Neural substrates for the perception of acutely induced dyspnea

Little is currently known about the brain regions involved in central proce ssing of dyspnea. We performed a functional imaging study with positron emi ssion tomography (PET) to assess brain activation associated with an import ant component of dyspnea, respiratory discomfort during loaded breathing. W e induced respiratory dis comfort in eight healthy volunteers by adding ext ernal resistive loads during inspiration and expiration. Brain activation w as characterized by a significant increase in regional cerebral blood flow (rCBF) (Z score of peak activation > 3.09). As compared with the unloaded c ontrol condition, high loaded breathing was associated with neural activati on in three distinct brain regions, the right anterior insula, the cerebell ar vermis, and the medial pens (respective Z scores = 4.75, 4.44 4.41). For these brain regions, we further identified a positive correlation between rCBF and the perceived intensity of respiratory discomfort (respective Z sc ores = 4.45, 4.75, 4.74) as well as between rCBF and the mean amplitude of mouth pressure swings (Delta Pm), the index of the main generating mechanis m of the sensation (respective Z scores = 4.67, 4.36, 4.31), suggesting a c ommon activation by these two parameters. Furthermore, we identified an are a in the right posterior cingulate cortex where neural activation was speci fically associated with perceived intensity of respiratory discomfort that is not related to Delta Pm (Z score = 4.25). Our results suggest that respi ratory discomfort related to loaded breathing may be subserved by two disti nct neural networks, the first being involved in the concomitant processing of the genesis and perception of respiratory discomfort and the second in the modulation of perceived intensity of the sensation by various factors o ther than its main generating mechanism, which may include emotional proces sing.