Sarah Kegat

The Unpleasantness of Perceived Dyspnea Is Processed in the Anterior Insula and Amygdala

RATIONALE The subjective perception of dyspnea, which is an impairing symptom in various cardiopulmonary diseases, consists of sensory (intensity) and affective aspects (unpleasantness). However, little is known about the cortical processing of the perception of dyspnea. OBJECTIVES To investigate the cortical areas associated with the processing of the affective unpleasantness of perceived dyspnea. METHODS Brain imaging study using functional magnetic resonance imaging in 14 healthy volunteers. MEASUREMENTS AND MAIN RESULTS Dyspnea was induced by inspiratory resistive loaded breathing with concomitant positive and negative emotional stimulation by viewing standardized emotional picture series. The blood oxygen level-dependent contrast was measured as an index of local neuronal activity while respiration was continuously monitored. Negative emotional stimulation during loaded breathing was associated with higher unpleasantness of perceived dyspnea when compared with loaded breathing with concomitant positive emotional stimulation (P < 0.05). The levels of intensity of perceived dyspnea, respiratory responses, and load magnitude were similar between both conditions. Higher unpleasantness of dyspnea was associated with neuronal activations in the limbic system-that is, in the right anterior insula and in the right amygdala (respective Z values = 3.93 and 3.15; P < 0.05). CONCLUSIONS The results of the present brain imaging study suggest that the unpleasantness of subjectively perceived dyspnea is processed in the right human anterior insula and amygdala.

Dyspnea and pain share emotion-related brain network.

The early detection of stimuli signalling threat to an organism is a crucial evolutionary advantage. For example, the perception of aversive bodily sensations such as dyspnea and pain strongly motivates fast adaptive behaviour to ensure survival. Their similarly threatening and motivating characters led to the speculation that both sensations are mediated by common brain areas, which has also been suggested by neuroimaging studies on either dyspnea or pain. By using functional magnetic resonance imaging (fMRI), we formally tested this hypothesis and compared the cortical processing of perceived heat pain and resistive load induced dyspnea in the same group of participants. Here we show that the perception of both aversive sensations is processed in similar brain areas including the insula, dorsal anterior cingulate cortex, amygdala and medial thalamus. These areas have a documented role in the processing of emotions such as fear and anxiety. Thus, the current study highlights the role of a common emotion-related human brain network which underlies the perception of aversive bodily sensations such as dyspnea and pain. This network seems crucial for translating the threatening character of different bodily signals into behavioural consequences that promote survival.

Down-Regulation of Insular Cortex Responses to Dyspnea and Pain in Asthma

RATIONALE Dyspnea is the impairing cardinal symptom of asthma but its accurate perception is also crucial for timely initiation of treatment. However, the underlying brain mechanisms of perceived dyspnea in patients with asthma are unknown. OBJECTIVES To study brain mechanisms of dyspnea in asthma. METHODS By using functional magnetic resonance imaging we compared the neuronal responses to experimentally induced dyspnea in patients with asthma and healthy controls. These brain activations were compared with neuronal responses evoked by pain to study neuronal generalization processes to another, similarly unpleasant, physiological sensation. MEASUREMENTS AND MAIN RESULTS While lying in the scanner, fourteen patients with mild-to-moderate asthma and fourteen matched healthy controls repeatedly underwent conditions of mild dyspnea, severe dyspnea, mild pain and severe pain. Dyspnea was induced by resistive loaded breathing. Heat pain of similar intensity was induced by a contact thermode. Whereas the sensory intensity of both sensations was rated similar by patients and controls, ratings of the affective unpleasantness of dyspnea and pain were reduced in patients. This perceptual difference was mirrored by reduced insular cortex activity, but increased activity in the periaqueductal gray (PAG) in patients during both increased dyspnea and pain. Connectivity analyses showed that asthma-specific down-regulation of the insular cortex during dyspnea and pain was moderated by increased PAG activity. CONCLUSIONS The results suggest a down-regulation of affect-related insular cortex activity by the PAG during perceived dyspnea and pain in patients with asthma. This might represent a neuronal habituation mechanism reducing the affective unpleasantness of dyspnea in asthma, which generalizes to other unpleasant physiological sensations such as pain.