Abstract
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.
Highlights
Respiratory sensations such as breathlessness are aversive and prevalent symptoms in many cardiorespiratory diseases
Significant activations were observed in the thalamus, caudate, putamen, precuneus, supramarginal gyrus, cingulate cortex, temporal lobe, somatosensory association cortex (SII), frontal cortex, and inferior parietal cortex using a threshold of p < 0.05 (FWE corrected)
The present study examined the brain activation patterns in response to transient inspiratory occlusions
Summary
Respiratory sensations such as breathlessness are aversive and prevalent symptoms in many cardiorespiratory diseases. Most studies have utilized resistive loads to measure brain substrates related to dyspnea[14,15,17,19,22,24,25], whereas a few other studies have used inhalation of elevated CO2 levels[26,27] or threshold loads, respectively[23] These studies found that sensorimotor areas such as the sensorimotor cortex, supplementary motor area, SII and thalamus, and emotion-related areas such as insular cortex, amygdala, anterior cingulate cortex (ACC), hippocampus, and periaqueductal gray (PAG) were activated with inspiratory resistive loads. We found that TIO elicited significant brain activations in the thalamus, caudate, premotor area, and SII18 Whether these brain activation patterns in response to transient inspiratory occlusions would differ between low- and high- anxious individuals remained unclear from these studies. The purpose of this fMRI study was to identify differences between high- and low-anxious individuals in their cortical and subcortical brain activation patterns associated with respiratory mechanosensation as elicited by inspiratory occlusions. In additional explorative analyses we examined the associations between brain activation patterns and individual levels of anxiety and breathlessness
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