RT Journal Article SR Electronic T1 Breathlessness and the body: Neuroimaging evidence for the inferential leap JF bioRxiv FD Cold Spring Harbor Laboratory SP 117408 DO 10.1101/117408 A1 Olivia K Faull A1 Anja Hayen A1 Kyle T S Pattinson YR 2017 UL http://biorxiv.org/content/early/2017/03/24/117408.abstract AB 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 learned from past experiences (priors), which are then checked against incoming afferent signals. In this model, psychological factors may act as moderators. They may either alter priors, or change the relative attention towards incoming sensory information, leading to more variable interpretation of an equivalent afferent input.In the present study we conducted a preliminary test of this model in a supplementary analysis of previously published data (Hayen 2017). We hypothesised that individual differences in psychological traits (anxiety, depression, anxiety sensitivity) would correlate with the variability of subjective evaluation of equivalent breathlessness challenges. To better understand the resulting inferential leap in the brain, we explored whether these behavioural measures correlated with activity in areas governing either prior generation or sensory afferent input.Behaviorally, anxiety sensitivity was found to positively correlate with each subject’s variability of intensity and unpleasantness during mild breathlessness, and with unpleasantness during strong breathlessness. In the brain, anxiety sensitivity was found to positively correlate with activity in the anterior insula 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.