The perception of clinical breathlessness is a complex experience, modulated by physical and psychological factors. Distinguishable types of breathlessness arising from different peripheral mechanisms have been delineated, experimental models of these specific types have been developed and advances have been made in multidimensional assessments. However, current knowledge about cerebral mechanisms of breathlessness is lacking. Functional brain imaging studies have identified involvement of certain cortical structures but interpretations of these data are limited by various assumptions.
Aim:The primary purpose of this thesis was to interrogate the validity of the conclusions drawn by recent brain imaging studies and to draw further inferences about cerebral mechanisms of dyspnoea from neurological patients undergoing deep brain stimulation (DBS) for relief of other symptoms. Focusing on experimentally induced ‘air hunger’ (the most unpleasant form of clinical breathlessness) two primary working hypotheses were generated: (i) Perceptual sensitivity to experimentally induced breathlessness will be greater during MRI brain scans due to greater anxiety associated with the MRI milieu (ii) DBS of motor-thalamic nuclei generates breathlessness
Method:(i) Experimental breathlessness was induced in healthy subjects in simulated brain scanners to measure the effects of psychological stress associated with the functional magnetic resonance imaging (fMRI) scanner. (ii) Experimental breathlessness was induced in patients with DBS of the ventral intermediate (VIM) and ventralis oralisposterior (VOP) nuclei of the thalamus when the implanted electrodes are activated(switched ‘ON’ to stimulate the brain tissue) and when they are not activated (switched ‘OFF’ to stop stimulating the brain tissue).The Dyspnoea-12 multidimensional tool was also used to assess breathlessness. (iii)Probabilistic tractography was used to estimate the white fibre connectivity from the seed area (VIM) in the brain to brain regions of interest and to compare these in patients who responded differently in (ii).
Results: (i) Healthy volunteers with anxiety scores at or above average levels increased air hunger sensitivity in the simulated fMRI environment whereas those with low anxiety responded in the opposite direction. (ii) Contrary to the hypothesis posed, motorThalamic DBS resulted in relief of air hunger in all but one of the 6 patients studied. (iii) Tractography suggested that those patients who improved with DBS ‘ON’ had stronger connections to the anterior parts of the brain (orbitofrontal cortex) in contrast to the stronger connectivity to the posterior areas of the brain in the one patient who improved with DBS ‘OFF’.
Conclusion :( i) Future functional brain imaging studies of breathlessness should screen healthy volunteers for anxiety in order to improve interpretation of activations detected. (ii) Neurological patients undergoing DBS provide a useful clinical model to explore cerebral mechanisms of breathlessness. While the dataare largely inconclusive due to limited numbers of patients, the orbitofrontal connections for dyspnoea relief has been flagged as being an important element of a cerebral network for dyspnoea. Potential new thalamic targets for dyspnoea relief are suggested. The novel findings of this study lay the groundwork for better understanding of cerebral mechanisms of dyspnoea and therefore potential new and more effective targets for relief of intractable dyspnoea – a goal that remains an urgent clinical need
