Development and Significance of the Spatial …...spatial auditory change complex (ACC), an...
Transcript of Development and Significance of the Spatial …...spatial auditory change complex (ACC), an...
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DevelopmentandSignificanceofthe
SpatialAuditoryChangeComplexin
AdultCochlearImplantUsers
RajeevMathew
Adissertationsubmittedinfulfilmentoftherequirementsforthe
degreeofDoctorofPhilosophy,UCL,2018
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Declaration
I,RajeevMathew,confirmthattheworkpresentedinthisthesisismyown.Where
informationhasbeenderivedfromothersources,Iconfirmthatthishasbeen
indicatedinthethesis.
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Acknowledgements
Althoughthisthesisstartswithadeclarationthatitismyownwork,Ihavebeenfar
fromaloneduringthelastthreeyears.Forthat,Ishallbeeternallygrateful.Ihadtwo
wonderfulacademicsupervisorsinDebbieVickersandJaimeUndurraga.Debbiehas
guided,supportedandencouragedmeovertheyears.Shehasalwaysbeenasourceof
positiveenergyandIadmireherasagreatproblemsolver.Despitehernumerous
commitments,shehasbeenincrediblygenerouswithhertime.Jaime’skindnessand
intelligencehavebeentrulyinspiring,andhehasbecomeagreatfriend.Despitebeing
ontheothersideoftheworld,hehasbeenaneverpresenthelp,particularlyfor
PythonandRrelatedqueries.Jaimewasresponsibleforintroducingmetotheworld
ofopensourceandImustconfessthatIamafullconvert!
ImustalsothankPatrickBoyle,GuopingLiandAzharShaidawhoprovidedguidance
duringtheearlystagesoftheproject.ThankyoutoLeahMeertonwhohelpedmeto
recruitparticipantsandwasalwaysonhandtoprovideaudiologicaladvice.Thanksalso
toDavidSelvaduraiandLilaPillingwhosupportedmetocontinuemyclinicalwork
duringmyPhDstudies.Ishallforeverbegratefultomysurgicalmentor,ParagPatel,
whohelpedmetokeepdevelopingasasurgeonoverthelastthreeyears.Hiswordsof
encouragementkeptmegoingwhenIneededthemthemost.
Thankstoalltheparticipantsinmyresearch.Ienjoyedourmanydiscussionsoverthe
courseofnumerouslongEEGtestingsessions.Ilearnedsomuchfromthemabout
whatitmeanstohavehearinglossandlifewithacochlearimplant.Thishasenthused
metokeepworkinginthefieldofhearingresearch.Ithasbeentouchingtoseepeople
giveupupsomuchoftheirtimewiththeonlymotiveofgivingbacktoothers.I
considerthisarealtestamenttothegoodnessofhumankind.
ThankstomyDadandMum,andbothofmysisters.Iamsogratefultothemfortheir
love,encouragementandprayersovertheyears.ThanksespeciallytomyAmmamma
who,asever,hasbeenatowerofsupport.Thankyoualsotomyfather-in-law,who
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havingdonehisPhDin50s,gavememuchinspiration,andmymother-in-lawwho
lookedafterustirelesslyeverysummer.
Imustthankthetwoladiesinmylife.ThankyoutomywonderfulwifeAshin,without
whosesupportnoneofthiswouldhavebeenpossible.Shehaslookedafterme
sacrificially,andherunderstandingandcarehaveknownnoend.Thanksalsotoour
daughterJessica.Thereisnothinglikethepurejoyofachildandthishadmadeit
excitingtogobackhomeeveryday.Ihaveenjoyedourmany‘littlechats’andboutsof
hystericallaughter.Iwillrememberthesethreeyearsasatimewhen,weasafamily,
grewstrongerandenjoyedmanywonderfulmomentstogether.Finally,Imustthank
GodforgivingmeallthatIhaveandmakingmewhoIam.
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Abstract
Despitetheirgreatsuccess,cochlearimplants(CIs)areassociatedwithawiderangein
speechperceptionoutcomes.InteractionsofelectrodecontactsontheCIarray,
resultinginimpairedtransmissionoftheauditorysignal,maycontributetopoor
outcomeincertainindividuals.Theaimofthisthesiswastodeterminewhetherthe
spatialauditorychangecomplex(ACC),anelectrophysiologicalmeasureofelectrode
discrimination,couldbeusedtoobjectivelyassesselectrodeindependence,witha
viewtousingthisasaclinicaltoolforpatientassessment.
Inaseriesofexperiments,thespatialACCandbehaviouralelectrodediscrimination
weremeasuredinadultCIusers.Itwasfoundthatitisfeasibletomeasurethespatial
ACCinCIdevicesfromdifferentmanufacturersandduringtheearlyperiodafter
switch-on.Therewasastrongrelationshipbetweenobjectiveandbehavioural
measuresofelectrodediscriminationandinseveralcases,thedevelopmentofthe
spatialACCprecededaccuratebehaviouraldiscrimination.Longitudinalmeasurements
revealedthattheamplitudeofthespatialACCandbehaviouraldiscriminationscores
increasedsignificantlyoverthefirst6to12monthsofCIuse,providingevidencefor
auditoryplasticity.Thetimecourseofadaptationvariedsubstantially,andwasslower
andmorelimitedincertainindividuals.Speechperceptionwasfoundtobemore
consistentlyrelatedtobehaviouralmeasuresofelectrodediscriminationthantothe
spatialACC.IncreasingstimulusintensityledtoasignificantincreaseinthespatialACC
amplitudeandbehaviouraldiscriminationscores.Byalteringtherecordingsetupand
stimuluscharacteristics,theefficiencyandsensitivityofspatialACCmeasurements
couldbeimproved.
ThesefindingsshowthatthespatialACCprovidesausefulmeasureofelectrode
independence.Itisproposedthatthesemeasurementscouldbeusedtoguideclinical
interventionsthatleadtoimprovedhearingoutcomeinCIusers.
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ImpactStatement
Inthisthesis,themethodologyforrecordingandassessingcorticalresponsesin
cochlearimplant(CI)userswasdeveloped.Furthermore,thefindingsshowthat
corticalresponsemeasurementsprovidemeaningfulinformationthatcouldbeused
fordecisionmakinginaclinicalsetting.Itisthereforeexpectedthatthisresearchwill
havesignificantimpactonresearchinthefieldofCIelectrophysiology,onindustrythat
isdevelopingCItechnologyandonclinicalpractice.
OneofthetraditionalchallengeswithmeasuringcorticalresponsesinCIusersisthe
presenceofelectricalartefactfromthedevice.Atechniqueforeffectivelyremoving
artefactwasdeveloped(Chapter2).Inaddition,atechniqueforobjectivelyassessing
corticalresponsesbasedonstatisticalcriteriawasdevelopedtodeterminewhethera
significantbrainresponsewaspresentornot(Chapter2).Useofsuchatechnique
makesinterpretationofbrainresponsessimpler,quickerandlesspronetobias.The
techniqueforrecordingcorticalresponsesinCIuserswasdevelopedtoimprovethe
efficiencyofrecordings(Chapter6).Theabovedevelopmentsinmethodologywill
makeiteasiertomeasurecorticalresponsesinCIusersintheresearchandclinical
settings.
Itwasfoundthatcorticalresponsemeasurementsprovidemeaningfulinformation
abouthowsignalsfromanimplantareencodedinthebrain.Insomecases,they
provideinformationoverandabovethatgainedbybehaviouraltesting.This
informationcouldbeusedtoguidetherehabilitationstrategy,includingimplant
programmingandauditorytraining.Futureresearchmustfocusonwhethertheuseof
corticalresponsemeasurementsleadtoactualgainsinhearingoutcomes.Itishoped
thatthefindingsofthisresearchwillencourageindustrytodevelopCIhardwareand
software,inordertofacilitatecorticalresponsemeasurements.Apotentialfuture
developmentofparticularinterestisremotemeasurementofcorticalresponses.This
wouldallowclinicianstogainawealthofinformationaboutauditoryprocessingwitha
CIandwouldalsosaveawealthoftimeforpatientsandcliniciansalike.
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Theimpactofthisthesiswillbedeliveredthroughpublicationinpeerreviewed
journals,presentationatinternationalconferencesandthroughfutureprojects.There
arealready2peerreviewedjournalpublicationsand13conferencepresentations
fromthisthesis.Furtherprojectsinvolvingcollaborationfromindustryandclinicians
arealreadyunderway.
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TableofContentsChapter1Introduction............................................................................................19
1.1HowaCIworks..........................................................................................................191.1.1ComponentsoftheCIsystem...................................................................................19
1.1.2Electricalstimulationoftheauditorynerve.............................................................21
1.1.3Soundprocessingstrategies.....................................................................................24
1.1.4FittingaCI.................................................................................................................25
1.2OutcomeswithCI–successandvariability................................................................261.3ChannelinteractionsasafactorlimitingCIoutcome..................................................281.4Reasonsforchannelinteractions...............................................................................301.5AssessmentofchannelinteractionsinCIusers..........................................................31
1.5.1Behaviouralmeasuresofchannelinteractions........................................................31
1.5.2Objectivesmeasuresofchannelinteractions...........................................................37
1.6CorticalresponsemeasurementsinCIusers..............................................................391.6.1TheP1-N1-P2complex.............................................................................................39
1.6.2RecordingCAEPs.......................................................................................................40
1.6.3TheproblemsofCIartefact......................................................................................41
1.6.4Corticalmeasuresofdiscrimination.........................................................................42
1.7ThespatialACC..........................................................................................................451.8Summaryandrationaleforthisstudy........................................................................471.9Aims..........................................................................................................................51
Chapter2GeneralMethods....................................................................................52
2.1StimuliforACCmeasurement....................................................................................522.2Stimulusintensityandloudnessbalancing.................................................................532.3EEGRecording...........................................................................................................542.4EEGProcessing..........................................................................................................552.5Behaviouralelectrodediscrimination........................................................................572.6Speechperceptiontesting.........................................................................................582.7Statisticalanalysis.....................................................................................................59
Chapter3ValidationofthespatialACCinadultCIusers..........................................60
Thischapterisbasedonthefollowingpublishedjournalarticle:.....................................603.1Abstract.....................................................................................................................603.2Introduction..............................................................................................................603.3Experiment1:Pilotphase–assessmentandremovalofCIartefact...........................62
3.3.1DesignandMethods.................................................................................................62
3.3.2Results......................................................................................................................66
3.4Experiment2:MeasurementofACCat1weekafterswitch-on..................................733.4.1DesignandMethods.................................................................................................73
3.4.2Results......................................................................................................................76
3.5Discussion.................................................................................................................863.5.1AssessmentandremovalofCIartefact....................................................................87
3.5.2CharacteristicsofthespatialACCat1weekafterswitch-on...................................87
3.5.3RelationshipbetweenthespatialACCandbehaviouraldiscrimination...................88
3.5.4Reasonsforpoorelectrodediscrimination..............................................................91
3.5.5Electrodediscriminationandspeechperception.....................................................91
3.6Conclusions...............................................................................................................92
Chapter4DevelopmentofthespatialACCandbehaviouralelectrodediscrimination
afterCIswitch-on....................................................................................................93
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4.1Abstract.....................................................................................................................934.2Introduction..............................................................................................................934.3Experiment3:DesignandMethods...........................................................................96
4.3.1Participants...............................................................................................................96
4.3.2Testprocedures........................................................................................................96
4.4Results.......................................................................................................................994.4.1Changesinbehaviouralelectrodediscrimination....................................................99
4.4.2Behaviouraldiscriminationcontrollingforstimulusintensity................................102
4.4.3DevelopmentofthespatialACC.............................................................................105
4.4.4RelationshipbetweenthespatialACCandbehaviouralelectrodediscrimination.109
4.4.5Relationshipbetweenelectrodediscriminationandspeechperception...............113
4.5Discussion...............................................................................................................1164.5.1Changesinelectrodediscriminationovertime......................................................117
4.5.2Reasonsforimprovedelectrodediscrimination.....................................................120
4.5.3RelationshipbetweenthespatialACCandbehaviouralelectrodediscrimination.122
4.5.4Electrodediscriminationandspeechperception...................................................125
4.6Conclusions.............................................................................................................126
Chapter5Theeffectofstimulusintensityonelectrodediscrimination..................127
5.1Abstract...................................................................................................................1275.2Introduction............................................................................................................1275.3Experiment4:DesignandMethods.........................................................................129
5.3.1Participants.............................................................................................................129
5.3.2Testprocedures......................................................................................................129
5.4Results.....................................................................................................................1335.4.1Effectofstimulusintensityonbehaviouraldiscrimination....................................133
5.4.2Effectofstimulusintensityoncorticalresponseamplitude..................................135
5.4.3RelationshipbetweenthespatialACCandbehaviouralelectrodediscrimination.138
5.4.4Relationshipbetweenelectrodediscrimination,thresholdlevelandDR..............142
5.4.5Relationshipbetweenelectrodediscriminationandspeechperception...............143
5.5Discussion...............................................................................................................1445.5.1Stimulusintensityandauditorycorticalresponses................................................145
5.5.2Stimulusintensityandbehaviouralelectrodediscrimination................................146
5.5.3RelationshipbetweenthespatialACCandbehaviouralelectrodediscrimination.148
5.5.4RelationshipbetweenelectrodediscriminationandCIprogrammeparameters..149
5.5.5Electrodediscrimination,levelandspeechperception..........................................149
5.6Conclusion...............................................................................................................150
Chapter6ImprovingtheclinicalapplicabilityofspatialACCmeasurements–apilot
study.....................................................................................................................151
6.1Abstract...................................................................................................................1516.2Introduction............................................................................................................1526.3Experiment5:DesignandMethods.........................................................................155
6.3.1Participants.............................................................................................................155
6.3.2StimuliforACCmeasurement................................................................................156
6.3.3EEGRecording........................................................................................................159
6.3.4EEGdataanalysis....................................................................................................160
6.4Results.....................................................................................................................1616.4.1Comparisonofsingleand64channelACCmeasurements....................................167
6.4.2ComparisonofefficiencyandsensitivityofsinglechannelACCmeasurementsusing
differentstimuli...............................................................................................................169
6.5Discussion...............................................................................................................1736.5.1RecordingthespatialACCwithalimitednumberofscalpchannels......................173
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6.5.2StimuluscharacteristicsandspatialACCmeasurements.......................................174
6.6Conclusion...............................................................................................................175
Chapter7GeneralDiscussion................................................................................176
7.1Summaryanddiscussionofmainfindings................................................................1767.2ClinicalimplicationsofthespatialACC.....................................................................1797.3Limitationsandfurtherstudies................................................................................1827.4Cochlearimplantation–currentlandscapeandfuturepriorities..............................1857.5Conclusion...............................................................................................................187
AppendixA:Test-retestreliabilityoftheACC........................................................188
Bibliography..........................................................................................................193
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ListofFigures
Figure2.1SchematicofthestimuliusedformeasuringthespatialACC.......................53
Figure2.2LayoutoftheBiosemi64channelEEGrecordingcap...................................54
Figure3.1.Schematicofthestimuliusedinexperiment1............................................65
Figure3.2Scalpvoltagemapsandtimewaveformforthefirstcomponentofspatial
filtering...................................................................................................................69
Figure3.3Corticalresponsesduringthesuprathresholdchangecondition..................70
Figure3.4Corticalresponsesforthreestimulusconditions..........................................71
Figure3.5.BoxplotofN1-P2amplitudeoftheonsetandACCresponseforthethree
stimulusconditions................................................................................................72
Figure3.6CorticalresponsesshowingagreementbetweentheACCandbehavioural
measurements.......................................................................................................78
Figure3.7Corticalresponsesfromelectrodepairsthatfailedonbehaviouraltesting
butpassedonobjectiveACCcriteria......................................................................80
Figure3.8RelationshipbetweenACCN1-P2amplitudeandbehaviouraldiscrimination
category..................................................................................................................82
Figure3.9Therelationshipbetweenmeanelectrodediscriminationd’scoreand
speechperception..................................................................................................85
Figure4.1Changeinmeanbehaviouralelectrodediscriminationscoreovertime.....101
Figure4.2Changeovertimeinthenumberofdiscriminableelectrodesasdefinedby
behaviouralpass-failrules....................................................................................102
Figure4.3ChangeinthemeanspatialACCamplitudeovertime................................107
Figure4.4Exampleofcorticalresponsedevelopment................................................108
Figure4.5ExamplesofcorticalresponseswithanobjectiveACCpassdespitethe
presenceofabehaviouralfail..............................................................................112
Figure4.6Changeinspeechperceptionovertime......................................................116
Figure4.7SpatialACCrecordingsusingstimuliwithdifferentdurations...................124
Figure5.1Relationshipbetweenstimulusintensityandbehaviouralelectrode
discriminationscoreaccordingtowhichelectrodepairwastested....................134
Figure5.2EffectofstimulusintensityontheN1-P2amplitude..................................136
Figure5.3RelationshipbetweenstimulusintensityandspatialACCsensitivity.........139
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Figure5.4CorticalresponseswithanobjectiveACCpassdespiteabehaviouralfailin
participantP1.......................................................................................................141
Figure5.5Relationshipbetweenreferenceelectrodeparametersandmean
behaviouralelectrodediscriminationscore.........................................................143
Figure5.6RelationshipbetweenreferenceelectrodeparametersandmeanspatialACC
amplitude.............................................................................................................143
Figure5.7Relationshipbetweensentenceperceptionscoreandmeasuresofelectrode
discrimination.......................................................................................................144
Figure6.1TerminologydescribingvarioustimeperiodsforACCstimuli.....................154
Figure6.2SchematicofstimuliusedformeasuringthespatialACCinexperiment5.158
Figure6.3Corticalresponsesforthedifferentmeasurementconditions...................166
Figure6.4SpatialACCamplitudeaccordingtonumberofscalprecordingchannels..167
Figure6.5SpatialACCSNRasafunctionofrecordingtimeandnumberofrecording
channelsforindividualparticipants.....................................................................168
Figure6.6SpatialACCSNRasafunctionofrecordingtimeandnumberofrecording
channelsforthemeandataacrossparticipants..................................................169
Figure6.7SpatialACCamplitudeaccordingtostimulustype......................................170
Figure6.8SpatialACCSNRasafunctionofrecordingtimeandstimulustypefor
individualparticipants..........................................................................................171
Figure6.9ACCSNRasafunctionofrecordingtimeandstimulustypeforthemean
dataacrossparticipants.......................................................................................172
Figure7.1FlowchartillustratingclinicaldecisionmakingwiththespatialACC...........181
Figure7.2StandardandmodifiedparadigmsforspatialACCmeasurements.............184
FigureA.1Auditoryevokedcorticalresponsesfor(A)testand(B)retestdata...........190
FigureA.2Individualauditoryevokedcorticalresponsetest-retestdata...................192
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ListofTables
Table3.1Demographicdetailsofparticipantsinexperiment1....................................64
Table3.2OutputofmixedmodelanalysisoffactorsaffectingcorticalresponseN1-P2
amplitude...............................................................................................................68
Table3.3Demographicdetailsofparticipantsinexperiment2....................................75
Table3.4Thenumberofdiscriminableelectrodepairsasdeterminedwithobjective
ACCandbehaviouralcriteriaaswellasspeechperceptionscores........................76
Table3.5Mean,standarddeviationandrangeforpeaklatenciesandpeak-to-peak
amplitudesatchannelFCz......................................................................................77
Table3.6OutputofmixedmodelanalysisoffactorsaffectingACCN1-P2amplitude..83
Table3.7ACCamplitudeatchannelFCzin2post-linguallydeafparticipants...............84
Table3.8CorrelationsbetweenspeechperceptionscoresandthespatialACC
measures................................................................................................................86
Table4.1Demographicdetailsofparticipantsinexperiment3....................................98
Table4.2Outputofmixedmodelanalysisoffactorsaffectingbehavioural
discriminationscore.............................................................................................100
Table4.3Detailsofelectrodeswhichwentfromabehaviouralfailtoabehavioural
passinexperiment3............................................................................................104
Table4.4Mixedmodelanalysisofchangeinbehaviouraldiscriminationscore
controllingforstimulusintensity.........................................................................105
Table4.5MixedmodelanalysisoffactorsaffectingchangeinACCN1-P2amplitude
overtime..............................................................................................................106
Table4.6MixedmodelanalysisoftheeffectoftimeafterswitchonlatencyofACC
peaks....................................................................................................................107
Table4.7Agreementbetweenobjectiveandbehaviouralelectrodediscriminationat
differenttimepoints............................................................................................111
Table4.8DetailsofelectrodeswithanobjectiveACCpassandabehaviouralfail.....111
Table4.9Mixedmodelanalysisoffactorsaffectingspeechperceptionwithbehavioural
electrodediscriminationasanindependentvariable..........................................114
Table4.10Mixedmodelanalysisoffactorsaffectingspeechperceptionincluding
spatialACCmeasuresasanindependentvariable...............................................115
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Table5.1Demographicdetailsofparticipantsinexperiment4..................................132
Table5.2Detailsoftheelectrodepairtestedinexperiment4....................................133
Table5.3Mixedmodelanalysisoffactorsaffectingbehaviouralelectrode
discriminationscore.............................................................................................135
Table5.4MixedmodelanalysisoffactorsaffectingACCresponseamplitude............137
Table5.5Mixedmodelanalysisoffactorsaffectingcorticalonsetresponseamplitude.
..............................................................................................................................138
Table5.6Agreementbetweenobjectiveandbehaviouralmeasuresofelectrode
discriminationatdifferentstimulusintensities....................................................139
Table6.1.Detailsofparticipantsandelectrodepairstestedinexperiment5............156
Table6.2SummaryofvarioustimeperiodsforspatialACCstimuliinexperiment5..157
Table6.3TimetakentoreachanSNRvalueof2,peakSNRvalueandHotelling-T2
resultintheACCresponsewindow.....................................................................173
TableA.1.Detailsofparticipantswithtest-retestdata...............................................188
TableA.2AmplitudesofN1-P2responsefortheonsetandACCresponseinthetest
andretestcondition.............................................................................................189
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ListofAbbreviations
AB AdvancedBionics
ACC acousticchangecomplex/auditorychangecomplex
ACE advancedcombinationencoder
AFC alternativeforcedchoice
ANSD auditoryneuropathyspectrumdisorder
BKB Bamford-Kowal-Bench
CAEP corticalauditoryevokedpotential
CAPT CHEARauditoryperceptiontest
CI cochlearimplant
CIF channelinteractionfunction
CIS continuousinterleavedsampling
CSI channelseparationindex
CT computedtomography
DC directcurrent
DR dynamicrange
EABR electricallyevokedbrainstemresponse
eACC electricallyevokedauditorychangecomplex
ECAP electricallyevokedcompoundactionpotential
EDL electrodediscriminationlimen
EEG electroencephalography
FS4 finestructure4
HDCIS highdefinitioncontinuousinterleavedsampling
Hotelling-T2 Hotelling'st-squared
ISI inter-stimulusinterval
LDL loudnessdiscomfortlevel
LME linearmixed-effects
MC mostcomfortable
MDS multi-dimensionalscaling
MIC monauralinteractioncomponent
MMN mismatchnegativity
NH normalhearing
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PCA principalcomponentanalysis
PSP platinumsoundprocessor
PTC psychophysicaltuningcurve
PPS pulsespersecond
RMS rootmeansquared
RN residualnoise
SMRT spectral-temporallymodulatedrippletest
SNR signal-to-noiseratio
SOA stimulusonsetasynchrony
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PublicationsandPresentations
Publications
1. MathewR,UndurragaJ,LiG,MeertonL,BoyleP,ShaidaA,SelvaduraiD,Jiang
D,VickersD.Objectiveassessmentofelectrodediscriminationwiththe
auditorychangecomplexinadultcochlearimplantusers.HearingResearch,
2017,354:86-101.
2. MathewR,VickersD,BoyleP,ShaidaA,SelvaduraiD,JiangD,UndurragaJ.
Developmentofelectrophysiologicalandbehaviouralmeasuresofelectrode
discriminationinadultcochlearimplantusers.HearingResearch,2018,367:74-
87.
OralPresentations
1. MathewR,UndurragaJ,BoyleP,ShaidaA,SelvaduraiD,JiangD,VickersD.
Squigglesonthebrain–objectiveassessmentofauditoryprocessingin
cochlearimplantusers.RoyalSocietyofMedicine,February2018.
2. MathewR,UndurragaJ,BoyleP,ShaidaA,SelvaduraiD,JiangD,VickersD.
BrainwavesandelectrodeInteractions.ENTMasterclass,Doncaster,January
2018.
3. MathewR,UndurragaJ,VickersD.AdvancedObjectiveMeasures.Advancesin
AuditoryImplants,UCLEarInstitute,London,July2017.
4. MathewR,UndurragaJ,LiG,ShaidaA,SelvaduraiD,JiangD,VickersD.
Measurementofcorticalauditoryresponsesforthepre-operativeassessment
andpost-operativerehabilitationofcochlearimplantpatients.’JointBritish-
ScandinavianOtologyMeeting,Uppsala,September2016.
5. MathewR,UndurragaJ,LiG,BoyleP,ShaidaA,SelvaduraiD,JiangD,Vickers
D.Objectivemeasurementofauditorydiscriminationdevelopmentafter
cochlearimplantation.ImprovingCochlearImplantPerformanceConference,
UCL,July2016.
6. MathewR,UndurragaJ,LiG,BoyleP,VickersD.Theacousticchangecomplex
asanobjectivemeasureofelectrodediscriminationinadultcochlearimplant
users.ObjectivesMeasuresinAuditoryImplants,Szeged,Hungary,June2016.
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PosterPresentations
1. MathewR,UndurragaJ,BoyleP,ShaidaA,SelvaduraiD,JiangD,VickersD.
‘MeasuringCentralAuditoryPlasticityinAdultCochlearImplantUserswiththe
AuditoryChangeComplex’.ConferenceonImplantableAuditoryProstheses,
California,USA,July2017.
2. MathewR,NimatR,UndurragaJ,MeertonL,SelvaduraiD,JiangD,VickersD.
‘Theeffectofstimulusintensityonauditoryevokedcorticalresponsesin
individualswithnormalhearingandcochlearimplants’.BritishCochlear
ImplantGroupMeeting,Birmingham,March2017.
3. MathewR,UndurragaJ,BoyleP,ShaidaA,SelvaduraiD,JiangD,VickersD.
‘Developmentoftheauditorychangecomplexaftercochlearimplantswitch-
on.’Basicauditoryscienceconference,Cambridge,September2016.
4. MathewR,UndurragaJ,LiG,MeertonL,BoyleP,ShaidaA,SelvaduraiD,Jiang
D,VickersD.‘Brainplasticityaftercochlearimplantation–anauditoryevoked
potentialstudy.’ImprovingCochlearImplantPerformanceConference,UCL,
July2016.
5. MathewR,UndurragaJ,LiG,BoyleP,VickersD.‘Pre-operativemeasurement
ofauditoryevokedcorticalresponsesinadultcochlearimplantcandidates.’
ObjectivesMeasuresinAuditoryImplants,Szeged,Hungary,June2016.
6. MathewR,UndurragaJ,LiG,BoyleP,SelvaduraiD,ShaidaA,VickersD.
‘Objectivemeasurementofelectrodediscriminationwiththeacousticchange
complex.’BritishCochlearImplantGroupMeeting,London,April2016.
7. MathewR,UndurragaJ,LiG,MeertonL,SelvaduraiD,ShaidaA,VickersD.
‘Pre-operativeassessmentofcochlearimplantcandidateswithauditoryevoked
corticalresponses.’BritishCochlearImplantGroupMeeting,London,April
2016.
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Chapter1 Introduction
ThefirstauditoryimplantinahumanwasperformedbyDjournoandEyriesinParisin
1957(WilsonandDorman,2008).Thisdeviceconsistedofaninductioncoilwithone
endplacedattheauditorynerveandtheotherwithinthetemporalismuscle.Withthis
device,thepatientcouldhearenvironmentalsoundsbutnotspeech.Overthenext30
yearsthemoderndaycochlearimplant(CI)wasdeveloped.Thisconsistsofamulti-
channelelectrodearrayinsertedinthecochleawitheachelectrodecontact
theoreticallystimulatingdistinctpopulationsofauditoryneurons.Thisdevicehas
enteredmainstreamclinicalpracticeandthereareapproximately600,000implant
usersworldwidewithmorethan1200individualsundergoingimplantationintheUK
everyyear(TheEarFoundation,2016).Although,thistechnologyhasproven
revolutionaryinrestoringhearingtoindividualswithprofounddeafness,thereis
significantvariabilityinhearingoutcomesinpaediatricandadultpopulations(Blamey
etal.,1996,2013;Niparkoetal.,2010;WooiTeohetal.,2004).Whiletherearemany
potentialcausesforthisvariability,oneimportantfactorthatmaycontributetopoor
outcomesisthenon-independenceofelectrodecontactsontheCIarrayresultingin
distortionofthetransmittedsoundsignal.Broadly,thegoalofthisresearchwasto
determinewhetheranelectrophysiologicalresponsefromthebraincalledthespatial
auditorychangecomplex(ACC),couldbeusedtoassesselectrodeindependencewith
aviewtousingthisasaclinicaltoolforpatientassessment.
Thischapterreviewstheliteraturethatisrelevanttotherationaleandmethodologyof
thisstudy.Thefollowingsectionswillprovidedetailsof(1)howaCIworks(2)hearing
outcomeswithaCI(3)evidencethatchannelinteractionslimithearingoutcomeand
(4)techniquesforassessingchannelinteractionsincludingcorticalauditoryevoked
potentials(CAEPs).
1.1HowaCIworks
1.1.1ComponentsoftheCIsystem
ThethreemainmanufacturersofCIdevicesareAdvancedBionics(AB),MED-ELand
CochlearLimited.ThemaincomponentsofCIdevicesconsistofthefollowing1)the
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microphonewhichpicksuptheacousticsignal2)thesoundprocessor,whichconverts
themicrophoneoutputtoelectricalsignals3)aheadpiecewithatransmittingcoil,
whichisheldinplacebyamagnetandusesradiofrequencytotransmitthesignal
transcutaneously4)theimplantreceiver/stimulator,whichdecodesinformationfrom
thetransmitterandgenerateselectricalstimuliand5)theelectrodearray,whichis
usedtostimulateauditoryneuronsinnervatingthecochlea.
Theelectrodearrayconsistsofmultipleelectrodecontacts,eachofwhichisintended
tostimulateadistinctpopulationofauditoryneurons.CIsattempttomimicnatural
tonotopicencodingbyrepresentinghighfrequenciesatthebasalendandlow
frequenciesattheapicalendofthearray.Thearrayisideallyplacedinthelower
compartmentofthecochlea,thescalatympani,whereitliesclosertotargetauditory
neurons.Theintra-cochlearlengthvariesfrom6to31mmfordifferentarraysdesigns
(BrantandRuckenstein,2016)butnoneofthecurrentarrayscoverthewholecochlear
length.Electrodearrayscanvaryintheirintendedpositionrelativetothemodiolus,
whereauditoryneuronsarelocated.Peri-modiolarelectrodesarepre-curvedand
shouldlieclosetothemodiolus,allowingmorefocusedneuralstimulation.Incontrast,
lateralwallelectrodesliefurtherfromthemodiolus,resultingingreatercurrent
spreadbutareassociatedwithlesstraumaticinsertions(BrantandRuckenstein,2016).
ACIstimulationchannelconsistsofanactiveandoneorseveralreferenceelectrodes
(Zhuetal.,2012).Forexample,inmonopolarmode,thereferenceelectrodeislocated
outsidethecochleaandtheactiveelectrodeislocatedwithinthecochlea.Inbipolar
mode,thereferenceelectrodeisaneighbouringintra-cochlearelectrode,whilstin
tripolarmodethereturnelectrodesare2intra-cochlearelectrodesoneithersideof
theactiveelectrode.Thereisevidencethatbipolarandtripolarstimulationmodes
producemorefocusedexcitationpatterns(BiererandMiddlebrooks,2002)ascurrent
flowsbetweenneighbouringelectrodesbutthiscomesatthecostofgreatercurrent
requirementsandshorterbatterylifeforthedevice.Thepartialtripolarmode(Bierer
andFaulkner,2010)hasbeendevelopedasacompromisetoimprovecurrentfocusing
whilstreducingcurrentrequirements–inthismodethecurrentreturnsfromthe
activeelectrodeto2neighbouringelectrodesaswellasanextra-cochlearreference
electrode.MostcurrentCIdeviceshoweverutilizemonopolarstimulationasthismode
21
requireslesscurrentandisassociatedwithsimilarlevelsofperformancetoother
stimulationmodes(MensandBerenstein,2005;Zwolanetal.,1996).
1.1.2Electricalstimulationoftheauditorynerve
1.1.2.1Siteofstimulation
CIsbypassthedamagedcochleaanddirectlystimulateauditoryneurons.Electrical
stimulationcanleadtoactivationoftheauditorynerveatseveralsitesincludingthe
peripheralprocesses,thecentralprocessorthrougheithermechanicalorelectrical
stimulationofinnerhaircells(JavelandShepherd,2000;Moxon,1971).Vanden
HonertandStypulkowski(1984),recordedsingleauditorynervefibreresponsesto
pulsatileelectricalstimulationincats.Lowstimulusintensitiesledtolonglatency
responses(500to800µs)associatedwithsignificantlatencyvariability.Incontrast,
highstimulusintensitiesledtoshort-latency(300to500µs)highlysynchronous
responses.Itwaspostulatedthatasstimulusintensityincreased,thesiteofactivation
shiftedfromperipheralprocessestothecentralprocessoftheauditoryneurons.This
wassupportedbythefindingsthatshort-latencylow-jitterresponseswerealso
obtainedinanimalsthatunderwentsurgicalremovaloftheperipheralprocessesand
spiralganglioncellbodies.Giventhatdeafnessisassociatedwithsignificant
degenerationoftheinnerhaircellsandperipheralprocesses(HinojosaandMarion,
1983;Nadoletal.,2001),itislikelythatthatinCIpatients,activationoftheauditory
nerveoccursinthecentralprocesses.
1.1.2.2Phaselockingofauditoryneurons
Moxon(1967)showedthattheabsoluterefractoryperiodofauditoryneuronsincats
wasasshortas500µs.However,nervefibrescouldnotfireatthemaximumpossible
rate.Itwasfoundthatforburstsofelectricalstimuli,themaximumrateofstimulation
was900pulsespersecond(pps)butthisfellto500ppsafteraround2minutes.In
comparisontoacousticstimulation,electricalstimulationleadstoagreaterlevelof
phaselockingofauditoryneurons.Javeletal.(1987),showedthattherewasoneto
onecorrespondenceofthedischargeofauditoryneuronswithelectricalpulsesupto
ratesof800pps.Theirstudyalsoshowedthatthedynamicrangeofauditoryneurons
22
wassmall(1to6dB,referenceto1µA)andincreasedwithstimulationrate.Similarto
Javeletal.(1987),Hartmannetal.(1984),showedthatelectricalstimulationledto
moresynchronousfiringoftheauditorynervecomparedtoacousticsstimulation,
thoughforhigherstimulationrates,largerstimulusintensitieswererequiredto
maintainphaselocking.Electricalstimulation,however,leadstomuchmore
deterministicfiringofauditoryneuronscomparedtoacousticstimulation.Clark
(1998),measuredinterspikeintervalhistogramsofunitsinthecatanteroventral
cochlear(AVCN)nucleus.Atlowstimulationrates,electricalstimulationledtofew
peaksintheintervalhistogramandverylittlejitter.However,athigherratesofaround
800pps,thefiringbecamemorestochasticwithagreaternumberofpeaksand
latencyjitter,similartoacousticstimulation.PaoliniandClark(1997)showedthatat
stimulationratesof1800pps,forwhichtheperiodofthestimulusapproachesthe
absoluterefractoryperiodofauditoryneurons,theresponseoftheAVCNneuronsis
notrelatedtothestimulusrate.
ShepherdandJavel(1997),comparedresponsecharacteristicsofauditoryneuronsin
hearinganddeafanimals.Theyshowedthatauditoryneuronsfromdeafanimals
displayedlittleornospontaneousactivity.Furthermore,neuronsfromdeafanimals
displayedlessjitterandpoorerphaselockingtoelectricalstimuli.Whilstauditory
neuronsfromdeafanimalscouldfireinresponsetoeverypulseatstimulationratesup
to800pps,fibresfromdeafanimalswerenotcapableofthisatratesabove400pps.
Auditoryneuronsfromdeafanimalsalsodisplayedabnormaldischargepatterns
alternatingbetweenperiodsofsynchronousfiringandcompleteinactivity.
Althoughelectricalstimulationleadstostrongphaselockingoftheauditoryneuronsin
animalexperiments,temporalprocessinginhigherauditorycentresappearstobe
muchpoorer.Clark(1969)measuredtheresponseofcellsinthesuperiorolivary
complexofcatsandfoundthatelectricalstimulationabove200to500ppsdidnot
producethesamefiringrateorpatternasanacoustictonewiththesamefrequency.
Merzenichetal.(1973),measuredinterspikeintervalhistogramsintheinferior
colliculusofcatsandfoundthatsinusoidalelectricalstimuliwereencodedinthe
dischargepatternofneuronsuptoratesof400to600pps.Thepoorerphaselocking
ofhigherauditorycentresmaybeduetothefactthatelectricalstimulationresultsin
23
stronginhibitioninthebrainstem.Furthermore,thesedatasuggestedthatspeech
information,whichincludesfrequenciesupto4000Hz,couldnotbeconveyedby
temporalcodingalone.
1.1.2.3Effectofstimulationmode
VandenHonert(1987),examinedhowresponsethresholdofauditorynervefibres
variedwithstimulationmode.Theelectricalthresholdofauditoryneuronswith
differentacousticcharacteristicfrequencieswasmeasuredforalargepopulationof
neurons.Formonopolarstimulation,theelectricalthresholdsweresimilaracrossthe
cochleaindicatingpoorspatialselectivity.Incontrast,withbipolarstimulation,
auditorynervefibresadjacenttostimulatedelectrodehadmuchlowerthresholds,
implyingbetterspatialselectivity.Thesefindingsaresupportedbycompoundaction
potentialresponseswithmonopolarstimulationinhumanCIusers,whicharebroader
whencomparedtoresponsesobtainedwithbipolarortripolarstimulation,indicatinga
broaderareaofneuralactivation(Milleretal.,2003).Electrophysiologicalstudiesin
theinferiorcolliculus(MerzenichandWhite,1977)andauditorycortex(Biererand
Middlebrooks,2002)showthatthegreaterspatialselectivityassociatedwithbipolar
andtripolarstimulationmodesismaintainedfurtheruptheauditorypathway.One
potentialdisadvantageofbipolarstimulationisthatitmayleadtobimodalpatternsof
stimulation,wheretwopeaksofstimulationareproducedattheactiveandreturn
electrodes(Kraletal.,1998;Undurragaetal.,2012).Thereisevidenceinhumansthat
theanodicphaseofanelectricalpulseismoreeffectiveatstimulatingauditory
neuronsthanthecathodicphase(Machereyetal.,2008;Undurragaetal.,2012)and
recentstudieshaveattemptedtomanipulatethepulseshapeinordertoavoid
multiplepeaksofexcitationthatmaybeassociatedwithfocusedstimulationmodes
(Undurragaetal.,2012).
1.1.2.4Effectofelectrodeposition
Thereisevidencethatthepositionoftheelectrodearrayinthecochleahasan
importantinfluenceonactivationoftheauditorypathwaybytheCI.Shepherdetal.
(1993)foundthatthethresholdoftheauditorybrainstemresponseincatswas
reducedbymovingthepositionoftheelectrodea)fromtheouterpartofthecochlea
24
towardsthemodiolusandb)towardstheosseousspirallaminaclosertothe
peripheralprocessesofauditoryneurons.Thisfindingisinlinewithevidencefrom
compoundactionpotentialmeasurementsinhumanCIusers,inwhomithasbeen
foundthatperi-modiolarelectrodeshavelessspreadofelectricalexcitationand
possiblylowerthresholds,comparedtomorelaterallyplacedelectrodes(Tsujietal.,
2009;vanWeertetal.,2005;Xietal.,2009).
1.1.3Soundprocessingstrategies
Soundprocessingreferstohowtheacousticsignalisencodedintoanelectrical
stimulus.Presentdaysoundprocessingstrategiesaregenerallybasedontemporal
envelopeextractionandarevariantsoftheContinuousInterleavedSampling(CIS)
strategy(Wilsonetal.,1991).First,aseriesofbandpassfiltersareusedtodecompose
theacousticsignalintofrequencycomponents.Thetemporalenvelopeofeachof
thesewaveformsisextractedandcompressedintothenarrowdynamicrange(DR)of
electricalhearing.Thecompressedenvelopeoutputisthenusedtomodulatefixed
rateelectricalpulsesatindividualelectrodes,withtheoutputofeachbandpassfilter
mappedtoasingleelectrodealongthearray.Arequirementforsafeelectrical
stimulationisthatpulsesmustbechargebalanced–thisistypicallyachievedbyusing
symmetricbiphasicpulses,whichconsistoftwophaseswithequalamplitudeand
durationbutoppositepolarities.Pulsetrainsacrossdifferentchannelsaretemporally
interleavedinordertoreducechannelinteractions.
Eachoftheimplantcompanieshasitsownspeechprocessingstrategywithfeatures
aimedatimprovingspectralortemporalencodingoftheacousticsignal.TheHighRes
strategyusedintheABdeviceisavariationofCISwhichuseshighstimulationratesto
providebettertemporalenvelopeinformationandarelativelyhighcutofffrequency
fortheenvelopedetector(WilsonandDorman,2008).TheHiRes120strategyusesa
techniquecalledcurrentsteeringtoimprovespectralresolutionbyincreasingthe
numberofstimulationsites.Thisisachievedwiththecreationof‘virtualchannels’
betweenelectrodecontacts,byvaryingtheproportionofcurrentdeliveredattwo
neighbouringsimultaneouslyactivatedelectrodes.Whilstthereisevidencethatthis
canleadtoanincreasednumberofpitchpercepts(Firsztetal.,2007),evidencefora
25
consistentgaininspeechperceptionwiththisstrategyislacking(Brendeletal.,2008;
Donaldsonetal.,2011).
HighDefinitionCIS(HDCIS)isusedintheMED-ELdeviceandissimilartoCIS,but
utilizesoverlappingbellshapedfilterswhichenabledeliveryofcurrentatvirtual
channels.Morerecently,themanufacturersoftheMED-ELdevicehaveimplemented
FineStructurestrategiessuchasFineStructure4(FS4)inordertoimprovetemporal
cuesinthelowfrequencies.InFS4,theapical4electrodesdonotusefixedrate
envelopebasedcoding;ratherstimulationpulsesaretriggeredbyzero-crossingsina
channel‘sband-passfilteroutput,therebyprovidingatemporalcode.MostCochlear
devicesuseann-of-mstrategy,where‘n’electrodewiththehighestenergyintheir
associatedanalysisfiltersarestimulatedoutofatotalof‘m’electrodes.Bylimitingthe
numberofactiveelectrodes,interactionsaretheoreticallyreducedwhilstpreserving
themostimportantaspectsoftheauditorysignal.Thisapproachisutilizedin
Cochlear’sAdvancedCombinationEncoder(ACE)strategy,whichalsouseshigh
stimulationrates.
1.1.4FittingaCI
TheCImustbeprogrammedforeachindividualtoensurethatitcanbeusedsafely
andeffectively–thisprocedureisusuallyreferredtoasfittingorprogramming(Wolfe
andSchafer,2014).Theintegrityofelectrodescanbecheckedwithimpedance
measurements,whichidentifyelectrodescontactswithanopencircuit(high
impedance)orashortcircuit(verylowimpedance).Thesemalfunctionalelectrodes
aretypicallyswitchedoff.Extra-cochlearelectrodes,identifiedonX-rayorconebeam
computedtomography(CT)imaging,arealsoswitchedoff.Akeyaspectofthefitting
procedureconsistsofdeterminingthelowerandupperlimitsofstimulation.This
involvesestimatingthethresholdlevelandmostcomfortable(MC)levelofstimulation
forindividualelectrodes.Typically,theseestimatesarebasedonbehavioural
responsesorverbalfeedback.Thismaynotbepossibleinyoungchildrenandinthese
situations,electrophysiologicalmeasurements,suchastheelectricallyevoked
compoundactionpotential(ECAP)(Alvarezetal.,2010;FranckandNorton,2001;
SeyleandBrown,2002),theelectricallyevokedstapediusreflex(Hodgesetal.,1997;
26
StephanandWelzl-Müller,2000),ortheelectricallyevokedauditorybrainstem
response(EABR)(Brownetal.,2000),maybeusedtodeterminestimulationlevels.
ThresholdandMClevelmeasurementsareusuallyperformedforasubsetof
electrodesandinterpolationisusedtodeterminestimulationlevelsfortherest.
Electrodesarethenloudnessbalancedbystimulatinganumberofelectrodesin
sequenceattheMClevelandadjustingtheirlevelsuntiltheyproducesimilarloudness
percepts.Theimplantisthenactivatedin‘livespeech’modewithallchannels
activatedandtheoverallvolumecanbeadjustedasnecessary.Theabovefitting
procedureisrepeatedseveraltimesduringthefirst6monthsafterswitch-on,asDR
increasesduringthisperiod(Hughesetal.,2001;Vargasetal.,2012)duetothe
developmentofloudnesstolerance.
Thereissomeflexibilitywithfittingparameterswhichvariesbetweenmanufacturers.
Forexample,selectionofthesoundprocessingstrategy,stimulationrate,numberof
maxima(i.e.numberof‘n’channels)forn-of-mstrategies,pulsewidth,sensitivity
(adjustsautomaticgaincontrolparameters)andtheinputDRofthemicrophone.
Patientscanbeprovidedwithspecializedprogrammes,whichcanbeselected
dependingonthelisteningsituation.Forexample,programmesareavailabletoaid
speechperceptioninnoisyconditions,toallowtheuseofwirelessexternallistening
accessoriesandtoreducenoiseduetowind.Dependingonthedeviceandaudiologist
recommendation,patientsmaybeabletocontrolthevolumeandsensitivitysettings
oftheirdevice.Incontrasttoadults,flexibilityisseldomprovidedforchildren.
1.2OutcomeswithCI–successandvariability
CIshaveproventobeoneofthegreatesttechnologicalinnovationsinmedicineinthe
20thcentury.Therestorationofhearingtoprofoundlydeafindividualshasfarreaching
personalandsocio-economicconsequences.Forexample,hearingrestorationwithaCI
isassociatedwithhighereducationalattainmentforchildren,improvedvocational
outcomesandbetterqualityoflife(Crowsonetal.,2017;EmmettandFrancis,2015;
Semenovetal.,2013).Nonetheless,studiesinadultsandchildrenhaveshownthat
cochlearimplantationisassociatedwithconsiderablevariabilityinhearingoutcomes.
Niparkoetal.(2010)assessedlanguagedevelopmentinchildrenimplantedbeforethe
27
ageof18monthsusingtheReynellDevelopmentalLanguageScale.Itwasfoundthat
after3yearsofCIuse,comprehensionscoresrangedfromapproximately2to65
points,withameanscoreofapproximately42points.Holdenetal.(2013),measured
wordrecognitionscoresinpost-linguallydeafenedadultsandfoundthatafter2years
ofCIuse,scoresrangedfrom3to90%withamedianscore65%.Eveninindividuals
withgoodspeechperceptioninquiet,outcomesaregenerallypoorformore
challengingauditorytasks.Thisincludespeechperceptioninnoise(Zeng,2004),
speakerrecognition(VongphoeandZeng,2005)andmusicappreciation(Kongetal.,
2004).
Someofthefactorsthatcontributetothevariationinhearingoutcomesaftercochlear
implantationarewellunderstood.Forpre-linguallydeafenedchildrenandadults,age
atimplantationisacriticaldeterminantofhearingoutcome.Specifically,outcomesare
poorerwithincreasingage(Kirketal.,2002;Nikolopoulosetal.,1999).Ifimplantation
isperformedaftertheageof7,thenopen-setspeechperceptionisparticularlypoor
(Fryauf-Bertschyetal.,1997;Manriqueetal.,1999).Thisisbecausethereisasensitive
periodforauditorydevelopment,beyondwhichauditoryplasticityisreducedand
auditorydeprivationleadstoabnormalpatternsofbrainconnectivity(Kraletal.,2016;
KralandSharma,2012;Sharmaetal.,2005a;Teohetal.,2004).Forpost-lingually
deafenedindividuals,durationofprofoundhearinglossisakeypredictorofhearing
outcome(Blameyetal.,2013;Holdenetal.,2013).Longerdurationofdeafnessis
associatedwithdegenerationofelementsintheperipheralauditorysystemaswellas
corticalreorganization(Nadoletal.,1989;Sandmannetal.,2012).Inbothpre-and
post-linguallydeafenedCIusers,speechperceptionisaffectedbythedurationofCI
use(Blameyetal.,2013).Outcomesinyoungchildrencontinuetoimproveformany
yearsastheyacquirelanguage(WooiTeohetal.,2004).Inadults,speechperception
usuallyplateausafteraround6–12monthsofCIuse(Lenarzetal.,2012;WooiTeoh
etal.,2004)thoughincertainindividuals,improvementmaycontinueforseveralyears
(Heywoodetal.,2016;Tyleretal.,1997).
Otherpatient/diseaserelatedfactorsthathavebeencorrelatedwithspeech
perceptionincludetheamountofpre-operativeresidualhearing(Holdenetal.,2013;
Lazardetal.,2012),modeofcommunication(HoltandSvirsky,2008;Osbergerand
28
Fisher,2000),socioeconomicstatus(HoltandSvirsky,2008;OsbergerandFisher,
2000),leveloffamilysupport(Holtetal.,2013),aetiologyofhearingloss(Blameyet
al.,1996;Greenetal.,2007;Matsushiroetal.,2002)andcognitivefunction(Holdenet
al.,2013).Devicerelatedfactorswhichhavebeencorrelatedwithspeechperception
includethepercentageofactiveelectrodesinthecochlea(Geersetal.,2003;Lazardet
al.,2012),depthofelectrodearrayinsertion(Holdenetal.,2013;Skinneretal.,2002)
andscalarpositionofCIelectrodecontacts(Holdenetal.,2013;Skinneretal.,2007).
Despiteanunderstandingofthesepredictivefactors,largescalesstudieshaveshown
thatmuchofthevarianceinCIoutcomesstillremainsunexplained(Blameyetal.,
1996;Lazardetal.,2012).Forexample,Lazardetal.(2012),assessedtheinfluenceof
15pre,periandpost-operativefactorsonspeechperceptionin2251patients.Usinga
generallinearmodel,itwasfoundthatonly22%ofthevarianceforspeechperception
inquietaswellasspeechperceptioninnoisecouldbeexplained.
1.3ChannelinteractionsasafactorlimitingCIoutcome
Giventhelargeunexplainedvarianceinspeechperceptionaswellastherelatively
pooroutcomesinchallenginglisteningsituations,thereisaneedtoidentifyand
addressfactorsthatreduceperformanceinindividualCIusers.Onesuchfactormaybe
thepresenceofelectricalinteractionsbetweenelectrodecontactsontheCIarray.
Thesetypesofinteractionswouldbeexpectedtoleadtodistortionofthetransmitted
soundsignalandpoorerspeechperception
CIstransmittheauditorysignalbymeansofalimitednumberofstimulationchannels.
Researchershaveattemptedtoinvestigatetheimportanceofthenumber,aswellas
independenceofstimulationchannels,usingsimulationsinNHindividualswith
vocodedspeech.Vocodersutilizeasignalprocessingtechniqueanalogoustothatina
CI–thesoundsignalisprocessedthroughaseriesofbandpassfilters,andthe
temporalenvelopewithineachfilterisextractedandusedtomodulatebandlimited
whitenoiseoratonecarrier(Rosenetal.,2015;Shannonetal.,1995).Thesestudies
haveshownthatmorecomplexlisteningtasksrequireagreaternumberofspectral
channelstoachieveagivenlevelofperformance(Shannonetal.,2004).Thuswhile
goodlevelsofspeech-in-quietcomprehensioncanbeachievedwithaslittleas4
29
spectralchannels(Friesenetal.,2001;Shannonetal.,1995),performancecontinues
toimprovewithupto20spectralchannelsforspeech-in-noiseperception(Friesenet
al.,2001)and64channelsformelodiccontourrecognition(Smithetal.,2002)inNH
listeners.Inadditiontothenumberofspectralchannels,theindependenceofthese
channelsisanimportantconsideration.Spectralsmearingcanbeintroducedby
alteringtheslopeofthecut-offfrequenciesofthebandpassfilters,andincreased
overlapofthefilteroutputsisassociatedwithsignificantlyreducedspeechperception
innoiseinNHlisteners(FuandNogaki,2005).
InpresentdayCIsystems,thenumberofbandpassfilters,correspondingtothe
numberofelectrodecontacts,isbetween12and22.However,thenumberof
‘effective’channelsareoftenfarfewer.ThishasbeenrevealedinstudiesofCIusers
withexperimentalmaps,wherethenumberofchannelscanbemanipulated.These
studieshaveshownthatspeechperceptionimproveswiththenumberofchannelsbut
plateausbeyond4to10channelsdependingontheindividualandthetask(Dorman
andLoizou,1998;Fishmanetal.,1997;Friesenetal.,2001).Thisappearstobethe
caseirrespectiveofstimulationmode,speechprocessingstrategyanddevice.Ofnote,
CIuserswithpoorspeechperceptionhavenomorethan4effectivechannels(Friesen
etal.,2001).
Thepresenceofchannelinteractionswouldalsobeexpectedtocontributetopoor
spectralresolutioninCIusers.Spectralrippletestshavebeenusedinresearchsettings
toprovideabroadmeasureofspectralresolutioninCIusers.Inthesetests,astimulus
whichhasbeenamplitudemodulatedinthefrequencydomainmustbediscriminated
fromastimuluswithadifferentrippledensity,aninvertedphaseorfroman
unmodulatedstimulus(AronoffandLandsberger,2013;HenryandTurner,2003;Saoji
etal.,2009;Wonetal.,2007).Spectralripplediscriminationscoresaresubstantially
poorerinCIuserscomparedtoNHindividuals(Henryetal.,2005;HenryandTurner,
2003).SpectralripplediscriminationscoresarehighlyvariablebetweenCIusers(Henry
etal.,2005;HenryandTurner,2003)andthesemeasureshavebeencorrelatedwith
voweldetection,consonantdetection,speechperceptioninquietandspeech
perceptioninnoise(Henryetal.,2005;HenryandTurner,2003;Lawleretal.,2017;
Wonetal.,2007).HenryandTurner(2003),examinedtheeffectofthenumberof
30
stimulationchannelsonspectralripplediscriminationability.ItwasfoundthatforCI
simulationswithNHindividuals,spectralripplescoresimprovedasthenumberof
channelsincreasedfrom1to16.Incontrast,CIusershadaperformanceplateauat4
to6channels.ThisprovidesfurtherevidencethatCIusersareunabletousethe
spectralinformationprovidedbythenumberofelectrodesintheirimplant.
Insummary,thestimulationchannelsinCIusersarenotindependentandpoorer
performersappeartohavefewer‘effective’channels.Thelevelofinteractions
betweenchannelsmaythereforebeanimportantpredictorofhearingoutcome
1.4Reasonsforchannelinteractions
AnumberoffactorscontributetointeractionsofCIstimulationchannels.TheCIarray
sitsinafluidfilledchamberandisseparatedfromtargetauditoryneuronsbyporous
bone.Asaresult,currentflowslongitudinallyalongthecochleacausingawidefieldof
electricalexcitation.Thespreadofcurrentwillalsobeaffectedbythearray-to-
modiolusdistance,whichinturnisaffectedbysurgicalplacementofthearrayand
electrodedesign(Cohenetal.,2006).Furthermore,thepresenceofpost-surgical
fibrosisandossification(PfingstB.etal.,1985;Somdasetal.,2007)willinfluence
currentpathways.Currentspreadcanalsoleadtoaphenomenoncalledcrossturn
stimulation-thisoccurswhenanelectrodestimulatesneuralelementsfromamore
apicalturnofthecochlea,ratherthanthetargetauditoryneuronsinthesameturn
(Frijnsetal.,2001).Profounddeafnessinadults,isassociatedwith‘holesinhearing’
duetoneuraldeadregions(IncesuluandNadol,1998;Moore,2001;Shannonetal.,
2002)andinthesecases,thecorrespondingCIelectrodewillonlyproduceanaudible
perceptifneighbouring‘non-target’neuronsarestimulated.Reducedspectral
resolutionduetochannelinteractionsisfurthercompoundedbymisalignment
betweenthefrequencyallocationofelectrodecontactsandthecharacteristic
frequenciesofthecorrespondingauditoryneurons,duetotheshortlengthofthe
electrodearrayrelativetothecochlea(Grasmederetal.,2014;Zengetal.,2014).Reiss
etal.(2007),however,showedthattheamountofmismatchbetweenallocatedand
perceivedfrequenciesreducedovertime,suggestingthatCIuserscanatleastpartially
adapttospectralmismatch.
31
1.5AssessmentofchannelinteractionsinCIusers
Identificationoftheextentandlocationofchannelinteractionscouldprovide
prognosticinformationandhelpguideinterventionsthatleadtoimprovedhearing.
Forexample,thereisevidencethatauditorytrainingandre-programmingoftheCI,in
individualswithchannelinteractions,leadstoimprovedhearingoutcome(Fuand
Galvin,2008;Salehetal.,2013).Whilstspectralrippletestsprovideabroadmeasure
ofspectralresolution,localizedassessmentsofinteractionsforindividualelectrodes
wouldbemoreinformative,fromaclinicalpointofview.Thiscanbeachievedwith
eitherbehaviouralorelectrophysiologicalmeasurements.Inthissection,themain
techniquesforassessingchannelinteractionsaresummarized.
1.5.1Behaviouralmeasuresofchannelinteractions
1.5.1.1Behaviouralelectrodediscrimination
Electrodediscriminationoffersasimpleassessmentofchannelindependence.Itis
measuredbyaskingCIuserstoidentifywhetherthesoundperceptsassociatedwith
twosequentiallystimulatedelectrodesaredifferent.Electrodediscriminationis
typicallymeasuredwitha2-alternativeforcedchoice(AFC)task.Thistechniquecanbe
usedtodefinethesmallestseparationbetweenelectrodesrequiredforaccurate
discrimination,whichistermedtheelectrodediscriminationlimen(EDL).EDLscanbe
measuredwithamethodofconstantstimuliorwithanadaptiveprocedure,bothof
whichproduceequivalentresults(BusbyandClark,1996).Itis,however,importantto
accuratelyloudnessbalanceelectrodesinordertoreducetheeffectofintensitycues
ondiscrimination.Randomlevelvariationscanbeusedinadditiontoloudness
balancinginordertoreduceintensitycues(Busbyetal.,2000;BusbyandClark,1996).
Ithasbeenarguedthatsuchvariationsinintensityallowamorefunctionallyrelevant
assessmentofdiscrimination(Henryetal.,2000).Ontheotherhand,changesin
stimuluslevelcanproduceperceivedchangesinpitch(Townshendetal.,1987)which
canmaketheresultsofthetaskdifficulttointerpret.
McKayetal.(1999),examinedtheeffectofstimulusintensityonelectrode
discriminationability.Higherstimulusintensitiesareassociatedwithbroaderpatterns
32
ofexcitationwithinthecochleacausingagreateramountofoverlapintheelectrical
fieldsofelectrodes.Itwasexpectedthenthatincreasingstimulusintensitywouldlead
topoorerelectrodediscrimination.Onthecontrary,itwasfoundthatincreasing
stimulusintensityactuallyledtoasignificantimprovementindiscriminationscores.
Theauthorsconcludedthatsuccessfulelectrodediscriminationdependson
differencesinthepeaksandedgesofthepatternofexcitationratherthantheamount
ofnon-overlapinexcitationfields.
EDLsinCIusersarehighlyvariable(BusbyandClark,1996;Dawsonetal.,2000;Zwolan
etal.,1997)andthereisevidencethatelectrodediscriminationability,particularlyin
theapicalandmidregionsofthearray,isrelatedtospeechperception(Busbyetal.,
2000;Dawsonetal.,2000;Henryetal.,2000).Busbyetal.(2000),showedthatin16
earlydeafenedparticipants,apicalEDLwasnegativelycorrelatedwithclosed-set
speechperception,withlargerEDLpredictingpoorerspeechscores.Dawsonetal.
(2000),measuredapicalandmidarrayEDLin17children.Theyshowedthatelectrode
discriminationabilitywasthestrongestpredictorofclosed-setspeechperception,and
thatfactorssuchasimplantexperienceanddurationofdeafnessdidnotaccountfor
furthervarianceinspeechrecognitionscoresintheirparticipants.Henryetal.(2000),
foundthatelectrodediscriminationinthepresenceofrandomlevelvariationwas
correlatedwiththeamountofspeechinformationperceivedinthelowandmid
frequencybands.ThrockmortonandCollins(1999)foundthatthenumberof
indiscriminableelectrodesontheCIarraywascorrelatedwithaveragemaskinglevel
measuredwithpsychophysicaltuningcurves(PTCs,seesection1.4.1.4).Inaddition,
thenumberofindiscriminableelectrodeswasnegativelycorrelatedwithperformance
onvowel,consonant,andsentencerecognitiontasks.Zwolanetal.(1997),foundno
correlationbetweenelectrodediscriminationandspeechperception.However,in
theirstudy,anumberofparticipantsonlyhadpartialelectrodeinsertionswhichmay
haveaccountedforthedifferenceinfindings.
Thereislimitedevidencethattheresultsofelectrodediscriminationtestingcanbe
usedtoguideinterventionstoimprovespeechperceptioninCIusers.Zwolanetal.
(1997),providedadultCIuserswithanexperimentalmapinwhichindiscriminable
electrodesweredeactivated,andshowedthat7outof9participantshadan
33
improvementinatleastonemeasureofspeechperception.Interestinglytherewasno
improvementinvowelorconsonantrecognitionanditwashypothesizedthatthe
improvementassociatedwithelectrodedeactivationmighthavebeenduetobetter
speechenvelopeinformation.Itmustbenotedthatin2participants,speech
perceptiondeterioratedmarkedly–oneoftheseparticipantsonlyhad3electrodes
afterdeactivation,whichmayaccountforthepoorerperformanceinthiscase.
Analternativeapproachtodeactivatingindiscriminableelectrodesistoprovide
electrodediscriminationtraining.Thisassumesthatindiscriminableelectrodeactually
dostimulatedifferentpopulationsofneurons,butthatthedifferenceinthe
stimulationpatternistoosmalltobeperceived.FuandGalvin(2008)reportedasingle
casestudyinwhichelectrodediscriminationtraininginanearlydeafenedlate
implantedindividual,resultedinlargeimprovementsinelectrodediscriminationd’
scores.Ofnote,theimprovementsindiscriminationscoresgeneralizedtountrained
electrodecontrasts.Furthermore,betterelectrodediscriminationwasassociatedwith
improvedvowelandconsonantrecognition.
Theadvantageofelectrodediscriminationtestingisthatitisquickandeasyto
perform.Dawsonetal.(2000)developedatechniqueformeasuringelectrode
discriminationbasedonplayaudiometryandshowedthatitcouldbemeasuredin
childrenasyoungas4yearsold.Inaddition,theresultsofelectrodediscrimination
testingaresimpletointerpretandcanbeusedtocreatepass-failrulesinorderto
defineareasofpoordiscriminability(ThrockmortonandCollins,1999;Zwolanetal.,
1997).Alimitationofelectrodediscriminationtestingisthattheabilitytoaccurately
discriminateelectrodesdoesnotimplyahealthyelectrode-neuralinterface.For
example,evenifcrossturnstimulationoradeadregionispresent,accurateelectrode
discriminationmaystillbepossible.
1.5.1.2Pitchranking
DuetothetonotopicarrangementoftheCIarray,itisexpectedthatthepitchpercept
willincreaseinanorderlyfashionfromtheapicaltobasalendoftheelectrodearray.
PitchrankingistypicallyassessedbystimulatingtwoCIelectrodesandasking
34
participantstoidentifywhichelectrodeisassociatedwithahigherpitch.Nelsonetal.
(1995),foundthatingeneral,placepitchwasorderedfromapextobaseinCIusers,
butincertainindividualspitchreversalsoccurredwherebyamorebasalelectrode
producedalowerpitchpercept.Whilstsomeindividualshadnearperfectpitchranking
abilityforadjacentelectrodesseparatedby0.75mm,othersonlyachievedperfect
performancewhenthespatialseparationbetweenelectrodeswas13mm,whichwas
morethanthreequartersofthearraylength.Pitchrankingabilityhasalsobeen
correlatedwithspeechperception(Collinsetal.,1997;Nelsonetal.,1995).
Anumberofstudieshaveusedtheresultsofpitchrankingtaskstore-programmethe
CI.Collinsetal.(1997),usedpitchrankingdatatore-orderthefrequencyallocationof
electrodesonanexperimentalprogramme,inordertoproduceanorderlypitch
percept.Ingeneral,theexperimentalprogrammewasassociatedwithworsespeech
perception–anumberofparticipantsdisplayedworsevowel,wordandsentence
recognitionscoreswithonlyafewparticipantsshowingimprovementsinsentence
perception.Thismayhavebeenbecauseparticipantsweretestedacutelyi.e.theydid
nothavetimetoadapttotheirexperimentalprogramme.Salehetal.(2013)measured
pitchrankingforadjacentelectrodepairsinCIusersofAB,MED-ELandCochlear
devices.Binomialsignificancewasusedtocreatepass-failrulesforpitchrankingof
electrodepairs.Thesedatawereusedtodeactivateelectrodesassociatedwithpoor
pitchranking.Participantsweregiven1monthtoadapttotheirresearchprogramme.
Itwasfoundthat20outof25participantsreportedanimprovementinsoundquality.
Furthermore,therewasasignificantimprovementinspeech-in-quietandspeech-in-
noisescores.
Vickersetal.(2016)usedasimilarapproachinCIusersbutonlyforthosewitha
CochleardeviceusingtheACEprocessingstrategy(n-of-m).IncontrasttoSalehetal.
(2013),directelectricalstimulationratherthanacousticstimulationwasusedto
measurepitchranking.Theyfoundthatdeactivationofelectrodeswithpoorpitch
ranking,resultedinnosignificantimprovementinspeechperceptionscorewhen
comparedtotheclinicalprogramme,andinfactledtoworsespectralresolutionas
measuredwiththespectral-temporallymodulatedrippletest(SMRT).Interestingly,
deactivationofelectrodeswithgoodpitchrankingresultedinsimilarspeech
35
perceptionscorestothatwhenelectrodeswithpoorpitchrankingweredeactivated.
Theauthorshypothesizedthatthelackofbenefitwasduetothefactthatonlyasmall
numberofelectrodesweredeactivated.Furthermore,thebenefitsofdeactivationmay
nothavebeenapparentwiththen-of-mstrategyutilizedinACE,inwhichonlya
proportionoftheavailableelectrodesareactiveatasinglepointintime.
Pitchrankingprovidesmorefunctionalinformationthanelectrodediscrimination.
However,itisamorechallengingtasktoperform,particularlyforyoungchildrenand
early-deafenedlate-implantedindividuals.Asdescribedabove,optimisationoftheCI
programmebasedonthepitchrankinghasledtomixedresults.
1.5.1.3Multidimensionalscaling
Multidimensionalscaling(MDS)isatechniquewhichisusedtoratetheperceptual
differencebetweenelectrodepairsandtakesintoaccountthepossibilitythatmultiple
percepts,ratherthanpitchalone,maychangewithelectrodelocation(McKayetal.,
1996).WithMDS,loudnessbalancedelectrodepairsarestimulatedinsequenceand
participantsratethedifferencebetweenthemonacontinuousscale.Thisprocedureis
performedforallpossibleelectrodepairsandcanbeusedtocalculateastimulus
spaceinwhichthedistancesbetweenelectrodesisrelatedtotherelativeperceptual
dissimilaritybetweenthem.TheresultsofMDScanbeusedtoguideelectrode
selection.Forexample,HenshallandMcKay(2001),deactivatedelectrodesthat
accordingtotheMDSstimulusspacewerenottonotopicallyordered,butthisdidnot
resultinimprovedspeechperception.McKayetal.(2002),createdanexperimental
programmebyselectingthe10electrodeswiththebestdiscriminationbasedonMDS
measurements.However,theexperimentalprogrammeresultedinequivalentor
worseoutcomeonvariousmeasuresofspeechperceptioncomparedtotheclinical
map.
MDSmeasurementsrequiretestingofallelectrodepairs,whichistimeconsumingand
limitsitsclinicalapplicability.FittingbasedonMDSalsoassumesthatperceptsacross
alldimensionsshouldchangeinanorderlyfashionalongtheelectrodearray.Whilst
thisistrueforpitch,itisnotknownhowtheperceptassociatedwithotherdimensions
36
shouldchange.Thistoomayunderliethelackofbenefitofre-programmingbasedon
MDSintheabovestudies.
1.5.1.4Psychophysicaltuningcurves
ChannelinteractionscanbemeasuredusingPTCs.Theseassessmentsarebasedonthe
principleofforwardmasking,wherebythethresholdofaprobestimuluscanbe
increasedbyapriormaskerstimulusdependingonthelevelofinteractionbetween
theprobeandmaskerelectrodes.Ifprobeandmaskerelectrodesstimulatesimilar
populationsofauditoryneurons,thentheprobethresholdisexpectedtoincreasebya
greateramount.PTCscanbemeasuredbymeasuringthethresholdofafixedprobe
electrodewhilstvaryingthemaskerelectrodelocation.ThePTCforasingleelectrode
therefore,providesanassessmentofhowthatelectrodeinteractswitheveryother
electrodeonthearray.TheshapeofthePTCscanvarysubstantiallyacrossthe
electrodearraywithinCIusers(Chatterjeeetal.,2006;Nelsonetal.,2008).PTCshave
anumberofinformativefeatures.Forexample,theremaybebroadeningorflattening
ofthePTCpeak,whichimpliesgreaterinteractionbetweenadjacentelectrodes
(Chatterjeeetal.,2006;ChatterjeeandShannon,1998;Nelsonetal.,2008).PTCscan
displaytipshifts,whereby,thegreatestlevelofmaskingisnotproducedwhenthe
maskerelectrodeisthesameastheprobeelectrode.Ithasbeenhypothesizedthat
thisindicatesthepresenceofaneuraldeadregionatthesiteoftheprobeelectrode.
PTCsmayalsodisplaysecondarypeaks-inthesecases,anadditionalarearemote
fromthesiteoftheprobeelectrodecausessignificantmasking.Itisthoughtthatthis
effectmayduetothepresenceofcrossturnstimulation(Nelsonetal.,2008).
PreviousstudieshavenotshownaconsistentrelationshipbetweenPTCmeasuresof
spatialtuningandspeechperception(Andersonetal.,2011;Boëxetal.,2003;Hughes
andStille,2008;ThrockmortonandCollins,1999).Furthermore,thesemeasurements
areverytimeconsuming,whichmakethemimpracticalforclinicalapplication.
37
1.5.2Objectivesmeasuresofchannelinteractions
Behaviouralmeasurementsofchannelinteractionsaredependentonattention,
cognitionandlinguisticability.Thiscanreducetheirreliabilityandmakesthem
unfeasibleinveryyoungchildren.Thislimitationcanbeovercomewiththeuseof
objectiveelectrophysiologicalmeasurementsthatnotrequireactiveparticipationinan
auditorytask.Thesetechniquesinvolvemeasuringtheneuralresponsetosound
stimuliatvariouslevelsoftheauditorypathway.Theobjectivesmeasuresofchannel
interactionsaresummarizedinthefollowingsections.
1.5.2.1ECAPchannelinteractionfunctions
ECAPscanbemeasuredbystimulatingindividualelectrodesandmeasuringthe
responseoftheauditorynervefromneighbouringintra-cochlearelectrodes.Similarto
PTCs,ECAPchannelinteractionfunction(CIFs)(Cohenetal.,2003)arebasedonthe
principleofforward-masking.ThereductionintheECAPresponseamplitudeofthe
probeelectrode,duetoaprecedingmasker,isassumedtoreflecttheamountof
overlapintheirstimulationfields.CIFsaretypicallyobtainedbymeasuringtheECAP
responseamplitudetoafixedprobe,whilstvaryingthelocationofthemaskeracross
thearray.ElectrophysiologicalrecordingsinCIusersareaffectedbyartefacts
associatedwithelectricalstimulationfromthedevice.Theartefactcanbemeasured
byrecordingtheresponsetothemaskerandprobepresentedinisolation,andusinga
subtractiontechniquetoisolatetheneuralresponse.Thespreadofexcitationwith
ECAPCIFsisusuallyquantifiedbymeasuringthefunctionwidth.Ingeneral,the
excitationprofileobtainedwithECAPCIFsshowsgoodagreementwithPTCs,though
thereissomeinter-individualvariability(Cohenetal.,2003;HughesandStille,2008).
TheECAPCIFcanalsobeusedtocalculateametriccalledthechannelseparationindex
(CSI)whichprovidesameasureofthenon-overlapinexcitationfieldsoftwo
electrodes(ScheperleandAbbas,2015a).TheCSIiscalculatedfromthedifference
betweentheCIFfunctionsoftwoelectrodesacrossthewholearray,withagreaterCSI
valueimplyinglessoverlap.HughesandAbbas(2006),showedthattheCSI,butnot
38
theCIFwidth,wascorrelatedwithpitchrankingability,suggestingthattheCSIisa
betterparameterforquantifyingspreadofexcitationfromCIFs.
MoststudieshavenotrevealedacorrelationbetweenECAPCIFmeasuresandspeech
perception(Cohenetal.,2003;HughesandAbbas,2006;HughesandStille,2008;van
derBeeketal.,2012).Morerecently,ScheperleandAbbas(2015a),examinedthe
relationshipbetweentheCSIandspeechperception.Threeexperimentalprogrammes
with7activeelectrodewerecreatedinordertovarythelikelihoodofchannel
interactions.Thiswasdonebyselectingeitheradjacentelectrodes,everysecond
electrodeoreverythirdelectrodefromtheCIarrayforeachoftheprogrammes.The
within-subjectanalysisinthisstudyshowedasignificantpositiverelationshipbetween
theCSIandspeechperception.However,theprogrammewiththelargestelectrode
separation,whichalsohadthelargestCSI,wasthemostsimilartotheuser’sclinical
programmeandthismayhaveconfoundedtheanalysis.Norelationshipbetweenthe
CSIandspeechperceptionwasfoundinthebetween-subjectanalysis.Duetothe
withinandbetweensubjectvariabilityinCIFs,thereisnocleardefinitionofwhat
constitutesasignificantinteractionandre-programminginterventionsbasedonECAP
CIFs,havenotyetbeenperformed.
1.5.2.2EABRmonauralinteractioncomponent
ChannelinteractionshavealsobeenassessedwiththeEABR.Gueveraetal.(2016)
measuredtheEABRtosimultaneousstimulationof4electrodesonthearray.In
addition,theEABRforeachoftheelectrodeswasmeasuredindividually.Amonaural
interactioncomponent(MIC)wascalculatedastheratioofthesumoftheindividual
responsestothesimultaneousresponse–alargeMICwashypothesizedtoindicate
greaterlevelsofchannelinteractions.ItwasfoundthatthesizeoftheMICwas
negativelycorrelatedwithperformanceonavowel-consonant-voweltest.Whilstthis
techniqueappearspromising,itrequiresfurthervalidation.Itwouldalsobeusefulto
measuretheMICforelectrodepairs,toprovideamorespatiallyspecificmeasureof
channelinteractions.Furthermore,ifthesemeasurementsaretobeusedtoguide
clinicalinterventionsinCIusers,itwillbenecessarytodefinewhatconstitutesa
significantinteractionbasedontheMIC.
39
1.5.2.3Corticalmeasuresofchannelinteractions
CAEPscanbeusedtoobjectivelyassesselectrodediscrimination,whichasdescribed
earlier,providesameasureofchannelinteractions.CAEPstakeintoaccountcentralas
wellasperipheralauditoryprocessingandthereforemayprovideamorefunctionally
relevantassessmentofchannelinteractionscomparedtotheECAPorEABR
measurements.TheCAEPsthatcanbeusedtoassessdiscriminationincludethe
mismatchnegativityresponse(MMN),theP300andtheACC.Thefocusofthisthesisis
theACCasameasureofelectrodediscrimination.Therefore,thebackgroundtoCAEPs
andtheirmeasurementwillbeprovidedinthefollowingsection.
1.6CorticalresponsemeasurementsinCIusers
1.6.1TheP1-N1-P2complex
CAEPscanbeevokedbyarangeofstimuliincludingclicks,tone-complexesand
speech.CAEPmeasurementsrequirethatparticipantsareawake,thoughnot
necessarilyattendingtotheauditorystimulus.Broadly,therearetwotypeofCAEPsi)
obligatoryresponses(alsotermedexogenousresponses),whichcanberecorded
duringpassivelisteningandii)endogenousresponses,whicharerecordedduring
activelisteningandwhosecharacteristicsvarywiththecognitivedemandofthetask
(Cone-WessonandWunderlich,2003).
ThemostcommonlystudiedCAEPisthecorticalonsetresponse,anobligatoryCAEP
thatoccurswhenthereisatransitionfromsilencetosound.Thisresponsetypically
occursatalatencyof50to300msaftersoundonsetandischaracterizedbytheP1-
N1-P2complex.TheP1,N1andP2waveshavebeenshowntohaveanumberof
generatorsinthebrain–themeasuredwavethereforerepresentsthesummationof
brainactivityfrommultiplesources(CrowleyandColrain,2004;Huotilainenetal.,
1998;Liégeois-Chauveletal.,1994;NäätänenandPicton,1987).Whilstinyoung
children,theP1responsedominatestheCAEP,N1andP2wavesaremoreprominent
inadultsandareusuallyusedtoevaluateauditoryprocessing.Theonsetresponseis
sensitivetostimulusfeaturessuchasfrequency,duration,intensityandinterstimulus
40
interval(ISI)aswellassubjectfactorssuchasage,wakefulnessandattention(Picton,
2010).Furthermore,theonsetresponseisaffectedbytheintegrityoftheauditory
pathway–ithasthereforebeenusedtoassesshearingthresholdsandhasgained
widespreadclinicaluseforthispurpose(LightfootandKennedy,2006).
TheonsetresponsehasbeenwidelyusedtostudythehearingpathwayinCIusers.A
numberofwell-knownstudieshaveusedCAEPmeasurementstoassessmaturationof
theauditorysysteminchildren(Pontonetal.,1996;PontonandEggermont,2001;
Sharmaetal.,2005a).Sharmaetal.(2005),showedthatinchildrenimplantedbefore
theageof3.5years,therewasrapiddevelopmentoftheCAEPcharacterizedbya
reductioninP1latencytowithinnormallimits.Incontrast,implantationaftertheage
of7wascharacterizedbyabnormalCAEPmorphologyandprolongedP1latencies.This
studyprovidedevidenceforasensitiveperiodofauditorydevelopmentinchildren.
Corticalonsetresponsecharacteristicshavebeencorrelatedwithspeechperceptionin
CIusers(Kellyetal.,2005;Makhdoumetal.,1998),suggestingthatthese
measurementscouldbeusedtoobjectivelyassesshearingbenefitwithaCI.More
recently,Visrametal.(2015)showedthatthecorticalonsetresponsethresholdswere
highlycorrelatedwithbehaviouralthresholds.ThisraisesthepossibilityofusingCAEPs
todeterminestimulationlevelsduringCIfitting.
1.6.2RecordingCAEPs
Whenasoundispresentedtotheauditorysystemanelectricalsignalistransmitted
throughthenervoussystemtotheauditorycortex.Itispossibletorecordthese
electricalsignalsfromthescalpnon-invasivelyusingelectro-encephalography(EEG)
(Luck,2005).Theelectricalpotentialofindividualneuronsistoosmalltoberecorded
fromthescalp.Rather,EEGrecordsvoltageduetothesynchronousactivityof
thousandsormillionsofneuronswhichhaveasimilarspatialorientation.Itisthought
thatEEGsignalspredominantlyrepresentpost-synapticpotentialsfrompyramidalcells
-thesecellslieperpendiculartothesurfaceoftheauditorycortexandarewellaligned
witheachother.Ascurrentflowsfromthebrain,throughthecerebrospinalfluid,skull
andscalptissue,itbecomesmoredispersedandattenuated,andthereforeactivity
fromdeepbrainregionsaremoredifficulttorecord.
41
Inadditiontoelectricalactivityfromthebrain,EEGsystemspickupbiologicaland
environmentalsourcesofelectricalnoise.EEGsystemsutilizedifferentialamplifiers
thatamplifythedifferencebetweenanactiveandreferenceelectroderelativetoa
groundelectrode.Thisprocessalsoremovessourcesofnoisewhicharecommonto
theactiveandreferenceelectrodes.Ananalog-to-digitalconverterthensamplesthe
EEGsignalandconvertsthevoltagefluctuationsintonumericalrepresentations.The
EEGsignalisthenusuallyfiltereddigitallyinordertoreducenoise.Highpassfiltering
removeslowfrequencynoiseduetomovementorchangesintheconductanceofthe
skinwhilstlowpassfilteringremoveshigherfrequencynoiseduetomuscle
contractionorelectricallinenoise(typically50-60Hz).Inaddition,specialized,artefact
reductiontechniquescanbeusedtoremoveartefacts,duetoeyemovementsorthe
heartbeat,forexample.
CAEPsaretimelockedtotheauditorystimuluswhilstmostsourcesofnoiseoccur
randomly.Therefore,bymeasuringtheevokedresponsepotentialovermanytrials
andaveragingtheEEGsignal,thebrainresponseisconsolidatedwhilstthenoiseis
attenuated.WhilstCAEPscanberecordedwithaslittleas3electrodes(active,
referenceandground),theuseofhighdensityrecording(eg64-128scalpchannels)
allowstheEEGsignaltobemeasuredatagreaternumberoflocations.Thiscanbe
particularlyusefulfornoisereductionalgorithmsaswellasforsourcelocalizationin
ordertoinvestigatetheEEGsignalgeneratorsiteswithinthebrain(Jatoietal.,2014).
1.6.3TheproblemsofCIartefact
CAEPrecordingsinCIusersrepresentaspecialcase,duetothepresenceoflarge
electricalartefactswhichcanbeseveralhundredtimestheamplitudeofthecortical
response(McLaughlinetal.,2013).ThecharacteristicsoftheCIartefactvarybetween
devicesandstimulationstrategy(Martin,2007;Violaetal.,2011)andconsistofa
numberofcomponentsi)Theradiofrequencycoilartefact,whichisintheMegahertz
rangeandistypicallyremovedbythelow-passfilterinthehardwareofEEGrecording
systemsii)Ahighfrequencyartefactrelatedtothepulsetrainsdeliveredthroughthe
CIarray-thiscanberemovedbyusingadigitallowpassfilterofaround30-40HzasCI
42
stimulationratesareusuallymuchhigherii)Directcurrent(DC)artefactwhichhasa
similaronsetandoffsettotheelectricalstimulus.Thisisthoughttoberelatedtoa
capacitanceeffectattheEEGchannel-scalpinterfaceortheCIelectrode-neuron
interface.TheDCartefactcanbeparticularlyproblematictoremove.
AnumberofmethodshavebeenusedtoreduceCIartefact(HofmannandWouters,
2010;Martin,2007).Theseincludetheuseofveryshortdurationstimuliwhichdonot
overlapwiththeCAEP,choosingareferenceelectrodelocationthatminimizesartefact
pickupandusingalternatingpolaritystimuli,whichreducestheeffectofpolarity
dependentartefacts.TheDCartefactcanalsominimizedbyensuringsimilarlowlevels
ofimpedanceontherecordingscalpchannels(McLaughlinetal.,2013).Despiteusing
thesemethods,substantialCIartefactmaystillbepresentandeffectivetechniquesare
thenrequiredtoremovethese.McLaughlinetal.(2013),haveshownthatitis
possibletoremovetheDCartefactbymodellingitfromthepulseamplitudeofthe
stimulus.Thistechniqueappearstobefeasibleevenwhenusingalimitednumberof
recordingchannels.AnalternativeapproachistousehighdensityEEGscalp
recordings.Thecorticalresponseandartefactsaremeasuredacrossthewholescalp
andthisallowsremovaloftheartefactusingtechniquessuchasbeamforming,spatial
filtering,principalcomponentanalysisandindependentcomponentanalysis(Campos
Violaetal.,2009;Martin,2007;WongandGordon,2009).Usinghighdensity
recordingsismoretimeconsumingbothintermsofdatacollectionanddata
processing.However,thesetechniqueshavebeenwidelyusedinCIusersandmaybe
morereliableformodellingandremovingartefactsfromdifferentdevicesand
individuals.
1.6.4Corticalmeasuresofdiscrimination
Inadditiontoassessingsounddetection,CAEPscanbeusedtoassessauditory
discrimination.Thisformsthebasisoftheiruseformeasuringchannelinteractions.A
summaryofthediscriminatoryCAEPsfollows.
43
1.6.4.1TheMMN
TheMMNisanobligatoryresponse,whichcanberecordedinapassivelistening
condition.Itisrecordedwithanoddballparadigmconsistingoffrequentstandard
stimuliandraredeviantstimuli(forareviewseeNäätänenetal.,2017).TheMMNis
usuallyseenasalatenegativityinthedifferencewavebetweentheresponsestothe
standardanddeviantstimuli.TheMMNcanbeusedasameasureofdiscriminationof
stimulusduration,frequencyandloudness.Inaddition,MMNcharacteristicssuchas
latencyandamplitudearewellcorrelatedwithpsychophysicalmeasurementsof
auditorydiscrimination(Näätänenetal.,2017).Typically,theratioofstandardto
deviantstimuliis4:1.Thismeansthatthedeviantstimulusisonlypresented20%of
thetimeandasaresult,alargenumberoftrialsareusuallyneededtorecordthe
MMN,whichmakesitatimeconsumingmeasurement.Moreefficient‘multi-feature’
MMNrecordingparadigmshavebeendevelopedbuttherearelimitednumbersof
studiesusingthesetechniquesinCIusers(Näätänenetal.,2017;Sandmannetal.,
2010).
TheMMNresponseisusuallysmallandalackofsensitivityattheindividuallevelhas
beenreportedbyanumberofinvestigators(BishopandHardiman,2010;Picton,1995;
Singhetal.,2004).TheMMNhasbeenusedasameasureofelectrodediscrimination
inCIusersinasinglestudy(Wableetal.,2000)inwhichthestandardanddeviant
stimuliwerepresentedbystimulatingdifferentelectrodes.InthestudybyWableetal.
(2000),itwasfoundthattheMMNcouldbemeasuredforvariouselectrodecontrasts
atthegrouplevelbutdataforindividualCIuserswasnotpresented.Nocorrelation
betweenspeechperceptionscoresandtheMMNwasfound.Thelackofrecording
efficiencyaswellasthepoorsensitivityattheindividuallevel,limitstheuseofthe
MMNasameasureofchannelinteractionsinCIusers.
1.6.4.2P300
TheP300isanendogenousCAEPthatprovidesanobjectiveassessmentofauditory
attentionanddiscrimination.LiketheMMN,itisrecordedwithanoddballparadigm
buttheparticipantisrequiredtoattendandrespondtothedeviantstimulus,for
examplebypressingabutton.TheP300isseenasapositivewaveoccurringata
44
latencyofaround300mstothedeviantstimulus.ThecharacteristicsoftheP300
responseareaffectedbytheprobabilityofoccurrenceofthedeviantstimulus,the
difficultyoftheauditorytaskaswellastheamountofeffortthataparticipantdevotes
tothetask(Luck,2005).AnumberofstudieshavefoundarelationshipbetweenP300
amplitudes/latenciesandspeechperceptioninCIusers(Groenenetal.,1996;Kilenyet
al.,1997;Kuboetal.,2001).Todate,theP300hasnotbeenusedtoassesselectrode
discriminationinCIusers.Asthesemeasurementsrequireactiveparticipationinan
auditorytask,theyofferlimitedbenefitcomparedtobehaviouralmeasuresof
electrodediscrimination.
1.6.4.3Theacousticchangecomplex
AnotherdiscriminatoryCAEP,whichhasgainedmuchinterestinrecentyears,is
acousticchangecomplex(alsoreferredtoastheauditorychangecomplexorACC).
ThisisanobligatoryCAEPthatoccursinresponsetoachangeinanongoingstimulus.
Theresponsetotheinitialpartofthestimulusisacorticalonsetresponse,which
occursduetoachangefromsilencetosound.Thesubsequentresponse,whichoccurs
duetoachangeintheongoingstimulus,istheACC.BoththeonsetandACCresponses
havesimilarmorphologiesanditisthoughtthatsimilarprocessesunderliethese
CAEPs.InordertorecordtheACC,itisnecessarytouselongdurationstimuliofseveral
hundredmillisecondsduration,sothatititisnotmaskedbythecorticalonset
response.
AmajoradvantageoftheACCovertheMMNisthatitcanberecordedwithgreater
efficiency.Withoddballparadigms,thedeviantstimulusistypicallypresentedon20%
oftrials,whilstforACCparadigmsthereisanacousticchangeoneverytrial.Martin
andBoothroyd(1999),reportedthattheaverageamplitudeoftheACCwas2.5times
largerthanthatoftheMMNandconcludedthattheACCprovidesamoresensitive
indexofdiscriminationcapacity.Furthermore,theACChasahightest-retestreliability
(FriesenandTremblay,2006;Tremblayetal.,2003)andthereisacloserelationship
betweenbehaviouraldiscriminationthresholdsandACCthresholds(Atchersonetal.,
2009;Heetal.,2012;Michalewskietal.,2005).Forexample,Heetal.(2012)
measuredbehaviouraldiscriminationandACCthresholdsin26NHadults.Themean
45
intensitydiscriminationthresholdwas1.77dBforbehaviouralmeasurementsand2dB
forACCmeasurements.Themeanfrequencydiscriminationthresholdwas3.55Hzfor
behaviouralmeasurementsand5.81HzfortheACC.Itwasfoundthatincreasingthe
magnitudeofchangeacrossdifferentacousticdimensions,ledtoconsistentchangesin
theACCamplitudebutnottheACClatency,indicatingthattheformerisabetter
measureofauditorydiscrimination.
AnumberofinvestigatorshavemeasuredtheelectricallyevokedACC(eACC)inCI
users.Friesenetal.(2006),firstmeasuredtheeACCtonaturalspeechtokens.Similar
toNHlisteners,itwasfoundthattheACChadgoodtest-retestreliabilityandthat
differentspeechtokensresultedindistinctACCresponses.Insubsequentstudies,the
eACChasbeenmeasuredtochangesinspectrum,intensityandtemporalgaps(Heet
al.,2013;Kimetal.,2009;Martin,2007).TheeACCtoachangeinplaceofstimulating
electrodehasbeentermedthespatialauditorychangecomplex(spatialACC)
(ScheperleandAbbas,2015b).Thisprovidesanobjectivemeasuresofelectrode
discrimination.StudiesrelatingtothespatialACCshallbereviewedinthefollowing
section.
1.7ThespatialACC
Brownetal.(2008),firstmeasuredthespatialACCin9post-linguallydeafadultswitha
Cochleardevice.AlloftheparticipantsintheirstudyhadbeenusingtheirCIforatleast
1year.Ingeneral,itwasfoundthattherewasamonotonicrelationshipbetween
electrodeseparationandACCamplitudei.e.asseparationincreased,spatialACC
amplitudealsoincreased.However,inthisstudy,electrodepairswerenotexplicitly
loudnessbalancedandthereforeitispossiblethatcorticalresponsesoccurreddueto
perceivedchangesinloudness.Therelationshiptobehaviouralelectrode
discriminationwasnotexaminedintheabovestudy.Subsequently,Hoppeetal.
(2010),measuredthespatialACCin16post-linguallydeafenedadultusersofthe
Cochleardevicewhohadbeenusingtheirimplantforatleast6months.Thespatial
ACCwasmeasuredatapical,midandbasalelectrodelocationsineachCIuserafter
loudnessbalancing.A3-AFCtaskwasusedtomeasurebehaviouraldiscriminationand
calculatead’scoreatthesamelocation.ThespatialACCcouldberecordedin88%of
46
cases.Furthermore,asignificantbutrelativelyweakcorrelationwasfoundbetween
thed’scoreandACCamplitudeandlatency.
Heetal.(2014),measuredtherelationshipbetweenthespatialACCandbehavioural
discriminationin15childrenwithauditoryneuropathyspectrumdisorder(ANSD).The
childrenintheirstudyallhadaCochleardeviceandhadbeenusingtheirCIforatleast
9months.LoudnessbalancingwasperformedandEDLsweremeasuredarounda
singleelectrodeinthemiddleofthearray,usingbothspatialACCandbehavioural
measuresofelectrodediscrimination.AspatialACC‘pass’wasdefinedontwocriteria:
i)mutualagreementbasedonvisualinspectionby2ratersii)rootmeansquared
(RMS)amplitudeoftheACCatleast50%greaterthanthatofthenoisefloor.
Behaviouralelectrodediscriminationwasmeasuredwitha2-AFCtaskandapasswas
definedasacorrectresponseforatleast4out6trials.Heetal.(2014),showedthat
thereisastrongrelationshipbetweenspatialACCandbehaviouralmeasuredof
electrodediscrimination.UnlikeBrownetal.(2008),anon-monotonicrelationship
betweenelectrodeseparationandspatialACCamplitudewasfound.Ofnote,spatial
ACCEDLsandACCamplitudesweresignificantlydifferentbetweengroupsofchildren
withgoodandpooropen-setspeechperception.
ScheperleandAbbas(2015b),examinedtherelationshipbetweenperipheraland
centralmeasuresofchannelinteractionsbymeasuringECAPCIFsandthespatialACC
in11post-linguallydeafenedadults.Alloftheparticipantshadatleast15monthsof
experiencewithaCochleardevice.Aperipheralmeasureofchannelinteractionsfor
electrodepairswascalculatedusingtheCSI.TherelationshipbetweentheCSIand
spatialACCamplitudeswasmodelledusingasaturatingexponentialfunction.
Althoughasignificantrelationshipwasfound,therewassubstantialvariationinthe
natureofthisrelationshipbetweenparticipants.ThefactthatACCamplitudewas
partiallyindependentoftheperipheralmeasuresofspatialselectivity,wasinterpreted
asprovidingevidenceofvariationincentralprocessingbetweenCIusers.Itwas
hypothesizedthatthedifferenceincentralprocessingmightaccountforthefailureto
findarelationshipbetweenECAPCIFsandspeechperceptioninpreviousstudies(as
describedinsection1.4.2.1).
47
Inafollow-upstudy,ScheperleandAbbas(2015a),examinedtherelationshipbetween
speechperceptionandcentralaswellasperipheralmeasuresofspatialselectivityin
thesameparticipants.Asdescribedinsection1.5.2.1,threeexperimentalmapswhich
variedintheirlikelihoodofchannelinteractionwerecreated.ECAPCIFswere
measuredandtheCSIwascalculatedforalladjacentpairsofelectrodes.Inaddition,
theindividualexponentialfunctionfromthefirststudywasusedtopredictthespatial
ACCamplitudeforadjacentelectrodepairsfromtheCSI.Thewithin-subjectanalysis
showedthatCSIandspatialACCamplitudeweresignificantpredictorsofspeech
perception,withtheCSIbeingthestrongerpredictor.Intheacrosssubjectanalysis,it
wasfoundthatspatialACCamplitudebutnotECAPCSIwassignificantlycorrelated
withspeechperception.
1.8Summaryandrationaleforthisstudy
MultiplelinesofevidenceshowthatthechannelsonaCIarrayarenon-independent.
Thepresenceofsubstantialchannelinteractionsandtheassociatedlossofspectral
resolution,maycontributetopooroutcomesinincertainCIusers.Althoughelectrode
discriminationprovidesafairlycoarsemeasureofchannelinteractionscomparedto
othertechniques,itiseasyandquicktomeasure.Furthermore,thefindingofpoor
electrodediscriminationissignificantasitimpliesthatthesoundsignalfromtheCIis
notbeingpreservedintheauditorypathway.Previousstudieshaveshownthatpoor
electrodediscriminationinCIusersisnotuncommonandthatthisisrelatedtopoor
speechperception.Furthermore,thereisevidencetosuggestthatidentificationof
areasofpoordiscriminationontheCIarray,mayallowinterventionsthatimprove
hearingoutcomesuchasauditorytrainingorre-programmingoftheCI.
Behaviouralassessmentsofelectrodediscriminationaredependentoncognition,
attentionandlanguage,whichlimitstheiruseindifficulttotestpatientgroupssuchas
youngchildren.ThislimitationmaybesurmountedbytheuseofthespatialACC,
whichisanobligatoryCAEPthatprovidesanobjectiveassessmentofelectrode
discrimination.PreviousstudiesofthespatialACChaveshownthatitisrelatedto
behaviouralmeasuresofelectrodediscriminationaswellasspeechperception.This
raisesthepossibilityofusingthisobjectivemeasuretoguideclinicalinterventionsthat
leadtoimprovedhearingoutcome.However,furthercharacterizationofthespatial
48
ACCisrequiredifitistobeusedasaclinicaltool.Furthermore,theaforementioned
studiesofthespatialACCsufferfromanumberoflimitationswhichshallbeoutlined
below.
Todate,thespatialACChasonlybeenmeasuredinrelativelyexperiencedCIusersand
itsdevelopmentovertimeisyettobedetermined.Previousstudiesinchildrenand
adults,haveshownthatcorticalresponsesundergosignificantmorphologicalchanges
duringthefirst6monthsafterswitch-on(Burdoetal.,2006;Jordanetal.,1997;
Pantev,2005;PontonandEggermont,2001;Sharmaetal.,2005a).Corticalresponses
inCIusersaretypicallysmallimmediatelyafterswitch-onandamplitudeincreases
withhearingexperience(Burdoetal.,2006;Sandmannetal.,2015).Itthereforemay
notbefeasibletomeasuretheACCintheearlyperiodafterswitch-on.Early
assessmentofelectrodediscriminationcouldhelptoguidemanagementduringthe
sensitiveperiodofauditorydevelopmentinchildren.Eveninadults,itwouldbeneficial
tousesuchassessmentstooptimizehearingperformanceassoonaspossible.Itwill
alsobeimportanttounderstandhowthespatialACCdevelopsovertimeinrelationto
behaviouraldiscrimination.If,forexample,thespatialACCdevelopsoveralongperiod
oftimewithCIlisteningexperience,thenprematurelyalteringclinicalmanagementon
thebasisofthesemeasurementsmaybedetrimentaltooutcome.
PreviousstudiesofthespatialACChaveonlyincludedparticipantswithaCochlear
device.Asdiscussedearlier,oneofthechallengeswithmeasuringCAEPsisthe
presenceofCIartefactwhichvariesbetweendevices(Violaetal.,2011).Whenusing
longdurationstimuli,asthefortheACC,theelectrophysiologicalresponsenecessarily
overlapswiththeCIartefact.Martinetal.(2007),measuredtheeACCtoachangein
secondformantfrequencyinanadultwiththeMED-ELdevice.Alargedevicerelated
scalpartefactwaspresentbuttheeACCcouldbeteasedapartusingsignalprocessing
techniques.Hoppeetal.(2010),alsoreportedsignificantscalpartefactwhen
measuringthespatialACCwiththeCochleardevice.ForthespatialACCtobeclinically
usefulitmustbemeasurableindifferentCIdevicesandtechniquesfordealingwith
artefactindifferentdevicesandindividualsarenecessary.
49
FurtherinvestigationintotherelationshipbetweenthespatialACCandbehavioural
electrodediscriminationiswarranted.Asdiscussedearlier,Hoppeetal.(2010),
showedasignificantbutweakrelationshipbetweenspatialACCamplitudeand
behaviourald’score.However,thisstudyincludedrepeatedmeasurementsfrom
individualswhichmayhaveartificiallyincreasedcorrelationcoefficients.Inthestudy
byHeetal.(2014),behaviouralelectrodediscriminationwasassessedwitha2-AFC
taskandapassrequiredatleast4correctresponseson6trials.Withthesecriteria,the
binomialprobabilityofachievingabehaviouralpassbychanceis34%andahighfalse
hitratewouldbeexpected.StrictercriteriashouldbeusedtovalidatethespatialACC
asameasureofelectrodediscrimination.Furthermore,inthestudybyHeetal.(2014),
thecriteriafordefininganACCpassincludedvisualassessmentoftheresponseby2
non-independentraters.Thismayhaveresultedinbiaswhenevaluatingthe
responses.Fromaclinicalpointofview,usingpass-failcriteriaisrelevantasthiscould
helptodeterminemanagementdecisionssuchaselectrodeselectionfordeactivation.
However,itwouldbefairerandquickertousestatisticalcriteriatocomparetheACC
responsetothenoisefloortodeterminethepresenceorabsenceofaresponse,rather
thanusingvisualcriteria.
TherelationshipbetweenthespatialACCandspeechperceptionalsoneedsfurther
examination.AlthoughHeetal.(2014),showedthattheEDLsmeasuredwiththe
spatialACCweresignificantlydifferentbetweengoodandpoorperformers,their
resultsmaynotbegeneralizable.Firstly,theparticipantswerechildrenwithANSDand
secondly,EDLsintheirstudypopulationrangedfrom1to2electrodes.Studiesinnon-
ANSDchildrenandadults,haveshownthatEDLsaremuchmorevariableandcanbeas
largeas9electrodes(BusbyandClark,1996;Dawsonetal.,2000;Kopelovichetal.,
2010;Zwolanetal.,1997).SchepereleandAbbas(2015a),foundthatspatialACC
amplitudewascorrelatedwithspeechperceptionscoresonacontinuousscale,but
thespatialACCamplitudewasnotmeasured,butratherwaspredictedfromECAPCIF
functions.TherelationshipbetweentheCSIandspatialACCvariedsubstantially
betweenindividuals(SchepereleandAbbas,2015b)andtherefore,theaccuracyofthe
predictedspatialACCvaluesisquestionable.
50
Itwillalsobeimportanttogainanunderstandingofhowthecharacteristicsofthe
spatialACCareaffectedbyfactorssuchasstimulusintensity,durationandISI.This
wouldallowasensitiveandefficientrecordingparadigmtobedevelopedforclinical
application.
51
1.9Aims
TheoverallaimofthisthesiswastodeterminewhetherthespatialACCcanbeusedto
assesselectrodediscriminationobjectivelyinCIuserswithaviewtousingthisasa
clinicaltoolforpatientassessment.Thespecificobjectiveswereto:
1) determinewhetherthespatialACCcanbemeasuredinCIdevicesfrom
differentmanufacturers(Chapter3)
2) determinewhetherthespatialACCcanbemeasuredintheearlyperiodafterCI
switch-onandwhetheritrelatestobehaviouralelectrodediscriminationatthis
stage(Chapter3)
3) assesshowbehaviouralandobjectivemeasuresofelectrodediscrimination
developswithCIexperience(Chapter4)
4) determinetherelationshipbetweenthespatialACCandbehaviouralelectrode
discriminationduringthefirstyearafterswitch-on(Chapter4)
5) examinetheeffectofstimulusintensityonthespatialACCandbehavioural
electrodediscrimination(Chapter5)
6) examinetherelationshipbetweenspeechperceptionandelectrode
discrimination,asmeasuredwiththespatialACCandabehaviouraltask
(Chapters3,4and5)
7) determinewhethertherecordingofthespatialACCcanbemademore
efficientandsensitiveforclinicalapplication(pilotstudy,Chapter6)
AppendixAconsistsofananalysisoftest-retestreliability.Thisanalysiswasperformed
retrospectivelywithdatathatwascollected>6monthspostCIactivationaspartof
theaboveexperiments.
52
Chapter2 GeneralMethods
ThissectiondescribescommonmethodologyusedfordatacollectioninChapters3to
5.Furtherdetailsforeachexperimentareprovidedintherelevantsection.InChapter
6,themethodologyforrecordingACCmeasurementswasdevelopedtoimprove
efficiencyandwillbedescribedseparately.
OnlyadultCIparticipantswererecruitedtothisstudy.Allparticipantshadfull
electrodearrayinsertionsandnormalelectrodeimpedances.Demographicdetailsof
participantsineachexperimentareprovidedintherelevantchapter.Thestudieswere
approvedbytheUKNationalHealthServiceResearchEthicsCommittee(14/LO/2076)
andtheUniversityCollegeLondonResearchEthicsCommittee(7161/002).All
participantsprovidedwritteninformedconsentpriortotestingandreceivedasmall
paymentfortakingpartinthestudy.
2.1StimuliforACCmeasurement
StimuliwereadaptedfromBrownetal.(2008).Theparticipantsownsoundprocessor
wasbypassedandelectrodeswerestimulateddirectlywithamonopolarconfiguration
througharesearchinterfacespecifictoeachCImanufacturer(RIB2forMED-ELand
BEDCSforABdevices).Aschematicofstimulithatweretypicallyusedisshownin
figure2.1.Stimuliwere800msindurationandconsistedofbiphasicpulsespresented
atarateof1000ppsandphasedurationof~50µs.Thefirstandlast12msofthe
stimulusconsistedofzeroamplitudepulses,duringwhichtheprocessorstill
communicateswiththeinternalreceiver.Thisperiodwasincludedtoreducepotential
overlapbetweenCIartefactandthecorticalresponse.Stimuliwerepresentedatarate
of0.51HzwhichresultedinanISIof1161ms.WhenmeasuringthespatialACCthere
wasachangeinstimulatingelectrodeat400mswhichisthemidpointofthestimulus.
Thefirstelectrodewillbereferredtoasthe‘referenceelectrode’andthesecond
electrodewillbereferredtoasthe‘testelectrode’.Thecorticalresponseselicitedby
thereferenceandtestelectrodeswillbereferredtoasthe‘onsetresponse’andthe
‘ACC’respectively.
53
Figure2.1SchematicofthestimuliusedformeasuringthespatialACC.Stimuliconsistedof
800msbiphasicelectricalpulsesat1000pulsespersecondwithachangeinstimulating
electrodeatthemidpointofthestimulus.TheISIwas1161ms.Thereferenceelectrodeis
showninredandthetestelectrodeisshowninblue.
2.2Stimulusintensityandloudnessbalancing
Foreachelectrode,thethresholdlevelwasmeasuredwithanascendingmethodof
adjustment.Stimulationbeganatalevelwhichwasinaudibleandincreasedin5µA
stepsuntilparticipantsreportedthattheycouldjusthearasound.Thethresholdlevel
wasdeterminedbyrepeatingthisprocedureuntilthesamevaluewasobtainedtwice
inarow.Themostcomfortablelevelforthereferenceelectrodewasdeterminedby
graduallyincreasingthestimulationleveluntilparticipantsindicatedthattheloudness
wasatpoint6ona10-pointABloudnesschart.Thisprocedurewasrepeatedtwiceand
theaverageofthetwoestimateswastakenastheMClevelofthereferenceelectrode.
ItisknownthattheACCamplitudeisaffectedbychangesinloudnessaswellas
spectrum(Kimetal.,2009;MartinandBoothroyd,2000).Inordertominimize
loudnesscueswhenswitchingtheactiveelectrode,electrodepairswerecarefully
loudnessbalanced.AloudnessbalancingprocedurewasadaptedfromHeetal.(2014).
ThestimulationlevelofthetestelectrodewasinitiallysetattheMClevelofthe
referenceelectrode.Thereferenceandtestelectrodewerethenstimulatedin
sequenceseparatedbyagapof600ms.Basedonfeedbackfromtheparticipant,the
experimenteradjustedthelevelofthetestelectrodeuntilbothstimuliwereperceived
tohavethesameloudness.Thisprocedurewasrepeatedatotalofthreetimesandthe
averagewasusedastheloudnessbalancedMClevelforthetestelectrode.
0 400 800 Time (ms)
Electrode AElectrode B
54
2.3EEGRecording
ResponseswererecordedusingaBioSemiActiveTwoEEGrecordingsystem.
Participantsworeacapwith64channelsarrangedaccordingtotheinternational10–
20system.Thecaplayoutisshowninfigure2.2.Thisapproachofusinghighdensity
scalprecordingswasusedtofacilitateartefactremovalandallowsuccessfulEEG
recordingsinagreaternumberofparticipants.Scalpchannelsoverlyingand
immediatelyadjacenttotheCIreceiverpackagewerenotconnected(typically1-5
electrodes).Twoadditionalchannelswereplacedontheleftandrightmastoid.Eye
movementswererecordedwithrightinfra-orbitalandrightlateralcanthuschannels.
Channelsvoltageoffsetwastypicallykeptbelow20mVandneverexceeded40mV.
Responseswererecordedatasamplingrateof16,384Hzataresolutionof24
bits/sample.Thecut-offfrequencyoftheinternallow-passfilterwas3334Hz.
Figure2.2LayoutoftheBiosemi64channelEEGrecordingcap(Biosemi,2018).
Therewere300epochsforeachconditionandtheorderofconditionswas
randomized.Participantsweregivenabreakevery10minutes.Duringtherecording
55
session,participantssatinacomfortablechairinanacousticallyisolatedsoundbooth
andwatchedasubtitledfilmoftheirchoice.Participantswereencouragedtositasstill
aspossible.
2.4EEGProcessing
Recordingswereprocessedoff-lineusingacustomanalysismoduleinPython2.7
writtenbyDrJaimeUndurraga.UnconnectedandpoorEEGelectrodecontactswere
automaticallydetectedandremovedfromtheanalysis.Dataweredownsampled
(1000Hz),band-passfilteredbetween2-30Hz(zero-phase,third-orderButterworth
filter)andreferencedtothecontralateralmastoid.Eyemovementandeyeblink
artefactwereremovedbymeansofastandardcorrelationsubtraction.EEGresponses
werede-noisedusingspatialfiltering(CheveignéandSimon,2008;Undurragaetal.,
2016)asfollows:
1) EpochsfromeachEEGchannelwerenormalizedandsubmittedtoprincipal
componentanalysis(PCA),wherecomponentswithnegligiblepowerwere
discarded.Theremainingcomponentswerenormalizedtoobtainasetof
orthonormalvectors.
2) Epochsweresubmittedtoabiasfunction.Thedefinitionofthebiasfunction
determinedtherotationmatrixobtainedonasecondPCA,andsoitsdefinition
dependsontheparticularproblem.Sincetheprimarilygoalwastoremovethe
DCcomponentoftheCIartefact,whichislargerthantheneuralresponse,the
biasfunctionwasdefinedasthemean.
3) AsecondPCAwasappliedtodataresultingfromthebiasfunction.This
resultedinarotationmatrixbiasedtowardstheevokedresponseinsteadof
unrelatedeventssuchasresidualeyeblinks,heartactivity,andotherongoing
brainactivity.
4) Therotationmatrixresultingfromstep3wasappliedtotherotationmatrix
obtainedinstep1.Theresultingcomponentswereorderedbydecreasingbias
scoresothattheycouldbedividedintoartefactcomponents(whichwere
discarded),signalcomponents(whichwerekept),andnoisecomponents
(whichwerealsodiscarded).
56
CIartefactwasidentifiedfromindividualcomponentsobtainedinstep4.Eachofthe
componentswereprojectedbacktothesensorspace.Acomponentwasconsidereda
CIartefactwhenthescalpmapshowedacentroidonthesideoftheimplanteddevice,
theamplitudewaslarge,andcomponentactivationsmatchedtheonset/offsetof
stimulation(Debeneretal.,2008).Thiswastypicallythefirstcomponent(theonewith
largestpower)andinafewcasesthesecondorthirdcomponentalsocontainedDC
artefacts.
Per-channeltimeaverageswereobtainedbyapplyingaweightedaveragingmethod
(DonandElberling,1994).Thismethodestimatesthevarianceofthenoisebytracking
oneorseveralfixedpointsovertimefromagivensubsetofconsecutiveepochs.Inthis
study,thepoweroftheresidualnoise(RN)wasestimatedbytracking256isochronal
points(7.5ms),fromasubsetofatleastfiveepochs.Thefinalsizewasdetermined
adaptivelybycomparingthevarianceofsuccessivesubsets(Silva,2009).Asthe
varianceofeachsubsetisknown,thefinalaverageisobtainedbyweightingeach
subsetbytheinverseofitsvariance.
ThepresenceorabsenceoftheACCwasdeterminedobjectivelybymeansofa
Hotelling’st-squared(Hotelling-T2)test(Goldingetal.,2009)whichisamulti-
dimensionalequivalentofthe(squared)univariatet-statistic.Inthiscontext,theEEG
datacanbeconsideredasamultivariatemeasure,i.e.severalsamplesalongatime
windowofinterestwhichencompassesthewaveformregionwheretheresponseis
expected.ThesamplessubmittedtotheHotelling-T2werechosenasinGoldingetal.
(2009).Thatis,withinagivenresponsewindowandforeachepoch,severalsample
binsweredeterminedbyaveragingsamplesevery40ms.Atypicalresponsewindow
hadalengthof200ms,between450–650msafterstimulusonsetfortheACC
response.ThistimewindowwaschosenasittypicallyencompassestheP1,N1andP2
peaksoftheACC.Thisledtoatotalofabout5binsperepoch-equivalenttohaving5
variablesperepoch.These5variables-sampled300timeseach-weresubmittedto
theHotelling-T2testwhichtestedtheprobabilitythatanylinearcombinationofthe5
variableshadameanvaluesignificantlydifferentfromzero.Incertaincases,the
responsewindowwasadjustedto450–700mstoaccountforalateP2,orshortened
to450–600mstoaccountforanabsentP2.AnobjectiveACCpassforanelectrode
57
pairwasdefinedasaHotelling-T2pvalue<0.05inatleast5outof9frontaland
centralscalpchannels,wheretheACCisusuallymostprominent(Cz,C1,C2,Fz,F1,F2,
FCz,FC1andFC2;C=central,F=frontal,FC=fronto-central;suffixzrepresents
midlinelocation,1representslocationtotheleftofmidlineand2representslocation
totherightofmidline).
Anautomaticpeakdetectionalgorithmwasusedtoidentifyevokedresponsepeak
amplitudeandlatency.P1wasdefinedasthemaximumpeakvoltagebetween30-
90msfortheonsetresponseandbetween430and490msfortheACC.N1was
definedastheminimumpeakvoltagebetween70and150msfortheonsetresponse
andbetween470and550msfortheACC.P2wasdefinedasthemaximumpositive
peakvoltageoccurringbetween150and290msfortheonsetresponseand550and
690msfortheACC.Responseswereinspectedvisuallyandthetimewindowswere
adjustedasnecessary.AlthoughtheHotelling-T2wasusedtodeterminewhetherthe
ACCwaspresentorabsent,themagnitudeoftheresponsewasquantifiedby
measuringpeakamplitude.DataarepresentedatthescalplocationFCzunless
otherwisestatedasthemagnitudeoftheACCistypicallylargestatthissite.
2.5Behaviouralelectrodediscrimination
Behaviouralelectrodediscriminationwasdeterminedusinga3-interval2-AFC
paradigm.Thefirstintervalalwayscontainedthereferenceelectrodestimulusandthe
testelectrodestimulusoccurredwithequalprobabilityineitherthesecondorthird
interval.Participantswereinstructedtochoosetheintervalthatwasdifferentand
feedbackwasnotprovided.Stimuliconsistedofalternatingpolaritybiphasicpulse
trainsfromasingleelectrode,withpulserateof1000pps,phasewidthof50µsand
durationof400ms.Eachintervalwas1.4slong.Therewereatotalof20trialsper
electrodepair.Theorderofelectrodepairstestedineachparticipantswasrandomized
whentestingbehaviouraldiscrimination.Abehaviouralpasswasdefinedasascoreof
atleast80%.Thiscut-offwaschosenasithasabinomialprobabilityof<0.01and
reducesthelikelihoodofafalsepositivepass.Inaddition,fromaclinicalpointofview,
ahighcutoffmightbemorerelevantasperformancecouldpotentiallybeimprovedby
addressingelectrodeswithlowerdiscriminationscores.Thebehaviouralscorewas
58
convertedtoad’score.Themaximumd’scorewas2.77basedonacorrectionfactor
forascoreof100%(StanislawandTodorov,1999).
2.6Speechperceptiontesting
SpeechperceptiontestingwasconductedinasoundtreatedboothusingtheAB-York
CrescentofSound(Kittericketal.,2011).Thecrescentofsoundisaspeakerarray,
whichhasbeendevelopedforclinicalandresearchspeechtesting.Forthepurposesof
thisstudyasinglespeakerfromthecentreofthearraywassufficient.Open-set
sentenceandclosed-setvowelperceptionweretested,withnofeedbackprovided.A
singlepresentationofthetestmaterialwasallowedduringeachtrial.Participantsused
theirownsoundprocessorwiththeirpreferredCImapandthenon-CIearwas
unaided.
Open-setsentenceperceptionwastestedwiththeBamford-Kowal-Bench(BKB)test.
Listenerswereaskedtorepeateachsentenceandweregivenascorebasedonthe
numberofkeywordscorrect.Twolistsof16sentences(100words)werechosen
randomlyfortesting.Presentationlevelwas70dBAinquiet.Closed-setvowel
perceptionwastestedwiththeCHEARAuditoryPerceptionTest(CAPT)vowelsub-test
(Vickersetal.,2018).TheCAPTwasusedbecauseitissensitivetospectraldifferences
inhearingaidfittingalgorithms(Marriageetal.,2018).TheCAPTisa4-AFC
monosyllabicword-discriminationtestspokenbyafemaleBritishEnglishspeaker.It
containsfivesetsoffourminimally-contrastiverealwordse.g.cat,cot,cut,cart.
Listenerswereaskedtorespondbychoosingfromfourpicturesonacomputerscreen.
Stimuliwerepresentedat60dBAinquiet.Thislevelwasintendedtobelowerthan
comfortableinordertochallengetheauditorysystemandunderstandhowwellan
individualcanunderstandspeechinnon-idealconditions.Thetestwasrepeatedto
giveatotalscoreoutof40.Thiswasconvertedtoad’scorewithamaximumof3.69
(StanislawandTodorov,1999).
Noneoftheparticipantshadsignificantresidualhearinginthecontralateralearexcept
forparticipantS10(seetable3.2).Itisunlikelythathearingfromthecontralateralear
affectedthisparticipant’sspeechscoresashisunaided(i.e.noCIorhearingaid)BKB
sentencescorewas0%.
59
2.7Statisticalanalysis
AllstatisticalanalyseswereperformedusingtheRsoftwarepackage(RDevelopment
CoreTeam,2015).ParametriccorrelationanalysiswasperformedwithPearson’s
correlationcoefficientandconfidenceintervalswerecalculatedbasedonthestandard
error.Non-parametriccorrelationanalysiswasperformedwithSpearman’srank
correlationcoefficientandconfidenceintervalswerecalculatedusingbootstrapping
with1000repetitions.Linearmixed-effects(LME)modelswereusedtoanalyze
datasetswithrepeatedmeasurementsastheyallowcomplexmodellingofrandom
effectsandcandealwithunbalanceddata(Baayenetal.,2008;Batesetal.,2015).The
factor‘subject’wassetasarandomeffectinthesemodels.Backwardstepwise
reductionwasusedtooptimizethemodel.VisualinspectionofresidualsandCook’s
distancecalculationwereusedtoidentifyoutliersandinfluentialdatapoints.The
effectsizeoffactorswasbasedonanestimateofthesemi-partialR2,whichwas
estimatedwiththeRsoftwarepackage‘r2glmm’(Jaegeretal.,2017).AnR2valueof
0.02–0.13isconsideredsmall,0.13–0.26mediumand>0.26large(Bakeman,2005).
60
Chapter3 ValidationofthespatialACCinadultCIusers
Thischapterisbasedonthefollowingpublishedjournalarticle:
MathewR,UndurragaJ,LiGetal.Objectiveassessmentofelectrodediscrimination
withtheauditorychangecomplexinadultcochlearimplantusers.Hear
Res.2017;354:86-101.doi:10.1016/j.heares.2017.07.008.
3.1Abstract
Thespatialauditorychangecomplex(ACC)isacorticalresponseelicitedbyachangein
placeofstimulation.Todate,thespatialACChasonlybeenmeasuredinrelatively
experiencedcochlearimplant(CI)userswithonetypeofdevice.Earlyassessmentof
electrodediscriminationcouldallowauditorystimulationtobeoptimizedduringa
potentiallysensitiveperiodofauditoryrehabilitation.Inthisstudy,adirectstimulation
paradigmwasusedtomeasurethespatialACCinbothpre-andpost-lingually
deafenedadults.ItisshownthatitisfeasibletomeasurethespatialACCinCIsfrom
differentmanufacturersandasearlyas1weekafterCIswitch-on.ThespatialACChas
astrongrelationshipwithperformanceonabehaviouraldiscriminationtaskandin
somecasesprovidesinformationoverandabovebehaviouraltesting.Thesedatashow
thatthespatialACCisafeasibleandvalidmeasureofelectrodediscriminationinCI
users.
3.2Introduction
SoundprocessingstrategieswithCIsassumethatelectrodesstimulatedistinct
populationsofneuronsinthecochleainatonotopicfashion.IfelectrodeswithintheCI
arrayareindiscriminable,speechcueswillbelostandspeechperceptionmaysuffer.
Thishasbeenconfirmedbyanumberofstudieswhichhaveshownthatpoorelectrode
discrimination,particularlyintheapicalandmidarray,isassociatedwithpoorspeech
perception(Busbyetal.,2000;Dawsonetal.,2000;Henryetal.,2000).Assessmentof
electrodediscriminationabilitymaybeofparticularimportance,asthereisevidence
thatspeechperceptioninindividualswithimpairedelectrodediscrimination,canbe
improvedbydeactivatingindiscriminableelectrodes(Salehetal.,2013;Zwolanetal.,
1997)orbyprovidingauditorytraining(FuandGalvin,2008).Giventhatthereisa
61
sensitiveperiodforauditorydevelopment(HoltandSvirsky,2008;Kraletal.,2006;
Nikolopoulosetal.,1999;Sharmaetal.,2005a),andthatauditoryexperienceduring
thisperiodhaslarge-scaleandlong-termeffects(deVillers-Sidanietal.,2007;Zhanget
al.,2001),itfollowsthatinterventionstooptimizeauditorystimulationthroughtheCI
shouldoccurasearlyaspossible.
TherehasbeengrowinginterestinmeasuringdiscriminationabilityinCIuserswiththe
ACC.Thisisanauditorycorticalpotentialwhichoccursinresponsetoachangeinan
ongoingstimulus.Theadvantageofelectrophysiologicalmeasurementsisthattheydo
notrequireactiveparticipationandcanbeperformedinyoungchildrenincluding
infants(ChenandSmall,2015;Martinezetal.,2013).Inaddition,thereisevidence
thatchangesinelectrophysiologicalmeasurementsprecedechangesinbehavioural
performance(Tremblayetal.,1998).TheACCmaythereforeprovideinformationover
andabovebehaviouraltestingandbeparticularlysuitedtoassessingwhetherstimulus
changeisencodedintheauditorypathwayintheearlyperiodafterCIswitch-on.
TheACCtoachangeinplaceofthestimulatingelectrodehasbeentermedthe‘spatial
ACC’(ScheperleandAbbas,2015b).ThereisevidencethatthespatialACCprovidesa
usefulmeasureofbehaviouraldiscrimination(Heetal.,2014b;Hoppeetal.,2010).
Hoppeetal.(2010)foundasignificantbutweakcorrelationbetweenbehavioural
discriminationd-primescoreandspatialACCamplitude.Heatal.(2014b)measured
therelationshipbetweenthespatialACCandbehaviouraldiscriminationinchildren
withauditoryneuropathyspectrumdisorder(ANSD).Usingpass-failrules,astrong
relationshipbetweenobjectiveandbehaviouralmeasureswasfound.
Todate,thespatialACChasonlybeenmeasuredinrelativelyexperiencedCIusersand
also,onlyinusersoftheCochleardevice.ForthespatialACCtobeclinicallyusefulit
mustbemeasurableindifferentdevices.Oneofthechallengeswithmeasuring
auditorycorticalresponsestolongstimuliisthepresenceofCIartefact,which
overlapstheelectrophysiologicalresponse,andvariesbetweendevicesand
stimulationstrategies(Martin,2007;Violaetal.,2011).Inaddition,itwouldbeuseful
tomeasurethespatialACCintheearlyperiodafterCIswitch-on.Anearlyassessment
ofelectrodediscriminationcouldhelptoguidemanagementduringasensitiveperiod
62
ofauditorydevelopmentinchildren.Eveninadults,itwouldbebeneficialtousesuch
assessmentstooptimizehearingperformanceassoonaspossible.Previousstudies
haveshownthatcorticalresponsesundergosignificantmorphologicalchangesduring
thefirst6monthsafterCIswitch-on(Pantev,2005;PontonandEggermont,2001;
Sharmaetal.,2005a).Pantev(2005),measuredcorticalresponsestofrequencyshifts
withMEGintwoadultswithmagnet-freeCIs.Corticalresponsescouldnotbedetected
intheseparticipantsforthefirst2-3monthsafterswitch-on.Todate,thespatialACC
hasnotbeensuccessfullymeasuredintheearlyperiodafterCIswitch-onandits
relationshiptobehaviouraldiscriminationduringthisperiodisthereforeunknown.
Theobjectivesofthisstudyweretodetermine:
1)whetherthespatialACCcanbemeasuredinindividualswithdifferentCI
manufacturer’sdevices
2)whetheritisfeasibletomeasurethespatialACCinpreandpost-linguallydeafened
adultsasearlyas1weekafterCIswitch-on
3)howthespatialACCisrelatedtobehaviouraldiscriminationduringthisperiod
4)ifthereisarelationshipbetweenmeasuresofelectrodediscriminationandspeech
perception.
Thestudyconsistsoftwoexperiments.Inthefirstexperiment,thespatialACCwas
measuredinexperiencedCIuserswithtwodifferentCImanufacturer’sdevices.Inthe
secondexperiment,thespatialACCwasmeasuredinnewlyimplantedCIusers.
3.3Experiment1:Pilotphase–assessmentandremovalofCIartefact
3.3.1DesignandMethods
3.3.1.1Participants
Therewerefourparticipants,ranginginagefrom18to68years.Allofthemhadbeen
usingtheirCIforatleast2yearsatthetimeoftesting,andhadaunilateralimplant
exceptforparticipantP2,whowasbilaterallyimplanted.Inthisparticipant,theear
whichwassubjectivelyreportedasbeingthebetterhearingearwaschosenfor
63
testing.TwoparticipantshadMED-ELdevicesandtheothertwohadanABdevice.
Demographicdetailsofstudyparticipantsareprovidedintable3.1.
3.3.1.2Testprocedures
Theaimofthisexperimentwastodeterminethefeasibilityofmeasuringthespatial
ACCinABandMED-ELdevices.Forexperiment1,thereferenceelectrodewaschosen
fromthemiddleofthearray.Thereferenceelectrodewaspairedwithanadjacenttest
electrode,whichwasdescribedbytheparticipantasclearlyhavingadifferentpitch.
Electrodepairingsareshownintable3.1.
EEGrecordingswereperformedin3conditionsasshowninfigure3.1.Inthe
‘suprathresholdchange’condition(figure3.1A),thereferenceelectrodewas
stimulatedfor400msfollowedbythetestelectrodeforanother400mswithnogap.
Stimulationlevelwasatthemostcomfortablelevelasdeterminedbytheloudness
balancingproceduredescribedintheGeneralMethods(Chapter2).Inaddition,there
weretwocontrolconditions.Thefirstcontrolconsistedofa‘suprathresholdno
change’condition(figure3.1B)inwhichthereferenceelectrodewasstimulatedfor
800msatthemostcomfortablelevel.Thisconditionwasincludedtoevaluatethe
effectofradiofrequencyorswitchartefactsontherecordings,astheprocessorswere
stillprogrammedto“switch”tothesameelectrodeat400ms.Thesecondcontrolwas
the‘subthresholdchange’condition(figure3.1C),inwhichstimulationlevelwasat10
µAbelowthethresholdlevelforbothtestandreferenceelectrodes.Bymeasuringthe
ACCinasubthresholdstimulationcondition,theCIartefactcanbemeasured
accuratelyandcomparedtoartefactisolatedwithsignalprocessingtechniquesin
suprathresholdstimulationconditions.Theorderofpresentationofconditionswas
randomized.EEGdatawereprocessedasdescribedintheGeneralMethodsandare
presentedatfronto-centralchannels.Inaddition,forexperiment1,dataforthe
averagescalpresponsearepresentedasthisallowsassessmentofwhetherartefact
hasbeenremovedacrossthewholescalp,asopposedtoasinglescalplocation.The
totalexperimentaltimewas1.5hoursforeachparticipant.
Table3.1Demographicdetailsofparticipantsinexperiment1.F=female,M=male,R=right,L=left,ABHR90K=AdvancedBionicsHiRes90K,FS4=Finestructure4,HDCIS=Highdefinitioncontinuousinterleavedsampling
Participant
ID Age Sex Ear
Risk factor for hearing
loss Communication
Duration profound
hearing loss (years)
Duration implant
use (years)
Electrode pair tested Device Electrode Processing
strategy
P1 41 F R Unknown oral 39.5 6 9 and 7 AB HR 90K 1J HiRes
P2 18 M R X linked inheritance oral + sign 10 2 6 and 8
MED-EL
CONCERTO Flex 28 FS4
P3 66 M L Unknown oral 16 9 9 and 11 AB HR 90K 1J HiRes
P4 68 M L
Guillian
Barre Syndrome
oral 5 5 6 and 10 MED-EL SONATA Flex 28 HDCIS
64
65
Figure3.1.Schematicofthestimuliusedinexperiment1.Stimuliconsistedof800msbiphasic
electricalpulsesat1000pulsespersecond.Thetestelectrodeisshowninblueandthe
referenceelectrodeisshowninred.(A)Inthesuprathresholdchangecondition,therewasa
changeinstimulatingelectrodeat400ms.Stimulationwasattheloudnessbalancedmost
comfortablelevel.(B)Inthesuprathresholdnochangecondition,thereferenceelectrodewas
stimulatedcontinuouslyfor800msatthemostcomfortablelevel.(C)Inthesubthreshold
changecondition,therewasachangeinstimulatingelectrodeat400msbutstimulationwasat
10µAbelowthresholdforthereferenceandtestelectrodes.ThisconditionwasincludedtomeasureCIartefactintheabsenceofacorticalresponse.
Suprathreshold change
Suprathreshold no change
Subthreshold change
0ms 400ms 800ms
(A)
(B)
(C)
66
3.3.2Results
3.3.2.1AssessmentofCIartefact
TheCIrelatedartefactvariedbetweenparticipants.ParticipantsP1andP3hadlargeCI
relatedartefactswhichcouldbeisolatedwithspatialfiltering.Thefirstcomponentsof
spatialfilteringforthe‘subthresholdchange’conditionand‘suprathresholdchange’
conditionareshowninfigure3.2.Thiscomponenthasanonsetandoffsetwhich
correspondstothedurationofelectricalstimulationandrepresentsCIDCartefact.
ScalpvoltagemapsshowthelocationofCIartefactonthesideoftheCIdevice.The
scalpartefactwaspredominantlyinthemidlineinparticipantP1butalsoextendedto
thesideoftheCI.InparticipantP3,artefactwaspredominantlyatlateralscalp
channelsonthesideoftheCI.Inneithercasewastherevisibleartefactonthe
contralateralscalpchannelsinanyofthestimulationconditions.Aswitchartefact,
associatedwithchangingthestimulatingelectrodewaspresentinthe‘suprathreshold
change’and‘subthresholdchange’conditions,butnotthe‘nochange’condition.In
participantsP2andP4,whobothhadMED-ELdevices,CIartefactwascomparatively
muchsmalleranddidnotaffecttheACC.
Ascanbeseeninfigure3.2,theCIartefactisolatedinthe‘subthresholdchange’
conditionand‘suprathresholdchange’conditionaresimilarinmorphology.In
participantP1,theartefactwasactuallylargerinthesubthresholdchangecondition
comparedtosuprathresholdchangecondition.ThesizeoftheDCartefactcan
occasionallychangeduringarecordingsessionandthismaybeduetoachangeinthe
impedancemismatchofrecordingelectrodes(McLaughlinetal.,2013).Figure3.3
showsthatspatialfilteringcanbeusedtoeffectivelyremoveCIartefactinthe
suprathresholdchangecondition.TheaveragescalpresponseisshownbeforeCI
artefactremovalinfigure3.3A.Afterremovingthefirstcomponentofspatialfiltering
(showninfigure3.2B),theonsetresponseandACCcanbeclearlyidentified.
67
3.3.2.2ACCinthetestandcontrolconditions
Inallfourparticipants,Hotelling-T2indicatedthattheACCwaspresentinthe
suprathresholdchangeconditionbutabsentinthetwocontrolconditions.Anexample
ofresponsesfromthethreestimulationconditioninparticipantP4isshowninfigure
3.4.Figure3.5showstheN1-P2peakamplitudeoftheonsetandACCresponseforthe
threestimulationconditioninall4participants.Alinearmixed-effectsanalysisofthe
relationshipbetweenN1-P2amplitudeandstimulationconditionacrossscalpchannels
wasperformed.ThedependentvariablewastheN1-P2amplitude.Fixedeffects
included‘condition’(suprathresholdchange,subthresholdchangeandnochange),
‘scalpchannel’(Cz,C1,C2,FCz,FC1,FC2,Fz,F1,andF2)and‘peaktype’(onset
responseorACC).Theinteractiontermfor‘condition’and‘peaktype’wasincludedin
themodelaswell.Thefactor‘scalpchannel’wasremovedfromthemodelasitwas
notsignificant(F(8,199)=0.91,p=0.512).Analysisofvarianceofthereducedmodel
showedthattherewasasignificanteffectof‘condition’(F(2,207)=443,p<0.001),
‘peaktype’(F(1,207)=308,p<0.001)andtheinteractionbetween‘condition’and
‘peaktype’(F(2,207)=75,p<0.001).Theoutputofthemodelisshownintable3.2.
Post-hocpairwisecomparisonswereperformedwithTukeycorrection.Thisshowed
thatfortheACC,therewasasignificantdifferencebetweentheN1-P2amplitudein
thesuprathresholdchangeconditionandbothcontrolconditions(p<0.001)butno
significantdifferencebetweenthetwocontrolconditions(p=0.118).Fortheonset
response,N1-P2amplitudewassignificantlydifferentbetweenall3conditions(p<
0.001).Inthenochangecondition,thesamepopulationofneuronsarestimulatedfor
twiceaslongasinthesuprathresholdchangeconditionineachtrialandneural
refractorinessmayaccountforthesmalleronsetresponseinthiscondition.
68
Table3.2OutputofmixedmodelanalysisoffactorsaffectingcorticalresponseN1-P2
amplitude
Factor
Degreesof
freedom
(numerator,
denominator)
F value Pvalue
Effectsize
95%
confidence
intervalof
effectsize
Initialmodel
Scalp
channel
(8,199) 0.91 0.512 0.035 0.023–0.137
Condition (2,199) 442 <0.001 0.816 0.779–0.850
Peaktype (1,199) 307 <0.001 0.607 0.533–0.675
Peaktype*
Condition
(2,199) 75 <0.001 0.429 0.338–0.521
Reducedmodel
Condition (2,207) 443 <0.001 0.811 0.773–0.845
Peaktype (1,207) 308 <0.001 0.598 0.525–0.666
Peaktype*
Condition
(2,207) 75 <0.001 0.429 0.331–0.512
Figure3.2Scalpvoltagemapsandtimewaveformforthefirstcomponentofspatialfiltering.DataareshownforparticipantsP1andP3inthesubthresholdchangecondition(A)andsuprathresholdchangecondition(B).Timewaveformsshowsthatthiscomponenthasanonsetandoffsetwhichmatchesthedurationofelectricalstimulation.ThiscomponentrepresentstheCIDCartefact.Timewaveformsareshownatthescalplocationwhereamplitudewaslargest-CzislocatedatthevertexandC5islocatedlaterallyontheleftsideofCz.Notethesimilarmorphologyoftheartefactinthesubthresholdandsuprathresholdchangecondition.Meanscalpvoltagemapsbetween50and120msafterstimulusonsetshowthatthedistributionofCIartefactisbiasedtowardsthesideoftheimplant.Isopotentialcontourlinesareshownonscalpvoltagemapswithblacklines.
P1
P3
(A) First component of spatial filtering subthreshold change condition
(B) First component of spatial filtering suprathreshold change condition
69
Figure3.3Corticalresponsesduringthesuprathresholdchangecondition.DataareshownforparticipantsP1andP3(A)Averagescalpresponsereferencedtothecontralateralmastoid,beforeCIartefactremoval.OnsetandoffsetartefactscanbeseeninbothcasesandacorticalresponsecannotbeidentifiedinparticipantP3.ScalpvoltagemapsatpeaktimepointsshowevidenceofCIartefact.(B)AveragescalpresponseafterCIartefactremoval.ClearonsetandACCresponsesarenowseenandscalpvoltagemapsappearnormal.Timewindowsusedtodetectpositiveandnegativepeaksfortheonsetresponse(P1,N1,andP2)andACC(cP1,cN1,andcP2)areshowninpinkandblue,respectively.Thehorizontallinescorrespondtothelevelofresidualnoise.
70
71
Figure3.4Corticalresponsesforthreestimulusconditions.DataareshownatchannelFczforparticipantP4.TheACCisseeninthesuprathresholdchangecondition(A)butnotthenochangecondition(B)orsubthresholdchangecondition(C).Hotelling-T2(HT2)pvaluesareshownoneachpanel.Theshadedareasandhorizontallinesareasdescribedinfigure3.3.
72
Figure3.5.BoxplotofN1-P2amplitudeoftheonsetandACCresponseforthethreestimulusconditions.Eachpointrepresentsadifferentscalplocation(Cz,C1,C2,FCz,FC1,FC2,Fz,F1,andF2)andadifferentcolourisusedforeachparticipant.Theupperandlowerhingesoftheboxplotscorrespondtothefirstandthirdquartiles,whilstthemedianisindicatedbythehorizontallinewithineachbox.
73
3.4Experiment2:MeasurementofACCat1weekafterswitch-on
3.4.1DesignandMethods
3.4.1.1Participants
Forexperiment2,tenparticipants(differenttothoseinexperiment1)wererecruited
andrangedinagefrom42to80years.Threeparticipantshadpre-lingualonsetof
deafnessandalltheothershadpost-lingualonsetofprofounddeafness.Sinceoneof
theobjectivesofthisstudywastoexaminetherelationshipbetweenelectrode
discriminationandspeechperception,participantswiththesamedevicewerechosen
toreducethepotentialvariabilityinoutcomesthatmightbecausedbydifferencesin
theimplantandelectrodearraydesignsuchasinter-electrodedistanceandarray
length.AllparticipantswereunilaterallyimplantedwithanABdeviceandtestedat
approximately1weekafterCIswitch-on(range7-14days).TheABHifocusMid-Scala
electrodewasusedinallparticipants,exceptforS4whohadaHifocus1Jelectrode.
Botharrayshave16electrodecontactsbuttheMid-Scalaelectrodehasanactive
lengthof15mmwithelectrodespacingsof1mm,whilstthe1Jelectrodeisalateral
wallelectrodeandhasanactivelengthof17mmwithelectrodespacingsof~1.1mm.
Demographicdetailsofparticipantsinexperiment2areshownintable3.3.
3.4.1.2TestProcedures
Themainobjectivesofthisexperimentweretodeterminewhetheritispossibleto
measurethespatialACCsoonafterCIswitch-onandhowthismeasurementrelatesto
behaviouralelectrodediscrimination.Asubsidiaryobjectivewastodeterminewhether
objectiveelectrodediscrimination(measuredwiththeACC)andbehaviouralelectrode
discriminationarerelatedtospeechperceptionatthisearlystage.
Onlythesuprathresholdchangeconditionwasusedinthisexperimentandthe
electrodepairs1-2,2-3,3-4and4-5weretested.Thesearetheapicalmostelectrodes
intheABdeviceandtypicallyencodefrequenciesof250-828Hz.Theseelectrodes
encodethefirstformantofvowelsandpreviousstudieshaveshownthattheapical
74
electrodesareimportantforspeechperception(Busbyetal.,2000;GeierandNorton,
1992;Henryetal.,2000).Loudnessbalancingwasperformedasdescribedinthe
GeneralMethods.Electrode3waschosenastheinitialreferenceelectrodeasitliesin
thecentreofthefiveelectrodeschosenfortesting.TheMClevelofelectrode3was
determinedandadjacentelectrodepairswereloudnessbalancedinthefollowing
order:electrode4withelectrode3,electrode5withelectrode4,electrode2with
electrode3andelectrode1withelectrode2.Loudnessbalancingwasperformedthree
timeandtheaveragewasusedasthefinalloudnessbalancedMClevel.Thestandard
deviationofthethreemeasurementswasonaverage4.77µA(range0-13µA).
Forexperiment2,atotalof40electrodepairsweretested(4electrodepairstestedin
10participants).EEGmeasurementsandprocessingwereperformedasdescribedin
theGeneralMethods.TheresponsewindowforHotelling-T2analysiswasadjustedin
4/40cases,to450–700msafterstimulusonset,duetoalateP2component.
Behaviouralelectrodediscriminationwastestedforall4electrodepairs.Speech
perceptiontestingincludedopen-setsentenceswithBKBsentences-in-quiet,and
closed-setvowelperceptionwiththeCAPTvoweltest.Detailsofbehaviouralelectrode
discriminationandspeechtestingareprovidedintheGeneralMethods.EEGand
behaviouraltestingwascompletedinasinglesession,whichlastedapproximately2.5
hoursincludingbreaks.
Table3.3Demographicdetailsofparticipantsinexperiment2.F=female,M=male,R=right,L=left,4F-PTA=fourfrequencypuretoneaverage,CI=cochlearimplant,HR90K=HiRes9
Participant Age Sex Ear Risk factor for
hearing loss Communication
Duration
profound hearing
loss (years)
4F-PTA non
CI ear (dB
HL)
Device Electrode Processing
strategy
S1 51 M R Unknown oral 10 116 HR 90K Mid Scala HiRes Optima-S
S2 50 F R Unknown oral + sign 50 115 HR 90K Mid Scala HiRes Optima-S
S3 42 F L Unknown oral 18 118 HR 90K Mid Scala HiRes Optima-S
S4 48 M L Maternal rubella oral 46 115 HR 90K 1J HiRes Optima-S
S5 47 F L Unknown oral 42 103 HR 90K Mid Scala HiRes Optima-S
S6 68 F L Unknown oral 10 100 HR 90K Mid Scala HiRes Optima-S
S7 57 F L Unknown oral + sign 57 120 HR 90K Mid Scala HiRes-S
S8 51 F R Unknown oral 5 96 HR 90K Mid Scala HiRes Optima-S
S9 48 M L Unknown oral 1 113 HR 90K Mid Scala HiRes Optima-S
S10 80 M L Unknown oral 10 78 HR 90K Mid Scala HiRes Optima-S
75
76
3.4.2Results
3.4.2.1CharacteristicsoftheACC
ThepresenceorabsenceofthespatialACCwasdefinedbasedonHotelling-T2criteria
asdescribedintheGeneralMethods.Thenumberofelectrodepairsthatelicitedan
ACCrangedfrom0-4ineachparticipantasshownintable3.4.TheACCresponse
morphologywassimilartothatoftheonsetresponseandtypicallyconsistedoftheP1-
N1-P2complex.Table3.5showsthepeaklatenciesandamplitudesoftheonsetand
ACCresponses,forrecordingswheretherewasanobjectiveACCpass.Thepeak
latenciesofP1,N1andP2componentsoftheACCresponseweresignificantlylonger
thanthatoftheonsetresponse(two-tailedpairedt-testp<0.001).Inaddition,N1-P2
amplitudeoftheACCwassignificantlysmallerthanthatoftheonsetresponse(paired
t-test,p<0.001).
Table3.4ThenumberofdiscriminableelectrodepairsasdeterminedwithobjectiveACCand
behaviouralcriteriaaswellasspeechperceptionscores.Dataareshownforindividual
participants.
Participant
ACC
Discrimination
Score
Behavioural
Discrimination
Score
Sentencescore
(BKB)(%)
Vowelscore
(CAPT)(%)
S1 2 2 80 65
S2 2 1 0 25
S3 4 4 61 40
S4 1 2 73 42.5
S5 0 0 2 65
S6 1 1 0 20
S7 1 0 0 25
S8 4 4 43 80
S9 4 4 70 82.5
S10 4 4 75 82.5
77
Table3.5Mean,standarddeviationandrangeforpeaklatenciesandpeak-to-peakamplitudes
atchannelFCz.Thefirstcolumnshowstheresponsetype(onsetorACC)andpeaklabel(P1,
N1andP2).
Peaklatencymeasurements(ms)
Waveform
componentMean Standarddeviation Range
OnsetP1 43 8 32-59
ACCP1 58 11 38-78
OnsetN1 101 8 86-121
ACCN1 118 15 97-143
OnsetP2 200 27 159-257
ACCP2 232 36 179-288
PeaktopeakN1-P2amplitude(µV)
Onsetresponse 6.71 1.76 3.27-9.56
ACC 2.96 0.92 1.26-4.60
3.4.2.2RelationshipbetweenbehaviouraldiscriminationandtheACC
3.4.2.2.1Relationshipusingpass-failcriteria
TherelationshipbetweenbehaviouraldiscriminationandthespatialACCwasassessed
usingpass-failrules.Briefly,abehaviouralpasswasdefinedasascoreof≥80%on
behaviouraltesting,andanobjectivepassrequiredasignificantresponse(Hotelling-T2
pvalue<0.05)at>4/9frontalandcentralscalpchannels.Therewasagreement
betweenobjectiveandbehaviouralmeasuresin35/40cases:therewere15electrode
pairswithabehaviouralfailandobjectivefail,20electrodespairswithabehavioural
passandobjectivepass,3electrodepairswithabehaviouralfailandobjectivepass
and2electrodepairswithabehaviouralpassandobjectivefail.Figure3.6showsan
exampleofcorticalresponsesinparticipantS1.Thisshowsthatinthesame
78
participant,theACCisabsentforanelectrodepairwithabehaviouralfail(figure3.6A)
butisclearlypresentforanelectrodepairwithabehaviouralpass(figure3.6B).
Figure3.6CorticalresponsesshowingagreementbetweentheACCandbehavioural
measurements.ResponseatFCzinparticipantS1areshown.Abehaviouralfailisassociated
withanabsentACC(A)whilstabehaviouralpassisassociatedwithaclearACCresponse(B).
Theelectrodepair,behaviouralscoreandHotelling-T2(HT2)pvalueareindicatedoneach
panel.Theshadedareasandhorizontallinesareasdescribedinfigure3.3.
TherelationshipbetweentheACCandbehaviouralmeasurementscanbefurther
examinedaccordingtodeafnessonset.Forthesevenpost-linguallydeafenedadults,
therewasagreementbetweenobjectiveandbehaviouralelectrodediscriminationfor
all28electrodepairs.Forthepre-linguallydeafenedadults,therewasagreement
betweenobjectiveandbehaviouraldiscrimination,for7outof12electrodepairs.
Therewereonlytwocasesfromthesameparticipant(S4)withabehaviouralpassbut
objectivefail.ThisparticipanthadsmallACCresponsesacrossallfourelectrodepairs
(range0.08-1.26µV).The3electrodepairswithanobjectivepassbutbehaviouralfail
werefromthe3pre-linguallydeafenedadults(participantsS2,S4andS7)andare
showninfigure3.7.Ofnote,electrodepair2-3inparticipantS2(figure3.7A)hada
discriminationscoreofonly45%butalargeACCamplitude(4.60µV).Thesedatashow
79
thatanACCresponsemaybepresentintheabsenceofaccuratebehavioural
discrimination.
80
Figure3.7Corticalresponsesfromelectrodepairsthatfailedonbehaviouraltestingbutpassed
onobjectiveACCcriteria.Dataarepresentedatarepresentativescalpchannelwhichisshown
oneachpanelwiththecorrespondingHotelling-T2(HT2)pvalue.Scalpvoltagemapsatpeak
timepointsareshownaboveevokedresponsepotentials,andshowasimilarpatternforthe
onsetandACCresponses.TheparticipantID,electrodepairandbehaviouraldiscrimination
scoreareshownaboveeachpanel.Theshadedareas,horizontallinesandscalpvoltagemaps
areasdescribedinfigure3.3.
81
3.4.2.2.2MixedmodelanalysisofrelationshipbetweenN1-P2peakamplitudeand
behaviouraldiscrimination
ThereappearstobeastrongrelationshipbetweentheACCandelectrode
discriminationwhenusingpass-failrules,especiallyinpost-linguallydeafenedadults.
TherelationshipbetweentheACCamplitudeandbehaviouraldiscriminationwas
examinednext.Abehaviouralpasswassetatascoreof80%apriori,butitispossible
thattheACCisencodedatlowerlevelsofbehaviouraldiscrimination.Theaimofthis
analysistherefore,wastodeterminewhetherelectrode-pairswithintermediate
discriminationscores(e.g.70%)hadlargerACCamplitudesthanthosewith
discriminationscoresaroundchance(e.g.50%).Electrodepairsweredividedinto
threecategoriesbasedonbehaviouraldiscriminationscore:‘poor’(score<60%),
‘intermediate’(score60-79%)and‘good’(score≥80%).Categoriesofbehavioural
discriminationwereusedduetothesmallnumberofparticipantsinthisstudy.Figure
3.8showstheACCN1-P2amplitudeaccordingtobehaviouraldiscriminationcategory.
Alinearmixed-effectsmodelwasusedtoexaminetherelationshipbetweenN1-P2
amplitudeandbehaviouraldiscriminationcategory.TheN1-P2peakamplitudewas
modelledwithfixedfactors‘behaviouralcategory’(poor,intermediateorgood),
‘deafnessonset’(pre-lingualorpost-lingual)and‘electrodepair’(1-2,2-3,3-4or4-5).
Theinteractiontermfor‘deafnessonset’and‘behaviouralcategory’wasalsoincluded
inthemodel.Thefactor‘electrodepair’waseliminatedfromthemodelasitwasnot
significant(F(3,24)=1.28,p=0.303).Analysisofvarianceofthereducedmodel
revealedasignificanteffectof‘behaviouralcategory’(F(2,31)=5.01,p=0.013)and
theinteractionbetween‘deafnessonset’and‘behaviouralcategory’(F(2,31)=3.39,p
=0.047).Theoutputofthemodelisshownintable3.6.
82
Figure3.8RelationshipbetweenACCN1-P2amplitudeandbehaviouraldiscrimination
category.Dependingonbehaviouraldiscriminationscore,electrodepairswerecategorizedas
being‘good’(score≥80%),‘intermediate’(60-79%)or‘poor’(<60%).Dataareshownfor
channelFCz.Eachpointrepresentsanindividualelectrodepair.Redandblackpointsarefrom
adultswithpre-lingualandpost-lingualonsetdeafnessrespectively.Theupperandlower
hingesoftheboxplotscorrespondtothefirstandthirdquartiles,whilstthemedianis
indicatedbythehorizontallinewithineachbox.
Post-hocpairwisecomparisonofthethreebehaviouralcategories,wasperformed
withTukeycorrection.Thisshowedthatinpost-linguallydeafenedindividuals,there
wasasignificantdifferenceinamplitudebetweenthegoodandpoorgroups(p=
0.020)andthegoodandintermediategroups(p<0.001).However,therewasno
significantamplitudedifferencebetweenthepoorandintermediategroups(p=
0.921).Forthepre-linguallydeafenedindividualsthenumberofdatapointsissmall
andtherewasnosignificantdifferenceinamplitudebetweenthepoor,intermediate
orgoodgroups(p>0.600forallcomparisons).
Thesedatashowthatinpost-linguallydeafenedadults,onlyhighlevelsofbehavioural
discriminationperformanceareassociatedwithaspatialACCresponse.Inpre-lingually
deafenedadults,theredoesnotappeartobeastrongrelationshipbetweenACC
amplitudeandbehaviouraldiscrimination.
83
Table3.6OutputofmixedmodelanalysisoffactorsaffectingACCN1-P2amplitude
Factor
Degreesof
freedom
(numerator,
denominator)
F
value
P
value
Effect
size
95%confidenceintervalofeffect
size
Initialmodel
Behavioural
category(2,28) 4.39 0.022 0.221 0.045–0.506
Deafness
onset(1,8) 0.05 0.830 0.006 0.000–0.506
Electrode
pair(3,24) 1.28 0.303 0.137 0.028–0.481
Behavioural
category*
deafness
onset
(2,28) 4.33 0.023 0.209 0.040–0.495
Reducedmodel
Behavioural
category(2,31) 5.01 0.013 0.227 0.053–0.497
Deafness
onset(1,8) 0.02 0.888 0.003 0.000–0.498
Behavioural
category*
deafness
onset
(2,31) 3.39 0.047 0.159 0.023–0.434
3.4.2.2.3Non-monotonicrelationshipbetweenN1-P2amplitudeandbehavioural
discriminationinpost-linguallydeafenedadults
Inpost-linguallydeafenedadults,thereappearstobeastrongrelationshipbetween
theACCN1-P2amplitudeandbehaviouraldiscrimination.Iftherewasamonotonic
relationshipbetweenbehaviouraldiscriminationandACCamplitude,thenwithina
participant,largerbehaviouraldiscriminationscorewouldbeassociatedwithlarger
amplitudeACCresponsesfor‘good’electrodepairs.Therewereonlytwoparticipants
84
whohadmorethan1electrodepairinthe‘goodcategory’whichwerenotallatthe
ceilinglevelofbehaviouraldiscrimination.Asseenintable3.7,evenforelectrodepairs
inthe‘goodcategory’,higherdiscriminationscoreswithinaparticipantarenot
necessarilyassociatedwithlargerACCamplitudes.Thissuggeststhatthereisanon-
monotonicrelationshipbetweenACCamplitudeandbehaviouraldiscrimination.
Table3.7ACCamplitudeatchannelFCzin2post-linguallydeafparticipants.Thisshowsthat
eveninthe‘goodcategory’(discriminationscore≥80%)ahigherdiscriminationscoreisnot
necessarilyassociatedwithahigherACCamplitude.
ParticipantElectrode
pair
Behavioural
discriminationscore(%)
N1-P2peak
amplitude(µV)
S1
1_2 70 0.66
2_3 75 1.00
3_4 100 2.34
4_5 85 4.46
S9
1_2 100 2.87
2_3 100 3.14
3_4 90 2.70
4_5 100 1.75
3.4.2.3Relationshipbetweenelectrodediscriminationandspeechperception
3.4.2.3.1Behaviouralelectrodediscriminationandspeechperception
Electrodediscriminationscoresforeachparticipantwerecollapsedtothemean
behaviourald’acrossthe4electrodepairs.Themeand’scorewasusedasthis
providesameasuresofdiscriminationabilityacrosstheapicalregionofthecochlea.
Therewasasignificantcorrelationbetweenmeanbehaviouralelectrode
discriminationd’andvoweld’(r=0.68,95%confidenceinterval[0.08,0.92],p=
0.032)andBKBsentencescore(r=0.73,95%confidenceinterval[0.19,0.93],p=
0.016).Thisrelationshipisshowngraphicallyinfigure3.9.AsthedistributionofBKB
scoreswasnon-normal,therelationshipwiththemeand’scorewasalsoexamined
85
withSpearman’srankcorrelationanalysis.Thisshowedatrendtowardssignificant
correlation(rho=0.63,95%confidenceinterval[-0.10,0.85],p=0.052).
Figure3.9Therelationshipbetweenmeanelectrodediscriminationd’scoreandspeech
perception.Open-setspeechperceptionscore,measuredwithBKBsentencesisshownin(A)
andclosed-setvowelperceptionmeasuredwithCAPTisshownin(B).Eachpointrepresents
datafromasingleparticipant.The95%confidenceintervalisshownbytheshadedarea.
3.4.2.3.2ThespatialACCandspeechperception
Anobjectivediscriminationscorewascalculatedforeachparticipantbytakingthe
meanoftheACCN1-P2peakamplitudeacrossthe4electrodepairs.Therewasno
significantcorrelationbetweentheobjectivediscriminationscoreandvowel
perceptionscore(r=0.37,95%confidenceinterval[-0.34,0.81],p=0.30)orsentence
perceptionscores(r=0.18,95%confidenceinterval[-0.51,0.73],p=0.62).The
relationshipbetweenthenumberofdiscriminableelectrodepairsdefinedusing
objectivepass-failcriteriaandspeechperceptionwasexaminedwithSpearman’srank
correlationcoefficient.Thisalsoshowednosignificantcorrelationwithvowel
(rho=0.54,95%confidenceinterval[-0.14,0.92],p=0.10)orsentenceperception
scores(rho=0.42,95%confidenceinterval[-0.23,0.82],p=0.22).Sincethe
relationshipbetweenthespatialACCandbehaviouraldiscriminationisnotasrobustin
pre-linguallydeafenedadults,theanalysiswasrepeatedinpost-linguallydeafened
adultsaloneandthisshowedasimilarpatternofresults(table3.8).
86
Table3.8CorrelationsbetweenspeechperceptionscoresandthespatialACCmeasures.
Resultsareshownforthewholegroupaswellasthesubgroupofadultswithpost-lingual
onsetofdeafness.
VariableCorrelation
type
Sentencescore Vowelscore
Correlation
coefficientand
95%confidence
interval
P
value
Correlation
coefficientand
95%confidence
interval
P
value
Allparticipants
MeanACCN1-
P2amplitudePearson’s 0.18[-0.51,0.73] 0.62 0.37[-0.34,0.81] 0.30
No.
discriminable
electrodes
Spearman’s 0.42[-0.23,0.82] 0.22 0.54[-0.14,0.92] 0.10
Adultswithpost-lingualonsetdeafnessonly
MeanACCN1-
P2amplitudePearson’s 0.63[-0.23,0.94] 0.13 0.48[-0.43,0.91] 0.28
No.
discriminable
electrodes
Spearman’s 0.47[-0.81,0.87] 0.28 0.56[-0.24,1.00] 0.19
3.5Discussion
ThisstudyshowsthatitispossibletomeasurethespatialACCindifferentCIdevices
andasearlyas1weekafterswitch-on.Thesamplesizeinbothexperimentsissmall
whichmaylimitthestatisticalanalysis.Nonetheless,thesedataindicatethatthereisa
strongrelationshipbetweenthespatialACCandbehaviouralmeasuresofelectrode
discrimination.Furthermore,incertaincasestheACCcouldberecordedintheabsence
ofaccuratebehaviouraldiscrimination.ThissuggeststhatthespatialACCreflects
encodingofstimuluschangeattheleveloftheauditorycortexandisnotnecessarily
relatedtotheperceptionofchangeitself.
87
3.5.1AssessmentandremovalofCIartefact
Thesizeanddistributionofartefactvariesbetweenindividualsanddevice.Inboth
experiments,itwasfoundthattheCIartefactwasusuallylimitedtothesideofthe
implantandwasneverpresentonthecontralateralside.Heetal.(2014)and
ScheperleandAbbas(2015a)showedthatitwasfeasibletomeasuretheACCusing1-2
midlinescalpchannelsintheCochleardevice.Thedatainthisstudysuggestthatsuch
anapproach,withfewscalpchannels,couldbeusedinotherCIdevicesprovided
artefactfreelocationsareselected(exploredfurtherinChapter6).
Theadvantageofmulti-channelscalprecordingsisthatCIartefactcanberemoved
allowingassessmentofcorticalresponsesatagreaternumberoflocationsaswellas
sourcelocalization.AnumberoftechniqueshavebeenusedtoremoveCIartefact
(Debeneretal.,2008;Martin,2007;McLaughlinetal.,2013).Spatialfilteringwas
foundtobeaneffectivetechniquewhichusuallyisolatesDCartefactin1-2
componentswhichmakesartefactidentificationrelativelysimpleandquick.In
addition,theartefactisolatedbyspatialfilteringinthesuprathresholdstimulation
conditionwassimilartothatinthesubthresholdstimulationcondition.Thisimplies
thattheneuralresponseisunlikelytobesignificantlyaffectedbyartefactremoval
withthistechnique.
3.5.2CharacteristicsofthespatialACCat1weekafterswitch-on
Inkeepingwithotherstudies(Brownetal.,2008;Heetal.,2014;ScheperleandAbbas,
2015b),itwasfoundthatthespatialACCmorphologywassimilartothatoftheonset
responseandwasdominatedbyN1andP2components.Heetal.(2014),showedthat
theACCinchildrenwithauditoryneuropathyisoftencharacterizedbyP1andN2
peaks.Thismaybeasignofauditoryimmaturityandthismorphologywasnot
observedinanyoftheparticipantsinthisstudyincludingpre-linguallydeafened
adults.Similartootherstudies(Brownetal.,2008;Heetal.,2014;Martinand
Boothroyd,1999),theamplitudeoftheACCwasfoundtobesignificantlysmallerthan
thatoftheonsetresponse.Inaddition,peaklatenciesoftheP1,N1andP2
componentsofthespatialACCweresignificantlylaterthanthatoftheonsetresponse.
88
OtherstudieshavereportedACCpeaklatencybeinglater(Heetal.,2012;Martinand
Boothroyd,1999),nodifferent(Brownetal.,2008;Heetal.,2012)orevenearlier(Kim
etal.,2009)thantheonsetresponsepeaklatency.Thismayrelatetothedifferent
stimuliusedinthesestudies.
3.5.3RelationshipbetweenthespatialACCandbehaviouraldiscrimination
3.5.3.1Relationshipinpost-linguallydeafenedadults
TherewasastrongrelationshipbetweentheACCandbehaviouraldiscrimination
performanceinpost-linguallydeafenedadults.TheACCcouldbeusedtopredicta
behaviouralpass/failaccuratelyin28/28electrodepairsin7adultparticipants.A
numberofotherstudieshavereportedastrongrelationshipbetweenobjectiveACC
andbehaviouralmeasuresofelectrodediscrimination.Heetal.(2014)foundastrong
relationshipbetweenthespatialACCandbehaviouralmeasurementsinCIchildren
withauditoryneuropathy.PresenceoftheACCwasdeterminedbasedonvisual
identificationofaresponseaswellasminimumamplitudecriteria.Behavioural
discriminationwastestedwitha2-AFCtaskandapasswasdefinedasascoreof≥4/6.
Accordingtobinomialprobability,withthesecriteria,apasscouldhavebeenachieved
bychancein34%ofcases.Stricterbehaviouralpasscriteriawereusedinthisstudyto
reducethefalsehitrate.Hoppeetal.(2010),reportedthattheACCcouldbe
measuredin88%ofcasesinwhichparticipantscouldsuccessfullydiscriminate
electrodesbutthecriteriaforassessingwhethertheACCwaspresentorabsentwere
notdefined.
Thewithin-subjectanalysis,showedthatonlyhighbehaviouraldiscriminationscores
areassociatedwithaspatialACC.Electrodepairswithintermediatediscrimination
scores,between60-80%,didnothavesignificantlydifferentamplitudestoelectrode
pairswithscoresatoraroundchancelevel(<60%).Thisfindingisinkeepingwithother
studies,whichhaveexaminedtherelationshipbetweentheACCandbehavioural
performanceinNHindividuals(Heetal.,2012;Michalewskietal.,2005).Inthestudy
byHeetal.(2012),behaviouralthresholdforfrequencydiscriminationwas
determinedwithanadaptiveprocedureestimating70.7%correctdetection.Itwas
89
foundthattheACCthresholdwassignificantlyhigherthanthebehaviouralthreshold
suggestingthatingeneral,onlybehaviouralscoresgreaterthan70.7%areassociated
withanACCresponse.Presumablyatlowerlevelsofbehaviouralperformance,
stimuluschangeisencodedlessreliablyintheauditorypathwayandtherearelimitsto
thesensitivityofrecordingfar-fieldresponsesrelatedtothestimulationparadigmand
thetechniqueitself.
Thedatafromthisstudysuggeststhatthereisanon-monotonicrelationshipbetween
ACCamplitudeandbehaviouraldiscrimination.Withinsubjects,electrodepairswith
thehighestbehaviouraldiscriminationscoresdidnotnecessarilyhavethelargestACC
amplitude.Otherstudieshavefoundanon-monotonicrelationshipbetweenspatial
ACCamplitudeandelectrodeseparationinCIusers(Heetal.,2014;Scheperleand
Abbas,2015b).Thereasonforthismaybebecausedifferentelectrodelocationsand
therefore,differentdipolelocationsarebeingcompared.Itmayalsobebecausethe
ACCisnotdirectlyrelatedtotheperceptionofstimuluschange.TheonsetN1
componentisassociatedwithencodinganddetectionofathreshold-levelauditory
stimulus(NäätänenandPicton,1987;Parasuramanetal.,1982).Thepresenceofthe
ACCmaythereforesignifythatastimuluschangeaboveacertainthresholdhas
occurredbuttheamplitudemaynotberelatedtostrengthofperception.
3.5.3.2Relationshipinpre-linguallydeafenedadults
Thisisthefirststudytoexaminetherelationshipbetweenbehaviouraldiscrimination
andtheACCinpre-linguallydeafenedadults.ThespatialACCcouldbeusedtopredict
behaviouraldiscriminationaccuratelyin7/12electrodepairsin3adultparticipants.In
addition,themixedmodelanalysis,showedthatACCamplitudedidnotdiffer
significantlybetweenelectrodepairswith‘good,‘intermediate’or‘poor’
discriminationscores.Giventhesmallsamplesize,theseresultsmustbeinterpreted
withcautionandshouldbeconsideredpreliminaryinnature.However,thedata
suggeststhatthespatialACCisalessreliablemeasureofbehaviouraldiscriminationin
pre-linguallydeafenedadultscomparedtothosewithpost-lingualdeafnessonset.
Thereweretwoelectrodepairsfromthesameparticipantwhichhadanobjectivefail
butbehaviouralpass.Alloftheresponsesforthisparticipantweresmall.
90
Aninterestingfindinginthisstudyisthatinall3pre-linguallydeafenedadults,the
spatialACCcouldberecordedintheabsenceofaccuratebehaviouraldiscrimination.
Therecouldbeanumberofexplanationsforthis.Firstly,itcouldbearguedthatthe
ACCoccurredduetoaperceivedchangeinloudnessiftheelectrodepairswerenot
loudnessbalancedproperly.However,thisisunlikely,asinthebehaviouraltask,
participantswereinstructedtochoosethesoundwhichwasdifferent;iftherewere
loudnesscues,thenhigherbehaviouralscoreswouldbeexpectedintheseindividuals.
Secondly,itcouldbethatthethresholdof80%forabehaviouralpass(binomial
probability<1%)wastoohigh.Evenifapasswasdefinedasascoreof≥75%(binomial
probability<5%)theseelectrodespairsstillwouldhaveabehaviouralfail.Inaddition,
oneparticipant(S2)hadadiscriminationscorebelowchancelevelbuthadalargeACC
amplitude.Itisalsonoteworthy,thatinthemixedmodelanalysisofACCamplitude
therewasnosignificantdifferencebetweenthepoorandintermediatebehavioural
discriminationcategoriesinpre-andpost-linguallydeafenedadults.Thissuggeststhat
thresholdof80%forabehaviouralpassisappropriateforthisexperimentalparadigm.
Itthereforeappears,thatincertainindividuals,thechangeinstimulatingelectrodeis
encodedattheleveloftheauditorycortexbutnotperceivedaccurately.AfterCI
switch-on,patientsundergoactiveandpassivelearning,gainedthroughauditory
experiencewiththeirCI.Thereisevidencethatlearninginducesdifferent
neurophysiologicalchangeswhichunderliefastandslowphasesoflearning(Atienza,
2002).ThepresenceoftheACCintheaboveparticipantsmaythereforeindicatethat
thattheyhavethepotentialtodevelopbehaviouraldiscriminationatalaterstage.This
hypothesisisexaminedanddiscussedfurtherinChapter4.Anotherpossible
explanationforthefailuretoperceiveanencodedstimulusisabnormalconnectivityof
theauditorycortexofcongenitallydeafenedindividuals.Ithasbeenproposedthat
congenitaldeafnesscanleadtofunctionaldecouplingoftheprimaryandsecondary
auditorycortex(KralandSharma,2012)andimagingstudieshaveprovidedevidence
ofabnormalpatternsofauditoryactivationincongenitallydeafindividuals(Gilleyet
al.,2008;Naitoetal.,1997).
91
Takentogether,theseresultssuggestthattheACCrepresentscorticalencodingof
stimuluschange;whilstthisencodingisusuallyassociatedwithchangedetection,this
maynotbethecaseintheearlystagesoflearningorinanauditorycortexwhichhas
failedtodevelopnormallyduetoauditorydeprivation.
3.5.4Reasonsforpoorelectrodediscrimination
Apicalelectrodediscriminationabilityvariedwidely,bothamongstpre-andpost-
linguallydeafenedindividualsinthisstudy.Inthemain,thisislikelytobedueto
peripheralfactorsincludingelectrodeplacement,currentspreadandspiralganglion
survival(Longetal.,2014;Pfingstetal.,1985).Electrodediscriminationisaffectedby
stimulusintensityinCIusers(McKayetal.,1999).Immediatelyafterswitch-on,theMC
levelisachievedwithrelativelylowstimulationlevelsandthiscouldhavecontributed
topoorelectrodediscriminationincertainindividuals.Furthermore,theMClevelisa
fairlyimprecisemeasureandtherefore,differencesinperceivedloudnesscouldhave
contributedtovariationinelectrodediscriminationability.Asdiscussedearlier,itwas
foundthatincertainindividuals,stimuluschangewasencodedintheauditorycortex
butnotaccuratelyperceived.Thissuggeststhatpoorbehaviouralelectrode
discriminationcanbeduetocentralaswellasperipheralfactors.
3.5.5Electrodediscriminationandspeechperception
Meanelectrodediscriminationd’scoreswerefoundtobecorrelatedwithopen-set
andclosed-setspeechperception.Apicalelectrodesencodelowfrequencieswhich
provideimportantcuesforspeechperception(LiandLoizou,2008).Althoughthe
samplesizeissmall,theseresultsareinkeepingwithDawsonetal.(2000)andBusby
etal.(2000),whofoundthatapicalEDLswerenegativelycorrelatedwithclosed-set
speechperception.Busbyetal.(2000)didnotfindarelationshipbetweenEDLand
open-setspeechperception.ThismaybebecauseinthestudybyBusbyetal.(2000),
apicalEDLsweremeasuredaroundasingleelectrode,whereasinthisstudyelectrode
discriminationabilitywasmeasuredacrossmultipleelectrodepairs.Asignificant
correlationbetweenspatialACCandspeechperceptionwasnotfoundevenafter
excludingpre-linguallydeafenedindividuals.Thestudywasunderpoweredforthis
92
analysisandthesignificancelevelsmustbeinterpretedwithcaution.Therelationship
betweenthespatialACCandspeechperceptionisexaminedanddiscussedfurtherin
Chapter4.
3.6Conclusions
ThisstudyshowsthatthespatialACCcanbemeasuredindifferentCIdevicesandatan
earlystageafterCIswitch-on.ItwillbeimportanttounderstandhowtheACCdevelops
inrelationtobehaviouraldiscriminationandthiswillbeexploredfurtherinChapter4.
ThespatialACCrepresentsencodingofstimuluschangeatthelevelofthecortexand
canprovideinformationoverandabovebehaviouraltesting.Thisraisesthepossibility
ofusingthisobjectivemeasuretoguidemanagementatanearly,andpotentially
criticalperiodofauditoryrehabilitation.
93
Chapter4 DevelopmentofthespatialACCandbehavioural
electrodediscriminationafterCIswitch-on
Thischapterisbasedonthefollowingpublishedjournalarticle:
MathewR,VickersD,BoylePetal.Developmentofelectrophysiologicaland
behaviouralmeasuresofelectrodediscriminationinadultcochlearimplantusers.
HearRes.2018Sep;367:74-87.doi:10.1016/j.heares.2018.07.002.
4.1Abstract
Theplasticityoftheauditorysystemenablesittoadapttoelectricalstimulationfrom
cochlearimplants(CI).Whilstspeechperceptionmaydevelopformanyyearsafter
implantactivation,verylittleisknownaboutthechangesinauditoryprocessingthat
underpintheseimprovements.Suchanunderstandingcouldhelpguideinterventions
thatimprovehearingperformance.Inthislongitudinalstudy,thechangeovertimein
electrodediscriminationwasexaminedinnewlyimplantedadultCIusers.Electrode
discriminationwasmeasuredwithabehaviouraltaskaswellasthespatialauditory
changecomplex(ACC).Itwasfoundthattherewassignificantimprovementin
electrodediscriminationabilityovertime,thoughincertainindividualstheprocessof
adaptationwasslowerandmorelimited.Therewasastrongrelationshipbetween
objectiveandbehaviouralmeasuresofelectrodediscriminationusingpass-failrules.In
severalcases,thedevelopmentofthespatialACCprecededaccuratebehavioural
discrimination.Thesedataprovideevidenceforplasticityofauditoryprocessingin
adultCIusers.Interventionswhichexploittheplasticityoftheauditorysystemto
improvebasicauditoryprocessing,couldhelptooptimizeperformanceinCIusers.
4.2Introduction
Electricalhearingimposesseverallimitationscomparedtoacoustichearingincluding
reducedDR,spectralmismatchbetweenthecharacteristicfrequenciesoftheauditory
neuronsandallocatedfrequenciesofthestimulationchannels,aswellasreduced
spectralresolution(Moore,2003).Learningtohearandcommunicateeffectivelywith
aCIrequiressignificantadaptationonthepartoftheauditorysystem.Tobeableto
fullyunderstandspeechwithaCI,theindividualneedstodevelopperceptualskills
94
fromdetectionanddiscriminationthroughtoidentificationandcomprehension(Erber,
1982).WhilstitiswellknownthataCIuser’sabilitytoidentifyspeechcanimprove
overlongperiodswithhearingexperience(Tyleretal.,1997),thetimecourseforthe
emergenceofdiscriminationabilityislesswellunderstood.
Understandingthetemporaldynamicsofdiscriminationabilitycouldprovideinsights
intobasicauditoryprocessinginCIusersandhelptoguidemanagement.Inthis
respect,assessmentofelectrodediscriminationisofparticularinterest.Electrode
discriminationprovidesameasuresofspatialresolution(Collinsetal.,1997;
ThrockmortonandCollins,1999)andhasbeencorrelatedwithspeechperceptionin
paediatricandadultCIusers(Busbyetal.,2000;Dawsonetal.,2000).Theresultsof
electrodediscriminationtestshavebeenusedtoguideinterventionsinCIusers,such
asdeactivationofelectrodesandauditorytraining,inordertoimprovehearing
performance(Salehetal.,2013;DeborahVickersetal.,2016;Zwolanetal.,1997).
However,ifsuchinterventionsaretobecarriedout,thenitwouldbehelpfulto
understandhowthesepsychophysicalabilitiesdevelopovertime.Ifperformance
improvesforlongperiodswithCIexperience,thenprematurelyintervening,for
examplebydeactivatingelectrodes,couldbedetrimental.Ifontheotherhand,
performanceimprovesrapidlyandthenplateaus,remappinginterventionsaremore
likelytobeappropriate.
RelativelyfewstudieshaveassessedtheemergenceofspectralprocessinginCIusers.
Sandmannetal.(2015)conductedalongitudinalstudyinnewlyimplantedpost-
linguallydeafadultCIuserswhoweregivenabehaviouraltaskinwhichtheyhadto
identifythedirectionofpitchchangeinafrequencymodulatedtonecomplex.
Participantswerefollowedupfor9monthsafterswitch-onbutperformancedidnot
increasesignificantlyafter2months.Thisstudysuggeststhatspectralprocessing,as
measuredwithataskinvolvingpitchjudgements,plateausveryquickly.Landsbergeret
al.(2018),measuredspectralresolutionwiththeSMRTinacrosssectionalstudyof
paediatricCIusersbetweentheagesof5and13years.Mostchildrenhadbeenusinga
CIforseveralyears(range0.8–11years)intheirstudy.ItwasfoundthatSMRTscores
werenotcorrelatedwithageorCIexperiencesuggestingthatthedevelopmentof
95
spectralresolutionisimpairedinearlydeafenedCIusers.Todatetherehavenotbeen
anylongitudinalstudiesassessingelectrodediscriminationinCIusers.
ThespatialACCisanobjectivemeasuresofelectrodediscrimination.InChapter3,
itwasshownthatthespatialACCcanbemeasuredinindividualswithdifferentCI
manufacturersdevicesandalsoinnewlyimplantedadultCIusers.Inaddition,astrong
relationshipbetweenobjectiveandbehaviouralmeasuresofelectrodediscrimination
wasfoundat1weekafterswitch-on.Interestingly,insomepre-linguallydeafenedlate
implantedindividuals,thespatialACCcouldbemeasureddespiterelativelypoor
behaviouraldiscrimination.Itwashypothesizedthatinthesecases,thepresenceof
theACCindicatedthepotentialtodevelopaccuratebehaviouraldiscriminationata
laterstage.
Theaimofthisfollowupstudyistodeterminehowelectrodediscriminationability
developsovertimes.Theobjectiveswereto:
1) determinehowthespatialACCandbehaviouralelectrodediscrimination
developoverthefirst6to12monthsafterswitch-on
2) examinetherelationshipbetweenthespatialACCandbehaviouralelectrode
discriminationduringthisperiod
3) examinetherelationshipbetweenmeasuresofelectrodediscriminationand
speechperception
96
4.3Experiment3:DesignandMethods
4.3.1Participants
Elevenparticipantsranginginagefrom42to80yearstookpartinthestudy.One
participantdroppedoutofthestudyafterthefirstrecordingsessionandwas
thereforeexcludedfromtheanalysis.Oftheremaining10participants,9hadtaken
partintheresearchinChapter3.Allparticipantswereunilaterallyimplantedwithan
ABHi-Res90Kimplant.Demographicdetailsofparticipantsareshownintable4.1.Of
note,deafnessonsetwaspre-orperi-lingualin3casesandpost-lingualinthe
remainderofparticipants.
4.3.2Testprocedures
ThespatialACC,behaviouralelectrodediscriminationandspeechperceptionwere
testedatthefollowingtimepointsafterswitch-on:1week(median10.5days,range7-
19days),3months(median92days,range81-108days)and6months(median180.5
days,range169-190days).Additionally,asubsetofparticipantsunderwent
behaviouraltestingat12monthsafterswitch-on(seebelow).
ThestimuliforEEGwereidenticaltothatinexperiment2(Chapter3)-800ms
alternatingpolaritybiphasicpulsetrainspresentedatarateof0.51Hz.The4most
apicalelectrodepairsweretested(1-2,2-3,3-4,4-5)ineveryparticipant.Stimuliwere
presentedattheloudnessbalancedMClevel.AsstimulationlevelsrequiredbyCIusers
generallyincreaseoverthefirst6monthsofCIuse(Vargasetal.,2012),theprocedure
fordeterminingstimulationlevelswasrepeatedateachvisituntil6months.
Therewereatotalof120EEGmeasurementsover6months(4electrodepairsfor10
participantsat3timepoints).EEGrecordingandprocessingwasperformedas
describedintheGeneralMethods(Chapter2).Anobjectivepasswasbasedon
Hotelling-T2criteriaduringtheresponsewindowof450–650ms.Theresponse
windowwasadjusted,to450–700msin8/120casesduetoalateP2peak,andto450
-600msin2/120cases,duetoanabsentP2peak.
97
Speechperceptionandbehaviouralelectrodediscrimination(forall4electrodepairs)
weremeasuredatthe1-week,3-monthand6-monthtimepoints.Inaddition,
behaviouralelectrodediscriminationtestingwasrepeatedat12monthsfor
participantswhohadnotachievedabehaviouralpassforall4electrodepairsby6
months.Thiswasmotivatedbythefindingthatanumberofelectrodepairshadan
objectivepassbutbehaviouralfailat6months.Testingat12monthswastherefore
performedtodeterminewhethertheseelectrodeswoulddevelopabehaviouralpass
atalatertime.Forthe12-monthtimepoint,thesamestimulationlevelsasat6
monthswereused.Loudnessbalancingwascheckedandrepeatedifparticipants
reportedadifferenceinloudness.
Speechperceptiontestingincludedopen-setBKBsentences-in-quiet,andtheclosed-
setCAPTvoweltest.EEG,behaviouralandspeechtestingweredoneinasinglesession
whichlastedapproximately2.5hoursincludingbreaks.
Table4.1Demographicdetailsofparticipantsinexperiment3.F=female,M=male,R=right,L=left,4F-PTA=four-frequencypuretoneaverage,CI=cochlearimplant.
Participant Age Sex Ear Communication
Durationprofound
hearing
loss(years)
Deafness
onset
4F-PTAnon
CIear(dB
HL)
Electrode
S1 51 M R oral 10 Post-lingual 116 MidScala
S2 50 F R oral+sign 50 Pre-lingual 115 MidScala
S3 42 F L oral 18 Post-lingual 118 MidScala
S4 48 M L oral 46 Pre-lingual 115 1J
S5 47 F L oral 42 Peri-lingual 103 MidScala
S6 68 F L oral 10 Post-lingual 100 MidScala
S8 51 F R oral 5 Post-lingual 96 MidScala
S9 48 M L oral 1 Post-lingual 113 MidScala
S10 80 M L oral 10 Post-lingual 78 MidScala
S11 65 F L oral 2.5 Post-lingual 98 MidScala
98
99
4.4Results
4.4.1Changesinbehaviouralelectrodediscrimination
Figure4.1showsthechangeovertimeinmeanbehaviouraldiscriminationscore
acrossthe4electrodepairsforeachparticipant.Asstatedinthemethods,12-month
datawasonlycollectedforparticipantswhohadnotachievedabehaviouralpassfor
all4electrodepairsby6months(S1,S2,S5,S6).
Inspectionoftheindividualdatashowsthattherewaslargevariabilityin
discriminationscoresaswellasthepatternofchangeovertime.ParticipantsS3,S8,S9
andS10hadexcellentperformancefrom1week,withscoresatornearceilinglevelfor
allelectrodepairs.ParticipantsS4andS11showedarapidincreaseinbehavioural
scoresachievingceiling/near-ceilinglevelby3months.Incontrast,participantsS2,S5
andS6hadrelativelypoordiscriminationtostartwithbutmeandiscriminationscore
increasedover12-months.OnlyparticipantS1showedadecreaseinmeanbehavioural
score.Thisparticipanthadexcellentdiscriminationforelectrodepairs3-4and4-5
throughoutthestudyandthedecreaseinmeanscorewasduetorandomvariationin
performanceforelectrodepairs1-2and2-3,forwhichthethresholdforabehavioural
passwasneverachieved.
Thechangeinbehaviouraldiscriminationscoreovertimewasanalyzedwithalinear
mixed-effectsmodel.Inordertoreduceceilingeffects,onlyelectrodepairsthatdid
nothaveadiscriminationscoreof100%at1weekwereincludedintheanalysis.The
dependentvariablewasthe‘behaviourald’score’foreachelectrodeandthe
independentvariableswere‘timeafterswitch-on’and‘electrodepair’(1-2,2-3,3-4,4-
5).Therewasnosignificanteffectof‘electrodepair’andthisfactorwastherefore
removedfromthemodel.Analysisofthereducedmodelshowedasignificanteffectof
‘timeafterswitch-on’(F(3,67)=5.01,p<0.001).Post-hocpairwisecomparisonswith
Tukeycorrectionshowedtherewasasignificantdifferenceforthe1weekvs12month
contrast(p=0.002)andatrendtowardssignificantdifferenceforthe1weekvs6
monthcontrast(p=0.054).Asummaryoftheanalysisisshownintable4.2.
100
Table4.2Outputofmixedmodelanalysisoffactorsaffectingbehaviouraldiscriminationscore.
Factor
Degreesof
freedom
(numerator,
denominator)
F
value
P
value
Effect
size
95%confidenceintervalofeffect
size
Initialmodel
Timeafter
switch-on(3,65) 5.05 <0.001 0.190 0.072–0.386
Electrode
pair(3,66) 1.05 0.375 0.045 0.009–0.214
Reducedmodel
Timeafter
switch-on(3,67) 5.01 <0.001 0.182 0.068–0.373
Changesinbehaviouralelectrodediscriminationwerealsoanalyzedintermsofthe
numberofelectrodeswithabehaviouralpass.Inthiscase,themaximumscoreforan
individualatanytimepointis4,correspondingtothenumberofelectrodepairs
tested.Thechangesovertimeinthenumberofelectrodeswithabehaviouralpassare
showninfigure4.2.Thisfigureshowsasimilarpatterntofigure4.1withimprovement
inelectrodediscriminationabilityforparticipantsS2,S5andS6between6and12
months.Thetotalnumberofelectrodeswithabehaviouralpassincreasedovertime
andwas25/40at1week,29/40at3monthsand30/40at6months.At12months,5
additionalelectrodepairsachievedabehaviouralpass.
ThesedatashowthatapicalelectrodediscriminationabilityvarieswidelyamongstCI
usersbutcancontinuetoimproveforupto12monthsafterswitch-onincertain
individuals.
101
Figure4.1Changeinmeanbehaviouralelectrodediscriminationscoreovertime.DataareshownforindividualCIusers.Notethatbehaviouralscoreswereonlymeasuredat12monthsinindividualswhohadnotachievedabehaviouralpassforall4electrodepairsby6months(S1,S2,S5,S6).Randomnoisehasbeenaddedtothediscriminationscoresinordertoimprovedatavisualization.
102
Figure4.2Changeovertimeinthenumberofdiscriminableelectrodesasdefinedbybehaviouralpass-failrules.DataareshownforindividualCIusers.Themaximumscorethatcanbeachievedatanytimepointis4correspondingtothenumberofelectrodepairstested.Behaviouralscoreswereonlymeasuredat12monthsinindividualswhohadnotachievedabehaviouralpassforall4electrodepairsby6months(S1,S2,S5,S6).Randomnoisehasbeenaddedtothebehaviouralpassscoreinordertoimprovedatavisualization.
4.4.2Behaviouraldiscriminationcontrollingforstimulusintensity
StudiesfromNHandCIpopulationshaveshownthatdiscriminationabilityimproves
withstimulationlevel(FreymanandNelson,1991;McKayetal.,1999).Inthisstudy,
mostparticipantsreportedhigherMClevelsovertimeandthereforehigher
stimulationlevelsweregenerallyusedfortestingatlatertimepoints.TheaverageMC
levelacrossparticipantswas250µAat1week,294µAat3monthsand313µAat6
months.Thus,theincreaseinstimulationlevelscouldpotentiallyaccountforthe
improvementinbehaviouraldiscriminationscores.
Inordertoinvestigatewhetherimprovementsinbehaviouraldiscriminationweredue
totheuseofhigherstimulationlevels,electrodepairswerere-testedatlatertime
103
pointusingtheoriginalstimulationlevelsfromearliertimepoints.Ifdiscrimination
scoresatthelatertimepointwerehigherthanthatobtainedwiththesame
stimulationlevelasoriginallyused,thenthiswouldprovideevidencethat
improvementsovertimewerenotjustduetotheuseofahigherstimulationlevel.
Behaviouralelectrodediscriminationwasthereforeretestedforelectrodepairswhich
improvedfromabehaviouralfailtoabehaviouralpass.Thiswasperformedata
medianof16monthsafterswitch-on(range12–20months)usingthe1-month
and/or3-monthstimulationlevels.Forexample,ifanelectrodepairdevelopeda
behaviouralpassat12months,thenitwasre-testedatthe1-weeklevel.Ifa
behaviouralpasswasachieved(score≥80%),thennofurthertestingwasperformed
butiftherewasabehaviouralfail,re-testingwasrepeatedusingthe3-monthlevel.
The6-monthlevelwasnotusedforre-testingasthiswasthesamelevelusedat12
months.Re-testingofelectrodediscriminationatearlierlevelswasdoneinaseparate
sessiontothemainexperimentinordertoreducewithinsessionlearningeffects.In
addition,loudnessbalancingwascheckedandrepeatedifnecessary,forallelectrode
pairsandstimulationlevels.
Theresultsofre-testingareshownintable4.3.Therewere10electrodepairsfrom5
participantsthatdevelopedabehaviouralpassfromabehaviouralfailwithCIlistening
experience.Whenretestedattheoriginal1-weeklevel,9outof10electrodepairshad
ahigherscore,with7oftheseachievingabehaviouralpass(score≥80%).Ofthe3
electrodepairswhichhadnotachievedabehaviouralpassatthe1weeklevel,2
achievedabehaviouralpasswhentestedatthe3-monthlevel.Ascanbeseenfrom
table4.3,improvementsoccurredirrespectiveofwhetherelectrodeswereloudness
balancedagainornot.Onlyoneelectrodefailedwhenre-testedatthe1-weekand3-
monthlevels(S6,electrode3-4).Thiselectrodehadabehaviouralfailat6months
(score=60%)butwhentestedat12months,withthesamestimuluslevel,a
behaviouralpasswasachieved(score=85%).Therefore,alltenelectrodepairsthat
originallyhadabehaviouralfail,hadabehaviouralpasswhenre-testedwiththesame
stimuluslevelatalatertimepoint.
104
Table4.3Detailsofelectrodeswhichwentfromabehaviouralfailtoabehaviouralpassinexperiment3.Originalscoreswhenabehaviouralfailwasachievedaswellasretestscoresatalatertimepointwiththesamelevelsareshown.MC=mostcomfortable.
Participant ElectrodeOriginalscoreat
MClevelanddate
Retestscore
atsamelevel
Dateof
retesting
Re-loudness
balanced
S22-3 45%,1week 85%
16monthsNo
3-4 60%,1week 85% Yes
S41-2 60%,1week 95%
20monthNo
4-5 70%,1week 95% No
S5
2-3 40%,1week 100%
16months
No
3-4 60%,1week 100% No
4-555%,1week 75% Yes
Yes55%,3months 80%
S6
2-375%,1week 75%
15months
No
No50%,3months 80%
3-450%,1week 55% No
No65%,3months 75%
S11 1-2 70%,1week 100% 12months No
Theeffectoftimeonbehaviouraldiscriminationscore,withfixedstimulationlevels
wasanalyzedwithalinearmixed-effectsmodel.Thedependentvariablewasthe
behaviourald’scoreandindependentvariablesincluded‘electrodepair’(1-2,2-3,3-4,
4-5),‘level’(1-weekor3-monthlevel)and‘time’(originalorre-test).Thisanalysis
showedthattherewasonlyasignificantmaineffectoftime(F(1,20)=32,p<0.001).A
summaryofthisanalysisisshownintable4.4.Thesedatademonstratethatelectrode
discriminationabilitycanimprovewithCIexperienceirrespectiveofstimulationlevel.
105
Table4.4Mixedmodelanalysisofchangeinbehaviouraldiscriminationscorecontrollingforstimulusintensity.
Factor
Degreesof
freedom
(numerator,
denominator)
F
value
P
value
Effect
size
95%confidenceintervalofeffect
size
Initialmodel
Time (1,20) 27 <0.001 0.614 0.484–0.886
Electrode
pair(3,20) 0.98 0.422 0.172 0.038–0.659
Level (1,20) 0.72 0.408 0.028 0.000–0.331
Reducedmodel
Time (1,20) 32 <0.001 0.614 0.373–0.805
4.4.3DevelopmentofthespatialACC
Figure4.3showsthechangeovertimeinmeanspatialACCamplitudeacross4
electrodepairsforeachparticipant.Thesolidblacklinerepresentsthegrandmean
acrossparticipantsandwas2.16µVat1week,2.65µVat3monthsand2.79µVat6
months.Inspectionoftheindividualdatarevealslargeinter-individualvariabilityin
spatialACCamplitudeandthechangesovertimeappeartobelessconsistentin
comparisontothebehaviouraldiscriminationscores.However,aclearincreasein
spatialACCamplitudewithtimecanbeobservedin7outof10participants.
ThechangeinspatialACCamplitudewasanalyzedwithalinearmixed-effectsmodel.
ThedependentvariablewasthespatialACCamplitudeforindividualelectrodepairs
andthefixedeffectsweretimeafterswitch-on(1week,3monthsand6months)and
electrodepair(1-2,2-3,3-4,4-5).Therewasnosignificanteffectofelectrodepairand
thisfactorwasthereforeremovedfromthemodel.Analysisofthereducedmodel
revealedasignificanteffectoftimeafterswitch-on(F(2,108)=4.93,p=0.009).A
summaryoftheanalysisisshownintable4.5.Post-hocanalysiswithTukeycorrection
showedthattherewasasignificantdifferenceinACCamplitudeforthe1weekvs6
monthscontrast(p=0.010)andatrendtowardssignificantdifferenceforthe1week
vs3monthcontrast(p=0.056).
106
Table4.5MixedmodelanalysisoffactorsaffectingchangeinACCN1-P2amplitudeovertime.
Factor
Degreesof
freedom
(numerator,
denominator)
F
value
P
value
Effect
size
95%confidenceintervalofeffect
size
Initialmodel
Timeafter
switch-on(2,105) 4.88 0.009 0.085 0.018–0.214
Electrode
pair(3,105) 0.67 0.574 0.019 0.004–0.126
Reducedmodel
Timeafter
switch-on(2,108) 4.93 0.009 0.084 0.018–0.210
AnalysisoftheACCwithpass-failcriteriaalsoshowedthatelectrodediscrimination
abilityimprovedwithtime.AccordingtoHotelling-T2criteria,thenumberof
electrodeswithanobjectivepasswas23/40at1week,28/40at3monthsand30/40
at6months.Figure4.4showsanexampleofcorticalresponsedevelopmentforan
electrodepairinparticipantS4–at1weekthespatialACCwasabsent(4.4A)butby3
monthsaclearresponsewaspresent(4.4B).
ThechangeinlatencyoftheACCwasonlyassessedforelectrodepairsforwhichthere
wasanobjectivepass,asameaningfullatencycannotbeobtainedwhentheACCis
absent.Thisanalysiswaslimitedbecausealargeproportionofthedatahadtobe
excluded.Themeanlatencyat1week,3monthsand6monthswas119ms,123msand
120msfortheACCN1peakand224ms,245ms,and237msfortheACCP2peak.Using
amixedmodelanalysis,asignificanteffectoftimeontheACCpeaklatencieswasnot
observed(table4.6).
107
Table4.6MixedmodelanalysisoftheeffectoftimeafterswitchonlatencyofACCpeaks.
Factor
Degreesof
freedom
(numerator,
denominator)
F
value
P
value
Effect
size
95%confidenceintervalofeffect
size
cN1peak
Timeafter
switch-on(2,64) 0.34 0.711 0.011 0.001–0.137
Electrode
pair(3,64) 2.09 0.110 0.089 0.020–0.276
cP2peak
Timeafter
switch-on(2,65) 0.30 0.740 0.009 0.001–0.134
Electrode
pair(3,65) 0.88 0.459 0.039 0.008–0.209
Figure4.3ChangeinthemeanspatialACCamplitudeovertime.Thebrokenlinesshowthemeanelectrodediscriminationscoresforeachindividual.Thesolidlineshowsthatthemeanscoresacrossallparticipantswitherrorbarsrepresentingthestandarderrorofthemean.DataatchannelFCzarepresented.
Figure4.4Exampleofcorticalresponsedevelopment.DataareshownforparticipantS4electrodepair1-2(A)At1weekafterswitch-on,thespatialACCisabsentandthereisabehaviouralfail.(B)At3monthsafterswitch-on,thereisalargespatialACCresponseassociatedwithabehaviouralpass.ThespatialACChasbeenhighlightedinred.BehaviouralscoresandtheHotelling-T2(HT2)pvaluesareindicatedoneachpanel.Thetimewindowsusedtodetectpositiveandnegativepeaksfortheonsetresponse(P1,N1,andP2)andACC(cP1,cN1,andcP2)areshowninpinkandblue,respectively.Scalpvoltagemapsforautomaticallydetectedpeaksaredisplayed,withblacklinesrepresentingisopotentialcontourlines.Thehorizontallinescorrespondtothelevelofresidualnoise.DataatchannelFCzarepresented.
108
109
4.4.4RelationshipbetweenthespatialACCandbehaviouralelectrodediscrimination
TherelationshipbetweenobjectiveACCandbehaviouralmeasuresofelectrode
discriminationusingpass-failrulesisshownintable4.7.Asdescribedinthemethods
section,anobjectiveACCpasswasbasedonHotelling-T2statisticalcriteriawhilsta
behaviouralpassrequiredadiscriminationscoreofatleast80%.Outof120
measurementsover6months,therewasagreementbetweenobjectiveand
behaviouralmeasuresin99cases:34/40at1week,35/40at3monthsand30/40at6
months.Therewere12electrodepairsfrom4participantsinwhichtherewasa
behaviouralpassbutanobjectivefail.Ofthesedisagreements,8werefromparticipant
S11(disagreements:2at1week,2at3monthsand4at6months).Asidefromthis
participant,therewereonly4electrodepairsfrom3participantsinwhichtherewasa
behaviouralpassbutanobjectivefail.
Interestingly,therewere9caseswheredisagreementwasduetoanobjectiveACC
passdespiteabehaviouralfail.Figure4.5showsexamplesofACCrecordingsthatfell
intothisgroup.Table4.8showsthatthedisagreementsarosefrom7electrodepairs
from4participants,3ofwhomhadpreorperi-lingualonsetdeafness.In6outofthese
7cases,electrodepairsdevelopedaccuratebehaviouraldiscriminationatalatertime
pointi.e.theACCprecededaccuratebehaviouraldiscrimination.Asseenintable4.4,
inmostcasesabehaviouralpasswasobtainedatthetestpointimmediatelyfollowing
theattainmentofanobjectivepass.However,forelectrodepair2-3inparticipantS2,
abehaviouralpasswasonlyobtainedat12monthsdespiteanobjectivepassbeing
presentfrom1weekonwards.ThesedataconfirmfindingsfromChapter3thata
stimuluschangemaybeencodedintheauditorypathwaydespitepoorbehavioural
discrimination.Furthermore,thelongitudinaldatashowsthatthepresenceoftheACC
indicatespotentialtodevelopaccuratebehaviouraldiscriminationlateron.
Therelationshipbetweenobjectiveandbehaviouralmeasuresofelectrode
discriminationwasalsoassessedbyperformingcorrelationanalysisacrossparticipants
betweenmeanbehaviourald’scoreandmeanACCN1-P2amplitudeateachtime
point.Pearson’scorrelationdidnotshowasignificantrelationshipatanytimepoint(1
week:r=0.59,95%confidenceinterval[-0.06,0.89],p=0.072;3months:r=0.55,
110
95%confidenceinterval[-0.12,0.88],p=0.098;6months:r=0.13,95%confidence
interval[-0.54,0.70],p=0.710;N=10forallcorrelations).Thecorrelationwas
particularlypoorat6monthswhichwasalsoreflectedinthegreaterlevelof
disagreementinthepass-failanalysisatthistimepoint,asseenearlier.Thestudywas
underpoweredforthisanalysisandthecorrelationanalysisshouldbeinterpretedwith
caution.
Table4.7Agreementbetweenobjectiveandbehaviouralelectrodediscriminationatdifferenttimepoints.
1week 3months 6months
Behavioural
Pass
Behavioural
Fail
Behavioural
Pass
Behavioural
Fail
Behavioural
Pass
Behavioural
Fail
ObjectivePass 21 2 26 2 25 5
ObjectiveFail 4 13 3 9 5 5
Totalagreement 34/40 35/40 30/40
Table4.8DetailsofelectrodeswithanobjectiveACCpassandabehaviouralfail.1W=1week,3M=3months,6M=6months,12M=12monthsandNA=notapplicable,NT=nottested.
Subjectand
electrode
Dateobjectivepassfirst
achieved
Datebehaviouralpassfirst
achieved
Behaviouralscores(%)
1W 3M 6M 12M
S21-2 6M NA(failat12M) 30 55 60 55
S22-3 1W(andat3Mand6M) 12M 45 55 45 85
S23-4 6M 12M 60 40 60 80
S44-5 1W 3M 70 100 100 NT
S52-3 3M 6M 40 70 85 NT
S54-5 6M 12M 55 55 50 85
S62-3 6M 12M 75 50 55 90
111
Figure4.5ExamplesofcorticalresponseswithanobjectiveACCpassdespitethepresenceofabehaviouralfail.TheparticipantID,electrodepair,testtimepointandcorrespondingbehaviouralscoreareshownaboveeachpanel.Dataarepresentedatarepresentativefronto-centralchannelwhichisindicatedoneachpanelalongwiththeHotelling-T2(HT2)pvalue.Shadedareasandhorizontallinesareasdescribedinfigure4.4.
11 2
113
4.4.5Relationshipbetweenelectrodediscriminationandspeechperception
Figure4.6showshowsentenceandvowelperceptionscoreschangedovertime.The
solidblacklinerepresentsthemeanspeechperceptionscoreacrossparticipants.Both
vowelperceptionandspeechperceptionimprovedinallparticipantswiththe
exceptionofS2,inwhomsentenceperceptionscoreremainedat0%.Thisparticipant
hadcongenitaldeafnessandusedbothoralandsignlanguage.
ItisinterestingtonotethatparticipantsS2,S5andS6,whohadrelativelypoor
electrodediscriminationat6months(seefigure4.1),werealsothreeofthepoorest
performersintermsofspeechperceptionat6months.Ontheotherhand,participant
S1couldonlydiscriminate2outof4electrodesaccuratelythroughoutthe12-month
studyperiodbuthadconsistentlyexcellentspeechperceptionscores.ParticipantS8
showedtheoppositepattern,withexcellentelectrodediscriminationbutrelatively
poorspeechperception.
Thefactorsaffectingspeechperceptionwereinvestigatedwithalinearmixed-effects
model,withthedependentvariable‘speechperceptionscore’(eithersentence
perceptionorvowelperceptionscore)andindependentvariables‘timeafterswitch-
on’(1week,3months,6months)and‘meanbehaviouralelectrodediscriminationd’
score’(averagedacross4electrodesforeachparticipant).Forsentenceperceptionas
thedependentvariable,therewasasignificantmaineffectoftimeafterswitch-on
(F(2,18)=4.80,p=0.022)andmeanbehaviouralelectrodediscriminationd’score
(F(1,18)=6.22,p=0.021).Similarlyforvowelperceptionscoreasthedependent
variable,therewasasignificantmaineffectoftimeafterswitch-onF(2,19)=6.84,p=
0.006)andmeanbehaviouralelectrodediscriminationd’score(F(1,14)=5.73,p=
0.032).Thesummaryofthisanalysisisshownintable4.9.
114
Table4.9Mixedmodelanalysisoffactorsaffectingspeechperceptionwithbehaviouralelectrodediscriminationasanindependentvariable.
Factor
Degreesof
freedom
(numerator,
denominator)
F
value
P
value
Effect
size
95%confidenceintervalofeffect
size
Sentenceperception
Timeafter
switch-on(2,18) 4.8 0.022 0.339 0.088–0.662
Behavioural
discrimination
d’score
(1,18) 6.2 0.021 0.198 0.007–0.514
Vowelperception
Timeafter
switch-on(2,19) 6.8 0.006 0.424 0.156–0.713
Behavioural
discrimination
d’score
(1,14) 5.7 0.032 0.039 0.010–0.654
InordertoinvestigatewhetherthereisarelationshipbetweenthespatialACCand
speechperception,themixedmodelanalysiswasrepeatedwithspeechperception
score(eithersentenceperceptionorvowelperceptionscore)asthedependent
variableand‘meanspatialACCamplitude’(averagedacross4electrodepairs),
‘numberofobjectivediscriminableelectrode’(rangingfrom0to4)and‘timeafter
switch-on’on’(1week,3months,6months)astheindependentvariables.The
analysisconfirmedasignificantmaineffectoftimeafterswitch-onforsentence
perception(F(2,18)=9.38,p=0.002)andforvowelperception(F(2,18)=9.79,p=
0.001).However,therewasnosignificanteffectofmeanspatialACCamplitudeor
numberofobjectivediscriminableelectrodeineithercase(table4.10).
115
Table4.10MixedmodelanalysisoffactorsaffectingspeechperceptionincludingspatialACCmeasuresasanindependentvariable.
Factor
Degreesof
freedom
(numerator,
denominator)
F
value
P
value
Effect
size
95%confidenceintervalofeffect
size
I Sentenceperception:initialmodel
Timeafter
switch-on(2,17) 6.0 0.010 0.406 0.311–0.787
Meanspatial
ACC
amplitude
(1,22) 0.57 0.459 0.023 0.000–0.279
Numberof
objective
discriminable
electrodes
(1,18) 2.7 0.118 0.120 0.001–0.456
Sentenceperception:reducedmodel
Timeafter
switch-on(2,18) 9.4 0.002 0.510 0.243–0.764
II Vowelperception:initialmodel
Timeafter
switch-on(2,18) 6.6 0.008 0.412 0.142–0.710
Meanspatial
ACC
amplitude
(1,25) 0.34 0.564 0.012 0.000–0.224
Numberof
objective
discriminable
electrodes
(1,23) 0.021 0.886 0.001 0.000–0.205
Vowelperception:reducedmodel
Timeafter
switch-on(2,18) 9.8 0.001 0.521 0.255–0.769
Thesedatashowthatbothsentenceandvowelperceptionimprovewithhearing
experienceinCIusers.Althoughbehaviouralandobjectivemeasuresofelectrode
116
discriminationarerelated,theformerappearstobethemoreimportantpredictorof
speechperception.
Figure4.6Changeinspeechperceptionovertime.Thebrokenlinesshowdataforindividualparticipantsandthesolidblacklinesshowsthemeanacrossparticipantswitherrorbarsrepresentingthestandarderrorofthemean.Theblackbrokenhorizontallineinthevowelperceptionpanelshowschancescoreinthe4-alternativeforced-choicetask.Randomnoisehasbeenaddedtospeechscoresinordertoimprovedatavisualization.
4.5Discussion
ThisstudyshowsthatelectrodediscriminationabilitycanimprovemarkedlywithCI
experienceandimprovementscanoccuroverrelativelylongperiodsoftime.Changes
inbehaviouralperformancewereparalleledbyanincreaseintheamplitudeofthe
spatialACCprovidingevidenceforplasticityofauditoryprocessinginadultCIusers.
Furthermore,thedataprovidesfurtherevidencethatbehaviouralelectrode
discriminationisasignificantpredictorofspeechperception.Targetingimprovements
inspatialresolutioncouldthereforeleadtobetterhearingoutcomesinCIusers.
117
4.5.1Changesinelectrodediscriminationovertime
Thisisthefirststudytoexaminechangesinelectrodediscriminationabilityovertime
inCIusers.Electrodediscriminationabilitycontinuedtoimproveforupto12months
afterswitch-onincertainindividuals.WhileitisknownthatspeechperceptioninCI
usersmayimproveformanyyears(Heywoodetal.,2016;Tyleretal.,1997),itwas
somewhatsurprisingthatdiscriminationof,whatareinprinciple,simplestimuliwould
continuetoimproveforsolong.Therelativelylongtimecourseofimprovementin
someindividualssuggeststhatcentralratherthanperipheralfactors,areresponsible
forthechangeinperformanceovertime.Thelateimprovementsoccurredinpoorer
performers,3ofwhomhadpreorperi-lingualonsetdeafness,indicatingthatthe
historyofhearinglossmayaccountforthedifferenttimecourseofadaptationin
differentindividuals.
Thedatasuggeststhattheimprovementsovertimewerenotjustduetotaskrelated
learningfortworeasons.Firstly,theimprovementsinbehaviouralscoresoverthefirst
6monthswereparalleledbyanincreaseinthemeanspatialACCamplitude.Secondly,
allbutoneparticipantcouldaccuratelydiscriminateatleastoneelectrodepairfrom
thefirsttestsession.Thisimpliesthatparticipantswerecompetentatthebehavioural
taskfromanearlystageandimprovementsindiscriminationabilityovertimewere
morelikelyduetoperceptualratherthantaskrelatedlearning.Forexample,
participantsS2andS6achievedabehaviouralpassforonlyasingleelectrodepairfrom
1weekto6monthsbutthenshowedimproveddiscriminationforotherelectrode
pairsat12months.
Thereislimitedevidencefromlongitudinalstudiesthatspectralresolutionimproves
withCIexperience.Sandmannetal.(2015),showedthatinpost-linguallydeafCIusers,
theabilitytojudgethedirectionofpitchchangeinamodulatedtonecomplex
increasedrapidlyuntil8weeksafterswitch-onandthereafterplateaued.The
individualbehaviouraldatawasnotpresentedinthatstudybuttherapidasymptotic
performanceissimilartothatseeninthegoodperformerswhoachievedelectrode
discriminationceilinglevelsby1weekto3monthsinthisstudy.Jeonetal.(2015)
provideevidenceofmorelongtermimprovementsinspectralresolutionusingspectral
118
ripplediscriminationtests.Post-linguallydeafenedadultswhohadspectralripple
scoresmeasuredinapreviousstudy(Henryetal.,2005)wereretestedseveralyears
later.ThemeandurationofCIusewas2yearsattheoriginaltestpointand12.5years
atthetimeofre-testing.In3outof4cases,scoresincreasedovertime,with
considerableimprovementin2cases.Incontrast,Landsbergeretal.(2018),foundthat
spectralresolutionasmeasuredwiththeSMRTdidnotimprovewithageinpaediatric
CIusers.However,thiswasacross-sectionalstudyandmostCIusershadbeenusing
theirdeviceforseveralyearssoitispossiblethatthespectralresolutionhadimproved
priortotesting.Thedifferentfindingsinthesestudiesarelikelyduetodifferencesin
thebehaviouraltaskandstudypopulations.However,takentogether,itappearsthat
improvementsinspectral/spatialresolutionpredominantlyoccurduringthefirstfew
weekstomonthsafterswitch-onbutfurthergainsmaybepossibleoverlongperiods
oftimeincertainindividuals.
Inthisstudy,improvementsinbehaviouralelectrodediscriminationwere
accompaniedbyanincreaseinspatialACCamplitudeoverthefirst6monthsofCIuse.
WhilstchangesinthespatialACCovertimehavenotbeenpreviouslyreported,a
numberofstudieshaveassessedlongitudinalchangesindiscriminationabilityinCI
usersusingMMNmeasurements(Lonkaetal.,2004,2013;PurdyandKelly,2016;
Vavatzanidisetal.,2015).Ingeneral,thesestudieshaveshownanincreaseinMMN
amplitudewithCIexperience,butinmostcasestheMMNcouldnotberecordedinthe
earlyperiodafterswitch-on.Asmoststudiesdonotreportconcurrentbehavioural
data,itisnotclearwhethertheearlyabsenceoftheMMNisduetotheinabilityofCI
userstodiscriminatetherelevantstimuliorduetoalackofsensitivityintherecording
paradigm.
Purdyetal.(2016),measuredtheMMNtoachangeinfrequencyusingpuretone
stimuliandshowedthatMMNamplitudeincreasedandlatencydecreasedduringthe
first9monthsofCIuse,thoughthiseffectwasnotstatisticallysignificant.Ofnote,the
MMNcouldnotberecordedinthefirstweekafterswitch-onin40%ofcases,despite
thestimulibeingbehaviourallydiscriminable,suggestingalackofrecordingsensitivity.
Similarly,Lonkaetal.(2004)and(2013),measuredtheMMNtovowelcontrastsanda
changeinpuretonefrequencyrespectively.Inbothstudies,theMMNcouldnotbe
119
recordeduntil1yearafterswitch-onduetolargeCIartefact.Nonetheless,therewasa
significantincreaseinMMNamplitudefrom1yearto2.5yearsafterswitch-on.
Behaviouraldiscriminationdatawerenotreportedintheirstudyalthoughconcurrent
improvementsinspeechperceptionoccurredoverthesameperiod.Pantev(2005),
reportedlongtermchangesinacousticACCresponses,usingacontinuouspuretone
stimuluswitharegular100Hzchangeinfrequency,in2post-linguallydeafenedadult
CIusers.TheACCcouldnotberecordedforthefirst2-3monthsafterswitch-onin
eithercase.Thereaftertheresponseincreasedinamplitudeuntil6monthsforone
userandfor2yearsintheotheruser.Theseelectrophysiologicaldataprovide
evidenceforlongtermchangesinauditorydiscrimination,whichisconsistentwiththe
findingsofthisstudy.
ThedatadidnotshowaneffectofCIexperienceonthelatencyoftheN1orP2
componentsofthespatialACCresponse.Itmustbenotedthatthestudywas
underpoweredforthisanalysisasonlymeasurementswithanobjectiveACCpass
couldbeincludedinordertoobtainameaningfullatencyvalue.Purdyetal.(2016),
examinedchangesinMMNlatencyforpuretonestimuliin10adultswithCIwhowere
followedupon5occasionsover9monthsafterswitch-on.Itwasfoundthattherewas
adecreaseintheMMNlatencyovertimebutthiswasnotstatisticallysignificant.
Lonkaetal.(2013),didnotfindaneffectofCIexperienceontheMMNlatency.In
contrast,anumberofstudieshavereportedthatwithCIexperience,thereisa
shorteningoflatencyofthecorticalonsetresponse(Burdoetal.,2006;Sandmannet
al.,2015;Sharmaetal.,2005b).ThisdifferencemaybebecausetheACCandMMNare
markersofauditorydiscriminationratherthandetection.Inaddition,Heetal.(2012)
showedthatincreasingthemagnitudeofchangeacrossdifferentacousticdimensions,
suchasfrequencyorintensity,ledtoconsistentchangesintheACCamplitudebutnot
theACClatency,indicatingthatthelatterisapoorermarkerofdiscrimination.
Animportantconfoundtoconsiderwithbehaviouralandelectrophysiological
measurementsovertimeisthestimuluslevel.Duringthefirst6monthsafterCI,
stimulationlevelsrequiredbypatientsincrease(Vargasetal.,2012)duetothe
developmentofloudnesstolerance.Itisknownthatforthecorticalresponsetosound
onset,increasingstimuluslevelleadstolargeramplitudeandshorterpeaklatencyin
120
bothNHandCIpopulations(Firsztetal.,2002;Pictonetal.,1976).Thiseffectof
stimuluslevelonevokedresponsehasnotbeencontrolledforintheaforementioned
MMNstudies.InCIusers,improvedelectrodediscriminationscoreswithstimuluslevel
hasbeenreported,thoughthereismuchvariabilitybetweenindividualsandeven
betweenelectrodelocationswithinanindividual(McKayetal.,1999;Pfingstetal.,
1999).Whenelectrodepairsthatoriginallyhadabehaviouralfail,werere-testedata
latertimepointwiththesamestimulationlevels,significantlyhigherdiscrimination
scoreswereobtained.Thisshowsthatimprovementsinbehaviouraldiscrimination
overtimecannotbecompletelyaccountedforbytheincreaseinstimulationlevel.Itis
stillpossiblethatthechangesinspatialACCamplitudeovertimewereduetolevel
effects.Nonetheless,itisanimportantfindingthatthespatialACCamplitudecan
increaseatarelativelyconstantperceptuallevelandthatthisisparalleledby
improvementsinbehaviouralelectrodediscrimination.Theeffectofstimuluslevelon
electrodediscriminationisexaminedfurtherinChapter5.
4.5.2Reasonsforimprovedelectrodediscrimination
Reissetal.(2007),showedthatthepitchperceptassociatedwithanindividual
electrodecanchangebyupto2octavesovertime.Thisappearstobedrivenbythe
spectralmismatchbetweentheallocatedfrequenciesoftheCIstimulationchannels
andthecharacteristicfrequenciesofthecorrespondingauditoryneurons.Hence,the
absoluteperceptassociatedwithanelectrodemaychangeovertime,butthisdoesnot
implybetterspatialresolution.Itisthereforeinterestingtoconsidertwoquestions.
Firstly,whatwasdrivingtheimprovementinspatialresolutioninCIusersgiventhat
theydidnotundergoanydiscriminationtraining?
Theimprovementscouldbeduetotop-downprocesses-exposuretospeechandthe
feedbackthatCIusersobtainthroughtheirdailyinteractions,areinessence‘passive
training’,whichcoulddrivebetterspatialresolution.Suchatop-downeffectwasseen
inthestudybyRosenetal.(1999),whoshowedthatconnecteddiscoursetracking
trainingresultedinimprovedvowelrecognitioninCIsimulationswithNHlisteners.
Improvementsinspatialresolutioncouldalsooccurduetopassiveexposureto
electricalstimulationthroughtheCI.Kurkelaetal.(2016)passivelyexposedratsto
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behaviourallyirrelevantspeechstimulifor36hours.TheyshowedthattheMMNfor
smallchangesinspectrotemporalsoundscouldberecordedinanimalspreviously
exposedtothesesoundsbutnotintheanimalsexposedtodifferentsounds.The
authorssuggestthatpassiveexposuretosoundscanresultinaformationoflong-term
memoryrepresentationwhichaidsauditorydiscrimination.
Secondly,howandwheredoimprovementsinspatialresolutionoccurintheauditory
pathway?
AnimalstudieshaveshownthatchronicauditorystimulationwithaCIleadstore-
organizationofcorticalandsub-corticalstructures(KralandTillein,2006;Mooreetal.,
2002).Whilsttonotopicrepresentationofsoundisabsentintheauditorycortexof
neonatallydeafenedcats,thereisevidencethatchronicstimulationwithaCIcanlead
topartialrestorationoftonotopicity(Fallonetal.,2009).Dinseetal.(2003),however,
foundthata3-monthperiodofCIstimulationinneonatallydeafenedadultcatsdidnot
leadtonormalpatternsofauditorycortexactivation.Rather,individualelectrodes
wereassociatedwithbroadpatternsofoverlappingcorticalactivationandreduced
corticatonotopycomparedtoNHcats.Theauthorssuggestthatperceptual
improvementsarenotduetorestorationofnormalpatternsofcorticalactivation,but
ratherareduetolearningeffectsmediatedbylargepopulationsofoverlapping
neurons.Thereisevidencethattheareaofcorticalactivationisrelatedtobehavioural
discriminationperformance.Recanzoneetal.(1993)showedthatfrequency
discriminationtraininginowlmonkeysledtoanincreaseintheareaofrepresentation
intheauditorycortex,aswellassharpercorticaltuningforthetrainedfrequencies.Of
note,theareaofrepresentationwascorrelatedwithbehaviouraldiscrimination
performancesuggestingthatthecorticalspatialcodeisimportantforfrequency
discrimination.ImprovedelectrodediscriminationinCIusers,maybeduetoincreased
corticalrepresentationofelectrodesinassociationwithhigherauditorylearning.
Thereis,however,evidencefortonotopicorganizationintheauditorycortexofadult
CIusers(Guiraudetal.,2007).Itisthereforepossiblethatlong-termuseofaCIleads
torestorationoftonotopyintheauditorypathway.Atthispointintime,the
mechanismbywhichauditorydiscriminationimprovesinCIusersremainspoorly
understoodandfurtherresearchintothisareaisrequired.
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4.5.3RelationshipbetweenthespatialACCandbehaviouralelectrodediscrimination
AhighlevelofagreementbetweenthespatialACCandbehaviouraldiscriminationwas
found.In12outof120caseshowever,theACCcouldnotberecordeddespite
accuratebehaviouraldiscrimination.Eightofthese‘falsenegative’recordingswere
fromparticipantS11.Theabsenceofaresponsewasthoughttobeduetooverlap
betweenaprolongedonsetresponseandtheACC.Thishypothesiswassubsequently
testedbymeasuringthespatialACCinthisparticipantusingalongerduration
stimulus.Twoconditionswereused,eachwithachangeinstimulatingelectrodeatthe
midpointofthestimulus.Thefirstconditionwasthestandardstimulus,which
consistedofbiphasicpulsesof800msdurationpresentedat0.51Hz.Forthetest
condition,thestimulushaddurationof1400msandwaspresentedatarateof0.4Hz.
Thesamestimulationlevelwasusedforbothconditions.Ascanbeseeninfigure4.7,
theACCisclearlyseeninthetestconditionbutnotthestandardcondition.Thisshows
thatthesensitivityofthespatialACCcanbeimprovedbyalteringstimulus
characteristicsandthisisexaminedfurtherinChapter6.
Disagreementbetweentheobjectiveandbehaviouralmeasurementsalsooccurred
whenasignificantspatialACCresponsewasrecordeddespitepoorbehavioural
discrimination.Thiswasobservedfor9electrodepairsfrom4CIusers.Previously,it
washypothesizedthatthepresenceofthese‘falsepositive’recordingsindicatedthe
potentialtodevelopaccuratediscrimination.Inthislongitudinalstudy,itwasshown
thatthisisindeedthecase.In8outof9‘falsepositive’recordings,abehaviouralpass
wasachievedatalaterdate.InterestinglyforparticipantS2,theACCforelectrodepair
2-3wasconsistentlypresentfrom1weekonwardsbutabehaviouralpasswasonly
achievedat12monthsafterswitch-on.
Tremblayetal.(1998),measuredMMNandbehaviouraldiscriminationaftertraining
participantstodiscriminatestimulithatdifferedinvoiceonsettime.Fouroutoften
participantsshowedsignificantchangesinMMNpriortochangesinidentification
ability.Similarly,Trautweinetal.(1998),measureddurationdiscriminationthresholds
withbehaviouralandMMNmeasurementsinCIusers.TheMMNthresholdwasfound
tobesmallerthanthebehaviouralthresholdin6/8casessuggestingtheMMNisa
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moresensitivemeasureofdiscrimination.Thegreatestdisparitybetweenobjective
andbehaviouralmeasureswasseeninpre-linguallydeafenedadults.Inthisstudy,3
outof4oftheparticipantswith‘falsepositive’ACCrecordingshadpre-orperi-lingual
onsetdeafness.Onlyoneparticipanthadpost-lingualonsetdeafness-althoughthis
participanthadprofounddeafnessfor10years,thedurationofbilateralhearingloss
was57years.Earlyonsetandlongdurationsofdeafness,arelikelyassociatedwitha
longertimecourseforauditorylearningandcouldaffectanindividual’sabilityto
perceiveastimuluschangethatisencodedintheauditorysystem.Further
confirmationofthesefindingsarerequired,butthesedatasuggestthattheACCmay
precedethedevelopmentofaccuratebehaviouralresponsesandthismaymakeit
particularlyusefulfromaclinicalpointofview.
Figure4.7SpatialACCrecordingsusingstimuliwithdifferentdurations.(A)TheACCisabsentforthestandardstimulus(800msduration,presentedat0.51Hz).(B)AclearACCresponseisseenfortheteststimulus(1400msduration,presentedat0.4Hz).Stimuliconsistedofbiphasicpulsesat1000ppswithachangeinstimulatingelectrodeatthemidpointofthestimulus.Hotelling-T2(HT2)pvaluesareshownaboveeachpanel.Dataareforelectrodepair4-5inparticipantS11andarepresentedatFCz.Shadedareasandhorizontallinesareasdescribedinfigure4.4.
124
125
4.5.4Electrodediscriminationandspeechperception
InkeepingwiththeresultsofChapter3,itwasfoundthatbehaviouralelectrode
discriminationscoreisasignificantpredictorofspeechperception.Itmustbebornein
mindthatonlyalimitedrangeofelectrodesweretestedinthisstudyandtheallocated
frequencieswouldonlycoverthefirstformantregionofspeech.Apicalelectrode
discriminationdoesnotnecessarilyreflectdiscriminationabilityintherestoftheCI
array.Thismayexplainthedisparitybetweenelectrodediscriminationperformance
andspeechperceptionincertainparticipantssuchasS8whohadexcellentapical
electrodediscriminationbutrelativelypoorsentenceperception,orS1whohad
relativelypoorapicaldiscriminationbutexcellentspeechperception.
AsignificantrelationshipbetweentheamplitudeofthespatialACCandspeech
perceptionwasnotfoundinthisstudy.Wableetal.(2000),measuredelectrode
discriminationaroundasingleapicalelectrodewiththeMMNanddidnotfinda
correlationbetweenspeechperceptionandMMNlatencyoramplitude.Thelackof
relationshipbetweentheACCamplitudeandspeechperceptionmaybeduetoa
numberofreasons.Firstly,thereislargeinter-subjectvariabilityinACCamplitude.This
variabilityhasbeenobservedinotherstudiesofNHandCIpopulations(Brownetal.,
2008;Heetal.,2012,2014)andislikelyaresultofdifferencesincorticalfoldingand
resultantdipoleorientations.InthestudybyHeetal.(2012),theACCamplitude
elicitedbyachangeinfrequencyof100Hz,variedfrom1.51to6.85µVinNH
individuals.Secondly,theACCresponsedidnotalwaysreflectbehavioural
discriminationability(discussedinsection4.5.3).InanumberofcasesthespatialACC
couldberecordeddespitepoorbehaviouraldiscriminationandappearedtoreflect
discriminationpotentialratherthanability.ItmaybethatthespatialACCisamore
stronglycorrelatedwithspeechperceptioninexperiencedCIusersinwhomthefull
potentialfordiscriminationhasbeenachieved.Indeed,Heetal.2014foundthatthe
EDLmeasuredaroundamid-arrayelectrodewiththespatialACCwasassociatedwith
speechperceptionwhencategorizedas‘good’or‘poor’.Ofnote,mostofthe
participantsintheirstudyhadseveralyearsofCIexperience.
126
Thesedataprovidefurtherevidencethatbehaviouralelectrodediscriminationis
relatedtospeechperception.Interventionsthatenhancespatialresolutionmay
thereforeimprovehearingperformance.
4.6Conclusions
Thisstudyprovidesbehaviouralandelectrophysiologicalevidenceforimprovementsin
discriminationabilityinCIusersovertime.Thisisparalleledbyimprovementsin
speechperception.Theabilityoftheauditorysystemtoadapttoelectricalstimulation
throughtheCIunderliestheexcellentoutcomesthatthistechnologyyields.This
processofadaptationisslowerandmorelimitedincertainindividualsandtargeted
therapiestoexploitauditoryplasticitymayhelpimprovehearingperformancefurther.
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Chapter5 Theeffectofstimulusintensityonelectrode
discrimination
5.1Abstract
InChapter4,itwasfoundthattheamplitudeofthespatialauditorychangecomplex
(ACC)increasedsignificantlyoverthefirst6monthsofcochlearimplant(CI)use.These
measurementscouldhavebeenconfoundedbychangesinloudnessperceptionthatCI
usersexperienceintheearlyperiodafterswitch-on.Theaimofthisstudywasto
determinetheeffectofstimulusintensityonthecharacteristicsoftheACCaswellas
itssensitivityasameasureofbehaviouralelectrodediscrimination.Behavioural
electrodediscriminationandthespatialACCweremeasuredinadultCIusersat
stimulusintensitiesrangingfrom40to80%oftheelectricaldynamicrange(DR).
IncreasingstimulusintensityledtoanincreaseinthespatialACCamplitudewhichwas
accompaniedbyimprovementsinbehaviouralelectrodediscrimination.Thesensitivity
ofthespatialACCasameasureofbehaviouraldiscriminationdecreasedatthelower
endoftheDR.Thesedatashowthatitisimportanttoconsidertheeffectofstimulus
presentationlevelwhenmeasuringthespatialACC.
5.2Introduction
InChapter4itwasfoundthatthespatialACCamplitudeandbehaviouralelectrode
discriminationscoresincreasedsignificantlyoverthefirst6to12monthsofCIuse.As
discussedinChapter4,thesemeasurementscouldhavebeenconfoundedbythe
effectofstimulusintensity.ThespatialACCandbehaviouraldiscriminationwere
testedattheMClevel,whichwasre-measuredateachtimepoint,inordertomaintain
arelativelyconstantperceptuallevel.However,inordertoachievethis,higher
stimulationlevelswererequiredovertimeinmostparticipants.
Studiesofthecorticalonsetresponsehaveshownthatincreasingstimulusintensity
leadstolargerpeakamplitudesandshorterpeaklatenciesinNH(Picton,2010)andCI
populations(Firsztetal.,2002).Unlikethecorticalonsetresponse,theACCisa
measureofauditorydiscriminationandtherefore,maybeaffecteddifferentlyby
128
changesinstimulusintensity.Todate,theeffectofstimulusintensityontheACChas
notbeencharacterized.
TherelationshipbetweenstimulusintensityandthespatialACCmightbeinferred
fromstudiesexaminingthetherelationshipbetweenstimulusintensityand
behaviouralelectrodediscrimination.McKayetal.(1999)showedthattherewasas
significantimprovementinbehaviouralelectrodediscriminationwithstimuluslevel,
althoughtheexactnatureoftherelationshipvariedbetweenandwithinindividualsfor
differentelectrodelocations.ChatterjeeandYu(2010)similarlyfoundthatelectrode
discriminationimprovedwithstimuluslevelinmostCIusers,irrespectiveofwhethera
bipolarormonopolarconfigurationwasused.Pfingstetal.(1999),didnotfinda
significanteffectoflevelonelectrodediscriminationscoreforadjacentelectrode
pairs.However,forelectrodelocationswheretheEDLwasgreaterthanone,therewas
asignificantimprovementindiscriminationscoreswithlevel.Basedonthesestudies,
itmightbeexpectedthatincreasingstimulusintensitywouldleadtoalarger
magnitudeACCresponse.
StimulusintensitymayalsoaffecttherelationshipbetweenthespatialACCand
behaviouralelectrodediscrimination.Inthepreviousstudiesthatfoundastrong
relationshipbetweenthespatialACCandbehaviouraldiscrimination(Chapters3and
4;Heetal.,2014)stimuliwerepresentedatloudbutcomfortablelevelsortheMC
leveli.e.intheupperpartoftheDR.Sincespeechisdynamic,theabilityto
discriminateelectrodesacrosstheDRmaybecorrelatedwithspeechperception.Ifthe
spatialACCistobeusedtoassesselectrodediscriminationatthelowerendoftheDR,
thenitwillbeimportanttodetermineitssensitivityasameasureofbehavioural
discriminationatlowerstimuluslevels.
IthasbeenhypothesizedthathighthresholdlevelsandsmallDRmeasurementsare
associatedwithanimpoverishedelectrode-neuralinterface(Bierer,2010).Ifthisisthe
case,thenitmightbeexpectedthatelectrodeswithhighthresholds/lowDRwillalso
havepoorelectrodediscrimination.Pfingstetal.(1999),usedabipolarconfiguration
andfoundthatbehaviouralelectrodediscriminationwascorrelatedwithDRbutnot
thresholdlevels.Therelationshipbetweenelectrodediscriminationandthreshold/DR
129
measurementswithamonopolarconfiguration,whichleadstobroaderpatternsof
excitation,isyettobeexamined.
Themainobjectivesofthisaimsofthisstudywereto:
1)determinetheeffectofstimulusintensityonthespatialACCamplitudeand
behaviouralelectrodediscriminationability
2)examinethesensitivityofthespatialACCasameasureofbehavioural
discriminationatdifferentstimulusintensitylevels
Subsidiaryobjectiveswereto:
3)examinetherelationshipbetweenelectrodediscriminationandthreshold/DR
measurements
4)examinetherelationshipbetweenelectrodediscriminationabilityacrosstheDRand
speechperception
5.3Experiment4:DesignandMethods
5.3.1Participants
Nineparticipantsranginginagefrom42to69yearswereincludedinthestudy.All
participantswereunilaterallyimplantedwithanABHiRes90Kdeviceandhadtaken
partinexperiment3(Chapter4).Demographicdetailsaresummarizedintable5.1.Of
note,4oftheparticipantshadpreorperi-lingualonsetdeafness.Whilstmost
participantshadaround1yearofCIexperience,P1hadbeenusingherCIforalmost7
yearsatthetimeoftesting.Noneoftheparticipantshadsignificantresidualhearingin
thecontra-lateralear.
5.3.2Testprocedures
ThestimuliforEEGwereasdescribedintheGeneralMethods(Chapter2)-800ms
alternatingpolaritybiphasicpulsetrainspresentedatarateof0.51Hz.Asingle
electrodepairwaschosenfortestingineachparticipant.Sincetheaimofthisstudy
wastodeterminetheeffectofstimuluslevelonelectrodediscrimination,itwas
130
importanttoavoidchoosinganelectrodepairwhichwasindiscriminablethroughout
theDR.Electrode4,whichtypicallyrepresentsfrequenciesof587to697HzintheAB
devicewaschosenasthereferenceelectrodeforallparticipants.Thisisbecause,in
previousexperimentswiththesameparticipants,itwasfoundthatthiselectrodewas
welldiscriminatedfromneighbouringelectrodes.TheDRofthereferenceelectrode
wasdeterminedusinganascendingmethodofadjustment.Stimulationbeganata
levelwhichwasinaudibleandincreasedin5µAstepsuntilparticipantsreportedthat
theycouldjusthearasound.Thethresholdlevelwasdeterminedbyrepeatingthis
procedureuntilthesamevaluewasobtainedtwiceinarow.Theloudnessdiscomfort
level(LDL)wasthendeterminedbygraduallyincreasingthestimulationleveluntil
participantsindicatedthattheloudnesswasatpoint9ona10-pointABloudness
chart.TheDRforthereferenceelectrodewascalculatedas20xlog10(LDL/Threshold
level).
Electrode4wasthenpairedwithaneighbouringelectrodefollowingashortscreening
procedurefordiscriminability.Electrode4wasinitiallypairedwithelectrode5inall
participantsanditsstimulationlevelwassetto80%oftheDR.Inordertoreduce
loudnesscueswhenswitchingelectrodes,aloudnessbalancingproceduresimilarto
thatdescribedintheGeneralMethods(Chapter2)wasused.Thestimulationlevelfor
thetestelectrodewassettothesamelevelasthereferenceelectrode.Thereference
andtestelectrodewerethenstimulatedinsequenceseparatedbyagapof600msand
thelevelofthetestelectrodewasadjusteduntilbothstimuliwereperceivedtohave
thesameloudness.Thisprocedurewasrepeatedandifthesamevaluewasobtained
consecutivelythenthislevelwasusedforthetestelectrode;ifnot,thenloudness
balancingwasperformedathirdtimeandtheaveragewasusedastheloudness
balancedlevel.
Participantswerethenaskedwhethertheyperceivedacleardifferenceinpitch
betweenelectrode4and5duringsequentialstimulationattheloudnessbalanced
level.Iftheyfailedtodoso,thenthesameelectrodepairwastestedat40%oftheDR
followingloudnessbalancing.Thiswasdone,aspreviousstudieshaveshownthat
electrodediscriminationcanbebetteratthelowerendoftheDRincertain
individuals/electrodelocations(McKayetal.,1999;Pfingstetal.,1999).Ifparticipants
131
stillfailedtoperceiveadifferenceinpitch,thenelectrode4waspairedwithelectrode
6andthescreeningprocedurewasrepeated.Alloftheparticipantsperceiveda
differenceinpitchwitheitherelectrode5or6,sonootherelectrodesweretested.
Thedetailsofelectrodespairstested,thresholdlevelandLDLforeachparticipantare
shownintable5.2.
Forthemainexperimenttherewere5conditionswhichvariedinstimulusintensity–
theseincludedstimulationlevelsof40,50,60,70and80%ofthelinearDRofthe
referenceelectrodecalculatedinµA.Ineachcasethecorrespondingloudness
balancedlevelofthetestelectrodewasdeterminedusingtheproceduredescribed
above.Thestandarddeviationoftheloudnessbalancingmeasurementswas1.81µA
(range0–8.66µA).
EEGrecordingandprocessingwasperformedasdescribedintheGeneralMethods.In
totaltherewere45EEGmeasurements(5conditionsfor9participants).
ThepresenceorabsenceoftheACCwasdeterminedbymeansoftheHotelling-T2test
intheACCresponsewindowfrom450–650msafterstimulusonset.For6/45
recordings,theresponsewindowwasadjustedto450-700ms,duetoalateP2
component.
Behaviouralelectrodediscriminationwastestedateachstimuluslevelandspeech
perceptionwastestedusingopen-setBKBsentences-in-quiet.Theproceduresfor
testingbehaviouraldiscriminationandspeechperceptionaredescribedintheGeneral
Methods.EEG,behaviouralandspeechtestingweredoneinasinglesessionwhich
lastedapproximately2.5hoursincludingbreaks.
Table5.1Demographicdetailsofparticipantsinexperiment4.F=female,M=male,R=right,L=left
Participant Age Sex EarRiskfactorfor
hearinglossCommunication
Ageatdeafness
onset(years)DurationofCIuse Electrode
P1 42 F R Unknown oral 1.5 6years10months 1J
S1 53 M R Unknown oral 41 14months MidScala
S2 52 F R Unknown oral+sign 0 12months MidScala
S3 44 F L Unknown oral 24 14months MidScala
S4 50 M L Maternalrubella oral 2 14months 1J
S5 48 F L Unknown oral 5 11months MidScala
S6 69 F L Unknown oral 58 10months MidScala
S8 52 F R Unknown oral 46 11months MidScala
S9 49 M L Unknown oral 47 8months MidScala
132
133
Table5.2Detailsoftheelectrodepairtestedinexperiment4.Thresholdandloudnessdiscomfortlevelsforthereferenceelectrode(electrode4)areshown.
Participant Electrode
pair tested
Threshold level
(µA)
Loudness discomfort
level (µA)
P1 4-6 75 240
S1 4-5 150 450
S2 4-5 140 460
S3 4-5 110 370
S4 4-5 130 630
S5 4-6 110 360
S6 4-6 120 450
S8 4-5 130 360
S9 4-5 110 370
5.4Results
5.4.1Effectofstimulusintensityonbehaviouraldiscrimination
Figure5.1showstheeffectofstimulusintensityonbehaviouraldiscrimination
accordingtowhichelectrodewastested(4-5or4-6).Thebrokenlinesshowindividual
datawhilstthesolidblacklinerepresentsthemeanscoreacrossparticipants.This
figureshowsthatinbothgroups,themeanbehaviouraldiscriminationscoreincreases
withstimulusintensityandthiseffectisgreatestinthelowerpartofDR.Thereis
howeversubstantialinter-individualvariabilityintherelationshipbetweenstimulus
intensityandbehaviouraldiscrimination.Whilstdiscriminationabilitywasexcellent
throughoutthetestedDRinmostparticipants,itwashighlydependenton
presentationlevelinparticipantsP1,S2,S5andS6.Ofnote,threeoftheseparticipants
wereintheelectrode4-6group.Electrodediscriminationdidnotdecreasesignificantly
withincreasingstimuluslevelinanyoftheparticipants.Althoughscoresfor
participantsS1andS6decreasedforthe80%DRcondition,thesewerestillabovethe
thresholdforabehaviouralpass(score≥80%).ThescoreforparticipantS2decreased
forthe70%DRconditionbutthenincreasedagainforthe80%oftheDR.Thenumber
ofparticipantswithabehaviouralpasswas4/9,6/9,8/9,7/9and9/9forthe5
intensityconditions(inascendingorderofstimulusintensity).
134
Figure5.1Relationshipbetweenstimulusintensityandbehaviouralelectrodediscriminationscoreaccordingtowhichelectrodepairwastested.Electrodepair4-6wastestedinindividualswhocouldnotdiscriminateelectrodepair4-5asdeterminedbyascreeningprocedure.ThebrokenlinesshowthedataforindividualCIusers.Thesolidblacklineshowsthemeanscoresacrossparticipantsineachgroupwitherrorbarsrepresentingthestandarderrorofthemean.Randomnoisehasbeenaddedtothediscriminationscoresinordertoimprovedatavisualization.
Theeffectofstimulusintensityonbehaviouraldiscriminationwasanalyzedwitha
mixed-effectsmodel.Thedependentvariablewasthebehaviouraldiscriminationd’
scoreandthefixedeffectsincluded‘stimulusintensity’,‘electrodepair’(4-5or4-6)
andtheinteractionterm.Theanalysisshowedthattherewasasignificanteffectof
‘stimulusintensity’(F(4,28)=15,p<0.001)andtheinteractionterm(F(4,28)=4.9,p=
0.0042)whilstthe‘electrodepair’wasnotsignificant(F(1,7)=4.5,p=0.072)(seetable
5.3).Post-hocpairwisecomparisonwithTukeycorrectionshowedthatforparticipants
inwhomelectrode4-5wastested,therewasonlyasignificantdifferencein
discriminationscorebetweencontrastsinvolvingthe40%DRcondition.The
behaviourald’scoreforthe40%DRconditionwassignificantlylowerthanthe60%,
70%and80%DRconditions(p<0.05forall3contrasts).Therewereonly3
participantsinwhomelectrode4-6wastested.Post-hocTukeytestshowedthatthere
wasasignificantdifferencebetweencontrastsinvolvingthe40%and50%DR
135
conditions.Thebehaviourald’scoreforboththe40%and50%DRconditionswere
significantlylessthanthe60%,70%and80%DRconditions(p<0.05forallcontrasts).
Table5.3Mixedmodelanalysisoffactorsaffectingbehaviouralelectrodediscriminationscore.
Factor
Degreesof
freedom
(numerator,
denominator)
F
value
P
value
Effect
size
95%confidence
intervalofeffectsize
Intensity (4,28) 15 <0.001 0.684 0.527–0.828
Electrode
pair(1,7) 4.5 0.072 0.389 0.012–0.821
Electrode
pair*
intensity
(4,28) 4.9 0.004 0.410 0.214–0.668
Thisanalysisshowsthatincreasingstimulusintensityleadstoimprovedbehavioural
electrodediscrimination,particularlyinthelowerpartoftheDR.Theeffectwasless
pronouncedinparticipantsinwhomelectrode4-5wastestedandthisislikelydueto
ceilingeffectsinthisgroup.
5.4.2Effectofstimulusintensityoncorticalresponseamplitude
Figure5.2AshowstherelationshipbetweenspatialACCN1-P2amplitudeandstimulus
intensity.Thesolidblacklinerepresentsthemeanamplitudeacrossallparticipants.
Therewasnoobviousdifferencebetweenparticipantsinwhomelectrodepair4-5or
4-6wastestedandthereforeallthedataareshowninasingleplot.Thisfigureshows
thatmeanspatialACCamplitudeincreaseswithstimulusintensitybutplateausaround
70%oftheDR.Similartothebehaviouraldata,theindividualdatadisplaysmuchinter-
individualvariability,bothintermsofabsoluteamplitudevaluesandtherelationship
withstimulusintensity.TheACCamplitudeincreasedwithstimulusintensityinmost
participantsexceptforS3inwhomtheACCamplitudewashighthroughouttheDR.
Thenumberofparticipantswithanobjectivepasswas1/9,3/9,6/9,7/9and9/9for
the5intensityconditions(inascendingorderofstimulusintensity).
136
Figure5.2EffectofstimulusintensityontheN1-P2amplitude.DataareshownforthespatialACCin(A)andforthecorticalonsetresponsein(B).ThebrokenlinesshowthedataforindividualCIusers.Thesolidblacklineshowsthemeanamplitudeacrossparticipantsineachgroupwitherrorbarsrepresentingthestandarderrorofthemean.
Amixed-effectsmodelwasusedtoanalyzethefactorsaffectingspatialACCN1-P2
amplitude.Thefixedeffectsincluded‘stimulusintensity’,‘electrodepair’andthe
interactionterm.Thisshowedthattherewasnosignificanteffectof‘electrodepair’or
theinteractiontermandthesefactorswerethereforeremovedfromthemodel(see
table5.4).Analysisofthereducedmodelshowedthattherewasasignificanteffectof
‘stimulusintensity’(F(4,32)=14,p<0.001).Post-hocpairwisecomparisonwithTukey
correctionshowedthattherewasonlyasignificantdifferenceincontrastsinvolving
the40%and50%DRconditions.Theamplitudeofthe40%conditionwassignificantly
lessthanthatofthe60%,70%and80%DRconditions(p<0.05forall3contrasts),
whilsttheamplitudeofthe50%conditionwassignificantlylessthanthatofthe70%
and80%DRconditions(p<0.01forbothcontrasts).
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Table5.4MixedmodelanalysisoffactorsaffectingACCresponseamplitude.
Factor
Degreesof
freedom
(numerator,
denominator)
F value Pvalue Effectsize
95%confidence
intervalofeffect
size
Initialmodel
Intensity (4,28) 11 <0.001 0.618 0.441–0.791
Electrode
pair(1,7) 2.0 0.205 0.218 0.001–0.741
Electrode
pair*
intensity
(4,28) 0.15 0.961 0.021 0.019–0.349
Reducedmodel
Intensity (4,32) 14 <0.001 0.639 0.478–0.793
Therelationshipbetweenstimulusintensityandthecorticalonsetresponseamplitude
isshowninfigure5.2B.Thisshowsthatthemeanonsetresponseamplitudealso
increaseswithstimulusintensitybuteffectivelyplateausat50%oftheDR.Amixed-
effectsanalysiswasconductedwiththedependentvariable‘onsetresponseN1-P2
amplitude’.Thefixedeffectsincluded‘stimulusintensity’,‘electrodepair’andthe
interactionterm.SimilartothespatialACCanalysis,therewasnosignificanteffectof
‘electrodepair’ortheinteractiontermandthesewerethereforeremovedfromthe
model(table5.5).Analysisofthereducedmodelshowedthattherewasasignificant
effectof‘stimulusintensity’(F(4,32)=4.0,p=0.010).Post-hocpairwisecomparisons
withTukeycorrectionshowedthattheamplitudeofthe40%DRconditionwas
significantlylessthan70%and80%DRconditions(p<0.05).Noneoftheother
contrastswerestatisticallysignificant.
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Table5.5Mixedmodelanalysisoffactorsaffectingcorticalonsetresponseamplitude.
Factor
Degreesof
freedom
(numerator,
denominator)
F value Pvalue Effectsize
95%confidence
intervalofeffect
size
Initialmodel
Intensity (4,28) 3.4 0.022 0.325 0.145–0.613
Electrode
pair(1,7) 4.3 0.077 0.380 0.010–0.818
Electrode
pair*
intensity
(4,28) 0.48 0.750 0.064 0.026–0.401
Reducedmodel
Intensity (4,32) 4.0 0.010 0.331 0.155–0.598
Thesedatashowthatsimilartobehaviouraldiscriminationscores,theamplitudeof
thespatialACCincreaseswithstimulusintensityandtheeffectisgreaterinthelower
partoftheDR.Stimulusintensityappearstohaveagreaterrelativeeffectonthe
spatialACCamplitudecomparedtotheonsetresponse,atleastintheDRthatwas
testedintheseparticipants.
5.4.3RelationshipbetweenthespatialACCandbehaviouralelectrodediscrimination
Therelationshipbetweenbehaviouralandobjectivemeasuresofelectrode
discriminationwasexaminedusingthepassfailrulesdescribedintheGeneral
Methods.Theresultsofthisareshownintable5.6.Theagreementbetweenboth
measureswas6/9,6/9,5/9,7/9and9/9forthe5intensityconditions(inascending
order).Thedisagreementswerepredominantlyduetoalackofsensitivityofthe
spatialACCinthelowerpartoftheDR.ThesensitivityofthespatialACCwas
calculatedastheproportionofelectrodepairswithabehaviouralpass(score≥80%)
whichhadasignificantspatialACCresponseaccordingtoobjectivepasscriteria.Figure
5.3showsthatthesensitivityoftheACCincreaseswithstimulusintensity.Two
disagreementsbetweenobjectiveandbehaviouralmeasuresoccurredduetothe
presenceofaspatialACCdespiteabehaviouralfailinparticipantP1.Figure5.4shows
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thecorticalresponsesforthesecases.OfnoteparticipantP1hadcongenitalonset
deafnessandthistypeof‘falsepositive’spatialACCwasobservedinChapters3and4.
Table5.6Agreementbetweenobjectiveandbehaviouralmeasuresofelectrodediscriminationatdifferentstimulusintensities.
Outcomeofobjectiveandbehaviouralmeasures
Stimulusintensity(%DR)
40% 50% 60% 70% 80%
BehaviouralfailObjectivefail
5 3 0 1 0
BehaviouralpassObjectivepass
1 3 5 6 9
BehaviouralfailObjectivepass
0 0 1 1 0
BehaviouralpassObjectivefail
3 3 3 1 0
Totalagreement 6/9 6/9 5/9 7/9 9/9
Figure5.3RelationshipbetweenstimulusintensityandspatialACCsensitivity.SensitivitywascalculatedastheproportionofelectrodepairswithabehaviouralpassthatalsohadanobjectiveACCpass.Thisproportionisshownaboveeachbar.
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Therelationshipbetweenobjectiveandbehaviouralmeasuresofelectrode
discriminationcanalsobeexaminedbycorrelatingthespatialACCamplitudeand
behaviourald’scoresacrossparticipants.ThespatialACCamplitudeandbehaviourald’
scoreswerecollapsedtothemeanacrossthe5intensityconditionsforeach
participant.Pearson’scorrelationshowedthattherewasnosignificantrelationship
betweenthetwomeasures(r=0.27,95%confidenceinterval[-0.48,0.79],p=0.48).
TheseresultsshowthatthespatialACCisamorereliablemeasureofelectrode
discriminationathigherstimulusintensitylevels.TheamplitudeofthespatialACC
appearstobeapoorpredictorofbehavioraldiscriminationacrossparticipants.
Figure5.4CorticalresponseswithanobjectiveACCpassdespiteabehaviouralfailinparticipantP1.Thestimuluslevel,behaviouralscoreandHotelling-T2(HT2)pvalueisindicatedoneachpanel.Thetimewindowsusedtodetectpositiveandnegativepeaksfortheonsetresponse(P1,N1,andP2)andACC(cP1,cN1,andcP2)areshowninpinkandblue,respectively.Thehorizontallinescorrespondtothelevelofresidualnoise.Scalpvoltagemapsforautomaticallydetectedpeaksaredisplayed,withblacklinesrepresentingisopotentialcontourlines.DataatchannelFCzarepresented.
141
142
5.4.4Relationshipbetweenelectrodediscrimination,thresholdlevelandDR
AmeasureofdiscriminationabilityacrosstheDRwasobtainedbycalculating1)the
meanbehaviourald’scoreand2)themeanspatialACCamplitudeacrossthe5
intensityconditionsforeachparticipant.Figure5.5showsthatthereisnoclear
relationshipbetweenmeanbehaviourald’scoreandthresholdlevelorDRofthe
referenceelectrode.CorrelationanalysiswasperformedwithPearson’scorrelationfor
thethresholdlevelandSpearman’srankcorrelationcoefficientfortheDR,sincethe
latterwasnotnormallydistributed.Thisshowedthatthereisnosignificant
relationshipbetweenmeanbehaviourald’scoreandthresholdlevel(r=0.22,95%
confidenceinterval[-0.52,0.77],p=0.57)orDR(rho=-0.13,95%confidenceinterval
[-0.76,0.76],p=0.75).Usingthemeanbehaviourald’scoreislimitedbythefactthat
mostparticipantshadreachedceilinglevelsby50-60%oftheDR.Therefore,the
correlationanalysiswasrepeatedusingthebehaviouraldiscriminationscoreforthe
40%DRconditionalone.Again,nosignificantrelationshipwasfound(forthreshold:r=
0.37,95%confidenceinterval[-0.39,0.83],p=0.33andforDR:rho=-0.14,95%
confidenceinterval[-0.81,0.74],p=0.72).TherelationshipbetweenmeanspatialACC
amplitudeandthresholdlevel/DRisshowninfigure5.6.Again,correlationanalysis
showednosignificantrelationshipbetweenmeanspatialACCamplitudeandthreshold
level(r=-0.42,95%confidenceinterval[-0.85,0.34],p=0.26)orDR(rho=0.05,95%
confidenceinterval[-0.74,0.74],p=0.91).
Thestudyisunderpoweredforthistypecorrelationanalysisandthepvaluesmust
thereforebeinterpretedwithcaution.Nonetheless,visualizationofthedatadoesnot
indicateanyclearrelationshipbetweenmeasuresofelectrodediscriminationand
threshold/DRusingamonopolarconfiguration.
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Figure5.5Relationshipbetweenreferenceelectrodeparametersandmeanbehaviouralelectrodediscriminationscore.Theabscissashowsreferenceelectrodethresholdlevel(A)orDR(B).Theordinateshowsmeanbehaviouraldiscriminationscoresacrossthe5intensityconditionsforeachparticipant.Correlationcoefficientsandpvaluesareshownaboveeachpanel.
Figure5.6RelationshipbetweenreferenceelectrodeparametersandmeanspatialACCamplitude.Theabscissashowsthresholdlevel(A)orDR(B)ofthereferenceelectrode.TheordinateshowsmeanspatialACCamplitudeacrossthe5intensityconditionsforeachparticipant.Correlationcoefficientsandpvaluesareshownaboveeachpanel.
5.4.5Relationshipbetweenelectrodediscriminationandspeechperception
Itwashypothesizedthatparticipantswhocoulddiscriminateelectrodeswellacross
thewholeDRrangewouldhavebetterspeechperception.Therelationshipbetween
sentenceperceptionandmeanelectrodediscriminationscoreacrossthe5intensity
conditionsisshowninfigure5.7.ParticipantS2,whowashadcongenitaldeafnessand
(A) r = 0.22 p = 0.57 (B) rho = -0.13, p = 0.75
(A) r = -0.42 p = 0.26 (B) rho = 0.05, p = 0.91
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wasatotalcommunicator(oralandsignlanguage),hadaspeechperceptionscoreof
0%andappearstobeanoutlier.Spearman’srankcorrelationanalysisshowedthat
thattherewasnosignificantrelationshipbetweensentenceperceptionscoreand
meanbehaviourald’score(rho=0.50,95%confidenceinterval[-0.26,0.95],p=0.17).
Incontrast,asignificantrelationshipbetweenmeanspatialACCamplitudeand
sentenceperceptionscorewasfoundusingSpearman’srankcorrelationanalysis(rho=
0.77,95%confidenceinterval[-0.08,1.00],p=0.021).Again,duetothesmallnumber
ofparticipantsitisdifficulttodrawstrongconclusionsfromthisdata.However,itis
possiblethatelectrodediscriminationabilityacrosstheDRisimportantforspeech
perception.
Figure5.7Relationshipbetweensentenceperceptionscoreandmeasuresofelectrodediscrimination.Open-setsentenceperceptionwasassessedwithBKBsentences.Themeanbehaviouraldiscriminationscore(A)andmeanspatialACCamplitude(B)werecalculatedbytakingtheaverageofthevaluesacrossthe5intensityconditionsforeachparticipant.ParticipantS2,whohadpre-lingualonsetdeafnessandusedtotalcommunication(oralandsignlanguage),ishighlightedasanoutlier.Correlationcoefficientsandpvaluesareshownaboveeachpanel.
5.5Discussion
ThisisthefirststudytoexaminetheeffectofstimulusintensityontheACC.Itwas
foundthatincreasingstimulusintensityledtoasignificantincreaseintheamplitudeof
thespatialACCaswellasthecorticalonsetresponse.Thiswasaccompaniedby
improvementsinbehaviouralelectrodediscrimination.Furthermore,thesensitivityof
(A) rho = 0.50, p = 0.17 (B) rho = 0.77, p = 0.021
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thespatialACCasameasureofbehaviouralelectrodediscrimination,wasfoundtobe
pooreratlowerstimuluspresentationlevels.
5.5.1Stimulusintensityandauditorycorticalresponses
Thefindingsofthisstudyareconsistentwithpreviousstudies,whichhaveshownthat
increasingstimulusintensityleadstoanincreaseintheamplitudeofthecorticalonset
responseinbothNH(Picton,2010)andCIpopulations(Firsztetal.,2002).Itwasfound
thatstimulusintensityhadagreaterrelativeeffectonthespatialACCamplitude
comparedtotheonsetresponseamplitude,intheDRtestedinthisexperiment.On
average,thespatialACCamplitudeincreasedwithlevelupto70%oftheDR,whilefor
theonsetresponseamplitudetherewaslittleeffectoflevelbeyond50%oftheDR.
ThisdifferencemaybeduetothefactthatthespatialACCisadiscriminatory
potential,whiletheonsetresponseoccursduetoachangefromsilencetosound.The
effectofstimulusintensityonthespatialACClatencywasnotanalyzed.Thisisbecause
asignificantspatialACCresponsewasabsentinalargeproportionofmeasurements,
particularlyatthelowerendoftheDR,andameaningfullatencycouldnotbe
obtainedinthesecases.
AcommonapproachinlongitudinalstudiesofauditoryevokedcorticalresponsesinCI
usersistopresentstimuliatarelativelyconstantperceptuallevel.Thiscanbe
achievedbypresentingstimuliatafixedacousticlevelwhilstparticipantsweartheir
ownsoundprocessors(Burdoetal.,2006;Sharmaetal.,2005a).Alternatively,
loudnessgrowthcanbemeasuredinordertodeterminethelevelwhichleadstoa
particularloudnesspercept,suchastheMClevel(PurdyandKelly,2016).Duetothe
developmentofloudnesstolerance,increasingstimuluslevelsarerequiredtoachieve
thesameloudnesspercept,particularlyduringtheearlyperiodafterCIswitch-on
(Hughesetal.,2001;Vargasetal.,2012).Inthisstudy,increasingstimulusintensity
wasassociatedwithanincreaseinloudnessperception-thereforethissituationisnot
directlycomparabletotheearlyperiodafterCIswitch-on.Nonetheless,thesedata
indicatethatstimuluslevelcouldcontributetochangesinCAEPsovertime,andthis
effectshouldbeconsideredinlongitudinalstudieswithCIusers.
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5.5.2Stimulusintensityandbehaviouralelectrodediscrimination
TheincreaseinspatialACCamplitudewithstimulusintensitywasaccompaniedbyan
improvementinbehaviouraldiscrimination.Thischangeinbehaviouralelectrode
discriminationwithpresentationlevelisgenerallyconsistentwithfindingsfromother
studies(ChatterjeeandYu,2010;McKayetal.,1999;Pfingstetal.,1999).Increasing
stimulusintensityresultsinabroaderpatternofexcitationinthecochlea.McKayetal.
(1999),suggestthatthefactthatelectrodediscriminationimprovesdespitethis
presumedbroadeningofexcitation,implieselectrodediscriminationdependson
differenceinthepeaksandedgesratherthantheamountonnon-overlapinthe
patternofexcitationassociatedwithindividualelectrodes.
Onaverage,behaviouralelectrodediscriminationscoreandspatialACCamplitude
increasedthroughoutthetestedDRinthisstudy.OthersstudiesinCIusershavealso
shownanimprovementindiscriminationperformancethroughouttheDR.McKayet
al.(1999),foundthatbehaviouralelectrodediscriminationscoreincreasedwithlevel,
whentestedat40%,70%and100%oftheDRinadultCIusers.Similarly,Pfingstand
Rai(1990),foundthatpulseratediscriminationimprovedwithlevelthroughoutthe
DR.ThisfindingscontrastswithNHlistenersinwhomfrequencydiscriminationlimens
improvewithpresentationlevelbutthenplateauat20–40dBsensationlevel
(FreymanandNelson,1991;PfingstandRai,1990;Wieretal.,1977).PfingstandRai
(1990),suggestthatthisdifferencemaybeaccountedforbyneuralsurvival.Thatis,
withgreaterneuralsurvival,activationofauditoryneuronswithincreasingstimulus
levelmaysaturateatlowerstimulusintensities.
Itwasfoundthatelectrodediscriminationwaspoorinmostindividualsatthelower
endoftheDR.Thelowestpresentationlevelusedinthisstudywas40%oftheDR,
whichisstillwellabovethreshold.Poorelectrodediscriminationatlowerstimulus
intensitiesmayreflectpoorerneuralsurvival.Asstimulusintensityincreases,
presumablythereisgreaterneuralrecruitment,makingtheperceptassociatedwith
individualelectrodesmoredistinct.ChatterjeeandYu(2010),foundthatelectrode
discriminationatthelowerendoftheDRwascorrelatedwithmodulationdetection
147
thresholds.Theauthorssuggestthatasimilarprocess,suchasneuralsurvivalmay
underlieperformanceonbothtasks.Furthermore,itwasfoundthatstimulusintensity
hadagreatereffectforelectrodelocationswithalargerdiscriminationlimeni.e.for
electrodepair4-6inthisstudy.Alargerdiscriminationlimenmayalsoreflectpoorer
neuralsurvivalandaconsequentgreaterleveldependence.Pfingstetal.(1999),
similarlyfoundthatlargerEDLswereassociatedwithagreaterleveldependencefor
discrimination.
Similartootherstudies,substantialinter-individualvariabilityintherelationship
betweenstimuluslevelandthespatialACC/behavioralelectrodediscriminationwas
found.IncontrasttoPfingstetal.(1999)andMcKayetal.(1999),electrode
discriminationabilitydidnotdeterioratesignificantlywithstimuluslevelinanyofthe
studyparticipants.Thevariabilitybetweenindividualsandelectrodelocations,could
beaccountedforbydifferencesattheelectrode-neuralinterface.Furthermore,itis
knownthattheloudnessgrowthfunctionsmayvaryconsiderablybetweenCIusers
(Shannon,1983).RecentevidencefromAnzaloneandSmith(2017),showsthat
loudnessgrowthmayevenvarydependingonthehistoryofhearingloss.Specifically,
loudnessgrowthfunctionsinearly-deafenedlate-implantedadultswerefoundtobe
differentfrompost-linguallydeafenedCIusers.Theperceivedloudnessassociated
withastimulusatafixedpointintheDRmayvarysignificantlybetweenCIusers.This
inturnmaycontributetovariabilityinelectrodediscriminationmeasures.
MiddlebrooksandBierer(2002),assessedtheeffectofstimuluslevelonauditory
corticalimagesofanaesthetizedguineapigs.Acutelydeafenedguineapigswere
implantedwitha6-channelelectrodearrayandthespatiotemporalpatternofneural
spikeactivitywasmeasuredacross16primaryauditorycortexlocationsspanning
approximately2–3octavesofthetonotopicaxis.Anartificialneuralnetworkwas
trainedtorecognizeanddiscriminatestimulifromdifferentelectrodesbasedonthe
spatiotemporalpatternsofcorticalactivity.Interestinglyitwasfoundthatincreasing
stimuluslevelwasassociatedwithawidercorticalimageaswellaspoorerelectrode
discriminationbytheartificialneuralnetwork.Thisisatoddswithfindingsfromthis
andotherstudies(ChatterjeeandYu,2010;McKayetal.,1999),whichhaveshown
thatelectrodediscriminationimproveswithstimuluslevel.Inthestudyby
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MiddlebrooksandBierer(2002),responsesfromonlyalimitedareaoftheprimary
auditorycortexweresampledandotherareasoftheauditorypathway(subcorticalas
wellascortical)mayplayanimportantroleindiscrimination.Furthermore,theguinea
pigsintheirstudywereacutelydeafenedandpresumablyhadgoodneuralsurvival,
whichcontrastswiththepoorneuralsurvivalexpectedinhumanCIusers;thistoomay
accountforthedifferenceinfindings.
Itisinterestingtoconsidertheperceptthatunderliesimproveddiscriminationwith
increasingstimuluslevel.Thebestevidencesuggeststhatelectrodediscriminationisa
multimodalpercept(Collinsetal.,1997;CollinsandThrockmorton,2000),which
includespitch,timbreandevenloudness.Townshendetal.(1987),showedthat
increasinglevelonafixedelectrodecanleadtochangesinpitchperceptionandthe
directionofpitchchangecanvarybetweenindividuals/electrodelocations.Itis
possiblethenthatincreasingstimuluslevel,leadsnotonlytoachangeintheabsolute
pitchelicitedbyanelectrodebutalsoanincreaseintherelativedifferenceinpitch
betweenneighbouringelectrodes.Inaddition,athigherstimuluslevels,ifthereisa
greaterdifferenceinpitch,itislikelythatloudnessbalancingbecomeslessaccurate.
Therefore,arelativeincreaseinloudnessdifferencebetweenelectrodesmayalso
contributetoimproveddiscriminationathigherpresentationlevels.
5.5.3RelationshipbetweenthespatialACCandbehaviouralelectrodediscrimination
ThestudybyHeetal.(2014)andtheresultsofChapters3and4,showedthatthereis
astrongrelationshipbetweenthespatialACCandbehaviouralelectrode
discrimination.Inthoseexperiments,stimuliwerepresentedat‘loudbutcomfortable’
levelsorattheMClevel,whichrepresentstheupperendoftheDR.Theresultsofthis
studyshowthatthesensitivityofthespatialACCasameasureofbehavioural
discriminationispooratlowerstimulusintensities.Itisthoughtthatthousandsor
evenmillionsofcorticalpyramidalneuronsmustbesynchronouslyactiveinorderto
measureCAEPswithEEG(Luck,2005).ThisimposeslimitsonthesensitivityofCAEP
measurementsparticularlyatthelowerendoftheDRwherelessneuralrecruitmentis
expected.Nonetheless,itmaybeofinteresttomeasurethespatialACCatarangeof
intensitieswhichreflectconversationalspeechandinordertodosoitwillbe
149
necessarytoimprovethesensitivityofspatialACCrecordings–thisisconsideredin
experiment5,Chapter6.
ParticipantP1wasfoundtohaveagoodbehaviouralelectrodediscriminationscorefor
the80%DRcondition.Forthe60%and70%DRconditions,behaviouraldiscrimination
scoreswerepoorbutspatialACCresponsescouldstillberecorded.Thepresenceof
theACCinthesecasestherefore,appearstoindicatethepotentialfordiscrimination,
whichisinkeepingwiththefindingsofChapter4.
5.5.4RelationshipbetweenelectrodediscriminationandCIprogrammeparameters
Inthisstudy,norelationshipbetweenelectrodediscriminationandthreshold/DR
measurementswasfound.Incontrast,Pfingstetal.(1999)usedabipolarconfiguration
andfoundthatbehaviouralelectrodediscriminationwascorrelatedwiththeDR,but
notthresholdlevel.InthestudybyPfingstetal.(1999),repeatedmeasuresfromthe
sameparticipantswereusedforthecorrelationanalysisandthismayhaveartificially
strengthenedthecorrelation.Monopolarstimulation,whichwasusedinthis
experiment,leadstobroadpatternsofexcitationinthecochlea.Therefore,
threshold/DRmeasurementswithamonopolarconfigurationmaylessaccurately
reflectthestatusoftheelectrode-neuralinterface.Thereisevidencetosuggestthat
thresholdmeasurementswithpartialtripolarstimulationprovideabetterassessment
oftheintegrityoftheelectrode-neuralinterface(Bierer,2010).Itmaytherefore,beof
interesttoexaminerelationshipbetweenelectrodediscriminationandfocused
thresholdmeasurements.
5.5.5Electrodediscrimination,levelandspeechperception
Anumberofstudieshaveconfirmedarelationshipbetweenelectrodediscrimination
andspeechperception(Busbyetal.,2000;Dawsonetal.,2000;Heetal.,2014;Henry
etal.,2000).Inallofthosestudies,electrodediscriminationwasmeasuredinthe
upperpartoftheDRaroundtheMClevel.Inthisstudy,nosignificantrelationship
betweenmeanbehaviouraldiscriminationscoreacrosstheDRandspeechperception
wasfound.Thismaybeduetothefactthatdiscriminationwasmeasuredatasingle
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electrodelocation.Incontrast,themeanspatialACCamplitudeacrosstheDRwas
correlatedwithspeechperception.Giventhesmallnumberofparticipants,the
findingsofthisanalysismustbeviewedwithcaution.Largerscalestudiesarerequired
todeterminewhetherelectrodediscriminationabilityacrosstheDRisrelatedto
speechperception.
5.6Conclusion
Inthisstudy,asignificanteffectofstimulusintensityonboththeamplitudeand
sensitivityofthespatialACCwasfound.IfthespatialACC,orindeedanytypeof
evokedresponsepotential,istobeusedasameasureofauditoryprocessingor
developmentinCIusers,thentheeffectofpresentationlevelshouldbecarefully
considered.
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Chapter6 ImprovingtheclinicalapplicabilityofspatialACC
measurements–apilotstudy
6.1Abstract
Inpreviouschapters,ithasbeenshownthatthespatialauditorychangecomplex(ACC)
providesavaluableobjectivemeasureofauditorydiscriminationincochlearimplant
(CI)users.Theaimofthispilotstudywastodeterminewhethertheefficiencyand
sensitivityofspatialACCmeasurementscouldbeimprovedbyusingalimitednumber
ofEEGrecordingchannelsandbyalteringstimulusfeatures.
ThespatialACCwasrecordedin5adultCIusers.Therewere4measurement
conditions:
(I)64channelscalprecordingwiththestandardstimulus(800msduration,changein
stimulatingelectrodeat400ms,andinter-stimulusinterval(ISI)of1161ms).
(II)Singlechannelscalprecordingwiththestandardstimulusasin(I).
(III)Singlechannelscalprecording,witha2424msstimulus,changeinstimulating
electrodeat1212msandISIof20ms.
(IV)Singlechannelscalprecording,witha3100msstimulus,changeinstimulating
electrodeat2424msandISIof20ms.
OutcomemeasuresincludedspatialACCN1-P2amplitude,signal-to-noise-ratio(SNR)
andtimetakentoachieveanSNRvalueof2.ItwasfoundthatspatialACCrecordings
obtainedwithasinglescalpchannel(conditionII)weresimilartothatobtainedwith
64scalpchannels(conditionI).Byalteringstimuluscharacteristics(conditionsIIIand
IV),itwaspossibletoimproverecordingefficiencyandsensitivity.Thesefindingsare
promisingfortheuseofthespatialACCasaclinicaltool.
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6.2Introduction
PreviousexperimentsinthisthesishaveshownthatthespatialACCisauseful
measureofelectrodediscrimination,whichhasgreatpotentialasaclinicaltooltoaid
assessmentandmanagementinCIusers.InorderforthespatialACCtobeclinically
applicable,itisnecessarythatthesemeasurementscanbeperformedinatime
efficientmanner.Inthischapter,techniquesforimprovingtheefficiencyand
sensitivityofspatialACCrecordingsshallbeconsidered.
FortheEEGrecordingsinpreviouschapters,thesetuptimewasapproximately20to
25minutesforeachparticipant.Thisincludesplacementofa64channelEEGcapwith
recordingelectrodesandoptimizationofvoltageoffsetsintheEEGsystem.The
rationaleforusinga64channelEEGcapwastoaidCIartefactremovalwithspatial
filtering(CheveignéandSimon,2008).AsthespatialACChadnotbeenrecordedinthe
ABdevicepreviously,asophisticatedandeffectiveartefactreductiontechniquewas
requiredtoensurecorticalresponseswereappropriatelyidentifiedincaselarge
electricalartefactswerepresent.InChapter3,however,itwasobservedthatCI
artefactwasusuallywelllocalizedandartefactfreescalplocationscouldalwaysbe
identified.Thisraisedthepossibilityofusingalimitednumberofrecordingchannels
forspatialACCmeasurements.
Indeed,previousgroupshavemeasuredthespatialACCwithasinglescalpelectrodein
theCochleardevice(Brownetal.,2008;Heetal.,2014;ScheperleandAbbas,2015b).
Forexample,Heetal.(2014),recordedthespatialACCdifferentiallybetweenFzand
thecontralateralmastoidwithFpzservingasthegroundelectrode.Twoocular
electrodeswerealsousedtoidentifyandremoveeyemovementartefacts.Usingthis
setup,itwasfoundthatthespatialACCcouldberecordedsuccessfullyandthatithad
astrongrelationshipwithbehaviouralelectrodediscrimination.Clearly,usingalimited
numberofrecordingelectrodeshastheadvantageofreducingthesetuptime.To
date,singlechannelrecordingsofthespatialACChavenotbeenperformedinusersof
theABorMED-ELdevice.
153
ThestimulususedtomeasuretheACCinpreviousexperimentsconsistedof
alternatingpolaritybiphasicpulsesof800msduration,withachangeinstimulating
electrodeat400ms.Thetotaltriallengthwas1961ms(presentationrate0.51Hz)and
therewere300trialsforeachstimulus.Therecordingtimeforasingleelectrodepair
wasapproximately10minutes.ThesetupandEEGrecordingtimefor4electrodepairs
exceeded1hour.Furthermore,inChapters3to5,itwasfoundthatthespatialACC
lackedsensitivityinseveralcasesi.e.asignificantspatialACCresponsecouldnotbe
recordedeventhoughtheparticipanthadaccuratebehaviouraldiscriminationforthe
sameelectrodepair.Fromaclinicalpointofview,itisvitaltoimprovethesensitivity
andefficiencyofspatialACCmeasurements.
InChapter4,alackofsensitivityofspatialACCmeasurementsinparticipantS11was
found.Byincreasingthestimulusdurationfrom800msto1400ms,itwaspossibleto
recordaclearspatialACCresponse(figure4.7).Usinglongerdurationstimuli,may
reducemaskingoftheACCbythecorticalonsetresponse.SmallandWerker(2012),
measuredtheACCtoconsonantcontrastsininfantsusingstimuliwithadurationof
564ms.TheyfoundfoundthatthetheACCcouldnotbereliablyrecordedfornon-
nativeHindidental-retroflex/daDa/stimuli,whichwasnotinkeepingwithfindings
fromapreviousbehaviouralstudy(WerkerandLalonde,1988).However,byincreasing
thestimulusdurationto820ms,theACCcouldberecordedsuccessfully(Chenand
Small,2015).ThesefindingssuggestthatACCrecordingsensitivitymaybeimprovedby
usinglongerdurationstimuli.
AnotherimportantdeterminantofCAEPresponsemagnitudeistheISI.TheISIisthe
periodbetweenstimulusoffsetandonset.Theperiodbetweenstimulusonsetfortwo
successivetrialshasbeentermedthestimulusonsetasynchrony(SOA).Therefore,the
SOAisthesumoftheISIandstimulusduration.Figure6.1showssomeofthe
terminologythatwillbeusedinthischaptertodescribevarioustimeperiodsrelevant
toACCstimuli.Severalinvestigatorshaveshownthatthecorticalonsetresponse
amplitudeincreaseswithincreasingISI,butasymptotessomewherebetween10and
20s(DavisandZerlin,1966;NelsonandLassman,1968).NelsonandLassman(1968),
foundthatcorticalresponseamplitudewasalogarithmicfunctionoftheISI.Itis
thoughtthatalongerISI,allowsgreaterrecoveryfromtheneuralrefractoryperiod
154
andthereforealargerneuralresponsetotheonsetofsound(Buddetal.,1998;
Pereiraetal.,2014).HillyardandPicton(1978),showedthatforafixedSOAof10.24s,
asstimulusdurationincreased(resultinginasmallerISI),theamplitudeofthecortical
onsetresponsedecreased.ThisstudyshowedthatthetheISIisamoreimportant
determinantofthecorticalonsetresponsemagnitudethantheSOA,andsuggeststhat
neuralrecoveryoccursduringthenon-stimulusperiod.
Kalaiahetal.(2017),foundthattheACCN1-P2amplitudeincreasedastheISIwas
increasedfrom500to2000ms.Thisshowsthat,similartothecorticalonsetresponse,
theISIhasanimportanteffectontheACCmagnitude.FortheACC,itispossiblethat
neuralrecoveryfromtherefractorystateoccursduringtheperiodofthereference
stimulus,aswellastheISI.Therefore,theoffsettoonsetperiodoftheteststimulus(b
toc’infigure6.1)maybeamoreimportantdeterminantoftheACCresponse
magnitudethantheISI.Ifthisisthecase,thenitshouldbepossibletorecordtheACC
evenwithashortISI.
Figure6.1TerminologydescribingvarioustimeperiodsforACCstimuli.Thereferencestimulusisshowninredandgivesrisetothecorticalonsetresponse.TheteststimulusisshowninblueandgivesrisetotheACC.Martinetal.(2010),examinedwhethertheefficiencyofACCrecordingscouldbe
improvedbyusingashorterISI.Thestimulususedwasasyntheticvowelwitha1000
Hzchangeinsecondformantfrequency.Perceptually,thiswasassociatedwitha
changeinvowelfrom/u/to/i/.Thestandardstimuluswas1000msindurationwitha
changeat500msandISIof1000ms.Theteststimuluswasacontinuousalternating
stimulus,withnosilentinterval(ISI=0ms)i.e.therewasachangein2ndformant
frequencyevery500msthroughouttherecordingperiod.Usingthisstimulus,the
recordingtimewashalvedandthenumberofacousticchangeswasdoubled,asthe
Time (ms)
a b c a' b' c' Reference stimulus
Test stimulus
a to a' = stimulus onset asynchrony (SOA) c to a' = inter-stimulus interval (ISI)
a to c = stimulus durationc to b' = test stimulus offset to onset
155
transitionfrom/u/to/i/and/i/to/u/couldbecombined.AlthoughreducingtheISIin
thisway,ledtoalossofthecomponentstructureoftheACCandsmallerACCRMS
amplitude,thesignal-to-noiseratio(SNR)andefficiencywasimprovedduetothe
largernumberoftrialsandreducedrecordingtime.
Whilstusing500mscontinuousalternatingstimulimayleadtoimprovedefficiency,it
maynotleadtoimprovedsensitivity.InthestudybyMartinetal.(2010),the
magnitudeoftheacousticchangewaslarge,andasignificantACCresponsecouldbe
recordedinmostparticipantsirrespectiveofthestimulusISI.If,however,the
magnitudeoftheacousticchangeissmallorcorticalresponsesaregenerallysmallina
givenparticipant,thenusingstimuliasperMartinetal.(2010),mayactuallyleadtoa
lossofsensitivityduetotheshorttimeperiodforneuronstorecoverfromtheir
refractorystate.
Itishypothesizedthatbetterrecordingsensitivityandefficiencycanbeachievedby
usinglongdurationcontinuousstimuli.Thepotentialadvantageofthisapproach
include1)reducedmaskingoftheACCbytheonsetresponse2)longeroffsettoonset
periodtoallowneuralrecoveryand3)doublingofthenumberofacousticchangesby
combiningtheresponsetobothdirectionsofchange.
Theoverallaimofthispilotstudywastoexplorewhethertheefficiencyandsensitivity
ofspatialACCrecordingscouldbeimproved.Thespecificobjectiveswereto
1) determinewhetheritisfeasibletomeasurethespatialACCwithsinglechannel
scalprecordings
2) examinewhetherthesensitivityandefficiencyofspatialACCrecordingscanbe
improvedbyusinglongdurationcontinuousstimuli
6.3Experiment5:DesignandMethods
6.3.1Participants
Fiveparticipantsranginginagefrom43to66yearswereincludedinthisexperiment.
AllparticipantswereABusersandhadtakenpartinpreviousexperiments.
Demographicdetailsaresummarizedintable6.1.
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Table6.1.Detailsofparticipantsandelectrodepairstestedinexperiment5.F=female,M=male,R=right,L=left
Participant Age Sex Ear
Ageat
deafness
onset(years)
Duration
ofCIuse
Electrode
array
Electrode
pair
tested
P1 43 F R 1.5 90months 1J 4-6
S1 53 M R 41 21months MidScala 4-5
S4 50 M L 2 19months 1J 4-5
S9 49 M L 47 14months MidScala 4-5
S11 66 F L 62.5 13months MidScala 4-5
6.3.2StimuliforACCmeasurement
Stimuliconsistedofalternatingpolaritybiphasicpulsetrainswitharateof1000pps
andphasedurationof~50µs.Therewasachangeinstimulatingelectrodeduringthe
stimulus–asinpreviousexperiments,theinitialelectrodeisreferredtoasthe
referenceelectrodeandthesubsequentelectrodeisreferredtoasthetestelectrode.
Eitherelectrodepair4-5or4-6wastestedineachparticipant(seetable6.1).These
electrodepairswerechosenastheywereassociatedwithabehaviouralpassin
previousexperimentsanditwasexpectedthatclearcorticalresponseswouldbe
obtained.Theparticipant’sownsoundprocessorwasbypassedandelectrodeswere
stimulatedthroughtheBEDCSresearchinterface.
Therewere3stimuluspresentationstrategies–stimulusA,whichwasusedin
previousexperiments,isreferredtoasthestandardstimulus,andstimuliBandCare
referredtoastheexperimentalstimuli.Aschematicofthestimuliisshowninfigure
6.2andthetimeperiodsforthesestimuliaresummarizedintable6.2.Althoughitwas
originallyintendedthattheexperimentalstimuliwouldproducecontinuous
stimulationwithoutasilentinterval,thiswasnotpossible.Insteadtherewasa20ms
silentintervalattheendofeachtrialafterthetestelectrode.Thisperiodisrequired
bytheABresearchinterfacetoloadthestimulusparametersforeverytrial.
Importantly,therewasnosilentinterval,duringthetransitionfromreferencetotest
electrode.
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Thethreestimuliwereasfollows
1. StimulusA(standardstimulus).Thestimulusdurationwas800mswitha
changeinstimulatingelectrodeat400ms.Thefirstandlast12msofthis
stimulusconsistedofzeroamplitudepulses.TheISIwas1161msandtrial
durationwas1961ms.
2. StimulusB.Thishadadurationof2424ms,withachangeinstimulating
electrodeat1212ms.TheISIwas20msandtrialdurationwas2444ms.By
lengtheningthestimuli,overlapbetweentheACCandonsetresponsewould
theoreticallybereduced.
3. StimulusC.Thishadadurationof3100mswithachangeinstimulating
electrodeat2424ms.TheISIwas20msandtrialdurationwas3120ms.Similar
tostimulusB,thereferencestimuluswaslongerindurationthaninstimulusA,
reducingpotentialoverlapbetweentheACCandonsetresponse.Theoffsetto
onsetperiodforthetestelectrodewas2444ms,whichwaslongerthanfor
bothstimuliAandB.
Table6.2SummaryofvarioustimeperiodsforspatialACCstimuliinexperiment5.ISI=inter-stimulusinterval.
Duration(ms)
StimulusStimulus
duration
Reference
electrode
Test
electrodeISI
Testelectrode
offsettoonset
period
StimulusA 800 400 400 1161 1573
StimulusB 2424 1212 1212 20 1232
StimulusC 3100 2424 676 20 2444
TheloudnessbalancedMClevelwasdeterminedforstimulusAusingtheprocedure
describedintheGeneralMethods(Chapter2).Thesamestimulationlevelwasusedfor
stimuliBandC.Itwasexpectedthattheselongerdurationstimuliwouldproducea
similarloudnesspercepttostimulusA,asthetemporalintegrationtimeistypicallyless
than100msforsuprathresholdstimuliinCIusers(Shannonetal.1983).Tobecertain
ofthis,loudnessbalancingwascheckedforstimuliBandCinallcases.
Figure6.2SchematicofstimuliusedformeasuringthespatialACCinexperiment5.Stimuliconsistedofbiphasicelectricalpulsesat1000pulsespersecondwithachangeinstimulatingelectrodeduringthestimulus.Theinitialelectrodeisreferredtoasthereferenceandisshowninred.Thesubsequentelectrodeisreferredtoasthetestelectrodeandisshowninblue.Thesolidverticallinesmarkthebeginning/endofeachtrial.StimulusAhadadurationof800mswithachangeinstimulatingelectrodeat400ms.StimulusBhadadurationof2424mswithchangeinstimulatingelectrodeat1212ms.StimulusChadadurationof3100mswithachangeinstimulatingelectrodeat2424ms.
0 400 800 1961
0 1212 2424
0 2424 3100 Time (ms)
(A)
(B)
(C)
Reference electrode Test electrode
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159
6.3.3EEGRecording
ABioSemiActiveTwoEEGsystemwasusedwitheitheroneofthefollowingrecording
configurations:
1) Standardrecordingwith64channelcap.ThetechniqueforEEGrecording
processingwereasdescribedintheGeneralMethods.Datawerereferencedto
thecontralateralmastoidandspatialfilteringwasusedtoremoveCIartefact.
Rightinfra-orbitalandrightlateralcanthuschannelswereusedtomeasureand
removeocularartefacts.
2) Singlescalpchannelrecording.Forthisconfiguration,asingleEEGrecording
channelwasplacedatCz.Thislocationliesinthemidline,midwaybetweenthe
nasionandinion,andisthereforeeasilyidentified.Furthermore,alargeACC
responsecanusuallyberecordedfromthissite.Theforeheadandcontralateral
mastoidwereusedforgroundandreferenceelectrodesrespectively.Right
infra-orbitalandrightlateralcanthuschannelswereusedtoremoveocular
artefacts.EEGprocessingwasthesameasforthe64channelrecordings,
exceptthatspatialfilteringwasnotperformed,asthisrequireshighdensity
EEGrecordings.
Intotaltherewerefourmeasurementconditions:
I) StimulusA,64channelscalprecording
II) StimulusA,singlechannelscalprecording
III) StimulusB,singlechannelscalprecording
IV) StimulusC,singlechannelscalprecording
Duetotimeconstraints,onlymeasurementsconditionsIandIIwereperformedin
participantS4.The4conditionswererecordedinseparateblocks.Theorderofthe
recordingconditionswasrandomized,althoughthe64channelrecordingwasalways
performedeitheratthebeginningorendofthesessionforpracticalreasons.The
numberoftrialsforEEGrecordingswas300forstimulusA,250forstimulusBand220
forstimulusC.Thiscorrespondstoarecordingtimeforasingleelectrodepairof9.8
minutesforstimulusA,10.2minutesforstimulusBand11.4minutesforstimulusC.
Thenumberoftrialsforthelongerdurationstimuliwasreducedtoavoidtoolonga
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recordingtimewhilstmaintainingasufficientnumberoftrialsforaveraging.
Participantsweregivenbreaksapproximatelyevery10to15minutes.Thetotal
experimentaltimewasaround2hoursforeachparticipant.
6.3.4EEGdataanalysis
ThemagnitudeoftheACCresponsewasquantifiedwithtwomethods:
1) ACCN1-P2amplitude–thiswasmeasuredusinganautomaticpeakdetection
algorithmasdescribedintheGeneralMethods.TheN1responsewasdefined
astheminimumpeakvoltagebetween70and150msafterelectrodechange
andP2wasdefinedasthemaximumpositivepeakvoltageoccurringbetween
150and290msafterelectrodechange.
2) ACCSNR–thiswascalculatedusingthefollowingequation:
SNR=(RMS2/RN2)-1 (6.1)
whereRMSistherootmeansquareamplitudeintheACCresponsewindow
andRNistheresidualnoiseestimate(DonandElberling,1994).
TheSNRwascalculatedasittakesintoaccountthenoisefloor.Atlowtrialsnumbers
theresidualnoiseistypicallyhighandthismaycontributetoalargeACCpeak
amplitude.Incontrast,SNRwillbesmallifthenoiselevelishigh.Therefore,for
smallertrialnumberthismethodofquantifyingtheACCmagnitudemaybemore
appropriatethantheN1-P2amplitude.TheACCresponsewindowwasdefinedasthe
periodbetween50–250msafterstimuluschangeasthistypicallyencompassesthe
P1,N1andP2peaks.Onlythetransitionfromreferencetotestelectrodewas
consideredatruechangeresponse.Although,theinitialaimwastocombinethe
transitionsfromtesttoreferenceandreferencetotestelectrodeforstimuliBandC,
thiswasnotperformedduetothepresenceofasilentintervalattheendofthetrialas
describedearlier.
AsignificantACCresponsewasdefinedashavinganSNRvalueofatleast2.Alinear
SNRof2correspondstoapproximately3dBwhichhasbeenusedasacutoffinother
studiesofevokedresponsepotentials(ElberlingandDon,1984)Thetimetakento
161
achieveanSNRof2wascalculatedwithlinearinterpolationandwasusedasa
measureofrecordingefficiency.
ThepresenceorabsenceoftheACCresponsewasalsodeterminedusingtheHotelling-
T2test(Goldingetal.,2009).ThesameACCresponsewindowasfortheSNRwasused.
ItwasexpectedthatACCresponseswhichhadanSNRvaluegreaterthan2wouldalso
haveaHotelling-T2pvalue<0.05.Thiswouldprovideadditionalconfirmationthatthe
chosencutoffSNRvaluewasappropriate.
6.4Results
Figures6.3showsthecorticalresponsemeasurementsforallparticipantsand
measurementconditions.Theseshallbereferredtointhetextinmoredetailinthe
followingsections.
162
163
164
165
Figure6.3Corticalresponsesforthedifferentmeasurementconditions.DataarepresentedatCzforparticipantsS4(A),P1(B),S1(C),S9(D)andS11(E).Themeasurementcondition,numberofrecordingscalpchannelsandstimulustypeareshownaboveeachpanel.Thetimewindowsusedtodetectpositiveandnegativepeaksfortheonsetresponse(P1,N1,andP2)andACC(cP1,cN1,andcP2)areshowninpinkandblue,respectively.Thehorizontallinescorrespondtothelevelofresidualnoise.
166
167
6.4.1Comparisonofsingleand64channelACCmeasurements
Theaimofthisanalysiswastovalidatesinglechannelrecordingsformeasuringthe
spatialACC.Inordertodothis,theACCatscalplocationCzformeasurement
conditions(I)and(II)werecompared.StimulusA,whichwasof800msdurationwas
usedinbothoftheseconditions.Visualinspectionoffigure6.3revealsthatsingle
scalpchannelEEGrecordingswererelativelyfreeofCIartefact.Furthermore,the
spatialACCresponsesformeasurementconditions(I)and(II)weresimilarinmost
cases.Figure6.4showsthattheN1-P2peakamplitudeofthespatialACCforthe2
measurementconditionswerebroadlysimilar.
Figure6.4SpatialACCamplitudeaccordingtonumberofscalprecordingchannels.Identicalstimuli(stimulusA)wereusedforbothrecordings.DataarepresentedatchannelCzforindividualparticipants.Theupperandlowerhingesoftheboxplotscorrespondtothefirstandthirdquartiles,whilstthemedianisindicatedbythehorizontallinewithineachbox.
168
ThechangeintheSNRoverrecordingtimeforbothmeasurementconditionswasalso
compared.Theindividualdataareshowninfigure6.5,andthemeandataacrossall
participantsareshowninfigure6.6.Thehorizontaldottedlineinthesefigures
representsthecriticalSNRvalueof2fordefiningasignificantACCresponse.These
figuresshowsthatthesinglechannelscalprecordingshavesimilarefficiencyand
produceACCresponseswithasimilarmagnitude,comparedto64channelrecordings.
ForparticipantS1,thecriticalSNRvalueof2wasreachedwiththesinglechannelbut
notthe64channelrecording.
Figure6.5SpatialACCSNRasafunctionofrecordingtimeandnumberofrecordingchannelsforindividualparticipants.SNRwascalculatedasperequation6.1(DonandElberling,1994).ThehorizontaldottedlinerepresentsthecriticalSNRvalueof2atwhichasignificantACCresponsewasdefined.DataarepresentedatchannelCz.
169
Thesetuptimes(applicationofconductivegelandrecordingelectrodes)forthesingle
channeland64channelscalprecordingswereapproximately5minutesand20
minutesrespectively.ThesedatashowthatforspatialACCmeasurementsinusersof
theABdevice,singlechannelscalprecordingsarefeasible,validandtimeefficient.
Figure6.6SpatialACCSNRasafunctionofrecordingtimeandnumberofrecordingchannelsforthemeandataacrossparticipants.ThehorizontaldottedlinerepresentsthecriticalSNRvalueof2atwhichasignificantACCresponsewasdefined.DataarepresentedatchannelCz.
6.4.2ComparisonofefficiencyandsensitivityofsinglechannelACCmeasurements
usingdifferentstimuli
TheaimofthisanalysiswastodeterminewhetherthesensitivityandefficiencyofACC
measurementscouldbeimprovedbyalteringstimuluscharacteristics.SpatialACC
recordingsfrommeasurementconditions(II),(III)and(IV)arethereforecompared–
thesewereallsinglechannelscalprecordingsbututilizedstimuliA,BandC
respectively.VisualinspectionoftheACCresponsesinfigure6.3showsthatlarger
magnituderesponsesweregenerallyobtainedfortheexperimentalstimuli(BandC)
comparedtothestandardstimulus(A).ThisisparticularlyevidentforparticipantS11,
170
inwhomnoclearspatialACCresponsecouldbevisualizedforstimulusA.Figure6.7
showsthatthespatialACCN1-P2amplitudeisconsistentlylargerfortheexperimental
stimulicomparedtothestandardstimulusforsinglechannelrecordings.However,it
mustbenotedthatfewertrialswereusedforexperimentalstimulirecordingsand
thereforehigherresidualnoiselevelscouldhavecontributedtolargerpeakamplitude
responses.
Figure6.7SpatialACCamplitudeaccordingtostimulustype.Allrecordingswereperformedwithasinglescalpchannel.Theupperandlowerhingesoftheboxplotscorrespondtothefirstandthirdquartiles,whilstthemedianisindicatedbythehorizontallinewithineachbox.
TheSNRprovidesafairercomparisonofresponsemagnitudewhencomparing
measurementconditionswithdifferentnumbersoftrialssinceitaccountsforthe
residualnoiselevel.Inordertocompareresponsemagnitudeandrecordingefficiency
forthedifferentmeasurementconditions,thechangeinSNRoverrecordingtimewas
analyzed.Theindividualandmeandataareshowninfigure6.8and6.9respectively.
ThefinalSNRaswellasthetimetakentoreachanSNRvalueof2areshownintable
171
6.3.Ofnote,anSNRvalueof2wasachievedwiththeexperimentalstimulibutnotthe
standardstimulusforparticipantS11.StimulusCproducedlargerresponsesandwas
moreefficientcomparedtostimulusAin4outof4cases.StimulusBproducedlarger
responsesandwasmoreefficientthanthestandardstimulusin3outof4cases.Table
6.4showsthatonlyACCmeasurementswhichachievedanSNRvalueof2,hada
statisticallysignificantHotelling-T2pvalue(p<0.05).Thissuggeststhatitis
reasonabletouseacut-offSNRvalueof2toprovideameasureofrecordingefficiency.
ThesedatashowthattheefficiencyandsensitivityofACCmeasurementscanbe
improvedbyalteringstimuluscharacteristics.
Figure6.8SpatialACCSNRasafunctionofrecordingtimeandstimulustypeforindividualparticipants.ThehorizontaldottedlinerepresentsthecriticalSNRvalueof2atwhichasignificantACCresponsewasdefined.
172
Figure6.9ACCSNRasafunctionofrecordingtimeandstimulustypeforthemeandataacrossparticipants.ThehorizontaldottedlinerepresentsthecriticalSNRvalueof2atwhichasignificantACCresponsewasdefined.
173
Table6.3TimetakentoreachanSNRvalueof2,peakSNRvalueandHotelling-T2resultintheACCresponsewindow.SNR=signal-to-noiseratio,HT2=Hotelling-T2.
Participant Outcome measure Stimulus A
(800 ms)
Stimulus B
(2424 ms)
Stimulus C
(3100 ms)
P1
Time (mins) for critical SNR 5.9 5.3 5.0
Peak SNR 11.3 16.7 37.5
HT2 p < 0.05 Yes Yes Yes
S1
Time (mins) for critical SNR 8.9 9.5 6.2
Peak SNR 3.0 2.9 15.7
HT2 p < 0.05 Yes Yes Yes
S9
Time (mins) for critical SNR 7.7 5.3 5.1
Peak SNR 6.5 17.9 29.7
HT2 p < 0.05 Yes Yes Yes
S11
Time (mins) for critical SNR NA 4.7 5.2
Peak SNR -0.1 24.1 26.7
HT2 p < 0.05 No Yes Yes
6.5Discussion
Inthispilotstudy,itwasfoundthatspatialACCmeasurementscouldbeperformed
withalimitednumberofEEGrecordingchannelsandthatrecordingefficiencyand
sensitivitycouldbeimprovedbyalteringstimuluscharacteristics.Despitethesmall
numbersofparticipants,theresultsofthisexperimentareencouragingfortheclinical
useofspatialACCmeasurements.
6.5.1RecordingthespatialACCwithalimitednumberofscalpchannels
ItwasfeasibletomeasurethespatialACCwithasinglescalpEEGrecordingchannelin
usersoftheABdevice.Despitetheabsenceofasophisticatedartefactremoval
technique,corticalresponseswererelativelyartefactfree,andonaverageweresimilar
tothatobtainedwith64channels.Byusingthisapproach,thesetuptimeforEEG
recordingswasreducedfromaround20to5minutes.Inaddition,thedatafiles
obtainedwithsinglechannelrecordingsareconsiderablysmallerandaretherefore
muchfastertoprocess.Singlechannelrecordingsrequireapplicationofconsiderably
lessconductivegeltothescalp,andthisispreferableforparticipants.ThespatialACC
174
hasbeenrecordedwithalimitednumberofscalpchannelsinusersoftheCochlear
device(Brownetal.,2008;Heetal.,2014;ScheperleandAbbas,2015b).Scheperle
andAbbas(2015b),recordedthespatialACCusingasingleEEGscalprecording
channelatCz.However,tworeferenceelectrodeswereusedwithoneatthe
contralateralmastoidandtheotheratIz(Inion).Foreverytrial,twodifferential
recordingswereaveragedinordertoreducetheresidualnoise.Thisapproachcould
beusedtoimproverecordingefficiencyfurther.
6.5.2StimuluscharacteristicsandspatialACCmeasurements
Inthisstudy,theeffectofchangingstimuluscharacteristicswasexaminedbyaltering
thestimulusduration,reducingtheISIandvaryingtheoffsettoonsettimeofthetest
electrode.Inordertodeterminetherelativeimportanceofthesedifferentfeaturesa
morecontrolledexperimentisrequired.Nonetheless,itwasfoundthatbyaltering
stimuluscharacteristics,thesamemagnituderesponsecouldbeobtainedinashorter
periodoftimeforexperimentalstimulicomparedtothestandardstimulusi.e.
efficiencywasimproved.Furthermore,inoneparticipant,asignificantspatialACC
response(asdefinedbySNRandHotelling-T2criteria)couldbeobtainedwiththe
experimentalstimuli,eventhoughthiswasnotpossiblewiththestandardstimulus.
ThelargestspatialACCresponseswereobtainedwithstimulusC.Inthiscase,the
durationofthetestelectrodewas676msanditsoffsettoonsetperiodwas2444ms.
TheACCresponsewaslargerforstimulusCcomparedtostimulusB,eventhoughthe
formerhadashortertestelectrodeduration.Itislikelythen,thatforstimulusC,the
largerACCresponsewasduetotheneuronsresponsiblefortheACChavingalonger
periodtorecoverfromtheirrefractorystate.StimulusBgenerallyproducedlarger
magnituderesponsescomparedtostimulusA.Thisisthoughttobeduetothelonger
durationofthereferenceelectrode,sincetheoffsettoonsetperiodforstimulusBwas
shortercomparedtostimulusA(stimulusB1232ms,stimulusA1573ms).Theuseof
longerdurationstimuli,reducesthepotentialoverlapbetweentheonsetandACC
responsesandconsequentmaskingofthelatter.Infigure6.3E,forstimulusB,itcanbe
seenthattheonsetresponseonlyreturnstobaselineataround500ms.Further
experimentsarerequiredtodeterminetheoptimumstimulusdurationformeasuring
175
thespatialACC.ChenandSmall(2015),showedthatACCreliabilitycouldbeimproved
byincreasingthestimulusdurationfrom564msto820ms.Forthesestimulitherewas
achangeinformantfrequencyatthemidpointofthestimulusandafixedISIof2200
mswasusedinbothcases.Therefore,thelargerresponsesobtainedwiththe820ms
recordingmayhavebeenduetoalongeroffsettoonsetperiodfortheteststimulusas
wellasreducedmaskingeffects.
Theresultsofthisexperimentwerelimitedbythefactthatitwasnotpossibleto
presentalternatingstimulicontinuouslyfortheteststimuli.Similartothemethod
usedinMartinetal.(2010),itwasintended,thattheresponsewindowsforthe
changefromreferencetotestelectrodeandfromtesttoreferenceelectrodewouldbe
combinedforthesestimuli.Ifthiswaspossible,therecordingtimecouldpotentiallybe
halved,resultinginasubstantialimprovementinefficiency.FurtherworkwiththeAB
researchinterfaceisrequiredinordertoachievethis.
6.6Conclusion
ThispreliminarystudyshowsthatsetuptimeforspatialACCmeasurementwiththeAB
devicecanbereducedbyusingalimitednumberofEEGrecordingchannels.
Furthermore,theefficiencyofEEGmeasurementscanbeimprovedbyincreasing
stimulusdurationandminimizingthesilentperiodinthestimulus.Furtherworkis
requiredtodeterminetheoptimalstimuluscharacteristicsforspatialACC
measurementsandothertechniquesforimprovingtheefficiency/sensitivityare
consideredinsection7.3oftheGeneralDiscussion.
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Chapter7 GeneralDiscussion
InthisthesisithasbeenshownthatthespatialACCprovidesausefulmeasureof
electrodediscriminationinCIusers.ThespatialACCrepresentsencodingofstimulus
changeintheauditorycortexandthereforeprovidesameasureofwhetherthesignal
fromtheCIisactuallypreservedintheauditorypathway.Theadvantageofthespatial
ACCoverbehaviouralassessments,isthatitisanobjectivemeasure,whichcanbe
performedindependentofattention,cognitionandlanguage.Thismakesitfeasibleto
useindifficulttotestpatientgroupsincludingyoungchildren.Itisproposedthatthis
kindofassessmentcouldbeusedtoguidemanagementofCIusersinordertoimprove
hearingoutcomes.Inthefollowingsectionsasummaryofthemainfindings,clinical
implicationsofthisworkandfuturestudiesshallbediscussed.
7.1Summaryanddiscussionofmainfindings
InChapter3,itwasfoundthatitisfeasibletomeasurethespatialACCinCIdevices
fromdifferentmanufacturersandintheearlyperiodafterCIswitch-on.Aneffective
techniqueforremovingCIartefactwasimplementedandACCresponseswith
amplitudesandlatenciessimilartothatreportedintheliteraturewereobtained.In
Chapters3to5,therelationshipbetweenthespatialACCandbehaviouralmeasuresof
electrodediscriminationwasexamined.Whenusingpass-failcriteria,therewas
generallyastrongrelationshipbetweenthespatialACCandbehaviouralelectrode
discrimination.Incertaincases,thespatialACCdidnotprovideasensitivemeasureof
behaviouraldiscrimination–thatis,asignificantspatialACCresponsecouldnotbe
recordedeventhoughtheparticipantcoulddiscriminatetheelectrodesbehaviourally.
InChapter5,itwasfoundthatthespatialACCsensitivitywasparticularlypoorat
stimulusintensitiesinthelowerpartoftheDR.However,theresultsofChapter6
suggestthatspatialACCsensitivitycanpotentiallybeimprovedbyalteringstimulus
characteristics.
InChapters3to5,itwasfoundthatincertainindividualsthespatialACCcouldbe
recordeddespiterelativelypoorbehaviouraldiscrimination.Thisindicatesthatthe
spatialACCrepresentsencodingofstimuluschangeintheauditorypathwayandthe
177
potentialfordiscrimination,ratherthantheactualperceptionofstimuluschange
itself.Indeed,inChapter4,itwasfoundthatmostindividualswhohada‘false
positive’spatialACC(spatialACCpass,behaviouralfail),developedaccurate
behaviouraldiscriminationatalaterpointintime.The‘falsepositive’spatialACCwas
observedinatotalof5CIusers,4ofwhomhadpreorperi-lingualonsetdeafness.
WhileitisexpectedthatthepresenceofthespatialACC,wouldnormallybeassociated
withchangedetection,itwashypothesizedthatthismightnotbethecaseduringthe
earlystagesofauditorylearningafterCIswitch-onorwhenthereisabnormalcortical
connectivityduetoauditorydeprivation,asmightbeexpectedinearly-deafenedlate-
implantedindividuals.
TherelationshipbetweenthespatialACCandbehaviouraldiscriminationwasalso
examinedbyperformingcorrelationanalysisbetweentheN1-P2peakamplitudeofthe
spatialACCandthebehaviouraldiscriminationscoreinChapters4and5.Thisanalysis
wasgenerallylimitedbythesmallnumberofparticipants.However,nosignificant
correlationwasfoundintheacrosssubjectanalysisi.e.ahigherspatialACCN1-P2
amplitudedidnotimplyabetterbehaviouraldiscriminationscore.Thisislikelydueto
thesubstantialinter-individualdifferencesincorticalresponsemagnitude.Thisismost
likelysecondarytovariationsincorticalfoldingandresultingdipoleorientations,which
areimportantindeterminingthesizeofthemeasuredEEGresponse.InChapter3,it
wasseenthatevenwithinaparticipant,anelectrodepairwithalargerspatialACC
amplitudedidnotnecessarilyhavealargerbehaviouraldiscriminationscore.Thismay
bebecausedifferentelectrodesareassociatedwithdifferentcorticaldipolelocations
andorientations.Furthermore,asdiscussedearliertheremaybeadissociation
betweenencodingandperceptionofstimuluschange.Thesefindingssuggest,caution
mustbeappliedwhencomparingthemagnitudeofACCresponsesfordifferent
electrodelocationsandindividuals.
ThelongitudinalstudyinChapter4,showedthatelectrodediscriminationimproved
withCIlisteningexperienceafterswitch-on.Duringthefirst6monthsofCIuse,the
proportionofelectrodeswithanobjectiveACCpassaswellastheamplitudeofthe
ACCresponseincreased.Thiswasparalleledbyimprovementsinbehaviouralelectrode
discriminationaswellasspeechperception.Notably,incertainindividuals,
178
improvementsinelectrodediscriminationweresubstantialandcouldoccurovera
relativelylongperiodoftime.Itwasfoundthathigherstimulationlevelswererequired
overtimeinordertoachievearelativelyconstantperceptuallevel.Thiscouldhave
contributedtotheimprovementsinbehaviouralandobjectivemeasuresofelectrode
discriminationovertime.However,whenelectrodepairswithpoorinitialbehavioural
electrodediscriminationwerere-testedatalatertimepointusingtheoriginal
stimulationlevels,significantlyhigherdiscriminationscoreswereobtained.Therefore,
theuseofhigherstimulationlevels,mightaccountforsomebutnotallofthe
improvementsinelectrodediscriminationthatoccurredovertime.Thesedataprovide
evidenceforauditoryplasticityinadultCIusers.Themechanismsthatunderliethisare
notwellunderstood,butthepossibilityoftonotopicre-organizationandhigher
auditorylearningwerediscussed.
Therelationshipbetweenelectrodediscriminationandspeechperceptionwas
examinedinChapters3to5.Asignificantrelationshipbetweenbehaviouralelectrode
discriminationandspeechperceptionwasfoundinChapters3and4.Thisisconsistent
withfindingsfromotherstudies(Busbyetal.,2000;Dawsonetal.,2000;Heetal.,
2014;Henryetal.,2000).Incontrast,asignificantrelationshipbetweenthespatial
ACCamplitudeandspeechperceptionwasnotfound.Theinter-individualvariabilityin
corticalresponsemagnitudemayhavecontributedtothisfinding.Theresultsof
Chapter5werenotinkeepingwiththeChapters3and4–itwasfoundthatthespatial
ACCamplitude,butnotbehaviouralelectrodediscrimination,wascorrelatedwith
sentenceperception.ThisresultsofChapter5areviewedwithcaution,astherewere
fewerparticipantsandelectrodediscriminationwasmeasuredforasingleelectrode
pair.Anappropriatelypoweredstudywithalargercohortofparticipantsandspatial
ACCmeasurementsatagreaternumberofelectrodelocationsisneededtodetermine
therelationshipbetweenthespatialACCandspeechperception.Itislikelythat
electrodediscriminationwillaccountforarelativelysmallproportionofthevariancein
speechperceptionoutcomes.Electrodediscriminationprovidesarelativelylow-level
assessmentofauditoryprocessing.Speechperception,however,iscomplexand
requirestheuseofspectral,temporalandlevelcuesaswellascognitiveability.While
itisexpectedthatCIuserswithpoorelectrodediscriminationwillhavepoorspeech
179
perception,individualswithgoodelectrodediscriminationmaynotnecessarilyhave
goodspeechperceptionifthereareotherlimitingfactors.
InChapter6,techniquesforimprovingtheclinicalapplicabilityofspatialACC
measurementswereexplored.Apilotstudyshowedthatitisfeasibletomeasurethe
spatialACCwithalimitednumberofEEGrecordingelectrodes,whichsubstantially
reducedthesetuptime.Furthermore,byalteringstimuluscharacteristicsitwas
possibletoobtainlargemagnituderesponsesmorequickly,therebyimproving
recordingefficiency.OtherchallengesandsolutionstousingspatialACCmeasurement
intheclinicalsettingshallbediscussedinsection7.3
7.2ClinicalimplicationsofthespatialACC
Thefindingsofthisthesishaveanumberofclinicalimplications.Firstly,thisstudy
providesevidenceforauditoryplasticityinadultCIusers,includingindividualswith
earlyonsetandlongdurationsofdeafness.Thiscapacityoftheauditorysystemto
adaptmayunderliethefactthatgoodresultscanbeachievedinthesegroups(Lundin
etal.,2014;Waltzmanetal.,2002).Factorssuchasdeafnessonsetandduration,in
themselves,shouldthereforenotbeconsideredcontraindicationstoimplantation.
Whatisclearfromthisstudyisthatthetimecourseforadaptationmayvarywidely
betweenCIusers–incertainindividuals,electrodediscriminationwasexcellentsoon
afterswitch-on,whilstinothersperformancewasinitiallypoorbutcontinuedto
improveforupto1year.Thisraisesthepossibilityofacceleratingauditoryadaptation
withfocusedtraininginpoorerperformers.Indeed,studiesinCIpopulationshave
shownthattraining,overaslittleas4weeks,canresultinmarkedimprovementsin
auditoryperformance,evenafterlongperiodsofpassiveadaptationtothespeech
processor(FuandGalvin,2008).FuandGalvin(2008),reportedanexperimentusing
electrodediscriminationtraininginonepre-linguallydeafenedadultCIuser.Training
resultedinimprovedelectrodediscriminationforbothtrainedanduntrainedelectrode
contrasts.Furthermore,thiswasassociatedwithimprovedconsonantandvowel
recognition.Althoughtheevidenceforelectrodediscriminationtrainingislimited,a
numberofotherstudieshaveshownthat‘bottom-up’trainingapproachesare
beneficial.Forexample,Fuetal.(2005a)foundthatphoneticcontrasttrainingresulted
180
insignificantlyimprovedvowel,consonantandsentencerecognitioninadultCIusers.
Inaddition,Fuetal.(2005b)showedthatvowelcontrasttraining,butnotsentence
training,inCIsimulationswithNHlistenersledtoimprovedvowelandconsonant
recognitionwithspectrallyshiftedspeech.Theauthorssuggestthatdeveloping
phonemerecognitionisparticularlyimportantincongenitallydeaflate-implanted
adultswhomustdevelopa‘centralspeechtemplate’.‘Bottom-up’training
approaches,usingelectrodeorphoneticcontrasts,maythereforebeparticularly
appropriateforpoorperformersinordertooptimizeperformanceasquicklyas
possible.
IftherearesignificantinteractionsintheelectricalfieldsofCIstimulationchannels,
thenitisunlikelythatauditorytrainingwillyieldbenefit.CIchanneldeactivationhas
beenutilizedasastrategytoreducechannelinteractionsandimproveperformance.
Thedecisiontodeactivateelectrodeshasbeenbasedonperformanceonbehavioural
tasksincludingelectrodediscrimination(Zwolanetal.,1997),pitchranking(Salehet
al.,2013;Vickersetal.,2016)andmodulationdetection(Garadatetal.,2013).Based
ontheresultsofthisstudy,twopointsarenoteworthy.Firstly,itisimportantto
understandthetemporaldynamicsofperformanceonpsychophysicaltasksiftheyare
tobeusedtoguideinterventions.Ifbehaviouralperformancecanimproveoverlong
periodsoftime,thenre-programmingproceduressuchaselectrodedeactivation,
shouldnotbeperformedprematurely.Secondly,itmaybebeneficialtomeasure
auditoryprocessingobjectivelywithmeasuressuchastheACCandMMN,as
behaviouralperformancecanlagbehindobjectivemeasurements.If,forexample,an
electrodepaircannotbediscriminatedbehaviourallybutisencodedintheauditory
pathway,asmeasuredwiththeACC,providingauditorytrainingislikelytobemore
appropriatethandeactivatingelectrodes.
Oneofthelimitationsofdeactivatingelectrodesisthatthefrequenciesofthese
channelshavetobereallocated,whichresultsinabroadeningofthebandwidthat
othersites.ZhouandPfingst(2014),showedthatalteringstimulationparametersat
selectedelectrodesitescanbeaneffectivealternativemethodtodeactivating
electrodesinordertoimproveCIperformance.Intheirstudy,theminimum
stimulationlevelsofelectrodeswiththepoorestmodulationdetectionthresholds
wereraisedbyincreasingthresholdlevelsontheclinicalprogrammesby5%.This
181
resultedinasignificantimprovementinspeechreceptionthreshold.Incontrast,
increasingthethresholdlevelforallelectrodesdidleadtobetterspeechperception.In
Chapter5,itwasshownthatelectrodediscriminationscoresandspatialACC
amplitudeincreasedwithstimulusintensity.Therefore,oneapproachtoimproving
electrodediscriminationandpotentiallyspeechperception,wouldbetoincrease
stimulationlevelsatelectrodesiteswithpoordiscrimination.SimilartoZhouand
Pfingst(2014),thiscouldbeachievedbyraisingthethresholdlevelontheclinical
programmeatselectedsites.Thismaybeparticularlyappropriateforelectrodepairs
thathavepoordiscriminationinthelowerpartoftheDRbutgooddiscriminationin
theupperpartoftheDR.
Figure7.1FlowchartillustratingclinicaldecisionmakingwiththespatialACC.DR=dynamicrange
SpatialACCmeasured atMClevel.Present?
No
Allowtimetoadapt/providetraining
Re-measurespatialACC -ifstillnotpresentswitch
electrodesoff
Yes
RemeasurespatialACC atlowerendofDR.Present?
Yes
Measurebehaviouraldiscrimination(iffeasible)
Goodbehaviouraldiscriminaion
Othercausesforpoorperformance?(CT,focused
thresholds)
Poorbehaviouraldiscrimination
Allowtimetoadapt/providetraining
No
Increasestimulationlevels
182
Insummary,itisproposedthatthespatialACCcouldbeusedtoguidemanagementin
CIusers.Figure7.1setsoutatheoreticalframeworkforhowthespatialACCmightbe
usedforclinicaldecisionmaking.Electrodediscriminationassessmentsareexpectedto
bemostusefulinpoorerperformers.ThespatialACCshouldinitiallybemeasuredat
theupperpartoftheDR(e.g.theMClevel)forapicalandmidarrayelectrodes.IfACC
responsesareabsent,thepatientshouldbeallowedtimetoadapttotheirCI.Ifthey
arealreadyexperiencedCIusers,targetedauditorytrainingshouldbeprovided.If
trainingdoesnotresultinthedevelopmentofaspatialACCresponse,thenre-
programmingtheCI,forexample,bydeactivatingelectrodesshouldbeconsidered.If
spatialACCresponsesarepresent,thentestingshouldberepeatedinthelowerpartof
theDR.IfresponsesareabsentinthelowerpartoftheDR,thenthresholdlevelson
theclinicalprogrammeshouldbeincreasedfortheproblemelectrodes.If,spatialACC
responsesarepresentintheupperandlowerpartsoftheDR,butbehavioural
discriminationispoor,adaptationtime/auditorytrainingshouldbeprovided.Ifonthe
otherhand,responsesarepresentthroughouttheDRandbehaviouraldiscrimination
isgood,thenotherreasonsforpoorperformanceshouldbeconsideredandfurther
investigationsmayberequired.Clearly,thisalgorithmishypothetical.Furtherresearch
isrequiredtodeterminethefinerdetailsofhowthespatialACCmightbeused
clinicallyandifinterventionsbasedonthesemeasurementsleadtoimprovedhearing
outcomes.
7.3Limitationsandfurtherstudies
ItwouldbeusefultovalidatethefindingsofthisstudyinalargercohortofCIusers
includingearly-deafenedlate-implantedindividuals,aswellaschildren.Previous
studieshaveshownthattheACCmeasurementscanbeperformedinyoungchildren
includinginfants(ChenandSmall,2015;Martinezetal.,2013).Furthermore,the
developmentoftheACCinpaediatricpopulationshasrecentlybeencharacterized
(Jeon,2016).ItisthereforeexpectedthatspatialACCrecordingsinchildrenare
feasible.InChapter4,itwasfoundthatincertainCIusers,electrodediscrimination
abilitywascontinuingtoimproveat1yearafterswitch-on.Therefore,itwouldbe
usefultohavealongerperiodoffollow-up,todeterminehowlongbehaviouraland
electrophysiologicalmeasuresofelectrodediscriminationtakestostabilize.
183
WhiletheabsenceofaspatialACCresponseindicatesthepresenceofchannel
interactionseitherinperipheralorcentralauditorysystem,thepresenceofaspatial
ACCresponsemustbeinterpretedwithcaution.Theabilitytodiscriminateelectrodes
accuratelydoesnotnecessarilyimplyahealthyelectrode-neuralinterface.Indeed,itis
expectedthatelectrodediscriminationmaybeaccuratedespitethepresenceofa
neuraldeadregionorcrossturnstimulation.Nonetheless,electrodediscriminationis
consideredtobeausefulmeasure,asitisfrequentlyimpairedandhasbeencorrelated
withspeechperceptioninanumberofstudies.Inpoorperformers,itoffersasimple
firstlineassessment.However,additionalevaluationoftheelectrodeneuralinterface,
forexamplewithfocusedthresholdmeasurementsorhighresolutionimaging,may
alsobeusefulinthesecases(Bierer,2010;Longetal.,2014;Nobleetal.,2014).
ImprovingtheclinicalapplicabilityofspatialACCmeasurementswasconsideredinthis
thesis.Animportantaspectofthisisreducingrecordingandsetuptime.Further
experimentsarerequiredtodeterminethestimuluscharacteristicsthatenablethe
mostefficientrecordingofspatialACCresponses.Iftherecordingparadigmcouldbe
mademoreefficient,thespatialACCcouldbemeasuredforagreaternumberof
electrodepairs.Duetotimeconstraints,thespatialACCwasmeasuredonlyfor
adjacentelectrodepairsattheapicalendoftheelectrodearray.Previousstudieshave
shownthatelectrodediscriminationinthelowandmidfrequenciesiscorrelatedwith
speechperception(Henryetal.,2000).Itwouldthereforebebeneficialtoassessthe
spatialACCforagreaternumberofelectrodepairsandthiswouldbefacilitatedbya
moreefficientrecordingparadigm.
Inthisexperiment,asingleelectrodepairwastestedineachEEGrecordingblock.Itis
knownthatrepeatedpresentationofanauditorystimulusisassociatedwitha
decreaseinthesizeofthecorticalresponse(NäätänenandPicton,1987).Onewayof
overcomingthis,whilstmeasuringthespatialACCformultipleelectrodepairs,would
betouseamulti-stimulusrecordingparadigm.ThiswouldinvolvemeasuringtheACC
formultipleelectrodepairs,presentedinrandomorderduringasinglerecording
block.Thistypeofmulti-stimulusparadigmisahighlyefficientmethodformeasuring
theMMN(Näätänenetal.,2004)andACC(Iversonetal.,2013).Thepredictabilityof
thestimulicouldbefurtherreducedbyrandomlyvaryingthestimulusduration.The
presenceorabsenceofthespatialACCwasdeterminedobjectivelywiththeHotelling-
184
T2testinadefinedresponsewindow.However,incertaincases,usuallyduetoavery
lateP2peak,theresponsewindowhadtobeadjusted.Inorder,toavoidthistypeof
manualadjustment,analgorithmfordeterminingtheresponsewindowbasedonthe
peaklatencyandamplitudecouldbedeveloped.
Thedynamicnatureofspeechmeansthatitwillresultinmultipletransitionsof
simultaneouslyactiveelectrodesontheCIarray.Incontrast,duringspatialACC
measurements,electrodesarestimulatedinisolationsequentially.ThespatialACC
therefore,maynotprovidearealisticmeasureofchannelinteractions.Inorderto
simulatethegreaterlevelofacrosschannelinteractionsthatareexpectedtooccurin
speech,theparadigmforrecordingthespatialACC(aswellasbehaviouralelectrode
discrimination),couldbemodifiedtoincludecontinuoussuprathresholdstimulation
fromflankingelectrodes.Thisisillustratedinfigure7.2.Inthestandardparadigm,
discriminationmaybepossibleduetodifferencesintheedgeoftheexcitationfieldsof
thereferenceandtestelectrodes.Byusingflankingelectrodes,‘edgeeffects’arelikely
tobelessprominent.Theuseofsuchamodifiedparadigmmayprovideamore
functionalmeasureofchannelinteractionswithastrongerrelationshiptospeech
perception.
Figure7.2StandardandmodifiedparadigmsforspatialACCmeasurements.Inthestandardparadigm(A),theACCisrecordedtotransitionsbetweenthereferenceandtestelectrodeswhicharepresentedinisolation.Inthemodifiedparadigm(B),thereisadditionalcontinuoussuprathresholdstimulationfromflankingelectrodes.TheuseoftheCIasanEEGrecordingdevice,isfurtherdevelopmentwhichmayhelp
toimprovetheclinicalapplicabilityofCAEPmeasurementsincludingthespatialACC.
Withthistechnique,theCIisusedtodeliverstimuliaswellasrecordcortical
responses.ThisavoidstheneedtoconnectexternalEEGrecordingelectrodes.Whilst
theuseoftheCItorecordtheECAPiswellestablished,measurementsoflonger
latencyauditoryresponseshavebeenlimitedbytheshortrecordingwindowofonlya
Time (ms) Time (ms)
Electrode B Electrode C
Electrode A
Electrode D
(A) Standard paradigm (B) Modified paradigm
185
fewmillisecondsthattheCIdeviceallows.McLaughlinetal.(2012),showedthatitis
possibletousetheextra-cochlearelectrodeintheCochleardevicetorecordCAEPs.
Althoughtherecordingwindowwaslimitedto1.6ms,theCAEPwasmeasuredby
samplingtheresponsetotheauditorystimulusevery10msatlatenciesbetween10to
300msafterstimulusdelivery.Althoughthis‘closedloop’techniquewasextremely
timeconsuming,itwasfoundthattheresponsesobtainedweresimilartothatwitha
conventionalexternalEEGrecordingsystem.Campbelletal.2012,showedthatinthe
Cochleardevice,itwaspossibletoextendtherecordingwindowto10ms,inorderto
measurethecochlearmicrophonicresponse.FuturedevelopmentsinCIhardwareand
softwaremaymaketheuseof‘closed-loop’CAEPmeasurementsmorepractical.Ifthis
typeofsystemcouldbedeveloped,thenCAEPmeasurementscouldevenbe
performedremotely.Thiswouldhelptosaveclinicaltimeandawealthofinformation
regardingindividualauditoryprocessingcouldbeobtainedandusedtoinformclinical
management.
7.4Cochlearimplantation–currentlandscapeandfuturepriorities
Itisestimatedthatonly5%ofadultswhoareeligibleforCIactuallyundergo
implantation(“TheEarFoundation,”2016).Partofthereasonforthisislackof
awarenessamonghealthprofessionalsaboutcandidacy.Recentworkhasrevealed
thatfollowingeducationofcommunityaudiologists,therewasa3-foldincreaseinthe
CIreferralrate(Raineetal.,2016).TheUKhasrelativelystringentcriteriaforCI
candidacycomparedtoothercountries(Vickersetal.,2016).Forexample,adultsmust
haveprofoundbilateralhearinglosswiththresholdsworsethan90dBHLat
frequencies≥2kHz.Thiscomparedtocriteriaofbilateralseverehearinglosswith
thresholds≥75dBHLatfrequencies≥2kHzinAustralia.Itisrecognizedthatmany
peoplewhoarejustoutsidethecurrentUKcandidacycriteriawouldbenefitfrom
implantation.Muchworkisnowgoingonatanationalleveltorelaxthecandidacy
criteria.Withgreatereducationofreferringcliniciansandachangeinthecandidacy
criteriathereispotentialforahugeincreaseinthenumberofCIsurgeriesoverthe
nextfewyears.
Thepotentialincreaseinthenumberofindividualsundergoingimplantationmeans
thatimplantprogrammeswillhavetoexpandornewimplantprogrammeswillneedto
186
besetup.Inaddition,themodelofcaremayneedtobechangedsothatmorecareis
providedremotelyandisdirectedbypatientsthemselves(Cullingtonetal.,2018;
Wesargetal.,2010).Ashighlightedintheintroduction,thereissignificantvariabilityin
CIoutcomesandasignificantproportionofpatientshavepooroutcomes(Niparkoet
al.,2010;WilsonandDorman,2008).Itwillthereforebecomeincreasinglyimportant
toidentifyandaddressthefactorsthatareassociatedwithpoorhearingoutcomes
afterCI.
Futureresearchmustalsofocusonindividualizingpatientcare.Oneofthegreat
challengeswithcochlearimplantresearchistheheterogeneityofthestudy
population.Patientshavedifferentaetiologies,durationofhearingloss,cochlear
anatomyandpatternsofneuralsurvival.InorderforCIuserstogainmaximumbenefit
fromtheirimplant,individualizeddeviceselection,surgeryandfittingwouldseem
appropriate.Forexample,itispossibletoindividualizethelengthofcochlearimplant
electrodes(MistríkandJolly,2016)andinsertiontechnique(Rauetal.,2015)basedon
pre-operativeimaging.Fittingoftheimplantcanbeindividualizedusingacombination
ofimaging,behaviouralandelectrophysiologicalmeasurementsincludingtheACC
(Cosentinoetal.,2016;Mathewetal.,2017;Nobleetal.,2014).Thiscanprovide
informationsuchasscalartranslocationofelectrodes,presenceofneuraldead
regions,andhigherauditoryprocessingproblems.Thereisgrowingevidencethat
auditorydeprivation,particularlyinearlychildhoodaffectsnotonlyhearingand
languagebutcognitivefunction(Kraletal.,2016).Therefore,ithasbeensuggested
thatauditoryrehabilitationcouldbeaidedbyindividualizedassessmentandtreatment
ofneuro-cognitivedeficits.
Thesetypesofindividualizedassessmentsarelikelytobetimeconsumingandmay
provetobeimpracticalintheclinicalsetting.Therefore,itwillbenecessarytodevelop
abatteryoftestsandrehabilitationmeasureswhichthepatientcanadminister
themselvesusingtechnology.ThisiscertainlyinlinewiththeNHSFiveYearForward
View(“NHSEngland,Harnessingtechnologyandinnovation,”2018)ofharnessing
technologyandinnovationtohelpbettertheirownhealth.Itwillalsobenecessaryto
determinewhichassessmentsandinterventionsprovidethemostbenefit.The
heterogeneityoftheCIpatientsoftenmakesgeneralizingthefindingsofsmallscale
studiesdifficult.Researchgrantsshouldthereforebegearedtowardslargescalemulti-
187
centrestudies.Thiswillrequireclosecollaborationbetweenclinicians,scientistsand
industry.ThistypeofmodelhasbeenadoptedincentressuchastheHearingHub,
SydneyandtheClusterofExcellenceHearing4All,Hannover.Inaddition,the
developmentofnational/internationalregistriesofCIpatientscouldhelptoprovide
usefulepidemiologicalandoutcomedata.Thesetypesofstrategiescouldenablethe
provisionoftrulytailoredpatientcareandallowindividualstogainmaximumbenefit
fromtheirdevice.
7.5Conclusion
ElectrophysiologicalmeasurementsinCIusersallowtheobjectiveassessmentofhow
soundisencodedintheauditorypathway.Inthisthesis,itwasshownthatthespatial
ACCisafeasibleandvalidmeasureofelectrodediscrimination.Thesemeasurements
canprovideinformationoverandabovebehaviouraltesting.Furthermore,they
provideevidenceofplasticityinadultCIusers.Thesetypesofobjectivemeasures
couldprovideprognosticinformationandhelptoguideinterventionsthatleadto
improvedhearingoutcome.Thewidespreaduseofcorticalresponsemeasurementsin
clinicalpracticecouldrepresentthenextmajordevelopmentinthefieldofauditory
implantsandthisareaofresearchholdsmuchpromise.
188
AppendixA:Test-retestreliabilityoftheACCPreviousstudieshaveshownthattheACChasgoodtest-retestreliabilityinboth
normalhearingandCIusers(FriesenandTremblay,2006;Heetal.,2014).Thissection
consistsofaretrospectiveanalysisoftest-retestreliabilityusingthemethodologyof
thisstudy.Thisdatawascollectedduringthepilotandexperimentalphaseof
experiments3,4and5(Chapters4to6).Onlydatathatwascollectedwiththesame
stimulationparameterswasincludedintheanalysis.Sincetest-retestdatawasusually
severalmonthsapart,onlydatacollectedatleast6monthspostCIswitch-onwas
includedintheanalysis,asitislikelythatplasticityismostpronouncedintheearly
periodafteractivation.Test-retestdatawasavailableforelectrodepair4-5in7
participantswithABdevices(seetableA.1).Testingwasperformedattheloudness
balancedMClevel.Themediantimebetweencollectionoftest-retestdatawas3
months(range2-4months).TestproceduresandEEGanalysiswasperformedas
describedintheGeneralMethods(Chapter2).
TableA.1.Detailsofparticipantswithtest-retestdata.
ParticipantTest data: time after
switch-on (months)
Re-test data: time after
switch-on (months)
P1 82 85
S3 6 8
S4 14 18
S5 6 9
S8 6 10
S9 8 10
S11 6 9
FigureA.1showsthegrandmeanresponseacrossparticipantsofthetestandretest
datawhilefigureA.2showstheindividualdata.Visualinspectionofthewaveforms
showsgoodcorrespondencebetweenthetest-retestdata.Furthermore,Pearson’s
correlationcoefficientrevealedastrongrelationshipbetweenthegrandmeandata(r
=0.956(95%confidenceinterval0.952–0.960),p<0.001)andindividualdata(r=
0.823to0.943,p<0.001).Thepeak-to-peakN1-P2amplitudeoftheonsetresponse
andspatialACCforthetestandretestdataareshownintableA.2.Wilcoxon’ssigned
189
rankstestrevealednosignificantdifferenceinthepeakamplitudeofthetest-retest
datafortheonsetresponse(V=10,p=0.58)ortheACC(V=17,p=0.69).The
agreementbetweenthepeakamplitudeofthetest-retestdatawasassessedwiththe
intraclasscorrelationcoefficient(ICC).Thisshowedstrongagreementfortheonset
response(ICC=0.78,F(6,7)=8.44,p=0.006)andtheACC(ICC=0.84,F(6,7)=11.7,p=
0.002).
Inconclusion,thesedatashowthatspatialACCmeasurementsinCIusershave
excellenttest-retestreliability.
TableA.2AmplitudesofN1-P2responsefortheonsetandACCresponseinthetestandretestcondition.
Participant
OnsetresponseN1-P2
amplitude(µV)
ACCresponseN1-P2
amplitude(µV)
Test Retest Test Retest
P1 9.43 9.00 3.56 3.28
S3 8.60 6.64 4.42 3.56
S4 6.07 6.18 2.86 2.74
S5 5.65 7.71 1.73 2.48
S8 7.92 7.39 2.61 2.83
S9 10.10 10.35 4.15 4.70
S11 10.44 9.87 1.41 2.12
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FigureA.1Auditoryevokedcorticalresponsesfor(A)testand(B)retestdata.Thethickpurplelineshowsthegrandmeandataacrossparticipantsandthethinbluelinesaretheindividualdata.ThePearson’scorrelationcoefficient,95%confidenceintervalsandp-valueareshownatthetopofthepanel.
5
0
5A
mpl
itud
e [
V]
0.0 0.2 0.4 0.6 0.8 1.0Time [s]
5
0
5
Am
plit
ude
[V
]
(A) Test data
(B) Retest data
Grand mean waveforms, r = 0.956 (0.952 - 0.960), p < 0.001
191
192
FigureA.2Individualauditoryevokedcorticalresponsetest-retestdata.TheparticipantID,Pearson’scorrelationcoefficient,95%confidenceintervalsandp-valueareshownatthetopofeachpanel.
193
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