Disease acceptance, but not perceived control, is uniquely associated with inflammatory bowel disease-related disability.

BACKGROUND AND AIMS: Disability, an important aspect of disease burden in patients with inflammatory bowel disease (IBD), has been suggested as a valuable clinical endpoint. We aimed to investigate how disease acceptance and perceived control, two psychological predictors of subjective health, are associated with IBD-related disability. METHODS: In this cross-sectional study, adult IBD patients from the University Hospitals Leuven received a survey with questions about clinical and demographic characteristics, disease acceptance and perceived control (Subjective Health Experience model questionnaire), and IBD-related disability (IBD Disk). Multiple linear regressions assessed predictors of IBD-related disability in the total sample and in the subgroups of patients in clinical remission or with active disease. RESULTS: In the total sample (N = 1250, 54.2% female, median [IQR] age 51 [39-61] years, 61.3% Crohn's disease, 34.9% active disease), adding the psychological predictors to the model resulted in an increased explained variance in IBD-related disability of 19% compared to a model with only demographic and clinical characteristics (R2adj 38% vs. 19%, p<.001). The increase in explained variance was higher for patients in clinical remission (ΔR2adj 20%, p<.001) compared to patients with active disease (ΔR2adj 10%, p<.001). Of these predictors, disease acceptance was most strongly associated with disability in the total sample (ß=-0.44, p<.001), as well as in both subgroups (ß=-0.47, p<.001 and ß=-0.31, p<.001 respectively). Perceived control was not significantly associated with disability when accounting for all other predictors. CONCLUSIONS: Disease acceptance is strongly associated with IBD-related disability, supporting further research into disease acceptance as a treatment target.

Brain mediators of negative affect-induced physical symptom reporting in patients with functional somatic syndromes.

Functional somatic syndromes (FSS) include fibromyalgia, irritable bowel syndrome (IBS), and others. In FSS patients, merely viewing negative affective pictures can elicit increased physical symptoms. Our aim was to investigate the neural mechanisms underlying such negative affect-induced physical symptoms in FSS patients. Thirty patients with fibromyalgia and/or IBS and 30 healthy controls (all women) watched neutral, positive and negative affective picture blocks during functional MRI scanning and rated negative affect and physical symptoms after every block. We compared brain-wide activation during negative versus neutral picture viewing in FSS patients versus controls using robust general linear model analysis. Further, we compared neurologic pain signature (NPS), stimulus intensity-independent pain signature (SIIPS) and picture-induced negative emotion signature (PINES) responses to the negative versus neutral affect contrast and investigated whether they mediated between-group differences in affective picture-induced physical symptom reporting. More physical symptoms were reported after viewing negative compared to neutral pictures, and this effect was larger in patients than controls (p = 0.025). Accordingly, patients showed stronger activation in somatosensory regions during negative versus neutral picture viewing. NPS, but not SIIPS nor PINES, responses were higher in patients than controls during negative versus neutral pictures (p = 0.026). These differential NPS responses partially mediated between-group differences in physical symptoms. In conclusion, picture-induced negative affect elicits physical symptoms in FSS patients as a result of activation of somatosensory and nociceptive brain patterns, supporting the idea that affect-driven alterations in processing of somatic signals is a critical mechanism underlying FSS.

Effects of transcutaneous auricular vagus nerve stimulation on P300 magnitudes and salivary alpha-amylase during an auditory oddball task.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neurostimulation technique that is thought to modulate noradrenergic activity. Previous studies have demonstrated inconsistent effects of taVNS on noradrenergic activity, which is possibly due to insufficient statistical power, suboptimal stimulation parameter settings, and data collection procedures. In this preregistered within-subject experiment, 44 healthy participants received taVNS and sham (earlobe) stimulation during two separate experimental sessions. Stimulation intensity was individually calibrated to the maximum level below pain. During each session, participants received the stimulation continuously ten minutes before an auditory novelty oddball task till the end of the experimental session. The P3b component of the event-related potential served as a marker of phasic noradrenergic activity, whereas P3a magnitude was explored as an index of dopaminergic activity. Salivary alpha-amylase (sAA) was measured as an index of tonic noradrenergic activity before and at the end of the stimulation. The taVNS and sham conditions did not differ in P3a or P3b magnitudes, nor sAA secretion. These findings call into question whether taVNS, administered continuously at high, nonpainful stimulation intensities, reliably augments noradrenergic activity via the vagus nerve.

Expiratory-gated Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) does not Further Augment Heart Rate Variability During Slow Breathing at 0.1 Hz.

As cardiac vagal control is a hallmark of good health and self-regulatory capacity, researchers are seeking ways to increase vagally mediated heart rate variability (vmHRV) in an accessible and non-invasive way. Findings with transcutaneous auricular vagus nerve stimulation (taVNS) have been disappointing in this respect, as its effects on vmHRV are inconsistent at best. It has been speculated that combining taVNS with other established ways to increase vmHRV may produce synergistic effects. To test this idea, the present study combined taVNS with slow breathing in a cross-over design. A total of 22 participants took part in two sessions of breathing at 6 breaths/min: once combined with taVNS, and once combined with sham stimulation. Electrical stimulation (100 Hz, 400 µs) was applied during expiration, either to the tragus and cavum conchae (taVNS) or to the earlobe (sham). ECG was recorded during baseline, 20-minutes of stimulation, and the recovery period. Frequentist and Bayesian analyses showed no effect of taVNS (in comparison to sham stimulation) on the root mean square of successive differences between normal heartbeats, mean inter-beat interval, or spectral power of heart rate variability at a breathing frequency of 0.1 Hz. These findings suggest that expiratory-gated taVNS combined with the stimulation parameters examined here does not produce acute effects on vmHRV during slow breathing.

Short bursts of transcutaneous auricular vagus nerve stimulation enhance evoked pupil dilation as a function of stimulation parameters.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a neurostimulatory technique hypothesised to enhance central noradrenaline. Currently, there is scarce evidence in support of a noradrenergic mechanism of taVNS and limited knowledge on its stimulation parameters (i.e., intensity and pulse width). Therefore, the present study aimed to test whether taVNS enhances pupil dilation, a noradrenergic biomarker, as a function of stimulation parameters. Forty-nine participants received sham (i.e., left ear earlobe) and taVNS (i.e., left ear cymba concha) stimulation in two separate sessions, in a counterbalanced order. We administered short bursts (5s) of seven stimulation settings varying as a function of pulse width and intensity and measured pupil size in parallel. Each stimulation setting was administered sixteen times in separate blocks. We expected short bursts of stimulation to elicit phasic noradrenergic activity as indexed by event-related pupil dilation and event-related temporal derivative. We hypothesised higher stimulation settings, quantified as the total charge per pulse (pulse width x intensity), to drive greater event-related pupil dilation and temporal derivative in the taVNS compared to sham condition. Specifically, we expected stimulation settings in the taVNS condition to be associated with a linear increase in event-related pupil dilation and temporal derivative. We found stimulation settings to linearly increase both pupil measures. In line with our hypothesis, the observed dose-dependent effect was stronger in the taVNS condition. We also found taVNS to elicit more intense and unpleasant sensations than sham stimulation. These results support the hypothesis of a noradrenergic mechanism of taVNS. However, future studies should disentangle whether stimulation elicited sensations mediate the effect of taVNS on evoked pupil dilation.

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

BACKGROUND: Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has received tremendous attention as a potential neuromodulator of cognitive and affective functions, which likely exerts its effects via activation of the locus coeruleus-noradrenaline (LC-NA) system. Reliable effects of taVNS on markers of LC-NA system activity, however, have not been demonstrated yet. METHODS: The aim of the present study was to overcome previous limitations by pooling raw data from a large sample of ten taVNS studies (371 healthy participants) that collected salivary alpha-amylase (sAA) as a potential marker of central NA release. RESULTS: While a meta-analytic approach using summary statistics did not yield any significant effects, linear mixed model analyses showed that afferent stimulation of the vagus nerve via taVNS increased sAA levels compared to sham stimulation (b = 0.16, SE = 0.05, p = 0.001). When considering potential confounders of sAA, we further replicated previous findings on the diurnal trajectory of sAA activity. CONCLUSION(S): Vagal activation via taVNS increases sAA release compared to sham stimulation, which likely substantiates the assumption that taVNS triggers NA release. Moreover, our results highlight the benefits of data pooling and data sharing in order to allow stronger conclusions in research.

Perceptual sensitivity to sensory and affective aspects of dyspnea: Test-retest reliability and effects of fear of suffocation.

Perceptual sensitivity for dyspnea (i.e. breathlessness) is often quantified using the slope of magnitude estimations plotted against the physical stimulus intensities of respiratory loads. This study investigated whether this slope and its stability varies as a function of (1) affective versus sensory aspects of dyspnea, and (2) interindividual differences in Fear of Suffocation. Eighty-three healthy women performed a load magnitude estimation task twice one week apart. Resistive loads of increasing magnitude (0-2.4-5-7.4-12.4-20 cmH20/l/s) were repeatedly presented for a single flow-targeted inspiration. One group rated the intensity of loads, another their unpleasantness. Neither slopes nor intercepts differed between sensory versus affective aspects of dyspnea. Intercepts were lower in the second compared to the first session. Fear of Suffocation was associated with flatter slopes. Test-retest reliabilities were low to moderate suggesting that perceptual sensitivity to dyspnea is less stable than commonly assumed.

The effects of unpredictability and negative affect on perception and neural gating in different interoceptive modalities.

Breathlessness and pain frequently co-occur in chronic conditions, and their unpredictability is often reported to amplify perception and negative affect (NA), however any common neural mechanisms remain largely unexplored. This study examined the effects of (unpredictable) bodily threat on perception and neural gating of respiratory and somatosensory stimuli. Healthy adults (N = 51) experienced brief paired inspiratory occlusions and electrocutaneous stimuli, with their neural activity monitored via electroencephalography. Neural gating was measured as a ratio of the N1 response to the second relative to the first stimulus in a pair. In 4/6 blocks, threatening stimulation, in form of additional loaded breaths or electrocutaneous pulses, was presented predictably or unpredictably. Participants reported: perceived intensity and unpleasantness of all stimuli, fear, trait NA and intolerance of uncertainty (IU). Threatening stimulation increased perception, fear, and N1 amplitudes, without affecting neural gating. There was no group effect of unpredictability, though interactions were found with NA and IU. Cross-modal correlations revealed significant baseline relationships in neural gating and perception, though not in their modulation by threat. The present findings demonstrate that respiratory and somatosensory modalities relate in baseline perception and neural gating, and exhibit similar modulation effects by unpleasant stimulation. Further research is encouraged to elucidate the underlying mechanisms of these relationships, and the potential interactions with stimulus unpredictability.

Learn to breathe, breathe to learn? No evidence for effects of slow deep breathing at a 0.1 Hz frequency on reversal learning.

This study sought to investigate whether slow deep breathing (SDB) facilitates reversal learning. We also explored whether SDB modulates the renewal effect. After learning a series of cue-outcome associations (early acquisition phase) in a predictive learning task, 37 participants paced their breathing according to a normal (NPB group; 0.2 Hz) or a slow (SDB group; 0.1 Hz) pattern while completing the reversal and renewal phases. Response correctness, heart rate variability (HRV, i.e., Root mean square of successive differences), and respiratory rate were assessed. Findings indicated that both groups adopted the targeted breathing pattern. As expected, the SDB (vs. NPB) group displayed a steeper rise in HRV from early acquisition to the later phases of the task during which the breathing manipulation took place. However, the performance of the NPB and SDB groups did not significantly differ in any phase of the predictive learning task. Despite the inconclusive findings on the effect of SDB on reversal and renewal, these results confirm that SDB can be performed while performing a learning task.

No evidence for a modulating effect of continuous transcutaneous auricular vagus nerve stimulation on markers of noradrenergic activity.

Although transcutaneous auricular vagus nerve stimulation (taVNS) is thought to increase central noradrenergic activity, findings supporting such mechanism are scarce and inconsistent. This study aimed to investigate whether taVNS modulates indirect markers of phasic and tonic noradrenergic activity. Sixty-six healthy participants performed a novelty auditory oddball task twice on separate days: once while receiving taVNS (left cymba concha), once during sham (left earlobe) stimulation. To maximize potential effects, the stimulation was delivered continuously (frequency: 25 Hz; width: 250 µs) at an intensity individually calibrated to the maximal level below pain threshold. The stimulation was administered 10 min before the oddball task and maintained throughout the session. Event-related pupil dilation (ERPD) to target stimuli and pre-stimulus baseline pupil size were assessed during the oddball task as markers of phasic and tonic noradrenergic activity, respectively. Prior to and at the end of stimulation, tonic pupil size at rest, cortisol, and salivary alpha-amylase were assessed as markers of tonic noradrenergic activity. Finally, we explored the effect of taVNS on cardiac vagal activity, respiratory rate, and salivary flow rate. Results showed a greater ERPD to both target and novelty compared to standard stimuli in the oddball task. In contrast to our hypotheses, taVNS did not impact any of the tested markers. Our findings strongly suggest that continuous stimulation of the cymba concha with the tested stimulation parameters is ineffective to increase noradrenergic activity via a vagal pathway.

Effect of slow, deep breathing on visceral pain perception and its underlying psychophysiological mechanisms.

BACKGROUND: Studies using somatic pain models have shown the hypoalgesic effects of slow, deep breathing. We evaluated the effect of slow, deep breathing on visceral pain and explored putative mediating mechanisms including autonomic and emotional responses. METHODS: Fifty-seven healthy volunteers (36 females, mean age = 22.0 years) performed controlled, deep breathing at a slow frequency (6 breaths per minute), controlled breathing at a normal frequency (14 breaths per minute; active control), and uncontrolled breathing (no-treatment control) in randomized order. Moderate painful stimuli were given during each condition by delivering electrical stimulation in the distal esophagus. Participants rated pain intensity after each stimulation. Heart rate variability and self-reported arousal were measured during each condition. KEY RESULTS: Compared to uncontrolled breathing, pain intensity was lower during slow, deep breathing (Cohen's d = 0.40) and normal controlled breathing (d = 0.47), but not different between slow, deep breathing and normal controlled breathing. Arousal was lower (d = 0.53, 0.55) and heart rate variability was higher (d = 0.70, 0.86) during slow, deep breathing compared to the two control conditions. The effect of slow, deep breathing on pain was not mediated by alterations in heart rate variability or arousal but was moderated by pain catastrophizing. CONCLUSIONS AND INFERENCES: Slow, deep breathing can reduce visceral pain intensity. However, the effect is not specific to the slow breathing frequency and is not mediated by autonomic or emotional responses, suggesting other underlying mechanisms (notably distraction). Whether a long-term practice of slow, deep breathing can influence (clinical) visceral pain warrants to be investigated.

The breathing brain: The potential of neural oscillations for the understanding of respiratory perception in health and disease.

Dyspnea or breathlessness is a symptom occurring in multiple acute and chronic illnesses, however, the understanding of the neural mechanisms underlying its subjective experience is limited. In this topical review, we propose neural oscillatory dynamics and cross-frequency coupling as viable candidates for a neural mechanism underlying respiratory perception, and a technique warranting more attention in respiration research. With the evidence for the potential of neural oscillations in the study of normal and disordered breathing coming from disparate research fields with a limited history of interdisciplinary collaboration, the main objective of the review was to converge the existing research and suggest future directions. The existing findings show that distinct limbic and cortical activations, as measured by hemodynamic responses, underlie dyspnea, however, the time-scale of these activations is not well understood. The recent findings of oscillatory neural activity coupled with the respiratory rhythm could provide the solution to this problem, however, more research with a focus on dyspnea is needed. We also touch on the findings of distinct spectral patterns underlying the changes in breathing due to experimental manipulations, meditation and disease. Subsequently, we suggest general research directions and specific research designs to supplement the current knowledge using neural oscillation techniques. We argue for the benefits of interdisciplinary collaboration and the converging of neuroimaging and behavioral methods to best explain the emergence of the subjective and aversive individual experience of dyspnea.

Inflammatory Bowel Disease-related Behaviours [IBD-Bx] Questionnaire: Development, Validation and Prospective Associations with Fatigue.

BACKGROUND AND AIMS: Disease-related behaviours that may maintain or worsen symptom burden remain largely unexplored in inflammatory bowel disease [IBD]. In this study, we developed and validated an instrument assessing IBD-related, modifiable behaviours and explored which behaviours prospectively correlate with fatigue, a debilitating and common symptom in IBD. METHODS: Initially, 72 items reflecting IBD-related behaviours were generated based on literature review and input from clinicians and people diagnosed with IBD. During wave 1, 495 IBD patients rated to what extent each behaviour was applicable to them. Additionally, disease activity, fatigue, IBD-related concerns and psychological variables were assessed. During a follow-up visit 4-12 weeks later [wave 2], a random selection of 92 patients from wave 1 completed the measures assessing the IBD-related behaviours, disease activity and fatigue once more. RESULTS: A principal component analysis with oblique rotation revealed seven components in the 72 IBD behaviours, which could be interpreted as: [1] Avoiding food and activities, [2] Access to toilets, [3] Avoidance of sex, [4] Cognitive avoidance, [5] Not sharing with others, [6] Alternative treatments and [7] Disease management. Each component was reduced to three to five representative items, resulting in a final, 25-item IBD-Bx questionnaire showing good concurrent validity [alphas > 0.63] and reliability. Almost all components were cross-sectionally related to levels of fatigue. Avoiding food and activities and Access to toilets significantly predicted fatigue at wave 2 when controlling for baseline fatigue. CONCLUSIONS: The IBD-Bx is a valid and reliable questionnaire of IBD-related behaviours, some of which predict future fatigue burden.

Effects of transcutaneous auricular vagus nerve stimulation on reversal learning, tonic pupil size, salivary alpha-amylase, and cortisol.

This study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) enhances reversal learning and augments noradrenergic biomarkers (i.e., pupil size, cortisol, and salivary alpha-amylase [sAA]). We also explored the effect of taVNS on respiratory rate and cardiac vagal activity (CVA). Seventy-one participants received stimulation of either the cymba concha (taVNS) or the earlobe (sham) of the left ear. After learning a series of cue-outcome associations, the stimulation was applied before and throughout a reversal phase in which cue-outcome associations were changed for some (reversal), but not for other (distractor) cues. Tonic pupil size, salivary cortisol, sAA, respiratory rate, and CVA were assessed at different time points. Contrary to our hypothesis, taVNS was not associated with an overall improvement in performance on the reversal task. Compared to sham, the taVNS group performed worse for distractor than reversal cues. taVNS did not increase tonic pupil size and sAA. Only post hoc analyses indicated that the cortisol decline was steeper in the sham compared to the taVNS group. Exploratory analyses showed that taVNS decreased respiratory rate but did not affect CVA. The weak and unexpected effects found in this study might relate to the lack of parameters optimization for taVNS and invite to further investigate the effect of taVNS on cortisol and respiratory rate.

Controlled breathing and pain: Respiratory rate and inspiratory loading modulate cardiovascular autonomic responses, but not pain.

Slow, deep breathing (SDB) is a common pain self-management technique. Stimulation of the arterial baroreceptors and vagal modulation are suggested, among others, as potential mechanisms underlying the hypoalgesic effects of SDB. We tested whether adding an inspiratory load to SDB, which results in a stronger baroreceptor stimulation and vagal modulation, enhances its hypoalgesic effects. Healthy volunteers performed SDB (controlled at 0.1 Hz) with and without an inspiratory threshold load. Controlled breathing (CB) at a normal frequency (0.23 Hz) was used as an active control. Each condition lasted 90 s, included an electrical pain stimulation on the hand, and was repeated four times in a randomized order. Pain intensity, self-reported emotional responses (arousal, valence, dominance), and cardiovascular parameters (including vagally-mediated heart rate variability) were measured per trial. A cover story was used to limit the potential effect of outcome expectancy. Pain intensity was slightly lower during SDB with load compared with normal-frequency CB, but the effect was negligible (Cohens d < 0.2), and there was no other difference in pain intensity between the conditions. Heart rate variability was higher during SDB with/without load compared with normal-frequency CB. Using load during SDB was associated with higher heart rate variability, but less favorable emotional responses. These findings do not support the role of baroreceptor stimulation or vagal modulation in the hypoalgesic effects of SDB. Other mechanisms, such as attentional modulation, warrant further investigation.

The test-retest reliability of the respiratory-related evoked potential.

The respiratory-related evoked potential (RREP) is an established technique to study the neural processing of respiratory sensations. We examined the test-retest reliability of the RREP during an unloaded baseline condition (no dyspnea) and an inspiratory resistive loaded breathing condition (dyspnea) over a one-week period. RREPs were evoked by short inspiratory occlusions (150 ms) while EEG was continuously measured. The mean amplitudes of the RREP components Nf, P1, N1, P2, and P3 were studied. For the no dyspnea condition, moderate test-retest reliability for Nf (intraclass correlation coefficient ICC: 0.73) and P1 (ICC: 0.74), good test-retest reliability for N1 (ICC: 0.89) and P3 (ICC: 0.76), and excellent test-retest reliability for P2 (ICC: 0.92) was demonstrated. For the dyspnea condition, moderate test-retest reliability was found for Nf (ICC: 0.69) and P1 (ICC: 0.57) and good test-retest reliability for N1 (ICC: 0.77), P2 (ICC: 0.84), and P3 (ICC: 0.77). This indicates that the RREP components Nf, P1, N1, P2, and P3, elicited by inspiratory occlusions, show adequate reliability in a test-retest study design with or without parallel sustained resistive load-induced dyspnea.

The repeated Montreal Imaging Stress Test (rMIST): Testing habituation, sensitization, and anticipation effects to repeated stress induction.

BACKGROUND: A psychosocial task that can induce comparable levels of stress repeatedly is fundamental to effectively study changes in stress reactivity over time or as a result of an intervention. However, existing tasks have struggled to provide consistent stress responses across repeated trials. AIM: The goal was to assess the efficacy of two different designs of the repeated Montreal Imaging Stress Test (rMIST) in reproducing the same pattern of reactivity over two separate sessions. METHODS: In two different studies, stress was induced using the rMIST on two separate sessions, one week apart. Each study used a different task design. In the first study (53 participants [45 women]; mean age=24.16 [SD=3.29]), the rMIST consisted of a single-longer stress exposure, while the second study (30 participants [27 women]; mean age=21.81 [SD=2.09]) consisted of several shorter stress exposures per session. Self-reported (i.e perceived stress [PS] and negative affect [NA]), physiological (i.e heart rate [HR], root mean square of successive differences [RMSSD]) and hormonal (i.e. salivary cortisol) measures of stress were used. RESULTS: Stress reactivity was comparable across the two repeated stress sessions in both studies. However, baseline HR in the second session increased relative to the first session in the first study, and there was no cortisol response. Additionally, there was a decrease in HR and HRV reactivity within the session on the second study, suggesting a habituation effect not between but within the session itself. CONCLUSION: The rMIST overcomes some of the challenges associated with repeated stress induction. However, an anticipation effect and a lack of cortisol response indicate that further adjustments to the task are necessary. Finally, task design is important for repeated stress reactivity.

The impact of unpredictability of dyspnea offset on dyspnea perception, fear, and respiratory neural gating.

Dyspnea is a debilitating and threatening symptom in various diseases. Affected patients often report the unpredictability of dyspnea episodes being particularly anxiety-provoking and amplifying the perception of dyspnea. Experimental studies testing dyspnea unpredictability together with related neural processes, physiological fear responses, and dyspnea-related personality traits are sparse. Therefore, we investigated the impact of unpredictability of dyspnea offset on dyspnea perception and fear ratings, respiratory neural gating and physiological fear indices, as well as the influence of interindividual differences in fear of suffocation (FoS). Forty healthy participants underwent a task manipulating the offset predictability of resistive load-induced dyspnea including one unloaded safety condition. Respiratory variables, self-reports of dyspnea intensity, dyspnea unpleasantness, and fear were recorded. Moreover, respiratory neural gating was measured in a paired inspiratory occlusion paradigm using electroencephalography, while electrodermal activity, startle eyeblink, and startle probe N100 were assessed as physiological fear indices. Participants reported higher dyspnea unpleasantness and fear when dyspnea offset was unpredictable compared to being predictable. Individuals with high levels of FoS showed the greatest increase in fear and overall higher levels of fear and physiological arousal across all conditions. Respiratory neural gating, startle eyeblink, and startle probe N100 showed general reductions during dyspnea conditions but no difference between unpredictable and predictable dyspnea conditions. Together, the current results suggest that the unpredictable offset of dyspnea amplifies dyspnea perception and fear, especially in individuals with high levels of FoS. These effects were unrelated to respiratory neural gating or physiological fear responses, requiring future studies on underlying mechanisms.

Investigating the stress-related fluctuations of level of personality functioning: A critical review and agenda for future research.

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the International Classification of Diseases (ICD-11) proposed a dimensional approach to the assessment of personality disorders (PDs). Both models dictate that the clinician first determines PD severity before assessing maladaptive traits, invoking the level of personality functioning (LPF) construct. We consider LPF a promising dimensional construct for translational research because of its clinical importance and conceptual overlap with the Research Domain Criteria (RDoC) Social Processes. We aim to identify biomarkers that co-vary with fluctuations in LPF in adulthood, ultimately to predict persistent decrease in LPF, associated with suicidality and morbidity. However, a theoretical framework to investigate stress-related oscillations in LPF is currently missing. In this article, we aim to fill this hiatus with a critical review about stress and LPF. First, we discuss acute stress and LPF. We briefly present the basics of the neurophysiological stress response and review the literature on momentary and daily fluctuations in LPF, both at a subjective and physiological level. Second, we review the effects of chronic stress on brain function and social behaviour and recapitulate the main findings from prospective cohort studies. This review underlies our suggestions for multimethod assessment of stress-related oscillations in LPF and our theoretical framework for future longitudinal studies, in particular studies using the experience sampling method (ESM).

The respiratory occlusion discrimination task: A new paradigm to measure respiratory interoceptive accuracy.

Interoception, or the sense of the internal state of the body, is hypothesized to be essential for a wide range of psychobiological processes and the development and perpetuation of several (mental) health problems. However, the study of interoceptive accuracy, the objectively measured capacity to detect or discriminate conscious bodily signals, has been hampered by the use of tasks with questionable construct validity and is often limited to studying interoception solely in the cardiac domain. We developed a novel task to measure interoceptive accuracy in the respiratory domain, the respiratory occlusion discrimination (ROD) task. In this task, interoceptive accuracy is defined as an individual's ability to detect small differences in lengths of short respiratory occlusions, assessed by means of an adaptive staircase procedure. This article describes a validation study (N = 97) aimed at investigating the internal consistency, test-retest reliability, and discriminant validity of the ROD task. The average just noticeable difference of lengths of respiratory occlusion was 74.22 ms, with large inter-individual variability (SD = 37.1 ms). The results of the validation study indicate acceptable internal consistency (Cronbach's alpha = 0.70), 1-week test-retest reliability (r = 0.53), and discriminant validity, as indicated by a lack of correlation between the ROD task and an auditory discrimination task with identical design (r = 0.18), and a weak correlation with breathing behavior (r = -0.27). The ROD task is a promising novel paradigm to study interoceptive accuracy and its role in various psychobiological processes and disorders.