The impact of unpredictability of dyspnea offset on dyspnea perception, fear, and respiratory neural gating

Abstract

Dyspnea is a debilitating and threatening symptom in various diseases. Affected patients often report the unpredictability of dyspnea episodes being particularly anxiety-provoking and amplifying the perception of dyspnea. Experimental studies testing dyspnea unpredictability together with related neural processes, physiological fear responses, and dyspnea-related personality traits are sparse. Therefore, we investigated the impact of unpredictability of dyspnea offset on dyspnea perception and fear ratings, respiratory neural gating and physiological fear indices, as well as the influence of interindividual differences in fear of suffocation (FoS). Forty healthy participants underwent a task manipulating the offset predictability of resistive load-induced dyspnea including one unloaded safety condition. Respiratory variables, self-reports of dyspnea intensity, dyspnea unpleasantness, and fear were recorded. Moreover, respiratory neural gating was measured in a paired inspiratory occlusion paradigm using electroencephalography, while electrodermal activity, startle eyeblink, and startle probe N100 were assessed as physiological fear indices.Participants reported higher dyspnea unpleasantness and fear when dyspnea offset was unpredictable compared to being predictable. Individuals with high levels of FoS showed the greatest increase in fear and overall higher levels of fear and physiological arousal across all conditions. Respiratory neural gating, startle eyeblink, and startle probe N100 showed general reductions during dyspnea conditions but no difference between unpredictable and predictable dyspnea conditions. Together, the current results suggest that the unpredictable offset of dyspnea amplifies dyspnea perception and fear, especially in individuals with high levels of FoS. These effects were unrelated to respiratory neural gating or physiological fear responses, requiring future studies on underlying mechanisms.

The effect of unpredictability on the perception of breathlessness: a narrative review

“…Similar trends towards higher fear in the condition with unpredictable and delayed inspiratory resistive loads have also been observed by Pappens et al ( 41 ). In the same vein, further manipulations of the (un)predictability of inspiratory resistive loads by von Leupoldt et al ( 25 ) and Jelinčić et al ( 26 ) showed that fear of breathlessness was exacerbated in unpredictable conditions for both onset and duration types of unpredictability. The effect of onset unpredictability can however be mitigated by Tan's et al results ( 38 ) showing that it concerns only the participants who started with the unpredictable condition, and not those who started with the predictable condition.…”

“…All studies included self-reports and/or psychophysiological measures (e.g., SCR or EMG startle response) of state fear and anxiety. Five of these studies included measures of trait fear and anxiety ( 25 , 36 – 38 ) or trait negative affectivity ( 26 ). Lastly, 3 studies included measures of neural activity such as functional magnetic resonance imaging (fMRI) ( 21 ) and RREPs ( 25 , 26 ).…”

“…Five of these studies included measures of trait fear and anxiety ( 25 , 36 – 38 ) or trait negative affectivity ( 26 ). Lastly, 3 studies included measures of neural activity such as functional magnetic resonance imaging (fMRI) ( 21 ) and RREPs ( 25 , 26 ). Two articles were identified as relevant, but later excluded because of an absence of time interval between the conditioned stimulus CS (CO 2 -enriched air for 5 s) and the unconditioned stimulus US (CO 2 -enriched air for 15 s) in the predictable condition, and because the CS and US were not distinguishable from one another in terms of intensity, thus making the dyspneic CO 2 stimulation period appear longer in the predictable than in the unpredictable condition ( 39 , 40 ).…”

“…Across the reviewed studies, results mainly showed that unpredictable breathlessness induces more anxiety and fear than predictable breathlessness ( 25 , 26 , 37 , 38 , 41 ). For instance, Schroijen et al ( 37 ) used cues to manipulate the predictability and anticipation of breathing occlusions.…”

“…Moreover, an increasing number of studies have investigated the neural mechanisms underlying the perception of breathlessness using different neuroimaging techniques such as functional magnetic resonance imaging ( 21 – 24 ) and electroencephalography (EEG) ( 25 – 32 ). These studies commonly reported activations during experimentally induced breathlessness in affect-related limbic brain areas ( 22 – 24 ) and respective associations with state and trait negative affect ( 24 , 33 ).…”