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Background: Past research highlighted the benefits of personalized repetitive transcranial magnetic stimulation (rTMS) for the treatment of chronic subjective tinnitus. Objective/Hypothesis: The objective was to investigate the feasibility of rTMS personalization by identifying individually optimal stimulation parameters in test sessions. Particularly, effectiveness and retest-reliability of different stimulation parameters were examined. Methods: Via electric-field guided rTMS, five patients were stimulated with different frequencies on three positions of the left and right superior temporal gyrus on 2 separate days. After each stimulation, the patients had to evaluate tinnitus loudness and discomfort of the used protocol. Results: Individualization of rTMS was possible in all five patients. Significant lower tinnitus loudness was found for 1 Hz stimulation. Positive correlations between 2 days were observed for hemisphere (left, right), position (mSTG, pSTG), and frequency (1, 10, 20 Hz). High-frequency stimulation produced high discomfort. Conclusion: Personalization of rTMS is considered as feasible. Consistency of parameter-specific tinnitus suppression is demonstrated.

Introduction: Chronic tinnitus is a condition estimated to affect 10–15% of the population. No treatment has shown efficacy in randomized clinical trials to reliably and effectively suppress the phantom perceptions, and little is known why patients react differently to the same treatments. Tinnitus heterogeneity may play a central role in treatment response, but no study has tried to capture tinnitus heterogeneity in terms of treatment response. Research Goals: To test if the individualized treatment response can be predicted using personal, tinnitus, and treatment characteristics. Methods: A survey conducted by the web platform Tinnitus Hub collected data of 5017 tinnitus bearers. The participants reported which treatments they tried and the outcome of the given treatment. Demographic and tinnitus characteristics, alongside with treatment duration were used as predictors of treatment outcomes in both an univariate as well as a multivariate regression setup. First, simple linear regressions were used with each of the 13 predictors on all of 25 treatment outcomes to predict how much variance could be explained by each predictor individually. Then, all 13 predictors were added together in the elastic net regression to predict treatment outcomes. Results: Individual predictors from the linear regression models explained on average 2% of the variance of treatment outcome. “Duration of treatment” was the predictor that explained, on average, most of the variance, 6.8%. When combining all the predictors in the elastic net, the model could explain on average 16% of the deviance of treatment outcomes. Discussion: By demonstrating that different aspects predict response to various treatments, our results support the notion that tinnitus heterogeneity influences the observed variability in treatment response. Moreover, the data suggest the potential of personalized tinnitus treatment based on demographic and clinical characteristics. publishedVersion

Introduction: Chronic tinnitus is a condition estimated to affect 10–15% of the population. No treatment has shown efficacy in randomized clinical trials to reliably and effectively suppress the phantom perceptions, and little is known why patients react differently to the same treatments. Tinnitus heterogeneity may play a central role in treatment response, but no study has tried to capture tinnitus heterogeneity in terms of treatment response. Research Goals: To test if the individualized treatment response can be predicted using personal, tinnitus, and treatment characteristics. Methods: A survey conducted by the web platform Tinnitus Hub collected data of 5017 tinnitus bearers. The participants reported which treatments they tried and the outcome of the given treatment. Demographic and tinnitus characteristics, alongside with treatment duration were used as predictors of treatment outcomes in both an univariate as well as a multivariate regression setup. First, simple linear regressions were used with each of the 13 predictors on all of 25 treatment outcomes to predict how much variance could be explained by each predictor individually. Then, all 13 predictors were added together in the elastic net regression to predict treatment outcomes. Results: Individual predictors from the linear regression models explained on average 2% of the variance of treatment outcome. “Duration of treatment” was the predictor that explained, on average, most of the variance, 6.8%. When combining all the predictors in the elastic net, the model could explain on average 16% of the deviance of treatment outcomes. Discussion: By demonstrating that different aspects predict response to various treatments, our results support the notion that tinnitus heterogeneity influences the observed variability in treatment response. Moreover, the data suggest the potential of personalized tinnitus treatment based on demographic and clinical characteristics.

Background: Past research highlighted the benefits of personalized repetitive transcranial magnetic stimulation (rTMS) for the treatment of chronic subjective tinnitus. Objective/Hypothesis: The objective was to investigate the feasibility of rTMS personalization by identifying individually optimal stimulation parameters in test sessions. Particularly, effectiveness and retest–reliability of different stimulation parameters were examined. Methods: Via electric-field guided rTMS, five patients were stimulated with different frequencies on three positions of the left and right superior temporal gyrus on 2 separate days. After each stimulation, the patients had to evaluate tinnitus loudness and discomfort of the used protocol. Results: Individualization of rTMS was possible in all five patients. Significant lower tinnitus loudness was found for 1 Hz stimulation. Positive correlations between 2 days were observed for hemisphere (left, right), position (mSTG, pSTG), and frequency (1, 10, 20 Hz). High-frequency stimulation produced high discomfort. Conclusion: Personalization of rTMS is considered as feasible. Consistency of parameter-specific tinnitus suppression is demonstrated.

Tinnitus can be a burdensome condition on both individual and societal levels. Many aspects of this condition remain elusive, including its underlying mechanisms, ultimately hindering the development of a cure. Interdisciplinary approaches are required to overcome long-established research challenges. This review summarizes current knowledge in various tinnitus-relevant research fields including tinnitus generating mechanisms, heterogeneity, epidemiology, assessment, and treatment development, in an effort to highlight the main challenges and provide suggestions for future research to overcome them. Four common themes across different areas were identified as future research direction: (1) Further establishment of multicenter and multidisciplinary collaborations; (2) Systematic reviews and syntheses of existing knowledge; (3) Standardization of research methods including tinnitus assessment, data acquisition, and data analysis protocols; (4) The design of studies with large sample sizes and the creation of large tinnitus-specific databases that would allow in-depth exploration of tinnitus heterogeneity.

Over the past few years extensive body of research was produced investigating the effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of chronic tinnitus with heterogeneous results. This heterogeneity is exemplified by two recently published large-scale clinical trials reporting different outcomes. Technical aspects of rTMS were suspected as a potential source for this incongruency. The aim of this systematic review is to examine the overall efficacy as well as to identify possible technical factors relevant for the effectiveness of rTMS tinnitus trials. Via a literature search appropriate original research papers were identified and rTMS parameters were extracted from each study arm for subsequent statistical analysis with respect to observed effects (significant vs. not significant pre-post rTMS effects). Our findings indicate that verum rTMS is superior to sham rTMS as demonstrated by the proportion of significant pre-post contrasts. Some relevant rTMS parameters (e.g., pulse waveform) are not reported. Lower rTMS stimulation intensity was associated with significant effects in verum rTMS arms. An additional stimulation of the DLPFC to the temporal cortex was not found to promote efficacy. Future research should consider differential effects of rTMS induced by technical parameters and strive for an exhaustive reporting of relevant rTMS parameters.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool potentially modulating pathological brain activity. Its clinical effectiveness is hampered by varying results and characterized by inter-individual variability in treatment responses. RTMS individualization might constitute a useful strategy to overcome this variability. A precondition for this approach would be that repeatedly applied protocols result in reliable effects. The condition tinnitus provides the advantage of immediate behavioral consequences (tinnitus loudness changes) after interventions and thus offers an excellent model to exemplify TMS personalization. Objective: The aim was to investigate the test���retest reliability of short rTMS stimulations in modifying tinnitus loudness and oscillatory brain activity as well as to examine the feasibility of rTMS individualization in tinnitus. Methods: Three short verum (1, 10, 20 Hz; 200 pulses) and one sham (0.1 Hz; 20 pulses) rTMS protocol were administered on two different days in 22 tinnitus patients. Before and after each protocol, oscillatory brain activity was recorded with electroencephalography (EEG), together with behavioral tinnitus loudness ratings. RTMS individualization was executed on the basis of behavioral and electrophysiological responses. Stimulation responders were identified via consistent sham-superior increases in tinnitus loudness (behavioral responders) and alpha power increases or gamma power decreases (alpha responders/gamma responders) in accordance with the prevalent neurophysiological models for tinnitus. Results: It was feasible to identify individualized rTMS protocols featuring reliable tinnitus loudness changes (55% behavioral responder), alpha increases (91% alpha responder) and gamma decreases (100% gamma responder), respectively. Alpha responses primary occurred over parieto-occipital areas, whereas gamma responses mainly appeared over frontal regions. On the contrary, test���retest correlation analyses per protocol at a group level were not significant neither for behavioral nor for electrophysiological effects. No associations between behavioral and EEG responses were found. Conclusion: RTMS individualization via behavioral and electrophysiological data in tinnitus can be considered as a feasible approach to overcome low reliability at the group level. The present results open the discussion favoring personalization utilizing neurophysiological markers rather than behavioral responses. These insights are not only useful for the rTMS treatment of tinnitus but also for neuromodulation interventions in other pathologies, as our results suggest that the individualization of stimulation protocols is feasible despite absent group-level reliability.