www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
ORIGINAL
ARTICLE
Analysis
of
electrically
evoked
compound
action
potential
of
the
auditory
nerve
in
children
with
bilateral
cochlear
implants
夽
Fernanda
Ferreira
Caldas,
Carolina
Costa
Cardoso,
Monique
Antunes
de
Souza
Chelminski
Barreto,
Marina
Santos
Teixeira,
Anacléia
Melo
da
Silva
Hilgenberg,
Lucieny
Silva
Martins
Serra,
Fayez
Bahmad
Junior
∗PostgraduatePrograminHealthSciences,UniversidadedeBrasília(UnB),Brasília,DF,Brazil
Received31May2014;accepted24December2014 Availableonline10December2015
KEYWORDS Child;
Cochlearnerve; Cochlearimplant; Evokedpotentials
Abstract
Introduction:Thecochlearimplantdevicehasthecapacitytomeasuretheelectricallyevoked compound action potentialoftheauditory nerve.Theneural responsetelemetryisused in ordertomeasuretheelectricallyevokedcompoundactionpotentialoftheauditorynerve.
Objective: Toanalyzetheelectricallyevokedcompoundactionpotential,throughtheneural responsetelemetry,inchildrenwithbilateralcochlearimplants.
Methods:Thisisananalytical,prospective,longitudinal,historicalcohortstudy.Sixchildren, aged1---4years,withbilateralcochlearimplantwereassessedatfivedifferentintervalsduring theirfirstyearofcochlearimplantuse.
Results:Thereweresignificantdifferencesinfollow-uptime(p=0.0082)andelectrodeposition (p=0.0019)intheT-NRTmeasure.Therewasasignificantdifferenceintheinteractionbetween timeoffollow-upandelectrodeposition(p=0.0143)whenmeasuringtheN1-P1waveamplitude betweenthethreeelectrodesateachtimeoffollow-up.
Conclusion: The electrically evoked compound action potential measurement using neural responsetelemetryinchildrenwithbilateralcochlearimplantsduringthefirstyearof follow-upwaseffective indemonstratingthesynchronizedbilateraldevelopmentoftheperipheral auditorypathwaysinthestudiedpopulation.
© 2015 Associac¸ão Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).
夽
Please citethisarticleas:Caldas FF,Cardoso CC,Barreto MASC,Teixeira MS,HilgenbergAMS,SerraLSM, etal. Analysis of elec-tricallyevokedcompoundactionpotentialoftheauditorynerveinchildrenwithbilateralcochlearimplants.BrazJOtorhinolaryngol. 2016;82:123---30.
∗Correspondingauthor.
E-mail:fayezbjr@gmail.com(F.BahmadJr.). http://dx.doi.org/10.1016/j.bjorl.2014.12.013
PALAVRAS-CHAVE Crianc¸a;
Nervococlear; Implantecoclear; Potenciaisevocados
Análisedopotencialdeac¸ãocompostodonervoauditivoevocadoeletricamenteem
crianc¸asusuáriasdeimplantecoclearbilateral
Resumo
Introduc¸ão:O implantecoclear tem a capacidade de medir opotencial de ac¸ãocomposto eletricamenteevocadodonervoauditivo(ECAP).Paraestaverificac¸ãoutiliza-seumamedida chamadatelemetriaderespostasneurais.
Objetivo:Analisar opotencial de ac¸ão compostoevocadoeletricamente, pormeioda neu-rotelemetriaderespostasneurais,emcrianc¸asusuáriasdeimplantecoclearbilateral.
Método: Trata-sedeumestudoanalítico,prospectivo,decoortehistóricalongitudinal.Foram recrutadasseiscrianc¸as,comidadesentrede1-4anos,usuáriasdeimplantecoclearbilateral. Estascrianc¸asforamavaliadasemcincomomentosduranteoprimeiroanodeusodoimplante coclear.
Resultados: Houvediferenc¸asignificativanotempodeacompanhamento(p=0,0082)eposic¸ão doeletrodo(p=0,0019)namedidadeT-NRT.Houvediferenc¸asignificativanainterac¸ãoentre tempo deacompanhamentoe posic¸ãodo eletrodo(p=0,0143)namedidadaamplitudedas ondasN1-P1entreostrêseletrodosacadatempodeacompanhamento.
Conclusão:Amensurac¸ãodoECAPpormeiodaNRTnascrianc¸ascomimplantecoclearbilateral duranteoprimeiro ano deacompanhamentofoi uma medidaimportantepara apresentaro desenvolvimentobilateral davia auditivaperiféricadeforma sincronizadanestapopulac¸ão estudada.
© 2015 Associac¸ão Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Publi-cado por Elsevier Editora Ltda. Este é um artigo Open Access sob a licença CC BY (https://creativecommons.org/licenses/by/4.0/deed.pt).
Introduction
The cochlear implant (CI) device is widely accepted and
has been considered one of the most important
thera-peutic options for patients with severe and/or profound bilateral sensorineural hearing loss, in cases whodid not achievesatisfactory auditoryperception benefitswiththe useofindividualsoundamplificationdevice(ISAD).TheCIs havebeen indicatedat progressivelyyounger agesdue to advancesinearlyaudiologicaldiagnosisandnew technolo-giesintheCIdevices.1
Overthelastdecades,bilateral CIsurgerybegantobe
performed, a procedure that can be performed
simulta-neouslyorsequentially.Thesimultaneoustechniqueisused whenthepatientreceivesthetwointernalcomponentsina singlesurgicalprocedure,andthesequentialone,whenthe patientreceivesthetwointernal componentsindifferent surgicalprocedures.
PatientswhorequireaCIhavebeenincreasinglychoosing thebilateralprocedure.Somestudieshaveshownthatthese patients benefit from improved speech in the perception withnoise2andimprovedsoundlocation.3,4
The process known as ‘‘Programming’’ or ‘‘Mapping’’ of the CIspeech processor is performed at regular inter-valspostoperatively.TheMappingprocessaimstodetermine theappropriatedynamicrangeofelectricalstimulationfor each electrodechannel. The dynamic range is the differ-encebetweenthedetectionperceptionthreshold(T-level) andloudness---maximumcomfort(levelC).5
Themeasurementoftheelectrodeimpedancetelemetry canprovideanindicationoftheelectrodeinterfacestatus inthetissues,aswellastheappropriateelectrodefunction. Significantchangesinthesemeasures canbeindicativeof
changes inthe surroundingtissueand/or changesin elec-trodefunction.Initialchangesinelectrodeimpedancecan beexpectedduetophysicalchangesintheelectrode-tissue interface.6
The CI has the capacity to measure the electrically
evoked compound action potential (ECAP) of the
audi-tory nerve. The system applies an electrical pulse to a specific intracochlear electrode and the evoked neural responseis recordedinan adjacent electrode.Ameasure called NeuralResponse Telemetry (NRT)is used to assess this potential. The system elicits a valid neural response and robust recordings. These responses are recorded and returnedtotheprogramming interfacesystem forclinical analysis.7,8
The ECAP providesa relatively direct measurement of theauditorynerveresponseafterelectricalstimulationand itismeasuredincurrentunits(CUs).9TheECAPwaveform
typicallyconsistsof aninitialnegativepeakfollowed bya positivepeak,calledN1andP1,respectively.7,8
The NRT threshold (T-NRT) is defined as the smallest amountofelectriccurrentthatcanevokethese physiologi-calresponses.StudieshaveshownthattheT-NRTmeasured intraoperativelyoratpostoperativeintervalscanbe corre-latedwiththepsychophysicaldetectionofthethreshold(T level)andthemaximumlevelofcomfort(Clevel)inpatients withCIs.Theamplitudeoftheresponse(measuredbetween N1andP1)varieswithincreasingstimulusintensityanditis measuredinmillivolts(V).10---12
Methods
ThestudywasapprovedbytheResearchEthicsCommittee (REC)ofFaculdade deCiênciasdaSaúde,Opinionnumber 571,432/2014.Theparticipants’parentsorguardianssigned thefreeandinformedconsentform(FICF)accepting their participationinthestudy.
This is ananalytical, prospective,longitudinal contem-porarycohortstudy.
Sample
Thestudyincludedsixchildren,fivefemalesandonemale. Agesrangedfrom1to4years.Thechildrenhadcongenital hearinglossand wereNucleus® bilateral cochlearimplant
users (Cochlear Corporation), having been submitted to simultaneous surgery and total electrode insertion. Data wereanalyzed betweenJanuary (2012)andMarch (2014). Participantswithunilateralcochlearimplant,auditory neu-ropathyspectrum disorder(ANSD),partialinsertionof the electrodearrayandthosesubmittedtothesequential tech-niqueduringinternalcomponentsurgerywasexcluded.
Equipment
A speechprocessor, external antenna (coil)with magnet, connectorcablebetweenspeechprocessorandtheexternal antenna,programminginterface---POD(ProgrammingPOD), andthecomputerusedtosendandreceiveneural informa-tionwereusedtoevaluateimpedancetelemetryandneural responses.
Procedure
The impedance telemetryand neural response recordings werecollectedthroughanAutoNRTsystem,usingthe soft-wareCustomSoundEP3.2versiontoperformintraoperative measurementsandCustomSound3.2forpostoperative mea-surements.
TheimpedancetelemetryandNRTwerefirstperformed intheoperatingroom,aftertheinternalcomponent inser-tionandwhile the child wasstillanesthetized,and these proceduresalsocontinuedtobecarriedoutinthe postop-erativeperiod.Duringtheintraoperativeperiod,theneural responseswererecordedinthe22electrodes;however,for theanalysisinthisstudyonlytheelectrodesE1,E11andE22 wereused.Postoperatively,theparticipantswereevaluated atfivemoments(first,third,sixthandtwelfthmonths)after surgery,andtheresponseswererecordedintheelectrodes E1,E11andE22.
The impedances were measured in the MP1
monopo-lar,MP2monopolar,MP1+2monopolarandCommonGround
(CG)modes.Valueswereconsiderednormalwhenbetween 0.7kand30k.Electrodeswithelectricalproblemssuch asshort circuits --- ‘‘short’’ (<0.7k) and open circuits ---‘‘open’’(>30k)werenotselected.
The parameters for ECAP recording were: interpulse
intervalof400s,stimulationrate of80Hz withseriesof
25s of pulsewidth, the number of presentations varied
between100and200pulsespersecondforamplifiergainsin,
respectively,50dB,thewindowforrecordingwas1600s.
Thecurrentlevelofthemaskingnoisewasfixedat10units abovethestimulationlevel.
AllparticipantsreceivedthesameparametersinCI pro-gramminginthepostoperativeperiod.Theparametersused were in accordance with the standardization of Cochlear Corporation:ACE (advancedcombination encoder) speech coding strategy, mode of stimulation MP1+2, stimulation rateof900pulses persecond perchannel,eightmaximas andpulsewidthof25s.
For each electrode, the characteristics of the T-NRT
thresholdand peakamplitude of N1-P1 waves were
com-pared between the returns. These measurements were
separatelycomparedfor:therightandleftear,theintraand postoperativeperiodsandelectrodeposition.Electrode01 (E01)wascalledbasal,electrode11(E11)wascalledmiddle andelectrode22(E22)wascalledapical.Thesenominations areinaccordancewiththeirpositionsinthecochlearregion. The ‘‘activation’’ of theCI electrodes occurredwithin onemonthaftertheintraoperativeperiod,whichwouldbe thefirst time thedevice wasactivated,thus sendingthe electricalsignaltotheauditorynervethroughthe22 intra-cochlear electrodes; after this period, the postoperative measurementswerestarted.
Fromeachmeasuredelectrode,onlythevalidresponses wereselected,thatis,theNRTresponseshadtobe identifi-able,eventhoughitisknownthatresponsesareincreasingly lessrobustintheelectricalthreshold.
Theanswerswereanalyzedthroughtheautomatic soft-ware function. The corresponding recording location was chosenfor theelectrodes tobeanalyzedin basal,middle andapicalform(E1,E11andE22electrodes).Whenthiswas notpossible,thatis,whentheseelectrodesdidnotrespond orwhenthechildrenshowedsomediscomfort,theclosest electrodes’responseswerenotconsidered.
Statisticalanalysis
Theresults ofthisstudy wereanalyzedby amixed-effect modelofanalysisofvarianceforrepeatedmeasures.Once themeasurementsofeachindividualwereobtainedinboth ears,inthethreeassessedelectrodesandduringfollow-up, afactorialdesignstructurewasusedinthemodel.
Whentheglobalp-valueofanyfactorwaslessthan0.05, a Bonferroni correction was used to adjust the multiple testedcomparisons.AnalyseswereperformedusingtheSAS 9.3software.
Results
Table1 shows the participants’ characterization. All chil-drenhadprofoundsensorineuralhearingloss,ofidiopathic etiology.
Table 2 shows the mean age of participants at the CI surgeryandthetimeof CIuse(months).Themeanageat surgerywas23.50months(standarddeviation5.43)andthe timeofcochlear implant use was14.67months (standard deviation6.50).
Table1 Characteristicsofparticipants.
Participants Etiology Typeanddegreeof
hearingloss
AgeatCIsurgery (months)
Cochlearimplant processor
TimeofCIuse (months)
1 Idiopathic Profoundsensorineural 14 CP810 5
2 Idiopathic Profoundsensorineural 22 CP810 12
3 Idiopathic Profoundsensorineural 24 CP810 16
4 Idiopathic Profoundsensorineural 24 CP810 16
5 Idiopathic Profoundsensorineural 27 CP810 14
6 Idiopathic Profoundsensorineural 30 CP810 25
CI,cochlearimplant.
Table2 Meanage(months)atsurgeryandtimeofCIuse.
Variable Mean Standarddeviation
AgeatCIsurgery 23.50 5.43
TimeofCIuse 14.67 6.50
CI,cochlearimplant.
Table3 Analysisofvariancechart.
Factors Fvalue p-value
Ear 3.50 0.1202
Time 4.80 0.0082a
Electrode 12.49 0.0019a
Ear×time 1.31 0.3035
Ear×electrode 0.10 0.9023
Time×electrode 0.66 0.7171
Ear×time×electrode 0.55 0.8086
ap-valuewithBonferroni correction.Statistically significant difference(p<0.05).
thevisualT-NRTandtheamplitudeofN1-P1waves,willbe shown.
T-NRTvisualmeasurement
Initially,weadjustedthemodelofmixed-effectanalysisof variancewithrepeatedmeasures.Weevaluatedthefactors: ear(rightandleft),timeoffollow-upbetween intraopera-tiveandpostoperativeperiodsandpositionofelectrodesin
thecochlea.Allthesemeasureswerealsocorrelatedwith eachother.TheresultsareshowninTable3.
Oncewedetectedsignificantdifferencesinthetimeof follow-up (p=0.0082) and electrode position (p=0.0019), the analysiswascontinued bycomparing themean T-NRT values,separatelyfor each factor,usingmultiple compar-isons two by two between the levelsof each factor with Bonferronicorrection.
Table4shows themeanvaluesandstandarddeviations forthefactors:ear,positionoftheelectrodesinthecochlea andtimeoffollow-upbetweenintraoperativeand postop-erativeperiods.Thesefactorswereassessedseparately.
Fig.1showsthemeanvaluesoftheT-NRTthresholdfor eachear,separately.
Fig.2showsthemeanvaluesforT-NRTmeasuredineach electrode,separately.Toanalyzetheseresults,three elec-trodes were assessedin each ear, at fivedifferent times, duringthefirstyearofCIuse.
Thus,atotalof180measurementswereperformed(60 foreachelectrode).Theresultsobtainedwere51 measure-mentsinbasalelectrodes, 49inmedialelectrodes and55 inapicalelectrodes,totaling155measurements.Itis note-worthythatparticipant1wasassessedonlyuptothefirst threemonths ofCI use,because shehad usedthe device foronly5months,andthus12measurementswerelost(2 in electrode E01, 2 in electrode E011 and 2 in electrode E22). Excluding this measurement in thisparticipant, 168 measurementsremained.Ofthisnumber,13measurements
showedabsenceintheNRTmeasurement.
Table 5 shows multiple comparisons for the electrode factorandp-valueswithBonferronicorrection.
Table4 Mean(currentunits)andstandarddeviationperfactor.
Ear Time Electrode Mean Standarddeviation
Right 174.79 2.51
Left 169.99 2.76
E01 180.49 2.88
E11 182.14 2.73
E22 156.15 2.76
Intra-op 188.64 3.77
1stmpostop 166.03 4.03
3rdmpostop 168.12 3.53
6thmpostop 167.68 3.62
12thmpostop 168.07 4.47
Ear
N Mean
T-NRT measurement Confidence interval for mean 95%
77
78
0 10 20 30 40 50 60 70 80 90 100110 120 130 140 150 160 170180 174.79
169.99
Right
Left
Figure1 MeanT-NRTvaluesforeachearseparately.
Electrode
01
11
22
0 10 20 30 40 50 60 70 80 90 100 110 120 130140 150 160 170 180190 51
N Mean
T-NRT measurement Confidence interval for mean 95%
180.49
182.14
156.15 49
55
Figure2 MeanT-NRT(currentunits)valuesineachelectrode.
Table5 Multiplecomparisonsfortheelectrodefactor. Multiplecomparisons---electrodefactor p-valuea
E01×E01
---E01×E11 1.0000
E01×E22 0.0060a
E11×E01 1.0000
E11×E11
---E11×E22 0.0036a
E22×E01 0.0060a
E22×E11 0.0036a
E22×E22
a p-value withBonferroni correction.Statisticallysignificant difference(p<0.05).
The meanvalue of T-NRTin electrode E01 was signifi-cantlyhigherthaninelectrodeE22(p=0.0075);themean valueofT-NRTinelectrode11wassignificantlyhigherthan inelectrode22(p=0.0035),whereasthemeanvaluesof T-NRTdidnotdiffersignificantlybetweenelectrodeE01and electrodeE11.
Table6shows multiplecomparisonsfor thetimefactor (p-values)withBonferronicorrection.
The mean value of T-NRT intraoperatively was signif-icantly higher than the mean T-NRT values in the first (p=0.0238) and third (p=0.0203) months of follow-up. There is no significant difference in other comparisons betweentimesoffollow-up(6thmonthand12thmonth).
Fig. 3 shows this significant difference of p-value betweenthe intraoperative periodandthe firstand third monthsoffollow-up.At6monthsand12monthsof follow-up,themeasuredT-NRTvalueswerenotsignificant.
MeasurementoftheN1-P1waveamplitude
IntheresultsoftheN1-P1waveamplitudemeasurements, initiallytheadjustmentofthemodelofmixed-effect analy-sisofvariancewithrepeatedmeasureswascarriedout.We evaluatedthefactors:ear(rightandleft),timeoffollow-up betweenintraoperativeandpostoperativeperiodsand posi-tionofelectrodesinthecochlea.Allthesemeasureswere alsocorrelatedwith each other.The results areshown in Table7.
Onceasignificantdifferencewasdetectedinthe inter-action between time of follow-up and electrode position (p=0.0143), the analysiswascontinuedby comparingthe meanvaluesofN1-P1waveamplitude,betweenthethree
electrodes at each time of follow-up, with the use of
Table6 Multiplecomparisonsforthetimeoffollow-upfactor.
Timefactor Multiplecomparisons---timefactor
Intra-op 1stmpostop 3rdmpostop 6thmpostop 12thmpostop
Intra-op --- 0.0238a 0.0203a 0.0970 0.1056
1stmpostop 0.0238a --- 1.0000 1.0000 1.0000
3rdmpostop 0.0203a 1.0000 --- 1.0000 1.0000
6thmpostop 0.0970 1.0000 1.0000 --- 1.0000
12thmpostop 0.1056 1.0000 1.0000 1.0000
---Intra-op,intraoperative;postop,post-operative;m,months.
200
190
180
170
160
0 1 2 3
Time (months)
T-NR
T measurement
˝-˝ Lower limit ˝•˝ Mean ˝-˝ Upper limit
4 5 6 7 8 9 10 11 12 13
Figure 3 Difference in T-NRT (current units) between the intraoperativeandthepostoperativefollow-upperiods.
multiple comparisons two by two between the levels of
eachelectrodeateachtime,withBonferronicorrection. Table 8 shows the mean values and the respective standarddeviations foreach electrodeandtime combina-tion.
Table 9shows multiple comparisons betweenthe elec-trodes at each time, adjusted by Bonferroni correction factor.
In the third month of follow-up in the postoperative period,themeanN1-P1waveamplitude(V)valuein
elec-trodeE11wassignificantlylowerthanthemeanN1-P1wave amplitudevalueinelectrodeE22(p=0.0285).
Fig.4 shows thissignificance ofthe p-value in the3rd monthoffollow-upbetweenE11andE22.
Discussion
While measuring impedance telemetry during the 12
months,normalvalueswereobserved for alltheassessed electrodes.Thus,itwasnotnecessarytoexcludeany elec-trodeforthemeasurementsusedinthisstudy.Theseresults alsoshowedintegrityofthecochlearimplantinternal com-ponent.ThesedataagreewiththestudybyHughesetal.,6
who reported that this measure provides an appropriate indicationabouttheelectrodeinterfacestatusintissue,as wellastheappropriatefunctionoftheelectrode.
Table7 Analysisofvariancechart.
Factors Fvalue p-value
Ear 1.75 0.2429
Time 3.57 0.0259a
Electrode 1.62 0.2458
Ear×time 0.35 0.8421
Ear×electrode 0.90 0.4387
Time×electrode 3.07 0.0143a
Ear×time×electrode 0.76 0.6380
ap-valuewithBonferroni correction.Statistically significant difference(p<0.05).
Table8 Meanandstandarddeviationforeachcombination oftimeandelectrodeinthemeasurementoftheamplitude ofN1-P1waves(V).
Time Electrode Mean Standard
deviation
Intra-op E01 12.7675 9.8181
Intra-op E11 20.6550 9.8181
Intra-op E22 17.3858 9.8181
1rdmpostop E01 23.6229 10.0431
1rdmpostop E11 22.6594 9.9920
1rdmpostop E22 24.1875 9.8181
3rdmpostop E01 17.2277 9.9069
3rdmpostop E11 15.7465 10.0292
3rdmpostop E22 26.2308 9.8181
6thmpostop E01 34.2599 10.8887
6thmpostop E11 31.0511 11.2435
6thmpostop E22 35.3715 10.8859
12thmpostop E01 45.7199 10.8762
12thmpostop E11 45.7500 10.7552
12thmpostop E22 59.2800 10.7552
Intra-op,intraoperative;postop,postoperative;m,months.
T-NRTvisualthreshold
InFig.1, therewasnosignificant differencebetween the ears (p=0.1202) in T-NRT measure and in the measured N1-P1waveamplitude(p=0.2429)(Table7).Thesefindings allowustoinferthatbilateralCIwithsimultaneoussurgical technique, for this study population, was effective for synchronizedneuralstimulationinbothears.The stimula-tionprovided bya cochlear implant issingle,and alarge electricpulsecanpromotegreaterstimulationonneurons fortheauditorynervetorespondtothestimulusinahighly
Table9 Multiplecomparisonsbetweentheelectrodesat eachfollow-upofthemeasurementofamplitudeofN1-P1 waves(V).
Multiplecomparisons tvalue p-valuea
Intra-op---E01×E11 −3.12 0.0645 Intra-op---E01×E22 −1.53 1.0000 Intra-op---E11×E22 1.59 1.0000 1stmpost-op---E01×E11 0.37 1.0000 1stmpost-op---E01×E22 0.23 1.0000 1stmpost-op---E11×E22 −0.16 1.0000 3rdmpost-op---E01×E11 1.03 1.0000 3rdmpost-op---E01×E22 −2.49 0.2925 3rdmpost-op---E11×E22 −3.46 0.0285a 6thmpost-op---E01×E11 0.65 1.0000 6thmpost-op---E01×E22 −0.25 1.0000 6thmpost-op---E11×E22 −0.87 1.0000 12thmpost-op---E01×E11 1.06 1.0000 12thmpost-op---E01×E22 −0.33 1.0000 12thmpost-op---E11×E22 −1.43 1.0000
60.00
01
0 1 2 3 4 5 6 7 8 9 10 11 12 11 22
Electrode
Time (months)
N1-P1 amplitude (µV)
50.00
40.00
30.00
20.00
10.00
Figure4 Meanvalue ofN1-P1wave amplitude(V) inthe thirdmonthoffollow-upbetweenE11andE22.
synchronized manner, allowing benefits for children with severehearingloss.13
Gordon et al.14 performed a study with EABR
(Electri-cally EvokedAuditoryBrainstem Response) andconcluded thatthereductionoflatenciesinthewavesmayreflectan increaseinneuralsynchronyoramorerapidnerve conduc-tion in the brain stem promoted by bilateral stimulation versusunilateralstimulation.
The ECAP through the NRT measure only peripherally
assesses the auditory pathway (auditory nerve), but it is importanttoemphasizethatthiselectricalstimulation trig-geredin theauditory pathwayis oneof theprecursorsto makeauditoryinformationeffectivelyarriveattheauditory cortex.10
Fig.2showsthemeanvaluesforT-NRTmeasurementin each electrodeseparately.Postoperatively,absences were observed inthe recordingsof thismeasure,which can be explainedbysomediscomfortduringtheprocedure(4
mea-surements) and the remaining by the absence of neural
responseperse(9measurements,thatis,4inelectrodeE01, 4inelectrodeE11and1inelectrodeE22).Thesedataare similartootherdatafromliterature.15Laietal.16statethat,
over time,the trendof NRTlevelsimprove andgenerally becomestable.Theseresponsestoelectricalstimulationof electrodesshowvariationsaccordingtotheirpositionwithin the cochlea and the density and integrity of the neural population.17
In this study, the mean T-NRT measurement (Table 4) duringtheintraoperative periodwas188.64 CUs,whereas in the postoperativeperiodit was166.03 CUs in the first month; 168.12 CUsin the thirdmonth; 167.68 CUs in the sixthmonth,and171.50CUsinthe12thmonth.Themean valueofT-NRTintheintraoperativeperiodwassignificantly higherthanthemeanT-NRTvaluesinthefirst(p=0.0238) andthird(p=0.0203)monthsoffollow-up.Thereisno sig-nificantdifferenceinothercomparisonsbetweenperiods(6, 9,12months).
However, in the studies of Tanamati et al.,18 Hughes
etal.,6ThaiVanetal.,10andMuhaimeedetal.19therewere
nostatisticallysignificantdifferencesintheT-NRTthreshold duringthefirstyearofdeviceprogramming.Laietal.16also
foundnosignificantdifferencein thismeasureinthefirst 15monthsofdeviceuse.Intheseliteraturefindings,theCI surgerywasperformedwithparticipantsfromdifferentage groups.OnlyinthestudyofTanamatietal.18ayoungerage
atsurgery wasobserved, before3years,but withno sta-tisticalsignificance. The ageat CIsurgery (23.50months) andthebilateralstimulationofthehearingnervecan jus-tifythe significantfindingduringthefirstthreemonthsin ourpopulation.
To justifythe absenceofsignificant correlation after3 months of CI use, it should be considered that the NRT measurement only allows an investigation of the neural responsivenesscapabilityintheperipheralauditorysystem. Thus,onecaninferthatthefirstthreemonthswere essen-tialforthestimulationoftheauditorynerveinthechildren followedinthisstudyandthattheneuralresponseremained inthepresenceofelectrical stimulationafterthisperiod.
The NRT measurement cannot guarantee that the
cogni-tive mechanisms involved in the auditory perception are activated.10
Table 5 shows that the mean value of T-NRT in elec-trode E01 was significantly higher than in electrode E22 (p=0.0075);themeanvalueofT-NRTinelectrodeE11was significantlyhigherthan inelectrodeE22(p=0.0035),and themeanvaluesofT-NRTdidnotdiffersignificantlybetween electrodesE01andE11.
ThesedataaresimilartothosereportedbyDeesetal.,20
Vlahovicet al.21 and Brown et al.,22 whoobserved a
sig-nificant effect between the apical and basal electrodes. Consideringtheliteraturefindingscorrelatedtothepresent
study data, we can assume that chronic stimulation of
thelow-frequencycochlearregionduringthepreoperative periodmayhave contributedtoimproveneuronalsurvival and/orimproveneuronalsynchronyofperipheralneuronsin theapicalportionofthecochlea,orthatperforminghearing rehabilitationpreoperatively,andtheactivationand devel-opmentofthecentralauditorypathwayscontributetothe functionalmaintenanceofspiralganglioncellsintheapical portionofthecochlea.21
N1-P1peakamplitude
InTable 7, the timeof CIuse and the electrodeposition were correlated, and there was a significant difference (p=0.0143)intheN1-P1amplitudewiththesefactors. Gor-donetal.13alsofoundsignificanceintheincreaseoftheN1
peakamplitudeintheECAPandintheVwaveinEABR, dur-ingthetimeofCIuse.Tanamatietal.18evaluatedthefirst
yearofCIuseandfoundthatinallelectrodestherewasan increaseintheN1peakamplitudebetweenthesecondand thirdreturns.
neurons, and thus a greater number can be recruited to establisharesponsewithsynchrony.13
Table9andFig.4showthat,inthethirdmonthof postop-erativefollow-up,themeanvalueofN1-PIwaveamplitude (V) in electrode E11 was significantly lower than the
meanN1-P1waveamplitudeinelectrodeE22(p=0.0285). Therewerenosignificantdifferencesforothercomparisons betweentheelectrodesateachtimeperiod.
Gordon et al.,23 Hughles et al.6 and Vlahovic et al.21
also found higher amplitude of ECAP in the apical
elec-trodes than in the medial and basal electrodes. These
resultssuggestthatelectricalstimulationofthebasal elec-trodesmayinvolveasmallernumberofspiralganglioncells, whencomparedtostimulationintheintermediateorapical electrodes.23 The amplitudes reflect the sum of the
neu-ronactivities,thatis,thenumberofneuronsthatrespond toastimulus,whichinturnindicatebetterpreservationof neuronalfunction.21
Considering thedata shown in this study,we observed thatthe auditorypathways in implantedchildren become more efficient during the first year of cochlear implant use,probablybecausethegroupsofnerves respondfaster and with a greater degree of synchrony. These activity-dependentprocessesareprobablyduetoincreasedsynaptic networks,andperhapstoanincreaseinmyelination.13
Conclusion
Basedontheanalysisofneuralresponsesinsixchildren eval-uatedinthefirstyearofuseofbilateralcochlearimplants, weconcludedthatthemeasurementofECAPbyNRTwasan importantmeasuretoassessthe bilateraldevelopmentof theperipheralauditorypathwayinasynchronizedmanner inthisassessedpopulation.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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