Publication: Gap prepulse inhibition and auditory brainstem-evoked potentials as objective measures for tinnitus in guinea pigs
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Abstract
Tinnitusorringingoftheearsisasubjectivephantomsensationnecessitatingbehavioralmodelsthatobjectivelydemonstratetheexistenceandqulityofthetinnitussensation.Thegapdetectiontestusestheacousticstartleresponseelicitedbyloudnoisepulsesanditsgatingorsuppressionbyprecedingsub-startlingprepulses.Gapsinnoisebandsserveasprepulses,assumingthatongoingtinnitusmasksthegapandresultsinimpairedgapdetection.Thistesthasshownitsreliabilityinrats,mice,andgerbils.Nodataexistsfortheguineapigsofar,althoughgapdetectionissimilaracrossmammalsandtheacousticstartleresponseisawell-establishedtoolinguineapigstudiesofpsychiatricdisordersandinpharmacologicalstudies.Hereweinvestigatedthestartlebehaviorandprepulseinhibition(PPI)oftheguineapigandshowedthatguineapigshaveareliablestartleresponsethatcanbesuppressedby15msgapsembeddedinnarrownoisebandsprecedigthestartlenoisepulse.Afterrecoveryofauditorybrainstemresponse(ABR)thresholdsfromaunilateralnoiseover-exposurecenteredat7kHz,guineapigsshoweddiminishedgap-inducedreductionofthestartleresponseinfrequencybandsbetween8and18kHz.Thissuggeststhedevelopmentoftinnitusinfrequencyregionsthatshowedatemporarythresholdshift(TTS)afternoiseover-exposure.Changesindischargerateandsynchrony,twoneuronalcorrelatesoftinnitus,shouldbereflectedinalteredABRwaveforms,whichwouldbeusefultoobjectivelydetecttinnitusanditslocalizationtoauditorybrainstemstructures.Therefore,weanalyzedlatenciesandamplitudesofthefirstfiveABRwavesatsuprathresholdsoundintensitiesandcorrelatedABRabnormalitieswiththeresulsofthebehavioraltinnitustesting.EarlyABRwaveamplitudesuptoN3wereincreasedforanimalswithtinnituspossiblystemmingfromhyperactivityandhypersynchronyunderlyingthetnnituspercept.Animalsthatdidnotdeveloptinnitusafternoiseexposureshowedtheoppositeeffect,adecreaseinwaveamplitudesforthelaterwavesP4–P5.Changesinlatencieswereonlyobservedintinnitusanimals,whichshowedincreasedlatencies.Thus,tinnitus-inducedchangesinthedischargeactivityoftheauditorynerveandcentralauditorynucleiarerepresentedintheABR.