Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

PURPOSE: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. METHODS: Nineteen patients (65 ± 11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking, and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free ("resting") fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks. RESULTS: The study was feasible (74-89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0-100 scale: - 7.9 ± 5.7, effect size [ES] = - 0.9 at mid-intervention; - 4.8 ± 7.3, ES = - 0.5 at post-intervention), CIPN signs (ES = - 1.0 and - 0.1), and physical function (ES = 0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R2 = 40-60%) and higher functional connectivity within the salience network (R2 = 20-40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R2 = 12%). CONCLUSION: Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. TRIAL REGISTRATION: Registered Jan 2017 on ClinicalTrials.gov as NCT03021174.

The acute effect of mindfulness-based regulation on neural indices of cue-induced craving in smokers.

Mindfulness has garnered attention for its potential in alleviating cigarette cravings; however, the neural mechanisms underlying its efficacy remain inadequately understood. This study (N=46, all men) aims to examine the impact of a mindfulness strategy on regulating cue-induced craving and associated brain activity. Twenty-three smokers, consuming over 10 cigarettes daily for at least 2 years， were compared to twenty-three non-smokers. During a regulation of craving task, participants were asked to practice mindfulness during smoking cue-exposure or passively view smoking cues while fMRI scans were completed. A 2 (condition: mindfulness-cigarette and look-cigarette) × 2 (phase: early, late of whole smoking cue-exposure period) repeated measures ANOVA showed a significant interaction of the craving scores between condition and phase, indicating that the mindfulness strategy dampened late-phase craving. Additionally, within the smoker group, the fMRI analyses revealed a significant main effect of mindfulness condition and its interaction with time in several brain networks involving reward, emotion, and interoception. Specifically, the bilateral insula, ventral striatum, and amygdala showed lower activation in the mindfulness condition, whereas the activation of right orbitofrontal cortex mirrored the strategy-time interaction effect of the craving change. This study illuminates the dynamic interplay between mindfulness, smoking cue-induced craving, and neural activity, offering insights into how mindfulness may effectively regulate cigarette cravings.

The role of interoceptive awareness in shaping the relationship between desire thinking and cigarette consumption.

Interoception, the ability to sense and interpret bodily sensations, has recently emerged as a crucial factor in substance use disorders, including smoking. However, the role of interoceptive awareness in tobacco use remains poorly understood. The relationship between interoceptive ability and addictive behavior is complex, and attempting to conceptualize it as a linear association is unlikely to fully capture the complexity of the mechanisms underlying cravings and urges. We hypothesized that the role played by interoceptive awareness in tobacco use is deeply linked to desire thinking, that is, the conscious and voluntary cognitive process orienting to prefigure images, information, and memories about positive target-related experiences. Desire thinking is typically observed in addiction, where it may contribute to interpreting specific bodily sensations, such as the perceived need for a cigarette. From this perspective, the physiological impact and inclination toward desire thinking contribute to a higher daily cigarette consumption, particularly in situations of low interoceptive awareness. To test this hypothesis, we assessed the physiological activation, the tendency toward desire thinking about smoking, cigarette consumption, and the interoceptive abilities of smoking volunteers. Through a moderation analysis, we showed that desire thinking about smoking predicts a higher number of cigarettes per day in individuals with lower interoceptive awareness (p < .05). These findings suggest that the relationship between desire thinking and interoceptive awareness is a fundamental component of tobacco use, highlighting the importance of taking into account the bodily feedback deriving from the cognitive representation of smoking in addiction research and therapy.

Exploring the role of neuronal-enriched extracellular vesicle miR-93 and interoception in major depressive disorder.

Major depressive disorder (MDD) is associated with interoceptive processing dysfunctions, but the molecular mechanisms underlying this dysfunction are poorly understood. This study combined brain neuronal-enriched extracellular vesicle (NEEV) technology and serum markers of inflammation and metabolism with Functional Magnetic Resonance Imaging (fMRI) to identify the contribution of gene regulatory pathways, in particular micro-RNA (miR) 93, to interoceptive dysfunction in MDD. Individuals with MDD (n = 41) and healthy comparisons (HC; n = 35) provided blood samples and completed an interoceptive attention task during fMRI. EVs were separated from plasma using a precipitation method. NEEVs were enriched by magnetic streptavidin bead immunocapture utilizing a neural adhesion marker (L1CAM/CD171) biotinylated antibody. The origin of NEEVs was validated with two other neuronal markers - neuronal cell adhesion molecule (NCAM) and ATPase Na+/K+ transporting subunit alpha 3 (ATP1A3). NEEV specificities were confirmed by flow cytometry, western blot, particle size analyzer, and transmission electron microscopy. NEEV small RNAs were purified and sequenced. Results showed that: (1) MDD exhibited lower NEEV miR-93 expression than HC; (2) within MDD but not HC, those individuals with the lowest NEEV miR-93 expression had the highest serum concentrations of interleukin (IL)-1 receptor antagonist, IL-6, tumor necrosis factor, and leptin; and (3) within HC but not MDD, those participants with the highest miR-93 expression showed the strongest bilateral dorsal mid-insula activation during interoceptive versus exteroceptive attention. Since miR-93 is regulated by stress and affects epigenetic modulation by chromatin re-organization, these results suggest that healthy individuals but not MDD participants show an adaptive epigenetic regulation of insular function during interoceptive processing. Future investigations will need to delineate how specific internal and external environmental conditions contribute to miR-93 expression in MDD and what molecular mechanisms alter brain responsivity to body-relevant signals.

Heightened interoception in adults with fibromyalgia.

Previous research suggests that the processing of internal body sensations (interoception) affects how we experience pain. Some evidence suggests that people with fibromyalgia syndrome (FMS) - a condition characterised by chronic pain and fatigue - may have altered interoceptive processing. However, extant findings are inconclusive, and some tasks previously used to measure interoception are of questionable validity. Here, we used an alternative measure - the Phase Adjustment Task (PAT) - to examine cardiac interoceptive accuracy in adults with FMS. We examined: (i) the tolerability of the PAT in an FMS sample (N = 154); (ii) if there are differences in facets of interoception (PAT performance, PAT-related confidence, and scores on the Private Body Consciousness Scale) between an FMS sample and an age- and gender-matched pain-free sample (N = 94); and (iii) if subgroups of participants with FMS are identifiable according to interoceptive accuracy levels. We found the PAT was tolerable in the FMS sample, with additional task breaks and a recommended hand posture. The FMS sample were more likely to be classified as 'interoceptive' on the PAT, and had significantly higher self-reported interoception compared to the pain-free sample. Within the FMS sample, we identified a subgroup who demonstrated very strong evidence of being interoceptive, and concurrently had lower fibromyalgia symptom impact (although the effect size was small). Conversely, self-reported interoception was positively correlated with FMS symptom severity and impact. Overall, interoception may be an important factor to consider in understanding and managing FMS symptoms. We recommend future longitudinal work to better understand associations between fluctuating FMS symptoms and interoception.

Virtual embodiment in fibromyalgia.

Chronic pain alters the experience of owning a body and leads to disturbances in bodily perception. We tested whether women with fibromyalgia (FM) are receptive to bodily illusions of owning a visible and progressively invisible body in immersive virtual reality (VR), and what modulates this experience. Twenty patients participated in two experimental sessions; each session included two conditions in a counterbalanced order. We found that patients with FM could indeed experience virtual embodiment. Sentiment analysis revealed significantly more positive reactions to the progressively invisible body, yet twice as many patients declared they preferred the illusion of a visible virtual body. A linear mixed model revealed that the strength of embodiment was positively associated with body perception disturbances and negatively associated with FM symptoms intensity. No effect of pain during the VR experience nor interoception awareness on embodiment was found. The results indicated that patients with FM are receptive to virtual bodily illusions and that the impact of the embodiment depends on affective reactions, the level of cognitive body distortions, and the intensity of symptoms. Importantly, there is a large variation among patients which should be considered in future VR-based interventions.

Psychological interventions for interoception in mental health disorders: A systematic review of randomized-controlled trials.

Disturbed interoception (i.e., the sensing, awareness, and regulation of internal body signals) has been found across several mental disorders, leading to the development of interoception-based interventions (IBIs). Searching PubMed and PsycINFO, we conducted the first systematic review of randomized-controlled trials (RCTs) investigating the efficacy of behavioral IBIs at improving interoception and target symptoms of mental disorders in comparison to a non-interoception-based control condition [CRD42021297993]. Thirty-one RCTs fulfilled inclusion criteria. Across all studies, a pattern emerged with 20 (64.5%) RCTs demonstrating IBIs to be more efficacious at improving interoception compared to control conditions. The most promising results were found for post-traumatic stress disorder, irritable bowel syndrome, fibromyalgia and substance use disorders. Regarding symptom improvement, the evidence was inconclusive. The IBIs were heterogenous in their approach to improving interoception. The quality of RCTs was moderate to good. In conclusion, IBIs are potentially efficacious at improving interoception for some mental disorders. In terms of symptom reduction, the evidence is less promising. Future research on the efficacy of IBIs is needed.

Modelos neuroeconómicos explicativos de la relación entre aversión al riesgo, impulsividad y cardiocepción en estudiantes universitarios: revisión de alcance / Explanatory neuroeconomics models of the relation between risk-aversion, impulsivity and cardioception in university students: a scoping review

Introducción: los modelos neuroeconómicos explican la toma de decisiones a partir de procesos neurofisiológicos, cognitivos y emocionales. La toma de decisiones se estudia a partir de otros subprocesos como la aversión al riesgo. La relación entre aversión al riesgo, impulsividad y/o interocepción es importante para determinar el rol de la conducta y cognición humanas en el mantenimiento de problemas de salud. Esto se ha estudiado en población universitaria, en la que se presentan factores de riesgo para la salud. Objetivo: sintetizar los modelos neuroeconómicos descritos en la literatura para establecer la relación entre la aversión al riesgo, impulsividad y/o la cardiocepción en estudiantes universitarios. Metodología: revisión tipo alcance realizada del 01 de junio al 30 de septiembre de 2021 en los recursos; PubMed, PsyInfo, Google Scholar, Sciencedirect, Scopus, Open dissertations y OpenGrey. Como criterio de inclusión se estableció que se tratara de investigaciones experimentales y observacionales en inglés o español en estudiantes universitarios que evaluaran la relación entre toma de decisiones, impulsividad y/o interocepción. No se filtró por fecha ni por tipo de acceso. Resultados: se rastrearon 1035 documentos, 14 cumplieron con los criterios de inclusión. Se identificaron cuatro modelos: neuroeconómico conductual, paradigma de descuento temporal, teoría biopsicológica de Gray y diferencias individuales. Se hallaron correlaciones positivas y negativas entre impulsividad, aversión al riesgo e interocepción. Conclusiones: según los estudios existe una relación entre impulsividad y aversión al riesgo, que dependiendo del modelo implementado será positiva o negativa. Las asociaciones con interocepción son poco concluyentes y requieren mayor investigación.

Introduction: neuroeconomic models explain decision making based on neurophysiological, cognitive, and emotional processes. Decision making is studied from other threads such as risk aversion. The relationship between risk aversion, impulsivity and/or interoception is important to determine the role of human behavior and cognition in the maintenance of health problems. This has been studied in the university population, in which health risk factors are present. Objective: to synthesize the neuroeconomic models described in the literature to establish the relationship between risk aversion, impulsivity and/or cardioception in university students. Methodology: scoping review carried out from June 1 to September 30, 2021, in the resources; PubMed, PsyInfo, Google Scholar, Sciencedirect, Scopus, Open dissertations, and OpenGrey. As inclusion criteria, it was established that they were experimental and observational investigations in English or Spanish in university students that evaluated the relationship between decision-making, impulsivity and/or interoception. It was not filtered by date or by type of access. Results: 1035 documents were searched, 14 met the inclusion criteria. Four models were identified: behavioral neuroeconomic, delaying discount paradigm, Gray's biopsychological theory, and individual differences. Positive and negative correlations were found between impulsivity, risk aversion, and interoception. Conclusions: according to the studies, there is a relationship between impulsivity and risk aversion, which depending on the model implemented will be positive or negative. Associations with interoception are inconclusive and require further investigation.

Self-reported interoception, worries and protective behaviors during the COVID-19 pandemic: a longitudinal study

Background Protective behaviors were essential for minimizing the spread of the virus during the coronavirus disease 2019 (COVID-19) pandemic. It is often assumed that awareness of bodily sensations (interoception) can improve decision-making and facilitate adaptive behavior. Objective This paper investigates cross-sectional and longitudinal relationships between different aspects of self-reported interoception, trait anxiety, COVID-related worry, and health protective behaviors. Methods The study was conducted on a community sample of 265 adults. The two data collection phases took place online, before (baseline) and during the second wave of the COVID-19 pandemic in Hungary. Results Contrary to our expectations, neither cross-sectional nor longitudinal associations were found between protective behaviors and indicators of self-reported interoception. However, worry at baseline predicted protective behaviors during the second wave, even after controlling for socio-economical characteristics and protective behaviors at baseline. Conclusion Our results highlight the adaptivity of health-related worry when behavioral steps to avoid threats are known and available. Also, higher level of perceived interoception did not appear to be health protective under these circumstances. (AU)

Mediterranean diet, interoception and mental health: Is it time to look beyond the 'Gut-brain axis'?

OBJECTIVE: A Mediterranean style diet (i.e., high in fruit, vegetables, fish, pulses, and wholegrains) is said to benefit psychological health. Many low-level interoceptive processes, such as those involved in the 'gut-brain' axis, are suggested to play a mechanistic role in in this relationship. However, interoceptive sensations in other domains, and at higher hierarchical levels of abstraction, have hitherto been overlooked. One domain often studied in relation to psychological health is cardioception. Therefore, we examined whether the Mediterranean diet was associated with first-order perceptual and second-order metacognitive cardioception. METHODS: Participants completed the Heartbeat Detection Task, the Heartbeat Counting Task, and the EPIC-Norfolk Food Frequency Questionnaire from which diet was quantified. RESULTS: Adherence to a Mediterranean style diet was associated with higher cardioceptive accuracy (i.e., perceptual performance) across both tasks. In addition, those consuming a Mediterranean diet had a better ability to detect errors in first order perceptual performance, and a lower prediction error (the magnitude of the difference between accuracy and confidence). DISCUSSION: These findings indicated that deepening our understanding of how interoceptive processes beyond the 'gut-brain' axis are shaped by diet could deepen our understanding of the link between diet and mental health and wellbeing.

Interoception in Practice: The Gut-Brain Connection.

Tony is a five and a half-year-old boy who has been a patient in your primary care practice since he was adopted at birth. He has been treated by a child and adolescent psychiatrist for behavioral concerns starting at age 3 years and has been diagnosed with autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD) combined type, anxiety disorder, and insomnia. He presents today with complaints of repeated emesis and refusal to eat or drink over the past 2 weeks and is now dehydrated. Tony was born at 30 weeks' gestational age by vaginal delivery with a birth weight of 4lbs 15oz and was described as minimally responsive at birth. There was known prenatal exposure to tobacco and methamphetamine and inadequate prenatal care. The maternal history is notable for a reported diagnosis of bipolar affective disorder, prostitution, and being unhoused at the time of delivery. Tony received antibiotics after delivery for presumed newborn infections. As an infant, he had kidney reflux, low serum ferritin, insomnia, and failure to thrive. Regarding developmental milestones, Tony was sitting up at 7 months, walking at 14 months, talking at 18 months, and speaking in full sentences by 24 months. When he presented to the psychiatric service at age 3 years, behavioral problems included irritability with destructive rages, excessive fears, separation anxiety, hyperactivity, and impulsivity with a lack of awareness of danger to the extent that he required a safety harness when in public and security locks in the home because of repeated elopements. Tony also had at the time of his initial presentation significant defiance, extreme tantrums, violent aggressive outbursts, cognitive rigidity, repetitive behaviors, resistance to change, frequent nondirected vocalizations, and self-injurious behaviors including slapping himself on the head and biting of his hands and feet. Review of systems includes complaints of frequent abdominal and neck pain, persistent insomnia, night terrors, restrictive eating habits with poor weight gain, and reduced sensitivity to pain. Treatment history included gabapentin and subsequently divalproex for seizure-like episodes (despite negative EEG) described as frequent staring spells with repetitive biting of his lips. Psychotropic medications were risperidone for irritability associated with autism and clonidine extended release for ADHD. He also took melatonin for sleep. During his well-child check at the age of 5 years, Tony is making good progress from a developmental standpoint, has age-appropriate expressive and receptive language skills, is fluent in both English and Spanish, is able to recite the alphabet, counts to 20, has learned to swim, and is demonstrating interest in planets and astrology. He is reported to have a secure attachment to his adoptive parents and is described as emotionally sensitive, caring, kind, considerate, and empathetic. He has good eye contact and can read facial expressions. He is affectionate and protective of his infant sibling, his biological sister, who is also adopted by his parents and now living in the home. Tony made an excellent adjustment to the start of kindergarten and up until this point was responding positively to his psychotropic medication regimen. But then at age five and a half, Tony experienced sudden and unexplained behavioral worsening, which was followed by the onset of recurrent vomiting and refusal to eat or drink. Comprehensive medical workup including upper endoscopy and biopsy resulted in a diagnosis of eosinophilic esophagitis (EoE). What would be your next step?

Boredom proneness, interoception, and emotional eating.

Emotional eating is associated with weight gain and difficulty losing weight during weight loss interventions. Theoretical and empirical work suggest boredom may be an important predictor of problematic eating behaviors. Yet, little work has examined the role of boredom in emotional eating. Further, individual differences in the ability to recognize internal cues (i.e., interoception) may alter the impact of boredom on emotional eating. This study hypothesized that boredom proneness would predict unique variance in emotional eating after accounting for negative and positive affect, and that the association between boredom proneness and emotional eating would be stronger among those with poorer interoceptive ability compared to those with better interoceptive ability. Hypotheses were tested in two large samples using multiple linear regression. Participants aged 18-65 were recruited from MTurk (n = 365; 59.2% female) and an undergraduate research pool (n = 461; 52.9% female). Participants completed self-report measures: Boredom Proneness Scale; Dutch Eating Behavior Questionnaire- Emotional Eating; Multidimensional Assessment of Interoceptive Awareness-2; Intuitive Eating Scale-2- Reliance on Hunger and Satiety Cues; and Positive and Negative Affect Schedule. Boredom proneness was a significant predictor of emotional eating in both samples, even accounting for the broad dimensions of negative and positive affect (ps < .001). Interoception did not moderate the association between boredom proneness and emotional eating in either sample (ps > .05), but was an independent predictor of emotional eating (ps < .001). Boredom proneness and interoceptive ability may warrant attention as targets in the prevention and treatment of emotional eating. Future work should continue exploring different emotion categories and different facets of interoception in emotional eating, as well as examine novel mechanisms that could inform intervention efforts.

Divalent metal cations stimulate skeleton interoception for new bone formation in mouse injury models.

Bone formation induced by divalent metal cations has been widely reported; however, the underlying mechanism is unclear. Here we report that these cations stimulate skeleton interoception by promoting prostaglandin E2 secretion from macrophages. This immune response is accompanied by the sprouting and arborization of calcitonin gene-related polypeptide-α+ nerve fibers, which sense the inflammatory cue with PGE2 receptor 4 and convey the interoceptive signals to the central nervous system. Activating skeleton interoception downregulates sympathetic tone for new bone formation. Moreover, either macrophage depletion or knockout of cyclooxygenase-2 in the macrophage abolishes divalent cation-induced skeleton interoception. Furthermore, sensory denervation or knockout of EP4 in the sensory nerves eliminates the osteogenic effects of divalent cations. Thus, our study reveals that divalent cations promote bone formation through the skeleton interoceptive circuit, a finding which could prompt the development of novel biomaterials to elicit the therapeutic power of these divalent cations.

At the heart of the interoception network: Influence of the parasubthalamic nucleus on autonomic functions and motivated behaviors.

The parasubthalamic nucleus (PSTN), a small nucleus located on the lateral edge of the posterior hypothalamus, has emerged in recent years as a highly interconnected node within the network of brain regions sensing and regulating autonomic function and homeostatic needs. Furthermore, the strong integration of the PSTN with extended amygdala circuits makes it ideally positioned to serve as an interface between interoception and emotions. While PSTN neurons are mostly glutamatergic, some of them also express neuropeptides that have been associated with stress-related affective and motivational dysfunction, including substance P, corticotropin-releasing factor, and pituitary adenylate-cyclase activating polypeptide. PSTN neurons respond to food ingestion and anorectic signals, as well as to arousing and distressing stimuli. Functional manipulation of defined pathways demonstrated that the PSTN serves as a central hub in multiple physiologically relevant networks and is notably implicated in appetite suppression, conditioned taste aversion, place avoidance, impulsive action, and fear-induced thermoregulation. We also discuss the putative role of the PSTN in interoceptive dysfunction and negative urgency. This review aims to synthesize the burgeoning preclinical literature dedicated to the PSTN and to stimulate interest in further investigating its influence on physiology and behavior.

The Interoceptive Sensitivity and Attention Questionnaire: Evaluating Aspects of Self-Reported Interoception in Patients With Persistent Somatic Symptoms, Stress-Related Syndromes, and Healthy Controls.

OBJECTIVE: This study aimed to validate the Interoceptive Sensitivity and Attention Questionnaire (ISAQ), a 17-item self-report measure assessing sensitivity and attention to interoceptive signals. METHODS: In study 1, exploratory and confirmatory factor analysis was performed in a student convenience sample (n = 1868). In study 2, ISAQ data of a healthy sample (n = 144) and various patient groups experiencing stress-related syndromes (overstrain, n = 63; burnout, n = 37; panic disorder [PD]. n = 60) and/or persistent somatic symptoms in daily life (irritable bowel syndrome, n = 38; fibromyalgia and/or chronic fatigue syndrome, n = 151; medically unexplained dyspnea [MUD], n = 29) were compared. RESULTS: Three subscales were revealed: (F1) sensitivity to neutral bodily sensations, (F2) attention to unpleasant bodily sensations, and (F3) difficulty disengaging from unpleasant bodily sensations. Overall, patients with fibromyalgia and/or chronic fatigue syndrome and patients with MUD scored significantly higher on F1 (p = .009 and p = .027, respectively) and F2 (p = .002 and p < .001, respectively) than healthy controls. Patients with PD had higher scores on subscales F2 (p < .001) and F3 (p < .001) compared with healthy controls, as well as higher scores on F2 compared with all other patient groups (pPD versus MUD = .008; all other p values < .001). CONCLUSIONS: Interoceptive sensibility-the self-reported aspect of interoception-is not a homogeneous or unitary construct. The subscales of the ISAQ differentiate healthy controls from patients with persistent somatic and/or stress-related complaints in daily life and distinguish different patient groups. The ISAQ can be used as a concise, reliable, and clinically relevant research tool to further disentangle adaptive and maladaptive aspects of interoceptive ability.

Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception.

The mechanisms that link visceral mechanosensation to the perception of internal organ status (i.e., interoception) remain elusive. In response to bladder filling, the urothelium releases ATP, which is hypothesized to stimulate voiding function by communicating the degree of bladder fullness to subjacent tissues, including afferent nerve fibers. To determine if PIEZO channels function as mechanosensors in these events, we generated conditional urothelial Piezo1-, Piezo2-, and dual Piezo1/2-knockout (KO) mice. While functional PIEZO1 channels were expressed in all urothelial cell layers, Piezo1-KO mice had a limited phenotype. Piezo2 expression was limited to a small subset of superficial umbrella cells, yet male Piezo2-KO mice exhibited incontinence (i.e., leakage) when their voiding behavior was monitored during their active dark phase. Dual Piezo1/2-KO mice had the most affected phenotype, characterized by decreased urothelial responses to mechanical stimulation, diminished ATP release, bladder hypoactivity in anesthetized Piezo1/2-KO females but not males, and urinary incontinence in both male and female Piezo1/2-KO mice during their dark phase but not inactive light one. Our studies reveal that the urothelium functions in a sex- and circadian rhythm-dependent manner to link urothelial PIEZO1/2 channel-driven mechanotransduction to normal voiding function and behavior, and in the absence of these signals, bladder dysfunction ensues.

Interoceptive Sensibility, Alexithymia, and Emotion Regulation in Individuals Suffering from Fibromyalgia.

INTRODUCTION: People suffering from fibromyalgia syndrome report various difficulties in emotional processing, possibly resulting from changes in bodily perception (interoception). In our study, we investigated the relationships between interoceptive sensibility (IS) and two disease-relevant emotional components (alexithymia and emotion regulation) in fibromyalgia sufferers compared to healthy individuals. METHODS: Fifty-five fibromyalgia sufferers and 55 healthy individuals, matched with regard to age and gender, participated in our cross-sectional study. All participants completed the following self-report measures: the Multidimensional Assessment of Interoceptive Awareness, the Toronto Alexithymia Scale, and the Emotion Regulation Skills Questionnaire. Depression and anxiety scores served as confounding variables. RESULTS: Fibromyalgia sufferers reported a stronger tendency to note as well as to avoid (unpleasant) body sensations. IS and psychopathology each explained about thirty percent of the variance in emotion regulation in fibromyalgia sufferers. Alexithymia was related to IS and emotion regulation in controls but not in fibromyalgia sufferers. CONCLUSION: Disturbances in interoception could be seen as the starting point of emotional difficulties in people with fibromyalgia. Following the fear-avoidance-model, experiential avoidance may restrict patients' ability to adaptively regulate emotional states, possibly initiating a vicious cycle of psychological distress and pain.

Effects of insular resection on interactions between cardiac interoception and emotion recognition.

The insular cortex is considered an important region for feeling emotions through interoception. Most studies that report the role of the insula in integrating interoception and emotion have used neuroimaging techniques such as functional magnetic resonance imaging (fMRI); however, there are limited neuropsychological studies. The effects of insular lesions on emotion and interoception have not been suitably investigated. In this study, we examined the role of the insular cortex in cardiac interoception and recognizing emotions from facial expressions by comparing them pre- and post-operatively in patients with glial tumors or brain metastases associated with the insular lobe. Although no significant difference in interoceptive accuracy was observed between the two phases, there were significant associations between the changes in interoceptive accuracy and sensitivity to expressions of anger and happiness. An increased error rate in the heartbeat counting task in the post-operation phase was associated with a decreased accuracy in recognizing anger and happiness. Since most patients had left insula lesions, generalizability of the findings to patients with right lesions is a future subject. To the best of our knowledge, this is the first study to examine the change in interoception and emotion after insular resection in humans. The study results indicate that removal of the insula affects the recognition of emotions such as anger and happiness through interoceptive processing.

Improving interoception and self-disgust in the treatment of patients with anorexia nervosa.

Anorexia nervosa (AN) is a mental disorder in which sufficient evidence points towards the presence of a high level of disturbed interoception and self-disgust. High arousal mood induction is a therapeutic technique that helps improve a patient's interoceptive capacities. With some adjustments to this technique such as adding a challenging behavior that induces a "flow" state or a mindfulness component such as in mindful awareness in body-oriented therapy (MABT), it is expected that patients with AN may benefit from an integrative treatment strategy that helps them improve their symptoms of high self-disgust and low interoception.

Cognitive Fatigue Effects on Physical Performance: The Role of Interoception.

The consensus of opinion, with regard to the effect of cognitive fatigue on subsequent physical performance, is that there is a small, negative effect, but there is no consensus regarding the mechanisms involved. When glucose levels are normal, undertaking cognitive tasks does not induce energy or neurotransmitter depletion. The adenosine hypothesis is questioned as cognitively induced increases in adenosine release are phasic and transient, while persistent effects of adenosine are tonic. Thus, the most likely explanation for a negative effect of cognitive fatigue would appear to be changes in perceptions of effort, for which there is some evidence from subjective participant feedback, while interoceptive theory would suggest a role for motivation levels. Cognitive fatigue and physical fatigue are dependent on interoceptive mechanisms, in particular the interactions between top-down predictions of effort from the dorsolateral prefrontal cortex (PFC) to the insula cortex, anterior cingulate cortex, ventromedial and ventrolateral PFC, and bottom-up feedback from the lamina I spinothalamic pathway, and the vagal and glossopharyngeal medullothalamic pathway. The dopaminergic mesocorticolimbic and the locus coeruleus-noradrenaline pathways are also vital. It would appear that cognitive fatigue leads to different predictions of the expected sensory consequences of undertaking the exercise than in the control condition and there is some evidence that motivation can overcome this. Much more research, in which motivation levels are manipulated, is necessary as the effects are small and the reasons for cognitive fatigue causing changes in predictions of sensory consequences are not clear.