Brain Micro- and Macro-Structural Characteristics Investigation in Fibromyalgia Using Multi-Modal Magnetic Resonance Imaging

Fibromyalgia (FM) is a chronic widespread pain condition that deeply impacts the lives of patients. Multiple symptoms such as fatigue, impaired cognition, and sleep disturbances among others are commonly described. Despite intensive research effort, no disease-specific mechanism uniquely explains the clinical presentation of FM. Nonetheless, current evidence points to a major role of the central nervous system for the main feature of this condition: pain and sensory augmentation. Neuroimaging techniques provide a window into the brain mechanisms that may play a role in FM. Several studies using functional magnetic resonance imaging (MRI) show abnormalities in pain processing in the brain of FM patients. Likewise, structural abnormalities are found using anatomical MRI however the findings are less consistent. The main goal of this dissertation was to comprehensively assess brain structural features of FM patients and matched controls at both micro- (cellular-level structures such as membranes, myelin as well as axonal density) and macro-structural (gross anatomical) levels as measured by diffusion-weighted and high-resolution anatomical MRI respectively. The results from diffusion MRI show evidence of widespread micro-structural white matter (WM) abnormalities in the brains of FM patients compared to controls, and also within relevant pain-related brain regions. These findings give support to the view that alterations in the brain of patients potentially contribute to the symptoms experienced by them. Conversely, macro-structural brain features showed little difference between patients and controls regarding gray matter (GM) characteristics. Between-group differences were only found for increased volume in the amygdalae and WM adjacent to the anterior cingulate cortex and left insula for FM patients relative to controls. Taken together these findings may indicate that structural abnormalities in the brain of FM patients are more widespread in the micro-structural level, while regional differences limited to subcortical structures and WM adjacent to pain-related cortical areas are more typical at the macro-structural level with no measurable impact to GM morphological characteristics.Doctor of Philosoph