Tobias Kleinjung

Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus.

OBJECTIVES: The pathophysiologic mechanisms of idiopathic tinnitus remain unclear. Recent studies demonstrated focal brain activation in the auditory cortex of patients with chronic tinnitus. Low-frequency repetitive transcranial magnetic stimulation (rTMS) is able to reduce cortical hyperexcitability. STUDY DESIGN: Fusing of the individual PET-scan with the structural MRI-scan (T1, MPRAGE) allowed us to identify exactly the area of increased metabolic activity in the auditory cortex of patients with chronic tinnitus. With the use of a neuronavigational system, this target area was exactly stimulated by the figure 8-shaped magnetic coil. In a prospective study, rTMS (110% motor threshold; 1 Hz; 2000 stimuli/day over 5 days) was performed using a placebo controlled cross-over design. Patients were blinded regarding the stimulus condition. For the sham stimulation a specific sham-coil system was used. Fourteen patients were followed for 6 months. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). SETTING: Tertiary referral medical center. RESULTS: Increased metabolic activation in the auditory cortex was verified in all patients. After 5 days of verum rTMS, a highly significant improvement of the tinnitus score was found whereas the sham treatment did not show any significant changes. The treatment outcome after 6 months still demonstrated significant reduction of tinnitus score. CONCLUSION: These preliminary results demonstrate that neuronavigated rTMS offers new possibilities in the understanding and treatment of chronic tinnitus.

Tinnitus: causes and clinical management

Tinnitus is the perception of sound in the absence of a corresponding external acoustic stimulus. With prevalence ranging from 10% to 15%, tinnitus is a common disorder. Many people habituate to the phantom sound, but tinnitus severely impairs quality of life of about 1-2% of all people. Tinnitus has traditionally been regarded as an otological disorder, but advances in neuroimaging methods and development of animal models have increasingly shifted the perspective towards its neuronal correlates. Increased neuronal firing rate, enhanced neuronal synchrony, and changes in the tonotopic organisation are recorded in central auditory pathways in reaction to deprived auditory input and represent--together with changes in non-auditory brain areas--the neuronal correlate of tinnitus. Assessment of patients includes a detailed case history, measurement of hearing function, quantification of tinnitus severity, and identification of causal factors, associated symptoms, and comorbidities. Most widely used treatments for tinnitus involve counselling, and best evidence is available for cognitive behavioural therapy. New pathophysiological insights have prompted the development of innovative brain-based treatment approaches to directly target the neuronal correlates of tinnitus.

Structural brain changes in tinnitus: Grey matter decrease in auditory and non-auditory brain areas

Tinnitus, the phantom perception of sound, is a frequent disorder that causes significant morbidity. The pathophysiological mechanisms involved in tinnitus generation are still under exploration. Electrophysiological and functional neuroimaging studies give increasing evidence for abnormal functioning both within the central auditory system and in non-auditory brain areas. However, observed changes show great variability, hence lacking a conclusive picture. Recently, structural alterations in the central nervous system have been detected in tinnitus patients by voxel-based morphometry (VBM). Here we aimed to replicate these findings in an independent study sample. We performed structural MRI scans in 28 tinnitus patients with normal audiometry and used VBM to compare results with a control group, matched for age, sex and hearing status. As major results we found significant grey matter decreases in the tinnitus group in the right inferior colliculus and in the left hippocampus. However, neither changes in the subcallosal area nor in the thalamus as described recently have been observed. Our results underscore that (1.) VBM allows to detect structural alterations in tinnitus patients, which seem to be related to tinnitus pathophysiology. (2.) Both, areas in the auditory and the limbic system are involved giving further evidence for the important role of the limbic system in the pathophysiology of tinnitus. (3.) Even groups with similar clinical characteristics might differ in the underlying neurobiological changes.

Consensus for tinnitus patient assessment and treatment outcome measurement: Tinnitus Research Initiative meeting, Regensburg, July 2006.

There is widespread recognition that consistency between research centres in the ways that patients with tinnitus are assessed and outcomes following interventions are measured would facilitate more effective co-operation and more meaningful evaluations and comparisons of outcomes. At the first Tinnitus Research Initiative meeting held in Regensburg in July 2006 an attempt was made through workshops to gain a consensus both for patient assessments and for outcome measurements. It is hoped that this will contribute towards better cooperation between research centres in finding and evaluating treatments for tinnitus by allowing better comparability between studies.

Tinnitus and depression

Abstract Objectives. Depressive symptoms are common in individuals with tinnitus and may substantially aggravate their distress. The mechanisms, however, by which depression and tinnitus mutually interact are still not fully understood. Methods. Here we review neurobiological knowledge relevant for the interplay between depression and tinnitus. Results. Neuroimaging studies confirm the existence of neural circuits that are activated both in depression and tinnitus. Studies of neuroendocrine function demonstrate alterations of the HPA-axis in depression and, more recently, in tinnitus. Studies addressing neurotransmission suggest that the dorsal cochlear nucleus that is typically hyperactive in tinnitus, is also involved in the control of attention and emotional responses via projections to the locus coeruleus, the reticular formation and the raphe nuclei. Impaired hippocampal neurogenesis has been documented in animals with tinnitus after noise trauma, as in animal models of depression. Finally, from investigations of human candidate genes, there is some evidence to suggest that variant BDNF may act as a common susceptibility factor in both disorders. Conclusions. These parallels in the pathophysiology of tinnitus and depression argue against comorbidity by chance and against depression as pure reaction on tinnitus. Instead, they stand for a complex interplay between tinnitus and depression. Implications for tinnitus treatment are discussed.

The impact of auditory cortex activity on characterizing and treating patients with chronic tinnitus – first results from a PET study

Conclusion: Unilaterally increased metabolic activity within the primary auditory cortex (PAC) represents a robust finding in tinnitus patients. Targeting these hyperactive areas with image-guided low frequency repetitive transcranial magnetic stimulation (rTMS) results in subjective tinnitus reduction. More pronounced activation of the PAC predicted higher resistance to rTMS. Objectives: [18F]deoxyglucose (FDG)-positron emission tomography (PET) was used to assess metabolic activity within the central auditory system in tinnitus. The study investigated whether patterns of neuronal activity correlate with clinical features or may be used for the prediction of treatment outcome. Patients and methods: Twenty patients with chronic tinnitus underwent PET imaging followed by low frequency rTMS treatment. Neuroimaging data were compared with clinical parameters and treatment outcome. Results: PET data demonstrated an asymmetric activation of the central auditory system. Seventeen patients revealed increased activity of the primary auditory cortex on the left side, three on the right side. The extent of hypermetabolic activity prior to treatment correlated significantly with tinnitus reduction after rTMS, but not with clinical characteristics such as tinnitus severity, tinnitus laterality or tinnitus duration.

Combined temporal and prefrontal transcranial magnetic stimulation for tinnitus treatment: a pilot study.

Objectives Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been proposed as a new treatment strategy for patients with chronic tinnitus. However, functional abnormalities in tinnitus patients also involve brain structures used for attentional and emotional processing, such as the dorsolateral prefrontal cortex. Therefore, we have developed a new rTMS treatment strategy for tinnitus patients that consists of a combination of high-frequency prefrontal and low-frequency temporal rTMS. Study Design A total of 32 patients received either low-frequency temporal rTMS or a combination of high-frequency prefrontal and low-frequency temporal rTMS. Treatment effects were assessed with a standardized tinnitus questionnaire (TQ). Results Directly after therapy there was an improvement of the TQ-score for both groups, but no differences between groups. An evaluation after 3 months revealed a remarkable benefit from the use of combined prefrontal and temporal rTMS treatment. Conclusion These results support recent data that suggest that auditory and nonauditory brain areas are involved in tinnitus pathophysiology.

Transcranial Magnetic Stimulation for the Treatment of Tinnitus: A New Coil Positioning Method and First Results

SummaryAuditory phantom perceptions are associated with hyperactivity of the central auditory system. Neuronavigation guided repetitive transcranial magnetic stimulation (rTMS) of the area of increased activity was demonstrated to reduce tinnitus perception. The study aimed at developing an easy applicable standard procedure for transcranial magnetic stimulation of the primary auditory cortex and to investigate this coil positioning strategy for the treatment of chronic tinnitus in clinical practice. The left gyrus of Heschl was targeted in 25 healthy subjects using a frameless stereotactical system. Based on individual scalp coordinates of the coil, a positioning strategy with reference to the 10--20-EEG system was developed. Using this coil positioning approach we started an open treatment trial. 28 patients with chronic tinnitus received 10 sessions of rTMS (intensity 110% of motor threshold, 1 Hz, 2000 Stimuli/day). Being within a range of about 20 mm diameter, the scalp coordinates for stimulating the primary auditory cortex allowed to determine a standard procedure for coil positioning. Clinical validation of this coil positioning method resulted in a significant improvement of tinnitus complaints (p<0.001). The newly developed coil positioning strategy may have the potential to offer a more easy-to-use stimulation approach for treating chronic tinnitus as compared with highly sophisticated, imaging guided treatment methods.

Textbook of tinnitus

The Spectrum of Neuro-AIDS Disorders presents, in 36 chapters, the relevant basic knowledge on human immunodeficiency virus (HIV) infection and the nervous system. The editors succeeded in acquiring the services of very well-known specialists in the field for every chapter, guaranteeing a deep understanding of the topics with respect to clinical problems and research results. For physicians who want comprehensive information, as well as for students and informed laymen, the book is easily readable. The prose is easily understandable, although on a high scientific level. The quality of the figures, tables, and illustrations is very good, and they all help to underline and explain the text. Another advantage is that the book addresses aspects that have rarely been the focus of interest (eg, neuro-AIDS disorders, gender and antiretroviral combination treatment, and neuro-AIDS disorders and ethnicity). The main sections 1 through 6 describe every topic of interest in the field, such as disorders primarily provoked by HIV infection, pathophysiological aspects, neuroimaging, comorbidities, neuro-AIDS disorders in special populations, and special health care issues. Everybody who has a diagnostic or therapeutic problem regarding neuro-AIDS disorders in clinical practice will find it helpful to read the corresponding chapter in the book. Additionally, the references in every chapter are excellent, so much so that the reader has the opportunity to broaden his or her knowledge. Thus, the book is highly useful and should be in every university library. Prose Illustrations Science Usefulness

Neural correlates of tinnitus duration and Distress: A positron emission tomography study

Cerebral 18F‐deoxyglucose positron emission tomography (FDG‐PET) has shown altered auditory pathway activity in tinnitus. However, the corresponding studies involved only small samples and analyses were restricted to the auditory cortex in most studies. Evidence is growing that also limbic, frontal, and parietal areas are involved in the pathophysiology of chronic tinnitus. These regions are considered to mediate perceptual, attentional, and emotional processes. Thus, the aim of the present study was the systematic evaluation of metabolic brain activity in a large sample of tinnitus patients. Ninety one patients with chronic tinnitus underwent FDG‐PET. The effects of tinnitus severity (assessed by a tinnitus questionnaire score), duration and laterality were evaluated with statistical parametric mapping (SPM) in whole brain analyses. In addition, region of interest analyses were performed for primary auditory areas. Tinnitus duration correlated positively with brain metabolism in right inferior frontal, right ventro‐medial prefrontal, and right posterior cingulate cortex. Tinnitus distress correlated positively with activation of left and right posterior inferior temporal gyrus as well as left and right posterior parahippocampal–hippocampal interface. Region of interest analysis demonstrated an overactivation of left in contrast to right Heschls gyrus independently from tinnitus laterality and anatomical hemispheric differences. Tinnitus duration and distress were associated with areas involved in attentional and emotional processing. This is in line with recent findings indicating the relevance of higher order areas in the pathophysiology of tinnitus. Earlier results of asymmetric activation of the auditory cortices in tinnitus were confirmed, i.e., left‐sided overactivation was found independently from tinnitus laterality. Hum Brain Mapp, 2013.