;18(3):231-40
references.pmid: 12621626
references.citation: Adv Exp Med Biol. 2012;970:553-72
references.pmid: 22351072
references.citation: Clin Neurophysiol. 2002 Mar;113(3):376-82
references.pmid: 11897538
references.citation: Mov Disord. 2006 Oct;21(10):1693-702
references.pmid: 16817194
references.citation: Clin Neurophysiol. 2002 Jul;113(7):1165-71
references.pmid: 12088713
references.citation: Exp Brain Res. 2007 Jul;180(4):583-93
references.pmid: 17562028
references.citation: Phys Ther. 2007 Jun;87(6):719-36
references.pmid: 17429003
references.citation: Brain. 2011 Aug;134(Pt 8):2312-20
references.pmid: 21742734
references.citation: Clin Neurophysiol. 2008 Mar;119(3):504-532
references.pmid: 18063409
references.citation: Exp Neurol. 2012 Aug;236(2):395-8
references.pmid: 22569102
references.citation: Nat Neurosci. 2003 May;6(5):501-6
references.pmid: 12665799
references.citation: Brain. 2009 Feb;132(Pt 2):309-18
references.pmid: 19050033
references.citation: N Engl J Med. 1998 Oct 8;339(15):1044-53
references.pmid: 9761807
references.citation: Neuropharmacology. 2008 Dec;55(7):1081-94
references.pmid: 18755202
references.citation: Neurology. 2007 Feb 27;68(9):704-5
references.pmid: 17325284
references.citation: J Physiol. 2010 Sep 15;588(Pt 18):3415-24
references.pmid: 20660568
references.citation: Exp Brain Res. 2009 Dec;199(3-4):377-90
references.pmid: 19499213
references.citation: Mov Disord. 2009 Feb 15;24(3):357-63
references.pmid: 18972549
references.citation: Brain Stimul. 2013 Jan;6(1):16-24
references.pmid: 22410476
references.citation: Prog Brain Res. 1986;64:161-74
references.pmid: 3088671
references.citation: Biochem Soc Trans. 2010 Apr;38(2):493-7
references.pmid: 20298209
references.citation: Clin Neurophysiol. 2013 Apr;124(4):697-707
references.pmid: 23085389
references.citation: J Neurosci. 2004 Jun 9;24(23):5283-91
references.pmid: 15190099
references.citation: Exp Neurol. 2011 Feb;227(2):296-301
references.pmid: 21145888
references.citation: Neuropharmacology. 2010 Jun;58(7):951-61
references.pmid: 20096294
references.citation: Nat Neurosci. 2006 Feb;9(2):251-9
references.pmid: 16415865
references.citation: J Physiol. 2012 May 15;590(10):2365-74
references.pmid: 22473780
references.citation: Neuropharmacology. 2005 Mar;48(4):503-16
references.pmid: 15755478
references.citation: J Neurosci. 2010 Oct 20;30(42):14182-93
references.pmid: 20962239
references.citation: Mov Disord. 2006 Dec;21(12):2201-5
references.pmid: 17219616
references.citation: Parkinsonism Relat Disord. 2008;14 Suppl 2:S145-9
references.pmid: 18583173
references.citation: Eura Medicophys. 2007 Jun;43(2):241-54
references.pmid: 17589415
references.citation: Cereb Cortex. 2008 Mar;18(3):648-51
references.pmid: 17591596
references.citation: Brain. 2001 Mar;124(Pt 3):558-70
references.pmid: 11222456
references.citation: Mov Disord. 2001 May;16(3):448-58
references.pmid: 11391738
references.citation: J Physiol. 1973 Jul;232(2):331-56
references.pmid: 4727084
references.citation: Neuron. 2012 Aug 23;75(4):556-71
references.pmid: 22920249
references.citation: Biol Psychiatry. 2008 Jan 15;63(2):231-3
references.pmid: 17604004
references.citation: Neurology. 2005 Aug 23;65(4):623-5
references.pmid: 16116131
references.citation: J Neurol Sci. 2000 Sep 15;178(2):91-4
references.pmid: 11018700
references.citation: Trends Neurosci. 2000 Oct;23(10 Suppl):S57-63
references.pmid: 11052221
references.citation: J Neurosci Methods. 2012;206(2):158-64
references.pmid: 22401794
references.citation: Trends Neurosci. 2007 Apr;30(4):176-84
references.pmid: 17335914
references.citation: Nat Neurosci. 2000 Sep;3(9):919-26
references.pmid: 10966623
references.citation: J Neurosci. 2003 Sep 17;23(24):8506-12
references.pmid: 13679419
references.citation: J Neurophysiol. 2007 Dec;98(6):3525-37
references.pmid: 17928554
references.citation: Science. 2008 Aug 8;321(5890):848-51
references.pmid: 18687967
references.citation: Mov Disord. 2006 May;21(5):639-45
references.pmid: 16353175
references.citation: J Clin Neurophysiol. 1996 Mar;13(2):164-71
references.pmid: 8849971
references.citation: J Comp Physiol Psychol. 1949 Jun;42(3):192-206
references.pmid: 18151779
references.citation: Neurology. 2011 Feb 15;76(7):601-9
references.pmid: 21321333
references.citation: J Neural Transm (Vienna). 2010 Feb;117(2):207-16
references.pmid: 20033235
references.citation: Mov Disord. 2002 May;17(3):467-73
references.pmid: 12112192
references.citation: J Neurosci. 2011 Apr 6;31(14):5294-9
references.pmid: 21471364
references.citation: Neurology. 2001 Nov 27;57(10):1899-901
references.pmid: 11723286
references.citation: Parkinsonism Relat Disord. 2007;13 Suppl 3:S259-62
references.pmid: 18267247
references.citation: J Comp Neurol. 1992 Nov 1;325(1):1-21
references.pmid: 1362430
references.citation: Annu Rev Neurosci. 1986;9:357-81
references.pmid: 3085570
references.citation: Clin Neurophysiol. 2012 Apr;123(4):815-21
references.pmid: 21945152
references.citation: Mov Disord. 2009 Jan 30;24(2):246-53
references.pmid: 18951540
references.citation: Prog Brain Res. 2010;183:169-82
references.pmid: 20696320
references.citation: Cereb Cortex. 2010 Aug;20(8):1926-36
references.pmid: 20019146
references.citation: Brain. 2006 Apr;129(Pt 4):1059-69
references.pmid: 16476674