How is information represented in real neural networks? Experimental results continue to provide evidence for presence of spiking patterns in network activity. The concept of polychronous groups attempts to explain these results by proposing that neurons group together to fire in non- synchronous but precise time-locked chains. Several methods for the detection of such groups have been proposed, however, they all employ extensive searching in network structure, which limits their usefulness. We present a new method by observing spiking dependencies in network activity to directly detect polychronous groups. Our method shows comparatively more efficient computation by trading off detection selectivity. The method allows for analysis of polychronous groups emerging in noisy networks. Our results support the existence of structure-forming properties of spontaneous activity in neural network.

GABAB receptors play an important role in regulation of neuronal excitability and stability of neural microcircuits. It is well known that dysregulation of slow GABAergic signalisation can lead to many pathological conditions (epilepsy, anxiety etc.). Current research indicates that the imbalance in the inhibitory transfer, caused by changes in the expression of GABABR in the auditory system could play an important role in the progression of tinnitus. The goal of the present thesis was to determine the distribution of the GABAB receptor and its auxiliary subunit KCTD12 in the mouse auditory cortex and the dorsal cochlear nucleus (DCN). Furthermore, a change in GABAB receptor localization in the DCN was observed in mice exposed to an acoustic stress. The GABAB receptor was expressed across the entire auditory cortex, both on the body and on the neuronal fibres. On the contrary, KCTD12 was found only in a particular subgroup of neurons that includes VIP (vasoactive intestinal peptide) and cholecystokinin positive interneurons., GABABR and KCTD12 protein were found in all layers and in all studied cells types (fusiform, cartwheel and stellate) of the DCN. Acoustic trauma of the WT mice resulted in GABAB receptor internalization specifically in fusiform cells that are the main projection neurons of the...

Communicating through speech is an important part of everyday life, and losing that ability can be devastating. Millions of patients around the globe have lost the ability to hear or speak due to auditory cortex deficits. Doctor’s ability to help these patients has been hindered by a lack of understanding of the speech processing mechanisms in the human auditory cortex. This dissertation focuses on enhancing our understanding of the mechanisms of speech encoding in human primary and secondary auditory cortices using two methods of electroencephalography (EEG) and electrocorticography (ECoG). Phonemes are the smallest linguistic elements that can change a word’s meaning. I characterize EEG responses to continuous speech by obtaining the time-locked responses to phoneme instances (phoneme-related potential). I show that responses to different phoneme categories are organized by phonetic features, and each instance of a phoneme in continuous speech produces multiple distinguishable neural responses occurring as early as 50 ms and as late as 400 ms after the phoneme onset. Comparing the patterns of phoneme similarity in the neural responses and the acoustic signals confirms a repetitive appearance of acoustic distinctions of phonemes in the neural data. Analysis of the phonetic and speaker information in neural activations reveals that different time intervals jointly encode the acoustic similarity of both phonetic and speaker categories. These findings provide evidence for a dynamic neural transformation of low-level speech features as they propagate along the auditory pathway, and form an empirical framework to study the representational changes in learning, attention, and speech disorders. Later in this dissertation, I use ECoG neural recordings to explore mechanisms of speech communication in real-world environments that require adaptation to changing acoustic conditions. I explore how the human auditory cortex adapts as a new noise source appears in or disappears from the acoustic scene. To investigate the mechanisms of adaptation, neural activity in the auditory cortex of six human subjects were measured as they listened to speech with abruptly changing background noises. Rapid and selective suppression of acoustic features of noise in the neural responses are observed. This suppression results in enhanced representation and perception of speech acoustic features. The degree of adaptation to different background noises varies across neural sites and is predictable from the tuning properties and speech specificity of the sites. Moreover, adaptation to background noise is unaffected by the attentional focus of the listener. The convergence of these neural and perceptual effects reveals the intrinsic dynamic mechanisms that enable a listener to filter out irrelevant sound sources in a changing acoustic scene. Finally, in the last chapter, I introduce the Neural Acoustic Processing Library (NAPLib). NAPLib contains a suite of tools that characterize various properties of the neural representation of speech, which can be used for characterizing electrode tuning properties, and their response to phonemes. The library is applicable to both invasive and non-invasive recordings, including electroencephalography (EEG), electrocorticography (ECoG) and magnetoecnephalography (MEG). Together, this dissertation shows new evidence for dynamic and adaptive processing of speech sounds in the auditory pathway, and provides computational tools to study the dynamics of speech encoding in the human brain.

Ces travaux de recherche ont eu pour objectif d’évaluer les capacités de discrimination des réponses des neurones et leur robustesse dans le bruit à chaque étage du système auditif. Nous avons ainsi quantifié la capacité de discrimination neuronale entre quatre vocalisations cibles conspécifiques masquées par un bruit stationnaire depuis le noyau cochléaire jusqu’au cortex auditif secondaire chez le cobaye anesthésié. La discrimination des vocalisations cibles par les populations neuronales a été fortement diminuée par le bruit dans toutes les structures, mais les populations du colliculus inférieur et du thalamus ont montré de meilleures performances que les populations corticales. La comparaison avec les réponses neuronales obtenues avec les vocalisations vocodées (38, 20 ou 10 bandes de fréquences) a révélé que la réduction des capacités de discrimination neuronale était principalement due à l'atténuation des modulations d'amplitude lente (< 20 Hz). En outre, nous avons quantifié la robustesse des réponses neuronales grâce à une méthode de classification automatique réalisée sur l’ensemble des données obtenues en présence du bruit stationnaire et d’un autre bruit appelé chorus. Cela a mis en évidence cinq catégories de comportements neuronaux (des plus robustes aux plus sensibles) et leurs proportions respectives sur l’ensemble du système auditif ainsi qu’au sein de chaque structure auditive. Cette analyse a montré également qu’il existait des neurones robustes à tous les étages du système auditif, bien qu’une proportion plus importante soit retrouvée au niveau du colliculus inférieur et du thalamus. Par ailleurs, la proportion de neurones robustes est plus faible dans le bruit chorus ce qui laisse suggérer que ce dernier est plus pénalisant que le bruit stationnaire. Il est important de souligner qu’une proportion non négligeable de neurones sous-corticaux et corticaux changent de comportement d’un bruit à l’autre de sorte que le comportement de ces neurones dans un bruit particulier est peu prédictible. Ces résultats démontrent donc que la discrimination neuronale en situation de dégradation acoustique est principalement déterminée par l’altération des modulations lentes d'amplitude à la fois au niveau sous-cortical et cortical et suggèrent que les structures sous-corticales contribuent de façon importante à la perception robuste d’un signal cible dans le bruit. / This research aimed at evaluating the discrimination abilities of neuronal responses and their robustness to noise at each stage of the auditory system, from the cochlear nucleus to the secondary auditory cortex. We quantified the neuronal discrimination performance between four conspecific vocalizations masked by a stationary noise in anesthetized guinea pig. Discrimination of target vocalizations by neuronal populations was significantly reduced by noise in all structures, but collicular and thalamic populations displayed better performance than cortical populations. The comparison with neuronal responses obtained with vocoded vocalizations (using 38, 20 or 10 frequency bands) revealed that the reduction in discrimination performance was mainly due to the attenuation of slow amplitude modulations (<20 Hz). In addition, we quantified the robustness of neuronal responses using an automatic classification method performed on the whole database obtained in presence of stationary noise and of another noise called “chorus” noise. This highlighted five categories of neural behavior (from robustness to sensitivity) and their respective proportions across the auditory system as well as within each auditory structure. This analysis demonstrated that robust neurons do exist at all stages of the auditory system, although a higher proportion was found in the inferior colliculus and thalamus. Moreover, the proportion of robust neurons is lower in the chorus noise, which suggests that the latter is more penalizing than the stationary noise. It is worth to point out that a significant proportion of subcortical and cortical neurons changed category from one background noise to another, so that the behavior of these neurons in a particular noise was unpredictable. These results provide clear evidence that neuronal discrimination in degraded acoustic conditions is mainly determined by alterations of slow amplitude modulations both at the subcortical and cortical level, and suggest that the subcortical structures significantly contribute to the robust perception of a target signal in noise.

No description available.

Tinnitus, ringing in the ears, is a phantom sound percept affecting roughly 10-20% of the total world population. Tinnitus severely impacts the quality of life of 10% of tinnitus sufferers, affecting their sleep, concentration, emotion, social enjoyment, and sometimes leading to depression and suicidal tendencies. In humans, most forms of tinnitus are associated with noise-exposure, leading to compensatory maladaptive plasticity of central auditory neurons. Human and animal studies suggest that tinnitus alters normal adult attentional resources. Human studies by McKenna, Hallam and Surlock 1996, suggested tinnitus-related impairment in sustained attention, vigilance, visual conceptualization and visuo-motor memory. Additionally, tinnitus may impact aspects of selective or divided attention as well as working and long-term memory. The involvement of primary auditory cortex and nicotinic signaling in selective attention, working and long-term memory has been well established. Neuronal nicotinic acetylcholine receptors (nAChRs) are present on presynaptic and postsynaptic inputs that innervate neurons across layers of primary auditory cortex (A1). Layer 5 pyramidal neurons (PNs) in the A1 are major output neurons, conveying auditory information to corticocortical and subcortical nuclei. The excitation of PNs is regulated by a complex microcircuitory of inhibitory neurons with vasointestinal peptide positive (VIP) neurons playing a key role in regulating the excitation. The focus of present studies was to: 1) Characterize tinnitus-related changes in the physiology and nAChR signaling of layer 5 PNs and VIP neurons in the A1 and 2) Determine the ability of nAChR partial/desensitizing agonists to ameliorate tinnitus pathology in subcellular studies. Wild-type, ChAT-Cre and VIP-Cre:Rosa26-loxP-stop-loxP-tdTomato (VIP-Cre:Rosa-tdTomato Long-Evans rats were used in the present study. CHAT-Cre rats allowed us to selectively express cre-inducible AAV-EF1a-DIO-hChR2(H134R)-EYFP and stimulate the cholinergic neurons of basal forebrain (BF). VIP-Cre:Rosa-tdTomato express fluorescent tdTomato protein in the VIP positive neurons allowing us to identify them under fluorescence microscopy using 550 nm wavelength. An established noise-exposure (one hour of 116 dB narrowband noise centered at 16 kHz) was used to induce behavioral tinnitus in a rat model. Approximately 50-60% noise-exposed animals (53/92) exhibited behavioral evidence of tinnitus with significant shifts in hearing threshold contiguous to the exposure frequency. Animals were classified as control, exposed tinnitus and non-tinnitus. In vitro whole-cell patch clamp recordings were performed in control and tinnitus animals. Results: Numerous tinnitus-related changes in the physiology of layer 5 PNs and VIP neurons, and changes in the activity of excitatory and inhibitory input neurons were observed. The resting membrane potential of A1 layer 5 PNs from tinnitus animals was significantly depolarized compared to PNs from unexposed controls. PNs from the A1 of animals with behavioral evidence of tinnitus showed increases in the frequency of excitatory and decreases in frequency of inhibitory spontaneous postsynaptic currents, which directly correlated with the rat’s tinnitus score. Optical stimulation of thalamocortical terminals from PNs in tinnitus animals evoked significantly larger excitatory/inward currents than in currents evoked in PNs from controls. A1 layer 5 PNs showed tinnitus-related decreases in postsynaptic gamma-amino butyric acid (GABA) signaling suggestive of GABA-A receptors (GABA-ARs) subunit switches or loss of GABA-ARs. VIP neurons favoring excitation of layer 5 PNs via disinhibition, were depolarized with significantly lower current to evoke action potentials (rheobase current). The excitability of VIP neurons was significantly increased, with this increase being strongly correlated to the rat’s tinnitus score. Tinnitus-related changes in nAChR signaling were then tested in layer 5 PNs and VIP neurons. Both PNs and VIP neurons receive cholinergic input from basal forebrain and were highly sensitive to nicotinic stimulation. Optical stimulation of basal forebrain (BF) terminals evoked a depolarizing current from VIP neurons. In tinnitus animals, layer 5 PNs showed a significant loss of nAChR signaling, while, VIP neurons showed tinnitus-related increase in responses to nicotinic stimulation. Most of the nAChR responses in auditory cortex are believed to be mediated via volume transmission of acetylcholine (ACh). Continuous voltage clamped recordings were used to examine the activity of excitatory and inhibitory neurons impacting PNs in the presence of bath applied ACh. We observed significant tinnitus-related changes in nAChR signaling with layer 5 PNs showing significantly larger GABAergic input after prolonged bath application of ACh. This led us to hypothesize that desensitization of nAChRs could increase/normalize the activity of GABAergic input neurons. To test this hypothesis, nAChR partial desensitizing agonists sazetidine-A and varenicline were used in cellular and behavioral studies. Immediately after bath application of sazetidine-A or varenicline, a dramatic increase in the activity of inhibitory input neurons onto PNs was observed. In a behavioral tinnitus test, both sazetidine-A and varenicline were effective in lowering the tinnitus-like behavior. In conclusion, we identified a significant tinnitus-related disruption in intrinsic physiology of layer 5 PNs and VIP neurons, with strong evidence of dysregulated cholinergic signaling. Partial/desensitizing agonists sazetidine-A and varenicline increased the activity of inhibitory input neurons, showing therapeutic potential in both subcellular and behavioral studies.

No description available.

The experiment tested the hypothesis that the acetylcholine (ACh) release in the rat auditory cortex is greater in rats undergoing auditory classical conditioning compared to rats in a truly random control paradigm where no associative learning takes place and that this is mediated by prefrontal afferent projections influencing the nucleus basalis magnocellularis (NBM), which in turn modulates ACh release in neocortex. Rats with bilateral ibotenic acid lesions of medial prefrontal and agranular insular cortices were tested in an auditory classical conditioning task while ACh was collected from the primary auditory cortex. It was hypothesized that lesions of these prefrontal areas would prevent learning-related increases of ACh release in the primary auditory cortex. The hypothesized results were supported. Results from this experiment provide unique evidence that medial prefrontal cortex projections to the NBM are important for mediating cortical ACh release during associative learning.

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.

The goal of this thesis is to investigate the functional role of the cortical column architecture within some of the existing brain coding theories. Here I focus on the hierarchical models of predictive coding and the 'phase of firing' coding hypothesis. Using an oddball paradigm consisting of a sequence of identical sounds interspersed with rare, unexpected sounds, one can observe a difference between the scalp potentials evoked by oddball and common sounds. This difference has been linked to predictive coding and novelty detection, and Stimulus Specific Adaptation (SSA) has been suggested as a likely substrate at the single neuron level. In order to simultaneously constrain hierarchical models of predictive coding, and so as to investigate the contributions that neural processing within the different cytoarchitectonic layers of the primary auditory cortex (A1) may make to SSA, I simultaneously recorded multi-unit activity and current source density (CSD) profiles across all layers in A1 of the rat in response to standard and oddball tones. Our results suggest that SSA arises at the level of the thalamocortical synapse and is further enhanced in the supragranular layers. The phase of low-frequency Local Field Potentials (LFPs) in primary sensory cortices carries stimulus related information and disambiguates the information about different stimuli evoking similar spike rates. However, it is yet unclear how these informative LFP phase values arise within the laminar organization of cortical columns. To address this issue, I performed CSD recordings in the area A1 of anaesthetized rats during the presentation of complex naturalistic sounds. Information theoretic analysis revealed that most LFP phase information originates from discrete CSD events consisting of strong granular-superficial-layer dipoles, likely triggered by bursts of thalamocortical activation. These events, which occur at rates of 2-4 Hz, reliably reset LFP phases at times of strong network excitation. They therefore provide a useful reference frame to measure neural activity with respect to salient times of stimulus history. CSD events display a diverse, stimulus-dependent morphology: these reflect the outcomes of cortical computations which result in varying extents of activation of infragranular output layers.