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Mechanisms Mechanisms of tinnitus Mechanisms Mechanisms of

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Mechanisms Mechanisms of tinnitus Mechanisms Mechanisms of Powered By Docstoc
					                                                                                                                                 1/22/2010




           Evidence for benefit
       from acoustic enhancement
                                                                                Mechanisms of tinnitus
                                                                             = aberrant neural spontaneous activity
                                                                    ► Tinnitus
                                                                     generated at some level of the auditory system
                            Arnaud Noreña
          Laboratoire « Neurobiologie intégrative et adaptative »                       tinnitus:
                                                                         « Peripheral » tinnitus: aberrant activity is present
                    UMR CNRS 6149, Marseille, France
                               6149 Marseille                                            nerve
                                                                         in the cochlear nerve, which propagates all the way
                      rnaud.norena@univ-
                     arnaud.norena@univ-provence.fr
                                                                         to the auditory cortex
                                                                         « Central tinnitus »: aberrant activity is not present
                                                                         in the cochlear nerve, and is generated in the
                                                                         auditory centers
                                                                          ►After   hearing loss (cochlear damages)




            Mechanisms of tinnitus                                              Mechanisms of tinnitus
►«                tinnitus:
     Peripheral » tinnitus: effects of salicylate                   ►«                tinnitus:
                                                                         Peripheral » tinnitus: effects of salicylate
     Aberrant neural activity in the cochlear nerve                      Aberrant neural activity in the cochlear nerve
      ►Increase   of FR: Evans and Borerwe (400mg/kg - 1982),             ►Increase   of FR: Evans and Borerwe (400mg/kg - 1982),
        Ruel et al. (2008)                                                  Ruel et al. (2008)
      ►Change                                          Activity:
                of the Average Spectrum Cochleoneural Activity:           ►Change                                          Activity:
                                                                                    of the Average Spectrum Cochleoneural Activity:
                                       (200mg/kg*2/day,
        Recording at RO, Cazals et al. (200mg/kg*2/day, 1998)                                              (200mg/kg*2/day,
                                                                            Recording at RO, Cazals et al. (200mg/kg*2/day, 1998)


                                                                          ►No  increase in FR: Stypulkowski (200mg/kg, 1990),
                                                                            Müller et al. (200mg/kg, 2003)
                                                                          ►Effectsof salicylate on auditory cortex (Sun et al., 2009;
                                                                                              press):
                                                                            Norena et al., in press): Hyperacusis?




            Mechanisms of tinnitus                                                   Models of tinnitus
► Section    of cochlear nerve:                                       Noise-
                                                                    ► Noise-trauma

     Pulec (1995): 101/151 (67%) suppression, 43/151                     Loeb and Smith (1967): 5 min exp (120 dB max)
     (28%) amélioration, 7/151 (5%) pas d’amélioration                   inducing 40 dB HL → 70-100% with tinnitus
                                                                                             70-
     (+aggravation)                                                      Atherley et al. (1968): 5 min exp 110 dB – 1/3rd oct
     Silverstein et al. (1986): 12/34 (35%), 14/34                       noise
     (41%), 8/34 (24%)
     Barrs & Brackmann (1984): 4/36 (11%), 18/36
     (50%), 14/36 (39%)




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             Mechanisms of tinnitus                                                             Mechanisms of tinnitus
►«            tinnitus:
     Central» tinnitus: effects of a noise trauma                                 ►«            tinnitus:
                                                                                       Central» tinnitus: effects of a noise trauma
                                                        (Liberman
     Decrease of spontaneous activity in cochlear nerve (Liberman and                                                                     (Liberman
                                                                                       Decrease of spontaneous activity in cochlear nerve (Liberman and
     Dodds, 1984)                                                                      Dodds, 1984)
               control        NBN, 2 kHz, 115 dB, 2h   NBN, 5.5 kHz, 109 dB, 2h
                                                                                                                                                      8-
                                                                                       Noise trauma increases vulnerability to aging (100 dB SPL, 2h, 8-16 kHz
                                                                                                         Liberman,
                                                                                       noise, Kujawa and Liberman, 2006, 2009): moderate and reversible HL
                                                                                       can cause acute and delayed degeneration of the cochlear nerve




             Mechanisms of tinnitus                                                             Mechanisms of tinnitus
►«            tinnitus:
     Central» tinnitus: effects of a noise trauma
                                                                                  ► Central    tinnitus:
                                                                                               tinnitus: effects of a noise trauma
                                                         (Liberman
     Decrease of spontanenous activity in cochlear nerve (Liberman and
     Dodds, 1984)                                                                      Reorganization of the cortical tonotopic map
                                                                    8-
     Noise trauma increases vulnerability to aging (100 dB SPL, 2h, 8-16 kHz
                       Liberman,
     noise, Kujawa and Liberman, 2006, 2009): moderate and reversible HL
     can cause acute and delayed degeneration of the cochlear nerve
     Decrease of stimulus-induced activity (Heinz et al., 2004, trauma: 50Hz
                 stimulus-               y(             ,     ,
     noise, 105 dB, 4h)




             Mechanisms of tinnitus                                                             Mechanisms of tinnitus
► Central    tinnitus:
             tinnitus: effects of a noise trauma                                  ► Central    tinnitus:
                                                                                               tinnitus: effects of a noise trauma
     Reorganization of the cortical tonotopic map                                      Reorganization of the cortical tonotopic map
                 stimulus-
     Increase of stimulus-iunduced responses                                                       stimulus-
                                                                                       Increase of stimulus-induced activity
      ► In             al. 2008),              al. 2002)
           VCN (Cai et al., 2008), IC (Wang et al., 2002) and cortex (Norena            ► In             al. 2008),              al. 2002)
                                                                                             VCN (Cai et al., 2008), IC (Wang et al., 2002) and cortex (Norena
           al. 2003)
        et al., 2003)                                                                        al. 2003)
                                                                                          et al., 2003)
                                                                                       Increase of spontaneous activity & synchrony
                                                                                        ► In                  al. 2009),                                al. 2003)
                                                                                               IC (Mulders et al., 2009), in auditory cortex (Norena et al., 2003)




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                  Mechanisms of tinnitus                                                                Mechanisms of tinnitus
► Central        tinnitus:
                 tinnitus: effects of a noise trauma                                                                                      RAN dist               RCN dist
                                                                                            Level distribution   I-O auditory nerve       I-O CN
         Reorganization of the cortical tonotopic map
                                                                                            P(I)                 R(I)                 P(RAN)         R(RAN) RCN(I)
                     stimulus-
         Increase of stimulus-induced activity
          ► In             al. 2008),              al. 2002)
               VCN (Cai et al., 2008), IC (Wang et al., 2002) and cortex (Norena
               al. 2003)
            et al., 2003)
         Increase of spontaneous activity & synchrony                                                   I (dB)               I (dB)              RAN                        RCN
          ► In                  al. 2009),                                al. 2003)
                 IC (Mulders et al., 2009), in auditory cortex (Norena et al., 2003)
         Down-
         Down-regulation of inhibitory neurotransmission (Milbrandt
            al. 2000;             al. 2006; 2008)
         et al., 2000; Argence et al., 2006; 2008)




                  Mechanisms of tinnitus                                                                Mechanisms of tinnitus
                                                    RAN dist               RCN dist                                                       RAN dist               RCN dist
  Level distribution       I-O auditory nerve       I-O CN                                  Level distribution   I-O auditory nerve       I-O CN

  P(I)                     R(I)                 P(RAN)         R(RAN) RCN(I)                P(I)                 R(I)                 P(RAN)         R(RAN) RCN(I)




                  I (dB)               I (dB)              RAN                        RCN               I (dB)               I (dB)              RAN                        RCN




                  Mechanisms of tinnitus                                                                 Acoustic enhancement
                                                    RAN dist               RCN dist                                                       RAN dist               RCN dist
  Level distribution       I-O auditory nerve       I-O CN                                  Level distribution   I-O auditory nerve       I-O CN

  P(I)                     R(I)                 P(RAN)         R(RAN) RCN(I)                P(I)                 R(I)                 P(RAN)         R(RAN) RCN(I)




                  I (dB)               I (dB)              RAN                        RCN               I (dB)               I (dB)              RAN                        RCN




                                         Tinnitus?
                                         Tinnitus?                                                                             Tinnitus?
                                                                                                                               Tinnitus?
                                       Hyperacusis?                                                                          Hyperacusis?




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              Acoustic enhancement                                                                                                                                                            Acoustic enhancement
                    Norena & Chery-Croze (2007)
                             Chery-                                                                                                                                                                        Chery-
                                                                                                                                                                                                  Norena & Chery-Croze (2007)
                                                                                          AT (dB SPL)
                                                                                                                                        Long-term spectrum
                                                                                                                                           of the signal
                                                                                                                                                                                    Audiogram:
                                                                                                                                                                                  ► Audiogram:      500-
                                                                                                                                                                                                    500-16 kHz, ½ oct step
    Freq                                                                                                                                                  E

8 or 16 kHz
                                                                                                                                          COF                                     ► Stimstored on a CD, played from a CD player
                                                                                                                          0
                                                                                                                                                                                   1-3h / day
                                                                                                                                                                 75 dB
                                                                                                                                                                                  ► Loudness          one-
                                                                                                                                                                                            Growth in one-half Octave Band
                                                                                                                                                                  max

                                                                                                                          75
                                                                                                                                                                                   (LGOB) (workshop)
                                                      Time                                                                                                                 Freq                                                (rep)
                                                                                                                                                                                     [15 levels between AT(f) and LDL(f) ] * 3 (rep)
     COF chosen visually, COF<f<flev_max (1/64 oct)
                          COF<f<f              oct)                                                                                                                                  7 categories (from « inaudible » to « too loud »)

     PT(f,t)=A(f)*sin(2*pi*f*t)*env(t)
     PT(f,t)=A(f)*sin(2*pi*f*t)*env(t)                                                                                                            (workshop)                        Follow-
                                                                                                                                                                                  ► Follow-up

     A(f)=10[(AT(f)-level_max)/20]
            [(AT(f)-level_max)/20]                                                                                                                                                   Bef, +2w, +5w, 10w, +15w, +1m after stopping
                                                                                                                                                                                     Bef,
                                                                                                                                                                                     stim




              Acoustic enhancement                                                                                                                                                            Acoustic enhancement
                             Chery-
                    Norena & Chery-Croze (2007)                                                                                                                                                             Chery-
                                                                                                                                                                                                   Norena & Chery-Croze (2007)


          Flow    COF                 Fhigh                                                                                                                                                Flow   COF    Fhigh


                                                                                                                                                                                                                                          0        20     40    60     80     100 20   40   60    80   100
                                                                                                                                                                                                                                                    Bef
                                                                                                                                                                                                                                      6             s2
                                                                                                                     ry




                                                                                                                                             0.5
                                                                                                                                             0 5 kHz (h i i i d)
                                                                                                                                                      (hearing-impaired)                                                              5             s5
                                                                                             Loudness response categor




                                                                                                                          too loud       0.5 kHz (normal-hearing)                                                                     4             s10
                                                                                                                                         COF                                                                                                        s15
                                                                                                                                                                                                                                      3
                                                                                                                          very loud      Fhigh
                                                                                                                                                                                                                                                    +1m
                                                                                                                                                                                                                                      2
                                                                                                                          loud           Flow
                                                                                                                                                                                                                                      1
                                                                                                                                                                                                                                      0                              1000 Hz                     4000 Hz
                                                                                                                          ok
                                                                                                                          soft                                                                                                        6




                                                                                                                                                                                                                  Loudness category
                                                                                                                                                                                                                                      5
                                                                                                                          very soft
                                                                                                                                                                                                                                      4
                                                                                                                          inaudible                                                                                                   3
                                                                                                                                                                                                                                      2
                                                                                                                                      0 10 20 30 40 50 60 70 80 90 100110                                                             1
                                                                                                                                                                                                                                      0                              5000 Hz                     8000 Hz
                                                                                                                                                 Level (dB SPL)                                                                               20        40     60      80     100 20   40   60    80   100
                                                                                                                                                                                                                                                   Intensity level (dB SPL)




              Acoustic enhancement                                                                                                                                                            Acoustic enhancement
                    Norena & Chery-Croze (2007)
                             Chery-                                                                                                                                                                     Moffat et al. (2009)

                                                                                                                                                                                  ► Hearing aid:
                                                                                                                                                                                            aid: open mold (with noise reduction
                                                      25
                                                                    s2-s0
                                                      20
                                                                    s15-s0
                                                      15            s+1m-s0
                                                      10
                                                      5                                                                                                                                     disabled),
                                                                                                                                                                                   controls disabled), « standard » & HF gain
                                                      0


                                                                                                                                                                                    Audiogram:
                                                                                                                                                                                  ► Audiogram:      250-
                                                                                                                                                                                                    250-8kHz
                                                      -5
                                                           Flow
                                                      25
                                                      20


                                                                                                                                                                                  ► Psychoacoustic       of tinnitus (workshop)
                                                      15            category vs s2 fl


                                                      10            category vs s15 fl
                                                                    category vs flow s+1m-s0
                                                      5
                                                      0
                                                      -5
                                                           COF
                                                                                                                                                                                     Loudness:
                                                                                                                                                                                     Loudness: matching procedure in the ipsilateral ear
                         Relative level change (dB)




                                                      25
                                                      20
                                                      15
                                                                                                                                                                                     Pitch or « tinnitus spectrum »: Relative contribution
                                                      10
                                                      5
                                                                                                                                                                                     of all frequency components of tinnitus
                                                      0
                                                      -5
                                                           Fhigh
                                                                      ft
                                                               ible so so
                                                                          ft            ok loud loud loud
                                                             ud ery                           ry too
                                                       ina      v                           ve
                                                               Loudness response category




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                                                                                                     1/22/2010




         Acoustic enhancement                               Acoustic enhancement
                  Moffat et al. (2009)                               Moffat et al. (2009)

 ► Tinnitus                             tones?
              pitch: matching with pure tones?    ► Tinnitus   pitch or « tinnitus spectrum »?
                                                                              tinnitus?
                                                      What is the bandwith of tinnitus?
           AT                                TP
                                                                                        tinnitus?
                                                      What is the dominant frequency of tinnitus?
                                                               AT                               TP




                                         F


                                                                                            F




         Acoustic enhancement                               Acoustic enhancement
                  Moffat et al. (2009)                               Moffat et al. (2009)

► Psychoacoustic   of tinnitus in the 3 groups    ► Hearing    aid gains




         Acoustic enhancement                               Acoustic enhancement
                  Moffat et al. (2009)                               Moffat et al. (2009)

 ►«   Standard » amplification                    ► Group   data




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         Acoustic enhancement                                     Acoustic enhancement
              Preliminary data on tinnitus                             Preliminary data on tinnitus
► Acousticsignal in the frequency band of               ► Acousticsignal in the frequency band of
 hearing loss                                            hearing loss




         Acoustic enhancement                                                  Conclusion I
              Preliminary data on tinnitus
► Acousticsignal in the frequency band of
                                                        ► Acoustic   enhancement improves hyperacusis
 hearing loss
                                                                enhancement may improve tinnitus (in
                                                        ► Acoustic

                    50%   50%
                                                              subjects)
                                                         some subjects)
                                                        ► Diagnostic   of the « Dead regions » (workshop)
                                                        ►«   Tinnitus loudness »: Visual Analog Scale




                    Conclusion II                                            Conclusion II
► Improvement       of acoustic stimulation             ► Improvement        of acoustic stimulation
               Freq                              P(I)                   Freq                              P(I)
         8 or 16 kHz                                              8 or 16 kHz


                                        I (dB)                                                   I (dB)



                                Time                                                     Time
               dB                                                       dB




                                       Freq                                                     Freq




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Acknowledgments

  Tinnitus Research Initiative
  France Acouphènes
  Agence Nationale pour la Recherche
  Fondation pour la Recherche sur le cerveau

  Sylviane Chery-Croze
  Stephane Gallego
  Kamel Adjout
  Hung Thai-Van
  Lionel Collet
  Jos Eggermont
  Greg Shaw




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