112翻译.docx

112翻译.docx

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112翻译

Evaluatingtheimpactofthedeepbrainstimulationinducedelectricfieldon

subthalamicneurons:

Acomputationalmodellingstudy

abstract

Deepbrainstimulation（DBS）isaneffectivesurgicaltreatmentusedtoalleviatethesymptomsofneurological

disorders,mostcommonlymovementdisorders.However,themechanismofhowtheapplied

stimuluspulsesinteractwiththesurroundingneuronalelementsisnotyetclearlyunderstood,slowing

progressanddevelopmentofthispromisingtherapeutictechnology.Toextendpreviousapproachesof

usingisolated,myelinatedaxonmodelsusedtoestimatetheeffectofDBS,weproposethattakinginto

accountentireneuronswillrevealstimulationinducedeffectsoverlookedbypreviousstudies.Wecompared

theDBSinducedvolumeoftissueactivated（VTA）usingarraysofwholecellmodelsofsubthalamic

nucleus（STN）excitatoryneuronsconsistingofacellbodyandananatomicallyaccuratedendritictree,to

thecommonmodelsofaxonarrays.OurresultsdemonstratethatSTNneuronshaveahigherexcitation

thresholdthanaxons,asstimulusamplitudes10timesaslargeelicitaVTArangeafifthofthedistance

fromtheelectrodesurface.However,theSTNneuronsdoshowachangeinbackgroundfiringratein

responsetostimulation,evenwhentheyareclassifiedassub-thresholdbytheVTAdefinition.Furthermore

thewholeneuronmodelsaresensitivetoregionsofhighcurrentdensity,asthedistributionof

firingiscentredontheelectrodecontactedgesTheseresultsdemonstratetheimportanceofaccurate

neuronmodelsforfullyappreciatingthespatialeffectsofDBSontheimmediatesurroundingbrainvolume

withinsmalldistancesoftheelectrode,whichareoverlookedbypreviousmodelsofisolatedaxons

andindividualneurons.

.2010ElsevierB.V.Allrightsreserved.

1.Introduction

Computationalmodelshaveproventobeextremelyusefulfor

visualizingandestimatingtheeffectsofextracellularstimulation

ofthehumanbrain,asinducedbytherapeuticdeepbrainstimulation

（DBS）.DBSisasurgical

treatmentusedtocombatthesymptomsofneurologicaldisorders,

mostcommonlymovementdisorderssuchasParkinson’sdisease,

tremoranddystoniaandincreasinglyforpsychologicaldisorders

itinvolvestheimplantationofquadripolarelectrodesintothehuman

brain,throughwhichahighfrequencytrainofconstantvoltageor

constantcurrentsquarepulsesisusedtostimulatethesurrounding

neuraltissue.Thesuccessofthetreatmentismarredonlybythe

lackofunderstandingofhowthestimulusinteractswithsurrounding

neuronalactivitytoinducetheobservedclinicalimprovement

particularly

asthetreatmentevolvedfromempiricalinvestigationsinthe

operatingtheatre.Restrictionsonexperimentalworkmakeinvestigations

ofthemechanismsextremelydifficult.Furthermore,direct

visualizationoftheinducedcurrentinvivoisatpresentimpossible,

duetosafetyissuesofmagneticresonanceimagingduringstimulation,

aswellasthelimitationofstimulusartefactonsimultaneous

electroencephalography,localfieldpotentialrecordingsandradiologicalimaging.Therefore,thepresentdayuse

ofDBSlacksatheoreticalframeworkandremainsbasedontrial

anderrorfordeterminingelectrodelocation,electrodemontage

andparametersettings,whichissub-optimal.Furthermore,future

developmentofDBSfornewdisordersandtargetsisslowedby

thenecessityoftakingthisempiricalapproach.Theseconstraints

furtherinhibitourabilitytounderstandhowthestimulusinteracts

withtheneuronsandtheneuronalnetworksinvolvedinthe

pathology.

HypothesesforthemechanismsunderlyingtheeffectsofDBSof

thesubthalamicnucleus（STN）,themostcommontargetforParkinson’s

disease,rangefromtheactivationoffibresofpassageleading

tooverexcitationofdownstreamstructuresandinturninhibiting

thethalamusandcortex,tothedisruptionofnetworkwide

pathologicalsynchronizationallowingthepatienttoemergefrom

disablingsymptomssuchastremor,rigidityandavarietyofakinesias

.Inrecentyears,twomodellingapproacheshaveproven

particularlyusefulandcontributedtoourabilitytoprobesuch

hypotheses.Thefirstfocusesonmodelsofsynchronizedactivity

inthebasalganglia,orthebasalgangliathalamocorticalnetwork

.While

thisisaninterestingapproachtoinvestigatingideasofdesynchronization

ofpathologicalsynchrony,mostmodelsdonottakeinto

accountthegeometryofthebraintissueandthespatialspread

ofcurrentinthebrainvolumesurroundingaDBSelectrode.The

secondusesafiniteelementmodeltovisualizetheelectricfield

distributionoverageometryofinterestandcouples

theresultstocablemodelsofsingleneurons

orarraysofaxonsforquantifying

thevolumeoftissueactivated（VTA）inthesurroundingbrain

volume.Si