rTMS Repetitive Transcranial Magnetic Stimulation - Brainbox ...

Repetitive transcranial magnetic stimulation (rTMS) is a method of non-invasive brain stimulation that involves applying TMS pulses at a rhythmic, ... rTMSRepetitiveTranscranialMagneticStimulation Repetitivetranscranialmagneticstimulation(rTMS)isamethodofnon-invasivebrainstimulationthatinvolvesapplyingTMSpulsesatarhythmic,repetitivefrequencytoasubjectforaprolongedperiodoftime. rTMSisabletoinduceincreasesordecreasesinexcitatoryorinhibitorypost-synapticpotentialsfollowingtheapplicationofalargenumberofTMSpulsestoonecorticalarea,whichcanbefollowedbyaperiodoftimewhereachangeincorticalexcitabilityinthesiteofstimulation(orthebroadernetworkcontainingthesitestimulation)(Fitzgeraldetal.,2006).ThischangeincorticalexcitabilitycanbeanexcitatoryoneoraninhibitoryonebutthischangetendstooutlasttheperiodofrTMSdelivered. Asaresult,rTMShasbeeninvestigatedasapotentialtherapeuticinterventionandiscurrentlyaUSFoodandDrugAdministration(FDA)approvedtreatmentfordepression,anxiety,andmigraine. Inadditiontoitstherapeuticuse,the‘offline’effectsofrTMShavealsobeenextensivelyusedasmeansoftransientlyinterferingwithcorticalareasofinterestandsubsequenltyobservingtheeffectsontaskperformancetoprovidecausalevidenceforbrainareaincognitiveprocess(e.g.Verbruggenetal.,2010). RepetitiveTMSdoesnotrequireabehaviouraltasktobeusedasphysiologicalprobe;itisalsopossibletorelyonneuroimagingmeasuressuchaselectroencephalography(EEG)(e.g.Rocchietal.,2018),magnetoencephalography(MEG)(e.g.Allenetal.,2014),magneticresonancespectroscopy(e.g.Allenetal.,2014),functionalmagneticresonanceimaging(fMRI)(e.g.Tupaketal.,2011)orpositronemissiontomography(e.g.Siebneretal.,2001). rTMSApplications Repetitivetranscranialmagneticstimulation(rTMS)wasinitiallyappliedtothemotorcortex(M1)ateitherafixedfrequencyorinpatternedburstsandtheconsequencesoftheserTMSprotocolswerethenrevealedbymeasuringwhethertheamplitudeofmotorevokedpotentials(MEPs)evokedbysinglepulsesofTMStoM1werechangedaftertheapplicationofrTMS.OneofthemostpopularrTMSprotocolsthatwasdevelopedusingthismethodwasthetaburststimulation(TBS)(Huangetal.,2005).TBSwasinspiredbytheideathattheapplicationoffourpulsesat100Hzseparatedbya5Hzintervalproduceplasticitylikechangesinhippocampalbrainslices(Capocchietal.,1992;Larson&Lynch,1986,1989).InrTMS,however,3(biphasic)pulseswereappliedatalowerfrequencyof50Hzduetohardwareconstraintsbuta5Hzintervalwasstillappliedtotheintervalbetweenburstsat80%ofactivemotorthreshold(Suppaetal.,2016).Initially,TBSwasfoundtoproduceexcitatoryorinhibitoryeffectsdependingonthe3pulseburstsweredeliveredfora2secondperiodfollowedbyaninterval(iTBS)orwhetherthe3pulseburstsweredeliveredcontinuously(cTBS)(Huangetal.,2005).TheapplicationofcTBSwasinitiallyfoundtodecreaseMEPamplitudeforuptoanhourwhereasiTBSwasfoundtoincreaseMEPamplitudefor~15minutes(Huangetal.,2005).SuchaneffectwasnolongpresentwhenanNMDAantagonistwasadministeredtosubjects,suggestingthataNMDA-dependentmechanismlinkedtolong-termpotentiation(LTP)orlong-termdepression(LTD)underliestheofflineeffectsofTBSonexcitabilityofthemotorcortex(Huangetal.,2007).  DespitetheearlypromiseofTBS,however,laterstudiesrevealedvariabilityintheresponsetoTBSwithsomeparticipantsshowedaneffectintheexpecteddirectionwhereasotherparticipantsshowedaneffectintheoppositedirection(Hamadaetal.,2013).Thisoutcomepromptedinvestigationintowhysuchintra-andinter-individualreasonsforwhysuchvariabilityexists(Suppaetal.,2016;Hinderetal.,2014)andwhetheradditionalTMSprotocolscanberevealedthatalsoshowrobustofflineeffects(Huangetal.,2009).Onenewprotocolthatisshowingpromisingeffectsisquadro-pulsestimulation(QPS),whichmonophasicpulseshapes,notbiphasicpulseshapes.QPSinvolvesadministeringburstscontaining4pulseswitha5secondintervalbetweenoneburstandasubsequentburst.InhibitoryorexcitatoryeffectsofQPShavebeenfoundtodependontheintervalseparatingeachpulsewithinaburst(Hamadaetal.,2008).A5ms(QPS-5)intervalbetweeneachpulsewasfoundtoincreaseMEPamplitudewhereasa50msintervalwasfoundtodecreaseMEPamplituderelativetobaseline(Hamadaetal.,2008).Whena5secondintervalwasused,80%ofparticipantsshowntheexpectedincreaseinMEPamplitudewhenQPS-5wasused(Nakamuraetal.,2016). rTMSPulseShapes TheimpactofthepulseshapehasalsobeenhighlightedbyQPSprotocols.OnestudykepttheQPSparameterstheexactlythesame,butdeliveredthepulsesthroughmonophasicorbiphasicstimulators,andalsovariedtheinterburstinterval(Nakamuraetal.,2016).ThisstudyrevealedthatmonophasicQPSledtolongerlastingofflineeffectsthanbiphasicQPS,highlightingthepotentialimpactofthemonophasicpulseshapeinrTMSprotocolsinadditiontoimportanceoftheIBIof5seconds.Thedifferencebetweenmonophasicandbiphasicpulseshapesalsohighlightsthatthepulse usedtoproduceofflineeffectsofanrTMSprotocolmaybeacriticaldeterminantofitsefficacy.Recentworkwithcontrollablepulseparameter(cTMS)deviceshasshownthatthedirectionofthemagneticpulseshape-biphasicormonophasic-canhaveanimpactontheefficacyofanrTMSprotocol.Moreover,themajorityoftherTMSprotocolsrecruitedbiphasicpulseshapesratherthanmonophasicpulseshapes.Arecentexperimenthasaltered thepulsewidthofamonophasicpulseandalsomanipulatedtheextenttowhichapulseshapeinbiphasic(Halawaetal.,2019).Theeffectof900TMSpulsesat1HzonMEPamplitudeschangeddependedonthepulseshapethatwasadministeredbythestimulator.Quasi-unidirectional,shorterpulseswidths(40μs,80μs)increasedMEPamplitudewhereasalongerpulsewidth(120μs)increasedMEPamplitude.However,changingtheoveralldirectionalityofaTMSpulse,causingittoresembleabiphasicpulseshape,ontheotherhand,increasedMEPamplitudeoncetherTMSprotocolwascompleted(Halawaetal.,2019).Thisexperimentemphasisesthattherearestillmanyparametersthatcanbealteredthathavenotyetbeenfullyexplored,whichcouldbecomeafuturebasisforoptimisingrTMSprotocolsorinventednewrTMSprotocolsaltogether. 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DuoMAGXT ElevateTMS DuoMAGTMSCoils rTMS