Abstract
Dyspnea is a prevalent and threatening cardinal symptom in many diseases including asthma. Whether patients suffering from dyspnea show habituation or sensitization toward repeated experiences of dyspnea is relevant for both quality of life and treatment success. Understanding the mechanisms, including the underlying brain activation patterns, that determine the dynamics of dyspnea perception seems crucial for the improvement of treatment and rehabilitation. Toward this aim, we investigated the interplay between short-term changes of dyspnea perception and changes of related brain activation. Healthy individuals underwent repeated blocks of resistive load induced dyspnea with parallel acquisition of functional magnetic resonance imaging data. Late vs. early ratings on dyspnea intensity and unpleasantness were correlated with late vs. early brain activation for both, dyspnea anticipation and dyspnea perception. Individual trait and state anxiety were determined using questionnaire data. Our results indicate an involvement of the orbitofrontal cortex (OFC), midbrain/periaqueductal gray (PAG) and anterior insular cortex in habituation/sensitization toward dyspnea. Changes in the anterior insular cortex were particularly linked to changes in dyspnea unpleasantness. Changes of both dyspnea intensity and unpleasantness were positively correlated with state and trait anxiety. Our findings are in line with the suggested relationship between the anterior insular cortex and dyspnea unpleasantness. They further support the notion that habituation/sensitization toward dyspnea is influenced by anxiety. Our study extends the known role of the midbrain/PAG in anti-nociception to an additional involvement in habituation/sensitization toward dyspnea and suggests an interplay with the OFC.
Highlights
The experience of dyspnea is the cardinal symptom in prevalent diseases such as asthma and chronic obstructive pulmonary disease (COPD)
In this study we investigated the development of perceived dyspnea intensity and unpleasantness over repeated blocks of dyspnea together with parallel changes of brain activation
We observed significant correlations of late vs. early dyspnea ratings with late vs. early brain activity during dyspnea anticipation and dyspnea perception. These correlations were restricted to a subset of our region-of interest (ROI), namely the orbitofrontal cortex (OFC), midbrain/periaqueductal gray (PAG), and the anterior insular cortex
Summary
The experience of dyspnea (breathlessness) is the cardinal symptom in prevalent diseases such as asthma and chronic obstructive pulmonary disease (COPD). Dyspnea perception has been shown to be modulated by several psychological factors, including attention, expectation, learning, Habituation and sensitization to dyspnea categorization and comparison processes, emotional predispositions, and current mood (e.g., Janssens et al, 2009; Lansing et al, 2009; Herigstad et al, 2011; Petersen et al, 2011, 2014). Via their influence on dyspnea perception these factors have a strong impact on coping strategies, disease management and disease progression (Hayen et al, 2013). Sensitization toward dyspnea seems more favorable as far as it might improve self-management by supporting the early initiation of actions during the onset of asthma exacerbations and by heightening the compliance with prescriptions
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