| Summary: | Aims and Objectives: The overall aim of this thesis was to investigate the neural correlates of tinnitus perception using different magnetic resonance imaging (MRI) techniques. The first objective was to investigate the neuro-functional reorganisation that may be associated with tinnitus-related emotional disturbances using functional MRI (fMRI). The second objective was to investigate the structural brain changes that are hypothesised to be associated with tinnitus perception. This investigation included an analysis of both grey and white matter using diffusion tensor imaging (DTI), a cortical thickness analysis (CTA) and voxel-based morphometry (VBM). The third objective was to investigate any correlations between the neuro-functional and the neuro-structural reorganisation that are associated with tinnitus and behavioural data, such as hearing thresholds, the Newman Handicap Inventory score and age. These analyses were performed for both the experimental and control groups. Methods: A total of 18 tinnitus sufferers and 15 age- and sex-matched healthy volunteers participated in the work that is presented in this thesis. The functional MRI study in this thesis utilised internationally standardised emotionally evocative pleasant and unpleasant visual and auditory stimuli. The fMRI paradigm consisted of a block design, during which the participants from the two groups (tinnitus and controls) viewed blocks of images and listened to sounds. The structural investigations in this thesis included DTI, CTA and VBM. Results: In the fMRI study, tinnitus sufferers exhibited significant hyperactivation in the limbic system, the prefrontal cortex (PFC) and the temporal lobe. Correlation analyses between the mean fMRI Blood Oxygen Level-Dependent (BOLD) signal and hearing thresholds revealed a significant positive correlation in the subjects with tinnitus but not the in the controls. This correlation was observed in the following regions: the right cingulate gyrus, the right medial frontal gyrus, the right superior temporal gyrus, the left inferior frontal gyrus and the left superior temporal gyrus. Tinnitus severity as measured using the Newman Tinnitus Handicap Inventory score (Newman THI) was observed to be positively correlated with the mean fMRI BOLD signal in the left superior temporal gyrus and the right cingulate gyrus. Tinnitus-like conditions induced the healthy controls to exhibit hyperactivity in the limbic system, the PFC and the temporal lobe. The DTI study demonstrated disrupted white matter (WM) integrity in the following bundles in the subjects with tinnitus relative to the control group: the left and right inferior fronto-occipital fasciculus, the corpus callosum, the left superior and inferior longitudinal fasciculus, and the left and right thalamic radiations. CTA revealed cortical thickness reductions in the subjects with tinnitus compared to the controls in a priori hypothesised regions of interest (ROI), which included the following regions: the temporal lobe, PFC, anterior cingulate cortex (ACC), cingulate gyrus (CG) and posterior cingulate gyrus (PCG). VBM revealed reduced grey matter (GM) volume in the left medial PFC in subjects with tinnitus compared to controls. Conclusion: Tinnitus perception may involve functional and structural changes in the following specific brain regions: the PFC, the temporal lobe (including the auditory cortex) and the limbic system. These structural changes may represent antecedent structural deficits that result in subsequent functional reorganisation, causing the tinnitus signal to arise.
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