Neural gating of respiratory sensations as a potential mechanism of dyspnea perception: State-of-the-art and future directions

Abstract

Context

Dyspnea – the subjective experience of breathing discomfort – is a prevalent and debilitating symptom in various chronic conditions, featuring a complex interplay of sensory, cognitive, and emotional factors contributing to its perception. In recent years, growing evidence emerged for the importance of neural processing in shaping symptom experiences such as dyspnea.

Objective

This frontiers review focuses on the neural gating of respiratory sensations (NGRS), as a potential neural mechanism underlying dyspnea perception. NGRS is measured by the repetition suppression of respiratory-related evoked potentials (RREP) elicited by paired inspiratory occlusions. NGRS may reflect the brain’s capacity to filter redundant respiratory input, and reduced NGRS may constitute a biomarker for aversive dyspnea experience.

Review

We summarize the current state-of-the-art on the relationships between NGRS and dyspnea, noting the inconsistent findings in healthy individuals along with promising evidence from clinical populations, such as chronic obstructive pulmonary disease (COPD). The inconsistent findings may be attributed to methodological limitations, including the significant variability in experimental designs and analytical choices hampering NGRS reliability, and the influence of top-down attention and expectations. In the final part of the review, we suggest future directions for the investigation of the NGRS-dyspnea relationship, including mechanistic research using advanced EEG analysis, mobile neuroimaging, and brain stimulation techniques to delineate the contributions of top-down and bottom-up mechanisms to NGRS.

Conclusions

By addressing the current knowledge gaps, this review forms a part of the concentrated effort to promote brain-based interventions for alleviating the distressing experience of chronic dyspnea.