Clearing the Fog: Characterization of the Phenotypic and Neurophysiological Features of Cognitive Dysfunction in Fibromyalgia

Project Summary Pain in the United States is common and costly, with over 1 in 3 individuals being afflicted, causing an economic burden approaching $600 billion annually. Fibromyalgia (FM) is characterized by widespread chronic pain and co-morbid symptoms of psychological disturbance, and cognitive dysfunction. Cognitive symptoms are particularly distressing and one of the most disabling aspects reported by patients. Neuroimaging techniques, such as electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), have identified central nervous system (CNS) mechanisms affecting the brain in these individuals, contributing to their ongoing pain. Objective cognitive impairments and subjective complaints have been consistently identified in FM; however, there remains a common discrepancy between subjective and objective findings in the literature and there is scarce information as to the relationship with observed CNS mechanisms. Therefore, a more comprehensive evaluation of this issue is needed. Furthermore, there remains a lack of sensitive clinical biomarkers pertaining to the nature of cognitive complaints in FM, the development of which is a vital next step towards effective interventions. To date, no study has systematically sought to understand cognitive dysfunction in FM by combining neuropsychological assessments, patient-reported measures, and neurophysiological (EEG) aspects. This empirical gap highlights a timely opportunity to understand and address a potential avenue for thorough understanding, diagnosis, and treatment of cognitive symptoms in FM. The proposed project and closely aligned training plan will fill this empirical gap by comparing subjective and objective cognitive assessments between individuals with FM and healthy controls. We will also use EEG to evaluate the neurophysiological features underlying cognitive dysfunction in FM and relationships with clinical outcomes using a cognitive paradigm shown to be sensitive to preclinical cognitive impairments. We will build from the robust framework of the Michigan Chronic Pain and Fatigue Research Center and an ongoing NCCIH- funded R01 to the primary mentor, Dr. DaSilva, to recruit a well characterized study sample and add a thorough examination of cognition. Specifically, we will use a cross-sectional design to assess subjective and objective cognitive functioning as well as the influence of co-morbid symptoms in FM on the relationship between objective and subjective elements (Aim 1). We will also utilize EEG to identify neural biomarkers of cognitive dysfunction based on performance on a memory task (Aim 2). Finally, as an exploratory aim (Aim 3) we will analyze fMRI data in a subset of the FM sample to evaluate the relationship between brain responses to pain and cognitive symptoms. The proposed training in FM, application of statistics to self-report measures, neuroimaging, and training in interventional approaches to guide future research (i.e., neuromodulation) will create the ideal foundation for the candidate to excel as an independent researcher and become a leading expert in the field, advancing our knowledge of cognitive symptoms in chronic pain conditions.