the plastic human brain cortex

28 Pages·2005·0.88 MB·English

AR245-NE28-15 ARI 11May2005 12:8
The Plastic Human
Brain Cortex
Alvaro Pascual-Leone, Amir Amedi,
g
s.or Felipe Fregni, and Lotfi B. Merabet
w
e
evi CenterforNon-InvasiveBrainStimulation,DepartmentofNeurology,BethIsrael
nualrnly. Demeaacilo:[email protected],aHrda.revdaurdMedicalSchool,Boston,Massachusetts02215;
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7-4LE 2005.28:377–401
5.28:37D COL danoni:u1r0e.v1.n1e4u6r/o.27.070203.144216 sctrroosksme,obdlianldpnlaesstsi,cniteyu,rcoorrethicaablislittiamtiuolna,tinoenu,rfoumncotdiounlaatlion,
Neurosci. 200by HARVAR Ar0Ce1nos4enp7ruyv-ra0eilg0dRh6eXtv(cid:1)/ic0e5w2/s00.07A52l1lb-ryights nAPelbaussrttoircimiatcyatgiisnagn intrinsic property of the human brain and repre-
ev. 0377$20.00 sentsevolution’sinventiontoenablethenervoussystemtoescape
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u. therestrictionsofitsowngenomeandthusadapttoenvironmen-
nn talpressures,physiologicchanges,andexperiences.Dynamicshifts
A
in the strength of preexisting connections across distributed neu-
ral networks, changes in task-related cortico-cortical and cortico-
subcortical coherence and modifications of the mapping between
behaviorandneuralactivitytakeplaceinresponsetochangesinaf-
ferentinputorefferentdemand.Suchrapid,ongoingchangesmay
befollowedbytheestablishmentofnewconnectionsthroughden-
dritic growth and arborization. However, they harbor the danger
thattheevolvingpatternofneuralactivationmayinitselfleadtoab-
normalbehavior.Plasticityisthemechanismfordevelopmentand
learning,asmuchasacauseofpathology.Thechallengewefaceisto
learnenoughaboutthemechanismsofplasticitytomodulatethem
toachievethebestbehavioraloutcomeforagivensubject.
377
AR245-NE28-15 ARI 11May2005 12:8
plasticityofthissort;sothatwemaywith-
Contents outhesitationlaydownasourfirstpropo-
sitionthefollowing,thatthephenomenaof
THECONCEPTOFPLASTICITY 378
habitinlivingbeingsareduetotheplasticity.
TWO-STEPCHANGES........... 379
(p.68)
THERAPIDLYSHIFTING
MAPPINGBETWEENBRAIN
Someyearslater,SantiagoRamo´nyCajal
ACTIVITYANDBEHAVIOR... 382
(1904)intheTexturadelSistemaNerviosoar-
THERISKOFCHANGEAND
guedthatbehavioralmodifiabilitymusthave
THEOPPORTUNITYFOR
ananatomicalbasisinthebrainandthusex-
INTERVENTION.............. 383
tended the notion of plasticity to the neural
PLASTICITYINTHESETTING
substrate.Consideringtheacquisitionofnew
OFBRAININJURY............. 384
g skills,Cajalwrote
or THEOCCIPITALCORTEXIN
ws. THEBLIND.................... 387
vie UNMASKINGCONNECTIONS: La labor de un pianista [...] es inacce-
e
nnualronly. TEXHPEEBRLIMINEDNFTO.L.D............... 390 slaiblaedqpuairsaicieo´lnhdoembnrueeviansedhuacbaidliodadyeasqruee-
urnals.anal use ESTCAOBNLNISEHCINTIGONNES:WOCCIPITAL qf´ıusiicear.ePmaruacehnotsenadn˜eorspdleenparma´ectnitceaemsteenctoalmy-
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01. GE SUMMARY......................... 395
7-4LE We argue that plasticity is an intrin-
ci. 2005.28:37RVARD COL T“PHlasEticC”OisNdCerEivPedTfrOomFPthLeAGSTreIeCkIwToYrd sttohoircruoptnuhrdgoeehproemsrutatatynnadiolfieffnseottsahrptmeaionannlaesnprvdsoyotrcuhhsacotosliyotnsgistseiecnqmaoultefrpnueocntesacssitiniboeolndef
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ev. ing plastic refers to the ability to undergo a behavior, is by design molded by environ-
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u. changeinshape.WilliamJames(1890)inThe mental changes and pressures, physiologic
n
An Principles of Psychology was the first to intro- modifications, and experiences. This is the
ducethetermplasticitytotheneurosciences mechanism for learning and for growth and
inreferencetothesusceptibilityofhumanbe- development—changes in the input of any
haviortomodification. neural system, or in the targets or demands
of its efferent connections, lead to system
Plasticity [...] means the possession of a
structureweakenoughtoyieldtoaninflu-
ence,butstrongenoughnottoyieldallat 1The labor of a pianist [...] is inaccessible for the un-
educated man as the acquisition of new skill requires
once.Eachrelativelystablephaseofequilib-
manyyearsofmentalandphysicalpractice.Inorderto
riuminsuchastructureismarkedbywhat fully understand this complex phenomenon it becomes
we may call a new set of habits. Organic necessary to admit, in addition to the reinforcement of
pre-establishedorganicpathways,theformationofnew
matter,especiallynervoustissue,seemsen-
pathwaysthroughramificationandprogressivegrowthof
dowedwithaveryextraordinarydegreeof thedendriticarborizationandthenervousterminals.
378 Pascual-Leoneetal.
AR245-NE28-15 ARI 11May2005 12:8
reorganizationthatmightbedemonstrableat juredbrain,takeoveroflostfunctionbyneigh-
thelevelofbehavior,anatomy,andphysiology boring systems (albeit perhaps incompletely
anddowntothecellularandmolecularlevels. orviadifferentstrategiesandcomputations),
Therefore, plasticity is not an occasional ortheemergenceofnewbehaviorsthatmay
stateofthenervoussystem;instead,itisthe prove adaptive or maladaptive for the indi-
normal ongoing state of the nervous system vidual.Plasticityattheneuralleveldoesnot
throughout the life span. A full, coherent speaktothequestionofbehavioralchangeand
accountofanysensoryorcognitivetheoryhas certainlydoesnotnecessarilyimplyfunctional
to build into its framework the fact that the recoveryorevenfunctionalchange.Thechal-
nervous system, and particularly the brain, lenge we face is to learn enough about the
undergoescontinuouschangesinresponseto mechanismsofplasticityandthemappingre-
modificationsinitsinputafferentsandoutput lationsbetweenbrainactivityandbehaviorto
g targets.Implicittothecommonlyheldnotion beabletoguideit,suppressingchangesthat
or
s. ofplasticityistheconceptthatthereisadefin- may lead to undesirable behaviors while ac-
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1. E thenervoussystemasacontinuouslychang-
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5.28:37D COL pearcohpesretynsaonrdy tihnepuotb,limgaottoorryaccotn,saesqsuoecniacteioonf, Cajal (1904) predicted that with the acqui-
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v. mative.Behaviorwillleadtochangesinbrain of these processes is in fact a necessary re-
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The mapping between behavioral mod- followinginitialreinforcementofpreexistent
ifiability (James 1890) and brain plasticity connections.Therefore,thescopeofpossible
(Cajal 1904) is not one to one. Therefore, plasticchangesisdefinedbyexistingconnec-
dependingonthecircumstances,neuralplas- tions,whicharetheresultofgeneticallycon-
ticity can confer no perceptible change in trolledneuraldevelopmentandareultimately
the behavioral output of the brain, can lead differentacrossindividuals.Reinforcementof
to changes demonstrated only under special existingconnections,ontheotherhand,isthe
testing conditions, or can cause behavioral consequenceofenvironmentalinfluences,af-
changes that may force the patient to seek ferentinput,andefferentdemand.
medicalattention.Theremaybelossofapre- Thesetwostepsofplasticityareillustrated
viously acquired behavioral capacity, release bythefollowingexperiment(Pascual-Leone
ofbehaviorsnormallysuppressedintheunin- 1996, Pascual-Leone et al. 1995). Normal
www.annualreviews.org • ThePlasticHumanBrainCortex 379
AR245-NE28-15 ARI 11May2005 12:8
subjectsweretaughttoperformwithonehand oftheactualmovements(Rolandetal.1987,
afive-fingerexerciseonapianokeyboardcon- Decety & Ingvar 1990). In doing so, men-
nected via computer musical interface. The tal practice alone may be sufficient to pro-
subjects were instructed to perform the se- motetheplasticmodulationofneuralcircuits
quenceoffingermovementsfluently,without placingthesubjectsatanadvantageforfaster
pauses,andwithoutskippinganykeys,while skilllearningwithminimalphysicalpractice,
payingparticularattentiontokeepingthein- presumably by making the reinforcement
tervalbetweentheindividualkeypressescon- of existing connections easier and perhaps
stant and the duration of each key press the speedinguptheprocessofsubsequentsprout-
same.Ametronomegaveatempoof60beats ingandconsolidatingofmemories.
perminutesforwhichthesubjectswereasked Once near-perfect level of performance
to aim, as they performed the exercise un- was reached at the end of a week of daily
g derauditoryfeedback.Subjectswerestudied practice, subjects were randomized into two
or
s. on five consecutive days, and each day they groups(Figure1B).Group1continueddaily
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e had a two-hour practice session followed by practiceofthesamepianoexerciseduringthe
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1. E (TMS) to map the motor cortical areas tar- tuallyaslowdecreaseinsizedespitecontin-
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v. nificantly(Figure1A).However,thisincrease follow-upandremainedstablethereafter.
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20- to 30-min rest period after the practice five-finger movement exercise correctly is
(and test) session (Pascual-Leone 1996). No associatedwithreorganizationinthecortical
suchmodulationinthecorticaloutputmaps motor outputs to the muscles involved in
was noted when maps were obtained before thetask.Therapidtimecourseintheinitial
eachdailypracticesession(Figure1A). modulationofthemotoroutputs,bywhicha
Remarkably,mentalpracticeresultedina certainregionofmotorcortexcanreversibly
similar reorganization of the motor outputs increaseitsinfluenceonamotoneuronpool,
to the one observed in the group of sub- is most compatible with the unmasking of
jectsthatphysicallypracticedthemovements previously existing connections (Jacobs &
(Figure 1C). Mental simulation of move- Donoghue1991,Sanesetal.1992).Support-
mentsactivatessomeofthesamecentralneu- ing this notion, the initial changes are quite
ral structures required for the performance transient: demonstrable after practice, but
380 Pascual-Leoneetal.
AR245-NE28-15 ARI 11May2005 12:8
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Figure1
Changesincorticaloutputmapsassociatedwithlearningafive-fingerexerciseonthepiano(modified
fromPascual-Leone1996,Pascual-Leoneetal.1995).A:Corticaloutputmapsforthefingerflexorsof
thetrainedandtheuntrainedhandsofarepresentativesubject(seetextandPascual-Leoneetal.1995for
detailsonmappingmethod).Notethemarkedchangesoftheoutputmapsforthetrainedhandfollowing
practiceandthelackofchangesfortheuntrainedhand.Notefurtherthesignificantdifferenceincortical
outputmapsforthetrainedhandafterthepracticesessionsondays3–5.B:Serialcorticaloutputmapsto
fingerflexorsinarepresentativesubjectduringfiveweeksofdaily(MondaytoFriday)practiceofthe
five-fingerexerciseonthepiano.Notethattherearetwodistinctprocessesinaction,oneaccountingfor
therapidmodulationofthemapsfromMondaystoFridaysandtheotherresponsiblefortheslowand
morediscretechangesinMondaymapsovertime.C:Averagecorticaloutputmapsforthefingerflexors
ofthetrainedhandinsubjectsundergoingdailyphysicalversusmentalpractice.Notethesimilarityin
outputmapswitheitherformofpractice.
www.annualreviews.org • ThePlasticHumanBrainCortex 381
AR245-NE28-15 ARI 11May2005 12:8
returningtobaselineafteraweekendrest.As A growing number of neuroimaging studies
thetaskbecomesoverlearnedoverthecourse have suggested a similar two-step process
of five weeks, the pattern of cortical activa- (Seitzetal.1990;Graftonetal.1992;Jenkins
tionforoptimaltaskperformancechangesas etal.1994;Karnietal.1995,1998).
other neural structures take a more leading
role in task performance. We suggest that
THERAPIDLYSHIFTING
flexible, short-term modulation of existing
MAPPINGBETWEENBRAIN
pathwaysrepresentsafirstandnecessarystep
ACTIVITYANDBEHAVIOR
leadinguptolonger-termstructuralchanges
in the intracortical and subcortical networks Behavior is the manifestation of the coordi-
as skills become overlearned and automatic. natedworkingsoftheentirenervoussystem.
As long as an output pathway to manifest
g the behavior is preserved (even if alternate
or
s. pathwaysneedtobeunmaskedorfacilitated),
w
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1. E contralateral to the moving hand and of the
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n
n Conversely,increasingexcitabilityinthecon-
A
tralateralM1(byapplicationoffast,repetitive
Figure2 TMS)leadstoadecreaseinactivationofros-
BrainactivationinfMRIwhilesubjectsperformedthesamerhythmic tralSMA.
handmovement(undercarefulkinematiccontrol)beforeandafter
In a very elegant study, Lee et al. (2003)
repetitivetranscranialmagneticstimulation(rTMS)ofthecontralateral
combining TMS and positron emission
motorcortex.FollowingshamrTMS(toprow)thereisnochangeinthe
significantactivationofthemotorcortex(M1)contralateraltothe tomography(PET)haveprovidedsupporting
movinghandandoftherostralsupplementarymotorcortex(SMA).After evidence to these notions and critically
M1activityissuppressedusing1HzrTMS(1600stimuli,90%ofmotor extendeditbyrevealingtheshiftsincortico-
thresholdintensity;middlerow),thereisanincreasedactivationofthe
cortical and cortico-subcortical connectivity
rostralSMAandofM1ipsilateraltothemovinghand.Increasing
underlyingthechangesincorticalactivation
excitabilityinthecontralateralM1usinghigh-frequencyrTMS(20Hz,
90%ofmotorthresholdintensity,1600stimuli;bottomrow)resultsina patterns (Figure 3). Following rTMS,
decreaseinactivationofrostralSMA. task-dependentincreasesinrCBFwereseen
382 Pascual-Leoneetal.
AR245-NE28-15 ARI 11May2005 12:8
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Nb posessucharisk.Faultypracticeorexcessive
ev. movement-related connectivity from the demandinthepresenceofcertainpredispos-
R SMAandpremotorcortextositesinprimary
u. ing factors (for example, genetic) may result
n sensorimotorcortex.
n inunwantedcorticalrearrangementandlead
A
Both of these experiments demonstrate
to disease. Focal hand dystonia in musicians
that in the face of a change in motor cor-
(Chamagne2003)issuchanexampleofpatho-
tex activity (in these cases transient disrup-
logicalconsequencesofplasticity.
tion induced by rTMS; Walsh & Pascual-
We examined five guitarists using fMRI
Leone 2003) performance of a relatively
during dystonic symptom provocation by
simple movement task can be maintained
means of an adapted guitar inside the mag-
by rapid operational remapping of motor
net(Pujoletal.2000).Asreferenceweused
representations, recruitment of additional
the activation pattern obtained in the same
motor areas, and task-related changes in
subjectsduringotherhandmovementsandin
cortico-cortical and cortico-muscular coher-
matchedguitarplayerswithoutdystoniadur-
ence(Strensetal.2002,Chenetal.2003,Lee
ingtheexecutionofthesameguitar-playing
etal.2003,Olivieroetal.2003).
www.annualreviews.org • ThePlasticHumanBrainCortex 383
AR245-NE28-15 ARI 11May2005 12:8
ultimately maladaptive, giving rise to symp-
toms of pathology. A sensory disturbance or
sensorimotor mismatch may play a crucial
role in contributing to the establishment of
suchanundesirablepatternofcorticalactiva-
tion(Hallett1995,Bara-Jimenezetal.1998,
Elbertetal.1998,Pantevetal.2001).
Regardless of the role that sensory
dysfunction may play, suppression of the
task-specificexcessiveactivationofthemotor
cortexhasbeneficialbehavioralconsequences
for the symptoms of dystonia. For example,
g application of slow, repetitive TMS to the
or
s. contralateralmotorcortexsuppressescortical
w
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1. E establishment of a more adaptive mapping
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Neurosby HA Figure4 exercises.Dystonicmusicianscomparedwith cporortpiceartlystoimftuhlaetinoenr.vIonuseistyhsetremcasies,uthtielipzeladsttioc
v. BOLDfMRIimages bothcontrolsituationsshowedasignificantly induceabehaviorallydesirableoutcome.
e ofanormalanda
R largeractivationofthecontralateralprimary
nnu. dpylasytoerniecxegcuuittainrg sensorimotor cortex that contrasted with a
A righthandarpeggios conspicuousbilateralunderactivationofpre- PLASTICITYINTHESETTING
inthescanner.Note motor areas (Figure 4). Our results coin- OFBRAININJURY
thegreateractivation cidewithstudiesofotherdystoniatypesbe-
Thatplasticityisacapacityofthebrainthat
ofthesensorimotor
causetheyshowanabnormalrecruitmentof
cortex(arrows) can be activated in response to an insult to
cortical areas involved in the control of vol-
contralateraltothe promote functional recovery or compensate
performinghandand untary movement. Our study demonstrates for lost function is a misconception. Rather,
thelackofactivation that the primary sensorimotor cortex in pa-
plasticityisalwaysactivated.Followingbrain
ofpremotorand tients with focal dystonia is overactive when
injury, behavior (regardless of whether nor-
supplementary
they are tested during full expression of the
motorcorticesinthe malormanifestinginjury-relateddeficits)re-
task-inducedmovementdisorder.Theimpli-
dystonicpatient. mainstheconsequenceofthefunctioningof
ModifiedfromPujol cationisthattheestablishedmappingbetween the entire brain, and thus the consequence
etal.2000. brainactivityandbehaviorisinadequateand
of a plastic nervous system. Symptoms are
384 Pascual-Leoneetal.
AR245-NE28-15 ARI 11May2005 12:8
not the manifestation of the injured brain creasedcorticalexcitabilityintheunaffected
region, but rather the expression of plastic hemisphere after a stroke. For example, in
changes in the rest of the brain. After a le- patients with acute cortical stroke, intracor-
sion, just like after an rTMS-induced shift ticalinhibitionisdecreasedandintracortical
in activity in the primary motor cortex (see facilitationincreasedintheunaffectedhemi-
above),parallelmotorcircuitsmightbeacti- sphere (Liepert et al. 2000). Furthermore,
vatedtoestablishsomealternativeinputtothe the interhemispheric inhibitory drive from
spinal motoneurons. These parallel circuits the unaffected to the affected motor cortex
mayoriginatefromthecontralateral,undam- in the process of voluntary movement gen-
agedprimarymotorarea(M1),bilateralpre- erationisabnormal(Muraseetal.2004).In-
motor areas (PMA), bilateral supplementary terestingly,thedurationofstrokeisinversely
motor areas (SMA), bilateral somatosensory correlatedtotheimbalanceoftheexcitability
g areas,cerebellum,basalganglia,etc.Aslong betweenthehemispheres.Adiseaseduration
or
s. asefferent,cortico-spinaloutputpathwaysex- ofmorethanfourmonthsafterstrokeonset
w
e ist, cortico-cortical and cortico-subcortico- results in a tendency to normalization of
vi
nualrenly. cthoertiicnavloilnvteedrafcutniocntisownailllnshetifwtowrkei,gahitmsiancgrotsos tuhneaffiencttreadcohretmicaislphfaecrieli(tSathiiomniz(uICetFa)l.o2f00t2h)e.
no
urnals.anal use eastdaebsliirsehdabseuhiatavbiolerablrraeisnulatc.tiCvaotniocenpmtuaapllyfoirt inpAutcufrteolmyatfhteeruanstdraomkea,giendcrteoastehdeindhaimbiatgoerdy
m arjoperso mrinigghatftbeerwbroaritnhinthjuinrykianngdolfeapdrioncgestsoesreosctocurar-- hcoenmsiisdpehrseriet ma amkaensifceosntacteipotnuaolfsaennseeurifaloante-
ded fro05. For tniiosnmsotfhfautnmctaiyonpraoscefietdtinpgartdliyffienrepnatramlleelcbhua-t toexmygpetntoancdongtlruoclopseerdileemsioanndalsaicntitvhitey,preenduumce-
Downloaon 07/17/ wtichicchhahnagveesvaaimriabtolemtiimniemfirzaemdeasm.Iangitei.alRpalpaisd- bsiroanooffththeestlerosikoen, a(Fnidguthreus5l)i.mHitotwheeveexr,teanf--
1. E functional improvement is likely to occur as ter an acute phase, and once the injury is
0G
7-4LE dysfunctional,butnotdamaged,neuronalel- stable, input to the perilesional area would
5.28:37D COL epmeneunmtsbrreacopvreorcfersosmestrheesoplovset.inPjuarrytisahlloyckdaamnd- smeeaxmimtiozebtehebceasptaabsilietyxcoitfatthoerypriensenrvaetudrneeuto-
ci. 200RVAR apgaeirdedneruerlaatliveelelymeqnutisckmlyayafbteerabthleetionsbueltrea-s roountpsuint.tIhfesoin,juforleldowtiisnsguethtoe dacriuvteebpehhaasvei,owrael
Neurosby HA wpreollv,etmhuesnct.oSnutrbisbeuqtuinegnttopreoacrelyssfeusn,octnicoentahleimfi-- mmiagnhytinextrpaehcetmaisshpihfteroifc)ininteterhraecmtiiosnpsh,efrriocm(ainnd-
v. naldamagehasbeenestablished,involvere- hibitorytoexcitatory.Shouldsuchashiftfail
e
R
u. learning(ratherthanrecovery)andwillfollow totakeplace,theresultingfunctionaloutcome
n
n thetwostepsdiscussedabove:initialunmask- may be undesirable, with limited behavioral
A
ingandstrengtheningofexistingneuralpath- restoration, in part owing to persistent in-
ways,andeventuallytheestablishmentofnew hibitory inputs from the intact to the dam-
structuralchanges. aged hemisphere (Figure 5). In fact, some
Theseconceptscanbeillustratedbyexam- neuroimagingstudiesdemonstratethatlong-
iningtheroleoftheipsilateralmotorcortexin term, persistent activation of the ipsilateral
therecoveryofhandmotorfunctionfollow- cortex during motor tasks is associated with
ingstroke.Afterstroke,thereisanincreasein poor motor outcomes, whereas a good mo-
theexcitabilityoftheunaffectedhemisphere, tor recovery is associated with a decrease in
presumably owing to reduced transcallosal activity in the unaffected and an increase in
inhibition from the damaged hemisphere theaffectedprimarysensorimotorcortexac-
and increased use of the intact hemisphere. tivity(Careyetal.2002,Rossini&DalForno
Several studies have demonstrated the in- 2004).Furthermore,thepatternofactivation
www.annualreviews.org • ThePlasticHumanBrainCortex 385
AR245-NE28-15 ARI 11May2005 12:8
Figure5
org Schematicillustrationshowingthatintheacutephaseafterastroke,increasedinhibitoryinput(withinor
s. acrossthehemispheres)maylimittheextensionofthelesion.Increasedexcitability(increased
w
e glutamatergicactivityandreducedGABAergicactivity)andpostischemicLTPharboranotherwise
vi
e increasedriskforfurtherdamage.However,aftertheacutephase,andoncetheinjuryisstable
nualrnly. (long-term),excitatoryinputincreasesexcitabilityandmayfurtherincreasetheefferent(e.g.,motor)
no output.Incontrast,inhibitoryinputatchronicstagesisamaladaptativestrategy,andtheresulting
urnals.anal use f(uinntcrtai-oonralinotuetrchoemmeismphayerbice)uonfdseuscihraibnlpeu,twsimthalyimdiiftfeedrbaechroasvsionreaulrraelsstoysrtaetmiosn.anNdoatecrtohsastitnhdeivsioduuracles.s
m arjoperso Nanedvleornthge-lteesrsm,thstiasgperso(vbildoceksaarrroowadsimndaipcaftoerandeeusirroambloedinuclraetaosreyorindteecrrveeansetiionnesxcwithaobisleitay)im. sdifferintheacute
ded fro05. For inwell-recoveredpatientsissimilartohealthy subjects,whereipsilateralmotorcortexacti-
wnloa07/17/ snuabljsetcutdsie(Wsoafrdpaettieanl.ts2f0o0l3lo)w.Mingoraesltornogkietuadnid- vhaatniodnmoonvefmunecnttisonisalinMdeRedI dreulraitnegdupnriimlataerrilayl
1. DoE on correlation of interhemispheric interactions to interhemispheric interactions (Kobayashi
77-40LLEG wpliothreftuhnecsteioinssaulemsefuasruthreesr.aIrfeconrereedcetd, nteoureox-- eotf oaln.e2h00em3)i,spahnedredirserduupctieosntroafnstchaelloascatliviinty-
8:3CO modulatory approaches targeting the intact hibitiontothecontralateralhemisphereand
05.2RD hemispheremaybeusefultolimitinjuryand canindeedimproveipsilateralmotorfunction
ci. 20RVA promoterecoveryafterastroke. (Kobayashi et al. 2004). However, Werhahn
eurosy HA moFtoorrcinosrttaenxcteh,rsouupgphresslsoiownroTfMtheSi(pPsialsactueraal-l eutatael.t(h2e00m3o)dcounladtuiocnteedffaescitmsiolafr1sHtuzdryTtoMeSvaol-f
Nb
v. Leone et al. 1998, Maeda et al. 2000) may theunaffectedhemisphereontheparetichand
e
R enhance motor performance in patients sta- andfounddifferentresults.Inthatstudy,1Hz
u.
n ble following the acute phase of a stroke. In rTMS of the unaffected hemisphere did not
n
A
patients 1–2 months after a stroke, Mansur affectthefingertappingintheparetichandin
etal.(2005)applied0.5HzrTMSfor10min asmallsampleoffivepatientsmorethanone
totheunaffectedhemispheretosuppresscor- yearafterastroke.Thetimesincethebrain
tical activity and thus release the damaged insultislikelytobeacriticalvariabletocon-
hemisphere from potentially excessive tran- sider.Studieswithlargersamplesofpatients
scallosal inhibition. The results of this pilot areneededtoinvestigatethisquestionfurther.
study support the notion that the overactiv- Behavioral motor therapy may also shift
ity of the unaffected hemisphere (ipsilateral cortical excitability balance between hemi-
hemisphere) may hinder hand function re- spheresandthusinfluenceoutcome.Forex-
covery,andneuromodulationcanbeaninter- ample, the beneficial effects of constraint-
ventionaltooltoacceleratethisrecovery.The inducedtherapyonmotorfunction(Mark&
findingsareconsistentwithresultsinnormal Taub 2004, Grotta et al. 2004) are achieved
386 Pascual-Leoneetal.