Respiratory sensations such as breathlessness are prevalent in many diseases and are amplified by increased levels of anxiety. Cortical activation in response to inspiratory occlusions in high- and low-anxious individuals was found different in previous studies using the respiratory-related evoked potential method. However, specific brain areas showed different activation patterns remained unknown in these studies. Therefore, the purpose of this study was to compare cortical and subcortical neural substrates of respiratory sensation in response to inspiratory mechanical occlusion stimuli between high- and low-anxious individuals using functional magnetic resonance imaging (fMRI). In addition, associations between brain activation patterns and levels of anxiety, and breathlessness were examined. Thirty-four (17 high- and 17 low-anxious) healthy non-smoking adults with normal lung function completed questionnaires on anxiety (State Trait Anxiety Inventory - State), and participated in a transient inspiratory occlusion fMRI experiment. The participants breathed with a customized face-mask while respiration was repeatedly interrupted by a transient inspiratory occlusion of 150-msec, delivered every 2 to 4 breaths. Breathlessness was assessed by self-report. At least 32 occluded breaths were collected for data analysis. The results showed that compared to the low-anxious group, the high-anxious individuals demonstrated significantly greater neural activations in the hippocampus, insula, and middle cingulate gyrus in response to inspiratory occlusions. Moreover, a significant relationship was found between anxiety levels and activations of the right inferior parietal gyrus, and the right precuneus. Additionally, breathlessness levels were significantly associated with activations of the bilateral thalamus, bilateral insula and bilateral cingulate gyrus. The above evidences support stronger recruitment of emotion-related cortical and subcortical brain areas in higher anxious individuals, and thus these areas play an important role in respiratory mechanosensation mediated by anxiety.
Cortical and subcortical mechanosensation of breathing can be measured by short respiratory occlusions. However, the corresponding neural substrates involved in the respiratory sensation elicited by a respiratory mechanical stimulus remained unclear. Therefore, we applied the functional magnetic resonance imaging (fMRI) technique to study cortical activations of respiratory mechanosensation. We hypothesized that thalamus, frontal cortex, somatosensory cortex, and inferior parietal cortex would be significantly activated in response to respiratory mechanical stimuli. We recruited 23 healthy adults to participate in our event-designed fMRI experiment. During the 12-min scan, participants breathed with a specialized face-mask. Single respiratory occlusions of 150 ms were delivered every 2–4 breaths. At least 32 successful occlusions were collected for data analysis. The results showed significant neural activations in the thalamus, supramarginal gyrus, middle frontal gyrus, inferior frontal triangularis, and caudate (AlphaSim corrected p < 0.05). In addition, subjective ratings of breathlessness were significantly correlated with the levels of neural activations in bilateral thalamus, right caudate, right supramarginal gyrus, left middle frontal gyrus, left inferior triangularis. Our results demonstrated cortical sources of respiratory sensations elicited by the inspiratory occlusion paradigm in healthy adults were located in the thalamus, supramarginal gyrus, and the middle frontal cortex, inferior frontal triangularis, suggesting subcortical, and cortical neural sources of the respiratory mechanosensation are thalamo-cortical based, especially the connections to the premotor area, middle and ventro-lateral prefrontal cortex, as well as the somatosensory association cortex. Finally, level of neural activation in thalamus is associated with the subjective rating of breathlessness, suggesting respiratory sensory information is gated at the thalamic level.
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