Brain stimulation-induced neuroplasticity underlying therapeutic response in phantom sounds.

Noninvasive brain stimulation can modify phantom sounds for longer periods by modulating neural activity and putatively inducing regional neuroplastic changes. However, treatment response is limited and there are no good demographic or clinical predictors for treatment outcome. We used state-of-the-art voxel-based morphometry (VBM) to investigate whether transcranial magnetic stimulation-induced neuroplasticity determines therapeutic outcome. Sixty subjects chronically experiencing phantom sounds (i.e., tinnitus) received repetitive transcranial magnetic stimulation (rTMS) of left dorsolateral prefrontal and temporal cortex according to a protocol that has been shown to yield a significantly higher number of treatment responders than sham stimulation and previous stimulation protocols. Structural magnetic resonance imaging was performed before and after rTMS. In VBM whole-brain analyses (P < 0.05, FWE corrected), we assessed longitudinal gray matter changes as well as structural connectivity between the ensuing regions. We observed longitudinal mesoscopic gray matter changes of left dorsolateral prefontal (DLPFC), left operculo-insular, and right inferior temporal cortex (ITC) in responders (N = 22) but not nonresponders (N = 38), as indicated by a group × time interaction and post-hoc tests. These results were neither influenced by age, sex, hearing loss nor by tinnitus laterality, duration, and severity at baseline. Furthermore, we found robust DLPFC-insula and insula-ITC connectivity in responders, while only relatively weak DLPFC-insula connectivity and no insula-ITC connectivity could be demonstrated in nonresponders. Our results reinforce the implication of nonauditory brain regions in phantom sounds and suggest the dependence of therapeutic response on their neuroplastic capabilities. The latter in turn may depend on (differences in) their individual structural connectivity. Hum Brain Mapp 39:554-562, 2018. © 2017 Wiley Periodicals, Inc.

A proof-of-concept study on the combination of repetitive transcranial magnetic stimulation and relaxation techniques in chronic tinnitus.

Interference of ongoing neuronal activity and brain stimulation motivated this study to combine repetitive transcranial magnetic stimulation (rTMS) and relaxation techniques in tinnitus patients. Forty-two patients were enrolled in this one-arm proof-of-concept study to receive ten sessions of rTMS applied to the left dorsolateral prefrontal cortex and temporo-parietal cortex. During stimulation, patients listened to five different kinds of relaxation audios. Variables of interest were tinnitus questionnaires, tinnitus numeric rating scales, depressivity, and quality of life. Results were compared to results of historical control groups having received the same rTMS protocol (active control) and sham treatment (placebo) without relaxation techniques. Thirty-eight patients completed the treatment, drop-out rates and adverse events were low. Responder rates (reduction in tinnitus questionnaire (TQ) score ≥5 points 10 weeks after treatment) were 44.7 % in the study, 27.8 % in the active control group, and 21.7 % in the placebo group, differing between groups on a near significant level. For the tinnitus handicap inventory (THI), the main effect of group was not significant. However, linear mixed model analyses showed that the relaxation/rTMS group differed significantly from the active control group showing steeper negative THI trend for the relaxation/rTMS group indicating better amelioration over the course of the trial. Deepness of relaxation during rTMS and selection of active relaxation vs. passive listening to music predicted larger TQ. All remaining secondary outcomes turned out non-significant. This combined treatment proved to be a safe, feasible and promising approach to enhance rTMS treatment effects in chronic tinnitus.

Structural brain changes following left temporal low-frequency rTMS in patients with subjective tinnitus.

Repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been used to treat patients with subjective tinnitus. While rTMS is known to induce morphological changes in healthy subjects, no study has investigated yet whether rTMS treatment induces grey matter (GM) changes in tinnitus patients as well, whether these changes are correlated with treatment success, and whether GM at baseline is a useful predictor for treatment outcome. Therefore, we examined magnetic resonance images of 77 tinnitus patients who were treated with rTMS of the left temporal cortex (10 days, 2000 stimuli/day, 1 Hz). At baseline and after the last treatment session high-resolution structural images of the brain were acquired and tinnitus severity was assessed. For a subgroup of 41 patients, additional brain scans were done after a follow-up period of 90 days. GM changes were analysed by means of voxel based morphometry. Transient GM decreases were detectable in several brain regions, especially in the insula and the inferior frontal cortex. These changes were not related to treatment outcome though. Baseline images correlated with change in tinnitus severity in the frontal cortex and the lingual gyrus, suggesting that GM at baseline might hold potential as a possible predictor for treatment outcome.

Reduced variability of auditory alpha activity in chronic tinnitus.

Subjective tinnitus is characterized by the conscious perception of a phantom sound which is usually more prominent under silence. Resting state recordings without any auditory stimulation demonstrated a decrease of cortical alpha activity in temporal areas of subjects with an ongoing tinnitus perception. This is often interpreted as an indicator for enhanced excitability of the auditory cortex in tinnitus. In this study we want to further investigate this effect by analysing the moment-to-moment variability of the alpha activity in temporal areas. Magnetoencephalographic resting state recordings of 21 tinnitus subjects and 21 healthy controls were analysed with respect to the mean and the variability of spectral power in the alpha frequency band over temporal areas. A significant decrease of auditory alpha activity was detected for the low alpha frequency band (8-10 Hz) but not for the upper alpha band (10-12 Hz). Furthermore, we found a significant decrease of alpha variability for the tinnitus group. This result was significant for the lower alpha frequency range and not significant for the upper alpha frequencies. Tinnitus subjects with a longer history of tinnitus showed less variability of their auditory alpha activity which might be an indicator for reduced adaptability of the auditory cortex in chronic tinnitus.

Multisite rTMS for the treatment of chronic tinnitus: stimulation of the cortical tinnitus network--a pilot study.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the auditory cortex has been shown to significantly reduce tinnitus severity in some patients. There is growing evidence that a neural network of both auditory and non-auditory cortical areas is involved in the pathophysiology of chronic subjective tinnitus. Targeting several core regions of this network by rTMS might constitute a promising strategy to enhance treatment effects. This study intends to test the effects of a multisite rTMS protocol on tinnitus severity. 45 patients with chronic tinnitus were treated with multisite stimulation (left dorsolateral prefrontal, 2,000 stimuli, 20 Hz; left temporoparietal, 1,000 stimuli, 1 Hz; right temporoparietal, 1,000 stimuli, 1 Hz). Results were compared with a historical control group consisting of 29 patients who received left temporal stimulation (2,000 stimuli, 1 Hz). Both groups were treated on ten consecutive working days. Tinnitus severity was assessed at three time points: at baseline, after the last treatment session (day 12) and after a follow-up period of 90 days. A change of tinnitus severity over time was tested using repeated measures ANOVA with the between-subjects factor treatment group. Both groups improved similarly from baseline to day 12. However, there was a difference on day 90: the multisite stimulation group showed an overall improvement whereas patients receiving temporal stimulation returned to their baseline level of tinnitus severity. These pilot data suggest that multisite rTMS is superior to temporal rTMS and represents a promising strategy for enhancing treatment effects of rTMS in tinnitus. Future studies should explore this new protocol with respect to clinical and neurobiological effects in more detail.

Cognitive Behavioral Group Therapy for Chronic Tinnitus in a German Tertiary Clinical Real-World Setting.

Cognitive behavioral therapy (CBT) was shown to be effective in reducing tinnitus-related distress in numerous controlled trials. Real-world data from tinnitus treatment centers are an important addition to controlled trials for demonstrating the ecological validity of the results from the randomized controlled trials. Thus, we provided the real-world data of 52 patients participating in CBT group therapies during the time period from 2010 to 2019. The groups consisted of five to eight patients with typical CBT content such as counseling, relaxation, cognitive restructuring, attention training, etc. applied through 10-12 weekly sessions. The mini tinnitus questionnaire, different tinnitus numeric rating scales and the clinical global impression were assessed in a standardized way and were analyzed retrospectively. All outcome variables showed clinically relevant changes from before to after the group therapy, which were still evident in the follow-up visit after three months. Amelioration of distress was correlated to all numeric rating scales, including tinnitus loudness but not annoyance. The observed positive effects were in a similar range as effects of controlled and uncontrolled studies. Somewhat unexpected was the observed reduction in loudness, which was associated with distress and the missing association of changes in distress with annoyance as it is generally assumed that standard CBT concepts reduce annoyance and distress, but not tinnitus loudness. Apart from confirming the therapeutic effectiveness of CBT in real-world settings, our results highlight the need for a clear definition/operationalization of outcome measures when investigating psychological interventions of tinnitus.

The more the merrier? Preliminary results regarding treatment duration and stimulation frequency of multisite repetitive transcranial magnetic stimulation in chronic tinnitus.

The current study examines two different protocols of repetitive transcranial magnetic stimulation (rTMS) targeting three key hubs of cortical tinnitus networks. Patients chose whether they preferred to undergo rTMS treatment for 10 or 20 sessions and were randomized to the different rTMS protocols thereafter. Ninety patients were enrolled in the study with a total dropout rate of 10%. Both rTMS protocols were well tolerated by the patients without any serious adverse events. Overall treatment effects were small both for 2 weeks and 4 weeks of treatment. There was no significant interaction effect between measurement time point and treatment group for neither of the outcome measures nor any differences regarding the applied treatment regimens. The effects of this study contradict former observations suggesting multisite rTMS protocols as promising neuromodulatory strategies. This lack of effect could not be enhanced by increasing the number of treatment sessions in our study.

Towards a unification of treatments and interventions for tinnitus patients: The EU research and innovation action UNITI.

Tinnitus is the perception of a phantom sound and the patient's reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden, with an estimated prevalence of 10%-20% among the adult population. The EU is funding a new collaborative project entitled "Unification of Treatments and Interventions for Tinnitus Patients" (UNITI, grant no. 848261) under its Horizon 2020 framework. The main goal of the UNITI project is to set the ground for a predictive computational model based on existing and longitudinal data attempting to address the question of which treatment or combination of treatments is optimal for a specific patient group based on certain parameters. Clinical, epidemiological, genetic and audiological data, including signals reflecting ear-brain communication, as well as patients' medical history, will be analyzed making use of existing databases. Predictive factors for different patient groups will be extracted and their prognostic relevance validated through a Randomized Clinical Trial (RCT) in which different patient groups will undergo a combination of tinnitus therapies targeting both auditory and central nervous systems. From a scientific point of view, the UNITI project can be summarized into the following research goals: (1) Analysis of existing data: Results of existing clinical studies will be analyzed to identify subgroups of patients with specific treatment responses and to identify systematic differences between the patient groups at the participating clinical centers. (2) Genetic and blood biomarker analysis: High throughput Whole Exome Sequencing (WES) will be performed in well-characterized chronic tinnitus cases, together with Proximity Extension Assays (PEA) for the identification of blood biomarkers for tinnitus. (3) RCT: A total of 500 patients will be recruited at five clinical centers across Europe comparing single treatments against combinational treatments. The four main treatments are Cognitive Behavioral Therapy (CBT), hearing aids, sound stimulation, and structured counseling. The consortium will also make use of e/m-health applications for the treatment and assessment of tinnitus. (4) Decision Support System: An innovative Decision Support System will be implemented, integrating all available parameters (epidemiological, clinical, audiometry, genetics, socioeconomic and medical history) to suggest specific examinations and the optimal intervention strategy based on the collected data. (5) Financial estimation analysis: A cost-effectiveness analysis for the respective interventions will be calculated to investigate the economic effects of the interventions based on quality-adjusted life years. In this paper, we will present the UNITI project, the scientific questions that it aims to address, the research consortium, and the organizational structure.

Staying Connected: Reaching Out to Psychiatric Patients During the Covid-19 Lockdown Using an Online Blog.

Health systems worldwide are challenged by the coronavirus pandemic and all medical specialties have struggle to meet the conflicting requirements for virus containment on the one hand and treatment of other medical conditions on the other. This holds true also for psychiatry. Per se, psychiatric patients are highly vulnerable to suffer from social isolation and loneliness. As a result of the Covid-19 pandemic and lockdown measures, unfortunately, this vulnerability is even further increased. As a part of its pandemic risk management, the outpatient clinic of the Psychiatric District Hospital Regensburg launched an online blog as a means of assisting patients who were required to stay home. Aim of the blog was to stay by patients' side in those uncertain times by offering an online connection to their therapists, by providing important information about the pandemic situation, by offering some ideas on how to build a daily routine and how to meaningfully spend their time at home during the lockdown. We also aimed at involving patients as experts in their own affairs by inviting them to contribute to the blog's shape and content. As a result of coordinated team effort, it was possible to launch a blog within few days, and this was perceived helpful by many patients. Overall, however, patient involvement turned out to be a challenge requiring more attention in future work.

Changes in Subjective-Objective Sleep Discrepancy Following Inpatient Cognitive Behavior Therapy for Insomnia.

Discrepancy between objective and subjective sleep parameters is a frequent symptom in persons suffering from insomnia. Since it has an impairing effect on daytime well-being and neglects possible positive objective improvements, it would be useful if it was treated. Apart from hypnotics, cognitive behavior therapy (CBT-I) is the therapy of choice for chronic forms of insomnia. However, there is limited information about whether CBT-I can also improve subjective-objective sleep discrepancy. We investigated a large sample of patients showing chronic forms of insomnia regarding their subjective-objective sleep discrepancy pre and post CBT-I. Objective sleep data were obtained from 3 nights (2 baseline nights and 1 night after therapy) using polysomnography in our sleep laboratory. All 92 patients participated in a 14-day inpatient program with CBT-I including psychoeducation about subjective-objective sleep discrepancy. Repeated measures analyses showed an improvement in subjective-objective sleep discrepancy parameters after CBT-I. Those parameters were also correlated with perceived quality of sleep. We conclude that CBT-I is a useful tool to improve subjective-objective sleep discrepancy in patients showing chronic forms of insomnia.

Daily high-frequency transcranial random noise stimulation of bilateral temporal cortex in chronic tinnitus - a pilot study.

Several studies emphasized the potential of single and multiple transcranial random noise stimulation (tRNS) sessions to interfere with auditory cortical activity and to reduce tinnitus loudness. It was the objective of the present study to evaluate the use of high-frequency (hf) tRNS in a one-arm pilot study in patients with chronic tinnitus. Therefore, 30 patients received 10 sessions of high frequency tRNS (100-640 Hz; 2 mA; 20 minutes) over the bilateral temporal cortex. All patients had received rTMS treatment for their tinnitus at least 3 months before tRNS. Primary outcome was treatment response (tinnitus questionnaire reduction of ≥5 points). The trial was registered at clinicaltrials.gov (NCT01965028). Eight patients (27%) responded to tRNS. Exactly the same number of patients had responded before to rTMS, but there were only two "double responders" for both treatments. None of the secondary outcomes (tinnitus numeric rating scales, depressivity, and quality of life) was significant when results were corrected for multiple comparisons. tRNS treatment was accompanied by tolerable side effects but resulted in temporal increases in tinnitus loudness in 20% of the cases (2 drop-outs). Our trial showed that hf-tRNS is feasible for daily treatment in chronic tinnitus. However, summarizing low treatment response, increase of tinnitus loudness in 20% of patients and missing of any significant secondary outcome, the use of hf-tRNS as a general treatment for chronic tinnitus cannot be recommended at this stage. Differences in treatment responders between tRNS and rTMS highlight the need for individualized treatment procedures.

A Pilot Study of Peripheral Muscle Magnetic Stimulation as Add-on Treatment to Repetitive Transcranial Magnetic Stimulation in Chronic Tinnitus.

While brain stimulation techniques have been examined as treatment options for chronic tinnitus for many years, they have recently been extended to multimodal treatment approaches. As chronic tinnitus is often accompanied by comorbid muscular tension in the neck and back, we performed a one-arm pilot study to explore the feasibility of a new multimodal treatment approach. In detail, repetitive peripheral magnetic stimulation (rPMS) of the back was performed before and after each session of repetitive transcranial magnetic stimulation (rTMS) of the brain. Data of 41 patients were analyzed, all of which were treated with ten sessions of rTMS of the left prefrontal and left temporoparietal cortex followed by rPMS of the neck and back muscles. Tinnitus severity was measured using the tinnitus questionnaire (TQ). Neck pain was assessed using the neck pain and disability scale (NPAD). The new treatment approach was feasible and well accepted by the majority of patients. However, the overall patient group did not improve significantly in either of the questionnaires. If patients were divided in different subgroups depending on whether they were suffering from neck pain or somatosensory tinnitus, explorative post-hoc tests suggested differential effects: patients with both neck pain and somatosensory tinnitus had better outcomes than patients without those conditions or with neck pain only. This was true for both the TQ and the NPAD. This effect was of transient nature though: the TQ score went back to its baseline level after a follow-up period of 12 weeks. Based on our results we recommend that in studies that investigate tinnitus treatments targeting somatosensory afferents patients should be stratified according to somatic co-morbidities and somatosensory influence on the tinnitus percept. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT02306447.

Individualized Repetitive Transcranial Magnetic Stimulation Treatment in Chronic Tinnitus?

BACKGROUND: Prefrontal and temporo-parietal repetitive transcranial magnetic stimulation (rTMS) in patients suffering from chronic tinnitus have shown significant but only moderate effectiveness with high interindividual variability in treatment response. This open-label pilot study was designed to examine the general feasibility of an individualized fronto-temporal rTMS protocol and to explore what criteria are needed for a more detailed evaluation in randomized clinical studies. METHODS: During the first session of a 2-week rTMS protocol, we applied different rTMS protocols to the left and right temporo-parietal and dorsolateral prefrontal cortex (DLPFC) in 25 tinnitus patients. Short trains of 1, 5, 10, and 20 Hz and continuous theta burst stimulation were applied, and patients were asked for immediate tinnitus reductions after each train. If a patient reported such improvements, rTMS treatment was applied over nine sessions with a combined protocol consisting of the most effective frontal and the most effective temporo-parietal stimulation protocol. Those patients who did not improve after the test session were treated with a standard prefrontal plus temporo-parietal protocol (20 Hz over left DLPFC + 1 Hz over temporo-parietal cortex). RESULTS: Almost half of the patients (12 of 25) reported immediate tinnitus reductions during the test session. In this group, the mean pre- to post-treatment amelioration in the tinnitus questionnaire was higher (medium to high effect sizes) in contrast to the patients who did not respond to the test session. Treatment outcome remained stable over a follow-up period of 10 weeks. DISCUSSION: Individualized rTMS was shown to be feasible and effective in chronic tinnitus. The results obtained from this study provide tentative evidence in support of an individualized rTMS treatment approach and might provide a basis for a "tailored" application of rTMS in tinnitus and other neuropsychiatric disorders.

1-Hz rTMS in the treatment of tinnitus: A sham-controlled, randomized multicenter trial.

BACKGROUND: Chronic tinnitus is a frequent, difficult to treat disease with high morbidity. OBJECTIVE: This multicenter randomized, sham-controlled trial investigated the efficacy and safety of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal cortex in patients with chronic tinnitus. METHODS: Tinnitus patients were randomized to receive 10 sessions of either real or sham 1-Hz-rTMS (2000 stimuli, 110% motor threshold) to the left temporal cortex. The primary outcome was the change in the sum score of the tinnitus questionnaire (TQ) of Goebel and Hiller from baseline to end of treatment. RESULTS: A total of 163 patients were enrolled in the study (real rTMS: 75; sham rTMS: 78). At day 12, the baseline mean of 43.1 TQ points in 71 patients assigned to real rTMS changed by -0.5 points; it changed by 0.5 points from a baseline of 42.1 in 75 patients randomized to sham rTMS (adjusted mean difference between groups: -1.0; 95.19% confidence interval: -3.2 to 1.2; p = 0.36). All secondary outcome measures including measures of depression and quality of life showed no significant differences either (p > 0.11). The number of participants with side-effects or adverse events did not differ between groups. CONCLUSION: Real 1-Hz-rTMS over the left temporal cortex was well tolerated but not superior compared with sham rTMS in improving tinnitus severity. These findings are in contrast to results from studies with smaller sample sizes and put the efficacy of this rTMS protocol for treatment of chronic tinnitus into question. TRIAL REGISTRATION: Controlled Trials: http://www.isrctn.com/ISRCTN89848288.

Triple-site rTMS for the treatment of chronic tinnitus: a randomized controlled trial.

Recent research indicates that tinnitus is related to alterations of neural networks including temporal, parietal, and prefrontal brain regions. The current study examines a rTMS protocol which targets three central nodes of these networks in a two-arm randomized parallel group trial. Overall, 49 patients with chronic tinnitus were randomized to receive either triple-site stimulation (left dorsolateral prefrontal stimulation, 1000 pulses, 20 Hz plus left and right temporoparietal stimulation, 1000 pulses each, 1 Hz) or single-site stimulation (left temporoparietal stimulation, 3000 pulses, 1 Hz). Both groups were treated in ten sessions. Tinnitus severity as measured by the tinnitus questionnaire was assessed before rTMS (day1), after rTMS (day12) and at two follow-up visits (day 90 and day 180). The triple-site protocol was well tolerated. There was a significant reduction in tinnitus severity for both treatment groups. The triple-site group tended to show a more pronounced treatment effect at day 90. However, the measurement time point x group interaction effect was not significant. The current results confirm former studies that indicated a significant reduction of tinnitus severity after rTMS treatment. No significant superiority of the multisite protocol was observed. Future approaches for the enhancement of treatment effects are discussed.

Repetitive transcranial magnetic stimulation induces oscillatory power changes in chronic tinnitus.

Chronic tinnitus is associated with neuroplastic changes in auditory and non-auditory cortical areas. About 10 years ago, repetitive transcranial magnetic stimulation (rTMS) of auditory and prefrontal cortex was introduced as potential treatment for tinnitus. The resulting changes in tinnitus loudness are interpreted in the context of rTMS induced activity changes (neuroplasticity). Here, we investigate the effect of single rTMS sessions on oscillatory power to probe the capacity of rTMS to interfere with tinnitus-specific cortical plasticity. We measured 20 patients with bilateral chronic tinnitus and 20 healthy controls comparable for age, sex, handedness, and hearing level with a 63-channel electroencephalography (EEG) system. Educational level, intelligence, depressivity and hyperacusis were controlled for by analysis of covariance. Different rTMS protocols were tested: Left and right temporal and left and right prefrontal cortices were each stimulated with 200 pulses at 1 Hz and with an intensity of 60% stimulator output. Stimulation of central parietal cortex with 6-fold reduced intensity (inverted passive-cooled coil) served as sham condition. Before and after each rTMS protocol 5 min of resting state EEG were recorded. The order of rTMS protocols was randomized over two sessions with 1 week interval in between. Analyses on electrode level showed that people with and without tinnitus differed in their response to left temporal and right frontal stimulation. In tinnitus patients left temporal rTMS decreased frontal theta and delta and increased beta2 power, whereas right frontal rTMS decreased right temporal beta3 and gamma power. No changes or increases were observed in the control group. Only non-systematic changes in tinnitus loudness were induced by single sessions of rTMS. This is the first study to show tinnitus-related alterations of neuroplasticity that were specific to stimulation site and oscillatory frequency. The observed effects can be interpreted within the thalamocortical dysrhythmia model assuming that slow waves represent processes of deafferentiation and that high frequencies might be indicators for tinnitus loudness. Moreover our findings confirm the role of the left temporal and the right frontal areas as relevant hubs in tinnitus related neuronal network. Our results underscore the value of combined TMS-EEG measurements for investigating disease related changes in neuroplasticity.

Validation of Screening Questions for Hyperacusis in Chronic Tinnitus.

BACKGROUND: We investigated the validity of the two hyperacusis items of the TSCHQ (Tinnitus Sample Case History Questionnaire) from the TRI (Tinnitus Research Initiative) database by comparing them with the German hyperacusis questionnaire GÜF. METHODS: We investigated the association of the GÜF with the TSCHQ screening questions for both the sum score and the single items with correlation, contrast, principal component, and discriminant analysis in a sample of 161 patients with chronic tinnitus. RESULTS: TSCHQ items and the GÜF total score were significantly associated with a special focus on fear and pain related hyperacusis. Factor analysis of the GÜF revealed the three factors "fear and pain related hyperacusis," "hearing related problems," and "problems in quality of life." A discriminant analysis showed a sensitivity of 64% and a specificity of 71% of the TSCHQ items for the establishment of tinnitus patient subgroups with and without hyperacusis. DISCUSSION: Both hyperacusis TSCHQ items can serve as screening questions with respect to self-reported hyperacusis in chronic tinnitus with a specific focus on fear and pain related hyperacusis. However, the multiple dimensions of hyperacusis should be considered for diagnosis and treatment in both scientific and clinical contexts.

Efficacy and Safety of Repeated Courses of rTMS Treatment in Patients with Chronic Subjective Tinnitus.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has shown promising effects in the treatment of chronic subjective tinnitus. However, little is known about maintenance treatment in order to achieve long-lasting improvements. OBJECTIVE: This study addresses the questions whether the repeated application of rTMS treatment can contribute to the maintenance or enhancement of treatment effects and if so in which cases repetitive treatment courses are beneficial. METHODS: 55 patients with chronic tinnitus were treated with two rTMS treatment courses with ten treatment sessions each. The mean intertreatment interval was 20.65 ± 18.56 months. Tinnitus severity was assessed before and after each treatment course. RESULTS: Both treatments were well tolerated and caused significant improvement of tinnitus severity. The main predictor for the outcome of the second treatment was the development of tinnitus distress in the phase between both treatment courses: the more patients worsened in this interval, the more they improved during the second treatment course. CONCLUSION: Repeated application of rTMS seems to be useful in tinnitus management and should preferentially be offered to patients who experience a worsening of their tinnitus during the intertreatment interval, irrespective of their response to the first treatment course.

Combined rTMS treatment targeting the Anterior Cingulate and the Temporal Cortex for the Treatment of Chronic Tinnitus.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a tinnitus treatment option. Promising results have been obtained by consecutive stimulation of lateral frontal and auditory brain regions. We investigated a combined stimulation paradigm targeting the anterior cingulate cortex (ACC) with double cone coil rTMS, followed by stimulation of the temporo-parietal junction area with a figure-of-eight coil. The study was conducted as a randomized, double-blind pilot trial in 40 patients suffering from chronic tinnitus. We compared mediofrontal stimulation with double-cone-coil, (2000 stimuli, 10 Hz) followed by left temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz) to left dorsolateral-prefrontal-cortex stimulation with figure-of-eight-coil (2000 stimuli, 10 Hz) followed by temporo-parietal stimulation with figure-of-eight-coil (2000 stimuli, 1 Hz). The stimulation was feasible with comparable dropout rates in both study arms; no severe adverse events were registered. Responder rates did not differ in both study arms. There was a significant main effect of time for the change in the TQ score, but no significant time x group interaction. This pilot study demonstrated the feasibility of combined mediofrontal/temporoparietal-rTMS-stimulation with double cone coil in tinnitus patients but failed to show better outcome compared to an actively rTMS treated control group.

The Relevance of the High Frequency Audiometry in Tinnitus Patients with Normal Hearing in Conventional Pure-Tone Audiometry.

OBJECTIVE: The majority of tinnitus patients suffer from hearing loss. But a subgroup of tinnitus patients show normal hearing thresholds in the conventional pure-tone audiometry (125 Hz-8 kHz). Here we explored whether the results of the high frequency audiometry (>8 kHz) provide relevant additional information in tinnitus patients with normal conventional audiometry by comparing those with normal and pathological high frequency audiometry with respect to their demographic and clinical characteristics. SUBJECTS AND METHODS: From the database of the Tinnitus Clinic at Regensburg we identified 75 patients with normal hearing thresholds in the conventional pure-tone audiometry. We contrasted these patients with normal and pathological high-frequency audiogram and compared them with respect to gender, age, tinnitus severity, pitch, laterality and duration, comorbid symptoms and triggers for tinnitus onset. RESULTS: Patients with pathological high frequency audiometry were significantly older and had higher scores on the tinnitus questionnaires in comparison to patients with normal high frequency audiometry. Furthermore, there was an association of high frequency audiometry with the laterality of tinnitus. CONCLUSION: In tinnitus patients with normal pure-tone audiometry the high frequency audiometry provides useful additional information. The association between tinnitus laterality and asymmetry of the high frequency audiometry suggests a potential causal role for the high frequency hearing loss in tinnitus etiopathogenesis.