TechniquesinCognitive

Neuroscience
TranscranialMagneticStimulation(TMS)

Dr.RogerNewport

LectureOverview
BriefhistoryofTMSandhowitworks

WhatcanTMSaddtoCognitiveNeuroscience?
WhatadvantagesarethereforTMSoverotherbrainbehaviortechniques?
Lesionsudies
Directcorticalstimulation
Imaging
TMS

DesignConsiderations
TMSsafety
Contraindications
Acceptablerisks
Ethics
Coilshape
Depthandspatialresolutionofstimulation
CoilLocalisation
Controlconditions

Stimulationtechniquesandeffects
HistoryofTMSandobligatoryfunnypictures

Merton&Morton(1980).Successful
TranscranialElectricalStimulation

Magnusson&
dArsonval(1896/1911)

Thompson,1910 Stevens,1911
 Barker, 1984

CommonrTMSmachines

Magstim Dantec

Transcranial Magnetic
Stimulation allows the Safe,
Non-invasive and Painless
Stimulation of the Human

Brain Cortex. Cadwell
ElectromagneticInduction

Introducesdisorderintoanormallyorderedsystem

LectureOverview
BriefhistoryofTMSandhowitworks

WhatcanTMSaddtoCognitiveNeuroscience?
WhatadvantagesarethereforTMSoverotherbrainbehaviortechniques?
Lesionsudies
Directcorticalstimulation
Imaging
TMS

OtherBrainBehaviorTechniques
LesionStudies
Dependenceofserendipityofnatureorexperimentalmodelsinanimals
Singleorfewcasestudies
mightbemorethanasinglelesion
lesionmaybelargerthanthebrainareaunderstudy
Cognitiveabilitiesmaybegloballyimpaired
Lesioncanonlybeaccuratelydefinedpostmortem
Thedamagedregioncannotbereinstatedtoobtaincontrolmeasuresthat
bracketthelesioninducedeffect
Comparisonsmustbemadetohealthycontrols;internaldoubledissociations
arenotpossible
Givenbrainplasticity,connectionsmightbemodifiedfollowinglesions

OtherBrainBehaviorTechniques

CorticalStimulation
Invasive
Limitedtothestudyofpatientswithbrain
pathologiesrequiringneurosurgical
interventions
StressfulsituationintheORandmedications
mightconditionsubjectsperformance
Timeconstraintslimittheexperimental
paradigms
Retestingisnotpossible

OtherBrainBehaviorTechniques

Neuroimaging(BrainMapping)

Noninvasiveidentificationofthe
braininjurycorrelatedwithagiven
behavior
Associationofbrainactivitywith
behaviorcannotruleout
epiphenomenon
Cannotdemonstratethenecessityof
givenregiontofunction
Neuroimagingtechniquesareusually
onlygoodeithertemporallyor
spatially,notboth(e.g.Pet&fMRI
lacktemporalresolution,EEGlacks
spatialresolution)

AdvantagesofTMSintheStudyofBrain
BehaviorRelations
Studyofnormalsubjectseliminatesthepotentialconfoundsof
additionalbrainlesionsandpathologicalbrainsubstrates
Acutestudiesminimizethepossibilityofplasticreorganization
ofbrainfunction
Repeatedstudiesinthesamesubject
Studymultiplesubjectswiththesameexperimentalparadigm
Studythetimecourseofnetworkinteractions
WhencombinedwithPETorfMRI,canbuildapictureofnot
onlywhichareasofbrainareactiveinatask,butalsothetime
atwhicheachonecontributestothetaskperformance.

Studyinternaldoubledissociationsandnetworkinteractionsbytargeting
differentbrainstructuresduringsingleataskanddisruptingthesamecortical

areaduringdifferentrelatedtasks
AdvantagesofTMS:VirtualPatients
causallinkbetweenbrainactivityandbehaviour
Braille Alexia
Reallesion TMSlesion

Cohenetal.,1997.
OccipitalTMS
Hamiltonetal.,2000. disruptsbraille
Reportedcaseofblind readinginearlyblind,
butnotcontrol
womanwholostabilityto subjects
readbraillefollowing
bilateraloccipitallesions

Blue=sighted;Red=Eblind
AdvantagesofTMS:Chronometry

Chronometry:
timingthe
contributionoffocal
brainactivityto
behavior

Role of visual
cortex in tactile
information
processing in
early blind
subjects
HamiltonandPascual
Leone,1998

Functionalconnectivityrelatebehaviourtothe
interactionbetweenelementsofaneuralnetwork

TMStoFEFcorrelationbetween
TMSandCBFat
i)stimulationsite
ii)distalregionsconsistentwith
Paus et al. TMS/PET knownanatomicalconnectivityof
monkeyFEF

Mappingandmodulationofneuralplasticity
rapidchanges
Rapidplasticitymapchangesin
corticalexcitabilityusing
TMS/MEPsduringalearningtask
(PacualLeoneetal.)

Cohenandcolleagues.
Modulationofcorticalexcitability
indeafferentationstudies.
TMSofplastichemisphere
increasesneuralresponse,
TMSofnonplastichemisphere
downgradesneuralresponseof
plastichemisphere.
SerialReactionTimeTask

Mappingandmodulationofneuralplasticity
slowchanges
Amputeecorticalexcitability
Measurechangesinmotor
excitabilityinneurologic
disorders(e.g.PD,HD)
Braille reader took 10-day holiday
from reading. Size of finger
representation shrank
dramatically until she returned to
work even time off over the
weekend quantitatively reduced
finger representation.
OtherusesforTMS
Clinicaltestspeed,orexistenceof,
ofcorticospinalconnections
(MS/stroke)
TherapyrTMDhaslongterm
effectsondepression
Summary:WhatcanTMSaddtoCognitive
Neuroscience?

VirtualPatients:causallinkbetweenbrainactivity
andbehavior
Chronometry:timingthecontributionoffocal
brainactivitytobehavior
Functionalconnectivity:relatebehaviortothe
interactionbetweenelementsofaneuralnetwork
Mapandmodulateneuralplasticity

LectureOverview
BriefhistoryofTMSandhowitworks

WhatcanTMSaddtoCognitiveNeuroscience?
WhatadvantagesarethereforTMSoverotherbrainbehaviortechniques?
Lesionsudies
Directcorticalstimulation
Imaging
TMS

DesignConsiderations
TMSsafety
Contraindications
Acceptablerisks
Ethics
Coilshape
Depthandspatialresolutionofstimulation
CoilLocalisation
Controlconditions

Stimulationtechniquesandeffects
Safety
SeizureinductionCausedbyspreadofexcitation.SinglepulseTMS
hasproducedseizuresinpatients,butnotinnormalsubjects.rTMShas
causedseizuresinpatientsandinnormalvolunteers.Visualand/or
EMGmonitoringforafterdischargesaswellasspreadingexcitation
mayreducerisk.

HearinglossTMSproducesloudclick(90130dB)inthemost
sensitivefrequencyrange(27kHz).rTMS=moresustainednoise.
Reducedconsiderablywithearplugs.

HeatingofthebrainTheoreticalpowerdissipationfromTMSisfew
milliwattsat1Hz,whilethebrain'smetabolicpoweris13W

EngineeringsafetyTMSequipmentoperatesatlethalvoltagesofup
to4kV.Themaximumenergyinthecapacitorisabout500J,equalto

dropping100kgfrom50cmonyourfeet.Sodontputyourteaonit.
Safety
ScalpburnsfromEEGelectrodesMildscalpburnsinsubjectswith
scalpelectrodescanbeeasilyavoidedusing,e.g.,smalllow
conductivityAg/AgClpelletelectrodes.

EffectoncognitionSlighttrendtowardbetterverbalmemory,
improveddelayedrecallandbettermotorreactiontime

LocalneckpainandheadachesRelatedtostimulationoflocal
musclesandnerves,siteandintensitydependant.Particularly
uncomfortableoverfrontotemporalregions.

EffectonMoodinnormalsSubtlechangesinmoodaresiteand
frequencydependant.HighfrequencyrTMSofleftfrontalcortex
worsensmood.HighfrequencyrTMSofrightfrontalcortexmay
improvemood.
Safety
FollowpublishedsafetyguidelinesforrTMS

MaximumsafedurationofsinglerTMStrainat110%MT
Frequency(Hz) Max.duration(s)
1 1800+
+minimumintertrain
5 10
interval
10 5 e.g.at20Hz@1.01.1
Tleave>5sintertrain
20 1.6
25 .84

Caution:Guidelinesnotperfect

SafetyContraindications
Metallichardwarenearcoil
Pacemakers
implantablemedicalpumps
ventriculoperitonealshunts
(casestudieswithimplantedbrainstimulatorsandabdominaldeviceshavenotshown
complications)
Historyofseizuresorhistoryofepilepsyinfirstdegreerelative
Medicineswhichreduceseizurethreshold
Subjectswhoarepregnant
(casestudieshavenotshowncomplications)
Historyofseriousheadtrauma
Historyofsubstanceabuse
Stroke
StatusafterBrainSurgery
Othermedical/neurologicconditionseitherassociatedwithepilepsyorinwhomaseizure
wouldbeparticularlyhazardous(e.g.increasedintracranialpressure)

SafetyTMSAdultSafetyScreen
Haveyouever:hadanadversereactiontoTMS?
Hadaseizure?
HadanEEG?
Hadastroke?
Hadaheadinjury(includeneurosurgery)?
Doyouhaveanymetalinyourhead(outsideofthemouth,)suchasshrapnel,surgical
clips,orfragmentsfromweldingormetalwork?(MetalcanbemovedorheatedbyTMS)
Doyouhaveanyimplanteddevicessuchascardiacpacemakers,medicalpumps,or
intracardiaclines?(TMSmayinterferewithelectronicsandthosewithheartconditionsare
atgreaterriskineventofseizure)
Doyousufferfromfrequentorsevereheadaches?
Haveyoueverhadanyotherbrainrelatedcondition?
Haveyoueverhadanyillnessthatcausedbraininjury?
Areyoutakinganymedications?(e.g.Tricyclicantidepressants,neurolepticagents,and
otherdrugsthatlowertheseizurethreshold)

Ifyouareawomanofchildbearingage,areyousexuallyactive,andifso,areyounotusing
areliablemethodofbirthcontrol?

Doesanyoneinyourfamilyhaveepilepsy?
DoyouneedfurtherexplanationofTMSanditsassociatedrisks?

EthicsGuidelines
InformedConsentdisclosureofallsignificantrisks,both
thoseknownandthosesuspectedpossible
PotentialBenefitmustoutweighrisk
EqualdistributionofriskParticularlyvulnerablepatient
populationsshouldbeavoided

LevelsofRisk
ClassIDirectclinicalbenefitisexpected,e.g.
depression.Levelofacceptablerisk(i.e.sz)ismoderate
ClassIIPotential,butunprovenbenefit,e.g.PD.Level
ofacceptableriskislow.
ClassIIINoexpectedbenefit.Willadvancegeneral
understanding.Requiresstringentsafetyguidelines.

Practical
T
considerations
Coilshape

The geometry
of the coil
determines the
focality of the
magnetic field
and of the
induced current
- hence also of
the targeted
brain area.

PracticalConsiderationsstimulationdepth
70x60 5mm

55x45 15mm
40x30 20mm
0 25mm

Cannotstimulatemedialorsubcorticalareas

Caution!
Allthefiguresquotedonthepreviouspageareestimated.

Knowledgeofthemagneticfieldinducedbythecoilisnot
sufficienttoknowtheinducedcurrentinthebrainandthatis
verydifficulttomeasure

ThepresumedintensityofTMSisusuallybasedonmotorthreshold
Butthisassumesauniformandconstantthresholdthroughoutcortex

Itispossiblethatdifferencesinbrainanatomymayleadtointer
individualdifferencesinthesubstratesofTMSeffects

Temporaleffectsdependonrecoveryrateofneuralarea

FurtherCaution!Spreadofactivation
andthepathofleastresistance

Coillocalisationhittingtherightspot

Findfunctionaleffect
M1handtwitch(MEP)
V5movingphosphenes

Findanatomicallandmark
inion/nasionear/earvertex
EEG10/20system

Moveasetdistancealongand
across(e.g.FEF=24cmanterior
and24cmlateraltohandarea)

Coillocalisationhittingtherightspot
But:notallbrainsarethesame

Paus et al.

MRIcoregistration
Functionalandstructuralscan
Frameless
e.g.eyemovementtestfromfunctional Stereotactic
andmapontostructural,thencoreg System

v.expensiveandlaborious
Stimulationtechniquesandpossibleeffects

+
+

Expectedeffect Connectedeffects Paradoxicaleffects

Singlepulse Pairedpulse Pairedpulse

rTMS(low/highfr.)
ControlConditions

Real

Differenthemisphere Different
effector
noeffect
Sham

Differentsite
OrinterleaveTMSwithnoTMStrials

Majoradvantagessummary
Reversiblelesionswithoutplasticitychanges
Repeatable
Highspatialandtemporalresolution
Canestablishcausallinkbetweenbrainactivationandbehaviour
Canmeasurecorticalplasticity
Canmodulatecorticalplasticity
Therapeuticbenefits

Majorlimitationssummary
Onlyregionsoncorticalsurfacecanbestimulated
Canbeunpleasantforsubjects
Riskstosubjectsandesp.patients
Stringentethicsrequired(cantbeusedbysomeinstitutions)
Localisationuncertainty

Stimulationleveluncertainty
 SuggestedReadings
WalshandCowey(1998)Magneticstimulationstudiesofvisualcognition.TrendsinCognitive
Sciences2(3),103110
VincentWalshandMatthewRushworth(1999)Aprimerofmagneticstimulationasatoolfor
neuropsychology.Neuropsychologia37,125135
Paus(1999)Imagingthebrainbefore,duringandaftertranscranialmagneticstimulation.
Neuropsychologia37.
Pausetal.(1997)Transcranialmagneticstimulationduringpositronemissiontomography:anew
methodforstudyingconnectivityofthehumancerebralcortex.JournalofNeuroscience17,3178
3184.
Cohen,L.G.etal.(1997)FunctionalrelevanceofcrossmodalplasticityinblindhumansNature
389,180183
PascualLeone,WalshandRothwell.(2000)Transcranialmagneticstimulationincognitive
neurosciencevirtuallesion,chronometry,andfunctional
connectivityCurrentOpinioninNeurobiology2000,10:232237
Hamiltonetal.,(2000)..AlexiaforBraillefollowingbilateraloccipitalstrokeinanearlyblind
woman.Neuroreport11:237240,2000
HamiltonandPascualLeone(1998).CorticalplasticityassociatedwithBraillelearning,Trends
inCognitiveSciences,Volume2,Issue5,1May1998,Pages168174
EricM.Wassermann.(1998).Riskandsafetyofrepetitivetranscranialmagneticstimulation:
reportandsuggestedguidelinesfromtheInternationalWorkshopontheSafetyofRepetitive
TranscranialMagneticStimulation,June57,1996Electroencephalographyandclinical

Neurophysiology108(1998)116