Breathlessness and the body: Neuroimaging clues for the inferential leap.

Breathlessness debilitates millions of people with chronic illness. Mismatch between breathlessness severity and objective disease markers is common and poorly understood. Traditionally, sensory perception was conceptualised as a stimulus-response relationship, although this cannot explain how conditioned symptoms may occur in the absence of physiological signals from the lungs or airways. A Bayesian model is now proposed, in which the brain generates sensations based on expectations learnt from past experiences (priors), which are then checked against incoming afferent signals. In this model, psychological factors may act as moderators. They may alter priors, change the relative attention towards incoming sensory information, or alter comparisons between priors and sensations, leading to more variable interpretation of an equivalent afferent input. In the present study we conducted a supplementary analysis of previously published data (Hayen et al., 2017). We hypothesised that individual differences in psychological traits (anxiety, depression, anxiety sensitivity) would correlate with the variability of subjective perceptions of equivalent breathlessness challenges. To better understand the resulting inferential leap in the brain, we explored where these behavioural measures correlated with functional brain activity across subjects. Behaviourally, anxiety sensitivity was found to positively correlate with each subject's variability of intensity and unpleasantness during mild breathlessness, and with variability of unpleasantness during strong breathlessness. In the brain, anxiety sensitivity was found to negatively correlate with precuneus activity during anticipation, positively correlate with anterior insula activity during mild breathlessness, and negatively correlate with parietal sensorimotor areas during strong breathlessness. Our findings suggest that anxiety sensitivity may reduce the robustness of this Bayesian sensory perception system, increasing the variability of breathlessness perception and possibly susceptibility to symptom misinterpretation. These preliminary findings in healthy individuals demonstrate how differences in psychological function influence the way we experience bodily sensations, which might direct us towards better understanding of symptom mismatch in clinical populations.