Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.

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.

Background: Dyspnea is the impairing cardinal symptom in COPD, but the underlying brain mechanisms and their relationships to clinical patient characteristics are widely unknown. This study compared neural responses to the perception and anticipation of dyspnea between patients with stable moderate-to-severe COPD and healthy controls. Moreover, associations between COPD-specific brain activation and clinical patient characteristics were examined. Methods: During functional magnetic resonance imaging, dyspnea was induced in patients with stable moderate-to-severe COPD (n = 17) and healthy control subjects (n = 21) by resistive-loaded breathing. Blocks of severe and mild dyspnea were alternating, with each block being preceded by visually cued anticipation phases. Results: During the perception of increased dyspnea, both patients and controls showed comparable brain activation in common dyspnea-relevant sensorimotor and cortico-limbic brain regions. During the anticipation of increased dyspnea, patients showed higher activation in hippocampus and amygdala than controls which was significantly correlated with reduced exercise capacity, reduced health-related quality of life, and higher levels of dyspnea and anxiety. Conclusions: This study suggests that patients with stable moderate-to-severe COPD show higher activation in emotion-related brain areas than healthy controls during the anticipation, but not during the actual perception of experimentally induced dyspnea. These brain activations were related to important clinical characteristics and might contribute to an unfavorable course of the disease via maladaptive psychological and behavioral mechanisms.

Dyspnea is the impairing, cardinal symptom patients with asthma repeatedly experience over the course of the disease. However, its accurate perception is also crucial for timely initiation of treatment. Reduced perception of dyspnea is associated with negative treatment outcome, but the underlying brain mechanisms of perceived dyspnea in patients with asthma remain poorly understood. We examined whether increasing disease duration in fourteen patients with mild-to-moderate asthma is related to structural brain changes in the insular cortex and brainstem periaqueductal grey (PAG). In addition, the association between structural brain changes and perceived dyspnea were studied. By using magnetic resonance imaging in combination with voxel-based morphometry, gray matter volumes of the insular cortex and the PAG were analysed and correlated with asthma duration and perceived affective unpleasantness of resistive load induced dyspnea. Whereas no associations were observed for the insular cortex, longer duration of asthma was associated with increased gray matter volume in the PAG. Moreover, increased PAG gray matter volume was related to reduced ratings of dyspnea unpleasantness. Our results demonstrate that increasing disease duration is associated with increased gray matter volume in the brainstem PAG in patients with mild-to-moderate asthma. This structural brain change might contribute to the reduced perception of dyspnea in some patients with asthma and negatively impact the treatment outcome.