Neural correlates coding stimulus level and perception of capsaicin-evoked urge-to-cough in humans

The perception of airways irritation is represented in a distributed brain network. However, the functional roles of sub-regions of this network are yet to be determined. The aim of this study was to measure brain activation in healthy participants as they inhaled two doses of capsaicin to identify dose-dependent and dose-independent responses. Blood oxygen level-dependent functional magnetic resonance imaging (fMRI) measures of brain responses during inhalation of saline, and a low and high dose of capsaicin were made from 16 healthy participants. Subjective ratings of the urge-to-cough were also made during capsaicin challenges. The majority of brain regions that were activated during capsaicin inhalation, including insula and mid cingulate cortex, showed graduated responses to the two doses of capsaicin. Prefrontal and parietal regions had dose-independent activation, whereas premotor regions and the cerebellum activated exclusively at the high dose of capsaicin. Activation in the somatosensory and mid-cingulate cortices correlated with ratings of urge-to-cough. In the brainstem, capsaicin produced dose-dependent activations in respiratory-related regions of the dorsal pons and lateral medulla. These data show dissociable response patterns to capsaicin inhalation that may represent different regional processes involved in monitoring and assessing stimulus intensity, determining the spatial localization of the stimulus and suppressing motor responses.