The mechanisms of tinnitus: perspectives from human functional neuroimaging

In this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural substrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power

Neuronale Korrelate und Prädiktoren der Tinnitussuppression mittels rauschhafter Stimuli

Tinnitus ist ein weltweit verbreitetes Krankheitsbild, das teilweise mit hoher Krankheitslast einhergeht. Trotzdem konnte bis dato weder ein Durchbruch bei der Therapie erzielt noch aussagekräftige diagnostische oder prognostische Marker bestimmt werden. Als neurophysiologische Korrelate konnten verschiedene Veränderungen der Hirnströme, unter anderem eine Abnahme der Alpha-Aktivität, identifiziert werden. Bezüglich Therapieversuchen ist ein Ansatz, der aktuell Gegenstand der Forschung ist, die Tinnitussuppression mittels akustischer Stimulation. Die Präsentation eines akustischen Stimulus führt dabei zu einer kurzfristigen Abnahme der Tinnituslautstärke der Betroffenen. Dies wird als residuale Inhibition bezeichnet. In dieser Arbeit soll der Einfluss von 3 rauschhaften Stimuli auf die Tinnituslautstärke und Alpha-Aktivität untersucht, sowie Prädiktoren für das Ansprechen auf akustische Stimulation identifiziert werden. Dazu rekrutierten wir 28 Probanden mit chronischem tonalem Tinnitus (Durchschnittsalter 53,11 Jahre, 4 weibliche Probanden). In einer ersten Sitzung wurden neuroanatomische Aufnahmen mittels Magnetresonanztomographie erstellt. An Tag 2 erfolgte die Audiometrie und das Tinnitusmatching. LDL, MML und SL wurden bestimmt und die 3 Stimuli WN, IBP und IBS erstellt. Anschließend wurde die akustische Stimulation mit gleichzeitiger Aufzeichnung eines EEGs durchgeführt und die Stimuli abschließend bewertet. Psychometrische Daten wurden über verschiedene online zur Verfügung gestellte Fragebögen erhoben. Es konnte gezeigt werden, dass alle 3 Stimuli zu einer Reduktion der Tinnituslautstärke führen. Direkt nach Ende der Stimulation war die Suppression durch WN stärker ausgeprägt als durch IBS. Die Tinnitussuppression war dabei zeitlich begrenzt, für alle Stimuli kam es zu einem Rückgang innerhalb der ersten 30s nach Stimulation. Ebenso kam es für alle Stimuli zu einer Reduktion der Alpha-Power nach akustischer Stimulation, stimulusspezifische Unterschiede traten dabei jedoch nicht auf. Diese war nicht mit der Reduktion der Tinnituslautstärke assoziiert. Auch konnte kein Zusammenhang von Tinnitussuppression und kortikaler Dicke festgestellt werden. Es konnte hingegen eine negative Korrelation der Dicke des auditorischen Kortex mit der Tinnitusbelastung, quantifiziert anhand des THI-Scores, identifiziert werden. Des Weiteren bestand eine positive Korrelation zwischen der BFI-2 Dimension Neurotizismus und Tinnitussuppression, für die Dimension Offenheit und den THI-Score konnten keine signifikanten Zusammenhänge mit der Tinnitussuppression festgestellt werden. Insgesamt sind wir zu gemischten Ergebnissen gekommen. Insbesondere die Suche nach Prädiktoren hat sich nicht als erfolgreich herausgestellt. In Zusammenschau mit aktueller Literatur lässt sich anzweifeln, ob universelle Prädiktoren der Heterogenität von Tinnitus gerecht werden können. Ebenso ist mangels einer gesunden Kontrollgruppe nicht klar, ob die in unserer Studie gemessenen Alpha-Power-Veränderungen tinnitusspezifisch oder physiologischer Natur sind. Dahingegen konnten wir zeigen, dass rauschhafte Stimuli grundsätzlich zur kurzfristigen Tinnitussuppression geeignet sind. Wenn sich in Studien mit längeren Stimulationsregimen nachhaltige Tinnitussuppression zeigt, so könnte sich akustische Stimulation insbesondere für die Gruppe der RI-Responder als Therapieoption etablieren

The auditory fingerprint : multidimensional characterization of individual pitch perception in musicians

Musicians have been repeatedly reported to show remarkable inter-individual differences in elementary hearing functions, sound perception mode, musical instrument preference, performance style, as well as musical abilities such as absolute- and relative pitch perception or auditory imagery (audiation). However, relevant literature in the field regarding perceptual and psychophysical aspects of sound and particularly pitch perception is highly contradictory, and subjective differences are mostly unconsidered. Moreover, it is largely unexplored how individual differences in (musical) pitch perception are related to further musical abilities and behavior. In the present work, “auditory fingerprints” were created basically based on a composite of five psychoacoustic hearing tests assessing subjective pitch perception in musicians. A total of 93 musicians, including 49 professionals and 44 amateurs, were individually measured for: (a) pitch perception preference (holistic vs. spectral mode), (b) relative pitch perception (musical interval recognition), (c) absolute pitch perception („perfect pitch“), (d) frequency discrimination threshold (just noticeable difference), and (e) auditory imagery of tone-sequences. Overall, eight psychoacoustic parameters were extracted and analyzed using statistical methods. In addition, preferences for musical instruments were evaluated. On the individual level, the results show a high inter-individual variability across the eight psychoacoustic parameters, reflecting clear individual differences in pitch perception and related musical abilities. In addition, principal component analysis (PCA) revealed four different main components to sufficiently represent coherent aspects of the psychoacoustic data, namely: tonal musicality, pitch & timbre preference, low-band sensitivity and high-band sensitivity. On the group level, multi-parametric cluster analyses revealed three sub-groups of subjects, showing significantly different results with respect to the underlying perceptional patterns. Consequently, at least three different modes of pitch perception are suggested, characterized by: 1. Pronounced analytic pattern recognition, focused on spectra / timbre and sensitive to single tones; 2. Pronounced holistic pattern recognition, focused on (missing) fundamental pitch and rather insensitive to single tones; 3. Less pronounced audiation and pitch detection abilities, linked to ambiguous multi-pitch sensations (“balanced mode”). Taken together, the findings suggest that individual “auditory fingerprints” extracted from psychoacoustic hearing tests, reflect remarkable inter-individual differences, but also typical patterns of perceiving (musical) pitch and sound. It can be concluded, that specific auditory characteristics are related to the individual musical (instrument) preference, style and performance of musicians, as well their learning abilities

Transcranial magnetic stimulation for the treatment of tinnitus

Tinnitus je velmi častý a obtěžující symptom, který lze charakterizovat jako percepci zvuku při absenci jeho zevního zdroje. Tinnitus je obtížně léčitelný a ve své vážné formě narušuje plnohodnotný život postiženého jedince. Zdá se, že tinnitus je výsledkem dysfunkční aktivace neuronální plasticity, která je indukována alterací senzorických a somatosenzorických vstupů. Adaptivní neuroplastické procesy vedou ke změnám rovnováhy mezi excitačními a inhibičními systémy na několika úrovních centrálního auditivního systému. Funkční zobrazovací metody dokumentují u pacientů s tinnitem zvýšenou neuronální aktivitu v oblasti primárního auditivního kortexu (PAC). Repetitivní transkraniální magnetická stimulace (rTMS) má schopnost indukovat změny neuronální excitability, které přetrvávají samotnou dobu stimulace. Aplikace nízkofrekvenční rTMS na oblast PAC má schopnost redukovat tuto hyperaktivitu navozením long term depression (LTD) a tím redukovat percepci tinnitu. Hlavním cílem naší studie bylo zkoumat v prospektivní, randomizované, placebem kontrolované studii, zda se výsledné ovlivnění příznaků chronického, farmakorezistentního tinnitu pomocí nízkofrekvenční rTMS lokalizované bezrámovou stereotaxí bude lišit od výsledného efektu placebo rTMS. K hodnocení efektu rTMS terapie byly použity subjektivní...Tinnitus is a common and often severely disabling symptom that is characterized by the perceived sensation of sound in the absence of an external stimulus. Traditional treatment approaches have limited efficacy. It is assumed, that tinnitus is connected with dysfunctional activation of neuronal plasticity induced by altered sensory and somatosensory input. Adaptive neuroplastic processes alter the balance between excitatory and inhibitory function of the auditory system at several levels. Functional imaging studies in tinnitus patients have revealed increased neronal activity of primary auditory cortex (PAC). Repetitive transcranial magnetic stimulation (rTMS) induces changes of neuronal activity that outlast the stimulation period. Low-frequency rTMS over the PAC region results in a decrease of cortical activity by inducing long term depression (LTD) and leads to reduced tinnitus perception. The aim of this study was to assess in prospective randomized placebo- controlled study the ability of active low-frequency rTMS guided by frameless stereotaxy to affect symptoms of chronic tinnitus compared to placebo stimulation. Treatment outcome was assessed by subjective specific questionnaires; Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ) and Visual analogue scales (VAS1, VAS2)...Department of Psychiatry First Faculty of Medicine and General University Hospital in PraguePsychiatrická klinika 1. LF a VFN v PrazeFirst Faculty of Medicine1. lékařská fakult

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

MULTIMODAL ASSESSMENT OF CETACEAN CENTRAL NERVOUS AUDITORY PATHWAYS WITH EMPHASIS ON FORENSIC DIAGNOSTICS OF ACOUSTIC TRAUMA

Cetaceans encompass some of the world’s most enigmatic species, with one of their greatest adaptations to the marine environment being the ability to “see” by hearing. Their anatomy and behavior are fine-tuned to emit and respond to underwater sounds, which is why anthropogenic noise pollution is likely to affect them negatively. There are many effects of noise on living organisms, and while knowledge on their entire palette and interplay remain incomplete, evidence for insults ranging from acoustic trauma over behavioral changes, to masking and stress, is accumulating. Humans are subject to peak interest in terms of medical research on noise-induced hearing loss. As major health concerns can be expected across species, addressing this problem in free-ranging cetacean populations will lead to a more sustainable management of marine ecosystems, more effective and balanced policies, and successes in conservation. While progress has been made in behavioral monitoring, electrophysiological hearing assessments and post-mortem examination of the inner ear of cetaceans, but very little is known about the neurochemical baseline and neuropathology of their central auditory pathways. In the present work, we reviewed the known effects of sound on cetaceans in both wild and managed settings and explored the value of animal models of neurodegenerative disease. We began by evaluating a row of antibodies associated with neurodegeneration in a more readily available species, the dog, where acute neurological insult could be derived from clinical history. We then set out to systematically validate a key panel of protein biomarkers for the assessment of similar neurodegenerative processes of the cetacean central nervous system. For this, we developed protocols to adequately sample cetacean auditory nuclei, optimized the immunohistochemical workflow, and used Western blot and alignment of protein sequences between the antigen targeted by our antibodies and the dolphin proteome. A Histoscore was used to semi-quantitively categorize immunoreactivity patterns and dolphins by age and presence of pathology. First results indicated significant differences both between sick and healthy, and young and old animals. We then expanded our list of validated antibodies for use in the bottlenose dolphin and the techniques used to assess them in a multimodal, quantitative way. 7T-MRI and stereology were implemented to assess the neuronal, axonal, glial and fiber tract counts in the inferior colliculus and ventral cochlear nucleus of a healthy bottlenose dolphin, which created a baseline understanding of protein expression in these structures, and the influence of tissue processing. This will make a valuable comparison for when positive controls of acoustic trauma would become available. Furthermore, we explored the connectome and neuronal morphology of auditory nuclei and experimented with probe designs and machine learning algorithms to quantify structures of interest. Comparisons with pathological human brains revealed similarities in the configuration of extracellular matrix components to those of a healthy dolphin, in line with existing knowledge on the tolerance to hypoxia in these diving animals. This could have interesting implications in future investigation of the evolutionary development of marine mammal brains, as well as help diversify out-of-the-box approaches to researching human neurodegenerative disease, as is being done with hibernating species. The data and methodologies described herein contribute to the knowledge on neurochemical signature of the cetacean central nervous system. They are intended to facilitate understanding of auditory and non-auditory pathology and build an evidence-based backbone to future policies regarding noise and other form of anthropogenic threats to the marine environment.Cetaceans encompass some of the world’s most enigmatic species, with one of their greatest adaptations to the marine environment being the ability to “see” by hearing. Their anatomy and behavior are fine-tuned to emit and respond to underwater sounds, which is why anthropogenic noise pollution is likely to affect them negatively. There are many effects of noise on living organisms, and while knowledge on their entire palette and interplay remain incomplete, evidence for insults ranging from acoustic trauma over behavioral changes, to masking and stress, is accumulating. Humans are subject to peak interest in terms of medical research on noise-induced hearing loss. As major health concerns can be expected across species, addressing this problem in free-ranging cetacean populations will lead to a more sustainable management of marine ecosystems, more effective and balanced policies, and successes in conservation. While progress has been made in behavioral monitoring, electrophysiological hearing assessments and post-mortem examination of the inner ear of cetaceans, but very little is known about the neurochemical baseline and neuropathology of their central auditory pathways. In the present work, we reviewed the known effects of sound on cetaceans in both wild and managed settings and explored the value of animal models of neurodegenerative disease. We began by evaluating a row of antibodies associated with neurodegeneration in a more readily available species, the dog, where acute neurological insult could be derived from clinical history. We then set out to systematically validate a key panel of protein biomarkers for the assessment of similar neurodegenerative processes of the cetacean central nervous system. For this, we developed protocols to adequately sample cetacean auditory nuclei, optimized the immunohistochemical workflow, and used Western blot and alignment of protein sequences between the antigen targeted by our antibodies and the dolphin proteome. A Histoscore was used to semi-quantitively categorize immunoreactivity patterns and dolphins by age and presence of pathology. First results indicated significant differences both between sick and healthy, and young and old animals. We then expanded our list of validated antibodies for use in the bottlenose dolphin and the techniques used to assess them in a multimodal, quantitative way. 7T-MRI and stereology were implemented to assess the neuronal, axonal, glial and fiber tract counts in the inferior colliculus and ventral cochlear nucleus of a healthy bottlenose dolphin, which created a baseline understanding of protein expression in these structures, and the influence of tissue processing. This will make a valuable comparison for when positive controls of acoustic trauma would become available. Furthermore, we explored the connectome and neuronal morphology of auditory nuclei and experimented with probe designs and machine learning algorithms to quantify structures of interest. Comparisons with pathological human brains revealed similarities in the configuration of extracellular matrix components to those of a healthy dolphin, in line with existing knowledge on the tolerance to hypoxia in these diving animals. This could have interesting implications in future investigation of the evolutionary development of marine mammal brains, as well as help diversify out-of-the-box approaches to researching human neurodegenerative disease, as is being done with hibernating species. The data and methodologies described herein contribute to the knowledge on neurochemical signature of the cetacean central nervous system. They are intended to facilitate understanding of auditory and non-auditory pathology and build an evidence-based backbone to future policies regarding noise and other form of anthropogenic threats to the marine environment

Vermessung des Corpus callosum bei Patienten mit Tinnitus und bei gesunden Menschen mit Hilfe der Magnetresonanztomographie

Der Pathomechanismus von Tinnitus ist weitgehend unbekannt. Die Krankheit ist durch eine Hypererregbarkeit gekennzeichnet, die aus einer Reduktion der inhibitorischen Prozesse und einer Amplitudenerhöhung auf verschiedenen Ebenen der Hörbahn resultiert. Man vermutet, dass bei Tinnitus-Patienten einige Gehirnregionen verändert sind, u.a. der mediale Anteil des Heschlschen Gyrus (mHG). Der mHG, in dem sich der primäre auditorische Cortex befindet, ist bei Patienten, die unter Tinnitus leiden, kleiner als bei gesunden Kontrollprobranden. Des Weiteren gibt es einen Zusammenhang zwischen der (den) von Tinnitus betroffenen Ohrseite(n) und der Seite der mHGVolumenreduzierung, der sich durch einen kleineren mHG ipsilateral zum betroffenen Ohr zeigt (Schneider et al., 2009). Das Corpus callosum (CC) ist eine der wichtigsten interhemisphärischen Verbindungen des Gehirns, die homotope und heterotope Bereiche des Hörcortex der linken und rechten Hemisphäre miteinander verbindet. Diese interhemisphärischen Projektionen sind sowohl exzitatorisch als auch inhibitorisch. In der vorliegenden Arbeit wird untersucht, ob sich das wahrgenommene Tinnitus-Geräusch im CC widerspiegelt. Unsere Hypothese war, dass ein volumenverminderter mHG zusammen mit einem CC, das in genau den Segmenten verkleinert ist, in denen die auditorische Information übertragen wird, eine geringere tonische Inhibition erzeugt und dadurch die Entstehung einer Tinnitus-bedingten Aktivität ermöglicht. Da in der Literatur auch Unterschiede im CC-Volumen zwischen Berufsmusikern und Nicht-Musikern beschrieben werden und die Personen dieser Studie diese beiden Gruppen repräsentieren, ist auch dieser Vergleich Teil der vorliegenden Arbeit. Die vorliegende MRT-Studie untersuchte mit Hilfe des medizinischen Bildbearbeitungsprogrammes MRIcro und der „Matlab image toolbox“ die mittsagittale Querschnittsfläche des CC von Tinnitus-Patienten im Vergleich zu gesunden Kontrollprobanden, bei denen in einer vorherigen Studie der mHG untersucht wurde. Nachdem das CC mittels MRIcro aufgrund von Intensitätsunterschieden zwischen den verschiedenen Gehirnstrukturen aus den MRT-Schnittbildern herausgeschnitten wurde, wurde es mit Hilfe der „Matlab image toolbox“ in Unterbereiche eingeteilt. Diese Bereiche wurden einerseits anhand des am häufigsten verwendeten CC-Morphometrieschemas definiert, das von Witelson eingeführt wurde und andererseits anhand des Klassifizierungsschemas nach Hofer & Frahm. Die Ergebnisse beider CC-Morphometrieschemata zeigen einen signifikanten Unterschied in der Subregion III (posteriorer Truncus des CC) zwischen den Gruppen (p = 0,007), wobei die Tinnitus-Patienten eine kleinere CC-Querschnittsfläche in der mittsagittalen Ebene aufweisen. Der betroffene CC-Bereich enthält nach dem Schema von Witelson einen Großteil der auditorischen Fasern, was die vorangegangene Hypothese bestätigt. Die weitläufige Annahme eines Zusammenhanges zwischen der hemisphärischen Asymmetrie und der Größe des CC kann in der vorliegenden Arbeit nicht bestätigt werden, da die Berechnung der Korrelation zwischen dem Asymmetrieindex der auditorischen Cortices und der Querschnittsfläche des CC kein signifikantes Resultat liefert (p = 0,159). Die Gegenüberstellung von den (Teil-)Volumina des auditorischen Cortex und der mittsagitalen Querschnittsfläche des CC und seiner Subregionen ergibt signifikante Effekte in zahlreichen Bereichen, am häufigsten in den Subregionen Hofer II, Hofer IV, Witelson I und Witelson II, was zu der Annahme führt, dass die Größe des CC durch die Cortexgröße vorbestimmt sein könnte. Die Analyse der Musiker- und Nicht-Musiker-Gruppen zeigt in Übereinstimmung mit früheren Studien bei Musikern u.a. eine größere mittsagittale Fläche im Bereich des Segmentes Hofer II (mittleres Drittel des anterioren Truncus) (p = 0,0199). Durch dieses Segment verlaufen sowohl Fasern des prämotorischen Cortex, die eine Rolle bei der sensorischen Bewegungsführung spielen, als auch Fasern des supplementär motorischen Cortex, die an der Planung von motorischen Bewegungen und an der bimanuellen Kontrolle beteiligt sind. Das CC von Personen mit chronischem Tinnitus zeigt einen kleineren posterioren Truncus, was die vorherigen Befunde eines kleineren mHG-Volumens in Abhängigkeit der betroffenen Ohrseite widerspiegelt. Ein kleineres mHG-Volumen zusammen mit einem kleineren CC in genau den Bereichen, die die auditorische Information übertragen, könnte zu einem geringeren Grad an tonischer Inhibition führen und somit die Entstehung einer Tinnitus-bedingten Aktivität fördern. Die bei den Musikern beobachteten Effekte könnten das Resultat der bimanuellen Aktivitäten während des intensiven musikalischen Trainings sein, die die strukturelle Entwicklung des CC, bedingt durch eine Zunahme der Myelination, der Axongröße oder der Anzahl der Fasern, die über das CC verlaufen, beeinflusst.The pathomechanism of tinnitus is largely unknown. The disorder is characterised by hyperexcitability that results from a reduction of inhibitory processes and gain increase at different stages of the auditory system. Several brain regions of tinnitus patients seem to be altered, including the medial partition of Heschl´s gyrus (mHG). The mHG is the anatomical site of the primary auditory cortex and is smaller in patients suffering from tinnitus than in healthy controls. Furthermore, there is a relationship between the side of the ear(s) affected by tinnitus and the side of the mHG volume reduction with a smaller mHG at the side ipsilateral of the affected ear (Schneider et al., 2009). The Corpus callosum (CC) is the main interhemispheric commissure of the brain connecting homotopic and heterotopic auditory areas of the left and the right hemisphere. These interhemispheric projections are both excitatory and inhibitory. Here, we investigate whether tinnitus is reflected in the CC volume. Our hypothesis was that a mHG that is reduced in volume, together with a CC that is smaller in those segments in which auditory information is transmitted, may generate a lesser amount of tonic inhibition and therefore facilitate the development of tinnitusrelated activity. As the literature also describes differences in the CC volume between professional musicians and non-musicians and the studied subjects represent both groups, we also investigate a comparison of those. This MRI study examined the midsagittal cross-sectional area of the CC of tinnitus patients and healthy controls in which an examination of the mHG was carried out before, using the medical image software MRIcro and the Matlab image toolbox. After having “cut out” the CC from the MRT slices with the aid of MRIcro utilizing intensity differences between the different brain structures, the CC was segmented into subregions with the Matlab image toolbox. These subregions were defined on the one hand according to the most common CC morphometry scheme introduced by Witelson and on the other hand according to the classification scheme by Hofer & Frahm. The results of both CC segmentation schemes reveal a significant difference (p = 0,007) in the subregion III (posterior midbody of the CC) with tinnitus patients showing a smaller CC crosssectional area in the midsagittal plane. According to the segmentation scheme developed by Witelson (1989), the affected CC segment is known to include most of the auditory fibres. These results confirm our hypothesis. The common assumption of a relationship between hemispheric asymmetry and the volume of the CC can´t be supported by the present study as the result of the correlation between the asymmetry index of the auditory cortices and the cross-sectional area of the CC doesn´t show significance (p = 0,159). The comparison of (partial) volumes of the auditory cortex and the midsagittal cross-sectional area of the CC and its subregions reveals many significant effects, especially in the subregions Hofer II, Hofer IV, Witelson I and Witelson II. Therefore it can be assumed that the CC volume is predetermined by the cortex volume. The analysis of the musician and non-musician groups is in agreement with previous studies showing a larger midsagittal area in the middle third of the anterior body of the CC (Hofer II area) in musicians (p = 0,0199). This area contains fibres from the premotor cortex, which is important in the sensory guidance of movements, as well as fibres from the supplementary motor area, which are involved in the planning of motor actions and bimanual control. People suffering from chronic tinnitus show a smaller posterior midbody of the CC reflecting the previous findings of a smaller mHG volume in dependence on the side of the affected ear. A smaller mHG volume together with a smaller CC in those segments that transfer auditory information could lead to a lesser degree of tonic inhibition and therefore to a facilitation of the development of tinnitus-related activity. The observed effects in musicians could result from interference of bimanual activities during intensive instrumental music training that could influence the structural development of the CC due to growth of myelination, axon size or the number of fibres crossing the CC