The unpleasantness of perceived dyspnea is processed in the anterior insula and amygdala

Rationale: The subjective perception of dyspnea, which is an impairing symptom in various cardiopulmonary diseases, consists of sensory (intensity) and affective aspects (unpleasantness). However, little is known about the cortical processing of the perception of dyspnea. Objectives: To investigate the cortical areas associated with the processing of the affective unpleasantness of perceived dyspnea. Methods: Brain imaging study using functional magnetic resonance imaging in 14 healthy volunteers. Measurements and Main Results: Dyspnea was induced by inspiratory resistive loaded breathing with concomitant positive and negative emotional stimulation by viewing standardized emotional picture series. The blood oxygen level-dependent contrast was measured as an index of local neuronal activity while respiration was continuously monitored. Negative emotional stimulation during loaded breathing was associated with higher unpleasantness of perceived dyspnea when compared with loaded breathing with concomitant positive emotional stimulation (P < 0.05). The levels of intensity of perceived dyspnea, respiratory responses, and load magnitude were similar between both conditions. Higher unpleasantness of dyspnea was associated with neuronal activations in the limbic system-that is, in the right anterior insula and in the right amygdala (respective Z values = 3.93 and 3.15; P < 0.05). Conclusions: The results of the present brain imaging study suggest that the unpleasantness of subjectively perceived dyspnea is processed in the right human anterior insula and amygdala.