Most bilateral cochlear implant (CI) users have horizontal sound-source localisation and speech perception in noise that is better than that of unilateral CI users and worse than that of normal-hearing listeners. The discrepancy between bilateral CI users and normal-hearing people is thought to partly represent technical limitations in current CI signal processing, which hinders the use of interaural time and level differences. One such limitation is the independent and unsynchronised signal processing in the two CIs. The Digisonic® SP Binaural (DSPB) CI aims to improve binaural hearing by providing synchronised processing of the acoustical inputs, using a single speech processor and two microphones. Two further studies have been published since the commencement of this research project on the spatial hearing ability of DSPB users. Although both these studies concluded that both horizontal sound-source localisation and speech perception in noise can be accessible though the DSPB CIs, consistently with what is provided by conventional bilateral CIs, these studies have some limitations that may have influenced their conclusions. For example, the way the localisation data of their subjects were analysed does not help to determine whether DSPB CI subjects can localise sounds at better than expected from guessing and whether their localisation ability is based on interaural cues or monaural cues introduced by the head shadow. Spatial benefits for speech perception were also not fully reported by the previous studies. The aim of the studies reported in this thesis was to address the limitations of the previous studies and explore in more depth the spatial benefits of the DSPB CIs. The spatial benefits experienced by eight DSPB CI subjects were assessed in horizontal sound-source localisation, speech perception in noise and self-reported measures. Their ability was also compared to eight unilateral CI subjects, who were chosen as likely to be representative of the better unilateral CI performers. Results showed that the majority of the postlingually deaf DSPB subjects could localise sounds at a better than chance range, defined by unbiased and biased guessing, which seems similar to previous results with conventional bilateral CI adults. Although the results for unilateral CI subjects indicate that monaural cues may provide some useful information for localisation, such cues were found to provide lower localisation accuracy than binaural cues provided by DSPB implants. Speech perception thresholds were also assessed with the speech and noise spatially co-located and separated. Results showed that, as with unilateral CI subjects, the DSPB subjects were not able to take advantage of separating speech from noise for speech perception. Results from the Speech, Spatial and Qualities of Hearing Scale indicated better self-reported spatial hearing ability for the DSPB than unilateral CIs groups, although it was not statistically significant. It is concluded that the DSPB CIs seem to provide advantages for horizontal localisation over unilateral CIs for the majority of postlingually deaf DSPB adults. There is, however, no evidence that the way the processing is synchronised in the DSPB CIs can offer any advantages over conventional bilateral CIs for localisation.

Whilst much research has focused on the general health needs of adolescents, little is known about the specific needs of teenagers who wear cochlear implants. Thus it is important to widen the knowledge base regarding the experiences of this population, and to assist professionals to support this age group more effectively. This qualitative study investigated teenage cochlear implant users’ perceptions of deafness, surgery, fitting of the device and life as a cochlear implant wearer in order to gain a more comprehensive understanding of teenagers’ experiences of living with a cochlear implant by putting their perspectives at the heart of the research. This was achieved by working with the teenagers collaboratively throughout the research. Phase one of the study involved engaging with a small group of teenagers with cochlear implants to develop a website that would allow them to share their experiences. In phase two, ten semi-structured interviews were undertaken and nine were analysed using template analysis. Some teenagers experienced great preoperative anxiety and significant post-operative pain. Anxiety and pain are physiologically linked so strategies for reducing their anxiety are discussed. There was also a mismatch between their expectations and the disappointing reality of adjusting to the device. Disconfirmation-expectancy theory suggests that expectations counselling may narrow this gap. However, over time they experienced significant functional and psychosocial benefits as a result of their lives being easier. Almost all described complex, flexible identities where they felt connections with both the hearing and deaf world. Theoretical models of deaf identity support this ‘bicultural’ state. However, the hearing world sometimes posed difficulties for them when the listening environment was challenging. By giving prominence to the teenagers’ voices this study has added new knowledge concerning their experience of surgery. The findings also more fully revealed the challenges of adjusting to the device and the impact of having a cochlear implant on the teenagers’ identities.

Residual hearing preservation is necessary for deaf patients to experience the full benefits of electro-acoustic stimulation cochlear implants. Hearing preservation is often considered a benchmark of successful atraumatic surgery and cochlear health preservation, making it an important goal of the procedure. The role of inflammatory status in hearing preservation has been empirically supported through the development of surgical protocols featuring corticosteroids. Its role is also inferred though investigations of inner-ear inflammatory responses, or studies of the inflammatory component in auditory pathologies. However, work directly investigating the effect of systemic inflammatory state on their audiological outcomes has never been attempted. A multi-method research strategy consisting of: a murine immunohisto chemical pilot study, a meta-analysis of cochlear implant adverse events, a meta-analysis of factors related to hearing preservation, and a preliminary longitudinal observational clinical outcomes study was implemented. The results from the studies were incorporated into a conceptual framework of the relationship between multiple factors and their effect on outcomes in cochlear implantation. This body of work suggests that cochlear inflammatory state is a significant effector of hearing preservation. It introduces the concept of an individual's systemic inflammatory state having bearings on their clinical outcomes. The consequences of this body of work include: i) suggested modifications to surgical protocols so as to maximise hearing preservation , ii) recommended routine monitoring of a patient's inflammatory state throughout their care pathway, iii) the importance of considering inflammatory state and the timing of a patient's surgery in order to allow for more stratified medicine, iv) a highlighted need for multi-centre collaborations in order to create a more exhaustive model of outcomes in hearing preservation surgery, and v) a need for deeper investigation of the pathophysiology of hearing loss for more guided research on deafness intervention.

Cochlear implant users are typically able to achieve high levels of speech recognition in quiet but struggle to follow speech even in moderate levels of background noise. It may be possible to improve cochlear implant users’ speech perception scores in noise, by making more efficient use of the limited bandwidth available for transmitting important speech information, rather than increasing the amount of information transmitted. Acoustic landmarks are locations in the speech signal which are rich in information and allow a listener to identify a particular speech sound as a vowel, sonorant consonant or obstruent consonant; it is around these regions that important speech cues tend to be concentrated. Obstruent consonants are signalled by sudden amplitude and spectral changes and the onset/offset of a period of noise. It has been shown that the auditory system is particularly responsive to rapid spectral changes, manifested as increased firing rates of auditory nerve fibres, particularly at onsets of signals. Cochlear implant users commonly confuse speech sounds with rapidly changing spectral patterns, possibly due to the poor transmission of obstruent landmark information. The aim of the present work was to develop an obstruent landmark enhancement strategy which could be integrated into current cochlear implant processing. The first stage of this process required the identification of obstruent landmarks from the noise-mixed speech stimuli. An existing automatic landmark detection algorithm did not achieve the high levels of accuracy required for use in the present study and so a set of hand-generated labels were created, and used to guide the proposed obstruent landmark enhancement strategy. A series of cochlear implant simulation experiments were conducted to help evaluate the strategy and guide further developments. Results from the simulation studies suggest that the proposed method of obstruent landmark enhancement does not help to improve speech recognition in noise for normal hearing listeners listening to a cochlear implant simulation. It is likely that the strategy outlined in this thesis did not help to improve the saliency of obstruent landmark events as the enhancement was applied to the noise as well as the target speech signal, making it difficult for listeners to resolve the boosted landmark information. However, the results also highlight the limitations of using cochlear implant simulations to evaluate the strategy and so the findings are not necessarily a predictor of actual cochlear implant user performance.

Distortion product otoacoustic emissions (DPOAEs) are small sounds believed to be the combination of distortion and reflection energy produced by the cochlea in response to stimulation with simultaneous pure tones. Although used clinically, the exact generation mechanisms associated with DPOAEs are not clear; this is especially the case for 2f2-f1. It is thought that 2f1-f2 and 2f2-f1 DPOAEs contain reflection (R) and distortion (D) energy; the D energy may arise from the region of overlap between the stimulus travelling waves while R energy is reflected from fixed points along the basilar membrane. Cochlear mechanics would suggest the two emissions cannot arise from the same cochlear location; current theories suggest the f2 characteristic place is important to 2f1-f2 while 2f2-f1 is generated more basally. Theories of DPOAE generation have been investigated using various techniques , including time domain investigations. Time domain investigations have often used the phase gradient latency (PGL) technique but this has inherent limitations. An alternative approach is primary tone phase variation (PTPV) - a phase rotation method described by Whitehead et al. (1996) that allows for specific DPOAEs to be extracted. This study has used PTPV to investigate DPOAEs generated by an ISVR developed cochlear model and DPOAEs recorded from 40 normal hearing ears (across two experiments); the overall aim of the study is to learn more about the generation of 2f1-f2 and 2f2-f1 emissions by viewing DPOAEs in the time domain with PTPV. Specific areas of interest are the effect of frequency ratio and primary ramping on the time course of 2f1-f2 and 2f2-f1, and how the time course of emissions varies with stimulus level and fine structure position. It is believed these areas will allow for theories of DPOAE generation to be tested. Output from simulations and recorded emissions supports what is already known and theorised about DPOAE generation. It would appear that 2f1-f2 and 2f2-f1 are the product of multiple components originating from a distributed cochlear source. Temporal behaviour of emissions is influenced by stimulus parameters including level, frequency and ratio. This investigation has contributed to knowledge by studying 2f1-f2 and 2f2-f1 emissions with the PTPV procedure and a novel onset latency estimation technique. Data was collected from a group of normal hearing participants and compared to output of a cochlear model.

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Noise-induced hearing loss (NIHL) is one of the most common sensory disabilities in humans. NIHL is ranked as the world's top industrial injury and a significant cause of hearing loss in teenagers, thus affecting many age groups. This research is timely since a recent study has demonstrated that NIHL has increased dramatically in adolescents, with a 30% increase in this group in the past 10 years, thus coining the term “MP3” generation. The implications of the "MP3" generation will lead to increasing long-term health costs and life-long hearing problems necessitating the use of hearing aids from a young age. Research has shown that exposure to acoustic trauma causes an increase in metabolic activity within the inner ear, with a initial peak in free radical production during the acoustic trauma (within hours) followed by a secondary peak at seven to 10 days after the trauma. Free radicals cause decreased cochlear blood flow, excitotoxic neuronal swelling, and induction of cell death within the inner ear. Recent studies have demonstrated that antioxidant treatments can scavenge free radicals and thus attenuate downstream effects of free radical production. While this has been a major breakthrough for NIHL research, the specific roles played by the different classes of free radicals (reactive nitrogen/oxygen species) remains unclear. The aims of this project were: AIM 1: To determine whether inhibition of reactive nitrogen species can prevent NIHL, using taurine as a nitric oxide scavenger. AIM 2: To establish if there was a dose-dependant response to any effect observed. The research directly addresses a prominent and recognised otolaryngological disease that affects mental and social health. The long-term goal is to develop a pharmaceutical therapy for NIHL to ultimately prevent a debilitating disease and improve human health. Our work also looks at early use of stem cell therapies to repair after acoustic trauma.

Age-related hearing loss (ARHL), or Presbycusis, is the most prevalent sensory impairment observed in the elderly. It is a progressive, symmetrical, age-related sensorineural hearing loss, most pronounced at higher frequencies. ARHL is a multifactorial disease, with contribution from both environmental and genetic factors. To date, little progress has been made in determining the genetic loci involved. The aim of my doctorate studies is to elaborate upon the genetics underlying ARHL through the identification and characterization of ENU-induced mouse models of ARHL. This approach has identified trombone, a recessive model of ARHL arising from the Harwell Ageing Screen. Recurrent auditory phenotyping at 2, 6, 9 and 12 months of age shows that affected animals display elevated ABR thresholds from 9 months of age, when compared to littermates, and these are further increased at 12 months of age. Genome mapping studies identified a 12.5Mb critical region on chromosome 2 and next generation sequencing identified a T>C mutation in the novel deafness gene Slc4a10, causing a leucine to proline substitution in the encoded protein. Immunohistochemical staining of cochlear sections demonstrates that Slc4a10 is expressed in the type II and V fibrocytes of the spiral ligament of wildtype mice, whereas no labelling is observed in Slc4a10^trmb/trmb mice. In addition, ultrastructural studies show progressive sensory hair cell loss (inner and outer) in the Slc4a10^trmb/trmb mice from >6 months of age. Furthermore, histological assessment of the lateral wall identified strial thinning in the Slc4a10^trmb/trmb mice. Given the expression pattern and morphological changes observed, endocochlear potentials were measured in these mice. This identified that Slc4a10^trmb/trmb mice have a chronically low endocochlear potential compared to their wildtype and heterozygous littermates. My findings establish the presence of Slc4a10 in the inner ear and suggest an important role for this sodium-coupled bicarbonate transporter in normal auditory function. I hypothesize that trombone is a novel model of strial presbycusis and further functional characterization of this model promises to increase our understanding of the pathobiology associated with age-related hearing loss.

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