While cochlear implants (CIs) have transformed the lives of hundreds of thousands of profoundly deaf individuals worldwide, the ability of individual patients to understand speech through their CI varies widely. The longitudinal study reported in this thesis aimed to investigate the role of cortical function and plasticity in helping to predict and explain variability in individual CI outcome. Speech-evoked cortical activations, measured using functional near-infrared spectroscopy (fNIRS), and behavioural measures of speech perception were acquired in adult CI recipients before implantation through to six months after CI activation. As anticipated, cochlear implantation enabled the significant recovery of auditory speech perception over the first six months of CI use, yet individual performance varied widely across CI users. fNIRS enabled the measurement of speech-evoked cortical activations from bilateral superior temporal cortex (STC) that were free from CI-generated artefacts. Cortical activation to visual speech measured before implantation was able to significantly predict future CI outcome measured following six months of CI use. This pre-implant measure of brain activity provided unique predictive value above that of well-established clinical characteristics, including the age-at-onset and duration of deafness. When examining changes in cortical activation from before to after implantation, a greater increase in STC activation to visual speech was found to be related to better CI outcome. These visual-related changes also predicted changes in STC activation to auditory speech. These results highlight the importance of visual speech cues and coupling between the auditory and visual modalities during the recovery of auditory function with a CI. Together, the findings demonstrate the potential of fNIRS as a brain-imaging tool that is uniquely well-suited for use in cochlear implantation. Future applications of this technology could help to explain individual variability in CI success and to deliver more accurate clinical prognoses for CI candidates.

Tinnitus is the phantom perception of sound. For some people tinnitus can have a detrimental impact on their quality of life. Negative emotional feelings associated with tinnitus play a major role in enhancing and maintaining its continued presence. Despite its high prevalence across the world, its neurophysiological underpinnings remain elusive and there is no universal cure. This thesis utilises data derived from an open-label, non-randomised clinical trial whose original aim was to evaluate the effect of hearing aids for hearing-impaired individuals with tinnitus. To achieve this, a range of patient-reported clinical measures, as well as functional magnetic resonance imaging (fMRI) were used to identify both clinical and neurophysiological markers of treatment-related change over a six-month period. Evidence for clinical impact of hearing aid provision in the management of tinnitus was examined. In study 1, tinnitus handicap was compared amongst two groups of chronic tinnitus patients; those opting for hearing aids (n=42) and age-matched controls who were not (n=14). A small statistically significant reduction in tinnitus handicap as measured by the Tinnitus Handicap Questionnaire was observed in the hearing aid group six months post-fitting compared to controls. However this was not clinically significant. Given the lack of evidence for strong clinical benefit, three further investigations were conducted to identify objective neurophysiological markers associated with the presence of tinnitus. These used baseline fMRI data (i.e. prior to any hearing aid provision) derived from the same age and hearing-matched groups (chronic tinnitus, n=12 and no tinnitus controls, n=11). Independent Component Analysis, region of interest analysis and Patel’s conditional dependence measures were used to investigate resting-state brain activity across the auditory network (study 2) and within the amygdala (study 3). Neither study found any between-group differences. Study 4 examined sound-evoked differences between groups by measuring the amygdala response to emotionally evocative soundscapes using a general linear model approach. Soundscapes rated as very pleasant or very unpleasant elicited stronger amygdala activity than neutral soundscapes (replicating a previous finding). However, activity in the tinnitus group was reduced compared to controls, contrary to our expectations. While results demonstrate that the objective quantification of tinnitus is possible, this nevertheless remains a challenging field. The investigation of resting-state and sound-evoked fMRI data derived from the same participant groups illustrates how neurophysiological markers of tinnitus may only become apparent given the right choice of experimental paradigm. The identification of a potential tinnitus-related biomarker in limbic, not auditory, brain regions leads us to speculate that functional imaging may be more sensitive to the emotional consequences of the tinnitus than the neural signature of the sound perception itself. Challenges and recommendations for future tinnitus research are identified.

The Tinnitus Functional Index (TFI) was developed in the USA as a standard for assessing the functional impact of tinnitus based on eight tinnitus-related domains. The finalised 25-item version was never formally validated. This PhD seeks to assess the psychometric properties of the questionnaire and evaluate its suitability as the tool of choice for use in the diagnostic and outcome assessment of tinnitus for clinical and research purposes in the UK. The primary objectives were to (i) determine whether the TFI is reliable, (ii) verify its factor structure, and (iii) evaluate its responsiveness to treatment-related change. These objectives were evaluated in two UK studies. The first was a prospective multi-centre longitudinal validation study in which 255 NHS patients were recruited from audiology clinics to complete the TFI over four different time points in a nine-month period. The second was a retrospective analysis of data collected on the TFI and a battery of other health questionnaires from 294 members of the general public who had previously participated in two-centre randomised controlled trial of a novel tinnitus device. Approaches to psychometric analysis included classical and modern test theories, including Rasch measurement theory. Both approaches led to similar conclusions. Seven of the eight subscales were reliable and valid in both studies, although not as sensitive as the original developers proposed. Classical testing showed the auditory subscale to be reasonably reliable, but Rasch modelling indicated that it did not measure the functional impact of tinnitus. The overall factor structure was not confirmed. The sleep and auditory subscales did not relate to the other subscales and did not fit the model. My recommendation is to calculate the composite TFI score using only six subscales. The sleep subscale should be scored separately and the auditory subscale should not be used.

Tinnitus, often defined as the perception of sound in the absence of an external stimulus, affects millions of people worldwide and, in extreme cases, can be severely debilitating. While certain changes within the auditory system have been linked to tinnitus, the exact underlying causes of the phenomenon have not, as yet, been elucidated. Animal models of tinnitus have considerably furthered understanding of the some of the changes associated with the condition, allowing researchers to examine changes following noise exposure, the most common trigger for tinnitus. This thesis documents the development of an animal model of tinnitus, using the guinea pig to examine neural changes following induction of tinnitus. In the first study, a novel adaptation of a behavioural test was developed, in order to be able to determine whether guinea pigs were experiencing tinnitus following the administration of sodium salicylate, a common inducer of tinnitus in humans. This test relies on a phenomenon known as prepulse inhibition, whereby a startle response can be reduced in amplitude by placing a gap in a low-level, continuous background noise immediately prior to the startling stimulus. The hypothesis for this test is that if the background sound is adjusted to be similar to an animal’s tinnitus (induced artificially following noise exposure or drug administration), the tinnitus percept will fill in the gap and the startle response will not be reduced. The results from this first study indicated that using the Preyer reflex (a flexion of the pinnae in response to a startling stimulus) as this startle measure was more robust in guinea pigs than the commonly-used whole-body startle. Furthermore, transient tinnitus was reliably identified following salicylate administration. Following the development and validation of this test, a study was conducted to determine whether guinea pigs experienced tinnitus following unilateral noise exposure. Neural changes commonly associated with the condition (increases in spontaneous firing rates and changes in auditory brainstem responses) were examined, to determine whether there were any differences between animals that did develop tinnitus following noise exposure and those that did not. Two different methods were applied to the behavioural data to determine which animals were experiencing tinnitus. Regardless of the behavioural criteria used, increased spontaneous firing rates were observed in the inferior colliculus of noise-exposed guinea pigs, in comparison to control animals, but there were no differences between tinnitus and no-tinnitus animals. Conversely, significant reductions in the latency of components of the auditory brainstem response were present only in the tinnitus animals. The final study examined whether the original hypothesis for the behavioural test (that tinnitus is filling in the gap) was valid, or whether there was an alternative explanation for the deficits in behavioural gap detection observed previously, such as changes in the temporal acuity of the auditory system preventing detection of the gap. Recordings were made in the inferior colliculus of noise-exposed animals, separated into tinnitus and no-tinnitus groups according to the behavioural test, as well as unexposed control animals, to determine whether there were changes in the responses of single-units in detecting gaps of varying duration embedded in background noise. While some minor changes were present in no-tinnitus animals, tinnitus animals showed no significant changes in neural gap detection thresholds, demonstrating that changes in temporal acuity cannot account for behavioural gap detection deficits observed following noise exposure. Interestingly, significant shifts in the response types of cells were observed which did appear to relate to tinnitus. The present data indicate that the Preyer reflex gap detection test is appropriate for examining tinnitus in guinea pigs. It also suggests that increases in spontaneous firing rates at the level of the inferior colliculus cannot solely account for tinnitus. Changes in auditory brainstem responses, as well as shifts in response types, do appear to relate to tinnitus and warrant further investigation.

It is common practice in psychophysical studies to investigate speech processing by manipulating or reducing spectral and temporal information in the input signal. Such investigations, along with the often surprising performance of modern cochlear implants, have highlighted the robustness of the auditory system to severe degradations and suggest that the ability to discriminate speech sounds is fundamentally limited by the complexity of the input signal. It is not clear, however, how and to what extent this is underpinned by neural processing mechanisms. This thesis examines the effect on the neural representation of reducing spectral and temporal information in the signal. A stimulus set from an existing psychophysical study was emulated, comprising a set of 16 vowel-consonant-vowel phoneme sequences (VCVs) each produced by multiple talkers, which were parametrically degraded using a noise-vocoder. Neuronal representations were simulated using a published computational model of the auditory nerve. Representations were also recorded in the inferior colliculus (IC) and auditory cortex (AC) of anaesthetised guinea pigs. Their discriminability was quantified using a novel neural classifier. Commensurate with investigations using simple stimuli, high rate envelope modulations in complex signals are represented in the auditory nerve and midbrain. It is demonstrated here that representations of these features are efficacious in a closed-set speech recognition task where appropriate decoding mechanisms are available, yet do not appear to be accessible perceptually. Optimal encoding windows for speech discrimination increase from of the order of 1 millisecond in the auditory nerve to 10s of milliseconds in the IC and the AC. Recent publications suggest that millisecond-precise neuronal activity is important for speech recognition. It is demonstrated here that the relevance of millisecond-precise responses in this context is highly dependent on the brain region, the nature of the speech recognition task and the complexity of the stimulus set.