Structural Brain Changes Related to Disease Duration in Patients with Asthma

Dyspnea is the impairing, cardinal symptom patients with asthma repeatedly experience over the course of the disease. However, its accurate perception is also crucial for timely initiation of treatment. Reduced perception of dyspnea is associated with negative treatment outcome, but the underlying brain mechanisms of perceived dyspnea in patients with asthma remain poorly understood. We examined whether increasing disease duration in fourteen patients with mild-to-moderate asthma is related to structural brain changes in the insular cortex and brainstem periaqueductal grey (PAG). In addition, the association between structural brain changes and perceived dyspnea were studied. By using magnetic resonance imaging in combination with voxel-based morphometry, gray matter volumes of the insular cortex and the PAG were analysed and correlated with asthma duration and perceived affective unpleasantness of resistive load induced dyspnea. Whereas no associations were observed for the insular cortex, longer duration of asthma was associated with increased gray matter volume in the PAG. Moreover, increased PAG gray matter volume was related to reduced ratings of dyspnea unpleasantness. Our results demonstrate that increasing disease duration is associated with increased gray matter volume in the brainstem PAG in patients with mild-to-moderate asthma. This structural brain change might contribute to the reduced perception of dyspnea in some patients with asthma and negatively impact the treatment outcome

Prenatal stress exposure is associated with increased dyspnea perception in adulthood

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Dyspnoea is the aversive cardinal symptom in various prevalent conditions such as respiratory, cardiovascular and neuromuscular diseases and is associated with great individual and socioeconomic burden [1]. Over the past years, several physiological and also psychological factors have been demonstrated to affect the perception of dyspnoea [1, 2]. For example, high levels of anxiety in adulthood were associated with increased dyspnoea perception in patients with asthma or chronic obstructive pulmonary disease (COPD), but also in healthy controls [2]. Moreover, adverse, separation-related experiences in childhood were linked to the subsequent development of increased anxiety and dyspnoea [3]. However, the effects of adverse experiences in early, prenatal life on dyspnoea perception remain widely unknown, although prenatal exposure to maternal stress and anxiety has convincingly been related to the development of other health and behavioural problems later in life, including impairments of the respiratory control system and high anxiety levels [4–9]. Therefore, this study investigated the relationship between prenatal exposure to maternal stress and the perception of dyspnoea in adulthood 28 years later

Neural responses to affective pictures while anticipating and perceiving respiratory threat

Emotional processes have an impact on the anticipation and perception of bodily threat sensations, such as breathlessness. However, little is known about the reverse influence of breathlessness on emotional processes, as well as its modulation by anxiety sensitivity (AS). Here, we investigated by means of visually evoked potentials how the perception versus anticipation of resistive-load-induced breathlessness (RLIB) influences emotional processing. High (HA) and low anxious (LA) participants viewed pictures of positive, neutral, or negative content under conditions of perceived RLIB, anticipated RLIB, or an unloaded baseline. The P2 (230–290 ms) was significantly less positive under perceived RLIB. Furthermore, the early late positive potential (LPP; 300–500 ms) was significantly less positive during both RLIB conditions, as compared to baseline. Overall, the P1 was significantly more positive in HA as compared to LA individuals. Additionally, across conditions, the late LPP (600–1,000 ms) was enhanced for positive and negative pictures as opposed to neutral ones for the LA group. In contrast, for the HA group only, the positive pictures elicited the typical enhanced LPP. Notably, for the HA participants, negative pictures elicited significantly blunted late LPPs during perceived RLIB as compared to anticipated RLIB and baseline. A reversed effect (i.e., more positivity) was observed for LA participants, suggesting motivational priming. Taken together, these results highlight the impact of perceived and anticipated respiratory threat on the neural processing of emotional picture stimuli, as well as its modulation by anxiety sensitivity levels

The longitudinal pattern of response when morphine is used to treat chronic refractory dyspnea

Background: While evidence supports using sustained release morphine for chronic refractory breathlessness, little is known about the longitudinal pattern of breathlessness intensity as people achieve symptomatic benefit. The aim of this study is to describe this pattern. Methods: This secondary analysis used breathlessness intensity scores (100mm visual analogue scale (VAS)) from a prospective, dose increment study of once daily (morning) sustained release morphine for chronic refractory breathlessness. Participants who achieved < 10% improvement over their own baseline at one week (10 mg) were titrated to 20mg and if no response, another week later to 30mg for one week. Time was standardized at the first day of the week in which participants responded generating twice daily data one week either side of symptomatic benefit. Analysis used random effect mixed modeling. Results: Of the 83 participants, 17/52 responders required > 10 mg: 13 participants (20 mg) and 4 (30 mg), contributing 634 VAS observations. In the week leading to a response, average VAS scores worsened by 0.3mm/ day ( p = 0.16); the average improvement in the first 24 hours of response was 10.9mm (7.0 to 14.7; p < 0.0001), with continued improvement of 2.2 mm/day ( p < 0.001) for six more days. Conclusion: When treating chronic refractory breathlessness with once daily sustained release morphine, titrate to effect, since inadequate dose may generate no response; and following an initial response, further dose increases should not occur for at least one week. Whether further benefit would be derived beyond day six on the dose to which people respond, and what net effect a further dose increase would have are questions yet to be answered

Evidence for a modulating effect of transcutaneous auricular vagus nerve stimulation (taVNS) on salivary alpha-amylase as indirect noradrenergic marker: a pooled mega-analysis

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Subjecting Elite Athletes to Inspiratory Breathing Load Reveals Behavioral and Neural Signatures of Optimal Performers in Extreme Environments

Background: It is unclear whether and how elite athletes process physiological or psychological challenges differently than healthy comparison subjects. In general, individuals optimize exercise level as it relates to differences between expected and experienced exertion, which can be conceptualized as a body prediction error. The process of computing a body prediction error involves the insular cortex, which is important for interoception, i.e. the sense of the physiological condition of the body. Thus, optimal performance may be related to efficient minimization of the body prediction error. We examined the hypothesis that elite athletes, compared to control subjects, show attenuated insular cortex activation during an aversive interoceptive challenge. Methodology/Principal Findings: Elite adventure racers (n = 10) and healthy volunteers (n = 11) performed a continuous performance task with varying degrees of a non-hypercapnic breathing load while undergoing functional magnetic resonance imaging. The results indicate that (1) non-hypercapnic inspiratory breathing load is an aversive experience associated with a profound activation of a distributed set of brain areas including bilateral insula, dorsolateral prefrontal cortex and anterior cingulated; (2) adventure racers relative to comparison subjects show greater accuracy on the continuous performance task during the aversive interoceptive condition; and (3) adventure racers show an attenuated right insula cortex response during and following the aversive interoceptive condition of non-hypercapnic inspirator

Cerebrovascular reactivity among native-raised high altitude residents: an fMRI study

Background: The impact of long term residence on high altitude (HA) on human brain has raised concern among researchers in recent years. This study investigated the cerebrovascular reactivity among native-born high altitude (HA) residents as compared to native sea level (SL) residents. The two groups were matched on the ancestral line, ages, gender ratios, and education levels. A visual cue guided maximum inspiration task with brief breath holding was performed by all the subjects while Blood-Oxygenation-Level-Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) data were acquired from them