Breathlessness in COPD: linking symptom clusters with brain activity

Abstract

RationaleCurrent models of breathlessness often fail to explain disparities between patients' experiences of breathlessness and objective measures of lung function. While a mechanistic understanding of this discordance has thus far remained elusive, factors such as mood, attention and expectation have all been implicated as important modulators of breathlessness. Therefore, we have developed a model to better understand the relationships between these factors using unsupervised machine learning techniques. Subsequently we examined how expectation-related brain activity differed between these symptom-defined clusters of participants.MethodsA cohort of 91 participants with mild-to-moderate chronic obstructive pulmonary disease (COPD) underwent functional brain imaging, self-report questionnaires and clinical measures of respiratory function. Unsupervised machine learning techniques of exploratory factor analysis and hierarchical cluster modelling were used to model brain-behaviour-breathlessness links.ResultsWe successfully stratified participants across four key factors corresponding to mood, symptom burden and two capability measures. Two key groups resulted from this stratification, corresponding to high and low symptom burden. Compared to the high symptom load group, the low symptom burden group demonstrated significantly greater brain activity within the anterior insula, a key region thought to be involved in monitoring internal bodily sensations (interoception).ConclusionsThis is the largest functional neuroimaging study of COPD to date and is the first to provide a clear model linking brain, behaviour and breathlessness expectation. Furthermore, it was possible to stratify participants into groups, which then revealed differences in brain activity patterns. Together, these findings highlight the value of multi-modal models of breathlessness in identifying behavioural phenotypes, and for advancing understanding of differences in breathlessness burden.

Baseline Psychological Traits Contribute to Lake Louise Acute Mountain Sickness Score at High Altitude

“…Mood and physical fatigue appear to be important perceptual modulators impacting individuals' symptom reporting (Finnegan et al, 2021 ; Harrison et al, 2021c ), therefore, we investigated the impact of these factors on AMS symptom burden in our cohort with hierarchical cluster analysis. Average Lake Louise AMS score over the trek clustered with self-reported measures of anxiety, agoraphobia, and neuroticism taken at sea level.…”

“…In particular, fatigue and anxiety may be the brain's manifestations of poor perceived self-efficacy and control, presenting as a state of learned helplessness (Stephan et al, 2016 ). Indeed, 1 study of breathlessness in 100 patients with Chronic Obstructive Pulmonary Disease demonstrated different behavioral profiles and brain activity in the anterior insula (a likely key interoceptive center) between a high and low symptom burden group, in the absence of any differences in spirometry between the two groups (Finnegan et al, 2021 ).…”

Breathlessness in a virtual world: An experimental paradigm testing how discrepancy between VR visual gradients and pedal resistance during stationary cycling affects breathlessness perception

“…A growing body of evidence [1–3, 5, 9, 11, 25–28] now suggests that breathlessness, far from simply arising as a product of peripheral inputs, includes steps of active interpretation and comparison with previously held expectations. In this study we demonstrated that as the observed VR hill gradient increased, participants’ reported breathlessness was also increased, independent of the physical effort applied to pedalling the bike.…”

Baseline psychological traits contribute to Lake Louise Acute Mountain Sickness score at high altitude

“…Mood and physical fatigue appear to be important perceptual modulators impacting individuals’ symptom reporting (Harrison et al, 2020b; Finnegan et al, 2021), therefore we investigated the impact of these factors on AMS symptom burden in our cohort with hierarchical cluster analysis. Average Lake Louise AMS score over the trek clustered with self-reported measures of anxiety, agoraphobia, and neuroticism taken at sea level.…”

“…In particular, fatigue and anxiety may be the brain’s manifestations of poor perceived self-efficacy and control, presenting as a state of learned helplessness (Stephan et al, 2016). Indeed, one study of breathlessness in 100 patients with Chronic Obstructive Pulmonary Disease demonstrated different behavioural profiles and brain activity in the anterior insula (a likely key interoceptive centre) between a high and low symptom burden group, in the absence of any differences in spirometry between the two groups (Finnegan et al, 2021). Therefore, we also hypothesised that self-report questionnaires characterising individuals’ baseline psychological state may correlate with their symptom burden over the expedition.…”