Investigating brain mechanisms of dyspnoea in humans with functional and structural MRI
Lead Research Organisation:
University of Oxford
Department Name: Clinical Neurosciences
Abstract
Dyspnoea is the uncomfortable shortness of breath that debilitates millions of patients with lung disease, heart failure and cancer. It is often very difficult to treat. The sensations of dyspnoea are processed in the brain, and we believe that psychological factors modify and amplify these sensations, frequently exacerbating symptoms.
In patients with chronic pain, neuroimaging has revealed a brain network that is responsible for processing pain and is strongly influenced by psychological factors. Preliminary studies suggest that there may be similarities in the way the brain processes the unpleasant aspects of dyspnoea.
This research will focus upon identifying brain mechanisms that process dyspnoea in healthy humans and in patients undergoing pulmonary rehabilitation therapy for chronic lung disease. We shall apply novel functional and structural magnetic resonance imaging techniques to assess how psychological factors influence the perception of dyspnoea.
The Oxford Centre for Functional MRI of the Brain (FMRIB) has developed highly sensitive MRI techniques combined with novel analysis tools to enable the success of these challenging studies. This research will provide new insights into the mechanisms of dyspnoea that may provide new therapies to relieve suffering in millions of patients.
In patients with chronic pain, neuroimaging has revealed a brain network that is responsible for processing pain and is strongly influenced by psychological factors. Preliminary studies suggest that there may be similarities in the way the brain processes the unpleasant aspects of dyspnoea.
This research will focus upon identifying brain mechanisms that process dyspnoea in healthy humans and in patients undergoing pulmonary rehabilitation therapy for chronic lung disease. We shall apply novel functional and structural magnetic resonance imaging techniques to assess how psychological factors influence the perception of dyspnoea.
The Oxford Centre for Functional MRI of the Brain (FMRIB) has developed highly sensitive MRI techniques combined with novel analysis tools to enable the success of these challenging studies. This research will provide new insights into the mechanisms of dyspnoea that may provide new therapies to relieve suffering in millions of patients.
Technical Summary
Background: Dyspnoea, the sensation of uncomfortable shortness of breath, is the primary symptom of chronic obstructive pulmonary disease (COPD), cardiac failure and some types of terminal cancer and is a major cause of disability and poor quality of life. COPD costs the NHS >£4 billion p.a., occupies >1 million inpatient UK bed days and generates ~40 million drug prescriptions each year. Dyspnoea due to COPD leads to ~25 million certified sickness days p.a. Pulmonary rehabilitation (PR), that includes exercise and education, is the most effective treatment for chronic dyspnoea of COPD. As subjective measures of dyspnoea correlate poorly with respiratory function and improvements due to PR therapy strongly suggest that mechanisms related to cognition and emotion contribute to its positive effects, we hypothesise that brain mechanisms cause amplification of respiratory sensations, exacerbating dyspnoea.
Aims: To understand how central nervous system (CNS) mechanisms contribute to dyspnoea.
Objectives: The identification of CNS biomarkers through integration of clinical, physiological and psychological measures with functional and structural magnetic resonance imaging (MRI) in healthy human volunteers and patients with chronic dyspnoea.
Design: Healthy volunteer studies: Three separate conventional BOLD functional MRI experiments exploring specific aspects of laboratory dyspnoea. Patient study: Longitudinal randomised parallel group study of structural and functional MRI measures in COPD patients before and after PR.
Methodology: In healthy volunteers I wish to separate the brain processing of unpleasantness of dyspnoea from its intensity and to determine how anticipation to dyspnoea is processed. These tightly controlled laboratory experiments will develop a platform for further investigating psychological and pharmacological manipulations of dyspnoea, and will inform design and analysis of the patient studies.
In patients with COPD pulmonary rehabilitation improves dyspnoea but not lung function. We hypothesise that PR will induce neural plasticity in brain regions related to improvement in dyspnoea symptoms, and that we will observe changes in functional activation due to altered cognitive and emotional processing.
Scientific and medical opportunities: The identification of dyspnoea-related biomarkers in the human brain will contribute to individualised and targeted treatments for dyspnoea which will result in improvement of an individual‘s quality of life and economic productivity. The extent of disease attributable to dyspnoea is sufficient for this to be a credible target to improve the burden of disease at a societal, as well as at the individual level.
Aims: To understand how central nervous system (CNS) mechanisms contribute to dyspnoea.
Objectives: The identification of CNS biomarkers through integration of clinical, physiological and psychological measures with functional and structural magnetic resonance imaging (MRI) in healthy human volunteers and patients with chronic dyspnoea.
Design: Healthy volunteer studies: Three separate conventional BOLD functional MRI experiments exploring specific aspects of laboratory dyspnoea. Patient study: Longitudinal randomised parallel group study of structural and functional MRI measures in COPD patients before and after PR.
Methodology: In healthy volunteers I wish to separate the brain processing of unpleasantness of dyspnoea from its intensity and to determine how anticipation to dyspnoea is processed. These tightly controlled laboratory experiments will develop a platform for further investigating psychological and pharmacological manipulations of dyspnoea, and will inform design and analysis of the patient studies.
In patients with COPD pulmonary rehabilitation improves dyspnoea but not lung function. We hypothesise that PR will induce neural plasticity in brain regions related to improvement in dyspnoea symptoms, and that we will observe changes in functional activation due to altered cognitive and emotional processing.
Scientific and medical opportunities: The identification of dyspnoea-related biomarkers in the human brain will contribute to individualised and targeted treatments for dyspnoea which will result in improvement of an individual‘s quality of life and economic productivity. The extent of disease attributable to dyspnoea is sufficient for this to be a credible target to improve the burden of disease at a societal, as well as at the individual level.