Understanding the Importance of Plasticity in the Brain Mechanisms of Dyspnoea Perception

Summary

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. This study aims to identify the importance of learning in the brain mechanisms of dyspnoea by investigating a cohort of patients with chronic breathlessness undergoing pulmonary rehabilitation . Pulmonary rehabilitation is a six-week course of exercise, education and group therapy that improves dyspnoea but does not improve lung function. This leads us to hypothesise that some of the beneficial effects of PR maybe due to changes in brain processing, potentially relating to a learning effect. Therefore to probe whether learning is important in the beneficial effects of pulmonary rehabilitation, we intend to modify learning with the drug d-cycloserine. D-cycloserine is an antibiotic that enhances learning due to its effects at N-methyl D-aspartate (NMDA) receptors in the hippocampus. Our previous study in a similar group of patients demonstrated the importance of the hippocampus in breathlessness perception, and we now wish to investigate this in more depth. The study involves collecting physiological, psychological and clinical measures on in conjunction with brain scanning, before, during and once after pulmonary rehabilitation. Subjects will either receive d-cyloserine or placebo before the first four pulmonary rehabilitation sessions.

Timeline

Start

2013-11

Primary completion

2018-12

Completion

2020-02

Publications

• Finnegan SL, Harrison OK, Ezra M, Harmer CJ, Nichols TE, Rahman NM, Reinecke A, Pattinson KTS. The effect of D-cycloserine on brain connectivity over a course of pulmonary rehabilitation - A randomised control trial with neuroimaging endpoints. PLoS One. 2025 Jun 2;20(6):e0323213. doi: 10.1371/journal.pone.0323213. eCollection 2025.
• Finnegan SL, Harrison OK, Booth S, Dennis A, Ezra M, Harmer CJ, Herigstad M, Guillaume B, Nichols TE, Rahman NM, Reinecke A, Renaud O, Pattinson KTS. The effect of d-cycloserine on brain processing of breathlessness over pulmonary rehabilitation: an experimental medicine study. ERJ Open Res. 2023 Apr 3;9(2):00479-2022. doi: 10.1183/23120541.00479-2022. eCollection 2023 Mar.
• Finnegan SL, Browning M, Duff E, Harmer CJ, Reinecke A, Rahman NM, Pattinson KTS. Brain activity measured by functional brain imaging predicts breathlessness improvement during pulmonary rehabilitation. Thorax. 2023 Sep;78(9):852-859. doi: 10.1136/thorax-2022-218754. Epub 2022 Dec 26.

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