Braz. j. . vol.81 número4

(1)

www.bjorl.org

Brazilian

Journal

of

OTORHINOLARYNGOLOGY

ORIGINAL

ARTICLE

Mismatch

negativity

in

children

with

specific

language

impairment

and

auditory

processing

disorder

夽

Caroline

Nunes

Rocha-Muniz

∗

_,

_Débora

_Maria

_Befi-Lopes,

_Eliane

_Schochat

SchoolofMedicine,UniversidadedeSãoPaulo(USP),SãoPaulo,SP,Brazil

Received14May2014;accepted12August2014 Availableonline10June2015

KEYWORDS

Electrophysiology; Auditoryperception; Auditoryperceptual disorders;

Evokedpotentials auditory;

Language development disorders

Abstract

Introduction:Mismatch negativity, an electrophysiological measure, evaluates the brain’s capacitytodiscriminatesounds,regardlessofattentionalandbehavioralcapacity.Thus,this auditoryevent-relatedpotentialispromisinginthestudyoftheneurophysiologicalbasis under-lyingauditoryprocessing.

Objective:Toinvestigatecomplexacousticsignals(speech)encodedintheauditorynervous systemofchildrenwithspecificlanguageimpairmentandcomparewithchildrenwithauditory processingdisordersandtypicaldevelopmentthroughthemismatchnegativityparadigm.

Methods:Itwasaprospectivestudy.75 children(6---12 years)participated inthisstudy: 25 childrenwithspecificlanguageimpairment,25withauditoryprocessingdisorders,and25with typicaldevelopment.Mismatchnegativitywasobtainedbysubtractingfromthewavesobtained bythestimuli/ga/(frequent)and/da/(rare).Measuresofmismatchnegativitylatencyand twoamplitudemeasureswereanalyzed.

Results:Itwaspossibletoverifyanabsenceofmismatchnegativityin16%childrenwithspecific languageimpairmentand24%childrenwithauditoryprocessingdisorders.Inthecomparative analysis,auditoryprocessingdisordersandspecificlanguageimpairmentshowedhigherlatency valuesandloweramplitudevaluescomparedtotypicaldevelopment.

Conclusion:Thesedatademonstratechangesintheautomaticdiscriminationofcrucial acous-ticcomponentsofspeechsoundsinchildrenwithspecificlanguageimpairmentandauditory processing disorders. It could indicate problems in physiological processes responsible for ensuringthediscriminationofacousticcontrastsinpre-attentionalandpre-consciouslevels, contributingtopoorperception.

夽 _Please_cite_this_article_as:_Rocha-Muniz_CN,_Lopes_DMB,_Schochat_E._Mismatch_negativity_in_children_with_specific_language_impairment

andauditoryprocessingdisorder.BrazJOtorhinolaryngol.2015;81:408---15. ∗_{Corresponding}_author.

E-mail:carolrocha@usp.br(C.N.Rocha-Muniz). http://dx.doi.org/10.1016/j.bjorl.2014.08.022

(2)

PALAVRAS-CHAVE

Eletrofisiologia; Percepc¸ãoauditiva; Transtornosda percepc¸ãoauditiva; Potenciaisevocados auditivos;

Transtornosdo desenvolvimentoda linguagem

Mismatchnegativityemcrianc¸ascomdistúrbioespecíficodelinguagemetranstorno doprocessamentoauditivo

Resumo

Introduc¸ão: MismatchNegativity(MMN),umamedidaeletrofisiológica,medeahabilidadedo cérebroemdiscriminarsons,independentedacapacidadeatencionalecomportamental.Assim, essepotencialmostra-sepromissornoestudodasbasesneurofisiológicasquesubjazo proces-samentoauditivo.

Objetivo: Investigaradiscriminac¸ãodesinaisacústicoscomplexos(fala)nosistemaauditivo pormeiodoMMN,comcrianc¸ascomdistúrbioespecíficodelinguagem(DEL),comparandocom transtornodoprocessamentoauditivo(TPA)edesenvolvimentotípico(DT).

Método: EstudoProspectivo.75 crianças(6-12 anos)participaramdeste estudo:25 crianças comDEL,25comTPAe25emDT.OMMNfoiobtidopormeiodasubtraçãodasondasobtidas pelosestímulos/ga/(frequente)e/da/(raro).ForamanalisadasasmedidasdelatênciadoMMN eduasmedidasdeamplitude.

Resultados: FoipossívelverificarausênciadoMMNem16%noTPAe24%DEL.Naanálise com-parativa,osgruposTPAeDELapresentaram maioresvalores latênciasemenoresvaloresde amplitudeemrelac¸ãoaoDT.

Conclusão:Estes dadosdemonstramumaalteração nadiscriminaçãoautomática de compo-nentesacústicoscruciaisdossonsdefalaemcriançascomTPAeDEL,oquepoderiaindicar alteraçõesnosprocessosfisiológicosresponsáveispeladiscriminaçãoprecisadecontrastes acús-ticosemníveispré-atencionaisepré-conscientes,contribuindoparaumapercepçãodeficiente. ©2015AssociaçãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial.Publicado por ElsevierEditoraLtda.Todososdireitosreservados.

Introduction

Abnormalities in auditory temporal processing have been oneof themain theories usedtotrytoexplain the etiol-ogyoflanguagedevelopmentdisorders.Thistheorysuggests thatoneofthecausesforlanguagedevelopmentdisorders (amongthem,specificlanguageimpairment[SLI])isrelated tochangesintheabilitytoprocesssoundsandabnormalities inneuralcodingofauditoryinformation,1---3_contributing_to

changesintheperceptionoffundamental acousticcuesin speechsoundsignals.

Despite nearlya centuryofresearch,noconsensushas yetbeenreachedonthephysiologicalbasisofcausality con-cerningthislanguagedevelopmentdisorder,astheresults of studies have failed tofind evidence of changes in the auditoryprocessing ofchildren withSLI.4,5_Therefore, _the

etiological causes of languagedevelopment disordersstill remaincontroversial.

Althoughstudiesusingbehavioralmeasureshaveshown inconsistent results, electrophysiological evaluationsbeen proven to be ideal for investigating the neural bases of speechperception;theyduenotinterferewiththe subjec-tivebehavioralresponseandareindependentofitandthey areusefulinestablishinganatomicalandfunctional associ-ationsinthehumanauditorysystem.6

Mismatch negativity (MMN) is an electrophysiological measurethat reflects the brain’s capacitytodiscriminate sounds,regardlessoftheindividual’sattentionaland behav-ioralcapacity.InitiallydescribedbyNäätänenetal.7_(1978),

MMNisacorticalevokedpotentialthatisdetectablewhen a change occursin themiddle of asequence of repeated acousticstimuli.8,9

Characterizedbyanegativedeflectionthatoccursafter theP2response,MMNusuallyoccursbetween150and250ms

afterthestimuluspresentation,withlatencyandamplitude varying,dependingonthestimulus.10---12

Moststudiesusesimpleparadigms,inwhichfrequentand infrequentstimuli(e.g.,1000Hzand1100Hztones, respec-tively)arepresentedinanoddballparadigm,similartothat used for the P300, with the infrequent stimulus eliciting MMN.7,10,12,13

However,MMNcanalsobe elicitedbychanges in com-plexstimuli suchasspeechsounds.14---18 _The _speech_signal

consistsofharmonically richelementsthatchangerapidly withrespecttofrequency.Thiscomplex,spectrum-temporal structure requires neural integrityfor accurate coding of itssignal.19 _The _acoustic_properties _of _speech_sounds _are

encoded at all levels of the auditory system and these acousticparametersarerepresenteddifferently alongthe auditorypathway.Additionally,thereisevidencethatthey areprobablymodified at eachlevel of theauditorynerve pathway.20 _Thus,_simultaneous _and_coordinated _activation

of large and different populations of neurons is required forspeechprocessing andunderstanding, fromtheeighth cranialnervesignaltransductiontothecortex.19

Basedonpreviouslyestablishedassociations,thisstudy aimed to assess the discrimination of complex acoustic signals(speech)intheauditorysystemthroughMMNin indi-vidualswithspecificlanguageimpairment(SLI),compared tochildrenwithauditoryprocessingdisorder(APD)and typ-icaldevelopment(TD).

Methods

(3)

Sample

Atotalof75childrenwereassessed,agedbetween6and12 years,inateachingandresearchcenteratauniversityinSão Paulo,Brazil.Allindividualshadhearingthresholds within thenormalrange(≤15dBHL)fortheassessedfrequencies

(500---4000Hz);speechrecognitionscoreswere>88%;normal tympanometricmeasures were seen; andalso an absence of neurological, cognitive, and psychiatric disorders. The individualsweredividedintothreegroups:

a) TDgroup:25childrenwithtypicaldevelopment, accord-ingtoinformationobtainedthroughinterviewswiththe parents/guardiansandteachers,withabsenceofschool difficulties,speech,andlanguagedisorders.Inaddition, thesechildrenhadnormalperformanceattheauditory processingassessment.

b) APDgroup:25childrendiagnosedwithAPData labora-toryofaudiologicalinvestigationofauditoryprocessing located in the same place where the study was con-ducted.The APDdiagnosis was achievedusing criteria established by the American Speech-Language-Hearing Association (ASHA),i.e. performancebelownormal for theageinatleasttwotestsof theauditoryprocessing assessment test battery. The minimum test battery appliedinthisgroupandtheTDgroupconsistedof tem-poralprocessingtests(testoffrequencyand/orduration pattern)andmonotic(speechwithnoiseand/orpicture with noise), and dichotic listening (dichotic digit test and/orStaggeredSpondaicWords[SSW]).

c) SLIgroup:25childrendiagnosedwithSLIusingthe inter-nationalreferencecriteria,1 _namely:_persistent _speech

and/or language difficulty in the absence of hearing loss; changes in cognitive development;speech motor developmentimpairment; comprehensive developmen-taldisorders,syndromes,andsensorineuralchanges;and acquired neurological lesions.21,22 _These _children _were

diagnosed and underwentspeech therapy in a specific laboratoryinthesamelocationwheretheresearchwas conducted.

Proceduresanddataanalysis

Afterthechildrenwereselectedandsubmittedtohearing screening,childrenwereaskedtochooseamovie(cartoon) towatchduringtheevaluation,withapresentationintensity ofapproximately40dB(A).15,23_Some_studies_have_found_that

individualsaremorecollaborativewhentheyarewatching avideoduringtheevaluationsessions.24,25

Theevent-relatedauditoryevokedpotential(MMN)was used to investigate mechanisms that permeate auditory sensory discrimination. MMN was obtained by presenting acousticspeechstimuli---plosiveconsonants/da/and/ga/. Thespeechstimuliweresynthesized26_with₄₈_kHz,_of₁₆_bit,

andlengthof100ms.Thestimuliconsistedoffiveformants, differentiatedattheonsetfrequenciesinthetransitionfrom thesecondtothethirdformant(Fig.1).

Stimuliwerepresentedat75dBintensityNNAwith anal-ysistimeof500ms,sensitivityof100␮V,and1---30Hzfilter

(with off-line filterfrom 1 to15Hz). Approximately 1600 stimuliwereused,ofwhich1400(86%)werecommon(/ga/)

and 200(14%) rare (/da/), presented ineight setsof 200 stimuli(175frequentand25rare),withafour-second inter-valbetweenthesets.Thestimuliwererandomlypresented (oddballparadigm)totriggerMMN,atarateof1.5stimuli per second. The stimuli were presented in the right ear, throughinsertearphonesbecausethereisevidenceofaright earadvantagefortheprocessingofspeechsounds.24

Thetracingswereobtainedthroughan electroneuromyo-graph,modelNavigatorPro(BiologicSystemsCorporation; NatusMedicalInc---Mundelein,UnitedStates).

AstheMMN,bydefinition, iselicitedonlyby adeviant or rare stimulus, the trace was obtained as follows: by subtractingthemeanof thetracingscorrespondingtothe stimulus /da/ presented in oddball paradigm /da/ (rare) fromthemeanofthetracingsobtainedinresponsetothe stimulus/ga/(frequent).15 _The _MMN_was_identified_as_the

waveofnegativepolarityandwithapproximatelatencyof 150---250mspost-stimulus(Näätänenetal.12₎_and_was

cap-turedbytheelectrodes inpositionsFz,M2(rightmastoid) andwiththeFpzasthegroundwire.27

Amplitudemeasurementswereanalyzedandcalculated by placing one of the reference cursors on the negative polaritypoint (MMN)and theother cursor onthe positive point previous toMLM toestablish theon-MMN amplitude andposteriortoMMNtoidentifytheoff-MMNamplitude.

Statisticalanalysis

Accordingtopreviouslyspecifiedobjectives,thestatistical methodaimedtocomparethegroupsregardingthe discrim-inationofcomplexacousticsignals(speech)intheauditory system throughthe MMN electrophysiological assessment. For this purpose, descriptive analyses were performed of the values obtained in the variables resulting from MMN --- latency (described in milliseconds--- ms)and amplitude (describedinmicrovolts---␮V)---bybuildingtableswiththe

valuesobservedinthedescriptivestatistics:mean,standard deviation, minimum, median, and maximum. To compare the test means in the three groups, analysis of variance (ANOVA)wasapplied.Thesignificancelevelwassetat0.05 and significant items were identified withan asterisk (*). When necessary,Tukey’smultiple comparisonmethodwas usedforfurtheranalysis.

Tocomplementthedescriptiveanalysis,a95%confidence interval(95%CI)wasusedtoassessvarianceofthemean. Thesignificancelevelwassetat5%.

Results

AllindividualsintheTDgroupexhibitedanMMN,response whereas only 84% of individuals in the APD group (21/25 subjects)and76%oftheSLIgroup(19/25subjects)showed theresponse.Therefore,individualsthatdidnotrespondto MMNwereexcludedfromthesubsequentanalysis.

Fig.2showsthetracingsobtainedbyMMNinanindividual fromeachgroup(TD,APD,andSLI).

(4)

/ga/

F

requency (Hz)

F

requency (Hz)

Time (ms) Time (ms)

/da/

Fig.1 Schematictracingsof/da/(black)and/ga/(red)stimuli.Superimposedtracingsshowingthedifferentiationinformant onset.

Typical development APD APD

(5)

Table1 Descriptivestatisticsfor themismatchnegativity(MMN) responsevalues,consideringthemeasuresoflatencyand amplitudeforallthreegroups.

MMNlatency On-MMNamplitude Off-MMNamplitude

TD APD SLI TD APD SLI TD APD SLI

Mean 205.33 239.67 241.54 2.44 2.28 1.65 2.44 2.44 1.28

SD 39.44 57.60 43.41 2.15 1.23 1.11 1.79 1.62 0.69

Minimum 140.78 152.23 164.72 0.39 0.67 0.20 0.24 0.20 0.35

Median 198.03 257.37 237.59 2.15 1.97 1.43 1.97 1.91 1.16

Maximum 276.11 308.38 313.59 11.10 4.69 4.30 7.87 5.54 2.64

theAPDgrouphadlatencyvaluesforMMN>257.37ms,i.e. abovethevalueof250msproposedbyNäätänenetal.12

For the measurement of on-MMN amplitude, the TD groupshowedhigheramplitudevalues,whencomparedto theAPDand SLI groups. However,for theoff-MMN ampli-tude,valuesobservedintheTDandAPDgroupswerevery similar.

Fig.3showsthebargraphwithconfidenceinterval(95%) ofthemeansandlevelofsignificancewhencomparingthe meansofthethreegroupsforlatencyandamplitude mea-surements.

For the mean values of MMN latency, a statistically significant difference was observed between groups (F

[2.62]=4.88, p=0.01*). Using Tukey’s post hoc test, we verifiedthatthissignificancewasobservedinthe compar-isonsbetweenAPDandTD(p=0.03*)andSLIandTDgroups (p=0.02*).

Regardingtheamplitudemeasurement,althoughtheTD groupshowedhigheramplitudes forboth theon-MMNand off-MMN amplitudes, the error bar chart indicated a sta-tisticallysignificant differencewhencomparingthegroups onlyfor theoff-MMN amplitude(F [2.62]=3.45;p=0.03). TheTukey’sposthoctestverifiedthatthissignificanceonly occurred in the comparisons between TD and SLI groups (p=0.03*).

Discussion

Basedonourresults,MMNelicitedbysmallacoustic differ-encesinspeechsounds(/da/and/ga/)wasclearlypresent inallchildrenintheTDgroup.Thisisconsistentwith pre-viousstudiesthatshowarobustMMNinnormalsubjects.28

Inother words,childrenfromtheTDgrouparecapableof differentiatingthestimuli,inoddballparadigm,regardless ofattentionalactivities.

However,in the SLIand APDgroups, the MMNwasnot elicitedinallindividuals.Furthermore,higherlatency val-uesandloweramplitudeswereobservedintheAPDandSLI groups,comparedtotheTDgroup(Table1andFig.2).This maymeanthatboththeAPDandtheSLIgroupsshowedsome impedimentatneurallevelstoaccuratelydiscriminatethe contrastsfromthestimuli.

Therefore,thispotentialalsoindicatesthatphonological deficitscancoexistwithdifficultiesin processingacoustic differencesbetweenstimuli.

The reduction and absence of the MMN response that wasobserved only in the population withchanges in this

study could contribute to the impairment of perception and acoustic representation at pre-attentional and pre-consciouslevelsofthispopulation.

AccordingtoUweretal.,29_children_with_SLI_show_specific

deficitsinautomaticdiscriminationbetweenconsonant-and vowel syllablesthat differbetweenpointsof articulation. Davidsetal.30_added_that_children_with_SLI_have_difficulties

inprocessingnon-verbalstimuliandthatmaycoincidewith phonologicaldeficits.

These studies, together with other studies in children withlanguagedisorders,16,17,29,31---33 _have _found_a _decrease

inspectrumcontrastcoding,expressedastheMMNchange inthispopulation,corroboratingthefindingsofthepresent study.

Onthecontrary,somestudieshavenotfoundthesame MMNresultsfor childrenwithSLI.34,35 _These_studies_found

noabnormalresponses toMMN inchildren withSLI, com-paredtochildrenwithtypicaldevelopment,bothforspeech stimuliandfornon-verbalstimuli(tone burst).Inaddition totheseaforementionedauthors,RoggiaandColares36

stud-iedMMNwithnon-verbalstimuliinchildrenwithAPD.The authors also failed to find differences between the APD groupandnormalchildren.

Even though MMN is described in the literature as an importanttoolintheinvestigationofchangesintheauditory processing of acousticstimuli,few studies have usedthis potentialinchildrenwithAPD.Wefound nostudiesinthe literaturethatsimultaneouslyassessedtheperformanceof childrenwithAPDandSLIusingthispotential.Thisfactcan beexplainedbythedifficultiesinfindingsufficientnumbers ofchildren withisolatedAPD,notassociatedwithreading and languageproblems;there isalso somedebate onthe diagnosisofAPD.37

Accordingtoresultsobtainedinthisstudy,wefoundthat theAPDandSLIgroupsexhibitedhigherlatenciesandlower amplitudes anda higher percentage of absent MMN com-pared to the TD group, but the APD and SLI groups had similarperformancesregardingtheMMN,andtherewereno statisticallysignificantdifferencesbetweenthetwogroups. Some studies show that changes in the discrimination ofsmallacousticdifferencesarecommoncharacteristicsin individualsdiagnosedwithAPDandSLI.MMNamplitudehas beenassociatedwithauditoryperceptualmeasuresandthe absenceofMMNindicatesincapacitytoperceiveany differ-encebetween thesounds.38 _Other _important _aspects_that

caninfluenceMMNarethechangesinshort-termmemory,12

(6)

350

300

250

200

150

50

0 0

1 2 3 4

MMN (ms) on-MMN off-MMN

DT TPA DEL DT TPA DEL

0 1 2 3 4

DT TPA DEL

100

Fig.3 Comparisonbetweenthemeansofthethreegroupsfor latencyandmismatchnegativity(MMN)amplitude.TD,typical development;APD,auditoryprocessingdisorder;SLI,specificlanguageimpairment.

changesfoundinMMNinthisstudywereexpected,asthe above-mentioned factorsare oftenaltered, both for chil-drenwithAPDandforchildrenwithSLI.

Altered MMN responses have typically been attributed to changes in the auditory cortex. However, this cannot beaffirmed, considering the present results indicate that changesinMMNleadtobehavioraldeficitsobservedinthe APD and SLI groups, as there is evidence of interactions betweenphysicalcharacteristicsofthestimulusand cogni-tiveoperations.Moreover,itwasnotpossibletodetermine whetherthechangesfoundinMMN,bothinthegroupwith APDandinthegroupwithSLI,havethesameorigin.

Thereisevidencethatencodedstimulationchangesare represented differently in the brain. Krauset al.39 _found

more robust MMN in response to the /bad/---/wa/ stimuli (in whichthe differenceis the durationbetween the for-mants),whencomparedtothe/ga/---/da/stimuli(inwhich thedifferenceliesinthetransitionbetweenthefrequency ofthesecondtothethirdformant).Theauthorsdefendthe hypothesisthattheregionsthatcontributetotheformation ofMMNvaryaccordingtothedifferencebetweenthestimuli used.40

Thus, other studies using MMN with different stimuli shouldbeemployedinthestudyofchildrenwithAPDandSLI inordertoinvestigatepossiblesimilaritiesanddifferences betweenthesechanges,andtostudy thereasonwhyonly someofthechildrenwithalterationsinauditoryprocessing developlanguagedisorders.

Another hypothesis that cannot be ruled out is the possibility that children with APD and SLI have a matu-rational delay in the overall development of the central nervoussystem.Thishypothesisstatesthatthe electrophys-iological differences in auditory responses seen between childrenwithAPDandSLIandnormalchildrenwould indi-cate neurodevelopmentalimmaturity.41,42 _It _is_known _that

themyelinationprocesscontinuesthroughchildhood,43_and

that these changes in auditory processing would reflect cortical development maturational delay. In spite of the consistency,someauthorscriticizethishypothesisbasedon studiesofchangesinchildrenwithlanguageandlearning dis-ordersthatpersistevenafteradolescenceuntiladulthood.44

Therefore,morelongitudinalstudies,particularlyforspeech sounds,areneededtodeterminewhetherthishypothesisis plausible.

The MMN in the present study appeared to reflect theneural responseto changes in stimuli, that had been employed in other studies to investigate the auditory cortical activity associated with extraction of phonetic informationfromacousticstimuli,informationessentialfor word recognition. Thus, the MMN is an appropriate tool for the evaluation of speech perception that specifically requires the ability toencode dynamic changesin acous-ticsignals.Anotheradvantage isthattheMMNappears to precedelinguisticandcognitiveprocessingatthisprocessing level.40

Consideringthevarioushypotheses,itisdifficultto con-cludewhich factorsareresponsiblefor thechangesfound inMMNand,also,whetherthesefactorsaresimilarly mani-festedintheSLIandAPDgroups.However,thepresentstudy showedthat,usingtheevent-relatedMMNpotential,itwas possibletostudy auditoryprocessingfor discriminationof acousticeventsindependentofanybehavioralresponse,as somechildrenhave attentionalproblems,45 _or_problems_in

languageexpression and/or reception, that can influence performanceat behavioraltests,commonlyusedtoassess auditoryprocessing.

Conclusion

(7)

andauditoryprocessingdisorders.Moreover,thesefindings showedevidenceofchangesinpre-attentional discrimina-tionof acoustic contrasts, both in children with APDand SLI.Theseresults suggestthat thisalterationinthe auto-maticcorticalchangedetectionprocessissimilarbetween childrenwithAPDandSLI.

Funding

Thisstudy wasfundedbyFundac¸ão deAmparoàPesquisa doEstadode SãoPaulo --- FAPESP, Process number(2009/ 18417-0).

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

References

1.TallalP,PiercyM.Defectsofnon-verbalauditoryperceptionin childrenwithdevelopmentdysphasia.Nature.1973;241:468---9. 2.Rocha-MunizCN, Befi-LopesDM, SchochatE.Investigationof auditory processing disorder and language impairment using the speech-evoked auditory brainstem response. Hear Res. 2012;294:143---52.

3.BasuM,KrishnanA,Weber-FoxC.Brainstemcorrelatesof tem-poral auditory processing in children with specific language impairment.DevSci.2009;13:77---91.

4.BishopDV,CarlyonRP,DeeksJM,BishopSJ.Auditory tempo-ralprocessingimpairment:neithernecessarynorsufficientfor causinglanguageimpairmentinchildren.JSpeechLangHear Res.1999;42:1295---310.

5.Tomblin B, Abbas PJ, Records NL, Brenneman LM. Auditory evoked response to frequency-modulated tones in children withspecific languageimpairment. JSpeechLangHear Res. 1995;38:387---92.

6.Skoe E, Kraus N. Auditory brain stem response to complex sounds:atutorial.EarHear.2010;31:302---24.

7.Näätänen R, Gaillard A, Mäntysalo S. Early selective atten-tion effectonevoked potentialreinterpreted. ActaPsychol. 1978;42:313---29.

8.Pakarinen S, Teinonen T, Shestakova A, Kwon MS, Kujala T, Hämäläinen H, et al. Fast parametric evaluation of central speech-soundprocessingwithmismatchnegativity(MMN).Int JPsychophysiol.2013;87:103---10.

9.PictonTW,AlainC,OttenL,RitterW,AchimA.Mismatch neg-ativity: differentwater inthe sameriver. AudiolNeurootol. 2000;5:111---39.

10.SamsM,HämäläinenM,AntervoA,KaukorantaE,Reinikainen K, Hari R. Cerebral neuromagnetic responses evoked by short auditorystimuli.ElectroencephalogrClinNeurophysiol. 1985;61:254---66.

11.He C,HotsonL,TrainorLJ.Developmentofinfantmismatch responsestoauditorypatternchangesbetween2and4months old.EurJNeurosci.2009;29:861---7.

12.NäätänenR,PaavilainenP,RinneT,AlhoK.Themismatch neg-ativity(MMN)inbasicresearchofcentralauditoryprocessing: areview.ClinNeurophysiol.2007;118:2544---90.

13.JinY,DíazB,ColomerM,Sebastiàn-GallèsN.Oscillation encod-ingofindividualdifferencesinspeechperception.PLOSONE. 2014;9:e100901.

14.MolfeseDL,MolfeseVL.Corticalresponsesofpreterminfants tophoneticandnonphoneticspeechstimuli.DevNeuropsychol. 1980;16:574---81.

15.KrausN,McGeeT,CarrellT,SharmaA,NicolT.Speech-evoked corticalevokedpotentials.JAmAcadAudiol.1993;4:238---48. 16.KrausN,McGeeTJ,CarrellT,ZeckerSG,NicolTG,KochDB.

Auditoryneurophysiologicresponsesanddiscriminationdeficits inchildrenwithlearningproblems.Science.1996;273:971---3. 17.Datta H, Shafer VL, Morr ML, Kurtzberg D, Schwartz RG.

Electrophysiologicalindicesofdiscriminationoflong-duration, phonetically similar vowels in children with typical and atypical language development. J Speech Lang Hear Res. 2010;53:757---77.

18.Banai K, Nicol T, Zecker SG, Kraus N. Brainstem timing: implications for cortical processingand literacy. JNeurosci. 2005;25:9850---7.

19.NicolT,KrausN.Speech-soundencoding:physiological manifes-tationsandbehavioralramifications.SupplClinNeurophysiol. 2004;57:628---34.

20.WarrenR.Auditoryperception:anewanalysisandsynthesis. Cambridge,UK:CambridgeUniversityPress;1999.

21.Leonard LB. Children with specific language impairment. Cambridge,MA:MITPress;1998.

22.Befi-Lopes,Avaliac¸ãoDM.diagnósticoeaspectosterapêuticos nosdistúrbiosespecíficosdelinguagem.In:FerreiraLP, Befi-LopesDM,LimongiSCO,editors.Tratadodefonoaudiologia.São Paulo:Roca;2004.p.547---52.

23.Dhar S, Abel R, Hornickel J, Nicol T, Skoe E, Zhao W, etal.Exploringtherelationshipbetweenphysiological meas-uresof cochlear and brainstem function. ClinNeurophysiol. 2009;120:959---66.

24.HornickelJ, SkoeE, Nicol T, Zecker S,Kraus N. Subcortical differentiationofvoicedstopconsonants:relationshipsto read-ingandspeechinnoiseperception.ProcNatlAcadSciUSA. 2009;106:13022---7.

25.KrizmanJ,SkoeE,KrausN.Stimulusrateandsubcortical audi-toryprocessingofspeech.AudiolNeurotol.2010;15:332---42. 26.KlattDH.Softwareforacascade/parallelformantsynthesizer.

JAcoustSocAm.1980;67:971---95.

27.JarperHA.Theten-twentysystemoftheInternational Federa-tion.ElectroencephalogrClinNeurophysiol.1958;10:371---5. 28.Baldeweg T, Hirsch SR. Mismatch negativity indexes

illness-specificimpairmentsofcorticalplasticity inschizophrenia:a comparisonwithbipolardisorderandAlzheimer’sdisease.IntJ Psychophysiol.2014;26:77---84.

29.UwerR,AlbrechtR,vonSuchodoletzW.Automaticprocessing oftonesandspeechstimuliinchildrenwithspecificlanguage impairment.DevMedChildNeurol.2002;44:527---32.

30.DavidsN,SegersE,vandenBrinkD,MittererH,vanBalkomH, HagoortP,etal.Thenatureofauditorydiscriminationproblems inchildrenwithspecificlanguageimpairment:anMMNstudy. Neuropsychologia.2011;49:19---28.

31.Holopainen IE, Korpilahti P, Juottonen K, Lang H, Sillan-paaM.Attenuatedauditoryevent-relatedpotential(mismatch negativity)inchildrenwithdevelopmentaldysphasia. Neurope-diatrics.1997;28:253---6.

32.KorpilahtiP.Auditorydiscriminationandmemoryfunctionsin SLIchildren:acomprehensivestudywithneurophysiologicaland behavioralmethods.ScandJLogPhoniatr.1995;20:131---9. 33.CeponieneR,CummingsA,WulfeckB,BallantyneA,Townsend

J. Spectral vs. temporal auditoryprocessing in specific lan-guage impairment: a developmental ERP study. Brain Lang. 2009;110:107---20.

34.BishopDV.Usingmismatchnegativitytostudycentralauditory processing in developmental language and literacy impair-ments:wherearewe,andwhereshouldwebegoing?Psychol Bull.2007;133:651---72.

(8)

36.RoggiaSM,ColaresNT.Omismatchnegativityempacientescom distúrbiosdoprocessamentoauditivo(central).BrazJ Otorhi-nolaryngol.2008;74:705---11.

37.FergusonMA,HallRL,RileyA,MooreDR.Communication, lis-tening,cognitiveandspeechperceptionskillsinchildrenwith auditoryprocessingdisorder(APD)orspecificlanguage impair-ment(SLI).JSpeechLangHearRes.2011;54:211---27.

38.GarridoMI,KilnerJM,StephanKE,FristonKJ.Themismatch negativity: a review of underlying mechanisms. Clin Neuro-physiol.2009;120:453---63.

39.KrausN, McGeeT.Mismatch negativity intheassessment of central auditoryfunction. Short course. Am J Audiol. 1994: 39---51.

40.KrausN,McGeeT,CarrellTD,SharmaA.Neurophysiologicbases ofspeechdiscrimination.EarHear.1995;16:19---37.

41.Wright BA, Zecker SG. Learning problems, delayed develop-ment,andpuberty.ProcNatlAcadSciUSA.2004;101:9942---6. 42.HautusMJ,SetchellGJ,WaldieKE,KirkIJ.Age-related improve-ments in auditory temporal resolution in reading-impaired children.Dyslexia.2003;9:37---45.

43.GieddJN,SnellJW,LangeN,RajapakseJC,CaseyBJ,Kozuch PL,etal.Quantitativemagneticresonanceimagingofhuman braindevelopment:ages4---18.CerebCortex.1996;6:551---60. 44.McArthurGM,BishopDV.Auditoryperceptualprocessingin

peo-plewithreadingandorallanguageimpairments:currentissues andrecommendations.Dyslexia.2001;7:150---70.