Can Temporal Repetitive Transcranial Magnetic Stimulation be Enhanced by Targeting Affective Components of Tinnitus with Frontal rTMS? A Randomized Controlled Pilot Trial

Peter Michael Kreuzer, Michael Landgrebe, Martin Schecklmann, Timm B Poeppl, Veronika Vielsmeier, Goeran Hajak, Tobias Kleinjung, Berthold Langguth, Peter Michael Kreuzer, Michael Landgrebe, Martin Schecklmann, Timm B Poeppl, Veronika Vielsmeier, Goeran Hajak, Tobias Kleinjung, Berthold Langguth

Abstract

Objectives: Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been investigated as a new treatment tool for chronic tinnitus during the last years and has shown moderate efficacy. However, there is growing evidence that tinnitus is not a pathology of a specific brain region, but rather the result of network dysfunction involving both auditory and non-auditory brain regions. In functional imaging studies the right dorsolateral prefrontal cortex has been identified as an important hub in tinnitus related networks and has been shown to particularly reflect the affective components of tinnitus. Based on these findings we aimed to investigate whether the effects of left low-frequency rTMS can be enhanced by antecedent right prefrontal low-frequency rTMS.

Study design: Fifty-six patients were randomized to receive either low-frequency left temporal rTMS or a combination of low-frequency right prefrontal followed by low-frequency left temporal rTMS. The change of the tinnitus questionnaire (TQ) score was the primary outcome, secondary outcome parameters included the Tinnitus Handicap Inventory, numeric rating scales, and the Beck Depression Inventory. The study is registered in clinicaltrials.gov (NCT01261949).

Results: Directly after therapy there was a significant improvement of the TQ-score in both groups. Comparison of both groups revealed a trend toward more pronounced effects for the combined group (effect size: Cohen's d = 0.176), but this effect did not reach significance. A persistent trend toward better efficacy was also observed in all other outcome criteria.

Conclusion: Additional stimulation of the right prefrontal cortex seems to be a promising strategy for enhancing TMS effects over the temporal cortex. These results further support the involvement of the right DLPFC in the pathophysiology of tinnitus. The small effect size might be due to the study design comparing the protocol to an active control condition.

Keywords: chronic tinnitus; dorsolateral prefrontal cortex; limbic system; neuromodulation; rTMS; transcranial magnetic stimulation.

Figures

Figure 1
Figure 1
(A) Tinnitus Questionnaire Score (TQ; mean ± SEM), (B) Tinnitus Handicap Inventory (THI; mean ± SEM), and (C) Beck Depression Inventory (BDI; mean ± SEM).

References

    1. Arfeller C., Vonthein R., Plontke S. K., Plewnia C. (2009). Efficacy and safety of bilateral continuous theta burst stimulation (cTBS) for the treatment of chronic tinnitus: design of a three-armed randomized controlled trial. Trials 10, 74.10.1186/1745-6215-10-74
    1. Beck A. T., Steer R. A. (1984). Internal consistencies of the original and revised Beck Depression Inventory. J. Clin. Psychol. 40, 1365–136710.1002/1097-4679(198407)40:4<1123::AID-JCLP2270400447>;2-B
    1. Cheeran B., Talelli P., Mori F., Koch G., Suppa A., Edwards M., Houlden H., Bhatia K., Greenwood R., Rothwell J. C. (2008). A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS. J. Physiol. (Lond.) 586, 5717–572510.1113/jphysiol.2008.159905
    1. Cohen J. (1988). Statistical Power for the Behavioral Sciences. Hillsdale, NJ: Erlbaum
    1. Crippa A., Lanting C. P., Van Dijk P., Roerdink J. B. (2010). A diffusion tensor imaging study on the auditory system and tinnitus. Open. Neuroimag. J. 4, 16–2510.2174/1874440001004010016
    1. Davidson R. J. (1992). Anterior cerebral asymmetry and the nature of emotion. Brain Cogn. 20, 125–15110.1016/0278-2626(92)90065-T
    1. De Ridder D., Elgoyhen A. B., Romo R., Langguth B. (2011). Phantom percepts: tinnitus and pain as persisting aversive memory networks. Proc. Natl. Acad. Sci. U.S.A. 108, 8075–808010.1073/pnas.1018466108
    1. Eichhammer P., Langguth B., Marienhagen J., Kleinjung T., Hajak G. (2003). Neuronavigated repetitive transcranial magnetic stimulation in patients with tinnitus: a short case series. Biol. Psychiatry 54, 862–86510.1016/S0006-3223(02)01896-6
    1. Frank E., Schecklmann M., Landgrebe M., Burger J., Kreuzer P., Poeppl T. B., Kleinjung T., Hajak G., Langguth B. (2011). Treatment of chronic tinnitus with repeated sessions of prefrontal transcranial direct current stimulation: outcomes from an open-label pilot study. J. Neurol. [Epub ahead of print].10.1007/s00415-011-6189-4
    1. Frank G., Kleinjung T., Landgrebe M., Vielsmeier V., Steffenhagen C., Burger J., Frank E., Vollberg G., Hajak G., Langguth B. (2010). Left temporal low-frequency rTMS for the treatment of tinnitus: clinical predictors of treatment outcome – a retrospective study. Eur. J. Neurol. 17, 951–95610.1111/j.1468-1331.2010.02956.x
    1. Gardner A., Pagani M., Jacobsson H., Lindberg G., Larsson S. A., Wagner A., Hallstrom T. (2002). Differences in resting state regional cerebral blood flow assessed with 99mTc-HMPAO SPECT and brain atlas matching between depressed patients with and without tinnitus. Nucl. Med. Commun. 23, 429–43910.1097/00006231-200205000-00002
    1. George M. S., Wassermann E. M., Williams W. A., Callahan A., Ketter T. A., Basser P., Hallett M., Post R. M. (1995). Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport 6, 1853–185610.1097/00001756-199510020-00008
    1. Giraud A. L., Chery-Croze S., Fischer G., Fischer C., Vighetto A., Gregoire M. C., Lavenne F., Collet L. (1999). A selective imaging of tinnitus. Neuroreport 10, 1–510.1097/00001756-199901180-00001
    1. Goebel G., Hiller W. (1994). The tinnitus questionnaire. A standard instrument for grading the degree of tinnitus. Results of a multicenter study with the tinnitus questionnaire. HNO 42, 166–172
    1. Hallett M. (2000). Transcranial magnetic stimulation and the human brain. Nature 406, 147–15010.1038/35018000
    1. Hayward G., Mehta M. A., Harmer C., Spinks T. J., Grasby P. M., Goodwin G. M. (2007). Exploring the physiological effects of double-cone coil TMS over the medial frontal cortex on the anterior cingulate cortex: an H2(15)O PET study. Eur. J. Neurosci. 25, 2224–223310.1111/j.1460-9568.2007.05430.x
    1. Herbsman T., Avery D., Ramsey D., Holtzheimer P., Wadjik C., Hardaway F., Haynor D., George M. S., Nahas Z. (2009). More lateral and anterior prefrontal coil location is associated with better repetitive transcranial magnetic stimulation antidepressant response. Biol. Psychiatry 66, 509–51510.1016/j.biopsych.2009.04.034
    1. Herwig U., Abler B., Schonfeldt-Lecuona C., Wunderlich A., Grothe J., Spitzer M., Walter H. (2003). Verbal storage in a premotor-parietal network: evidence from fMRI-guided magnetic stimulation. Neuroimage 20, 1032–104110.1016/S1053-8119(03)00368-9
    1. Hesser H., Weise C., Rief W., Andersson G. (2011). The effect of waiting: a meta-analysis of wait-list control groups in trials for tinnitus distress. J. Psychosom. Res. 70, 378–38410.1016/j.jpsychores.2010.12.006
    1. Jastreboff P. J. (1990). Phantom auditory perception (tinnitus): mechanisms of generation and perception. Neurosci. Res. 8, 221–25410.1016/0168-0102(90)90031-9
    1. Khedr E. M., Abo-Elfetoh N., Rothwell J. C., El-Atar A., Sayed E., Khalifa H. (2010). Contralateral versus ipsilateral rTMS of temporoparietal cortex for the treatment of chronic unilateral tinnitus: comparative study. Eur. J. Neurol. 17, 976–98310.1111/j.1468-1331.2010.02965.x
    1. Kimbrell T. A., Little J. T., Dunn R. T., Frye M. A., Greenberg B. D., Wassermann E. M., Repella J. D., Danielson A. L., Willis M. W., Benson B. E., Speer A. M., Osuch E., George M. S., Post R. M. (1999). Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism. Biol. Psychiatry 46, 1603–161310.1016/S0006-3223(99)00103-1
    1. Kleinjung T., Eichhammer P., Landgrebe M., Sand P., Hajak G., Steffens T., Strutz J., Langguth B. (2008). Combined temporal and prefrontal transcranial magnetic stimulation for tinnitus treatment: a pilot study. Otolaryngol. Head Neck Surg. 138, 497–50110.1016/j.otohns.2007.12.022
    1. Kleinjung T., Eichhammer P., Langguth B., Jacob P., Marienhagen J., Hajak G., Wolf S. R., Strutz J. (2005). Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus. Otolaryngol. Head Neck Surg. 132, 566–56910.1016/j.otohns.2004.09.134
    1. Kleinjung T., Fischer B., Langguth B., Sand P., Hajak G., Dvorakova J., Eichhammer P. (2007a). Validation of the German-version Tinnitus Handicap Inventory (THI). Psychiatr. Prax. 34, 140–14210.1055/s-2006-940218
    1. Kleinjung T., Steffens T., Sand P., Murthum T., Hajak G., Strutz J., Langguth B., Eichhammer P. (2007b). Which tinnitus patients benefit from transcranial magnetic stimulation? Otolaryngol. Head Neck Surg. 137, 589–59510.1016/j.otohns.2007.06.618
    1. Kleinjung T., Langguth B. (2009). Strategies for enhancement of transcranial magnetic stimulation effects in tinnitus patients. Int. Tinnitus J. 15, 154–160
    1. Kleinjung T., Steffens T., Landgrebe M., Vielsmeier V., Frank E., Burger J., Strutz J., Hajak G., Langguth B. (2011). Repetitive transcranial magnetic stimulation for tinnitus treatment: no enhancement by the dopamine and noradrenaline reuptake inhibitor bupropion. Brain Stimul. 4, 65–7010.1016/j.brs.2010.03.007
    1. Landgrebe M., Langguth B., Rosengarth K., Braun S., Koch A., Kleinjung T., May A., De Ridder D., Hajak G. (2009). Structural brain changes in tinnitus: grey matter decrease in auditory and non-auditory brain areas. Neuroimage 46, 213–21810.1016/j.neuroimage.2009.01.069
    1. Landgrebe M., Zeman F., Koller M., Eberl Y., Mohr M., Reiter J., Staudinger S., Hajak G., Langguth B. (2010). The Tinnitus Research Initiative (TRI) database: a new approach for delineation of tinnitus subtypes and generation of predictors for treatment outcome. BMC Med. Inform. Decis. Mak. 10, 42.10.1186/1472-6947-10-42
    1. Langguth B., Kleinjung T., Frank E., Landgrebe M., Sand P., Dvorakova J., Frick U., Eichhammer P., Hajak G. (2008). High-frequency priming stimulation does not enhance the effect of low-frequency rTMS in the treatment of tinnitus. Exp. Brain Res. 184, 587–59110.1007/s00221-007-1228-1
    1. Langguth B., Landgrebe M., Kleinjung T., Sand G. P., Hajak G. (2011). Tinnitus and depression. World J. Biol. Psychiatry 12, 489–50010.3109/15622975.2011.575178
    1. Lanting C. P., De Kleine E., Eppinga R. N., Van Dijk P. (2010). Neural correlates of human somatosensory integration in tinnitus. Hear. Res. 267, 78–8810.1016/j.heares.2010.04.006
    1. Lanting C. P., De Kleine E., Van Dijk P. (2009). Neural activity underlying tinnitus generation: results from PET and fMRI. Hear. Res. 255, 1–1310.1016/j.heares.2009.06.009
    1. Leaver A. M., Renier L., Chevillet M. A., Morgan S., Kim H. J., Rauschecker J. P. (2011). Dysregulation of limbic and auditory networks in tinnitus. Neuron 69, 33–4310.1016/j.neuron.2010.12.002
    1. Lockwood A. H., Salvi R. J., Burkard R. F., Galantowicz P. J., Coad M. L., Wack D. S. (1999). Neuroanatomy of tinnitus. Scand. Audiol. Suppl. 51, 47–52
    1. Lockwood A. H., Salvi R. J., Coad M. L., Towsley M. L., Wack D. S., Murphy B. W. (1998). The functional neuroanatomy of tinnitus: evidence for limbic system links and neural plasticity. Neurology 50, 114–120
    1. Lorenz I., Muller N., Schlee W., Langguth B., Weisz N. (2010). Short-term effects of single repetitive TMS sessions on auditory evoked activity in patients with chronic tinnitus. J. Neurophysiol. 104, 1497–150510.1152/jn.00370.2010
    1. May A., Hajak G., Ganssbauer S., Steffens T., Langguth B., Kleinjung T., Eichhammer P. (2007). Structural brain alterations following 5 days of intervention: dynamic aspects of neuroplasticity. Cereb. Cortex 17, 205–21010.1093/cercor/bhj138
    1. Mirz F., Gjedde A., Ishizu K., Pedersen C. B. (2000). Cortical networks subserving the perception of tinnitus – a PET study. Acta Otolaryngol. Suppl. 543, 241–24310.1080/000164800454503
    1. Moller A. R. (2003). Pathophysiology of tinnitus. Otolaryngol. Clin. North Am. 36, 249–266, v–vi.10.1016/S0030-6665(02)00170-6
    1. Murphy B., Herrman H., Hawthorne G., Pinzone T., Evert H. (2000). Australian WHOQoL Instruments: User’s Manual and Interpretation Guide. Melbourne: Australian WHOQol Field Study Centre
    1. Norena A., Cransac H., Chery-Croze S. (1999). Towards an objectification by classification of tinnitus. Clin. Neurophysiol. 110, 666–67510.1016/S1388-2457(98)00034-0
    1. Paus T., Castro-Alamancos M. A., Petrides M. (2001). Cortico-cortical connectivity of the human mid-dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation. Eur. J. Neurosci. 14, 1405–141110.1046/j.0953-816x.2001.01757.x
    1. Plewnia C., Reimold M., Najib A., Reischl G., Plontke S. K., Gerloff C. (2007). Moderate therapeutic efficacy of positron emission tomography-navigated repetitive transcranial magnetic stimulation for chronic tinnitus: a randomised, controlled pilot study. J. Neurol. Neurosurg. Psychiatr. 78, 152–15610.1136/jnnp.2006.095612
    1. Rauschecker J. P., Leaver A. M., Muhlau M. (2010). Tuning out the noise: limbic-auditory interactions in tinnitus. Neuron 66, 819–82610.1016/j.neuron.2010.04.032
    1. Ridding M. C., Rothwell J. C. (2007). Is there a future for therapeutic use of transcranial magnetic stimulation? Nat. Rev. Neurosci. 8, 559–56710.1038/nrn2169
    1. Rossi S., De Capua A., Ulivelli M., Bartalini S., Falzarano V., Filippone G., Passero S. (2007). Effects of repetitive transcranial magnetic stimulation on chronic tinnitus: a randomised, crossover, double blind, placebo controlled study. J. Neurol. Neurosurg. Psychiatr. 78, 857–86310.1136/jnnp.2006.105007
    1. Schecklmann M., Landgrebe M., Poeppl T., Kreuzer P., Maenner P., Marienhagen J., Wack D., Kleinjung T., Hajak G., Langguth B. (2011). Neuronal correlates of tinnitus duration and distress: a positron emission tomography study. Hum. Brain Mapp. [Epub ahead of print].10.1002/hbm.21426
    1. Schlee W., Hartmann T., Langguth B., Weisz N. (2009a). Abnormal resting-state cortical coupling in chronic tinnitus. BMC Neurosci. 10, 11.10.1186/1471-2202-10-11
    1. Schlee W., Mueller N., Hartmann T., Keil J., Lorenz I., Weisz N. (2009b). Mapping cortical hubs in tinnitus. BMC Biol. 7, 80.10.1186/1741-7007-7-80
    1. Schlee W., Weisz N., Bertrand O., Hartmann T., Elbert T. (2008). Using auditory steady state responses to outline the functional connectivity in the tinnitus brain. PLoS ONE 3, e3720.10.1371/journal.pone.0003720
    1. Schmidt B., Hanslmayr S. (2009). Resting frontal EEG alpha-asymmetry predicts the evaluation of affective musical stimuli. Neurosci. Lett. 460, 237–24010.1016/j.neulet.2009.05.068
    1. Schutter D. J. (2010). Quantitative review of the efficacy of slow-frequency magnetic brain stimulation in major depressive disorder. Psychol. Med. 40, 1789–179510.1017/S003329171000005X
    1. Shulman A. (1995). A final common pathway for tinnitus – the medial temporal lobe system. Int. Tinnitus J. 1, 115–126
    1. Siebner H. R., Filipovic S. R., Rowe J. B., Cordivari C., Gerschlager W., Rothwell J. C., Frackowiak R. S., Bhatia K. P. (2003). Patients with focal arm dystonia have increased sensitivity to slow-frequency repetitive TMS of the dorsal premotor cortex. Brain 126, 2710–272510.1093/brain/awg282
    1. Siebner H. R., Lang N., Rizzo V., Nitsche M. A., Paulus W., Lemon R. N., Rothwell J. C. (2004). Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J. Neurosci. 24, 3379–338510.1523/JNEUROSCI.5316-03.2004
    1. Siebner H. R., Peller M., Willoch F., Minoshima S., Boecker H., Auer C., Drzezga A., Conrad B., Bartenstein P. (2000). Lasting cortical activation after repetitive TMS of the motor cortex: a glucose metabolic study. Neurology 54, 956–963
    1. Smith J. A., Mennemeier M., Bartel T., Chelette K. C., Kimbrell T., Triggs W., Dornhoffer J. L. (2007). Repetitive transcranial magnetic stimulation for tinnitus: a pilot study. Laryngoscope 117, 529–53410.1097/MLG.0b013e31806009fe
    1. Vanneste S., De Ridder D. (2011). Bifrontal transcranial direct current stimulation modulates tinnitus intensity and tinnitus-distress-related brain activity. Eur. J. Neurosci. 34, 605–61410.1111/j.1460-9568.2011.07778.x
    1. Vanneste S., Focquaert F., Van De Heyning P., De Ridder D. (2011). Different resting state brain activity and functional connectivity in patients who respond and not respond to bifrontal tDCS for tinnitus suppression. Exp. Brain Res. 210, 217–22710.1007/s00221-011-2617-z
    1. Vanneste S., Plazier M., Der Loo E., De Heyning P. V., Congedo M., De Ridder D. (2010a). The neural correlates of tinnitus-related distress. Neuroimage 52, 470–48010.1016/j.neuroimage.2010.04.029
    1. Vanneste S., Plazier M., Ost J., Van Der Loo E., Van De Heyning P., De Ridder D. (2010b). Bilateral dorsolateral prefrontal cortex modulation for tinnitus by transcranial direct current stimulation: a preliminary clinical study. Exp. Brain Res. 202, 779–78510.1007/s00221-010-2183-9
    1. Voisin J., Bidet-Caulet A., Bertrand O., Fonlupt P. (2006). Listening in silence activates auditory areas: a functional magnetic resonance imaging study. J. Neurosci. 26, 273–27810.1523/JNEUROSCI.2967-05.2006
    1. Weisz N., Dohrmann K., Elbert T. (2007a). The relevance of spontaneous activity for the coding of the tinnitus sensation. Prog. Brain Res. 166, 61–7010.1016/S0079-6123(07)66006-3
    1. Weisz N., Muller S., Schlee W., Dohrmann K., Hartmann T., Elbert T. (2007b). The neural code of auditory phantom perception. J. Neurosci. 27, 1479–148410.1523/JNEUROSCI.3711-06.2007

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