Selected Abstracts From Recent Publications in Cardiopulmonary Disease Prevention and Rehabilitation

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Herigstad M, Faul OK, Hayen A, Evans E, Hardinge FM, Wiech K, Pattinson KTS
Eur Resp J. 2017. 50(3). pii: 1701029. doi: 10.1183/13993003.01029-2017.
Abstract: Breathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology (“over-perception”). Pulmonary rehabilitation profoundly affects breathlessness, without influencing lung function. Learned associations influence brain mechanisms of sensory perception. We hypothesised that improvements in breathlessness with pulmonary rehabilitation may be explained by changing neural representations of learned associations.
In 31 patients with COPD, we tested how pulmonary rehabilitation altered the relationship between brain activity during a breathlessness-related word-cue task (using functional magnetic resonance imaging), and clinical and psychological measures of breathlessness.
Changes in ratings of breathlessness word cues positively correlated with changes in activity in the insula and anterior cingulate cortex. Changes in ratings of breathlessness-anxiety negatively correlated with activations in attention regulation and motor networks. Baseline activity in the insula, anterior cingulate cortex and prefrontal cortex correlated with improvements in breathlessness and breathlessness-anxiety.
Pulmonary rehabilitation is associated with altered neural responses related to learned breathlessness associations, which can ultimately influence breathlessness perception. These findings highlight the importance of targeting learned associations within treatments for COPD, demonstrating how neuroimaging may contribute to patient stratification and more successful personalised therapy.
Editor's Comment: Breathlessness is by far the most limiting symptom associated with COPD. The majority of interventions applied are aimed at improving this in particular and pulmonary rehabilitation (PR) is reliably associated with benefit. Surprisingly little is known about the neurocognitive determinants of dyspnea and, until fairly recently, even the areas of the brain involved were poorly defined. It is also being recognized that the reason dyspnea correlates poorly with pulmonary function abnormalities is because there are learned associations that amplify the unpleasant components. Improvements in dyspnea following pulmonary rehabilitation, especially since they occur in the absence of pulmonary function improvement, may include neural changes in these learned associations.
This study evaluated 31 patients with mild-moderate COPD with brain functional magnetic resonance imaging (fMRI) before and after standard PR, looking for changes in activity patterns, in relation to word cues to trigger symptoms. Brain responses were evaluated in the presence of this provoked breathlessness and anxiety. After PR there was a significant improvement in anxiety responses, and this showed a negative correlation with activity in the posterior cingulate cortex, angular gyrus, primary motor cortex, and supramarginal gyrus. Improvements in breathless rating were positively correlated with activity in the left anterior insula, left posterior insula, left supramarginal gyrus, and anterior cingulate cortex, but, overall, there was no significant improvement in word cue provoked breathlessness after PR. A change in responses over pulmonary rehabilitation was positively correlated with baseline activity in the ventromedial prefrontal cortex and anterior cingulate cortex (anxiety ratings), and in the anterior insula (bilateral), orbitofrontal cortex, and motor cortex (breathlessness ratings). These areas comprise much of the stimulus valuation network, and these findings suggest that people with greater brain activity during word-cue presentation are more likely to benefit from pulmonary rehabilitation, particularly with regard to anxiety.
This study explores an infrequently used technique, fMRI, and an area of word cue triggered symptom responses that are not currently evaluated in any routine clinical setting. By mapping these areas of anxiety and breathlessness associated brain activity, it offers new insights into the neural localization of symptoms and their possible value in predicting PR benefit, and underlines the complex learned patterns and associations that produce unpleasant symptoms in patients with COPD. It is too early to attest to the validity of such assessments, but they do add an objectively quantitative tool to an area that is notoriously subjective in its measurement at present.
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