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This thesis sets out to improve the intelligibility of a target speech sound source when presented with simultaneous masking sounds. A summary of the human hearing system and methods for spatialising sounds is provided as background to the problem. A detailed review of relevant research in auditory masking, auditory continuity and speech intelligibility is discussed. Angular separation and sound object differentiation through amplitude modification are used to enhance a target speech sound. A novel method is developed for achieving this using only the binaural signals received at the ears of a listener. This new approach is termed an auditory lens. Psychoacoustic evaluation of the auditory lens processing has shown comparable intelligibility scores to direct spatialisation techniques which require prior knowledge of sound source spectral content and direction. The success of the auditory lens has led to a number of potential further research projects that will take the processing system closer to a real wearable product.

Simulations of monaural cochlear implants in normal-hearing listeners have shown that the deleterious effects of upward spectral shifting on speech perception can be overcome with training. This thesis examines whether the same is true when simulating bilateral stimulation. Can listeners adapt to upward-shifted speech information presented together with contralateral unshifted information? In two series of experiments, perceptual adaptation was investigated for both speech in quiet with a large interaural spectral mismatch, and speech in noise with a moderate interaural spectral mismatch. For speech in quiet, a six-channel dichotic sine-carrier vocoder simulated the binaurally mismatched frequency-to-place map. Odd channels were presented to one ear with an upward shift equivalent to a 6 mm basilar membrane distance, while even channels were presented to the contralateral ear unshifted. For speech in noise, the number of vocoded channels was increased to ten, and the upward spectral shift applied to the odd channels was decreased to 3.8 mm. Prior to vocoding, speech was combined with speech-shaped noise at a signal-to-noise ratio of 10 dB (or 0 dB for vowels). Listeners were trained with Connected Discourse Tracking for 5.3 hours or 10 hours, with the binaurally mismatched processor and/or just the shifted monaural bands. Speech perception was tested with sentence and vowel tests before, during and after training. Listeners showed adaptation to the upwardly shifted speech, but for nearly every speech test, intelligibility with the binaurally mismatched processor matched intelligibility with just the unshifted bands. Consistent with earlier findings with monaural spectral shifts, then, this research suggests that listeners are capable of adapting to a spectral shift, even in the presence of background noise. However, they appear to be resistant to integrating mismatches in frequency-place maps between the ears. A theory of “better ear” listening is proposed to account for this resistance. The findings are consistent with psychophysical studies of binaural hearing, which show maximal ITD and ILD sensitivity for similar interaural cochlear places. In optimizing bilateral cochlear implants for speech perception, it may thus be important to keep frequency-to-place maps similar in the two ears.

Objectives: To investigate the impact of tinnitus on the patient and their partner, in terms of psychological distress. To consider the influence of tinnitus severity, gender, hearing impairment, relationship quality and coping style. Method: Twenty-two patients and partners were recruited. A postal questionnaire was used. This included the General Health Questionnaire - 30 item, Golombok Rust Inventory of Marital State, Tinnitus Handicap Inventory and Coping Inventory for Stressful Situations. Questionnaires were also designed to ascertain information such as demographic details and consequences of tinnitus. Data were subjected to a content and statistical analysis. Results: Low levels of psychological distress were reported both by patients and partners and no significant difference was found between their distress levels. Higher distress was unrelated to increased relationship difficulty. Partners of those with hearing impairment reported higher distress. Hearing impaired patients and their partners reported fewer relationship problems. Gender was unrelated to psychological distress, or to tinnitus severity. An association between severe tinnitus and increased distress was found for both patients and partners. Severe tinnitus was however, unrelated to relationship difficulty. Patients with severe tinnitus used avoidant and emotion coping more than those with mild tinnitus. Coping style and patient gender interacted; females tended to engage in emotion and avoidant coping more than males. Partners reported that their relationship and communication with the patient were negatively influenced by tinnitus. Conclusion: Tinnitus did not lead to increased distress in patients compared to partners; however, partners reported problems related to tinnitus. Severe tinnitus related to increased distress in patients and partners. Severe tinnitus as measured by the Tinnitus Handicap Inventory, may be useful in indicating which patients (and partners) are likely to experience psychological difficulties.

Trauma and damage to the delicate structures of the inner ear frequently occurs during insertion of electrode array into the cochlea. This is strongly related to the excessive manual insertion force of the surgeon without any tool/tissue interaction feedback. The research is examined tool-tissue interaction of large prototype scale (12.5:1) digit embedded with distributive tactile sensor based upon cochlear electrode and large prototype scale (4.5:1) cochlea phantom for simulating the human cochlear which could lead to small scale digit requirements. This flexible digit classified the tactile information from the digit-phantom interaction such as contact status, tip penetration, obstacles, relative shape and location, contact orientation and multiple contacts. The digit, distributive tactile sensors embedded with silicon-substrate is inserted into the cochlea phantom to measure any digit/phantom interaction and position of the digit in order to minimize tissue and trauma damage during the electrode cochlear insertion. The digit is pre-curved in cochlea shape so that the digit better conforms to the shape of the scala tympani to lightly hug the modiolar wall of a scala. The digit have provided information on the characteristics of touch, digit-phantom interaction during the digit insertion. The tests demonstrated that even devices of such a relative simple design with low cost have potential to improve cochlear implants surgery and other lumen mapping applications by providing tactile feedback information by controlling the insertion through sensing and control of the tip of the implant during the insertion. In that approach, the surgeon could minimize the tissue damage and potential damage to the delicate structures within the cochlear caused by current manual electrode insertion of the cochlear implantation. This approach also can be applied diagnosis and path navigation procedures. The digit is a large scale stage and could be miniaturized in future to include more realistic surgical procedures.

Acoustic over exposure (AOE) triggers hearing loss alongside a decreased excitability in the dorsal cochlear nucleus (DCN) within 3 to 5 days post exposure. On a longer time scale (from 6 weeks onwards) AOE can also generate phantom auditory perceptions known as tinnitus alongside a spontaneous hyperactivity in the DCN. The delayed onset of this hyperactivity relative to the early onset of hearing loss and decreased excitability suggests intermediate plastic changes in the DCN that remain to be identified. The first aim of this thesis was to identify in vitro, AOE-induced changes in synaptic plasticity within the DCN that could underlie the subsequent development of tinnitus. The second aim was to identify means of reversing the in vitro changes in synaptic plasticity triggered by AOE. The final aim was to test whether reversing the identified AOE-induced changes in synaptic plasticity could prevent the onset of tinnitus. Wistar rats were exposed to a loud (110 dB SPL) single tone (15 kHz) for a period of 9 hours (AOE protocol). Auditory brainstem response recordings performed 3 to 5 days later showed a significant increase of the rat’s hearing threshold for frequencies above 8 kHz. Field potential recordings of auditory nerve compound action potentials revealed a decreased amplitude and conduction velocity which was confirmed using computational modelling studies. Whole cell recordings of auditory nerve evoked excitatory post synaptic currents (EPSCs) revealed a decrease in EPSC amplitudes after AOE due to a decreased number of release sites. Field potential recordings of parallel fibre evoked activity performed 3 to 5 days following AOE showed that AOE prevented the induction of long term potentiation (LTP) otherwise observed at multisensory DCN synapses. Whole cell recordings of parallel fibre evoked EPSCs in fusiform cells revealed this to be due to an increased release probability after AOE. Perfusion of D-AP5 (an NMDA receptor antagonist) promoted the induction of LTP otherwise deficient after AOE. Perfusion of D-AP5 or elevating the concentration of magnesium in the extracellular medium decreased the release probability after AOE. Based on these findings, subsets of rats were placed on a high magnesium diet (in combination with magnesium injections) immediately after AOE. This reduced the behavioural evidence of tinnitus measured as deficits in silent gap detection. In conclusion, following AOE, the absence of LTP induction in the DCN due to an increased release probability constitutes an in vitro deficit prior to the later onset of tinnitus. Decreasing release probability at DCN multisensory synapses after AOE allowed AOE induced tinnitus to be targeted and reversed in an animal model.

Outcome measures for adult cochlear implant (CI) users are needed to evaluate music rehabilitation tools. Music questionnaires developed for CI users may capture real-world music experiences better than music perception tests but have not been designed to measure outcomes. A new reliable and valid instrument measuring a wide range of music experiences and the impact of music on the quality of life (QOL) of adult CI users could be more appropriate for the assessment of music rehabilitation. This PhD thesis made steps towards the development of such a measure. Music-related Quality of Life (MRQOL) was defined as a function of music experiences and their importance in life. On the basis of this concept, two initial pools of questionnaire items were developed, one assessing musical abilities, attitudes and activities and another one assessing their importance. The items were generated using focus group data from 30 adult CI users and reviewed by 24 professionals for face validity and refinement. After completion of both sets of questions by 147 adult CI users, 18 items were selected for each set with the use of traditional psychometric techniques. The items grouped together into two meaningful domains (perception and engagement) with high reliability and some evidence for construct validity. Scores of ‘music perception and engagement’ and importance for the 18 items can be combined to measure the impact of music on QOL. The meaning of individual ‘impact’ scores and the ability of the questionnaire to measure changes have to be further studied. This thesis broadens the understanding of CI users’ relationship with music and the effects of music on their QOL. Novel aspects of music experience were identified. The MRQOL measure has the potential to become a standard measure of music-specific outcomes and of the impact of music on the QOL of adult CI users and hearing-impaired adults in general, with potential clinical utility.

Ototoxicity is the damage to the ear from exposure to medications. The inner ear is the commonest site of damage where cochlear and/or vestibular functions are affected. Ototoxic medications can cause irreversible toxicity, with aminoglycosides (AGs) and cisplatin being the most established agents. A series of studies are reported in this research under three main themes. Theme A focused on audiological assessments and assessment tools; Theme B focused on causation; and Theme C focused on the impact of ototoxicity and current service provision. The main Theme A study was a clinical observational study with a cross-sectional design assessing the auditory status of children with cystic fibrosis (CF) exposed to AGs. Theme B investigated potential risk factors and aspects in genetics that may be associated with increasing patient susceptibility to the ototoxic effect of AGs. Theme C assessed the effect of ototoxicity on the quality of life (QoL) of children surviving cancer. It also included a survey of current UK practice regarding auditory monitoring for ototoxicity. The novel outcomes of these studies included showing that the prevalence of AG ototoxicity in children with CF is higher than previously reported and evaluating the efficacy of auditory assessment tools. They stressed the importance of choosing appropriate criteria to define ototoxicity and identified potential risk factors associated with it. The genetic studies highlighted a rare case of normal hearing in a child with the m.1555 A>G mutation despite exposure to AGs. They complemented the limited research on the impact of ototoxicity in children on their QoL and on current practice. The latter identified gaps in the provision of ototoxicity monitoring services in the UK, especially due to the absence of nationally agreed guidelines. This research has generated recommendations for several future studies and has informed the clinical management of patients with CF.

This thesis examines the effect of dual tasking on dynamic balance in patients with unilateral peripheral vestibular disorders, both in indoor laboratory and in outdoor urban environments. A novel dual-tasking the functional gait assessment test (FGA) and an outdoor urban walking task around London Bridge using an accelerometer device were used to examine the effect of dual tasking on walking velocity and acceleration of various body segments. In addition, behavioural assessment using the dys-executive syndrome tests battery (BADs) was undertaken to assess participants’ cognitive abilities and their impact on performance under the dual task condition. The above measures were first applied to healthy participants assigned to young and old age groups (Chapter 3). Although both study groups had reduced FGA scores under the dual tasking condition, the older healthy group had significantly lower scores that may increase their risk of falls. The trunk medio-lateral (ML) acceleration was significantly reduced in older healthy adults, and the trunk attenuation rate (TAR) was reduced in dual tasking. Case control trials were carried out to compare the performance of patients diagnosed with unilateral peripheral vestibular disorders (UVD) relative to healthy age matched controls, while carrying indoor assessment (Chapter 4) and outdoor assessment tasks (Chapter 5). The addition of cognitive tasks adversely affected the FGA scores in both groups, though UVD group had a significantly higher risk of falls (in Chapter 4). Cognitive scores were significantly lower in the UVD group in three sub-tests of the BADs test battery. Walking velocity was significantly reduced in the patients group under single and dual task conditions (Chapter 5). Cognitive tasking resulted in significant reduction in the anterior-posterior (AP) and vertical (V) acceleration of the UVD group. ML head acceleration was significantly higher than ML Trunk Acceleration in UVD with dual tasking. In conclusion, our novel approach of implementing a dual tasking paradigm while walking in an outdoor environment showed that dual tasking interferes with postural stability. This will most likely put patients at risk of falls in multitasking situations commonly encountered in everyday life. This finding could be used to inform patient rehabilitation programmes currently in use.

Otosclerosis is a common form of conductive hearing loss. It is characterised by abnormal bone remodelling within the otic capsule, leading to formation of sclerotic lesions of the temporal bone. Encroachment of these lesions on to the footplate of the stapes in the middle ear leads to stapes fixation and subsequent conductive hearing loss. The hereditary nature of otosclerosis has long been recognised due to its recurrence within families, but its genetic aetiology is yet to be characterised. Although many familial linkage studies and candidate gene association studies to investigate the genetic nature of otosclerosis have been performed in recent years, progress in identifying disease causing genes has been slow. This is largely due to the highly heterogeneous nature of this condition. The research presented in this thesis examines the molecular and genetic basis of otosclerosis using two next generation sequencing technologies; RNA-sequencing and Whole Exome Sequencing. RNA–sequencing has provided human stapes transcriptomes for healthy and diseased stapes, and in combination with pathway analysis has helped identify genes and molecular processes dysregulated in otosclerotic tissue. Whole Exome Sequencing has been employed to investigate rare variants that segregate with otosclerosis in affected families, and has been followed by a variant filtering strategy, which has prioritised genes found to be dysregulated during RNA-sequencing. This has identified multiple variants predicted to be involved in splicing within genes involved in the bone disorder Osteogenesis Imperfecta, indicating a shared genetic aetiology for this condition and otosclerosis and a possible disease mechanism involving alternative splicing in the stapes. Whilst the hereditability of otosclerosis remains elusive, the identification of new candidate genes will make a significant contribution to the current literature. It is hoped that long term, this research will help reveal disease mechanisms and thereby improve treatment options for otosclerosis patients.