Facial muscle activations by functional electrical stimulation

Facial muscle activations by functional electrical stimulation

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Ilves, M., Lylykangas, J., Rantanen, V., Mäkelä, E., Vehkaoja, A., Verho, J., ... Surakka, V. (2019). Facial muscle activations by functional electrical stimulation. Biomedical Signal Processing and Control, 48, 248-254.

https://doi.org/10.1016/j.bspc.2018.10.015 Year

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Biomedical Signal Processing and Control

j o u r n a l h o m e p a g e :w w w . e l s e v i e r . c o m / l o c a t e / b s p c

Facial muscle activations by functional electrical stimulation

Mirja Ilves

, Jani Lylykangas

, Ville Rantanen

, Eeva Mäkelä

, Antti Vehkaoja

, Jarmo Verho

, Jukka Lekkala

, Markus Rautiainen

, Veikko Surakka

aResearchGroupforEmotions,Sociality,andComputing,TampereUnitforComputer-HumanInteraction,FacultyofCommunicationSciences,Universityof Tampere,Kanslerinrinne1,33014,Tampere,Finland

bBiomeditechInstituteandFacultyofBiomedicalSciencesandEngineering,TampereUniversityofTechnology,Tampere,Finland

cDepartmentofClinicalNeurophysiology,MedicalImagingCentre,PirkanmaaHospitalDistrict,Tampere,Finland

dFacultyofMedicineandLifeSciences,UniversityofTampere,Tampere,Finland

a r t i c l e i n f o

Articlehistory:

Received20November2017

Receivedinrevisedform8October2018 Accepted22October2018

Keywords:

Unilateralfacialparalysis Facialmuscle

Electricalstimulation

a b s t r a c t

Thepresentaimwastoinvestigatetranscutaneousfacialmusclestimulationinordertotakefurther stepsindevelopingfacialpacingtechnology,whichcanofferanewtreatmentoptionforpatientswith unilateralfacialparalysis.Thistechnologyultimatelymeasuresmuscleactivationsfromonesideofthe faceandsimultaneouslyactivatesthecorrespondingmusclesoftheothersidewithelectricalstimulation.

Fourfacialmusclelocations—frontalis,orbicularisoculi,zygomaticusmajor,andorbicularisoris—ofthe healthyparticipants(N=24)werestimulatedtoproduceaneyebrowraise,eyeblink,smile,andlippucker, respectively.Theresultsshowedthatavisuallyobservablemovementoftheforeheadandthelowerlip wasachievedinallparticipants.Onaverage,thestimulationsatthemovementthresholdwereratedas tolerableintermsofpainratingsandneutralintermsofpleasantnessratings.Completeeyeblinkwas achievedin22participants,andmostdidnotexperiencepainfulsensations.Thestimulationofthecheek evokedobservablemovementin23participants,butthestimulationalsooftenresultedinconcurrent activationoftheeye,mouth,andnosearea.Theresultssuggestthattranscutaneousstimulationseems tobeapromisingmethodfordevelopingfurtherfacialpacingtechnology.

©2018TheAuthor(s).PublishedbyElsevierLtd.ThisisanopenaccessarticleundertheCCBYlicense (http://creativecommons.org/licenses/by/4.0/).

1. Introduction

Unilateralfacial paralysisisa conditioninwhich onesideof thefacefunctionsnormallywhilefunctionsontheothersideare impairedandinwhichthefacemaylookasymmetricalatrest.The mostcommonformofunilateralfacialparalysisisBell’spalsy[1].It isalsotermedasidiopathicfacialparalysis,whichmeansthecause ofparalysisisunknown.TheannualprevalenceforBell’spalsyis 20–30casesper100,000,thusaffectingaboutonein60–70peo- pleintheirlifetime[1–3].About70%ofpatientshavefullrecovery withinthreemonths,buttheother30%areleftwithfacialdysfunc- tionalitiesofvaryingdegrees[4].InadditiontoBell’spalsy,other causesoffacialparalysisthatmorefrequentlyleadtolonglasting orpermanentfacialdysfunctionalitiesincludetrauma,infections (e.g.,borreliosisandherpeszoster),tumordiseases,surgicalinter- ventions,andcongenitalparalysis.

Apersonsuffering fromfacialparalysismayhave functional deficitslike problems withspeaking, eating, drinking, and eye

∗Correspondingauthor.

E-mailaddress:mirja.ilves@sis.uta.fi(M.Ilves).

blinking.Inaddition,thefacehasakeyroleinsocialcommuni- cationin conveyingimportantinformation aboutone’sidentity, personality,andemotions.Facialparalysisreducesone’sabilityto expressfacialemotions,andapersonsufferingfromitoftenexpe- riencespsychologicaldistressbecauseofthealteredappearance [5,6].Thus,theconditiondramaticallydiminishesthequalityof one’slifeinmanydimensions.Currenttreatmentoffacialparalysis consistsmainlyofsurgicalreanimationandbehavioralrehabilita- tion,bothofwhichhavebeenshowntobesomewhatfunctional [7,8].Athirdoptionthatthisstudyisespeciallyfocusedonisto developtechnologythatcouldstimulatefacialmusclesinaway thatwould atleastallowcriticalsymmetricalfunctioningtobe regained.

Facialpacingreferstotechnologythatmeasureselectricmus- cleactivationswithfacialelectromyography(EMG)frommuscles oftheintactsideofthefaceandsimultaneouslyactivatesthecor- respondingmusclesoftheother(paralyzed)sidewithfunctional electricalstimulation(FES).Reanimatingthefacialfunctionsofthe paralyzedsidebyutilizingtheactivityofthenon-paralyzedone couldresultinregainingthesymmetryoffacialbehavior[9].

Although the idea of facial pacing was presented several decadesago,themajorityofstudieshavefocusedoninvestigat- https://doi.org/10.1016/j.bspc.2018.10.015

1746-8094/©2018TheAuthor(s).PublishedbyElsevierLtd.ThisisanopenaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

ingthefeasibilityofelectricalstimulationinanimalmodelswith implantableelectrodesthatwouldinvolvehighlyintrusivesurgery toinstall[10–12].However,facialpacingcanalsobeimplemented noninvasivelybymeasuringandstimulatingmuscleactivitiestran- scutaneouslyusinganexternalfacialprostheticdevicewhichcould bedevelopedassmallandwearableinthefuture[13].Itisnote- worthythatinmostcases,irrespectiveofthecauseoftheparesis, thefacialmusculaturesystemremainsfunctional,althoughmuscle atrophystartstoproceedearlyfromtheonsetofparalysis.Patients specificallyrecoveringfromacutefacialpalsyandpatientswhose recoveryprocesshasbeenincompletebutwhosefacialnervehas notfullydegeneratedcouldbenefitfromsucha device.Patients couldavoidsurgeries,whichalwayshaverisksofcomplications.In addition,transcutaneouselectricalstimulationcouldpossiblybe utilizedinfacialexercisetherapy.Forexample,suchtherapycould beutilizedtopreventmuscleatrophyortorestorethevolumeand functionofthemusclesinchronicdenervation[14–16].

Earlierhumanstudieshavefocusedonstudyingthedetection andproductionofaneyeblink[17–21].FrigerioandCavallari[18]

demonstrateda natural-likeeyeblinkwithhealthy humanpar- ticipantsusingthetranscutaneousstimulationofthefacialnerve branchtoactivatetheorbicularisoculimuscle.Further,inaprelim- inarystudywiththreefacialparalysisparticipants,transcutaneous electricalstimulationcausedacompleteblinkbelowthemaximal discomfortthresholdin twoout ofthreepatients[21]. Inaddi- tion,inthestudyofFrigerioetal.[20],acompleteeyeclosurewas achievedwithtranscutaneousfacialnervestimulationin55%of participantswithacuteunilateralfacialparalysis.

Theinability toblink is themost eminentfunctional deficit causedbyfacialparalysis.Thisisduetothedysfunctionaleyepro- tectionandlackofmoistureovertheeye,whichcanleadtosevere cornealdamage[22,23].However,otherfacialfunctionsalsohave asignificantroleindailybehaviorsandinemotionalandsociallife especially.Themostfrequentconsequencesofincompleterecovery afterfacialparalysisareweaknessesinfrontalwrinkling,opening themouth,smiling,orlippuckering[24].Theonlyhumanstudy regardingthestimulationofareasotherthantheorbicularisoculi muscleisthestudyofKuritaetal.[25].Theyusedlocalanesthetics toinduceatransientparalysisofthefrontalismuscleforhealthy volunteers.Needle-type electrodeswere inserted intoboth the non-paralyzedsidetodetectmuscleactivityandintotheparalyzed sidetostimulatethemuscle.Theresultsshowedfunctionalandaes- theticallyacceptablefacialmovementcreatedbytheactivationof theparalyzedfrontalismuscleusingEMGmeasurementsfromthe un-anesthetizedsidetocreatecorrespondingmuscleactivitywith FES.Tosummarize,studiesinvestigatingmorewidelythetranscu- taneousstimulationoffacialmusclesseemtobeinfrequent.Thus, thereisaclearneedandmotivationtostudyboththestimulation ofotherfacialmuscles,aswellasrelatedsubjectivesensationsand feelingscausedbyelectricalstimulation.

To furtherinvestigate the potential of transcutaneous facial pacing,wehaveestablishedamultidisciplinaryprojectthatfirst developstechnology[13],thentestsitwithintactparticipants,and finallyrunstestswithpatientswithfacialparalysis.Theaimof thepresentstudywastostudytheelectricalstimulationoffacial muscles withhealthy humanparticipants in order togain fur- therknowledgeofthepotentialoffacialpacing.Atthispoint,we wereespeciallyinterestedinthepossibilityofevokingintended muscleactivations, what kindofstimulation amplitudes would berequired toevokethem,andwhatkindofsubjectiveexperi- encesthestimulationswouldevoke.Morespecifically,weaimedto studythreecurrentlevels:(a)aminimumcurrentparticipantscan sense,(b)aminimumcurrentrequiredtoevokeavisuallyobserv- ablemovement,and(c)amaximumcurrentstilltolerableforthe stimulation.Stimulationwaveformparametersotherthanthecur- rentamplitudewerekeptconstant.Further,wecollectedratings

ofexperiencedpleasantness,naturalness,andpainfulnessofthe stimulations.Fourfacialmusclelocationswerechosenforthestim- ulation:theorbicularisoculitoproduceaneyeblink,thefrontalis toproduceaneyebrowraise,thezygomaticusmajortoproducea smile,andtheorbicularisoristoproducealippucker.

2. Methods 2.1. Participants

Twenty-four healthy voluntary participants (15 males, 9 females) withan age range of 21–63 (M=37.1, SD=12.0) took partinthestudy.Thestudywasacceptedbytheethicalcommit- teeofPirkanmaaHospitalDisctrict(R15067),andeachparticipant signedaninformedconsentformpriortotheirparticipation.Ten participantshadpreviousexperiencewithelectricalstimulation ofmuscles(e.g.,transcutaneouselectricalnervestimulation),one wasuncertain,andtheresthadnosuchexperience.Thepartici- pants’averagebodymassindex(BMI)was25.2(SD=3.1).BMIwas computedbecauseadiposetissuehashigherelectricalresistivity comparedtomostothertissues.Electricalcurrentflowsthrough thepathofleastresistance,andasubcutaneousadiposetissuemay workasaninsulatorlayerdirectingthecurrentflowawayfromit andtheunderlyingmuscle.

2.2. Equipmentandstimulatedmuscles

Thefacialpacingdeviceisdevelopedandmanufacturedbyour academic consortium.In the current study,theFES functional- ity ofthe pacingapparatuswasused. Aseparate PCisused to adjustthestimulationparametersandtostorethemeasurement data.ThedeviceandthePCcommunicatewirelesslythroughWi-Fi connection.Generationofthestimulationsignalsallowsvarying stimulus waveform parameters, such as stimulus phase (posi- tiveandnegative)durationandpulserepetitionfrequency(fora detaileddescriptionofthedevice,see[13].Theselectedcurrent waveform usedin this study wasa biphasicsquare wave with symmetricpositiveandnegativephases(equalwidth,equalampli- tude). Thefollowing parameters of thestimulation were used:

positiveandnegativephaseduration0.4msandpulserepetition frequency250Hz.Pulsetraindurationwas80msfortheorbicularis oculiand1000msforthefrontalis(intheforehead),thezygomaticus major(inthecheek),andtheorbicularisoris(aroundthemouth),as seeninFig.1.Thestimulationparameterswerebasedonliterature [18,20,26,27]andexplorativepilottesting.Commercialstimulation electrodesmadefromcarbonizedrubberwereattachedtotheskin abovethestimulatedmusclesaccordingtotheguidelinesforEMG recording[28].Videosoffacialbehaviorwererecordedforoffline visualanalysisat50framespersecondwithaPanasonicV750dig- italvideocamerathatwasplacedinfrontoftheparticipant.

2.3. Procedure

Whenaparticipantarrived,theexperimenterintroducedthe electricallyshielded,soundattenuatedlaboratoryandaskedthe participanttofilloutaninformedconsentformandabackground questionnaire.Then,theparticipantwasseatedinfrontofthevideo camera.Beforetheactualexperiment,apracticetrialwasrunto getparticipantsusedtothestimulationandtheprocedure.Forthis purpose,stimulationelectrodeswereattachedtothelefthandover themusclesofthethenareminence.Duringthepracticephase,this areaofthehandwasstimulatedandtheexperimentalprocedure wasconducted.

After the practice phase, the stimulation electrodes were attachedtotheleftsideoftheparticipants’faceforstimulating

Fig.1. Placementoftheelectrodes:orbicularisoculi(upperleft),frontalis(upperright),zygomaticusmajor(lowerleft),andorbicularisoris(lowerright).Photographspublished withpermissionfromthesubject.

onemuscleatatime.Theorderofthestimulationsiteswascoun- terbalancedasfollows:

-Frontalis,orbicularisoculi,zygomaticusmajor,andorbicularisoris (n=8),

-Zygomaticusmajor,orbicularisoris,frontalis,andorbicularisoculi (n=8),

-Orbicularisoris,frontalis,orbicularisoculi,andzygomaticusmajor (n=8).

Thestimulationwasrepeatedfivetimesateachamplitudelevel startingfromlevel 0.5mA.Followingthis, theamplitudeofthe stimulationwasincreasedin0.5mAintervalsuntiloneofthefol- lowingoccurred:

1Thestimulationcausedacutaneoussensationreportedbythe participant(i.e.,perceptionthreshold).

2Thefacialmusclemovementwasobservedbytwoexperimenters (i.e.,movementthreshold).Inthecase oftheorbicularis oculi, theamplitudewasincreaseduntilaneyelidmovement(i.e.,eye twitch)wasevoked.

3Theparticipantwantedtostopthestimulation(i.e.,tolerability threshold)orthemaximumstimulationamplitude(10mA)was achieved.Inthecaseoftheorbicularisoculi,theamplitudewas increaseduntilaneyeclosure(i.e.,blink)wasevokedoruntilthe participantreportedthetolerabilitythresholdbeingreached.

Aftereachamplitudelevel,theexperimenteraskedthepartic- ipant’sconfirmationtocontinue byasking“Willyoucontinue?”

Theparticipantevaluatedthepleasantnessandpainfulnessofthe stimulationaftereach ofthethreestimulationphases(i.e.,per-

ceptionthreshold, movementthreshold, tolerability/eyeclosure threshold).Atthemovementandtolerability/eyeclosurethresh- old,theparticipantalsoratedthefeltnaturalnessofthemovement (i.e.,hownaturalthemovementfelt).Followingthepointwhere themovementthresholdwasachieved,theparticipantgaverat- ingsofpainfulnessofthestimulationateachstimulationamplitude level. The pleasantness and naturalnessscales werenine-point bipolarratingscalesvaryingfrom1(unpleasant/unnatural)to9 (pleasant/natural),with5representingthecenter(neitherunpleas- ant/unnaturalnorpleasant/natural)ofthescale.Thepainrating scalewasaonedimensionalnine-pointscalerangingfromnotatall painfultoverypainful.Attheendoftheexperiment,theparticipant wasaskedtochoosethemostpleasantornaturalstimulusloca- tion(s).Theywerealsoencouragedtogiveadditionalcomments.

2.4. Dataanalysis

In respect to eye blink stimulation, data from two par- ticipants was discarded. One participant wanted to stop the stimulationbecauseoffeelingdiscomfortalready beforeaneye twitch waselicited. The data of one participant was discarded becauseof excessiveblinking irrespective of stimulation. Thus, thedataanalysisinrespecttoeyeblinkstimulationisbasedon n=22. Amplitude threshold data was analyzed using one-way repeated measures analysis of variance (ANOVA). Greenhouse- Geisseradjusteddegrees offreedomwereusedwhenviolations ofsphericityoccurred.Bonferronicorrectedpairwiset-testswere usedforpost-hoccomparisons.Thesubjectiveratingdatawasana- lyzedusingFriedmantests.Ifastatisticallysignificanteffectwas found,Wilcoxonsigned-ranktestwasusedforpairwisecompar- isons.Thedifferencesbetweentheparticipantswhohadordidnot

Fig.2.Theaverageamplitudelevels(andSEMs)foreachthreshold.

Fig.3.Theaveragepainratings(andSEMs)foreachthreshold.

havepreviousexperiencewithelectricalstimulationweretested withindependentsamplest-tests.TheassociationsbetweenBMI and current thresholdsand betweenBMI and theratingswere testedusingthePearsonproductmomentcorrelationcoefficient.

Theeyetwitchandeyeclosureweredeterminedofflinefrom framebyframeanalysisofthevideorecordings.Toexcludenatu- rallyoccurringeyeblinksevokedbythesensationintheskin,the amountofeyeclosureweredeterminedfromsituationswhenonly thestimulated-sideeyelidmoved.Videosfocusingontheforehead, cheek,andmouthstimulationswerealsovisuallyanalyzedinorder tocodewhichpartsofthefacemovedateachstimulationlevel.

3. Results

3.1. Forehead,cheek,andmouth

Average amplitude levels and Standard Error of the Means (SEMs)fortheperception,movement,andtolerabilitythresholds areshowninFig.2.Aone-wayANOVAwithstimulationlocationasa withinsubjectfactorwasconductedseparatelyforeachthreshold.

Theeffectofthestimuluslocationwasstatisticallysignificantonly forthemovement threshold,F(1,33)=34.96,p<.001, ␩2=0.47.

Post-hocpairwisecomparisonsshowedthattheamplitudelevelto elicitamovementwassignificantlylowerfortheforeheadthanfor thecheek(MD=1.76,p<.001,d=1.81)andthemouth(MD=0.78, p<.001,d=0.95).Theamplitudeleveltoelicitamovementwasalso significantlylowerforthemouththanforthecheek(MD=0.98, p<.01,d=0.78).

TheaveragedpainratingsarepresentedinFig.3.AFriedman testwithstimulationlocationasawithinsubjectfactorwascon- ductedseparatelyfortheperception,movement,andtolerability thresholds.Theeffectofthestimuluslocationwasstatisticallysig- nificantforthepainratingatthemovementthreshold,␹=16.10, p<.001.Post-hocpairwisecomparisonsshowedthatthestimula- tionoftheforeheadwasratedaslesspainfulthanthestimulation ofthecheek (Z=3.38,p<.001)and mouth(Z=2.07,p<.05).The

Fig.4.Theaveragepainratingsasafunction ofstimulusamplitudefromthe momentavisiblemovementwasevoked.

Fig.5. Theaveragepleasantnessratings(andSEMs)foreachthreshold.

effectofthestimuluslocationwasalsostatisticallysignificantfor thetolerabilitythreshold,␹=9.94,p<.01.Post-hocpairwisecom- parisonsshowedthatthestimulationofthemouth(Z=2.93,p<.01) andforehead(Z=2.01,p<.05)wereratedasmorepainfulthanthe stimulationofthecheek.

Painratingsincreasedalongtheincreaseofstimulusamplitudes (seeFig.4).Wenotethatattheendoftheexperimentmanyof theparticipantsexplainedthatalthoughtheywereaskedtogive painratingsafterstimulations,thestimulationswerenotactually painful.Thefeelingtheyexperiencedandevaluatedwasdescribed moreasadiscomfortthanaspain.

Themean ratingsfor pleasantness arepresentedin Fig.5.A Friedmantestwithstimulationlocationasawithinsubjectfactor wasstatisticallysignificantforthemovementthreshold,␹=17.61, p<.001. Post-hoc pairwise comparisons showed that the stim- ulation of the forehead was rated as more pleasant than the stimulationofthecheek(Z=3.50,p<.001)andthemouth(Z=2.75, p<.01).Further,thestimulationofthemouthwasratedasmore pleasantthanthestimulationofthecheek(Z=2.91,p<.01).

Themeanratingsforthenaturalnessofmovementarepresented inFig.6.AFriedmantestwithstimulationlocationasawithinsub- jectfactorwasstatisticallysignificantforthemovementthreshold,

␹=6.43,p<.05.Post-hocpairwisecomparisonsshowedthatthe stimulatedmovementoftheforeheadwasratedasmorenatural thanthestimulatedmovementofthecheek(Z=2.67,p<.01).The otherpairwisecomparisonswerenotstatisticallysignificant.

3.2. Eyeblink

Averageamplitudelevelsfortheperception,eyetwitch,and eyeclosurethresholdsareshowninFig.7.Thestimulationofthe orbicularisoculimusclecausedaneyetwitchwithintheamplitude rangeof1.5–2.5mA(M=2.2mA)andacompleteeyeclosurewithin theamplituderangeof2.5–5.0mA(M=3.6mA).

Fig.6. Theaverageratingsofnaturalness(andSEMs)foreachthreshold.

Fig.7. Theaverageamplitudelevels(andSEMs)forblinkstimulationateachthresh- old.

Fig.8.Theaveragepainratings(andSEMs)forblinkstimulationateachthreshold.

Theofflinevideoanalysisrevealedthataneyetwitchin14par- ticipantsandaneyeclosurein9participantswasachievedearlier thanwasobservedinrealtimeduringtheexperiment.Thus,therat- ingsofpleasantnessandnaturalnessinthesecaseswerediscarded.

Thepainratingdataismorecompletebecausetheywerecollected aftereachstimulation amplitudelevelafterthemovementwas noticedinrealtime.Averagepainratingsfortheperception,eye twitch,andeyeclosurethresholdsareshowninFig.8.Thereported averagepainratingforthecurrentthresholdtoelicitaneyetwitch was1.8(SD=1.5,n=16)and3.0(SD=1.7,n=20)forthecurrent thresholdtoelicitablink.

3.3. Concurrentmuscleactivations

Thevideoanalysisrevealedthatthestimulationofthefrontalis causedaneyebrowraise,thestimulationoftheorbicularis oculi caused aneye blink, and the stimulationof the orbicularis oris causedalippucker,aswasintended.Thiswasaccomplishedby stimulatingthelocationsconventionally usedinEMG measure-

Table1

Theresultsofthevideoanalysisatthemovementthresholdlevelregardingactiva- tionswhilestimulatingthecheek.

Thenumberof participants(%)

Movementlocationatthe movementthreshold

5(22%) Cheekarea

7(30%) Moutharea

4(17%) Mouthareaandnose

7(30%) Mouthareaandsideofthe

nose

Table2

Thenumber(andpercentages)ofparticipantswhoratedspecificstimuluslocations asthemostpleasantornatural.

Themostpleasant Themostnatural

Forehead 9(37.5%) 5(20.8%)

Eyeblink 4(16.7%) 8(33.3%)

Cheek 3(12.5%) 3(12.5%)

Mouth 7(29.2%) 4(16.7%)

mentsofthegivenmuscles[28].Further,thevisualanalysisshowed thatthestrongerthestimulation,thelargerthemovement.Quan- tifyingtheextentofthemovementswasbeyondthescopeofthis study.

Thestimulationofthezygomaticusmajorwasmorechalleng- ing.Videoanalysisatthemovementthresholdlevelrevealedthat stimulationofthecheekactivatedthecheekareain22%ofthepar- ticipants.Withtherestoftheparticipants,stimulationofthecheek activatedfirsteitherthemusclesinthemoutharea,boththemouth andnosearea,orboththemouthandlaterallythenosearea(see Table1).Furtheranalysisshowedthatwhenthestimulationampli- tudewasincreased,theactivationinthecheekareawasbetter (butnotpurely)achievedin22outof24participants(M=5.1mA, SD=1.5mA).Inaddition,with19participants,stimulationofthe cheekalsoevokedmovementintheeyelidbeforeorafterreaching themovementthreshold.

3.4. Theeffectsofbackgroundvariables

Pairwisecomparisonsbetweentheparticipantswithandwith- outpreviousexperienceonelectricalstimulationdidnotshowany statisticallysignificantdifferencesintheratingsofpain,pleasant- ness,ornaturalnessofthemovement.

Therewasastatisticallysignificantalthoughsmallcorrelation between BMI and the amplitude level for forehead movement (r(22)=0.41,p<.05)andbetweenBMIandtheamplitudelevelfor cheekmovement(r(21)=0.46,p<.05).Therewerenostatistically significantassociationsbetweenBMIandtheratingsofpain,pleas- antness,ornaturalnessofthemovement.

3.5. Preferenceevaluations

Table2presentshowmanyparticipantsrateddifferentstimulus locationsasthemostpleasantorthemostnatural.Theresponses werespreadevenlyamongthelocations,buttheforeheadreceived themost“themostpleasant”mentions,andtheeyeblinkreceived themost“themostnatural”mentions.

4. Discussion

Previousanimalstudiesandthefirststudieswithhumanpar- ticipantshaveshownthatfacialpacingcanbeusedingenerating facialmuscleactivationsinunilateralfacialparalysis.Inadditionto reliableandfastdetectionofmuscleactivations,successfulstimu- lationoffacialmusclesisneededfordynamic,symmetrical,and cosmeticallyacceptablereanimation. Of course,thestimulation

alsoneedstobetolerable.Thus,knowledgeaboutthesensations andfeelingsevokedbyelectricalstimulationisneededconsider- ingtheeverydayuseoffacialpacingdevices.Theexistinghuman studieshaveconcentratedmainlyontheproductionofeyeblinks, andresearchabouttheelectricalstimulationofotherfacialmus- clesislargelymissing.Inthepresentstudy,westimulatednotonly theeyeareatoinduceeyeblinks,butalsotheforehead,cheek,and mouthtoproduceeyebrowraises,smiles,andlippuckers.Thus,the presentresearchwasthemostcomprehensivestudyinvestigating transcutaneouselectricalstimulationoffacialmusclestodate.

Ourfindingsareverypromising,astheyshowedthata visu- allyobservablemovementoftheforeheadandthelowerlipwas achievedinallparticipants.Further,thecheekstimulationresulted inobservableactivationin23outof24participants.Completeeye blinkwasachievedinallparticipants(n=22)exceptthetwowho werediscardedforobviousreasons.

Inrespecttoforehead,cheek,andmouth,thestimulationswere sensedalreadyataround1mA.Thesefacialmovementswerevisu- allyobservablefollowing 2–4mAstimulations. It is noteworthy thatstimulationsweretolerateduntilupto7–8mA.Painratings showedthatatbothperceptionandobservablemovementlevels thestimulationswerenotverypainful,butcheekstimulationswere experiencedasmorepainfulthantheotherstimulations.Atthetol- erabilitylevel,thepainratingswerequitehighalreadybutstillnot atthemaximumendofthescale,however.Pleasantnessratings interestinglyshowedthatatperceptionandmovementthresholds thestimulationswerefeltintheforeheadandmouthareaaspleas- ant.Thecheekstimulationat themovement levelwasratedas unpleasant.Theratingsofnaturalnessforthesefacialareasshowed thatstimulationswereratedasmildlyunnatural,butforthecheek areatheywerethemostunnatural.Ratingsofpain,pleasantness, andnaturalnessinrespecttocheekareaprobablyreflectthefact thattheamplitudelevelrequiredtoelicitthemovementwassig- nificantlylowerfortheforeheadandthemouththanforthecheek.

However,thestimulationofthecheekwasratedaslesspainful atthetolerability thresholdthanthestimulation ofthemouth, eventhoughtheamplitudelevelsdidnotdifferbetweenstimulus locations.Wenotethatattheendofthestudymanyparticipants spontaneouslyindicatedthateventhoughtheywereaskedtogive painratings,thestimulationswerenotactuallypainfulbutmerely uncomfortable.Thus,theresultssuggestthatthestimulationscaus- ingmorevisiblemovementelicitunpleasantsensationsbutmaybe notthatmuchpain.Thisnotionisvaluableforthefuturedevelop- mentoffacialpacingmethods.

Acompleteeyeclosurewasachievedwiththeaverageampli- tude level of 3.6mA, while in a previous study that included individuals with acute facial paralysis [20], the mean current requiredfor eyeblinkgenerationwas7.2mA.Thedifferencein resultscanbeexplainedbytheapproximatelytwiceashighpulse repetitionfrequency(250Hz)inthecurrentstudycomparedtothe one(100–150Hz)inFrigerioetal.[20].Thetotalchargedeliveredto themusclewithinatimeunitstaysthesamewhenthepulserepe- titionfrequencyisdoubled,andtheamplitudecanbehalvedgiven thatthedurationofasinglepulseisthesameinbothcases.Thus, thepresentedresultsandtheonesbyFrigerioetal.[20]suggest thatthetotalchargewithinatimeunitrequiredforthestimulation staysthesamedespitetheacutefacialparalysisoftheindividuals intheirstudy.

TherewasalsoasmallpositivecorrelationbetweenBMIandthe amplitudelevelsforcheekandforeheadmovements.However,BMI hadnoeffectonthemaximumtolerabilityofstimulationamplitude levelsortheratingsofthestimulation.Thisisprobablybecause peoplewithhigherBMIgenerallyhavemorefattissueinthefacial area,thusresultinginalargercurrentrequiredtoactivatethemus- cle;theoperationofthesensorynervoussystemisnotaffectedby theamountoffattissue.

Ourfindingsfurthershowedthatthestimulationofthecheek areawasthemostchallenging.Withsomeparticipants,thestim- ulationofthecheekevokedactivationmoreinthemouthornose areathaninthecheek.Thisreferstotheactivationoftheorbicularis orisandlevatorlabiisuperiorismuscles.Inaddition,thestimulation ofthecheekareaalsoresultedinconcurrenteyelidtwitchesin manyparticipants.Theseconcurrentactivationswereprobablydue totheactivationspreadingthroughfacialnervebranchesorfattis- sue.Thelowereyelidoforbicularisoculiaswellaszygomaticusmajor muscle,forexample,receivesinnervationmainlyfromthezygo- maticbranchofthefacialnerve.Thissharedinnervationislikely toexplainpartoftheconcurrentactivations.Anotherlikelyrea- sonisthattheorbicularisoculiandzygomaticusmajormusclesare closelyconnectedbytheplexusofthenervescalledzygo-orbicular plexuswhichcrossesovertheorbicularisoculi,zygomaticusmajor andzygomaticusminormuscles[29].Thecheekareaalsocontains more fattissue than theforehead,eye,and mouth areas.Thus, onefuturechallengeistoinvestigatehowtranscutaneousstim- ulationcanbetargetedmorespecificallytothezygomaticusmajor muscle.

Thesomatosensorynervesandtheirfunctionalityintheindi- vidualswithfacialparalysisispreserved.Thus,thesensationsand feelings evokedbyelectricalstimulationarelikely quitesimilar amongthehealthyparticipantsandindividualswithfacialparal- ysis.Infuturestudieswithpeoplehavingfacialparalysis,wewill investigatedoestheactivationspreadhappenwhilestimulating theirfacialmuscles.

One concernis related totheelectrical stimulation of para- lyzedfacialmusclesandsynkinesis;doestheelectricalstimulation contribute thefacial synkinesis. Theterm synkinesis meansan abnormalsynchronizationoftheinvoluntarymovementofasingle muscleoragroupofmusclesduringthecontractionofintended muscle[30].Thecauseoftheconditionremainsunclear,butitmay relate,forexample,tothemisdirectionofregeneratingaxons,or thechanges in thesynaptic connectionsbetweenmotoneurons inducedby injury totheiraxons[31–33]. Somestudiesonrats havesuggestedthatdailyelectricalstimulationofthefacialnerve canfacilitatethedevelopmentoffacialsynkinesis[e.g.,34].How- ever,humanstudieshaveshownthattheelectricalstimulationof facialmusclesorfacialnervetrunkbranchesissafeduringearly phaseofthefacialpalsyandtherehavenotbeensignificantdif- ferencesinsynkinesisbetweenelectricalstimulationandcontrol groups[35,36,8].

Themainlimitationof thisstudywasthatit wasconducted in healthy volunteers. However, tothe best of ourknowledge, therearenostudiesthathaveinvestigatedcomprehensivelytran- scutaneous electrical stimulation of the human facial muscles orcollectedsubjectiveratingsaboutthestimulations.Thus, the current study provided knowledge about the esthetics of the stimulated movements and the tolerability of the stimulations with differentamplitude levels and different parts of theface.

Our future studieswill include findingoutthe requiredstimu- lationamplitudes toevokemovementinthemusclesof people withfacialparalysisandexploringmorepreciselysensationsand feelings evoked by the stimulation. It is possible that higher amplitudes are needed toactivate paralyzed muscles,thus, we are developing stimulation techniques to alleviate the experi- ences of pain or discomfort,as wellas the unpleasantness the stimulation causes. Further,we are developing the actualpac- ingsoftwarefortheprototypedevicetoprocessEMGsignalsin realtime,automaticallydeterminestimulationwaveformparam- eters, and triggerthe stimulation.One important research line isrelated totheelectrode development.Inordertomake tran- scutaneouselectrodesmoreunnoticeableandusableineveryday

use,theinvestigationofthin,transparent,andelasticmaterialsis needed.

5. Conclusion

In conclusion, the present study investigated how electrical stimulationcanevokeaneyebrowraise,asmile,alippucker,and aneyeblink, aswellaswhat thesubjective experiencesare in respecttothestimulations.Theresultsshowedvisuallyobservable movementoftheforeheadand thelowerlipin allparticipants.

Stimulationsevoking smallmovementswereratedasrelatively pleasantandtolerable.Thestrongerthestimulationwasthelarger themovementandthehigherthepainratingswere.Electricalstim- ulationevoked complete eyeblinksin 22 participants,and the sensationwasratedmainlyastolerable.Stimulationofasmilewas morechallenging,mostlikelyduetotheactivationspreadingto otherpartsoftheface.Infollow-upstudies,wewillinvestigate themeanstoalleviatetheuncomfortableexperiencescausedby thestimulation,studyhow wecouldstimulate thezygomaticus majormoreaccurately,andtestthestimulationwithpatientswith unilateral facial paralysis.Regarding a longerterm perspective, noninvasive,transcutaneoussolutionscouldbeanewtreatment option,especiallyforpatientsrecoveringfromacutefacialpalsy andforpatientswhosefacialnervehasnotfullydegeneratedpro- motingtheweakandincompletemovementsoftheparalyzedside.

Declarationsofinterest None.

Acknowledgements

ThisresearchwasfundedbytheAcademyofFinland:funding decisionnumbers278529,276567,and278312.

AppendixA. Supplementarydata

Supplementarymaterialrelatedtothisarticlecanbefound,in theonlineversion, atdoi:https://doi.org/10.1016/j.bspc.2018.10.

015.

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