Introdução: Plasticidade auditiva refere-se a mudanças que ocorrem no sistema sensorial responsável pela transmissão da informação acústica. A plasticidade do sistema nervoso auditivo central está relacionada a capacidade de adaptação através da reintrodução de estímulos por meio de aparelhos de amplificação sonora ou implante coclear. Essas mudanças são observadas a partir do desempenho de pacientes com o uso do aparelho de amplificação sonora, e podem ser verificadas por meio dos potenciais evocados auditivos de longa latência. Objetivo: caracterizar os Potenciais Evocados Auditivos de Longa Latência (PEALL) em adultos e idosos com perda auditiva neurossensorial, verificando os efeitos da estimulação auditiva por meio da comparação destes potenciais pré e pós adaptação do Aparelho de Amplificação Sonora Individual (AASI). Metodologia: Participaram deste estudo 15 indivíduos adultos e idosos, de ambos os gêneros, de 55 a 85 anos de idade, com perda auditiva neurossensorial de grau leve a moderado com simetria entre as orelhas, sem experiência prévia com qualquer tipo de dispositivo de amplificação sonora. Os indivíduos foram encaminhados pelas empresas de aparelho auditivo WIDEX, Audibel e o Espaço Reouvir, tratando-se de novos usuários de AASI. Os PEALL foram realizados nas condições com e sem AASI, a 60 e 75 dBnNA em campo sonoro, em dois momentos: primeira avaliação realizada até uma semana após a adaptação do AASI e a segunda avaliação realizada após 6 meses da adaptação do AASI. Resultados: Na comparação da primeira avaliação com a segunda avaliação, na condição sem AASI a 60 dBnNA, observou-se diferença estatisticamente significante na latência do componente P1 (p-valor= 0,034). Na condição sem AASI a 75 dBnNA, observou-se diferença estatisticamente significante para a latência do componente P300 (p-valor 0,031) e para a amplitude P2N2 (p-valor 0,024), com diminuição da latência e aumento da amplitude na segunda avaliação. Por sua vez, na comparação da primeira avaliação com a segunda avaliação, na condição com AASI a 75 dBnNA, obteve-se uma diferença estatisticamente significante na latência do componente N2 (p-valor 0,009) e na amplitude P2N2 (p-valor 0,024), com aumento da amplitude na segunda avaliação. Evidenciou-se, também, diferença significante na amplitude P1N1 (p-valor 0,024) na condição com AASI a 60 dBnNA. Conclusão: Os PEALL com estímulo de fala demonstraram ser um importante procedimento para ser utilizado na prática clínica, visando monitorar a plasticidade neuronal do Sistema Nervoso Auditivo Central frente à estimulação auditiva (uso de AASI), em adultos e idosos com perda auditiva neurossensorial de grau leve a moderado / Introduction: Auditory plasticity refers to changes that occur in the sensory system responsible for the transmission of acoustic information. The plasticity of the central auditory nervous system is related to the capacity of adaptation through the reintroduction of stimuli of sound amplification devices or cochlear implants. These changes are observed from the performance of patients with the use of the sound amplification apparatus, and can be verified by long-latency auditory evoked potentials. Purpose: To characterize long latency auditory evoked potentials (LLAEP) in adults with sensorineural hearing loss, verifying the effects of auditory stimulation by comparing these before and after adaptation potentials of the Individual Sound Amplification (AASI). Methodology: Fifteen adult and elderly individuals of both genders, aged 55 to 85 years, with mild to moderate sensorineural hearing loss with symmetry between the ears, without prior experience with any type of sound amplification device. The subjects were referred by hearing aid companies WIDEX, Audibel and Espaço Reouvir, in the case of new hearing aids users. The LLAEP were performed in the conditions with and without AASI, at 60 and 75 dBnNA in sound field, in two moments: first evaluation performed up to one week after AASI adaptation and the second evaluation performed after 6 months of AASI adaptation. Results: In the comparison of the first evaluation with the second evaluation, in the condition without AASI at 60 dBnNA, a statistically significant difference was observed in the latency of the P1 component (p-value = 0.034). In the condition without AASI at 75 dBnNA, a statistically significant difference was observed for the latency of the P300 component (p-value 0.031) and for the P2N2 amplitude (p-value 0.024), with latency decrease and amplitude increase in the second evaluation. In the comparison of the first evaluation with the second evaluation, in the condition with AASI at 75 dBnNA, there was a statistically significant difference in the latency of the N2 component (p-value 0.009) and in the P2N2 amplitude (p-value 0.024) , With amplitude increase in the second evaluation. There was also a significant difference in P1N1 amplitude (p-value 0.024) in the condition with AASI at 60 dBnNA. Conclusion: The LLAEP was an important procedure to be used in clinical practice, aiming to monitor the neural plasticity of the Central Auditory Nervous System in front of auditory stimulation (hearing aids use) in adults and elderly patients with mild to moderate sensorineural hearing loss of amplification and the importance of neural plasticity of the Central Auditory Nervous System

Background: A link between musical expertise and auditory temporal processing abilities was examined. Material and methods: Trained musicians (n=13) and non-musicians (n=12) were tested on speech tasks (phonetic identification, speech recognition in noise) and non-speech tasks (temporal gap detection). Results: Results indicated musicians had shorter between-channel gap detection thresholds and sharper phonetic identification functions, suggesting that perceptual reorganization following musical training assists basic temporal auditory processes. Conclusions: In general, our results provide a conceptual advance in understanding how musical training influences speech processing, an ability which, when impaired, can affect speech and reading competency.

No description available.

Estudamos os efeitos da estimulação elétrica no nucleus basalis magnocelular (Meynert), núcleo colinégico que projeta aferências para o córtex cerebral e tem sido associado a mecanismos de aprendizagem e memória. Verificamos os efeitos eletrofisiológicos induzidos pela estimulação elétrica do núcleo basalis pareado com apresentação de um tom puro. Caracterizamos a dinâmica da atividade elétrica neural do cortex auditivo primário e de núcleos subcorticais relacionados à circuitaria da aprendizagem e memória, durante o condicionamento auditivo nos momentos de aquisição e de revocação além correlacioná-las a dinâmica de freqüência cardiaca, variável que pode exprimir a relevância de um estímulo / Acetilcholine is related to learning and memory and is related to cortical activation. We studied the effects electrically stimulating the basal forebrain - the main cholinergic afferent to the cortex, while presenting paired and unpaired pure tones. Mathematical techniques were used to analyze electrophysiological data. The dynamics from primary auditory cortex and related subcortical nuclei were correlated to the auditory conditioning. We also correlated brain activity to the heart dynamics, considered a reliable measure of learning and conditioning, an interesting approach that uncovers the relevance of stimulus that is not detectable through other behavioral variables

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)...

Onze pacientes com diagnóstico de esquizofrenia pelo DSM-IV-TR e alucinações auditivas mesmo em uso de clozapina foram distribuídos aleatoriamente para receber estimulação magnética transcraniana de repetição (EMTr) ativa (n=6) ou inativa (n=5) no córtex têmporo-parietal esquerdo. Um total de 160 minutos de EMTr a 1 Hz foi administrada ao longo de 10 dias, 90% do limiar motor, com desenho paralelo, com pacientes e avaliadores cegos, em desenho controlado com grupo inativo. Houve um efeito de grupo significativo nos escores da escala de alucinações (realidade e influência: p=0,0360 e p=0,0493 respectivamente) e no subitem sintomas positivos da PANSS. A EMTr ativa em associação com clozapina pode ser administrada com segurança para tratar as alucinações auditivas. Embora a amostra consistia de pacientes extremamente refratários, estes resultados sugerem haver alguns efeitos da EMTr a 1 Hz no córtex têmporo-parietal esquerdo. / Eleven schizophrenics patients according to DSM-IV-TR criteria and experiencing auditory hallucinations in spite of treatment with clozapine were randomly allocated to receive repetitive transcranial magnetic stimulation (rTMS) (n=6) or sham stimulation (n=5) over left temporo-parietal cortex. A total of 160 minutes of 1 Hz rTMS was administered over 10 days at 90% motor threshold, with patients and raters blind to treatment modality, using a sham-controlled, parallel design. There was a significant group effect for the Auditory Hallucinations Rating Scale scores (reality and attencional salience: p=0.0360 and p=0.0493 respectively) and the sub item positive symptoms of PANSS. Active rTMS in association with clozapine can be administered safely to treat auditory hallucinations. Although the sample consisted of extremely refractory patients, the results suggest some effects of 1 Hz rTMS over Left temporoparietal.

L'éminence ganglionnaire médiale (MGE) produit la grande majorité des interneurones GABAergiques corticaux synthétisant la parvalbumine. Les neuroblastes issus de la MGE migrent sur une longue distance avant d'atteindre leur destination finale. A ce jour, on ne sait pas s'il existe des mécanismes moléculaires les guidant vers des régions corticales données. Je montre que deux protéines apparentées aux cadhérines, cdhr23 et cdhr15, ont un rôle déterminant dans le développement d'interneurones du cortex auditif et de manière spécifique. Chez la souris et le macaque, ces deux protéines sont co-synthétisées par des neuroblastes issus de la MGE pendant leur migration. Chez les souris déficientes pour Cdhr23 ou Cdhr15, les neuroblastes synthétisant cdhr15 ou cdhr23 s'accumulent dans le télencéphale basal, ne parviennent pas à pénétrer dans le néocortex et présentent in vitro des défauts de polarité cellulaire. Cdhr15 intervient dans la survie des précurseurs d'interneurones à parvalbumine pendant la première semaine postnatale. Les souris mutantes pour Cdhr23 ou Cdhr15 présentent à trois semaines un nombre réduit d'interneurones à parvalbumine dans leur cortex auditif mais pas dans les cortex avoisinants. Cette diminution est associée à une disposition aux crises audiogènes. Mes résultats indiquent que des précurseurs d'interneurones du cortex auditif sont équipés de protéines d'adhérence déterminantes pour leur migration et leur intégration dans le cortex auditif. Ils suggèrent l'existence d'un possible mécanisme moléculaire général fondé sur un " code d'adhérence " qui déterminerait les neuroblastes GABAergiques dès leur naissance à intégrer une aire corticale donnée. / The medial ganglionic eminence (MGE) gives rise to the majority of cortical GABAergic interneurons that synthetize parvalbumin. Neuroblasts born in the MGE undergo a long distance migration before reaching their final target. Up to now, it is unknown whether any molecular mechanism guides them to specific cortical regions. I show that two cadherin-related proteins, cdhr23 and cdhr15, have a critical role in the development of interneurons of the auditory cortex, specifically. In mice and macaque, the two proteins are co-synthetized in neuroblasts from the MGE during their migration. In mouse mutants for Cdhr23 or Cdhr15, neuroblasts synthetizing cdhr15 or cdhr23 accumulate in the basal telencephalon, fail to enter the neocortex and present in vitro cell polarity defects. Cdhr15 is involved in the survival of parvalbumin interneuron precursors during the first postnatal week. Mutant mice for Cdhr23 and Cdhr15 show at three weeks a reduced number of parvalbumin interneurons in the mouse auditory cortex but not the neighbouring ones. This decrease is associated with a susceptibility to audiogenic seizures. My results reveal that interneuron precursors of the auditory cortex are endowed by specific adhesion proteins critically involved in their migration and integration in the auditory cortex. They suggest a possible general molecular mechanism based on an "adhesion code” that would determine GABAergic neuroblasts from their birth to a specific cortical region.

Le processus du traitement de la parole est latéralisé au niveau cortical. En effet la théorie de l’échantillonnage asymétrique suggère que le signal acoustique est segmenté sous forme d’unités discrètes, et ensuite traité par les deux cortex auditifs non primaires en utilisant des fenêtres d’intégrations respectivement adaptées aux traitements des modulations lentes et rapides du signal de la parole. L’objectif de cette thèse était d’étudier les concepts de cette théorie au moyen de deux approches (psychophysique et neurophysiologique), en s’intéressant à l’activation corticale dans les deux hémisphères en fonction de la nature du signal auditif présenté. Les résultats révèlent que les scores d’intelligibilité de ces stimuli sont plus importants quand les modulations rapides arrivent au cortex auditif gauche et les modulations lentes arrivent au cortex auditif droit. Les résultats de l’IRMf démontrent une interaction entre l’enveloppe des stimuli présentés et les rythmes corticaux. Les deux cortex auditifs présentaient des asymétries inter-hémisphériques en réponse à ces stimuli. En outre, l’activité neuronale augmente avec les performances. Dans l'ensemble, les résultats de nos études vont dans le sens des prédictions de la théorie d’échantillonnage asymétrique. Nous supposons que, l’application des effets de la théorie de la latéralisation auditive dans le traitement du signal auditif pourrait améliorer la perception de la parole chez les personnes sourdes profonds en développant les stratégies de codage des Implants cochléaire de manière à les alignées sur les propriétés corticales d’échantillonnages intrinsèques / Speech perception consists of a set of bilateral computations that take continuously varying acoustic waveforms as input and generate discrete representations. Hypothesis of ‘asymmetric sampling in time’, suggests that auditory functional asymmetries can be explained by differences in temporal sampling between the two auditory cortices. We suggest that asymmetry in auditory cortical oscillations could play a role in speech perception by fostering hemispheric triage of information across the two hemispheres. Due to this asymmetry, fast speech temporal modulations, could be best perceived by the left auditory cortex, while slower modulations would be better captured by the right one. The aim of this thesis was to study and to test the validity of the predictions of the AST theory by investigating psychophysical and neurophysiological approach. They focus on the cortical activation in both hemispheres according to the nature of the auditory signal presented to both ears. Our results show that when we provide a different part of the speech envelope to each ear, word recognition is facilitated when the temporal properties of speech match the rhythmic properties of auditory cortices. We further show that the interaction between speech envelope and auditory cortices rhythms translates in their level of neural activity (as measured with fMRI). In the left auditory cortex, the neural activity level related to stimulus/brain rhythm interaction predicts speech perception facilitation. This interaction impacts speech perception performance. We propose that this lateralization effect could have practical implications in the framework of bilateral cochlear implants

Depuis quelques années, des recherches décrivent des effets alarmants de l’exposition à des environnements acoustiques artificiels sur les propriétés fonctionnelles des neurones du système auditif. L’objectif de ce projet était de déterminer si une exposition à très long terme à une intensité sonore, qui n’est pas reconnue par les législations pour provoquer des pertes permanentes ou temporaires (80dB SLP 8h/jour), induisait ou pas des changements au niveau des audiogrammes et des propriétés fonctionnelles des neurones du cortex auditif primaire.Des rattes adultes (Sprague Dawley) ont été exposées entre 3 mois à 18 mois (selon les groupes) à un milieu acoustique mimant les environnements sonores quotidiens de la majorité de la population et dont les effets n’ont jamais été étudiés sur de telles durées. L’originalité de ce projet réside dans l’analyse des effets à tous les niveaux du système auditif depuis le niveau périphérique (ABRs) jusqu’au niveau central (électrophysiologie corticale) ainsi que les conséquences possibles au niveau comportemental. Une tâche d’apprentissage perceptif inédite a été mise au point afin d’évaluer les effets de l’exposition. Au cours du vieillissement, nos données montrent une baisse des performances comportementales, une atteinte progressive des seuils ABRs et des atteintes de certains paramètres des réponses neuronales comme (i) la latence, (ii) la durée, (iii) la détection de silence dans une vocalisation, (iv) le suivit d’une modulation d’amplitude, (v) la reproductibilité des réponses à une vocalisation. Le principal effet de l’exposition à un environnement bruité est l’apparition d’un TTS après 6 à 12 mois d’exposition (qui disparait complètement en 3 semaines), sans que cela ait, de façon très surprenante, la moindre conséquence notable sur les seuils ABRs, l’activité évoquée corticale, ou les performances de discrimination des animaux. Ces résultats nous incitent à la prudence sur la généralisation des conclusions à tirer des expositions à des environnements bruités artificiels. / Over the last few years, studies have described alarming effects of exposure to artificial acoustic environments on the functional properties of neurons in the auditory system. The aim of this project was to determine if long-lasting exposure at a sound intensity which is not recognized by the legislation to cause permanent or temporary hearing loss (80 dB SLP 8h/ day) induced, or not, changes in the audiograms and functional properties of neurons in theprimary auditory cortex. Adult female rats (Sprague Dawley) were exposed over 3 to 18 months (depending on the group) to an acoustic environment mimicking daily sound environments surrounding a large part of the population, and whose effects have never been studied on such durations. The originality of this project lies in analyzing the effects at alllevels of the auditory system from peripheral (via ABRs) to central levels (cortical electrophysiology) and also the possible consequences at the behavioral level. A new perceptual learning task has been developed to assess the effects of exposure. During aging, our data showed a decrease in behavioral performance, a gradual impairment of ABRs thresholds as well as an impairment in parameters of the neural responses such as (i) the response latency, (ii) response duration, (iii) the ability to detect silence in a vocalization (iv) or to follow an amplitude modulation, (v) the reproducibility of response to vocalization. The main effect of exposure to a noisy environment is the appearance of a Temporary Threshold Shift (TTS) after 6 to 12 months of exposure (which completely disappears in three weeks). Surprisingly, this long lasting TTS had apparently no e ffect on ABRs thresholds, the evokedcortical activity, or the animal’s discrimination performance. These results encourage us to be quite cautious in generalizing the conclusions to be drawn from exposures to artificial noisyenvironments.

Introduction This dissertation studied structures and functions of auditory cortex in musicians with a rare auditory perception called absolute pitch (AP) using an in-vivo neuroimaging technique magnetic resonance imaging (MRI). The absolute pitch is defined as an ability to recognize pitch chroma, which is musical naming in the twelve-tone equal-temperament (12-TET) system (e.g., “C#”), of any given tonal sound without external references. It has been of interest of many psychologists since the experimental methods have been introduced in psychology over a century. Early behavioral experiments reported many findings that were validated in later studies with computerized measurement of behaviors. Over the recent two decades, in-vivo neuroimaging studies have found alteration in structures and functions of the brains of musicians with AP compared to control musicians without AP. However, quantitative models on the behaviors of neural systems behind the AP have not been suggested yet. Of course, neuronal modeling is a challenging problem in cognitive neuroscience studies in general. In order to generate such models to explain auditory perceptions such as AP, detailed information on structures and functions of neural systems must be obtained. In this context, we examined microarchitecture of the auditory cortex in musicians with AP using ultra- high field MRI that currently enables the highest spatial resolution of in-vivo imaging at the moment. In addition, we examined the functional connectivity between the auditory cortex and the other regions of the whole cortex. In the dissertation, detailed introduction of the pitch chroma perception is given throughout the human auditory systems from peripheral apparatus to non-primary auditory cortex in the Chapter I. In-depth discussion on the in-vivo imaging techniques, image processing, and statistical inferences focusing on the strength and potential pitfalls of the methods and their common practice in the Chapter II. In the Chapter III and IV, I explained MRI studies of the PhD project in details with discussions on the findings. Finally in the Chapter V, I summarized the major findings and discuss possible interpretation based on the framework of ‘dual auditory pathway hypothesis’. Study of Myeloarchitecture In the first study (Chapter III), a novel MRI sequence named magnetization-prepared two rapid gradient echo (MP2RAGE) was used to investigate cortical myelination. Myeloarchitecture of cerebral cortex is the one of the important histological concepts to understand organization of cortical column as well as cytoarchitecture. Neurons in the cortex are not only linked to the other distant neurons through the white matter but also connected vertically and horizontally to adjacent neurons. These short/long-distance axonal connections form myeloarchitecture of the cortex. The MP2RAGE sequence estimates a physical quantity called longitudinal relaxation rates (R1), which is sensitive to myelin concentration of the tissue. When compared to control musicians without AP, we found greater R1 in the anterior part of the right supratemporal plane in the musicians with AP. Given the finding was specific to the middle depth of cortex, the finding is unlikely related to long-distance axonal connections but likely to local connections. The precise location of the group difference was determined as the right planum polare in the template brain as well as in all individual brains. Based on the finding, I speculated that the working principles of the AP processes might be related to the dual auditory pathway hypothesis. In the theory, spatial auditory information is processed along the dorsal pathway (from the primary auditory cortex, to planum temporale, supramarginal gyrus, parietal lobules, and dorsolateral prefrontal cortex) whereas non-spatial auditory information is processed along the ventral pathway (from the primary auditory cortex to planum polare, temporal pole, anterior insular, and ventrolateral prefrontal cortex) in analogous to visual system. Because pitch chroma is spatially invariant property of an auditory object, and also it is less useful for auditory scene segregation compared to separation based on general pitch range (i.e., pitch height), I suggested the observation of cortical myelin in the anterior non-primary auditory cortex might be related to the absolute recognition of pitch chroma in AP listeners. Another potential implication of the heavy myelination is the function of myelination in neural development. In a rat model, it was demonstrated that the myelination of cortex triggers protein interactions that greatly restrict neuroplasticity after the ‘critical period’ of normal development. From genetic studies, it has been found that the onset of musical training is crucial in the acquisition of AP. Since the planum polare is related to pitch chroma processing, the increase of myelination in this region might indicate the preservation of the pitch chroma representation. Study of Intrinsic Functional Connectivity In the second study (Chapter IV), to further test the hypothesis that this highly myelinated planum polare works differently in the auditory networks, analysis of intrinsic functional connectivity using functional MRI (fMRI) measurement acquired during resting was performed. Although spontaneous neural activities during resting was once regarded as Gaussian noise without particular information, extensive researches revealed that the resting-state data (fMRI and also M/EEG) bears substantial information on the subnetworks of brain that subserve various perceptual and cognitive functions. Particularly for the perception of AP, it has been known that spontaneous and unintended recognition of pitch chroma from ambient sounds such as the siren of an ambulance. Thus it is reasonable to assume that the AP-specific network would be constantly active even at rest. From the resting-state fMRI data, greater cross-correlations between the right planum polare, which was found to be highly myelinated, and several cortical areas including the right lateral superior temporal gyrus, the anterior insula, and the left inferior frontal cortex were found in musicians with better AP performance. Moreover, greater cross-coherences between the right planum polare and the medial part of superior frontal gyrus, the anterior cingulate cortex, and the left planum polare were found in musicians with greater AP performance. As speculated, the involvement of the ventral auditory pathway in the AP-specific resting state network was strongly suggested from the tightened functional coupling between anterior supratemporal planes and the left inferior frontal cortex. Interestingly, the right planum polare exhibited greater cross-coherence with the important hub regions of the default mode network, i.e., anterior cingulate cortex and medial parts of the superior frontal cortex and the orbitofrontal cortex, implicating a link between the auditory network and default-mode network in AP listeners. This might be related to constant AP processes in AP listeners, which results in spontaneous and unintentional recognition of AP. Conclusion In the dissertation, novel MRI data from musicians with AP were provided adding knowledge of the myeloarchitectonic characteristics and related intrinsic functional connectivity of the auditory cortex to the current understanding on the neural correlates of AP. The findings were in favor of the proposed involvement of the ventral auditory pathway, which is known for processing spatially invariant properties of auditory objects. Further studies on neural behaviors of the auditory cortex in relation to the myeloarchitecture are needed in developing computational models of AP in the future. / Einleitung Diese Dissertation untersucht Strukturen und Funktionen des auditorischen Kortex in Musikern mit einer seltenen auditorischen Wahrnehmen, dem absoluten Gehör (aG), mit Hilfe des in-vivo Bildgebungsfahrens der Magnetresonanztomographie (MRT). Das absolute Gehör bezeichnet die Fähigkeit die Tonklasse (z.B. „C#“) innerhalb des 12-tönigen Systems gleichmäßiger Stimmung (12-TET) ohne externe Referenz benennen zu können. Das Phänomen des absoluten Gehöres ist Gegenstand psychologischer Untersuchungen seitdem die experimentellen Methoden vor über einem Jahrhundert vorgestellt wurden. Erste behaviorale Experimente berichteten zahlreiche Ergebnisse, die später in computer-gestützten Messverfahren validiert werden konnten. In den letzten 20 Jahren konnten Studien, unter Nutzung bildgebender Verfahren, Veränderungen in der Struktur und Funktion in den Gehirnen von Musikern mit absolutem Gehör feststellen. Bisher wurden jedoch noch keine quantitativen Modelle vorgestellt, die das Verhalten neuronaler Systeme beschreiben, die dem absoluten Gehört zugrunde liegen. Die Modellierung neuronaler Systeme stellt ein anspruchsvolles Problem der gesamten kognitiven Neurowissenschaften dar. Detaillierte Informationen bezüglich der Struktur und Funktion des neuronalen Systems müssen gesammelt, um mit Hilfe von Modelle auditorische Empfindungen wie das absolute Gehör erklären zu können. In diesem Zusammenhang haben wir die Mikroarchitektur des auditorischen Kortex von Musiker mit absolutem Gehör mit Hilfe eines ultrahohem Feld-MRTs untersucht; eine Methode mit der derzeit höchsten räumlichen Auflösung aller in-vivo Bildgebungsverfahren. Außerdem wurde die funktionelle Konnektivität zwischen dem auditorischen Kortex und anderen Regionen des gesamten Kortex untersucht. In Kapitel I der Dissertation wird detailliertes Grundwissen zur Empfindung von Tonklassen, vom menschlichen auditorischen System bis zum nicht-primären auditorischen Kortex, vermittelt. Eine vertiefte Diskussion der in-vivo Bildgebungsverfahren, der Bildverarbeitung und den statistischen Rückschlüssen ist Thema von Kapitel II, mit einem Fokus auf der üblichen Verwendung, den Stärken und potentiellen Fehlern der verwendeten Methoden. In den Kapiteln III und IV habe ich die MRT-Studien der Doktorarbeit erklärt und die Ergebnisse diskutiert. Kapitel V fasst die wesentlichen Forschungsergebnisse zusammen und diskutiert eine mögliche Interpretation der Ergebnisse auf Grundlage der Dual Auditory Pathway Hypothese. Untersuchung der Myelinarchitektur In der ersten Studie (Kapitel III) wurde eine neuartige MRT Sequenz, die magnetization-prepared two rapid gradient echo (MP2RAGE) Sequenz, genutzt um die kortikale Myelinisierung zu untersuchen. Die Myelinarchitektur des zerebralen Kortex ist eine der wichtigsten histologischen Konzepte, um sowohl die Organisation einer kortikalen Kolumne als auch die Zytoarchitektur zu verstehen. Die Neuronen des Kortex sind nicht nur an entfernte Neuronen über die weiße Substanz gekoppelt, sondern auch durch vertikale und horizontale Verbindungen an unmittelbar benachbarte Neuronen. Diese kurzen und langen axonalen Verbindungen formen die Myelinarchitektur des Kortex. Die MP2RAGE Sequenz bewertet die longitudinalen Relaxations Raten (R1), welche sensitiv für die Myelinkonzentration des untersuchten Gewebes ist. Verglichen mit einer Kontrollgruppe von Musikern ohne aG konnten wir einen höheren R1- Wert im anterioren Teil der rechten supra-temporalen Ebene in Musikern mit aG feststellen. Da das Ergebnis spezifisch für eine mittlere Tiefe des Kortex war ist es wahrscheinlicher, dies auf lokale Verbindungen als auf lange axonale Verbindungen zurückzuführen. Als genauer Ort der Gruppendifferenz wurde das rechte planum polare sowohl in einem idealisierten Gehirn als auch in den individuellen Gehirnen der Probanden festgestellt. Aufgrund dieses Ergebnisses habe ich die Hypothese aufgestellt, dass die Wirkungsweise des absoluten Gehörs mit der Dual Auditory Pathway-Theorie zusammenhängt. Diese Theorie besagt, dass räumliche auditorische Information entlang einer dorsalen Bahn (vom primären auditorischen Kortex zum planum temporale, supramarginalen Gyrus, Parietallappen und dorsolateralen präfrontalen Kortex) und nicht-räumliche Informationen entlang einer ventralen Bahn (vom primären auditorischen Kortex zum planum polare, Temporalpol, anterior insular und ventrolateralen präfrontalen Kortex), ähnlich dem visuellen System, verarbeitet werden. Da die Tonklasse eine räumlich invariante Eigenschaft eines auditorischen Objektes ist und es zudem für die auditorische Szenenunterscheidung weniger bedeutsam ist als die generelle Tonhöhe, habe ich die Vermutung angestellt, dass das kortikale Myelin im anterioren nicht-primären auditorischen Kortex mit dem absoluten Gehört für die Tonklasse im Zusammenhang steht. Eine weitere Implikation der starken Myelinisierung betrifft die Funktion von Myelin in der neuronalen Entwicklung. Im Tiermodell einer Ratte konnte gezeigt werden, dass die Myelinisierung des Kortex Proteininteraktionen auslöst, die die Neuroplastizität nach einer ‚kritischen Periode‘ der normalen Entwicklung erheblich einschränkt. Genetische Studien haben gezeigt, dass der Beginn der musikalischen Ausbildung für die Entwicklung des absoluten Gehöres entscheidend ist. Da das planum polare mit der Verarbeitung von Tonklassen in Verbindung gebracht wird, könnte ein Anstieg der Myelinisierung in diesem Bereich einen Erhalt der Tonklassenrepräsentation bedeuten. Untersuchung der intrinsischen funktionellen Konnektivität In der zweiten Studie (Kapitel IV) wurde die Hypothese, dass das stark myelinisierte planum polare in den auditorischen Netzwerken verschieden wirkt, mittels funktioneller MRT (fMRT) im entspannten Wachzustand weiter untersucht. Spontane Hirnaktivität wurde lange Zeit als Gaußsches Rauschen ohne spezielle Informationen angesehen. Umfangreiche Studien konnten jedoch zeigen, dass Messungen des Ruhezustandes, sowohl fMRT als auch M/EEG, Information bezüglich der Sub-Netzwerke tragen, die Hirnfunktionen der Wahrnehmung und Kognition unterstützen. Besonders in Bezug auf die Wahrnehmung mit absolutem Gehör konnte festgestellt werden, dass Umgebungstöne wie die Sirene eines Krankenwagens unbewusst hinsichtlich der Tonklasse erkannt werden. Diese Erkenntnis stützt die Annahme, dass das aG-Netzwerk auch im Ruhezustand aktiv ist. Mit Hilfe der fMRT-Daten wurde festgestellt, dass die Kreuzkorrelation zwischen dem stark myelinisierten rechten planum polare und weiteren kortikalen Arealen wie dem rechten lateral- superioren temporalen Gyrus, der anterioren insula und dem linken inferior-frontalen Kortex in Musikern mit besserer aG-Performanz erhöht ist. Weiterhin wurde eine erhöhte Kreuzkorrelation zwischen dem rechten planum polare und dem medialen Teil des superior-frontalen Gyrus, dem anterioren cingulate Kortex und dem linken planum polare in Musikern mit noch besser aG- Performanz festgestellt. Die erhöhte funktionelle Kopplung der anterioren supra-temporalen Ebene mit dem linken inferior-frontalen Kortex bekräftigt die Hypothese, dass der ventrale auditorische Pfad in dem aG- spezifischen Netzwerk des Ruhezustands beteiligt ist. Bemerkenswerterweise zeigte das rechte planum polare eine erhöhte Kreuzkorrelation mit wichtigen Hub-regionen des Default-Mode Netzwerkes, also dem anterioren cingulate Kortex und medialen Teilen des superior-frontalen Kortex, sowie dem orbito-frontalen Kortex. Dies bedeutet eine Verknüpfung des auditorischen Netzwerkes und des Default-Mode Netzwerkes in Menschen mit absolutem Gehör und könnte mit aG-Prozessen zusammenhängen, die die spontane und unbewusste Erkennung des absoluten Gehörs erlauben. Schlussfolgerung In dieser Dissertation wurden MRT-Daten von Musikern mit absolutem Gehör untersucht und damit zur Erweiterung des Wissensstandes bezüglich der Myelinarchitektur und der damit zusammenhängenden funktionellen Konnektivität des auditorischen Kortex beigetragen. Die Ergebnisse sprechen zugunsten der Einbindung des ventralen auditorischen Pfades, bekannt für die Verarbeitung räumlich-invarianter Eigenschaften auditorischer Objekte. Weitere Untersuchungen bezüglich des neuronalen Verhaltens des auditorischen Kortex in Verbindung mit der Myelinarchitektur sind notwendig, um quantitative Modelle des absoluten Gehörs entwickeln zu können.