title: Emerging concepts in the physiological basis of dystonia.
abstract: Work over the past 2 decades has led to substantial changes in our understanding of dystonia pathophysiology. Three general abnormalities appear to underlie the pathophysiological substrate. The first is a loss of inhibition. This makes sense considering that it may be responsible for the excess of movement and for the overflow phenomena seen in dystonia. A second abnormality is sensory dysfunction which is related to the mild sensory complaints in patients with focal dystonias and may be responsible for some of the motor dysfunction. Third, evidence from animal models of dystonia as well as from patients with primary dystonia has revealed significant alterations of synaptic plasticity characterized by a disruption of homeostatic plasticity, with a prevailing facilitation of synaptic potentiation, together with the loss of synaptic inhibitory processes. We speculate that during motor learning this abnormal plasticity may lead to an abnormal sensorimotor integration, leading to consolidation of abnormal motor engrams. If so, then removing this abnormal plasticity might have little immediate effect on dystonic movements because bad motor memories have already been ''learned'' and are difficult to erase. These considerations might explain the delayed clinical effects of deep brain stimulation (DBS) in patients with generalized dystonia. Current lines of research will be discussed from a network perspective. © 2013 Movement Disorder Society.
authors.affiliation: Department of Neurosciences, Psychiatry, and Anaesthesiological Science, University of Messina, Messina, Italy. angelo.quartarone@unime.it
authors.forename: Angelo
authors.initials: A
authors.lastname: Quartarone
authors.forename: Mark
authors.initials: M
authors.lastname: Hallett
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D004421:Dystonia / Q000150:complications*; D006801:Humans; D009069:Movement Disorders / Q000209:etiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D012678:Sensation Disorders / Q000209:etiology*
keywords: dystonia; sensory-motor plasticity; basal ganglia; transcranial magnetic stimulation
references.citation: J Appl Physiol (1985). 2009 Nov;107(5):1513-8
references.pmid: 19713426
references.citation: Parkinsonism Relat Disord. 2004 Jul;10(5):293-6
references.pmid: 15196508
references.citation: Mov Disord. 2005 Dec;20(12):1564-70
references.pmid: 16092106
references.citation: Trends Neurosci. 2006 Apr;29(4):192-9
references.pmid: 16519953
references.citation: J Physiol. 2005 Aug 15;567(Pt 1):293-300
references.pmid: 15946961
references.citation: J Neurosci. 2004 Mar 10;24(10):2585-91
references.pmid: 15014134
references.citation: J Neurol Neurosurg Psychiatry. 2008 Sep;79(9):985-90
references.pmid: 17634214
references.citation: Mov Disord. 2012 Apr;27(4):533-8
references.pmid: 22344674
references.citation: Mov Disord. 2009 Jul 30;24(10):1427-36
references.pmid: 19306289
references.citation: Brain. 2001 Mar;124(Pt 3):537-45
references.pmid: 11222454
references.citation: Lancet. 2000 Jun 24;355(9222):2220-1
references.pmid: 10881900
references.citation: Mov Disord. 2011 Aug 1;26(9):1698-702
references.pmid: 21495074
references.citation: Curr Biol. 2008 Dec 9;18(23):1839-43
references.pmid: 19026538
references.citation: Adv Neurol. 1983;37:177-88
references.pmid: 6134442
references.citation: Ann Neurol. 2003 Jul;54(1):102-9
references.pmid: 12838525
references.citation: Ann Neurol. 2001 Oct;50(4):521-7
references.pmid: 11601503
references.citation: Brain. 2000 Mar;123 Pt 3:572-84
references.pmid: 10686179
references.citation: Mov Disord. 2005 Mar;20(3):335-41
references.pmid: 15486996
references.citation: Mov Disord. 2008 Dec 15;23(16):2319-27
references.pmid: 18816801
references.citation: Ann Neurol. 2006 May;59(5):825-34
references.pmid: 16634038
references.citation: J Neurosci. 2006 Jan 11;26(2):716-21
references.pmid: 16407569
references.citation: Neurology. 1988 Jul;38(7):1005-12
references.pmid: 3386815
references.citation: Mov Disord. 2011 Jun;26(7):1274-81
references.pmid: 21506166
references.citation: Neuroscience. 2009 Nov 24;164(1):220-9
references.pmid: 19162138
references.citation: J Neurol Neurosurg Psychiatry. 1995 Nov;59(5):493-8
references.pmid: 8530933
references.citation: Cerebellum. 2005;4(2):90-6
references.pmid: 16035190
references.citation: Brain. 2003 Dec;126(Pt 12):2586-96
references.pmid: 14506068
references.citation: J Neurosci. 1982 Jan;2(1):32-48
references.pmid: 7054394
references.citation: Ann Neurol. 2002 May;51(5):593-8
references.pmid: 12112105
references.citation: Neurology. 2003 Nov 11;61(9):1228-31
references.pmid: 14610125
references.citation: Brain. 2004 Aug;127(Pt 8):1899-908
references.pmid: 15231585
references.citation: PLoS One. 2010 Oct 26;5(10):e13602
references.pmid: 21049057
references.citation: Neurology. 2006 Nov 28;67(10):1740-1
references.pmid: 17130402
references.citation: Neurochirurgie. 1999 May;45(2):139-44
references.pmid: 10448655
references.citation: Science. 2004 Jun 25;304(5679):1926-9
references.pmid: 15218136
references.citation: Brain Stimul. 2009 Apr;2(2):108-17
references.pmid: 20633408
references.citation: Clin Neurophysiol. 2010 Jul;121(7):987-91
references.pmid: 20181514
references.citation: Clin Neurophysiol. 2010 Sep;121(9):1551-1554
references.pmid: 20382069
references.citation: Clin Orthop Relat Res. 1998 Jun;(351):102-6
references.pmid: 9646753
references.citation: J Neurol Neurosurg Psychiatry. 2009 Dec;80(12):1315-9
references.pmid: 19541688
references.citation: Ann Neurol. 2009 Aug;66(2):146-54
references.pmid: 19743446
references.citation: J Cereb Blood Flow Metab. 2008 Jun;28(6):1127-38
references.pmid: 18231115
references.citation: J Neural Transm Suppl. 2006;(70):485-8
references.pmid: 17017571
references.citation: Mov Disord. 2008 Mar 15;23(4):558-65
references.pmid: 18074393
references.citation: Brain. 2009 Oct;132(Pt 10):2871-7
references.pmid: 19690095
references.citation: Electroencephalogr Clin Neurophysiol. 1992 Dec;85(6):355-64
references.pmid: 1282453
references.citation: Exp Brain Res. 2009 Feb;192(4):651-6
references.pmid: 18815775
references.citation: J Neurosci. 2004 Mar 31;24(13):3379-85
references.pmid: 15056717
references.citation: Mov Disord. 2010 Feb 15;25(3):289-99
references.pmid: 20063427
references.citation: Ann N Y Acad Sci. 2008 Oct;1142:179-99
references.pmid: 18990127
references.citation: Nature. 2000 Jul 13;406(6792):147-50
references.pmid: 10910346
references.citation: Mov Disord. 2005 Nov;20(11):1488-95
references.pmid: 16078218
references.citation: Ann Neurol. 1998 Nov;44(5):828-31
references.pmid: 9818942
references.citation: Mov Disord. 2011 Aug 15;26(10):1913-21
references.pmid: 21547950
references.citation: Clin Neurophysiol. 2010 Jan;121(1):98-103
references.pmid: 19906559
references.citation: Brain. 2009 Mar;132(Pt 3):749-55
references.pmid: 19151081
references.citation: Nature. 1998 Feb 26;391(6670):892-6
references.pmid: 9495341
references.citation: J Neurosci. 2009 Apr 29;29(17):5597-604
references.pmid: 19403826
references.citation: Brain. 2011 Jul;134(Pt 7):2106-15
references.pmid: 21705425
references.citation: Neuroimage. 2003 Oct;20(2):1329-38
references.pmid: 14568501
references.citation: Brain. 2009 Mar;132(Pt 3):756-64
references.pmid: 19179376
references.citation: Mov Disord. 2002 Mar;17(2):346-53
references.pmid: 11921122
references.citation: Clin Neurophysiol. 2011 Sep;122(9):1816-9
references.pmid: 21419696
references.citation: Mov Disord. 2011 Apr;26(5):852-7
references.pmid: 21370265
references.citation: Mov Disord. 2012 Sep 15;27(11):1425-31
references.pmid: 22886735
references.citation: J Neurol Neurosurg Psychiatry. 2009 Jan;80(1):80-3
references.pmid: 19091711
references.citation: Exp Neurol. 2013 Feb;240:64-74
references.pmid: 23142185
references.citation: Neurology. 2007 Jul 24;69(4):376-80
references.pmid: 17646630
references.citation: J Neurosci. 2008 Oct 8;28(41):10363-9
references.pmid: 18842895
references.citation: Neurobiol Dis. 2011 May;42(2):177-84
references.pmid: 20817092
references.citation: Prog Neurobiol. 1996 Nov;50(4):381-425
references.pmid: 9004351
references.citation: Exp Neurol. 2006 Dec;202(2):480-6
references.pmid: 16930593
references.citation: Cereb Cortex. 2004 May;14(5):555-61
references.pmid: 15054071
references.citation: Brain. 2003 Dec;126(Pt 12):2597-608
references.pmid: 12937079
references.citation: N Engl J Med. 2005 Feb 3;352(5):459-67
references.pmid: 15689584
references.citation: Neurology. 1999 Feb;52(3):529-37
references.pmid: 10025782
references.citation: Ann Neurol. 1995 Aug;38(2):155-62
references.pmid: 7654062
references.citation: Mov Disord. 2010 Dec 15;25(16):2800-8
references.pmid: 20979122
references.citation: Arch Phys Med Rehabil. 2002 Oct;83(10):1342-8
references.pmid: 12370865
references.citation: Mov Disord. 2005 May;20(5):545-51
references.pmid: 15641012
references.citation: Curr Opin Neurol. 2008 Aug;21(4):484-90
references.pmid: 18607211
references.citation: Neurology. 1997 Oct;49(4):1054-9
references.pmid: 9339689
references.citation: Neurology. 1996 Aug;47(2):508-20
references.pmid: 8757029
references.citation: Restor Neurol Neurosci. 2010;28(4):449-57
references.pmid: 20714069
references.citation: Exp Brain Res. 2011 Mar;209(3):437-42
references.pmid: 21305376
references.citation: Trends Cogn Sci. 2009 Apr;13(4):182-9
references.pmid: 19286414
references.citation: Brain. 2001 Apr;124(Pt 4):757-68
references.pmid: 11287375
references.citation: Eur J Neurol. 2003 May;10(3):239-47
references.pmid: 12752397
references.citation: J Physiol. 2004 Jun 1;557(Pt 2):689-700
references.pmid: 15047772
references.citation: Ann Neurol. 2002 Jan;51(1):93-101
references.pmid: 11782988
references.citation: Curr Biol. 2009 Oct 13;19(19):1637-41
references.pmid: 19800236
references.citation: Mov Disord. 2003 Jun;18(6):673-82
references.pmid: 12784271
references.citation: Mov Disord. 2006 Oct;21(10):1650-5
references.pmid: 17058185
references.citation: Mov Disord. 1998 Jan;13(1):118-24
references.pmid: 9452336
references.citation: Stroke. 2004 Nov;35(11):2484-8
references.pmid: 15375297
references.citation: Mov Disord. 2004 Jan;19(1):54-9
references.pmid: 14743361
references.citation: Clin Neurophysiol. 2004 Feb;115(2):348-55
references.pmid: 14744576
references.citation: Med Probl Perform Art. 2010 Mar;25(1):3-9
references.pmid: 20795373
references.citation: Mov Disord. 2011 May;26(6):958-67
references.pmid: 21626542
references.citation: J Med Invest. 2001 Aug;48(3-4):142-6
references.pmid: 11694953
references.citation: Brain. 2005 Aug;128(Pt 8):1943-50
references.pmid: 15872016
references.citation: Neurology. 2005 Apr 26;64(8):1391-6
references.pmid: 15851729
references.citation: Mov Disord. 2006 Dec;21(12):2181-6
references.pmid: 17078060
references.citation: Neurology. 2000 Dec 26;55(12):1869-73
references.pmid: 11134387
references.citation: Brain. 2000 Sep;123 ( Pt 9):1813-29
references.pmid: 10960045
references.citation: Brain. 1998 Jul;121 ( Pt 7):1195-212
references.pmid: 9679773
references.citation: Neuron. 2010 Jul 29;67(2):294-307
references.pmid: 20670836
references.citation: Neurobiol Dis. 2011 May;42(2):162-70
references.pmid: 21168494
references.citation: Neurobiol Dis. 2011 May;42(2):185-201
references.pmid: 21303695
references.citation: Brain. 2006 Oct;129(Pt 10):2709-21
references.pmid: 16921180