Pain by mistake:investigating a link between error-related negativity and pain avoidance behavior

ABSTRACT: Pain can be considered as a signal of "bodily error": Errors put organisms at danger and activate behavioral defensive systems. If the error is of physical nature, pain is the warning signal that motivates protective action such as avoidance behavior to safeguard our body's integrity. Interestingly, an important component of neural error processing, the error-related negativity (ERN), has been found to be related to avoidance in anxiety disorders. The present study is the first to extend these findings to pain and investigate the relationship between ERN and pain-related avoidance behavior. It was hypothesized that individuals with larger ERN amplitudes would show more pain-related avoidance behavior and would be more persistent in their avoidance despite changes in the environment. Fifty-three healthy individuals performed the Eriksen Flanker task during which their brain activity upon correct and erroneous motor responses was recorded by means of high-density electroencephalography. Avoidance behavior was assessed with an arm-reaching task using the HapticMaster robot arm. Results showed that, in contrast to our hypothesis, avoidance was not related to ERN amplitudes. Surprisingly, persons with elevated ERN amplitudes showed low levels of avoidance specifically during early acquisition trials. In contrast to earlier findings in anxiety disorders, individuals with elevated ERN amplitudes did not engage in more pain-related avoidance behavior. In fact, the opposite pattern was found at the start of acquisition: individuals with higher compared to lower ERN amplitudes were slower in learning to avoid pain. Replications and future studies on the relationship between ERN and avoidance behavior are needed

Is it a painful error?:The effect of unpredictability and intensity of punishment on the error-related negativity, and somatosensory evoked potentials

We examined how predictable and unpredictable punishment intensity contingent on error commission modulated ERN amplitudes. We recorded the ERN in 35 healthy volunteers performing the Eriksen flanker task. Errors were punished with predictable nonpainful, painful or unpredictable electrical stimulation. Furthermore, we investigated trait anxiety. We observed that ERN amplitudes did not differ across conditions, nor were there significant effects of anxiety. In contrast, we found that predictable painful punishments led to smaller Error Positivity (Pe). The effects of predictability and intensity were present in Somatosensory Evoked Potentials elicited by the punishments. N1 amplitudes were increased for painful compared to nonpainful stimulation, and P2/P3 amplitudes for painful compared to nonpainful, and for unpredictable compared to predictable stimulation. We suggest that unpredictability and increased painfulness of punishments enhance the potential motivational significance of the errors, but do not potentiate ERN amplitudes beyond the ones elicited by errors punished with predictable nonpainful stimulation

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

The Impact of Unpredictability on Dyspnea Perception, Anxiety and Interoceptive Error Processing

Dyspnea is a prevalent interoceptive sensation and the aversive cardinal symptom in many cardiorespiratory diseases as well as in mental disorders. Especially the unpredictability of the occurrence of dyspnea episodes has been suggested to be highly anxiety provoking for affected patients. Moreover, previous studies demonstrated that unpredictable exteroceptive stimuli increased self-reports and electrophysiological responses of anxiety such as the startle probe N100 as well as amplified the processing of errors as reflected by greater error-related negativity (ERN). However, studies directly examining the role of unpredictability on dyspnea perception, anxiety, and error processing are widely absent. Using high-density electroencephalography, the present study investigated whether unpredictable compared to predictable dyspnea would increase the perception of dyspnea, anxiety and interoceptive error processing. Thirty-two healthy participants performed a respiratory forced choice reaction time task to elicit an interoceptive ERN during two conditions: an unpredictable and a predictable resistive load-induced dyspnea condition. Predictability was manipulated by pairing (predictable condition) or not pairing (unpredictable condition) dyspnea with a startle tone probe. Self-reports of dyspnea and affective state as well as the startle probe N100 and interoceptive ERN were measured. The results demonstrated greater dyspnea unpleasantness in the unpredictable compared to the predictable condition. Post hoc analyses revealed that this was paralleled by greater anxiety, and greater amplitudes for the startle probe N100 and the interoceptive ERN during the unpredictable relative to the predictable condition, but only when the unpredictable condition was experienced in the first experimental block. Furthermore, higher trait-like anxiety sensitivity was associated with higher ratings for dyspnea unpleasantness and experimental state anxiety ratings. The present findings suggest that unpredictability increases the perception of dyspnea unpleasantness. This effect seems related to increased state and trait anxiety and interoceptive error processing, especially when upcoming dyspnea is particularly unpredictable, such as in early experimental phases. Future studies are required to further substantiate these findings in patients suffering from dyspnea

Prenatal stress exposure is associated with increased dyspnoea perception in adulthood

Prenatal exposure to maternal stress is associated with increased perception of dyspnea in adulthood 28 years later

The Effects of Repeated Dyspnea Exposure on Response Inhibition

In order to treat dyspnea (=breathlessness) successfully, response inhibition (RI) as a major form of self-regulation is a premise. This is supported by research showing that self-regulation is associated with beneficial behavioral changes supporting treatment success in patients. Recent research showed that dyspnea has an impairing effect on RI, but the effects of repeated dyspnea exposure on RI remain unknown. Therefore, the present study tested the effects of repeated resistive load-induced dyspnea on RI over a 5-day period. Healthy volunteers (n = 34) performed the standard version of the Stroop task during baseline and dyspnea conditions on the first and fifth testing day and underwent an additional dyspnea exposure phase on each testing day. Variables of interest to investigate RI were reaction time, accuracy as well as the event-related potentials late positive complex (LPC) and N400 in the electroencephalogram. Reduced accuracy for incongruent compared to congruent stimuli during the dyspnea condition on the first testing day were found (p < 0.001). This was paralleled by a reduced LPC and an increased N400 for incongruent stimuli during the induction of dyspnea (p < 0.05). After undergoing dyspnea exposure, habituation of dyspnea intensity was evident. Importantly, on the fifth testing day, no differences between baseline, and dyspnea conditions were found for behavioral and electrophysiological measures of RI. These findings demonstrate that the impairing effect of dyspnea on RI disappeared after repeated dyspnea exposure in healthy participants. Translated to a clinical sample, it might cautiously be suggested that dyspnea exposure such as dyspnea perceived during physical exercise could reduce the impairing effect of dyspnea on RI which might have the potential to help increase self-regulation abilities and subsequent treatment efforts in dyspneic patients

Делистинг как инструмент управления ценностью для акционеров

Цель: выделить драйверы, влияющие на решение о делистинге, с целью построения инвестиционной стратегии для потенциальных бенефициаров сделок ухода публичных компаний с биржи Задачи: 1) Провести теоретический обзор проблемы исследования с идентификацией природы и принципов феномена делистинга; 2) Проанализировать главные причины для добровольного делистинга; 3) Провести обзор процедур ухода с биржи; 4) Провести эмпирическое исследование относительно оценки влияния независимы переменных на решение о делистинге; 5) Предложить рекомендации для менеджеров и индивидуальных инвесторов; 6) Сделать общее заключение, суммируя результаты и подтверждая достижение цели. Основные результаты: Рекомендации сформированы в таблицы для распространения между определенными целевыми группами. Данные материалы считаются удобными в использовании и не требуют глубокого профессионального погружения в вопросы феномена делистинга. Предложена инвестиционная стратегия для бенефициаров сделок ухода публичных компаний с биржи.Goal: to identify drivers of delisting process in order to build investment strategy for potential beneficiaries of the going private transactions Objectives: 7) To make the theoretical overview of the research problem with identification of nature and principles related to delisting phenomena; 8) To analyze the main reasons for voluntary delisting; 9) To overview procedures for going private transactions; 10) To conduct an empirical study regarding evaluation of variables influenced the decision to delist; 11) To provide the recommendations applicable for managers and individuals; 12) To make a general conclusion on the research paper summing up all the results and confirming of achievement the stated goal. Main results: The recommendations are formed in tables for distribution among particular target groups and considered to be user-friendly and adopted for different level of diving into voluntary delisting topic. The managerial implications suggest built investment strategy for those who are interested in obtaining benefits from public-to-private transactions

Impact of Disease-Specific Fears on Pulmonary Rehabilitation Trajectories in Patients with COPD

Disease-specific fears predict health status in chronic obstructive pulmonary disease (COPD), but their role in pulmonary rehabilitation (PR) remains poorly understood and especially longer-term evaluations are lacking. We therefore investigated changes in disease-specific fears over the course of PR and six months after PR, and investigated associations with PR outcomes (COPD assessment test (CAT) and St. Georges respiratory questionnaire (SGRQ)) in a subset of patients with COPD (n = 146) undergoing a 3-week inpatient PR program as part of the STAR study (Clinicaltrials.gov, ID: NCT02966561). Disease-specific fears as measured with the COPD anxiety questionnaire improved after PR. For fear of dyspnea, fear of physical activity and fear of disease progression, improvements remained significant at six-month follow-up. Patients with higher disease-specific fears at baseline showed elevated symptom burden (CAT and SGRQ Symptom scores), which persisted after PR and at follow-up. Elevated disease-specific fears also resulted in reduced improvements in Quality of Life (SGRQ activity and impact scales) after PR and at follow-up. Finally, improvement in disease-specific fears was associated with improvement in symptom burden and quality of life. Adjustment for potential confounding variables (sex, smoking status, age, lung function, and depressive symptoms) resulted in comparable effects. These findings show the role of disease-specific fears in patients with COPD during PR and highlight the need to target disease-specific fears to further improve the effects of PR

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