An investigation of tinnitus using behavioural and functional imaging measures

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