1

DevelopmentandSignificanceofthe

SpatialAuditoryChangeComplexin

AdultCochlearImplantUsers

RajeevMathew

Adissertationsubmittedinfulfilmentoftherequirementsforthe

degreeofDoctorofPhilosophy,UCL,2018

2

Declaration

I,RajeevMathew,confirmthattheworkpresentedinthisthesisismyown.Where

informationhasbeenderivedfromothersources,Iconfirmthatthishasbeen

indicatedinthethesis.

3

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

4

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.

5

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.

6

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.

7

Theimpactofthisthesiswillbedeliveredthroughpublicationinpeerreviewed

journals,presentationatinternationalconferencesandthroughfutureprojects.There

arealready2peerreviewedjournalpublicationsand13conferencepresentations

fromthisthesis.Furtherprojectsinvolvingcollaborationfromindustryandclinicians

arealreadyunderway.

8

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

9

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

10

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

11

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

12

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

13

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

14

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

15

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

16

PCA principalcomponentanalysis

PSP platinumsoundprocessor

PTC psychophysicaltuningcurve

PPS pulsespersecond

RMS rootmeansquared

RN residualnoise

SMRT spectral-temporallymodulatedrippletest

SNR signal-to-noiseratio

SOA stimulusonsetasynchrony

17

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.

18

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.

19

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

20

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

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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).

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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

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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

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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.

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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

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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

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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,

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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

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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

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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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