Comparing single-site with multisite rTMS for the treatment of chronic tinnitus - clinical effects and neuroscientific insights: study protocol for a randomized controlled trial

Astrid Lehner, Martin Schecklmann, Peter M Kreuzer, Timm B Poeppl, Rainer Rupprecht, Berthold Langguth, Astrid Lehner, Martin Schecklmann, Peter M Kreuzer, Timm B Poeppl, Rainer Rupprecht, Berthold Langguth

Abstract

Background: Several years ago, repetitive transcranial magnetic stimulation (rTMS) of the auditory cortex has been introduced as a treatment approach for chronic tinnitus. Even if this treatment is beneficial for a subgroup of patients, the overall effects are limited. This limitation may be due to the fact that the auditory cortex is only one of several brain areas involved in tinnitus. Whereas auditory areas are considered to code for tinnitus loudness, conscious perception of and attention allocation to tinnitus is supposed to be reflected by network activity involving frontal and parietal cortical areas. The aim of the present study is to influence this frontoparietal network more efficiently by perturbing the most important nodes with rTMS.

Methods/design: This is a randomized, double-blind, parallel-group study. Patients receive rTMS treatment on 10 consecutive working days using either the multisite rTMS protocol (left dorsolateral prefrontal, 1,000 stimuli, 20 Hz; left temporoparietal, 1,000 stimuli, 1 Hz; right temporoparietal stimulation, 1,000 stimuli, 1 Hz) or a single-site protocol (unilateral stimulation of the temporoparietal cortex, 3,000 stimuli, 1 Hz). Individuals aged 18 to 70 years with chronic tinnitus ≥6-month duration and a Tinnitus Handicap Inventory score ≥38 are recruited for the study. A total of 50 patients are needed to detect a clinical relevant change of tinnitus severity (α = 0.05; 1 - β = 0.80). Primary outcome measures are the change in the Tinnitus Questionnaire score from baseline to the end of treatment as well as the number of treatment responders as defined by a reduction in the Tinnitus Questionnaire score of ≥5 points. Furthermore, changes in brain structure and activity are assessed using (functional) magnetic resonance imaging and electroencephalography in the resting state. Those measurements are also performed in 25 healthy control subjects.

Discussion: This study is designed to reveal whether network stimulation is superior to single-site stimulation in the treatment of chronic tinnitus. Furthermore, the comparison between tinnitus patients and healthy controls and the longitudinal effects of both rTMS treatment protocols on brain structure and function allow inferences to be made about the neural correlates of tinnitus.

Trial registration: Clinical Trials: NCT01663324.

Figures

Figure 1
Figure 1
Visit schedule. EEG, electroencephalography; (f)MRI, (functional) magnetic resonance imaging; rTMS, repetitive transcranial magnetic stimulation.

References

    1. Hoffman HJ, Reed GW. In: Tinnitus: Theory and Management. Snow JB, editor. Lewiston, NY: BC Decker Inc; 2004. Epidemiology of tinnitus; pp. 16–41.
    1. Langguth B. A review of tinnitus symptoms beyond ‘ringing in the ears’: a call to action. Curr Med Res Opin. 2011;27:1635–1643. doi: 10.1185/03007995.2011.595781.
    1. Kaltenbach JA, Godfrey DA. Dorsal cochlear nucleus hyperactivity and tinnitus: are they related? Am J Audiol. 2008;17:148–161. doi: 10.1044/1059-0889(2008/08-0004).
    1. Melcher JR, Sigalovsky IS, Guinan JJ Jr, Levine RA. Lateralized tinnitus studied with functional magnetic resonance imaging: abnormal inferior colliculus activation. J Neurophysiol. 2000;83:1058–1072.
    1. Arnold W, Bartenstein P, Oestreicher E, Romer W, Schwaiger M. Focal metabolic activation in the predominant left auditory cortex in patients suffering from tinnitus: a PET study with [18F]deoxyglucose. ORL J Otorhinolaryngol Relat Spec. 1996;58:195–199. doi: 10.1159/000276835.
    1. Adjamian P, Sereda M, Hall DA. The mechanisms of tinnitus: perspectives from human functional neuroimaging. Hear Res. 2009;253:15–31. doi: 10.1016/j.heares.2009.04.001.
    1. Lanting CP, de Kleine E, van Dijk P. Neural activity underlying tinnitus generation: results from PET and fMRI. Hear Res. 2009;255:1–13. doi: 10.1016/j.heares.2009.06.009.
    1. Roberts LE, Eggermont JJ, Caspary DM, Shore SE, Melcher JR, Kaltenbach JA. Ringing ears: the neuroscience of tinnitus. J Neurosci. 2010;30:14972–14979. doi: 10.1523/JNEUROSCI.4028-10.2010.
    1. Weisz N, Dohrmann K, Elbert T. The relevance of spontaneous activity for the coding of the tinnitus sensation. Prog Brain Res. 2007;166:61–70.
    1. Eichhammer P, Langguth B, Marienhagen J, Kleinjung T, Hajak G. Neuronavigated repetitive transcranial magnetic stimulation in patients with tinnitus: a short case series. Biol Psychiatry. 2003;54:862–865. doi: 10.1016/S0006-3223(02)01896-6.
    1. Kleinjung T, Eichhammer P, Langguth B, Jacob P, Marienhagen J, Hajak G, Wolf SR, Strutz J. Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus. Otolaryngol Head Neck Surg. 2005;132:566–569. doi: 10.1016/j.otohns.2004.09.134.
    1. Plewnia C. Brain stimulation: new vistas for the exploration and treatment of tinnitus. CNS Neurosci Ther. 2011;17:449–461. doi: 10.1111/j.1755-5949.2010.00169.x.
    1. Plewnia C, Vonthein R, Wasserka B, Arfeller C, Naumann A, Schraven SP, Plontke SK. Treatment of chronic tinnitus with theta burst stimulation: a randomized controlled trial. Neurol. 2012;78:1628–1634. doi: 10.1212/WNL.0b013e3182574ef9.
    1. Kleinjung T, Langguth B. Strategies for enhancement of transcranial magnetic stimulation effects in tinnitus patients. Int Tinnitus J. 2009;15:154–160.
    1. Burton H, Wineland A, Bhattacharya M, Nicklaus J, Garcia KS, Piccirillo JF. Altered networks in bothersome tinnitus: a functional connectivity study. BMC Neurosci. 2012;13:3. doi: 10.1186/1471-2202-13-3.
    1. Maudoux A, Lefebvre P, Cabay JE, Demertzi A, Vanhaudenhuyse A, Laureys S, Soddu A. Auditory resting-state network connectivity in tinnitus: a functional MRI study. PLoS One. 2012;7:e36222. doi: 10.1371/journal.pone.0036222.
    1. Schlee W, Hartmann T, Langguth B, Weisz N. Abnormal resting-state cortical coupling in chronic tinnitus. BMC Neurosci. 2009;10:11. doi: 10.1186/1471-2202-10-11.
    1. Schlee W, Mueller N, Hartmann T, Keil J, Lorenz I, Weisz N. Mapping cortical hubs in tinnitus. BMC Biol. 2009;7:80. doi: 10.1186/1741-7007-7-80.
    1. Schlee W, Weisz N, Bertrand O, Hartmann T, Elbert T. Using auditory steady state responses to outline the functional connectivity in the tinnitus brain. PLoS One. 2008;3:e3720. doi: 10.1371/journal.pone.0003720.
    1. De Ridder D, Elgoyhen AB, Romo R, Langguth B. Phantom percepts: tinnitus and pain as persisting aversive memory networks. Proc Natl Acad Sci U S A. 2011;108:8075–8080. doi: 10.1073/pnas.1018466108.
    1. Lehner A, Schecklmann M, Poeppl TB, Kreuzer PM, Vielsmeier V, Rupprecht R, Landgrebe M, Langguth B. Multisite rTMS for the treatment of chronic tinnitus: stimulation of the cortical tinnitus network – a pilot study. Brain Topogr. 2013;26:501–510. doi: 10.1007/s10548-012-0268-4.
    1. Goebel G, Hiller W. The tinnitus questionnaire. A standard instrument for grading the degree of tinnitus. Results of a multicenter study with the tinnitus questionnaire. HNO. 1994;42:166–172.
    1. Langguth B, Goodey R, Azevedo A, Bjorne A, Cacace A, Crocetti A, Del Bo L, De Ridder D, Diges I, Elbert T, Flor H, Herraiz C, Ganz Sanchez T, Eichhammer P, Figueiredo R, Hajak G, Kleinjung T, Landgrebe M, Londero A, Lainez MJ, Mazzoli M, Meikle MB, Melcher J, Rauschecker JP, Sand PG, Struve M, Van de Heyning P, Van Dijk P, Vergara R. Consensus for tinnitus patient assessment and treatment outcome measurement: tinnitus research initiative meeting, Regensburg, July 2006. Prog Brain Res. 2007;166:525.
    1. Hallam RS, Jakes SC, Hinchcliffe R. Cognitive variables in tinnitus annoyance. Br J Clin Psychol. 1988;27(Pt 3):213–222.
    1. Nelting M, Finlayson NK. Geräuschüberempfindlichkeits-Fragebogen (GÜF) Göttingen: Hogrefe; 2004.
    1. Khedr EM, Abo-Elfetoh N, Rothwell JC, El-Atar A, Sayed E, Khalifa H. Contralateral versus ipsilateral rTMS of temporoparietal cortex for the treatment of chronic unilateral tinnitus: comparative study. Eur J Neurol. 2010;17:976–983. doi: 10.1111/j.1468-1331.2010.02965.x.
    1. Rossi S, De Capua A, Ulivelli M, Bartalini S, Falzarano V, Filippone G, Passero S. Effects of repetitive transcranial magnetic stimulation on chronic tinnitus: a randomised, crossover, double blind, placebo controlled study. J Neurol Neurosurg Psychiatry. 2007;78:857–863. doi: 10.1136/jnnp.2006.105007.
    1. Hoffman RE, Boutros NN, Berman RM, Roessler E, Belger A, Krystal JH, Charney DS. Transcranial magnetic stimulation of left temporoparietal cortex in three patients reporting hallucinated ‘voices’. Biol Psychiatry. 1999;46:130–132. doi: 10.1016/S0006-3223(98)00358-8.
    1. Jasper HH. The ten-twenty electrode system of the international federation. Electroencephalogr Clin Neurophysiol. 1958;10:371–375.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi