| Summary: | Fibromyalgia syndrome (FMS) is a widespread chronic pain disorder affecting 2−5% of the general population and particularly women of middle age (McBeth and Mulvey, 2012). The syndrome is frequently comorbid with a variety of clinical, functional and psychological disorders (Weir et al., 2006) and associated with a large socio-economic burden (Lachaine et al., 2010). In spite of significant previous research, the underlying aetiology and pathophysiology of FMS is not fully understood (Schmidt-Wilcke and Clauw, 2011). However, aberrant structural and functional brain alterations have been proposed as a casual or maintaining factor of the disorder (Schweinhardt et al., 2008). This thesis utilised functional and structural imaging methods and novel experimental paradigms to explore brain alterations in FMS patients. A comprehensive review of previous experimental findings was performed to identify novel research questions. EEG and MRI data for 5 unique studies was collected over two sessions. In the first study dynamic mechanical stimulation was applied to the forearm of FMS patients and healthy participants, and an ERD analysis of corresponding EEG data was performed. The results revealed that FMS patients exhibited alterations to cortical excitability during brushing stimuli which correlated with clinical measures. These findings indicate that abnormal processing of innocuous somatosensory stimulation may contribute to the pathophysiology and clinical symptom severity of FMS. Secondly, an ERP analysis of EEG data from the observation of pain and non-pain pictures was performed. FMS patients exhibited differences in ERP components and source activation patterns during observation of pain pictures relative to healthy people. Alterations to processing of observed pain occurred in parahippocampal gyrus and may relate to clinical and psychological aspects of FMS, this finding could be utilised to further understand the heterogeneity of psychological profiles of FMS patients in order to better target therapeutic interventions. The third study of the thesis describes a novel comparison of functional connectivity with resting-state network structures utilising fMRI recordings. Functional connectivity with default mode network structures was shown to be altered in FMS. This finding may reflect an ongoing time-dependent reorganisation of resting-state networks due to ongoing chronic pain. In the fourth study, a morphological analysis of subcortical structures was performed using high-resolution T1-weighted MR images. FMS patients demonstrated alterations to the morphology of the brainstem, an important structure in descending nociceptive control. Volumetric alterations in this structure correlated with clinical measures of symptom severity suggesting an important role for brainstem alterations in FMS pain symptoms. In the final study the microstructural integrity of white matter was compared between FMS patients and healthy participants. Although no significant differences were identified the findings indicate that FMS is not likely to be related to abnormal development of white matter tracts. Therefore structural alterations associated with FMS are likely to occur only in the grey matter.
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