Roland W. Esser

Emotions and neural processing of respiratory sensations investigated with respiratory-related evoked potentials.

Objective Patients with respiratory diseases such as asthma and chronic obstructive pulmonary disease frequently experience respiratory sensations, which are often perceived as unpleasant or threatening. However, the accurate perception of respiratory sensations is important for the management and treatment of these diseases. Emotions can substantially influence the perception of respiratory sensations and might affect the course of respiratory diseases, but the underlying neural mechanisms are poorly understood. The respiratory-related evoked potential (RREP) recorded from the electroencephalogram is a noninvasive technique that allowed first studies to examine the impact of emotions on the neural processing of respiratory sensations. Methods In this review, we will briefly introduce the importance of the perception of respiratory sensations and the influence of emotions on respiratory perception. We then provide an overview on the technique of RREP and present a systematic review on recent findings using this technique in the context of emotions. Results and Conclusions The evidence currently available from studies in healthy individuals suggests that short-lasting emotional states and anxiety affect the later RREP components (N1, P2, P3) related to higher-order neural processing of respiratory sensations, but not the earlier RREP components (Nf, P1) related to first-order sensory processing. We conclude with a discussion of the implications of this work for future research that needs to focus on respiratory patient groups and the associated clinical outcomes.

Brain Responses during the Anticipation of Dyspnea

Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.

Brain mechanisms of short-term habituation and sensitization toward dyspnea.

Dyspnea is a prevalent and threatening cardinal symptom in many diseases including asthma. Whether patients suffering from dyspnea show habituation or sensitization toward repeated experiences of dyspnea is relevant for both quality of life and treatment success. Understanding the mechanisms, including the underlying brain activation patterns, that determine the dynamics of dyspnea perception seems crucial for the improvement of treatment and rehabilitation. Toward this aim, we investigated the interplay between short-term changes of dyspnea perception and changes of related brain activation. Healthy individuals underwent repeated blocks of resistive load induced dyspnea with parallel acquisition of functional magnetic resonance imaging data. Late vs. early ratings on dyspnea intensity and unpleasantness were correlated with late vs. early brain activation for both, dyspnea anticipation and dyspnea perception. Individual trait and state anxiety were determined using questionnaire data. Our results indicate an involvement of the orbitofrontal cortex (OFC), midbrain/periaqueductal gray (PAG) and anterior insular cortex in habituation/sensitization toward dyspnea. Changes in the anterior insular cortex were particularly linked to changes in dyspnea unpleasantness. Changes of both dyspnea intensity and unpleasantness were positively correlated with state and trait anxiety. Our findings are in line with the suggested relationship between the anterior insular cortex and dyspnea unpleasantness. They further support the notion that habituation/sensitization toward dyspnea is influenced by anxiety. Our study extends the known role of the midbrain/PAG in anti-nociception to an additional involvement in habituation/sensitization toward dyspnea and suggests an interplay with the OFC.

Dyspnea catastrophizing and neural activations during the anticipation and perception of dyspnea

Dyspnea is an aversive symptom in various diseases. High levels of negative affectivity are typically associated with increased dyspnea and changes in its neural processing. Recently, more dyspnea-specific forms of negative affectivity such as dyspnea catastrophizing were suggested to contribute to increased perception of dyspnea beyond effects of rather unspecific negative affectivity such as general anxiety levels. The involved neural mechanisms have not yet been explored. Therefore, the present retrospective analysis examined the associations of dyspnea catastrophizing with neural activations during the anticipation and perception of dyspnea. Sixty-six healthy volunteers underwent 20 blocks of inspiratory resistive load breathing with parallel acquisition of fMRI data. Loads inducing either severe or mild dyspnea (dyspnea conditions) were presented in alternating order, with each condition being visually cued (anticipation conditions). Dyspnea catastrophizing and general trait anxiety were measured with the Breathlessness Catastrophizing Scale (BCS) and the State-Trait Anxiety Inventory, respectively. Correlating the BCS scores with neural activations during the perception of dyspnea yielded no significant results. However, during the anticipation of dyspnea, BCS scores correlated positively with activations of the anterior cingulate cortex (ACC), even after controlling for general anxiety levels. These activations in the ACC were not related to concurrent respiratory parameters. Results suggest that dyspnea catastrophizing in healthy volunteers is associated with stronger ACC recruitment during dyspnea anticipation. Given the established role of the ACC in processing affective states, affect regulation, and antinociception, this might reflect increased affective and/or top-down modulatory processing in individuals with higher dyspnea catastrophizing when anticipating dyspnea.

Brain Activation during Perception and Anticipation of Dyspnea in Chronic Obstructive Pulmonary Disease

Background: Dyspnea is the impairing cardinal symptom in COPD, but the underlying brain mechanisms and their relationships to clinical patient characteristics are widely unknown. This study compared neural responses to the perception and anticipation of dyspnea between patients with stable moderate-to-severe COPD and healthy controls. Moreover, associations between COPD-specific brain activation and clinical patient characteristics were examined. Methods: During functional magnetic resonance imaging, dyspnea was induced in patients with stable moderate-to-severe COPD (n = 17) and healthy control subjects (n = 21) by resistive-loaded breathing. Blocks of severe and mild dyspnea were alternating, with each block being preceded by visually cued anticipation phases. Results: During the perception of increased dyspnea, both patients and controls showed comparable brain activation in common dyspnea-relevant sensorimotor and cortico-limbic brain regions. During the anticipation of increased dyspnea, patients showed higher activation in hippocampus and amygdala than controls which was significantly correlated with reduced exercise capacity, reduced health-related quality of life, and higher levels of dyspnea and anxiety. Conclusions: This study suggests that patients with stable moderate-to-severe COPD show higher activation in emotion-related brain areas than healthy controls during the anticipation, but not during the actual perception of experimentally induced dyspnea. These brain activations were related to important clinical characteristics and might contribute to an unfavorable course of the disease via maladaptive psychological and behavioral mechanisms.

Breathlessness amplifies amygdala responses during affective processing

Breathlessness is an aversive symptom in many prevalent somatic and psychiatric diseases and is usually experienced as highly threatening. It is strongly associated with negative affect, but the underlying neural processes remain poorly understood. Therefore, using fMRI, the present study examined the effects of breathlessness on the neural processing of affective visual stimuli within candidate brain areas including the amygdala, insula, and anterior cingulate cortex (ACC). During scanning, 42 healthy volunteers, mean (SD) age: 29.0 (6.0) years, 14 female, were presented with affective picture series of negative, neutral, and positive valence while experiencing either no breathlessness (baseline conditions) or resistive-load induced breathlessness (breathlessness conditions). Respiratory measures and self-reports suggested successful induction of breathlessness and affective experiences. Self-reports of breathlessness intensity and unpleasantness were significantly higher during breathlessness conditions, mean (SD): 45.0 (16.6) and 32.3 (19.8), as compared to baseline conditions, mean (SD): 1.9 (3.0) and 2.9 (5.5). Compared to baseline conditions, stronger amygdala activations were observed during breathlessness conditions for both negative and positive affective picture series relative to neutral picture series, while no such effects were observed in insula and ACC. The present findings demonstrate that breathlessness amplifies amygdala responses during affective processing, suggesting an important role of the amygdala for mediating the interactions between breathlessness and affective states.