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

Abstract

BackgroundSeveral 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/designThis 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.DiscussionThis 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 registrationClinical Trials: NCT01663324

Involvement of cortico-subcortical circuits in normoacousic chronic tinnitus: A source localization EEG study

“…Our data suggest a hyperexcitabihty of the thalamo-cortical circuits involving the left inferior temporal and parietal lobules, as revealed by the resting-state and ERPs analyses. These results could be used to personalize treatment options in these subjects, especially using repetitive transcranial magnetic stimulation, which has shown benefits in tinnitus sufferers (Plewnia et al, 2003;De Ridder et al, 2006;Vanneste et al, 2011;Lehner et al, 2013). Indeed, the results we obtained in the opened eyes condition could be of particular interest to improve rTMS protocols in tinnitus.…”

Individualized Repetitive Transcranial Magnetic Stimulation Treatment in Chronic Tinnitus?

“…Descriptive analyses indicate a remarkable superior effect of the individualized treatment in contrast to standard treatment even if the standard treatment with two or three stimulation sites was shown to be more effective than single-site stimulations (36, 66, 67, 69). Individualized rTMS in chronic tinnitus might provide a basis for an individualized, “tailored” rTMS-based therapeutic approach also in other neuropsychiatric disorders.…”

“…Patients who experienced tinnitus improvement in the testing session might have developed higher expectations with respect to the daily treatment, which could have contributed to the better outcome. However, active control conditions have especially been recommended in rTMS studies due to the inherent limitations of sham conditions (36, 66, 67). For future studies using this individualized approach, we would suggest the splitting of the patients reporting changes in tinnitus perception into two arms—one arm treated with the individualized protocol and one arm treated with a standard protocol.…”

Combined transcranial magnetic stimulation in the treatment of chronic tinnitus

“…In general, TMS protocols with <1 Hz frequency are considered inhibitory protocols and used mostly for the treatment of tinnitus . An increasing amount of data also suggest that the efficacy of rTMS therapy in tinnitus can be enhanced by stimulating frontal or prefrontal cortical areas in addition to the temporoparietal cortex . These results are in line with increased functional connectivity between frontal and temporal cortical areas in tinnitus patients on imaging …”