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The mature central nervous system (CNS) has the capacity to reorganise when there is a change in sensory input. However, studies using the N1 cortical auditory evoked potential, or its magnetic homolog N1m, have not consistently demonstrated evidence of plasticity in adults with late onset unilateral deafness. In addition, little is known about the time course of experience-related plasticity in adults with unilateral deafness. The aim of the studies described in this thesis was to investigate plasticity in adults with unilateral deafness, using N1 auditory evoked potentials. Deafness occurred as a result of surgery for the removal of an acoustic neuroma. The stimuli were 500-Hz and 4-kHz tones presented monaurally to the intact ear, and the data were analysed using global field power and dipole source analysis. In the first study (Chapter 3), hemispheric asymmetries in the N1 response were measured in a group of 24 normally hearing adults at presentation levels of 40, 60 and 80 dB sensation level (SL). The results revealed that the mean hemispheric asymmetry was greater for the 4-kHz stimulus but there was no significant effect of presentation level. In addition, the results revealed that the magnitude of hemispheric asymmetry depended on the ear of stimulation; a trend for larger asymmetries was observed following stimulation of the left ear. The results of the study provide confidence that the methodology is suitable for measuring hemispheric asymmetries in individuals with unilateral deafness. The effect of stimulus level is important since this will vary in plasticity studies involving individuals with late onset unilateral deafness due to their pure tone sensitivity thresholds. Clarifying the effect of stimulus frequency in normally hearing adults is important since the effect of stimulus frequency on plasticity following unilateral deafness has not been reported previously.In the second study (Chapter 4), N1 responses were measured in 19 adults with unilateral deafness (10 and 9 right- and left-sided deafness respectively). Stimuli were typically presented at 60 dB SL. The results revealed that there was significantly greater mean activity and a shift towards reduced hemispheric asymmetries compared with 19 audiogram-matched controls. Similar changes were apparent after both right- and left-sided deafness, and for both 500-Hz and 4-kHz stimuli. Therefore the results reveal evidence of experience-related plasticity that mirrors the findings reported in animal models. The reduced hemispheric asymmetries were reflected in the dipole source model used in this thesis by changes in dipole strength, location and orientation. These findings may explain the inconsistencies reported in previous studies that have used N1 or N1m, where dipole location and orientation have not always been taken into adequate consideration.In the third study (Chapter 5), longitudinal measurements were made in six adults just prior to the onset of complete unilateral deafness, and at 1-, 3- and 6-months after the onset (4 right-sided and 2 left-sided deafness respectively). The results from the second study were further analysed by splitting the data into two groups: nine participants with <2 years deafness and 10 with ≥2 year's deafness. The results from the longitudinal data revealed that there was a significant difference in mean activity across the four conditions. For both stimulus types an increase in mean activity occurred after the onset of deafness, and hemispheric asymmetries were reduced. The biggest changes occurred within 1-month, although further increases were noted in some individuals with ≥2 year's duration of deafness. Changes that continue over this period of time suggest different physiological mechanisms for plasticity within the human central auditory system.

When a baby is born deaf, a cochlear implant is often recommended as a medical habilitation tool to the parents. A cochlear implant is designed to bypass a damaged cochlea and stimulates auditory nerve directly, from where signals are sent all the way to the auditory cortex where sounds are perceived. We expect that a deaf child can detect and discriminate speech sounds with this device. With continuous auditory experiences, we hope that the auditory cortex of the deaf child can be developed as children with normal hearing do. Can a cochlear implant facilitate the development of the auditory brain? This study attempts to answer this question, exploring developmental effects on evoked potentials measured at the cortical level. Early-implanted, pre-lingually deafened cochlear implant users showed similar developmental patterns of cortical auditory evoked potentials to those of normal hearing listeners. However, the responses, related to sound discrimination, were affected by noise more in cochlear implant users. This may be related to perceptual abilities of cochlear implant users in harder listening conditions. The findings indicate that cortical auditory evoked potentials, related to both detection and discrimination, can be used to document the long developmental trajectory of the central auditory system in both normal hearing listeners and cochlear implant users. This study suggests that these responses can be used as a tool for estimating behavioral performance in cochlear implant users.

In der vorliegenden Arbeit sind physiologische und anatomische Auswirkungen einer Lärmexposition auf subcortikale Strukturen des zentralen auditorischen Systems zu unterschiedlichen Zeitpunkten posttraumatisch untersucht worden. Dabei sollte zwischen akuten (TTS-Gruppe) und langfristigen Effekten (PTS-Gruppe) unterschieden werden. Normalhörende Mäuse wurden für 3 Stunden mit einem Bandrauschen (5-20 kHz) bei 115 dB SPL beschallt und mittels Hirnstammaudiometrie der Hörverlust bestimmt. In der TTS- und der PTS-Gruppe lag im Vergleich zur Kontrolle eine signifikante Hörschwellenverschiebung mit einem höheren Hörverlust in der TTS-Gruppe vor. Zur Untersuchung zentraler Veränderungen wurden neuronale Spontanaktivitäten mittels Einzelzellableitungen im Hirnschnitt ermittelt. Weiterhin sind histologisch die Zelldichten in den Versuchsgruppen bestimmt worden. Außerdem wurde ein manganverstärktes MRT durchgeführt, um die calciumabhängige Aktivität darzustellen. Die untersuchten auditorischen Strukturen waren der Nucleus cochlearis (CN), der inferiore Colliculus (IC) und der mediale Kniehöckers (MGB). Die Ergebnisse zeigen, dass es einen Unterschied in den akuten und langfristigen Auswirkungen einer Lärmexposition gibt. In der TTS-Gruppe sind ausschließlich die Kerngebiete des CN im Hirnstamm betroffen, was auf direkte Einwirkungen der Lärmexposition hindeutet und akute toxische Exzitation im Gewebe auslösen kann. In der PTS-Gruppe treten physiologische und anatomische Veränderung in höheren Strukturen der Hörbahn auf. Dabei kann es sich sowohl um späte direkte Lärmauswirkungen als auch um plastische Veränderungen handeln, die durch die lärminduzierte Deprivation ausgelöst wurden. Einerseits kommt es zu einem dramatischen Zellverlust in den untersuchten Gebieten. Zum anderen steigt die calciumabhängige Aktivität in einigen Strukturen stark an. Dies kann sowohl durch veränderte neuronale Aktivitätsmuster, aber auch durch plastische und neurodegenerative Prozesse bedingt sein. / In the present study, noise-induced physiological and anatomical changes in subcortical structures of the central auditory system were investigated at different posttraumatic stages. Thus, it should be distinguished between acute (TTS group) and long-term (PTS group) effects of noise damage. Normal hearing mice were exposed to a band noise (5-20 kHz) for 3 hours at 115 dB SPL. Auditory brainstem responses were measured to determine the produced hearing loss. A significant threshold shift was detectable in the TTS as well as in the PTS group. This effect was greater in TTS animals. To investigate central changes, neuronal spontaneous activities were recorded from single units in brain slices. Further, cell densities were determined by histological techniques. In addition, calcium dependent activity was measured using manganese enhanced MRI. Investigations were carried out in central auditory structures of the cochlear nucleus (CN), the inferior colliculus (IC) and the medial geniculate body (MGB). The results demonstrate a difference in acute and long-term effects of noise exposure. In the TTS group, only the CN in the brainstem was affected, indicating a direct noise impact leading to acute excitotoxicity. In the PTS group, physiological and anatomical changes could also be observed in higher structures of the auditory pathway. The effects can be related to long-lasting noise damage as well as neural plasticity caused by deprivation of auditory input. The results show a dramatic cell loss within the investigated structures. Further, there is an increase in calcium dependent activity in several auditory brain regions which can be caused by changes in neuronal activity patterns, neuroplasticity and neurodegenerative processes.