The interrelationships between brain, cognition, and behaviour are complex but can be more clearly characterised by studying disorders with an underlying genetic basis. This thesis examined these interrelationships in the context of Williams syndrome (WS), a neurodevelopmental genetic disorder that affects aspects of cognition, behaviour, and brain structure. The principal aims of this thesis were to evaluate the cognitive, behavioural, and neuroanatomical profile of WS individuals and to explore the relationships between aspects of the cognitive and behavioural profile and the neuroanatomical changes that are evident in WS. Three general hypotheses, and 10 specific hypotheses, were postulated as a means of exploring these aims. The first general hypothesis predicted that WS individuals would demonstrate distinct features within their cognitive and behavioural profile. Specifically, it was predicted that WS individuals would show relative strengths on verbal tasks and significant deficits on visuospatial and mathematical tasks, in contrast to control participants who were predicted to show a more even profile. It was also predicted that WS individuals would show evidence of heightened affect in response to music and demonstrate hypersociability as compared to control participants

Thesis (M. Communication Pathology)--University of Pretoria, 2009. / Includes bibliographical references.

<p>Auditory sensations can arise from objects in our environment or from our own actions, such as when we speak or make music. We must able to distinguish such sources of sounds, as well as form new associations between our actions and the sounds they produce. The brain is thought to accomplish this by conveying copies of the motor command, termed corollary discharge signals, to auditory processing brain regions, where they can suppress the auditory consequences of our own actions. Despite the importance of such transformations in health and disease, little is known about the mechanisms underlying corollary discharge in the mammalian auditory system. Using a range of techniques to identify, monitor, and manipulate neuronal circuits, I characterized a synaptic and circuit basis for corollary discharge in the mouse auditory cortex. The major contribution of my studies was to identify and characterize a long-range projection from motor cortex that is responsible for suppressing auditory cortical output during movements by activating local inhibitory interneurons. I used similar techniques to understand how this circuit is embedded within a broader neuromodulatory brain network important for learning and plasticity. These findings characterize the synaptic and circuit mechanisms underlying corollary discharge in mammalian auditory cortex, as well as uncover a broad network interaction potentially used to pattern neural associations between our actions and the sounds they produce.</p> / Dissertation

Early language experience is thought to be essential to develop a high level of linguistic proficiency in adulthood. Impoverished language input during childhood has been found to lead to functional changes in the brain. In this study, we explored if delayed exposure to a first language modulates the neuroanatomical development of the brain. To do so, voxel-based morphometry (VBM) was carried out in a group of congenitally deaf individuals varying in the age of first exposure to American Sign Language (ASL). To explore a secondary question about the effect of auditory deprivation on structural brain development, a second VBM analysis compared deaf individuals to matched hearing controls. The results show that delayed exposure to sign language is associated with a decrease in grey-matter concentration in the visual cortex close to an area found to show functional reorganization related to delayed exposure to language, while auditory deprivation is associated with a decrease in white matter in the right primary auditory cortex. These findings suggest that a lack of early language experience alters the anatomical organization of the brain.

The interrelationships between brain, cognition, and behaviour are complex but can be more clearly characterised by studying disorders with an underlying genetic basis. This thesis examined these interrelationships in the context of Williams syndrome (WS), a neurodevelopmental genetic disorder that affects aspects of cognition, behaviour, and brain structure. The principal aims of this thesis were to evaluate the cognitive, behavioural, and neuroanatomical profile of WS individuals and to explore the relationships between aspects of the cognitive and behavioural profile and the neuroanatomical changes that are evident in WS. Three general hypotheses, and 10 specific hypotheses, were postulated as a means of exploring these aims. The first general hypothesis predicted that WS individuals would demonstrate distinct features within their cognitive and behavioural profile. Specifically, it was predicted that WS individuals would show relative strengths on verbal tasks and significant deficits on visuospatial and mathematical tasks, in contrast to control participants who were predicted to show a more even profile. It was also predicted that WS individuals would show evidence of heightened affect in response to music and demonstrate hypersociability as compared to control participants

The interaural level difference (ILD) is a sound localization cue first computed in the lateral superior olive (LSO) by comparing the loudness of sounds between the two ears. In the auditory cortex, one class of neurons is excited by contralateral but not ipsilateral monaural sounds. These "EO" neurons prefer ILDs where contralateral sounds are louder than ipsilateral sounds. Another class, the "PB" neurons, are unresponsive to monaural sounds but respond predominantly to binaural ILDs, when both ears receive simultaneous sounds of roughly equal loudness (0 ILD). Behavioral studies show that ILD sensitivity is invariant to increasing sound levels. However, in the LSO, ILD response functions shift towards the excitatory ear as sound level increases, indicating level-dependence. Thus, changes in firing rate can indicate either a change in sound location or sound level, or both. This suggests a transformation in level-sensitivity between the LSO and the perception of sound sources, yet the location of this transformation remains unknown. I performed recordings in the auditory cortex of the rat to test whether neurons were invariant to overall sound level. I found that with increasing sound levels, ILD responses were level-dependent, suggesting that level invariance of ILD sensitivity is not present in the rat auditory cortex. In general, neurons follow one of two processing strategies. The tuning of cortical cells typically follows the "inheritance strategy", such that the spiking output of the cell matches that of the excitatory synaptic input. However, cortical tuning can be modified by inhibition in the "local processing strategy". In this case, neurons are prevented from spiking at non-preferred stimuli by inhibition that overwhelms excitation. The tuning strategy of cortical neurons to ILD remains unknown. I performed whole-cell recordings in the anesthetized rat and compared the spiking output with synaptic inputs to ILDs within the same neurons. I found that the PB neurons showed evidence of the local processing strategy, which is a novel role for cortical inhibition, whereas the EO neurons utilized the inheritance strategy. This result suggests that an auditory cortical circuit computes sensitivity for midline ILDs. This dissertation includes previously published/unpublished co-authored material.

O implante coclear tem sido indicado para a reabilitação de crianças com Espectro da Neuropatia Auditiva, com ampla variação no desempenho na percepção de fala. Caso o desenvolvimento das estruturas auditivas centrais não ocorra normalmente, pode-se presumir que as habilidades perceptuais que são a base para a percepção e produção da fala também não se desenvolverão normalmente. Nesse contexto, é possível questionar se a maneira como o sistema auditivo dessas crianças responde à estimulação elétrica após o período de privação sensorial poderia ser uma das justificativas para a variabilidade no resultado obtido com o implante coclear. O objetivo deste estudo foi caracterizar o componente P1 dos potenciais evocados auditivos de longa latência em indivíduos com Espectro da Neuropatia Auditiva usuários de implante coclear e correlacioná-los com o desempenho na percepção de fala e secundariamente a outras variáveis relacionadas ao implante coclear. Participaram do estudo 14 crianças com Espectro da Neuropatia Auditiva, usuárias de implante coclear, de ambos os sexos, na faixa etária de 4 a 11 anos. Foi realizada a pesquisa dos potenciais evocados auditivos de longa latência com estimulação acústica, utilizando estímulo de fala /da/ apresentado em campo livre, e a avaliação da percepção de fala por meio do protocolo GASP (BEVILACQUA; TECH, 1996). Como resultado, foi constatado que foi possível registrar o componente P1 em 85,7% desta população, sendo que o valor da latência do componente P1 apresentou correlação significante com o tempo de privação sensorial demonstrando que quanto maior o tempo de privação sensorial, maior a latência do componente P1. Não foi observada correlação significante entre o componente P1 e o tempo de uso do implante coclear. Foi observado que quando separados os indivíduos em grupos de acordo com o desempenho na percepção de fala, aqueles que apresentaram um melhor desempenho possuíam a latência do componente P1 estatisticamente menor, comparados ao de pior desempenho. Com os resultados obtidos neste estudo foi possível caracterizar o componente P1 dos potenciais evocados auditivos de longa latência em crianças com Espectro da Neuropatia Auditiva usuárias de implante coclear e demonstrar a correlação com o desempenho de percepção de fala e tempo de privação sensorial. Em crianças com Espectro da Neuropatia Auditiva, o componente P1 pode servir como um preditor do desempenho da criança usuária de implante coclear para a percepção de fala. / The cochlear implant has been recommended for the rehabilitation of children with Auditory Neuropathy Spectrum, with wide variation in performance in speech perception. If the development of central auditory structures does not occur normally, one can assume that the perceptual abilities that are the basis for the perception and speech production will not develop normally either. In this context one might question if the way the auditory system of these children respond to electrical stimulation after a period of sensory deprivation could be one of the reasons for this variability in the results obtained with the cochlear implant. The aim of this study was to characterize the P1 component of long-latency auditory evoked potentials in cochlear implanted individuals with Auditory Neuropathy Spectrum and correlate it with performance in speech perception and secondarily to other variables related to cochlear implant. The study included 14 cochlear implanted children with Auditory Neuropathy Spectrum, of both sexes, aged from four to eleven years. We studied the long-latency auditory evoked potential with acoustic stimulation, using speech stimuli presented in open field, and assessment of speech perception by means of GASP test (BEVILACQUA; TECH, 1996). As a result, we found that it was possible to register the P1 component in 85.7% of this population, and the P1 component latency value showed a significant correlation with the duration of sensory deprivation showing that the longer the duration of sensory deprivation, the greater the latency of the P1 component. There was no significant correlation between the P1 component and the time of cochlear implant use. It was observed that when the individuals were separated into groups according to performance on speech perception, those who performed better had the P1 component latency statistically lower when compared to the worst performers. With the results obtained from this study it was possible to characterize the P1 component of long-latency auditory evoked potentials in cochlear implanted children with Auditory Neuropathy Spectrum and demonstrate a correlation with the performance of speech perception. In children with Auditory Neuropathy Spectrum, the P1 component may serve as a predictor of the performance of a cochlear implanted child for speech perception.

No description available.

Des preuves convergentes ont attribué aux interneurones de l’inhibition périsomatique (IIPs) un rôle clé dans la production des oscillations gamma (OG). J’ai sondé optogénétiquement l'effet de l'inhibition périsomatique réduite sur les OG et l'apprentissage associatif dans le cortex auditif des souris se comportant librement. Contrairement aux expectatives, je n'ai pas observé une réduction des OG pendant l'inhibition des IIPs, mais plutôt une forte augmentation de l'amplitude dans les OG. L'amplification du potentiel évoqué auditif (PEA) N15, ainsi que l'absence d'une augmentation de la synchronisation entre le cortex et le thalamus, suggèrent que la diminution de l'inhibition périsomatique désinhibe le cortex auditif et favorise la génération intracorticale des OG. Dans une autre expérience, j’ai montré que l'inhibition des IIPs a détérioré l'apprentissage et a produit une réduction liée à l'expérience dans le PEA N15. Enfin, j’ai trouvé que l'abaissement de l'inhibition optogénétique livré à IIP et le réapprentissage des souris ont renforcé les OG auditivement induites. / Convergent evidence has attributed to perisoma-inhibiting interneurons (PIIs) a key role in the generation of gamma oscillations (GO). I optogenetically probed the effect of reduced perisomatic inhibition on GO and associative learning in the auditory cortex of freely behaving mice. Contrary to expectations, I did not observe a reduction in GO during inhibition of PIIs, but rather a strong increase in the amplitude of GO. The amplification of the auditory-evoked potential (AEP) N15, together with the absence of an increase in synchrony between the cortex and the thalamus, suggest that decreased perisomatic inhibition disinhibits the auditory cortex and promotes the intracortical generation of GO. In a different experiment, I showed that inhibition of PIIs impaired learning and produced an experience-related reduction in the AEP N15. Lastly, I found that lowering the optogenetic inhibition delivered to PIIs and retraining mice enhanced auditory-induced GO.

L’implant cochléaire, la neuroprothèse la plus répandue et la plus réussie de nos jours, permet à des sujets sourds profonds de récupérer une perception auditive permettant une compréhension du langage. Bien que les technologies et les processeurs actuels aient grandement évoluées depuis ces vingt dernières années, la stratégie optimale pour coder l'intensité sonore dans l’implant n’a pas encore été trouvée. L'accès à des indices physiologiques est difficile chez le patient humain alors qu’il est relativement simple chez l’animal. Le but de cette thèse était de développer un modèle animal (cobaye) d'implantation cochléaire et d'étudier la réponse du système auditif à différentes stratégies de stimulation. Les réponses du nerf auditif et des neurones du cortex auditif primaire ont été obtenues lors de stimulations via un implant cochléaire simplifié.Nous avons observé que l’importante variabilité inter-individuelle dans l’efficacité de 2 stratégies (augmentation d’amplitude vs. de durée des pulses électriques) à augmenter les réponses du nerf auditif se répercute au niveau du cortex auditif. Les tests de nouvelles formes de pulses (pulses asymétriques ou en rampes) sur les réponses des neurones corticaux suggèrent que ce type de pulses permettrait de réduire l’étendue corticale activée par la stimulation électrique même aux charges les plus élevées. Là aussi, une importante variabilité inter-individuelle a été observée. Cela a conduit à ce que les activations corticales les plus proches de l’activation normalement observée par des sons purs, soient obtenues soit avec une forme de pulses soit une autre. Cette thèse prône donc qu’il est indispensable d’avoir accès à de nombreuses stratégies de stimulation sur chaque sujet afin de choisir celle la plus adaptée pour un patient donné. / Cochlear implant, the most successful neuroprosthesis allows deaf subjects to recover auditory perception and speech intelligibility. Over the last decades, the technology and the coding strategies in cochlear implants have been largely improved but the optimal strategy for coding loudness is still problematic. Human studies face a lot of restrictions especially regarding the collection of electrophysiological events. The primary goal of this thesis is to develop an animal model (guinea pig) of implantation and to study the auditory system's responses for different strategies for coding sound loudness (increase in amplitude vs. duration of electrical pulses). We studied the responses of the auditory nerve and primary auditory cortex obtained with electrical stimulation delivered through a simplified cochlear implant.We observed that the large inter-individual variability in the efficacy of these two classical strategies for increasing auditory nerve responses is reflected in the auditory cortex. Testing new forms of pulses (asymmetric pulses or ramped pulses) suggests that this type of pulses would reduce the evoked responses of cortical neurons even at the highest injected charges. Again, a large inter-individual variability was observed. As a consequence, for each animal, the cortical response the closest from the activation normally observed with pure tones, is obtained either with one form of pulses or another. This thesis advocates that it is essential to have access to several stimulation strategies on each subject in order to choose the most appropriate for a given patient.