Repetitive transcranial magnetic stimulation for the treatment of chronic subjective tinnitus: Optimization of treatment effects

Subjective tinnitus is a highly prevalent and for many patients very debilitating condition for which there is still no cure. As tinnitus has been shown to be associated with changes of neural activity in different areas of the cortex, repetitive transcranial magnetic stimulation (rTMS) has been used as a treatment tool in order to interfere with these changes. Up to now, treatment success is limited and strategies to enhance treatment effects are clearly needed. The three studies of this cumulative dissertation address the question how rTMS treatment of patients suffering from chronic subjective tinnitus can be optimized. Study 1 tested whether treatment response was associated with grey matter (GM) changes and whether pre-treatment GM volume might be a potential predictor for treatment success. Although transient GM changes in the insulae and the bilateral inferior frontal cortex were observed, these changes were not correlated to treatment outcome. It was shown, however, that GM volume in the frontal cortex and the lingual gyrus might be possible predictors for treatment response. While traditionally, rTMS targeted the auditory cortex of tinnitus patients, study 2 and study 3 examined a new protocol which stimulated three sites successively in order to better interfere with cortical networks involved in tinnitus pathophysiology: the left dorsolateral prefrontal cortex and the left and right temporoparietal cortices. Study 2 was a pilot study which tested the new protocol in a one-arm open label study and compared the results with a historical control group of patients receiving traditional single-site stimulation. The results suggested that the triple-site protocol might show better long-term effects. As a consequence, the new protocol was explored in more detail in study 3 in order to replicate the result in a randomized controlled parallel group trial. In this study, the superiority of the multisite protocol was only seen on a descriptive but not on a statistical significant level. In a concluding discussion, the methods used in this work and future approaches for the enhancement of rTMS treatment effects are discussed

Grasping Virtual Objects Benefits Lower Aptitude Learners’ Acquisition of Foreign Language Vocabulary

Acknowledgements Special thanks go to the Ars Electronica Centre, Linz, and to co-workers who aided in the study implementation, particularly Christoph Kremer, Erika Mondria, and the staff of the Future Lab. Supported by the Johannes Kepler Open Access Publishing Fund. Funding Open access funding provided by Johannes Kepler University Linz.Peer reviewedPublisher PD

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

Abstract 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

Quantitative myocardial perfusion SPECT/CT for the assessment of myocardial tracer uptake in patients with three-vessel coronary artery disease: Initial experiences and results

BACKGROUND To evaluate quantitative myocardial perfusion SPECT/CT datasets for routine clinical reporting and the assessment of myocardial tracer uptake in patients with severe TVCAD. METHODS MPS scans were reconstructed as quantitative SPECT datasets using CTs from internal (SPECT/CT, Q_INT) and external (PET/CT, Q_EXT) sources for attenuation correction. TPD was calculated and compared to the TPD from non-quantitative SPECT datasets of the same patients. SUVmax, SUVpeak, and SUVmean were compared between Q_INT and Q_EXT SPECT datasets. Global SUVmax and SUVpeak were compared between patients with and without TVCAD. RESULTS Quantitative reconstruction was feasible. TPD showed an excellent correlation between quantitative and non-quantitative SPECT datasets. SUVmax, SUVpeak, and SUVmean showed an excellent correlation between Q_INT and Q_EXT SPECT datasets, though mean SUVmean differed significantly between the two groups. Global SUVmax and SUVpeak were significantly reduced in patients with TVCAD. CONCLUSIONS Absolute quantification of myocardial tracer uptake is feasible. The method seems to be robust and principally suitable for routine clinical reporting. Quantitative SPECT might become a valuable tool for the assessment of severe coronary artery disease in a setting of balanced ischemia, where potentially life-threatening conditions might otherwise go undetected

Predictors for rTMS response in chronic tinnitus

Background: Repetitive transcranial magnetic stimulation (rTMS) has been studied as a treatment option for chronic tinnitus for almost 10 years now. Although most of these studies have demonstrated beneficial effects, treatment results show high interindividual variability and yet, little is known about predictors for treatment response. Methods: Data from 538 patients with chronic tinnitus were analyzed. Patients received either low-frequency rTMS over the left temporal cortex (n = 345, 1 Hz, 110% motor threshold, 2000 stimuli/day) or combined temporal and frontal stimulation (n = 193, 110% motor threshold, 2000 stimuli at 20 Hz over left dorsolateral prefrontal cortex plus 2000 stimuli at 1 Hz over temporal cortex). Numerous demographic, clinical, and audiological variables as well as different tinnitus characteristics were analyzed as potential predictors for treatment outcome, which was defined as change in the tinnitus questionnaire (TQ) score. Results: Both stimulation protocols resulted in a significant decrease of TQ scores. Effect sizes were small, however. In the group receiving combined treatment, patients with comorbid temporomandibular complaints benefited more from rTMS than patients without those complaints. In addition, patients with higher TQ scores at baseline had more pronounced TQ reductions than patients with low TQ baseline scores. Also, patients who had already improved from screening to baseline benefited less than patients without initial improvement. Conclusions: The results from this large sample demonstrate that rTMS shows only small but clinically significant effects in the treatment of chronic tinnitus. There are no good demographic or clinical predictors for treatment outcome

Neuroimaging and Neuromodulation: Complementary Approaches for Identifying the Neuronal Correlates of Tinnitus

An inherent limitation of functional imaging studies is their correlational approach. More information about critical contributions of specific brain regions can be gained by focal transient perturbation of neural activity in specific regions with non-invasive focal brain stimulation methods. Functional imaging studies have revealed that tinnitus is related to alterations in neuronal activity of central auditory pathways. Modulation of neuronal activity in auditory cortical areas by repetitive transcranial magnetic stimulation (rTMS) can reduce tinnitus loudness and, if applied repeatedly, exerts therapeutic effects, confirming the relevance of auditory cortex activation for tinnitus generation and persistence. Measurements of oscillatory brain activity before and after rTMS demonstrate that the same stimulation protocol has different effects on brain activity in different patients, presumably related to interindividual differences in baseline activity in the clinically heterogeneous study cohort. In addition to alterations in auditory pathways, imaging techniques also indicate the involvement of non-auditory brain areas, such as the fronto-parietal “awareness” network and the non-tinnitus-specific distress network consisting of the anterior cingulate cortex, anterior insula, and amygdale. Involvement of the hippocampus and the parahippocampal region putatively reflects the relevance of memory mechanisms in the persistence of the phantom percept and the associated distress. Preliminary studies targeting the dorsolateral prefrontal cortex, the dorsal anterior cingulate cortex, and the parietal cortex with rTMS and with transcranial direct current stimulation confirm the relevance of the mentioned non-auditory networks. Available data indicate the important value added by brain stimulation as a complementary approach to neuroimaging for identifying the neuronal correlates of the various clinical aspects of tinnitus

Trauma-Associated Tinnitus: Audiological, Demographic and Clinical Characteristics

Background: Tinnitus can result from different etiologies. Frequently, patients report the development of tinnitus after traumatic injuries. However, to which extent this specific etiologic factor plays a role for the phenomenology of tinnitus is still incompletely understood. Additionally, it remains a matter of debate whether the etiology of tinnitus constitutes a relevant criterion for defining tinnitus subtypes. Objective: By investigating a worldwide sample of tinnitus patients derived from the Tinnitus Research Initiative (TRI) Database, we aimed to identify differences in demographic, clinical and audiological characteristics between tinnitus patients with and without preceding trauma. Materials: A total of 1,604 patients were investigated. Assessment included demographic data, tinnitus related clinical data, audiological data, the Tinnitus Handicap Inventory, the Tinnitus Questionnaire, the Beck Depression Inventory, various numeric tinnitus rating scales, and the World Health Organisation Quality of Life Scale (WHOQoL). Results: Our data clearly indicate differences between tinnitus patients with and without trauma at tinnitus onset. Patients suffering from trauma-associated tinnitus suffer from a higher mental burden than tinnitus patients presenting with phantom perceptions based on other or unknown etiologic factors. This is especially the case for patients with whiplash and head trauma. Patients with posttraumatic noise-related tinnitus experience more frequently hyperacousis, were younger, had longer tinnitus duration, and were more frequently of male gender. Conclusions: Trauma before tinnitus onset seems to represent a relevant criterion for subtypization of tinnitus. Patients with posttraumatic tinnitus may require specific diagnostic and therapeutic management. A more systematic and - at best - standardized assessment for hearing related sequelae of trauma is needed for a better understanding of the underlying pathophysiology and for developing more tailored treatment approaches as well.Fil: Kreuzer, Peter M.. Universitat Regensburg; AlemaniaFil: Landgrebe, Michael. Universitat Regensburg; AlemaniaFil: Schecklmann, Martin. Universitat Regensburg; AlemaniaFil: Staudinger, Susanne. Universitat Regensburg; AlemaniaFil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Vielsmeier, Veronika. The TRI Database Study Group; AlemaniaFil: Kleinjung, Tobias. The TRI Database Study Group; AlemaniaFil: Lehner, Astrid. The TRI Database Study Group; AlemaniaFil: Poeppl, Timm B.. The TRI Database Study Group; AlemaniaFil: Figueiredo, Ricardo. The TRI Database Study Group; AlemaniaFil: Azevedo, Andréia. The TRI Database Study Group; AlemaniaFil: Binetti, Ana Carolina. The TRI Database Study Group; AlemaniaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. The TRI Database Study Group; AlemaniaFil: Rates, Marcelo. The TRI Database Study Group; AlemaniaFil: Coelho, Claudia. The TRI Database Study Group; AlemaniaFil: Vanneste, Sven. The TRI Database Study Group; AlemaniaFil: de Ridder, Dirk. The TRI Database Study Group; AlemaniaFil: van de Heyning, Paul. The TRI Database Study Group; AlemaniaFil: Zeman, Florian. The TRI Database Study Group; AlemaniaFil: Mohr, Markus. The TRI Database Study Group; AlemaniaFil: Koller, Michael. The TRI Database Study Group; Alemani

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

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