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Program and Abstract Book: Sixth International Conference on Tinnitus Tinnitus: The Art and Science of Innovation

Program and Abstracts
Sixth International Conference on Tinnitus
Tinnitus: The Art and Science of Innovation
Organized by the
Tinnitus Research Initiative Foundation
&
The TRI Tinnitus Unit Antwerp, Belgium,
part of Brain Research center Antwerp for Innovative and Interdisciplinary
Neuromodulation (BRAI2N), Antwerp University Hospital & Antwerp University
Organizing Office
Marina Pieters
TRI/BRAI2N
UZA, Wilrijkstraat 10
2650 Edegem, Belgium
Phone + 32 3 821 45
Fax +32 3 821 44 25
E-Mail Marina.Pieters@uza.be
www.brai2n.org
Scientific Office
Tinnitus Research Initiative
University of Regensburg
Bezirksklinikum
Universitaetsstrasse 84
93053 Regensburg, Germany
Phone +49 941 941 2096
Fax +49 941 2025
E-Mail info@tinnitusresearch.org
www.tinnitusresearch.org
The organizers want to thank the people who have helped organizing this
Conference, especially Marina Pieters in Bruges and Susanne Staudinger and
Sylvia Dorner-Mitschke in Regensburg.
Artwork cover Jan Fabre ©2012
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Welcome to TRI2012
As the host of the sixth international TRI Tinnitus Conference we welcome
you to Brugge.
If we want to find a cure for tinnitus within a short timeframe, classical
science alone will not suffice. We need to involve people who think innovatively, and
not only creative scientists from other research domains, but also natural innovators
such as artists and philosophers. Even though they are not directly involved in
tinnitus research, these innovators can help us by Socrates discussions to generate
novel conceptual ideas of what phantom perceptions are, and how they arise. The
integration of science and innovative exploration goes back to the very foundational
spirit of the TRI when it was conceived by Matteo de Nora. Inviting creative
scientists from other fields has also been a tenet in these meetings, and TRI Brugge
2012 definitely has this aspiration. The aim of the TRI2012 meeting is to explore the
notion that art, philosophy and science are different sides of the same coin and use
different but complementary approaches to seeing and solving a problem. Thus, by
joining forces make a quantum leap in our journey towards a cure for tinnitus.
It is a great pleasure to introduce you to Brugge. The city of Bruges is a
World Heritage Site of UNESCO, and since the Middle Ages considered the ‘Venice
of the North’. Upon visiting Bruges, you will immediately notice that this city has
always carefully cherished its architectural and artistic treasures from the past. The
current city boundaries still coincide exactly with those of the medieval city center,
and the spaces and structures that were so typical of Bruges in the past have been
preserved. Take your time to walk through busy squares, refreshing parks, and
quiet, intimate cobbled streets, and do not forget to visit the modest almshouses as
well as the imposing patrician’s homes.
We hope you will enjoy your visit to Brugge and that the Conference will
provide you with novel ideas on tinnitus, perhaps leading to innovative studies on
the pathophysiology and treatments for the benefit of patients with this enigmatic
disease.
Dirk De Ridder, Ana Belen Elgoyhen, Berthold Langguth,
Paul Van de Heyning & Sven Vanneste
Brugge, June 2012
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TABLE OF CONTENTS
Overview Scientific Program ...................................................................................................................................................... 6
Detailed Scientific Program ........................................................................................................................................................ 7
Wednesday June 13, 2012 ........................................................................................................................................................ 17
08:00 - 09:00 p.m. OPENINGS SPEAKER ............................................................................................................................ 17
Thursday June 14, 2012 ............................................................................................................................................................ 17
9:00 - 10:15 a.m. PLENARY TALKS ...................................................................................................................................... 17
10:45 a.m. - 12:45 p.m. SESSION 1: Treatment Chair: Claudia Coelho Room: Morus ........................................................ 18
10:45 a.m. - 12:45 p.m. SESSION 2: Auditory & Cognitive Changes Chair: Sylvie Herbert Room: Erasmus ...................... 20
1:45 - 3:00 p.m. PLENARY TALKS ........................................................................................................................................ 22
04:00 - 05:30 p.m. SESSION 3: Pathophysiology Chair: Susan Shore Room: Morus .......................................................... 23
04:00 - 05:30 p.m. SESSION 4: Functional Imaging Chair: Winfried Schlee Room: Erasmus .............................................. 25
05:30 - 07:30 p.m. POSTER SESSION ................................................................................................................................. 27
Pathophysiology ..................................................................................................................................................................... 27
Auditory and Cognitive Sciences ........................................................................................................................................... 30
Treatment ............................................................................................................................................................................... 34
Functional Imaging ................................................................................................................................................................. 42
Friday June 15, 2012 ................................................................................................................................................................. 46
9:00 - 10:30 a.m. PLENARY TALKS ...................................................................................................................................... 46
10:45 a.m. - 12:45 p.m. SESSION 5: Treatment Chair: Michael Kilgard Room: Morus ........................................................ 47
10:45 a.m. - 12:45 p.m. SESSION 6: Auditory & Cognitive Changes Chair: Larry Roberts Room: Erasmus ....................... 49
1:45 - 4:15 p.m. PLENARY TALKS ........................................................................................................................................ 51
4:15 p.m.- 5:30 p.m. SESSION 7: Treatment Chair: Richard Tyler Room: Morus ................................................................. 52
4:15 p.m. - 5:30 p.m. SESSION 8: Pathophysiology Chair: Grant Searchfield Room: Erasmus ........................................... 53
Saturday June 16, 2012 ............................................................................................................................................................. 55
9:00 - 10:15 a.m. PLENARY TALKS ...................................................................................................................................... 55
10:45 a.m. - 12:45 p.m. SESSION 9: Functional Imaging Chair: Tony Cacace Room: Morus .............................................. 55
10:45 a.m. - 12:45 p.m. SESSION 10: Auditory & Cognitive changes Chair: Deborah Hall Room: Erasmus ....................... 58
1:45 - 3:00 p.m. PLENARY TALKS ........................................................................................................................................ 61
Index of Authors ........................................................................................................................................................................ 63
Program Sixth International Conference on Tinnitus
6
OVERVIEW SCIENTIFIC PROGRAM
June13thJune14thJune15th June16th
09:00am
KeynoteSpeaker:
Tinnitus:fromCochleatoCortex
PaulVandeHeyning
KeynoteSpeaker:
Neuralandmusicsyntax
GyorgyBuzsáki
KeynoteSpeaker:
Computationalmodelsoftinnitus
RolandSchaette
09:45am
InvitedSpeaker:
Vertigoasavestibularphantom
percept
FlorisWuyts
InvitedSpeaker:
Hyperacusis,misophoniaand
phonophobia
AageMøller
InvitedSpeaker:
Thefutureofmedicine‐A
marketingperspective
JensGutsche
10:1511:45amCoffeeBreak
10:45am
Session1:
Treatment
Chair:C.Coelho
Session2:
Auditory&
Cognitive
Changes
Chair:S.Hébert
Session5:
Treatment
Chair:M.Kilgard
Session6:
Auditory&
Cognitive
Changes
Chair:L.Roberts
Session9:
Functional
Imaging
Chair:T.Cacace
Session10:
Auditory&
Cognitive
changes
Chair:D.Hall
12:4501:45pm Lunch
01:45pm
KeynoteSpeaker:
Tinnitus:brainactivityand
connectivity
NathanWeisz
KeynoteSpeaker:
Theneuralcorrelatesof
consciouspercepts
StevenLaureys
KeynoteSpeaker:
Nihilnovesubsole:fillinginthe
boxesoftheneurophysiological
tinnitusmodel
PawelJ.Jastreboff
02:30pm
InvitedSpeaker:
ATechnologyPushforElectrical
Neuromodulation
WouterSerdijn
KeynoteDiscussion:
Artvs.Science
JanFabre‐GyorgyBuzsáki
Closingsession:
BertholdLangguth
03:00pm
CoffeeBreak
03:15pm
CoffeeBreak
03:30pm
InvitedSpeaker:
Subjectivetinnitus,illusions,
arts,andvirtualworlds
AlainLondero
03:45pm
InvitedSpeaker:
IstheUniversitytherightplace
forinnovation?Ahistorical
approach
HildeSymoens
04:00pm
Session3:
Pathophysiology
Chair:S.Shore
Session4:
Functional
Imaging
Chair:W.Schlee
04:15pmSession7:
Treatment
Chair:R.Tyler
Session8:
Pathophysiology
Chair:
G.Searchfield
05:30pm
Opening
registration
desk
PosterSession
&
Apéro
06:30pm
Picasso Exhibition
07:30pm
08:00pmOpenings
Speaker:
Academic
Freedom
RikTorfs
Banquet
09:00pmMusical
intermezzo
Arias
ValeriePeeters
09:10pmWelcome
Cocktail
Sixth International Conference on Tinnitus Program
7
DETAILED SCIENTIFIC PROGRAM
Wednesday, June 13
05:30
08:00p.m.
Opening registration desk
08:00‐
09:00p.m.
Openings Speaker
Academicfreedom:separationfromreligionANDstate?
RikTorfs
09:00
09:10p.m.
Musical intermezzo
Arias
ValeriePeeters
09:10p.m.
‐
Welcome Cocktail
Thursday, June 14
09:00‐
09:45a.m.
KeynoteSpeaker
Tinnitus:fromCochleatoCortex
PaulVandeHeyning
09:45‐
10:15a.m.
InvitedSpeaker
Vertigoasavestibularphantompercept
FlorisWuyts
‐‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐‐
10:45am‐
12:45p.m.
Session1:Treatment
Chair:ClaudiaCoelho
(Room:Morus)
1 NamE.C.,HanS.S.,WonJ.Y.,LeeK.U.,ChunW.,
ChoiH.K.,LevineR.A.:ClonazepamQuietsTinnitus:
aRandomizedCrossoverStudywithGinkgoBiloba
2 SmithP.F.,Vagal,S.,McNamaraE.,DarlingtonC.L.,
ZhengY.:EffectsofLBACLOFENonChronicTinnitus
inducedByAcousticTraumaInRats
3 CoelhoC.,WittS.,JiH.,MarlanHansenM.,Gantz
B.J.,TylerR.:ZinctoTreatTinnitusintheElderly:a
randomizedplacebocontrolledcrossovertrial
4 AzevedoA.,VannesteS.,DeRidderD.:Theeffectof
naltrexoneontheperceptionanddistressintinnitus:
Anopenlabelpilotstudy
5 DepireuxD.:Preventingtheemergenceoftinnitus
posttraumawithdrugloadednanoparticles
6 VandeHeyningP.,CoxT.,MaierH.,MuehlmeierG.,
MorawskiK.,LisowskaG.,MeyerT.:Efficacyand
safetyofAM101inthetreatmentofacuteinnerear
tinnitusADoubleBlind,Randomised,Placebo
ControlledPhaseIIStudy
Session2:Auditory&CognitiveChanges
Chair:SylvieHébert
(Room:Erasmus)
1 ShiNaePark,SeongCheonBae,KyoungHoPark,Sang
WonYeo:ClinicalCharacteristicsandTherapeutic
ResponseofObjectiveTinnitusduetoMiddleEar
Myoclonus:ALargeCaseSeries
2 HallD.A.,WallenhorstC.,MartinezC.:Theincidenceof
disablingtinnitus:ApopulationlevelUkcohortStudy
3 WallenhorstC.,MartinezC.,HallD.A.:Riskfactorsfor
developingadisablingtinnitus:ApopulaitonlevelUK
cohortstudy
4 KamA.C.S.,SungJ.K.K.,LeeT.,WongT.K.C.,vanHasseltC.A.:
Clinicalevaluationofacomputerizedselfadministered
tinnitusmeasurementsystem
5 FournierP.,BasileCE.,HutchinsS.&HébertS.:
Improvingtinnituspitchmatching:implicationsfor
neurophysiologicalmodelsandclinicalpractice
6 vanGendtM.J.,BoyenK.,deKleineE.,vanderLaan
B.F.A.M.,LangersD.R.M.,vanDijkP.:Psychoacoustics
andneuralcorrelatesofgazeevokedtinnitus
12:45‐01:45p.m.‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐LUNCH‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐LUNCH‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐LUNCH‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
01:45‐
02:30p.m.
KeynoteSpeaker
Auditoryalpha:fromclinicaltocognitiveneuroscienceandback
NathanWeisz
02:30‐
03:00p.m.
InvitedSpeaker
ATechnologyPushforElectricalNeuromodulation
WouterSerdijn
‐‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐‐
03:30‐
04:00p.m.
InvitedSpeaker
VirtualReality(VR)insubjectivetinnitusmanagement
AlainLondero
04:00‐ Session3:PathophysiologySession4:FunctionalImaging
Program Sixth International Conference on Tinnitus
8
05:30p.m.Chair:SusanShore
(Room:Morus)
1 CacaceA.T.,HuJ.,RomeroS.,SalamyJ.,XuanY.:
Noiseinducedtinnitus:Selectedneurobiochemiocal,
anatomical,andpsychometricchangesfollowingrTMS
includingothermetabolicrelatedeffects
2 KiddA.R.,TurnerJ.G.,CasparyD.M.,BaoJ.:GABA
signalingcomponentsintheMGBandhippocampusof
ratswithchronictinnitus
3 CederrothC.R.,HudspethA.J.:Geneticevidenceforthe
contributionofglutamateinototoxicmediatedhearing
lossandtinnitus
4 DehmelS.,ParikhM.,BledsoeS.C.,ShoreS.E.:
ChangesinSomatosensoryAuditoryIntegrationin
InferiorColliculusAccompanyNoiseInducedTinnitus
5 GraftonG.,AhmedS.R.,BrouardJ.,LobarinasE.,
SalviR.,BarnesN.M.:Roleofthe5HTsystemin
tinnitus:asystematicstudyusingananimalmodel
fromNeurodynamicalMultiscaleModeling
6 HeeringaA.N.,SegenhoutJ.M.,VanDijkP.:Theacute
andchroniceffectofnoisetraumaonneuronalactivity
intheinferiorcolliculusoftheguineapig.
Chair:WinfriedSchlee
(Room:Erasmus)
1 SchleeW.,VannesteS.,DeRidderD.,LangguthB.,
KolassaIT.:Doagingprocessesaffecttinnitus
perceptionanddistress?
2 DelbW.:AreTinnitusRelatedDistressandTinnitus
LoudnessDistinctTinnitusFeaturesorJustTwosidesof
theSameMedal?ResultsfromEpidemiological,EEG‐
andfMRI‐Studies
3 SongJ.J.,VannesteS.,VandeHeyningP.,DeRidder
D.:“Distressedaging”:Thedifferencesinbrainactivity
betweenearly‐andlateonsettinnitus
4 GevenL.I.,DeKleineE.,PaansA.M.J.,Willemsen
A.T.M.,VanDijkP.:Asymmetryinprimaryauditory
cortexactivityintinnituspatientsandcontrols
5 MaudouxA.,VannesteS.,DeRidderD.,VanheckeW.,
VandeHeyningP.,CabayJ.E.,DemertziA.,Laureys
S.,SodduA.,LefebvrePh.,GomezF.:Investigatingthe
TinnitusBrainUsingRestingstatefMRI
6 HusainF.:TheEffectofTinnitusonRestingState
FunctionalConnectivity
05:30
07:30p.m.
PosterSession
&
Apéro
Sixth International Conference on Tinnitus Program
9
Friday, June 15
09:00‐
09:45a.m.
KeynoteSpeaker
Neuralsyntax:whatdoesmusicoffertoneuroscience(andviceversa)
GyorgyBuzsáki
09:45‐
10:15a.m.
InvitedSpeaker
NeurophysiologicalaspectsonMisophonia,Phonophobia,HyperacusisandExplodingHeadSyndrome
AageMøller
‐‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐‐
10:45a.m.‐
12:45p.m.
Session5:Treatment
Chair:MichaelKilgard
(Room:Morus)
1 YlikoskiJ.,LehtimäkiJ.,MalkavaaraK.,YlikoskiM.,
YrttiahoS.,MäkeläJ.:Soundtherapyplus
TranscutaneousVagusNerveStimulationinthe
treatmentofpatientswithtinnitus.
2 KilgardM.P.,VranaW.A.,BorlandM.S.,Vanneste
S.,DeRidderD.,SloanA.M.,RennakerR.L.:
OptimizingVNSDirectedNeuralPlasticityforthe
TreatmentofChronicTinnitus
3 VannesteS.,KilgardM.,EngineerN.,TarverB.,De
RidderD.:Pairedvagusnervestimulationfor
tinnitus‐Pilotstudyresults
4 ViaudDelmonI.,LonderoA.,BonfilsP.,WarusfelO.:
Virtualrealityexposuretherapyforunilateral
tinnitus
5 ShlamkovitchN.:TheeffectofHyperbaricOxygen
Treatment(HBOT)onposttraumaticcentraltype
chronicdisablingtinnitus
6 PerrotX.,SimonE.,RocheL.,FornoniL.,RichardS.,
DubreuilC.,TruyE.,NorenaA.,BoisselJ.P.,RoyP.,
ColletL.,andonbehalfoftheMagTINstudygroup:
Safetyandefficacyassessmentofconventionallow‐
andhighfrequencyrepetitivetranscranialmagnetic
stimulationforthetreatmentofchronictinnitus:
Dosimetricapproach
Session6:Auditory&CognitiveChanges
Chair:LarryRoberts
(Room:Erasmus)
1 RabauS.,GillesA.,KleinePunteA.,WaelkensB.,
WoutersK.,CoxT.,JanssensdeVarebekeS.,Vande
HeyningP.:Correlationbetweenthepsychoacoustic
measurement,questionnairesandpatientglobal
impressionofchangeinpatientswithacutetinnitus
2 RobertsL.E.,ThompsonD.C.,andBosnyakD.J.:Neural
plasticityincentralauditorystructuresisexpressed
differentlyintinnitus
3 MeltserI.,EkB.,HébertS.,&CanlonB.:Centralgain:
Behaviouralandbiologicalresponsesintwostrainsof
mice
4 SalviR.,ChenG.D.,ManoharS.:SalicylateInduces
HyperactivityandTonotopicShiftinAmygdalaand
AuditoryCortex
5 RüttigerL.,SingerW.,ZuccottiA.,PanfordWalshR.,
MatsumotoM.,ZimmermannU.,JaumannM.,FranzC.,
GeislerH.S.,KöpschallI.,RohbockK.,XiongH.,Varakina
K.,LeeS.C.,VerpoortenS.,SchimmangT.,KnipperM.:
Molecularbasisoftinnitus
6 WallhäusserFrankeE.,DelbW.:TinnitusandInsomnia:
Ishyperarousalthecommondenominator?
12:45‐01:45p.m.‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐LUNCH‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐LUNCH‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐LUNCH‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
01:45‐
02:30p.m.
KeynoteSpeaker
Theneuralcorrelatesofconsciouspercept
StevenLaureys
02:30‐
03:15p.m.
KeynoteDiscussion
Artvs.Science
JanFabre‐GyorgyBuzsáki
‐‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐‐
03:45‐
04:15p.m.
InvitedSpeaker
IstheUniversitytherightplaceforinnovation?Ahistoricalapproach
HildeDeRidderSymoens
04:15‐
05:30p.m.
Session7:Treatment
Chair:RichardTyler
(Room:Morus)
1 BaumannU.,HelbigS.,StöverT.:Mechanically
InducedTinnitusObservedinCochlearImplantUsers
withResidualHearing
2 ViirreE.:Neuroethicalissuesintinnitusresearchand
care
3 ArnoldR.,RoggeroneM.A.C.,BoumaJ.,VanDijkP.:
Multidisciplinaryassessmentandtreatmentoftinnitus:
AFollowupstudy
4 TylerR.,WalkerK.,WittS.,KillianM.,DillierN.,van
DijkP.,LaiW.K.:Tinnitussuppressionwithmixed
backgroundstimuliinawearablecochlearimplant
5 KleinePunteA.,HofkensA.,MertensG.,DeBodtM.,
VandeHeyningP.:Sustainedsuppressionofsevere
tinnituswithMEDELcochlearimplantsinsinglesided
deafness:8yearsexperience
Session8:Pathophysiology
Chair:GrantSearchfield
(Room:Erasmus)
1 EstolaM.:Kinesiatapingtotreattinnitus
2 SearchfieldG.D.,WiseK.,KobayashiK.:Gametraining
oftinnitus
3 WienerV.,HaenecourL.:Whenandwhyusing
vertebralmaneuversasatinnitustreatment.
4 DesmetJ.,DeBodtM.andVandeHeyningP.:Tinnitus
inpatientswithsinglesideddeafnesspriortoandafter
aboneconductiondevicetrial
5 TassP.A.,AdamchicI.,HauptmannC.:Counteracting
tinnitussymptomsandrelatedcerebralsynchonyby
acousticCRneuromodulation
Program Sixth International Conference on Tinnitus
10
05:30
06:30p.m.
06:30
08:00p.m.Picasso Exhibition
08:00p.m.‐
B A N Q UE T
Saturday, June 16
09:00‐
09:45a.m.
KeynoteSpeaker
Mechanismsoftinnitusdevelopment:Computationalmodels,experimentaltests,andimplicationsfortreatment
RolandSchaette
09:45‐
10:15a.m.
InvitedSpeaker
Thefutureofmedicine‐Amarketingperspective
JensGutsche
‐‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐‐CoffeeBreak(30min)‐‐‐‐‐‐‐‐‐‐
10:45a.m.‐
12:45p.m.
Session9FunctionalImaging
Chair:TonyCacace
(Room:Morus)
1 DietzenT.,BalkenholT.,DelbW.: Neurofeedback
TreatmentinTinnitusPatients:AComparativeStudy
ofdifferentTreatmentStrategies
2 HartmannT.,LorenzI.,MüllerN.,LangguthB.and
WeiszN.:Fireandforget:comparisonoftheeffects
ofneuromodulaitonbylowfrequencyrTMSand
neurofeedbackonoscilatoryprocessesrelatedto
tinnitus
3 GolmD.,SchmidtSamoaC.,DechentP.,Kröner
HerwigB.:NeuralCorrelatesofTinnitusAnnoyance:
ResultsfromanEmotionalStroopTask
4 BensonR.R.,GattuR.,CacaceA.T.:Increased
Fractionalanisotropy(FA)isasymmetricand
localizedprimarilytowhitemattertracksintheleft
hemisphere:Adiffusiontensorimagingstudyof
noiseinducedtinnitus
5 HusainF.:Changesassociatedwithtinnitusand
hearinglossinfunctionalbrainnetworksinvolvedin
shorttermmemoryandattention
6 SchecklmannM.,TupakS.,ZellerJ.,HarnischW.,
GianiA.,FallgatterA.J.,LangguthB.:Functional
nearinfraredspectroscopyasnewandinnovative
neuroimagingtoolintinnitus?
7 LangersD.R.M.,DeKleineE.,VanDijkP.:Lackof
tonotopiccorticalreorganizationintinnitus
8 WinelandA.M.,BurtonH.,PiccirilloJ.F.:Functional
connectivitynetworksintinnitus:Theimportanceof
bother
Session10:Auditory&Cognitivechanges
Chair:DeborahHall
(Room:Erasmus)
1 HooverS.:GuidetoDiagnosisoftheThreeTypesof
ChronicTinnitus
2 EsteveFraysseM.J.,OhresserM,HolerHoudouxC.H.,
BranchereauB.,LocheV.,PannetierB.,AttardA.,
GeoffrayB.,VertallierM.,PantinA.S.,LinaGranadeG.,
LevratF.,NouriN.: Correlationanalysisbetweenvisual
analogicscaleintenisty(VASI)andannoyance(VASA)and
3QuestionnairesSTSS(1),TRQ(2)andTHI(3)intinnitus
patients:Neuralplasticityincentralauditorystructuresis
expresseddifferentlyintinnitus
3 HallD.A.,WanMohammedN.,StockdaleD.(onbehalf
oftheTinnitusPrioritySettingPartnership):Patientand
clinicalperspectivesonunansweredquestionsabout
tinnitustreatment:TheJamesLindAllianceexperience.
4 PackerM.D.:EstablishingaHearingHealthImprovement
Network:TheU.S.DepartmentofDefenseHearingCenter
ofExcellence
5 GillesA.,VanHalG.,DeRidderD.,VandeHeyningP.:
Epidemiologyofnoiseinducedtinnitusinadolescents
6 AdvaniJ.,YágüezHervasL.,McKennaL.:Theeffectsof
tinnitusonworkingmemory
7 MargaretM.Jastreboff,PawelJ.Jastreboff:Decreased
soundtolerance(hyperacusisandmisophonia):clinical
implications
8 MertensG.,KleinePunteA.,DeBodtM.,VandeHeyningP.:
Doestinnitusaffectspeechperceptioninthecontralateral
earinpatientssufferingfromsinglesideddeafness
treatedbycochlearimplantation?
12:45‐01:45p.m.‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐LUNCH‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐LUNCH‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐LUNCH‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
01:45‐
02:30p.m.
KeynoteSpeaker
Nihilnovesubsole:fillingintheboxesoftheneurophysiologicaltinnitusmodel
PawelJ.Jastreboff
02:30‐
03:00p.m.
ClosingSession
BertholdLangguth
Sixth International Conference on Tinnitus Program
11
Thursday, June 14, 5:30 – 7:30 p.m
Posters
Pathophysiology
P1. Methodological optimization of tinnitus assessment using prepulse inhibition of the acoustic starle reflex
Longenecker R.J., Galazyuk A.V.
P2. The biomarker of tinnitus
Goto F., Saruta J., Kanzaki S., To M., Tsutsumi T., Tsukinoki K., Ogawa K.
P3. Tinnitus triggered by use of oral ciprofloxacin: case report
Davila D.V., Saba C.M.
P4. Behavioral effects of two tinnitus inducers (noise exposure and salicylate) in guinea pigs
Berger J.I., Coomber B., Shackleton T.M., Wallace M.N. & Palmer A.R.
P5. Neural and histological correlates of tinnitus in guinea pigs
Coomber B., Berger J., Leggett R.C., Shackleton T.M., Palmer A.R. & Wallace M.N
P6. BDNF and GDNF genes exert sexually dimorphic effects on tinnitus symptomatology
Sand P., Langguth B., Vielsmeier V., Landgrebe M., Kleinjung T.
P7. Analysis of the association between tinnitus and arterial hypertension: preliminary data
Figueiredo R. R., Azevedo A.A., Penido N.O.
P8. Spontaneous firing rates in auditory cortex in response following long-term exposure to non-traumatic
auditory stimuli: a potential tinnitus correlate?
Munguia R., Pienkowski M., Eggermont JJ.
P9. Hints for motor cortex excitability as biomarker for neuroplasticity in tinnitus
Schecklmann M., Lehner A., Kreuzer P.M., Poeppl T.B., Landgrebe M., Langguth B.
P10. Management of the fluctuating tinnitus.
Soraya Hoover
Auditory and Cognitive Sciences
P11. Temporomandibular joint disorder, headache, and neck pain: hints for putative tinnitus subtypes
Schecklmann M.,Lehner A.,Kreuzer P.M.,Poeppl T.B., Vielsmeier V., Landgrebe M., Langguth B.
P12. Prevalence and characteristics of tinnitus after noise exposure during recreational activities
Degeest S., Corthals P., Vinck B., Keppler H.
P14. Efficacy of Ear Plug have to evaluate with Real Ear Plugged Response
Nakagawa.M.
P15. An evaluation of the content and quality of tinnitus information on websites preferred by general
practitioners
Fackrell K., Hoare D.J., Smith S., McCormack A., Hall D.A.
P16. Posttraumatic Tinnitus: a TRI Database Evaluation
Kreuzer, P.
P17. Cognitive speed as an objective measure of tinnitus
Das S.K., Wineland A.M., Kallogjeri D., Piccirillo J.F.
P18. Validation of the chinese mini tinnitus questionnaire
Kam A.C.S., Tong M.C.F., van Hasselt C.A.
P19. A study of prognotic factors for tinnitus retraining therapy by using a multivariate analysis
Sakashita T., Kato S., and Yamane H.
P20. Tinnitus: Distinguishing Between Subjectively Perceived Loudness and Tinnitus-Related Distress
Wallhäusser-Franke E., Balkenhol T., Delb W.
P21. Genetics of family members with Tinnitus
Cacace A.T., Knipper M., Bolz H.
P22. The prevalence of tinnitus in children in Poland
Raj-Koziak D., Skarżyński H., Kochanek K., Bartnik G., Fabijańska A.
P23. Tinnitus in school age
Guimarães T.G., Leite-Barros P.A.M., Mota L.A.A., Pimentel G.A.
P24. Residual Hearing Area Quantification (RHAQ) in Cochlear Implant users suffering from Partial Deafness
Program Sixth International Conference on Tinnitus
12
Mertens G., Anderson I., Kleine Punte A., De Bodt M. and Van de Heyning P.
Treatment
P25. Neuroscience and psychoanalysis on tinnitus research
Vergara R.
P26. Reduction of Tinnitus Severity by the Centrally Acting Muscle Relaxant Cyclobenzaprine: An Open-Label
Pilot Study
Coelho C.
P27. Internet-based sound therapy (IBST) for tinnitus
Bergholm M., Lehtimäki J., Sariola J., Ylikoski M., Pirvola U., Ylikoski J.
P28. Effect of Different Sounds on the Treatment Outcome of Tinnitus Retraining Therapy
Suh Myung-Whan
P29. Transcranial direct current stimulation (tDCS) intensity and duration effects on Tinnitus suppression
Shekhawat G.S, Searchfield G.D.
P30. Multisite rTMS for the treatment of chronic tinnitus: stimulation of the cortical tinnitus network – a pilot
study
Lehner A., Schecklmann M., Poeppl T. B., Kreuzer P. M., Vielsmeier V., Landgrebe M., Langguth B.
P31. Comparison of the Therapeutic Efficacy of One-on-One vs. Small-Group Counseling based on Modified
Tinnitus Retraining Therapy
Shi-Nae Park, Seong-Cheon Bae, Dong-Kee Kim, Kyoung-Ho Park, Sang-Won Yeo.
P32. Multicentric study in slight hipoacusias, disabling Tinnitus and integral therapy of tinnitus
Moreno Vidal C., Hernando Leal M.V., Fernández Chávez M.A., Ibeas Franco L., Antón Canales A., Jimeno Brabo
C., Serna Peinado P., Lopez Marquez M.M., Gonzalez Garcia D., Toledano Quintana A., Olivares Checa M.,
Martinez Mintegui D., Starczewska Navarro P., Pérez Duarte U., García Cabrera V.
P33. Effectiveness of bilateral repetitive trancranial magnetic stimulation in patients with chronic tinnitus
Hoekstra C.E.L., Versnel H., Neggers S.F.W., Niesten M.E.F., Van Zanten G.A.
P34. Prognostic models for changes in tinnitus handicap after cochlear implantation
Kloostra F.J.J., Arnold R., Van Dijk P.
P35. Acoustic CR neuromodulation counteracts imbalance of causal interactions of brain areas in patients with
subjective chronic tonal tinniuts
Silchenko A. N., Adamchic I., Hauptmann C., Tass P.A.
P36. Suppression of tinnitus in a patient with unilateral sudden hearing loss: case-report
Fioretti A., Peri G., Eibenstein A.
P37. Computational analysis of long-lasitng desynchonization by electrical and sensory coordinated reset
neuromodulation
Popovych O.V. and Tass P.A.
P38. Transcranial direct current stimulation (tDCS) induces short- and long-lasting of improvement of tinnitus
intensity and discomfort: evidences from additional recruitment
Garin P., Gilain C., Van Damme J-P., de Fays K., Jamart J., Ossemann M., Laloux P., Vandermeeren Y.
P39. Palatal muscle resection for intractable palatal myoclonus causing tinnitus
Heo K.W., Jung H., Kim J.R.
P40. Autologous cartilage injection for the patulous Eustachian tube
Kong S.K., Lee I.W., Goh E.K., Lee H.J.
P41. Effects of Memantine on Chronic Tinnitus induced By Acoustic Trauma In Rats
Zheng Y., McNamara E., Stiles L., Darlington C.L., Smith P.F
P42. Antioxidant treatment in noise-induced tinnitus: A literature review and study preparation
Gilles A., Peeters J., Ihtijarevic B., Rabau S., Kleine Punte A., De Ridder D., Van de Heyning P.
P43. Tinnitus affects what and where processing
Park C., Searchfield G.D.
P44. Correlation type of masker noise of the minimum masking level and Tinnitus Questionnaire in chronic
tinnitus patients
Rabau S., Waelkens B., Wouters K., Cox T., Janssens de Varebeke S., Van de Heyning P.
P45. Effects of frequency discrimination training on tinnitus: results from a series of randomized trials
Hoare D.J., Kowalkowski V.L., Hall D.A.
P46. No effect of tinnitus intensity and distress on speech in noise results in single-sided dea patients
Desmet J., Kleine Punte A., de Bodt M. and Van de Heyning P.
Sixth International Conference on Tinnitus Program
13
P47. Results of otoacoustic emissions and efferent suppression in subjects with chronic tinnitus after noise
exposure during recreational activities
Keppler H., Corthals P., Vinck B., Degeest S.
P48. Combining “TAILOR-MADE NOTCHED MUSIC TRAINING (TMNMT)” with left auditory cortex tDCS: an
explorative study
Teismann H., Wollbrink A., Okamoto H., Pantev C.
P49. Tinnitus and normal hearing - a study of 175 cases.
Fabijańska A., Smurzyński J., Kochanek K., Raj-Koziak D., Bartnik G., Skarżyński H.
P50. Spatial & temporal perception
An Y.H., Oh S.H., Choi B.H., Koo J.W., Song J.J., Shim H.J.
P52. Nanotheranostics: application to Tinnitus research
Cacace A.T., Holt A.G., Castracane J., Bergkvist M.
Functional Imaging
P53. Lessons from two-ALE meta-analyses of PET studies on tinnitus and cochlear implant
Song J.J., Vanneste S., Van de Heyning P., Jeong Hun Jang, De Ridder D.
P54. Changes of oscillatory activity in the tinnitus network and related tinnitus relief induced by CR
neuromodulation
Adamchic I., Hauptmann C., Toth T., Tass P.A.
P55. Deceased evoked brain activity in left auditory cortex of tinnitus subjects durin attentional task
performance
Amaral A.I.A., Langers D.R.M.
P56. Inverse correlation of tinnitus loudness and hearing impairment with gamma-band power
Balkenhol T., Wallhäusser-Franke E., Delb W.
P57. An fMRI study of emotional processing in tinnitus using affective sounds
Husain F.T.
P58. Central activity in a young tinnitus population: A qEEG analysis
Gilles A., Vanneste S., De Ridder D., Van de Heyning P.
P59. Factors affecting electrophysiological correlates of tinnitus
Bosnyak D.J., Bruce I.C., and Roberts, L.E.
14
15
Abstracts
Abstracts of oral presentations Sixth International Conference on Tinnitus
16
Sixth International Conference on Tinnitus Abstracts of oral presentations
17
WEDNESDAY
JUNE 13, 2012
08:00 - 09:00 p.m.
OPENINGS SPEAKER
ACADEMIC FREEDOM: SEPARATION FROM RELIGION AND STATE?
Rik Torfs
Rik Torfs is professor of Canon Law at the Catholic University of Louvain, Belgium, journalist, media figure and senator. As an
academic and politician he is ideally placed to give the opening lecture on science, risks and society. His opening lecture will
bring us back to one of the driving questions of the TRI ? Should society, TRI and other players involved in scientific research
combine explorative and solidifying approaches, or should society limit risky scientific research?
Academic freedom is a highly discussed issue in our days. It is always in danger. Yet the enemies differ. Who are they?
Churches, large companies, bureaucrats, politicians, emancipation movements all qualify. Let us look for deeper causes and
lasting solutions.
THURSDAY
JUNE 14, 2012
9:00 - 10:15 a.m.
PLENARY TALKS
9:00 - 9:45 a.m. – Keynote Speaker
TINNITUS: FROM COCHLEA TO CORTEX
Paul Van de Heyning
Paul Van de Heyning is an ENT Professor at the University
Hospital Antwerp, Belgium and Dean of the faculty of
Medicine at the Antwerp University. He published more than
300 articles mainly on tinnitus and hearing and is an
international expert on Cochlear implants and its influence
on phantom sounds in tinnitus patients. Paul Van de
Heyninig is co-director of the Brain Research center
Antwerp for Innovative and Interdisciplinary
Neuromodulation (BRAI2N) and TRI tinnitus clinic Antwerp.
Tinnitus is the auditory perception of the sound or sounds
that do not correspond with sounds in the surrounding of
the patient. It consists of two processes. The first is the
bottom-up process in the auditory system in which the
cochlea is the main input. A second process is a top-down
process which is neurocognitive in nature and controls the
awareness of the sound percept. Both processes do not
only involve the auditory system responsible for tinnitus
loudness but also the extra auditory central nervous
system, generally involved in tinnitus distress. The complex
nature of these interactions has become clear by the
evidence that auditory and non-auditory processes are
network activities between different parts of the brain.
Investigations have to disentangle the different components
of these networks and their interplay. Future therapies have
to target the individually main driving physiopathological
processes, which often will have actions aswell on the
bottom-up as on top-down processes. Whereas at the
beginning purely audiological an auditory treatments often
failed and neither mere neurophysiological approaches
could cure the tinnitus percept, current and future
translational auditory neurocognitive approaches open the
way to a better understanding of tinnitus and its auditory
percept, and so the development of cures. However as
were we stand today, we cannot emphasize enough the
importance of using noise protective measures by
youngsters and older people during loud music events or
noisy activities.
___________________
9:45 - 10:15 a.m. – Invited Speaker
VERTIGO AS A VESTIBULAR PHANTOM PERCEPT
Floris Wuyts
Floris Wuyts is professor of biomedical physics, and Head
of AUREA (Antwerp University Research centre for
Equilibrium and Aerospace), and visiting professor at the
University of Ghent, Belgium, and University College, UK.
He has lectured widely (among those also for the NATO)
and collaborates with both NASA and ESA. As an expert on
vertigo, he will extend the well-known analogy between
phantom pain and phantom sound to vertigo as a phantom
equilibrium perception.
Vertigo is per definition the sensation of self-motion when
no self-motion is occurring or the sensation of distorted self-
motion during an otherwise normal head movement. With
other words: “vertigo is the illusion of movement”. The
vestibular system uses a multitude of information, coming
from vision, proprioception, the vestibular organs, auditive
cues etc, to build an internal model of ‘how we are oriented
in space”. Any persistent conflict between this internal
model and afferent signals from one of these sensors leads
to motion sickness, with symptoms of vertigo, nausea, and
eventually vomiting. Patients with a lesion in their inner ear
caused by e.g. Meniere’s disease, labyrinthitis or Benign
Paroxysmal Positional Vertigo suffer also from vertigo, but
recently, “vestibular migraine” has been recognized as a
very common cause of vertigo. Thus, vertigo can arise also
purely at the level of the brain. Recent studies using PET,
fMRI and methods such as Diffusion Tensor Imaging have
revealed new insights in how vestibular information is being
processed at cortical levels. During this talk, the author will
present the latest insights in how misinterpreted motion can
lead to vertigo.
Abstracts of oral presentations Sixth International Conference on Tinnitus
18
10:45 a.m. - 12:45 p.m.
SESSION 1: Treatment
Chair: Claudia Coelho
Room: Morus
CLONAZEPAM QUIETS TINNITUS: A RANDOMIZED
CROSSOVER STUDY WITH GINKGO BILOBA
Nam E.C., Han S.S., Won J.Y., Lee K.U., Chun W., Choi
H.K., Levine R.A.
1 Kangwon National University, School of Medicine,
Department of Otolaryngology, Institute of Medical Science,
Chuncheon, Republic of Korea; 2 Kangwon National
University, School of Medicine, Department of Internal
Medicine, Institute of Medical Science, Chuncheon,
Republic of Korea; 3 Kangwon National University, School
of Medicine, Department of Psychiatry, Chuncheon,
Republic of Korea; 4 Kangwon National University, School
of Medicine, Department of Pharmacology, Institute of
Medical Science, Chuncheon, Republic of Korea; 5 Harvard
Medical School, Departments of Otolaryngology and
Neurology, Boston, USA
Background: A recent review stated that no drugs provide
replicable long-term reduction of tinnitus impact. However,
two well-designed studies using the short-acting
benzodiazepine, alprazolam, found a significant quieting of
tinnitus using a visual analog scale (VAS). No well-designed
studies have assessed the impact upon tinnitus of long-
acting benzodiazepines.
Materials and Methods: Open-label, randomized,
crossover study of 38 adults (27 M, 11 F) with tinnitus for
more than 2 months randomized to either clonazepam or
ginkgo for the first 3 weeks. For the next 2 weeks no
medication was taken. For the final 3 weeks, subjects
received the other drug. The initial dose was one tablet
daily (clonazepam 0.5 mg; ginkgo 40 mg). Subjects
increased the dose by one tablet every 3 days to a
maximum of 4 tablets hs until a satisfactory decrease in
tinnitus loudness or intolerable side effects occurred.
Tinnitus was assessed with pitch- and loudness-matching,
tinnitus handicap inventory (THI), and VAS of loudness,
duration, and annoyance.
Results: Comparing before and after, clonazepam
significantly improved tinnitus loudness (74% of subjects),
duration (63%), annoyance (79%), and THI score (61%),
whereas ginkgo showed no significant differences for any of
these measures. Three subjects heard no tinnitus with
clonazepam, zero with ginkgo.
Conclusion: This third well-designed study establishes
benzodiazepines as a drug class that can significantly quiet
tinnitus. As a long-acting medication, clonazepam is
preferable to alprazolam, because long half-life medications
have less withdrawal issues and better compliance due to
once a day dosing.
___________________
EFFECTS OF L-BACLOFEN ON CHRONIC TINNITUS
INDUCED BY ACOUSTIC TRAUMA IN RATS
Smith P.F., Vagal S., McNamara E., Darlington C.L.,
Zheng Y.
Department of Pharmacology and Toxicology, School of
Medical Sciences, University of Otago Medical School, and
the Brain Health Research Centre, University of Otago,
Dunedin, New Zealand.
Background: Neurophysiological studies suggest that
tinnitus is associated with neuronal hyperactivity in auditory
brain regions. Consequently, one avenue for drug therapy
has been the use of anti-epileptic and anti-spasticity drugs.
One such drug is the anti-spasticity agent, baclofen,
although the clinical evidence supporting its efficacy has
been unconvincing to date. The aim of this study was to
investigate the effects of L-baclofen in an animal model of
noise-induced tinnitus.
Materials and Methods: Sixteen male Wistar rats were
divided into acoustic trauma (n = 8) and sham control (n =
8) groups. The acoustic trauma consisted of a 16 kHz, 110
dB pure tone delivered unilaterally for 1 h under
anaesthesia. Auditory function was assessed using auditory
brainstem-evoked response (ABR) thresholds. The
behavioural signs of tinnitus were measured by a
conditioned lick suppression paradigm at 2 weeks after
acoustic trauma and during the drug treatment period. L-
baclofen, the more active isomer of baclofen, at 1, 3 or 5
mg/kg s.c doses, or its vehicle, was administered 1 h before
testing.
Results: Acoustic trauma resulted in a significant increase
in ABR thresholds at 8, 16 and 20 kHz (P < 0.008). It also
resulted in a significant decrease in the suppression ratio
(SR) compared to sham controls in response to 20 kHz
tones, but not broadband noise or 10 kHz tones, in pre-drug
and vehicle control testing (P < 0.002). For the 3 and 5
mg/kg doses, L-baclofen significantly reversed the
frequency-specific decrease in the SR in the acoustic
trauma group.
Conclusion: The more active isomer of baclofen, L-
baclofen, may reduce tinnitus caused by acoustic trauma.
___________________
ZINC TO TREAT TINNITUS IN THE ELDERLY: A
RANDOMIZED PLACEBO CONTROLLED CROSSOVER
TRIAL
Coelho C., Witt S., Ji H., Marlan Hansen, M., Gantz B. J.,
Tyler R.
Several reports suggest that zinc, which is involved in
several neural transmissions systems throughout the
auditory pathway, might help some tinnitus patients.
However, prior studies used inadequate experimental
designs. Therefore, we tested the effectiveness of zinc to
reduce tinnitus in a randomized placebo controlled design.
We focused on subjects over 60 years of age, who are
more likely to have a zinc deficiency. In phase 1, 58
subjects were randomized to receive 50mg of zinc/ day for
4 months and 58 subjects received a placebo. After a 1
month washout period, the two groups were crossed over to
receive the alternative regime. Pre and post measures were
made of the Tinnitus Handicap Questionnaire and tinnitus
loudness and annoyance (0-100% scales). 5 of 93 (5.4%)
subjects showed a significance decrease in the tinnitus
Handicap Questionnaire during zinc treatment compared to
2 of 94 (2.1%) during placebo treatment. 5 of 93 (5.4%)
subjects showed a significance decrease in the tinnitus
Handicap Questionnaire during zinc treatment compared to
2 of 94 (2.1%) during placebo treatment. 6 of 93 (5.1%)
subjects showed a significance decrease in loudness during
zinc treatment compared to 3 of 93 (3.2%) during placebo
treatment. 4 of 93 (4.3%) subjects showed a significance
decrease in annoyance during zinc treatment compared to
4 of 93 (4.3% during placebo treatment). The group
analysis showed increment following zinc treatment of 22.0
to 23.7 points on the questionnaire, of 67.8 to 68.1 on
loudness rating and of 59.7 to 61 on annoyance rating,
none of which were statistically significant.
___________________
Sixth International Conference on Tinnitus Abstracts of oral presentations
19
THE EFFECT OF NALTREXONE ON THE PERCEPTION
AND DISTRESS IN TINNITUS: AN OPEN LABEL PILOT
STUDY
Andréia Azevedo1, Sven Vanneste2,3, & Dirk De Ridder2
1 OTOSUL, Clinical and Research Tinnitus Center, Volta
Redonda, Brazil
2 Brai²n, Tinnitus Research Initiative Clinic Antwerp &
Department of Neurosurgery, University Hospital
Antwerp, Belgium
3 Department of Translational Neuroscience, Faculty of
Medicine, University of Antwerp, Belgium
Tinnitus is a perceived sensation of sound without actual
acoustic stimulation. Currently there are no standardized
drug therapies for the treatment of tinnitus patients. A
potential novel treatment for chronic tinnitus is naltrexone.
Tinnitus can be considered an auditory phantom
phenomenon similar to phantom pain. Excitatory opioid
responses are selectively blocked by low doses of
naltrexone while inhibitory responses are not as such
having an analgesic effect. However, tinnitus can also be
induced by apoptosis of neuronal tissue within the auditory
pathway. Recent studies showed that high doses of
naltrexone have a neuroprotective effect via modulation of
mitochondrial apoptotic pathways. This implicates a
protective role for the opioid antagonist against injurious
stimuli activating the death receptor-linked apoptotic
pathway. The aim of the present study is to investigate
three doses of naltrexone, namely 5, 12.5 and 50 mg and
determine their influence on tinnitus complaints. We
conducted a four weeks single-center, single-arm, open-
label treatment study. Eighty-six patients received the drug
treatment, while 30 patients received no treatment. Overall
tinnitus distress was significantly reduced for the drug
treatment group, while for the waiting control group this was
not the case. No significant effect could be obtained for
tinnitus intensity. A closer look at the data indicates that this
effect is mainly generated due to a significant difference in
the 50 mg drug treatment group for tinnitus distress.
___________________
PREVENTING THE EMERGENCE OF TINNITUS POST-
TRAUMA WITH DRUG-LOADED NANOPARTICLES
Didier Depireux
University of Maryland College Park, Institute for Systems
Research
Following noise trauma, treatment of injury and
inflammation of the cochlea is essentially dependent on the
ability to deliver drugs to the inner ear structures. To this
end, nanoparticles are a natural candidate because of their
biocompatibility, the ability to load them with a variety of
drugs, and the promise they can deliver their payloads
without causing additional injury or trauma to the inner ear.
We have used superparamagnetic nanoparticles with a
maghemite core, coated with a chitosan and loaded with
fluorescent proteins for visualization. We measured the
penetration of the cochlear space by these particles as a
function of the particles’ diameter, external field strength
and duration of exposure to the external magnetic field
while the particles are being actively steered by a
configuration of magnets, both pulling from the contralateral
side of the skull and pushing from the ipsilateral side. We
also demonstrated their elimination through the lymphatic
system, starting within days of administration. We are
testing the effectiveness of magnetically pushed
nanoparticles functionalized with prednisolone on
preventing the emergence of tinnitus in a rat model of
noise-trauma induced tinnitus, and we will report on this
new method of drug delivery, how much reduction of
tinnitus we obtain, and possible future developments.
Efficacy and safety of AM-101 in the treatment of acute
inner ear tinnitus – A Double Blind, Randomised, Placebo
Controlled Phase II Study
EFFICACY AND SAFETY OF AM-101 IN THE
TREATMENT OF ACUTE INNER EAR TINNITUS –
A DOUBLE BLIND, RANDOMISED, PLACEBO
CONTROLLED PHASE II STUDY
Van de Heyning P.1, Cox T.2, Maier H.3, Muehlmeier G.3,
Morawski K.4, Lisowska G.5, Meyer T.6
1 Dept. of ENT, Head and Neck Surgery, Antwerp
University Hospital, Antwerp, Belgium;
2 Dept. of ENT, Head and Neck Surgery, Virga Jesse
Hospital, Hasselt, Belgium;
3 Dept. of ENT, Head and Neck Surgery, German Armed
Forces Hospital Ulm, Ulm, Germany;
4 Dept. of Otolaryngology, Medical University of Warsaw,
Warsaw, Poland; 5Private ENT practice, Tarnowskie
Góry, Poland;
6 Auris Medical AG, Basel, Switzerland
Glutamate excitotoxicity following cochlear insult may
trigger aberrant excitation of the auditory nerve, which is
perceived as tinnitus. AM-101, a small molecule NMDA
receptor antagonist, is currently being developed for the
intratympanic treatment of acute inner ear tinnitus.
Following positive outcomes from a previous study, a phase
II trial aimed to evaluate AM-101’s efficacy and safety in a
larger number of patients. In a double blind, randomised,
placebo controlled study a total of 248 subjects with
persistent tinnitus no older than three months from acute
noise trauma, otitis media or sudden deafness were
enrolled. They received three i.t. injections of AM-101 270
µg/mL, AM-101 810 µg/mL or placebo over three
consecutive days. Study subjects returned for follow-up on
Days 7, 30 and 90. The primary efficacy endpoint was the
change in MML to Day 90; changes in tinnitus loudness and
annoyance were co-primary efficacy endpoints. Secondary
efficacy outcome variables included: sleep impact scores,
TBF-12 questionnaire, loudness match and patient global
impression of change. Safety was evaluated by the
frequency of clinically relevant changes in hearing and of
adverse events. The study overall failed to meet its primary
efficacy endpoint as no significant differences in the change
of MML were observed between treatment groups.
However, AM-101 810 µg/mL showed substantial and
statistically significantly better reductions in tinnitus
loudness, sleep impact and tinnitus impairment in patients
suffering from acute tinnitus with established cochlear origin
than placebo. In contrast, the subgroup of sudden deafness
related tinnitus did not show conclusive results. The study
drug as well as i.t. injections were well tolerated. The study
established proof of concept in man for AM-101 in the
treatment of tinnitus arising from cochlear glutamate
excitotoxicity. It confirmed the importance of careful
definition and selection of target treatment groups and the
choice of appropriate outcome variables. Psychoacoustic
measures, despite their appeal as “semi-objective”
measure, do not seem to be sufficiently reliable for efficacy
assessments.
Abstracts of oral presentations Sixth International Conference on Tinnitus
20
10:45 a.m. - 12:45 p.m.
SESSION 2:
Auditory & Cognitive Changes
Chair: Sylvie Herbert
Room: Erasmus
CLINICAL CHARACTERISTICS AND THERAPEUTIC
RESPONSE OF OBJECTIVE TINNITUS DUE TO
MIDDLE EAR MYOCLONUS: A LARGE CASE SERIES
Shi-Nae Park, Seong-Cheon Bae, Kyoung-Ho Park,
Sang-Won Yeo.
Department of Otolaryngology-HNS, Seoul St. Mary’s
Hospital, The Catholic University of Korea, College of
Medicine, Seoul, Korea
Objectives: To evaluate the clinical characteristics and
therapeutic response of tinnitus due to middle ear
myoclonus (MEM) and to suggest appropriate diagnostic
methods.
Method: This study included 58 patients with tinnitus
diagnosed with MEM, who were seen from January 2004 to
July 2011. Clinical and audiological characteristics were
investigated. The therapeutic responses to counseling,
medical therapy, and surgical therapy were evaluated.
Results: Patients had a mean age of 29.8 (range 6–70)
years: 20.7% (n=12) were <10 years, 39.7% (n=23) were
<20 years, 74.1% (n=43) were <40 years, and 5.2% (n=3)
were 60 years. Remembered stressful events and noise
exposure were associated with the onset of MEM in 51.8%
(n=30) and 27.6% (n=16) of patients, respectively. The
most frequent nature of the tinnitus was a crackling sound.
MEM associated with forceful eyelid closure was observed
in 15% of patients. Impedance audiogram and
otoendoscopic examinations of the tympanic membrane
were helpful tools for diagnosing MEM. With medical
therapy, more than 75% of patients exhibited complete or
partial remission of their tinnitus. Patients with intractable
MEM who underwent sectioning of the middle ear tendons
had very good outcomes.
Conclusion: Tinnitus due to middle ear myoclonus seems
to occur in young patients and to be related to stress or
noise. Information about the clinical characteristics and
therapeutic response of this less-common type of tinnitus
will be helpful for its early and appropriate diagnosis and
treatment.
___________________
THE INCIDENCE OF DISABLING TINNITUS: A
POPULATION-LEVEL UK COHORT STUDY
Hall D.A.1, Wallenhorst C.2, Martinez C.3
1 NIHR National Biomedical Research Unit in Hearing
(NBRUH), University of Nottingham, UK
2 Mathematician, Frankfurt, Germany
3 Consultant epidemiologist, Frankfurt, Germany
Introduction: Long-term incidence studies are particularly
valuable for identifying factors associated with tinnitus
development. Nevertheless, prospective incidence studies
are costly to run and only two major studies have so far
been reported (Beaver Dam, Wisconsin, US and Blue
Mountains Hearing Study, Sydney, Australia).
Aim: To estimate the incidence rate of ‘disabling tinnitus‘
(DT) that burdens the UK National Health Service.
Patients and Methods: The source population was the
subset of general practices in the UK contributing primary
care data to the General Practice Research Database
(GPRD). We identified all patients with DT (01 January
2001 to 31 December 2011). DT was defined as the first
recording (index day) of tinnitus symptoms by the general
practitioner which led to follow-up examinations or specific
treatment (at both primary and secondary care levels) within
28 days. Among 44.6 million person-years of observation in
the 11-year period, we identified 23,672 incident cases of
DT. Overall incidence rate of DT was 5.3 per 10,000
person-years, increasing from 3.9 (2001) to 6.6 (2011). It
increased with age and was highest in the 60-69 age group
(12.5 in men and 10.8 in women, per 10,000 person-years).
Of the total, 7.2% had a previous diagnosis of Ménière's
disease or vestibular disorder, 17.2% of hearing loss,
25.3% of ‘non-disabling’ tinnitus (i.e. not meeting the DT
criteria) and 0.1% of acoustic neuroma. Our population-
level findings for DT confirm and extend previous research
conducted in regional cohort groups.
___________________
RISK FACTORS FOR DEVELOPING A DISABLING
TINNITUS: A POPULAITON-LEVEL UK COHORT
STUDY
Wallenhorst C.1, Martinez C.2, Hall D.A.3
1 Mathematician, Frankfurt, Germany
2 Consultant epidemiologist, Frankfurt, Germany
3 NIHR National Biomedical Research Unit in Hearing
(NBRUH), University of Nottingham, UK
Introduction: Baseline factors associated with the risk of
tinnitus can inform the more efficient allocation of public
health resources or target prevention campaigns.
Aim: Identify risk factors for developing a ‘disabling tinnitus’
(DT).
Patients and methods: The source population was the
General Practice Research Database (GPRD), a primary
care database in the UK. From January 2001 to December
2011, all patients with first-time DT with no prior recording
of hearing loss or ‘non-disabling tinnitus’ and a control
cohort free of hearing loss and tinnitus (disabling or non-
disabling) were identified. The control cohort was matched
on each DT case’s year of birth, gender, date of first DT
diagnosis (index day) and general practice. In a case-
control analysis, adjusted odds ratios (ORs) were estimated
using conditional logistic regression for potential risk factors
discussed in the literature. We also included the factors
smoking, drinking, BMI and socioeconomic status. ORs with
95% confidence intervals (CI) were provided for risk factors
present in the 90 days, 182 days or recorded any time
before the index day.
Results: We found 14,648 cases of DT and 53,958
matched controls. Adjusted ORs were increased for ear
infections within 90 days (OR: 10.08; CI: 8.18-12.43),
Ménière's disease/vestibular disorders within 182 days
(9.32; 7.32-11.87), otosclerosis (3.84; 1.87-7.92), acoustic
neuroma (3.78; 1.59-8.97), head injury within 90 days (3.73;
1.75-7.96), obsessive compulsive disorders (1.65; 1.19-
2.28) and rheumatological conditions (1.44; 1.37-1.50).
Conclusion: This study confirms established risk factors
(head injury), and other factors previously discussed (ear
infections, vestibular disorders and rheumatological
conditions).
___________________
Sixth International Conference on Tinnitus Abstracts of oral presentations
21
CLINICAL EVALUATION OF A COMPUTERIZED SELF-
ADMINISTERED TINNITUS MEASUREMENT SYSTEM
Kam A.C.S.1,2, Sung J.K.K.1,2, Lee T.3, Wong T.K.C.1,2,
van Hasselt C.A.1,2
1 Department of Otorhinolaryngology, Head & Neck
Surgery, Chinese University of Hong Kong, Hong Kong;
2 Institute of Human Communicative Research, Chinese
University of Hong Kong, Hong Kong;
3 Department of Electronic Engineering, Chinese University
of Hong Kong, Hong Kong
Introduction: The basic step in most tinnitus management
programs is to quantify the characteristics, including pitch
and loudness, of the perceived tinnitus. The success of
some contemporary tinnitus management approaches, such
as tinnitus notched therapy, relies on the accuracy of the
tinnitus pitch matched. Our research team developed a self-
administered tinnitus measurement system which is
capable to measure tinnitus frequency in one hertz
resolution via a smartphone.
Aim: To investigate the feasibility and accuracy of the self-
administered tinnitus measurement system.
Materials and Methods: Twenty patients with subjective
tinnitus were recruited in the Audiology clinic in a hospital
setting. The subjects completed the conventional
procedures or the automated tinnitus measurement in a
randomized order. Subjects were asked to rate on a 100-
point visual analog scale on the similarity of the measured
tinnitus tone and loudness and the one perceived. Tinnitus
pitch and loudness obtained with both methods were
compared. Test-retest reliability of both methods was
investigated.
Results: There was no significant difference in the
thresholds of unmasked air-conduction hearing obtained
with the computerized self-administered hearing test via a
smartphone and those obtained with standard pure-tone
audiometry. Comparable variability was observed for within-
session repeated tinnitus pitch and loudness measured via
both conventional and the automated method. There was
no significant difference in VAS rating on similarity between
the measured and perceived tinnitus pitch and loudness for
repeated measures in the same session.
Conclusion: It is feasible to perform tinnitus pitch and
loudness measurement with the self-administered system
via a smartphone.
___________________
IMPROVING TINNITUS PITCH MATCHING:
IMPLICATIONS FOR NEUROPHYSIOLOGICAL
MODELS AND CLINICAL PRACTICE
Fournier P.1,2,3, Basile C-E. 1,2,3 Hutchins S.2 & Hébert S. 1,2,3
1 École d’Orthophonie et d’Audiologie, Université de
Montréal;
2 CRBLM, Center of Research on Brain, Music and
Language,
3 CRIUGM, Centre de recherche Institut Universitaire de
Gériatrie de Montréal
Background: Psychoacoustical measurements of tinnitus
have led to important neuroscientific models. However,
conflicting data coexist, some supporting the notion that
tinnitus consists of a single pitch whereas others support
that tinnitus spectrum mirrors hearing loss. We tested the
hypotheses that i) tinnitus may be characterized by either
the prominent pitch within the hearing loss region (using a
discrete frequency mode of presentation) or by a single
pitch (using continuous pitch presentation) and ii) that
musical experience improves tinnitus pitch-matching
abilities.
Material and Methods: Musicians and non-musicians with
high-frequency tinnitus participated in two tinnitus-matching
tasks and were retested several weeks later. The
Touchscreen task consisted in a wide range of discrete
frequencies that participants had to rate for their likeness to
their tinnitus pitch and loudness. The Slider task consisted
of a continuous frequency presentation (in 1Hz steps) that
participants had to match to their tinnitus by moving a slider.
Results: The two methods yielded highly concordant
results. Mean likeness ratings for tinnitus followed a similar
trend as for hearing loss, i.e., higher likeness ratings were
ascribed to the frequency regions most affected by hearing
loss in both groups. No significant differences in the
predominant pitch were identified between the two
methods. Moreover, musical experience did not improve
tinnitus pitch matching.
Conclusions: Both participant-oriented methods replicated
previous findings that the predominant tinnitus frequency
usually lies within the hearing loss region, in accordance
with the neural synchrony theory (versus tonotopic
expansion).
___________________
PSYCHOACOUSTICS AND NEURAL CORRELATES OF
GAZE-EVOKED TINNITUS
van Gendt M.J.1, Boyen K.1,2, de Kleine E.1,2, van der
Laan B.F.A.M.1, Langers D.R.M.1,2, van Dijk P. 1,2
1 University of Groningen, University Medical Center
Groningen, Department of Otorhinolaryngology / Head
and Neck Surgery, The Netherlands
2 Graduate School of Medical Sciences (Research School
of Behavioural and Cognitive Neurosciences), University
of Groningen, The Netherlands.
Background: The goal of this study was to identify
mechanisms that underlie gaze-evoked tinnitus (GET), the
perception of a phantom sound that is elicited or modulated
by eye movement.
Materials and Methods: GET was investigated in 18
subjects who underwent surgical removal of a tumour in the
cerebellopontine angle. They all perceived tinnitus that was
modulated or evoked with peripheral gaze. Nine normal-
hearing control subjects were included. Psychoacoustics
and functional magnetic resonance imaging (fMRI) were
performed. The tinnitus percept and modulations were
matched in loudness, pitch and bandwidth to a sound
presented at the ear contralateral to the side of surgery.
Functional MRI measurements were performed with sound
stimuli and eye movement tasks.
Results: The gaze-evoked tinnitus changes were variable
across subjects. Typically, the perceived modulations
comprised increases in loudness and pitch and decreases
in bandwidth. For gaze directions that yielded considerable
loudness modulation of the tinnitus, region of interest
analyses showed significantly more activation of the
auditory cortices compared to gaze directions that yielded a
minor or no increase in tinnitus loudness. Moreover, the
perception of an increased tinnitus loudness tended to
coincide with increased activation in the inferior colliculi and
the basal ganglia.
Conclusions: These results show that gaze evoked tinnitus
loudness is represented by neural activity in auditory
cortical areas and tends to be correlated with neural activity
in non-auditory areas as well, suggesting a failure of cross-
modal inhibition and sustained hyperactivity related to the
tinnitus.
Abstracts of oral presentations Sixth International Conference on Tinnitus
22
1:45 - 3:00 p.m.
PLENARY TALKS
1:45 - 2:30 p.m. – Keynote Speaker
AUDIT ORY ALPH A: FROM CLINICAL TO COGNITIVE
NEUROSCIENCE AND BACK
Nathan Weisz
Nathan Weisz is one of the leading tinnitus researchers in
the world, moving from the University of Konstanz in
Germany to the University of Trente, Italy. He was awarded
a large grant by the European Research Council in 2011,
permitting him to set up a new laboratory. The scientific
mission of Nathan’s research group is to advance the
understanding of the functional relevance of spontaneous
brain oscillations. Besides fundamental experiments with
healthy participants, his approach includes the investigation
of abnormal brain rhythms in pathologies like tinnitus and
their relationship with behavioral symptoms. In order to
pursue these goals he uses MEG, EEG, TMS and
behavioral experiments. He will talk about the relevance of
spontaneous brain activity and functional connectivity for
understanding the pathophysiology of tinnitus.
Alpha oscillations are an omnipresent feature of ongoing
brain activity. Initially thought to reflect an "idling" state,
current cognitive neuroscientific research indicate strong
alpha to represent a state of relative inhibition. While these
notions have been mainly gained from studies in the visual
as well as sensorimotor systems, works in the auditory
modality have been scarce. Based on our initial findings of
reduced alpha activity in tinnitus patients, I will in this talk
review some of the current cognitive neuroscientic works
from my lab indicating that alphalike oscillations in the
auditory system play a similar functional role as in other
sensory systems. More specifically I will present data
showing their relationship to (normal) auditory phantom
percepts as well as attention. My main argument will be that
with regards to tinnitus, reduced auditory alpha activity may
constitute a useful proxy for the assumed excitatory-
inhibitory imbalance that has been suggested for this
condition and that one useful avenue for treatment of
chronic tinnitus may lie in selectively enhancing auditory
cortical alpha. At the end of my presentation I will review
some of our attempts with respect to this goal.
___________________
2:30 - 3:00 p.m. – Invited Speaker
A TECHNOLOGY PUSH FOR ELECTRICAL
NEUROMODULATION
Wouter Serdijn
Wouter Serdijn is Associate Professor at the faculty of
Information Technology and Systems (now Electrical
Engineering, Mathematics and Computer Science) at the
Technical University of Delft, in The Netherlands.. He is
also Editor-in-Chief of IEEE Transactions on Circuits and
Systems. His research as an electrical engineer focuses on
cochlear implants and brain stimulators, and his team is
developing both invasive and non-invasive technology for
the treatment of tinnitus. His talk will focus on these
technologies and how engineers and clinicians can
collaborate to fight tinnitus.
Due to favorable results from actual monitoring, treatment
and clinical trials, but equally important, due to advances in
microelectronics, wireless communications, batteries, bio-
compatible materials and software, the potential clinical
value of electronic neuromodulators for the treatment of
brain related disorders such as tinnitus is gradually being
recognized. Yet, despite the miracles they can bring,
current devices are severely limited in functionality and
performance. In the Biomedical Electronics group at Delft
University of Technology we try to push the technology for
wearable and implantable devices, such as cochlear
implants and neurostimulators. This talk will address some
of the shortcomings of existing cochlear implants and
neurostimulators and sketch an avenue for the development
of future devices that, e.g., do not suffer from "the wiring
problem", that offer energy-efficient stimulation, readout of
evoked compound action potentials, closed-loop operation
and allow the patient to exercise various electrical
stimulation patterns by means of a smart phone.
___________________
1:45 - 2:30 p.m. – Keynote Speaker
VIRTUAL REALITY (VR) IN SUBJECTIVE TINNITUS
MANAGEMENT
Alain Londero
Alain Londero is a well-known ENT surgeon and artist living
in Paris, France. As one of the leaders in the French tinnitus
field he works in the hôpital Georges Pompidou de Paris,
where he has been involved in all aspects of tinnitus
treatments, from audiological approaches, to cognitive
behavior therapy, but also including brain stimulation
techniques as well as the development of virtual reality to
treating tinnitus. His tinnitus related work and artistic
expressions fuse in this virtual reality world but also in some
of his paintings, where he often uses cochlear structures as
inspiration for beautiful pictural creations.
Subjective Tinnitus (ST) is a phantom auditory percept
frequently triggered by a loss in auditory input inducing
maladaptive neuroplastic efforts within brain circuitries to
compensate such a deficit. Perceptually, ST could be
described as the emergence of an auditory form resulting
from a negative figure/ground contrast between normally
and abnormally processed frequencies, in other words the
illusory perception of “missing information” during the
auditory scene analysis. The correlation between ST
features and hearing-loss laterality or spectrum supports
this theory. Moreover clinical patterns and therapeutic
management of ST are quite similar to those displayed in
chronic pain following amputation, another example of
“missing information” condition. As conditioning techniques
using Virtual Reality (VR) have been shown to be both
theoretically interesting and effectively useful in amputated
patients, we have developed an innovative set-up with
dedicated auditory and visual 3D VR environments. In this
set-up, unilateral subjective tinnitus sufferers are given the
possibility to voluntarily manipulate an auditory and visual
image of their ST (tinnitus avatar). The main aim of such a
technique is to give the patients the ability to transfer their
subjective auditory perception to the tinnitus avatar,
allowing them to take control and gain agency on this multi-
sensory displayed percept. We have conducted a
randomized clinical trial in a series of 131 patients.
Following this trial, VR is well accepted as patients
managed to immerse themselves in VR environments.
Overall results indicate that VR is able to significantly
improve tinnitus intrusiveness versus waiting list (THI
p=.025, STSS p=.047).
Sixth International Conference on Tinnitus Abstracts of oral presentations
23
04:00 - 05:30 p.m.
SESSION 3: Pathophysiology
Chair: Susan Shore
Room: Morus
NOISE-INDUCED TINNITUS: SELECTED
NEUROBIOCHEMICAL, ANATOMICAL, AND
PSYCHOMTRIC CHANGES FOLLOWING RTMS
INCLUDING OTHER METABOLIC-RELATED EFFECTS
Cacace A.T., Hu J., Romero S. Salamy J., Xuan, Y.
1 Department of Communication Sciences & Disorders,
Wayne State University, Detroit, USA; 2 Department of
Radiology, Wayne State University School of Medicine,
Detroit, USA; 3 Department of Psychology, Union College,
Schenectady, USA.
Background: Repetitive transcranial magnetic stimulation
(rTMS) is an experimental procedure showing positive
effects in suppressing tinnitus. Yet, mechanisms-of-action
are not well understood. Moreover, because a large
percentage of adults with tinnitus also have
hyperinsulinemia, metabolic issues and synergic effects
with hearing loss is an area-of-interest. Thus, understanding
the relationships between neurobiochemical, anatomical,
psychometric, and metabolic variables are challenges
requiring resolution to advance the field.
Materials and Methods: Using a single-blinded sham-
controlled crossover design, Experiment 1 examined if
rTMS affects tinnitus and whether it alters brain chemistry,
brain anatomy, self perceived changes in questionnaire
responses, and loudness levels following 5 sequential days-
of-stimulation. Twenty-five adults, 24-80 years with a history
of tinnitus and noise induced hearing loss participated.
rTMS was applied to the temporal lobe of the left
hemisphere (110% above motor threshold of the thumb-
abductor muscle, at 1-Hz, pulse duration ~400 µs). In
Experiment 2, we evaluated the relationship between Type-
2 diabetes and tinnitus, based on a single-subject design.
Blood-glucose levels, blood-pressure, self perceived
questionnaire scores, and tinnitus-loudness levels were
assessed twice per day, over a contiguous 30-day period.
Results: Neurobiochemical and psychometric changes
were associated with pre-post actual rTMS. Most notably,
glutamate was down regulated and loudness levels
decreased under these conditions. Significant differences
between blood-glucose levels and tinnitus-loudness levels
were observed in PM vs. AM time periods; other significant
relationships were also observed.
Conclusions: rTMS significantly altered neurobiochemical
and psychometric factors related to tinnitus. Time-of-day
effects of blood-glucose levels, psychometric correlates,
and other effects observed in Type-2 diabetes may be
associated with tinnitus-related distress.
___________________
GABA SIGNALING COMPONENTS IN THE MGB AND
HIPPOCAMPUS OF RATS WITH CHRONIC TINNITUS
Kidd A.R.1, Turner J.G.2,3, Caspary D.M.3 and Bao, J1
1 Washington University School of Medicine, Dept. of
Otolaryngology, St. Louis, MO, USA;
2 Illinois College, Dept. of Psychology, Jacksonville, IL,
USA;
3 Southern Illinois University School of Medicine,
Springfield, IL, USA
Background: Animal models have facilitated significant
research into the biological mechanisms underlying tinnitus.
Initially, the spontaneous neural activity associated with
tinnitus relies on afferent input from the cochlea. However,
over time, the spontaneous activity is "centralized" and
becomes somewhat independent of the peripheral input.
Interestingly, numerous studies have suggested that both
the auditory and limbic systems are involved in the
centralization that corresponds to the transition from
temporary to chronic tinnitus. Although multiple
mechanisms likely play a role in the etiology of chronic
tinnitus, increasing evidence suggests inhibitory γ-amino
butyric acid (GABA) signaling may be altered in chronic
tinnitus.
Materials and Methods: We used intense unilateral noise
exposure to induce tinnitus in rats. We used the gap
prepulse inhibition of the acoustic startle (GPIAS) to identify
animals with chronic tinnitus-like behavior. We collected
and extracted RNA from brain samples from auditory (MGB)
and non-auditory structures (hippocampus). The expression
of multiple GABA signaling components was assessed by
qRT-PCR.
Results and Discussion: We found that hippocampal
expression of the mRNA encoding the GABAA receptor
gamma 2 subunit was significantly lower in rats with chronic
tinnitus-like behavior than in control rats or noise exposed
rats that did not develop tinnitus. Because this subunit is
particularly important for postsynaptic clustering of major
GABAA receptor subtypes, and it plays an important role in
experience-dependent plasticity, we are further studying its
spatial changes in the hippocampus. Analysis of GABA
regulation in the medial geniculate body (MGB) is ongoing
and will be presented.
___________________
GENETIC EVIDENCE FOR THE CONTRIBUTION OF
GLUTAMATE IN OTOTOXIC-MEDIATED HEARING
LOSS AND TINNITUS
Cederroth C.R., Hudspeth A.J.
The Rockefeller University and Howard Hughes Medical
Institute, Department of Sensory Neuroscience, New York,
10065 NY, USA.
Background: Glutamate is thought to be the primary cause
of noise- and medication-induced tinnitus. However,
functional evidence for the role of glutamate in causing
tinnitus is lacking. Here, we take advantage of the known
resistance of mice to ototoxicity to test the hypothesis that
glutamate causes drug-induced hearing loss and tinnitus in
mice lacking GLAST. GLAST is a glutamate transporter
present in support cells that pumps back the excess of
glutamate released by inner hair cells during stimuli. Mice
lacking GLAST display enhanced sensitivity to noise due to
greater glutamate levels in the inner hair cell – afferent fiber
synaptic cleft.
Material and Methods: We administered wild-type and
GLAST KO mice with cisplatin or salicylate, measured their
hearing functions by means of ABR and DPOAEs,
evaluated the perception of tinnitus by the gap-detection
method.
Results: Whereas wild-type mice showed no sensitivity to
cisplatin and little deficit in the gap-perception (60%
suppression of the startle-response versus 80% in vehicle
treated mice), mice lacking GLAST showed elevated
hearing thresholds up to 40 dB shifts with cisplatin, and
25% of suppression of the startle response, being highly
suggestive of severe tinnitus percept.
Conclusions: Our results suggest that GLAST contributes
to cisplatin-mediated hearing loss and tinnitus caused by
salicylate. GLAST deficiency may serve as a model to study
tinnitus in mice. Genetic differences in humans causing
differential cochlear expression of GLAST may thus
underlie people’s degree of susceptibility in developing
hearing loss or tinnitus. Finally, GLAST agonists may also
prove useful to prevent from tinnitus induction by noise or
medication.
Abstracts of oral presentations Sixth International Conference on Tinnitus
24
CHANGES IN SOMATOSENSORY-AUDITORY
INTEGRATION IN INFERIOR COLLICULUS
ACCOMPANY NOISE INDUCED TINNITUS
Dehmel S, Parikh M, Bledsoe SC, Shore SE
University of Michigan, Dep. Otolaryngology, Ann Arbor,
USA
Background: Ascending projections from a somatosensory
structure, the spinal trigeminal nucleus (Sp5), and the
cochlear nucleus converge in the guinea pig external
nucleus of the inferior colliculus (ICx). Pairing electrical
stimulation of the Sp5 with auditory stimulation suppresses,
and sometimes enhances, neural activity in the ICx. Here
we investigated the effects of noise-induced hearing loss on
neural activity as well as somatosensory influence in the
ICx and central nucleus of the IC (ICc).
Materials and Methods: Guinea pigs were unilaterally
noise exposed. Gap detection testing monitored the
development of tinnitus. After recovery of ABR thresholds,
in vivo extracellular recordings were performed with 16
channel Neuronexus probes. Sp5 was electrically
stimulated with bipolar concentric stimulation electrodes.
Unit responses were examined before and during bimodal
Sp5-sound stimulation. Recording and data analysis was
performed by TDT software and hardware and SPSS.
Results: Noise exposure resulted in tinnitus in half of the
animals, increased spontaneous rates in the ICx and
reduced dynamic ranges of tone responses. Suppressive
and enhancing bimodal integration occurred in ICx and ICc
in normal control animals. After noise-exposure ICx showed
primarily bimodal suppression, especially in animals with
tinnitus while ICc showed primarily bimodal enhancement.
Conclusions: Previous findings show tinnitus accompanied
by bimodal enhancement in DCN, suggesting bimodal
stimulation elicits an opposite effect in ICx of tinnitus
animals. Bimodal effects in ICC might reflect mostly
transmission of already-processed information from DCN.
ICx, on the other hand, appears to process bimodal
information independently of DCN.
___________________
ROLE OF THE 5-HT SYSTEM IN TINNITUS: A
SYSTEMATIC STUDY USING AN ANIMAL MODEL
Grafton G.1, Ahmed S.R.1, Brouard J.1, Lobarinas E.2,
Salvi R.2, Barnes N.M.1
1 University of Birmingham, Department of Clinical and
Experimental Medicine, Birmingham, UK;
2 University of Buffalo, Center for Hearing and Deafness,
Buffalo, USA
Background: Serotonin (5-HT) has multiple functions in the
brain, many of which are involved in emotion, attention and
mood control. It is also present in the auditory system and
has been implicated in tinnitus. Many scattered tinnitus
trials with various drugs that target the 5-HT system have
produced mixed results with the choice of drugs rather
arbitrary. In our research we have started to systematically
study the changes in 5-HT receptors and other components
of the 5-HT system in various parts of the auditory system
of animals with deafness-induced tinnitus.
Materials and Methods: Using a rat model of tinnitus
(GPIAS) we have performed a detailed systematic screen of
whether the 5-HT system is perturbed following induction of
tinnitus. Tinnitus was induced unilaterally and bilateral brain
regions were collected and analysed separately by
quantitative PCR to determine changes in gene expression.
Results: We have analysed eleven brain regions with a
panel of eleven genes and have described significant
changes in gene expression of several key 5-HT related
genes.
Conclusions: Using sensitive molecular biological
techniques we have started to detail the changes in gene
expression that occur in different parts of the auditory
system following the induction of tinnitus. We have exciting
preliminary data showing co-ordinated changes in gene
expression in various parts of the brain in these animals.
This works holds out the prospect of targeted use of already
existing drugs to treat tinnitus and for the longer term, the
hope of rational design of specific drug treatments.
___________________
THE ACUTE AND CHRONIC EFFECTS OF NOISE
TRAUMA ON NEURONAL ACTIVITY IN THE INFERIOR
COLLICULUS OF THE GUINEA PIG
Heeringa A.N.1,2, Segenhout J.M.1, Van Dijk P.1,2
1 Department of Otorhinolaryngology, University Medical
Center Groningen, Groningen, The Netherlands;
2 Graduate School of Medical Sciences, School of
Behavioral and Cognitive Neurosciences, University of
Groningen, Groningen, The Netherlands
Background: Exposure to loud noise often results in
(temporary) hearing loss and immediately occurring tinnitus.
Additionally, noise trauma affects neuronal activity of the
central auditory system. The aim of the current project is to
study immediate changes in inferior colliculus (IC) activity
after noise trauma and how these develop over several
weeks.
Materials and Methods: Anesthetized guinea pigs were
subjected to noise trauma (1hr, 11kHz, 124 dB). By
measuring auditory brainstem responses (ABR), hearing
thresholds were determined. Acute and chronic changes in
neuronal activity of the IC were investigated by multichannel
electrophysiology.
Results: Preliminary analyses of acute effects to noise
trauma showed an ABR threshold shift to tones of 11 kHz
and 22 kHz, whereas thresholds of 3 kHz, 6 kHz and click
stimuli were unaffected. Likewise, tuning to tones
completely disappeared in neurons with a characteristic
frequency (CF) above 11 kHz. Spontaneous firing rate of IC
neurons was increased (p<0.001). However, it appeared
that a systematic increase of spontaneous activity was only
present in neurons with a low CF.
Conclusion: Noise trauma resulted in an acute threshold
shift at the high frequencies, measured with both ABR and
electrophysiology. Against our expectations, noise trauma
resulted in an immediate increase of spontaneous activity of
IC neurons with a low tuning frequency and not of neurons
tuned to high frequencies (at and above the trauma
frequency). Further analysis will show to what extend these