Kyle Pattinson graph.jpg

Treating breathlessness via the brain

How neuroscience could help treat chronic breathing disorders

Wednesday, September 27, 2017

Professor Kyle Pattinson is a neuroscientist in the Nuffield Department of Clinical Neurosciences at the University of Oxford, and an Honorary Consultant Anaesthetist at Oxford University Hospitals NHS Trust. 

Kyle explains how neuroscience could help doctors to personalise treatment for people with chronic breathing disorders.

Breathlessness, the distressing feeling of inadequacy in our breathing, is a major cause of suffering for people with chronic respiratory disease. Breathlessness is often poorly explained by medical tests of lung function. Breathing is inextricably tied up with our emotions, as both a symptom and/or cause of distress. In particular, individuals with chronic lung disease may have greater anxiety about their breathing as a constant reminder of their condition, whereas expected breathlessness experienced during athletic performance may evoke less worry.

The brain takes protective measures to avoid breathlessness by forming conditioned associations between certain activities (such as walking up the stairs or hurrying for the bus) and the likelihood of symptom exacerbation. However, these fear-avoidance behaviours can severely hinder quality of life. We now have strong reason to believe that these expectations can also materially alter the perception of breathlessness.

The ‘Bayesian Brain Hypothesis’ is a new way of thinking about the how the brain perceives the world. Instead of passively receiving sensory inputs, it integrates expectations ('priors') with incoming neural information. In the case of breathlessness, these may be signals from the nerves in the lungs and chest wall. Thus, both priors and neural information influence breathlessness. Strong expectations can tip the balance of perception away from incoming neural information and towards the priors, as the brain takes its ‘best guess’ from the information at hand. Personality and psychology (e.g. anxiety, depression, body awareness) may make some people more susceptible to developing strong priors, and once these expectations are embedded, they can be difficult to ‘un-learn’. 

The influence of expectations and psychology on how the brain generates breathlessness is the subject of a recent article published in the European Respiratory Journal. Scientists at the University of Oxford have studied how pulmonary rehabilitation might recalibrate sensory perception networks in people with COPD. 

Pulmonary rehabilitation is one of the best treatments for breathlessness in COPD, also improving anxiety, depression, and quality of life. However, pulmonary rehabilitation has no effect on lung function - suggesting that the neural traffic from the lungs probably doesn't change. Thus, according to the Bayesian Brain Hypothesis, improvements in breathlessness would be due to changes in the balance between priors and neural traffic that combine to generate breathlessness.

In the study, participants with COPD underwent functional magnetic resonance brain imaging while viewing word cues related to breathlessness (e.g. "walking uphill"), before and after a course of pulmonary rehabilitation. These word cues allowed them to probe the brain activity relating to learned associations that influence prior generation.

The main finding was that people who had benefitted the most from pulmonary rehabilitation had greater decreases in activity in the parts of the brain linked to prior generation, namely the insula and anterior cingulate cortices. This suggests that (at least part of) the beneficial effect of pulmonary rehabilitation might be a learning effect from weakened priors. Perhaps repeated exercise breathlessness in a 'safe' setting, helps participants un-learn fear associations? Improvements in breathlessness-anxiety were also related to increases in brain activity within attention and motor-regulating areas, suggesting brain activity was less dominated by emotions. Lastly, the finding that people with stronger priors derive the most improvements in breathlessness from pulmonary rehabilitation adds further weight to this idea.

So, what next? We now have a clearer idea of how learning influences breathlessness perception networks in the brain. Future research will test the ideas in the present paper to develop a much more comprehensive understanding of how the brain generates breathlessness in clinical populations. To effectively treat breathlessness, we can use this information to develop individualised and targeted treatments that could work hand-in-hand with disease-modifying therapies, to really improve symptoms and quality of life in a meaningful way.



Mari Herigstad et al.  Treating breathlessness via the brain: changes in brain activity over a course of pulmonary rehabilitation. European Respiratory Jounal (2017)  DOI: 10.1183/13993003.01029-2017

Olivia Faull et al. Breathlessness and the body: Neuroimaging clues for the inferential leap, Cortex (2017). DOI: 10.1016/j.cortex.2017.07.019

Anja Hayen et al. Understanding dyspnea as a complex individual experience, Maturitas (2013). DOI: 10.1016/j.maturitas.2013.06.005 

Olivia Faull and Kyle Pattinson. The cortical connectivity of the periaqueductal gray and the conditioned response to the threat of breathlessness. Elife (2017) DOI: 10.7554/eLife.21749


Related reading on breathlessness

NHS IQ Breathlessness Pilots

Diagnosing breathlessness: in conversation with Professor Mike Morgan, NHS England’s Respiratory NCD