Testing the monitor and acceptance theory: the role of training-induced changes in monitoring- and acceptance-related capacities after attention-based, socio-emotional, or socio-cognitive mental training in reducing cortisol stress reactivity.

Mindfulness-based interventions have become a popular means to reduce stress. However, the specific mechanisms driving observed stress reduction remain understudied. The Monitor and Acceptance Theory suggests that the cultivation of monitoring and acceptance skills are necessary moderators of practice-induced stress reduction. In the context of the ReSource Project, a large healthy adult sample underwent three 3-month mental training modules targeting either attentional (Presence module), socio-affective (Affect module) or socio-cognitive skills (Perspective module). In the current study, the development of a range of inter-individual differences in mindfulness-, interoception- and compassion-related traits - which mapped to either monitoring or acceptance categories - was tracked. The relationship of these training-induced changes with cortisol stress reactivity after the three distinct 3-month training modules was explored. We found that stress sensitivity was particularly modulated by a differential adaptivity of one cultivated attentional capacity - Attention regulation - which predicted higher cortisol reactivity after mere attention training (Presence) but was associated with lower stress-induced cortisol release after additional socio-affective and socio-cognitive practice (Affect and Perspective). However, this effect did not survive multiple comparisons correction, and analyses were limited by the sample size available. We conclude that our study provides preliminary support of the Monitor and Acceptance Theory, lending weight to the advantage of primary attentional increases in order to fully harness the beneficial effects of socio-affective training, ultimately leading to stress reduction. Although training-induced increases in acceptance were not directly shown to contribute to lowering cortisol stress reactivity, the data suggest an additional benefit of socio-affective and socio-cognitive training that is not directly captured within the current analyses. Our study corroborates the importance of going beyond the training of attention monitoring to foster stress resilience, and highlights that mental training relies on the co-development of several interacting processes to successfully attenuate stress. Further exploring the overarching concept of acceptance in future research may prove beneficial to the theoretical framework of MAT, and in understanding the processes by which stress reduction occurs.

General and anxiety-linked influences of acute serotonin reuptake inhibition on neural responses associated with attended visceral sensation.

Ordinary sensations from inside the body are important causes and consequences of our affective states and behaviour, yet the roles of neurotransmitters in interoceptive processing have been unclear. With a within-subjects design, this experiment tested the impacts of acute increases of endogenous extracellular serotonin on the neural processing of attended internal sensations and the links of these effects to anxiety using a selective serotonin reuptake inhibitor (SSRI) (20 mg CITALOPRAM) and a PLACEBO. Twenty-one healthy volunteers (fourteen female, mean age 23.9) completed the Visceral Interoceptive Attention (VIA) task while undergoing functional magnetic resonance imaging (fMRI) with each treatment. The VIA task required focused attention on the heart, stomach, or visual sensation. The relative neural interoceptive responses to heart sensation [heart minus visual attention] (heart-IR) and stomach sensation [stomach minus visual attention] (stomach-IR) were compared between treatments. Visual attention subtraction controlled for the general effects of CITALOPRAM on sensory processing. CITALOPRAM was associated with lower interoceptive processing in viscerosensory (the stomach-IR of bilateral posterior insular cortex) and integrative/affective (the stomach-IR and heart-IR of bilateral amygdala) components of interoceptive neural pathways. In anterior insular cortex, CITALOPRAM reductions of heart-IR depended on anxiety levels, removing a previously known association between anxiety and the region's response to attended heart sensation observed with PLACEBO. Preliminary post hoc analysis indicated that CITALOPRAM effects on the stomach-IR of the amygdalae corresponded to acute anxiety changes. This direct evidence of general and anxiety-linked serotonergic influence on neural interoceptive processes advances our understanding of interoception, its regulation, and anxiety.

Effects of a Chatbot-Based Intervention on Stress and Health-Related Parameters in a Stressed Sample: Randomized Controlled Trial.

BACKGROUND: Stress levels and the prevalence of mental disorders in the general population have been rising in recent years. Chatbot-based interventions represent novel and promising digital approaches to improve health-related parameters. However, there is a lack of research on chatbot-based interventions in the area of mental health. OBJECTIVE: The aim of this study was to investigate the effects of a 3-week chatbot-based intervention guided by the chatbot ELME, specifically with respect to the ability to reduce stress and improve various health-related parameters in a stressed sample. METHODS: In this multicenter two-armed randomized controlled trial, 118 individuals with medium to high stress levels were randomized to the intervention group (n=59) or the treatment-as-usual control group (n=59). The ELME chatbot guided participants of the intervention group through 3 weeks of training based on the topics stress, mindfulness, and interoception, with practical and psychoeducative elements delivered in two daily interactive intervention sessions via a smartphone (approximately 10-20 minutes each). The primary outcome (perceived stress) and secondary outcomes (mindfulness; interoception or interoceptive sensibility; subjective well-being; and emotion regulation, including the subfacets reappraisal and suppression) were assessed preintervention (T1), post intervention (T2; after 3 weeks), and at follow-up (T3; after 6 weeks). During both conditions, participants also underwent ecological momentary assessments of stress and interoceptive sensibility. RESULTS: There were no significant changes in perceived stress (ß03=-.018, SE=.329; P=.96) and momentary stress. Mindfulness and the subfacet reappraisal significantly increased in the intervention group over time, whereas there was no change in the subfacet suppression. Well-being and momentary interoceptive sensibility increased in both groups over time. CONCLUSIONS: To gain insight into how the intervention can be improved to achieve its full potential for stress reduction, besides a longer intervention duration, specific sample subgroups should be considered. The chatbot-based intervention seems to have the potential to improve mindfulness and emotion regulation in a stressed sample. Future chatbot-based studies and interventions in health care should be designed based on the latest findings on the efficacy of rule-based and artificial intelligence-based chatbots. TRIAL REGISTRATION: German Clinical Trials Register DRKS00027560; https://drks.de/search/en/trial/DRKS00027560. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-doi.org/10.3389/fdgth.2023.1046202.

Changes in interoceptive accuracy related to emotional interference in somatic symptom disorder.

OBJECTIVE: The somatic symptom disorder (SSD) is characterized by one or more distressing or disabling somatic symptoms accompanied by an excessive amount of time, energy and emotion related to the symptoms. These manifestations of SSD have been linked to alterations in perception and appraisal of bodily signals. We hypothesized that SSD patients would exhibit changes in interoceptive accuracy (IA), particularly when emotional processing is involved. METHODS: Twenty-three patients with SSD and 20 healthy controls were recruited. IA was assessed using the heartbeat perception task. The task was performed in the absence of stimuli as well as in the presence of emotional interference, i.e., photographs of faces with an emotional expression. IA were examined for correlation with measures related to their somatic symptoms, including resting-state heart rate variability (HRV). RESULTS: There was no significant difference in the absolute values of IA between patients with SSD and healthy controls, regardless of the condition. However, the degree of difference in IA without emotional interference and with neutral facial interference was greater in patients with SSD than in healthy controls (p = 0.039). The IA of patients with SSD also showed a significant correlation with low-frequency HRV (p = 0.004) and high-frequency HRV (p = 0.007). CONCLUSION: SSD patients showed more significant changes in IA when neutral facial interference was given. These results suggest that bodily awareness is more affected by emotionally ambiguous stimuli in SSD patients than in healthy controls.

Interoceptive training impacts the neural circuit of the anterior insula cortex.

Interoception is the perception of afferent information that arises from anywhere and everywhere within the body. Recently, interoceptive accuracy could be enhanced by cognitive training. Given that the anterior insula cortex (AIC) is a key node of interoception, we hypothesized that resting functional connectivity (RSFC) from AIC was involved in an effect of interoceptive training. To address this issue, we conducted a longitudinal intervention study using interoceptive training and obtained RSFC using fMRI before and after the intervention. A heartbeat perception task evaluated interoceptive accuracy. Twenty-two healthy volunteers (15 females, age 19.9 ± 2.0 years) participated. After the intervention, interoceptive accuracy was enhanced, and anxiety levels and somatic symptoms were reduced. Also, RSFC from AIC to the dorsolateral prefrontal cortex (DLPFC), superior marginal gyrus (SMG), anterior cingulate cortex (ACC), and brain stem, including nucleus tractus solitarius (NTS) were enhanced, and those from AIC to the visual cortex (VC) were decreased according to enhanced interoceptive accuracy. The neural circuit of AIC, ACC, and NTS is involved in the bottom-up process of interoception. The neural circuit of AIC, DLPFC, and SMG is involved in the top-down process of interoception, which was thought to represent the cognitive control of emotion. The findings provided a better understanding of neural underpinnings of the effect of interoceptive training on somatic symptoms and anxiety levels by enhancing both bottom-up and top-down processes of interoception, which has a potential contribution to the structure of psychotherapies based on the neural mechanism of psychosomatics.

Neural mechanisms of respiratory interoception.

Respiratory interoception is one of the internal bodily systems that is comprised of different types of somatic and visceral sensations elicited by different patterns of afferent input and respiratory motor drive mediating multiple respiratory modalities. Respiratory interoception is a complex system, having multiple afferents grouped into afferent clusters and projecting into both discriminative and affective centers that are directly related to the behavioral assessment of breathing. The multi-afferent system provides a spectrum of input that result in the ability to interpret the different types of respiratory interceptive sensations. This can result in a response, commonly reported as breathlessness or dyspnea. Dyspnea can be differentiated into specific modalities. These respiratory sensory modalities lead to a general sensation of an Urge-to-Breathe, driven by a need to compensate for the modulation of ventilation that has occurred due to factors that have affected breathing. The multiafferent system for respiratory interoception can also lead to interpretation of the sensory signals resulting in respiratory related sensory experiences, including the Urge-to-Cough and Urge-to-Swallow. These behaviors are modalities that can be driven through the differentiation and integration of multiple afferent input into the respiratory neural comparator. Respiratory sensations require neural somatic and visceral interoceptive elements that include gated attention and detection leading to respiratory modality discrimination with subsequent cognitive decision and behavioral compensation. Studies of brain areas mediating cortical and subcortical respiratory sensory pathways are summarized and used to develop a model of an integrated respiratory neural network mediating respiratory interoception.

Alcohol effects on interoception shape expectancies and subjective effects: a registered report using the heart rate discrimination task.

AIMS: Alcohol acutely impacts interoceptive processes, which in turn affect the perception of alcohol effects and the development of alcohol expectancies. However, previous research is limited by the tools used to measure cardiac interoception and subjective alcohol effects. This registered report proposes a re-examination of previous findings using a state-of-the-art measure of interoceptive capacity, the heart rate discrimination task, and measurements of subjective alcohol effects across both ascending and descending limbs. METHODS: In a double-blind, placebo-controlled experiment, n = 36 participants were given 0.4 g/kg of ethanol, and a baseline measure of alcohol expectancies was obtained. Changes in interoceptive capacity after beverage administration, along with measures of light-headedness, mood, and biphasic alcohol effects, were assessed over two sessions. HYPOTHESES: As registered in this secondary data analysis, alcohol was expected to acutely impact different indices of interoceptive capacity, and those changes were hypothesized to correlate with subjective alcohol effects and expectancies. Analyses were conducted only following in-principle acceptance. RESULTS: Alcohol-induced changes in interoceptive capacity predicted the development of light-headedness, stimulation, and negative mood. Changes in interoceptive capacity were also correlated with negative alcohol expectancies, as measured 2 weeks prior to the experiment. These effects were unique to the interoceptive condition, as null effects were observed in an exteroceptive control task. DISCUSSION: This report offers a replication of key previous findings that alcohol impacts interoceptive processes to shape the detection of subjective alcohol effects. We propose that, through repeated drinking occasions, bodily responses feed into the experience of intoxication, shaping future expectancies about alcohol effects.

The anterior cingulate cortex is involved in intero-exteroceptive integration for spatial image transformation of the self-body.

Spatial image transformation of the self-body is a fundamental function of visual perspective-taking. Recent research underscores the significance of intero-exteroceptive information integration to construct representations of our embodied self. This raises the intriguing hypothesis that interoceptive processing might be involved in the spatial image transformation of the self-body. To test this hypothesis, the present study used functional magnetic resonance imaging to measure brain activity during an arm laterality judgment (ALJ) task. In this task, participants were tasked with discerning whether the outstretched arm of a human figure, viewed from the front or back, was the right or left hand. The reaction times for the ALJ task proved longer when the stimulus presented orientations of 0°, 90°, and 270° relative to the upright orientation, and when the front view was presented rather than the back view. Reflecting the increased reaction time, increased brain activity was manifested in a cluster centered on the dorsal anterior cingulate cortex (ACC), suggesting that the activation reflects the involvement of an embodied simulation in ALJ. Furthermore, this cluster of brain activity exhibited overlap with regions where the difference in activation between the front and back views positively correlated with the participants' interoceptive sensitivity, as assessed through the heartbeat discrimination task, within the pregenual ACC. These results suggest that the ACC plays an important role in integrating intero-exteroceptive cues to spatially transform the image of our self-body.

Probing corporeal awareness in women through virtual reality induction of embreathment illusion.

We capitalized on the respiratory bodily illusion that we discovered in a previous study and called 'Embreathment' where we showed that breathing modulates corporeal awareness in men. Despite the relevance of the issue, no such studies are available in women. To bridge this gap, we tested whether the synchronization of avatar-participant respiration patterns influenced females' bodily awareness. We collected cardiac and respiratory interoceptive measures, administered body (dis)satisfaction questionnaires, and tracked participants' menstrual cycles via a mobile app. Our approach allowed us to characterize the 'Embreathment' illusion in women, and explore the relationships between menstrual cycle, interoception and body image. We found that breathing was as crucial as visual appearance in eliciting feelings of ownership and held greater significance than any other cue with respect to body agency in both women and men. Moreover, a positive correlation between menstrual cycle days and body image concerns, and a negative correlation between interoceptive sensibility and body dissatisfaction were found, confirming that women's body dissatisfaction arises during the last days of menstrual cycle and is associated with interoception. These findings have potential implications for corporeal awareness alterations in clinical conditions like eating disorders and schizophrenia.

Skeletal interoception in osteoarthritis.

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the organism. Among its various forms, skeletal interoception specifically regulates the metabolic homeostasis of bones. Osteoarthritis (OA) is a complex joint disorder involving cartilage, subchondral bone, and synovium. The subchondral bone undergoes continuous remodeling to adapt to dynamic joint loads. Recent findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone, resulting in subchondral bone sclerosis in OA. The skeletal interoception is also a potential mechanism for chronic synovial inflammation in OA. In this review, we offer a general overview of interoception, specifically skeletal interoception, subchondral bone microenviroment and the aberrant subchondral remedeling. We also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA, as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

Inter-brain entrainment (IBE) during interoception. A multimodal EEG-fNIRS coherence-based hyperscanning approach.

This work examined the impact of interoceptive manipulation and the presence of a shared goal on inter-brain entrainment (IBE) during a motor synchronization task. A multimodal functional Near Infrared Spectroscopy - Electroencephalogram (fNIRS-EEG) system-based hyperscanning approach was applied to 13 dyads performing the motor synchrony task during an interoceptive (focus on the breath) and control condition. Additionally, two version of the motor task-one with and one without a clearly defined common goal-were presented to participants to emphasize the task's collaborative purpose. The multimodal approach was exploited to record the electrophysiological (EEG) cortical oscillation and hemodynamic (oxy-Hb and deoxy-Hb) levels. Results revealed significant correlations between EEG delta, theta, and alpha band and hemodynamic oxy-Hb in the left compared to right hemisphere for the interoceptive confronted with the control condition. This significant EEG/fNIRS IBE correlation was also found for delta and theta band whereas the task was presented with an explicit shared goal confronted with the no-social version. In addition to separate functional connectivity EEG and fNIRS analysis, this study proposed a novel analysis pipeline including statistical tests for examining the coherence between functional connectivity EEG-fNIRS signals within couples. Besides proposing methodological advancements on EEG-fNIRS signals hyperscanning analysis, this research demonstrated that, in dyads undertaking a motor synchronization task, both the interoceptive attention to respiration and an explicit joint intention activate left anterior regions.

Effects of mindfulness-based interventions on symptoms and interoception in trauma-related disorders and exposure to traumatic events: Systematic review and meta-analysis.

Interoception is defined as the sense of the internal state of the body. Dysfunctions in interoception are found in several mental disorders, including trauma-related conditions. Mindfulness-Based Interventions (MBIs) have been shown to influence interoceptive processes. Randomised controlled trials (RCTs) have investigated whether MBIs impact symptoms and interoception in patients with trauma-related disorders. We undertook a systematic review and meta-analysis to synthesize these data. We included RCTs with an MBI arm which enrolled adult patients with trauma related-disorders or exposure to a traumatic experience, and addressed changes in interoception and trauma-related symptoms. A random-effects multivariate meta-analytic model was performed to quantify group differences in score change from baseline to follow-up. Twelve studies were included in the systematic review, and eleven in the meta-analysis. Overall, MBIs showed small to moderate positive effects on both interoception and symptoms. Despite a high heterogeneity in results, sensitivity analyses confirmed the robustness of the findings. We conclude that the efficacy of MBIs on trauma-related symptoms and interoception is supported by randomised evidence. However, further research is needed to understand whether changes in interoception might underpin the effectiveness of MBIs in trauma-related disorders.

Interoception moderates the association between alexithymia and anxiety symptoms / La interocepción modera la asociación entre la alexitimia y los síntomas de ansiedad

In 2019, 301 million people were living with an anxiety disorder. Recently, alexithymia and interoception has been considered to play a key role to understand anxiety symptoms. Both constructs are related to each other and together interfere with emotional regulation; however, its relationship has been much debated. A recent two-stage model proposed interoception as a moderator in the relation between alexithymia and anxiety symptoms. Therefore, the aim of the present research was to study how this model could explain the anxiety symptoms. Two hundred forty-one healthy participants completed the General Health Questionnaire, the Toronto Alexithymia Scale and the Multidimensional Assessment of Interoceptive Awareness. Results verified that interoception moderates the association between alexithymia and anxiety symptoms, showing that, for alexithymia to be positively associated with the magnitude of these symptoms, at least a medium level of interoception is necessary. (AU)

En 2019, se estimaba que 301 millones de personas vivían con un trastorno de ansiedad. Recientemente, se ha considerado que tanto la alexitimia como la interocepción desempeñan un papel clave en la comprensión de los síntomas de ansiedad. Ambos constructos están relacionados entre sí y juntos interfieren en la regulación emocional; sin embargo, su relación ha sido objeto de mucho debate. Recientemente, un nuevo modelo de dos etapas propuso la interocepción como moderador en la relación entre la alexitimia y los síntomas de ansiedad. El objetivo de la presente investigación es estudiar cómo este modelo podría explicar los síntomas de ansiedad. 241 participantes sanos completaron el Cuestionario de Salud General, la Escala de Alexitimia de Toronto y la Evaluación Multidimensional de la Conciencia Interoceptiva. Los resultados verificaron que la interocepción modera la asociación entre la alexitimia y los síntomas de ansiedad, mostrando que, para que la alexitimia esté positivamente relacionada con la magnitud de estos síntomas, es necesario al menos un nivel medio de interocepción. (AU)

mGlu2 and mGlu3 receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats.

RATIONALE: The subjective effects of alcohol are associated with alcohol use disorder (AUD) vulnerability and treatment outcomes. The interoceptive effects of alcohol are part of these subjective effects and can be measured in animal models using drug discrimination procedures. The newly developed mGlu2 and mGlu3 negative allosteric modulators (NAMs) are potential therapeutics for AUD and may alter interoceptive sensitivity to alcohol. OBJECTIVES: To determine the effects of mGlu2 and mGlu3 NAMs on the interoceptive effects of alcohol in rats. METHODS: Long-Evans rats were trained to discriminate the interoceptive stimulus effects of alcohol (2.0 g/kg, i.g.) from water using both operant (males only) and Pavlovian (male and female) drug discrimination techniques. Following acquisition training, an alcohol dose-response (0, 0.5, 1.0, 2.0 g/kg) experiment was conducted to confirm stimulus control over behavior. Next, to test the involvement of mGlu2 and mGlu3, rats were pretreated with the mGlu2-NAM (VU6001966; 0, 3, 6, 12 mg/kg, i.p.) or the mGlu3-NAM (VU6010572; 0, 3, 6, 12 mg/kg, i.p.) before alcohol administration (2.0 g/kg, i.g.). RESULTS: In Pavlovian discrimination, male rats showed greater interoceptive sensitivity to 1.0 and 2.0 g/kg alcohol compared to female rats. Both mGlu2-NAM and mGlu3-NAM attenuated the interoceptive effects of alcohol in male and female rats using Pavlovian and operant discrimination. There may be a potential sex difference in response to the mGlu2-NAM at the highest dose tested. CONCLUSIONS: Male rats may be more sensitive to the interoceptive effects of the 2.0 g/kg alcohol training dose compared to female rats. Both mGlu2-and mGlu3-NAM attenuate the interoceptive effects of alcohol in male and female rats. These drugs may have potential for treatment of AUD in part by blunting the subjective effects of alcohol.

Generalization of a positive-feature interoceptive morphine occasion setter across the rat estrous cycle.

INTRODUCTION: Interoceptive stimuli elicited by drug administration acquire conditioned modulatory properties of the induction of conditioned appetitive behaviours by exteroceptive cues. This effect may be modeled using a drug discrimination task in which the drug stimulus is trained as a positive-feature (FP) occasion setter (OS) that disambiguates the relation between an exteroceptive light conditioned stimulus (CS) and a sucrose unconditioned stimulus (US). We previously reported that females are less sensitive to generalization of a FP morphine OS than males, so we investigated the role of endogenous ovarian hormones in this difference. METHODS: Male and female rats received intermixed injections of 3.2 mg/kg morphine or saline before each daily training session. Training consisted of 8 presentations of the CS, each followed by access to sucrose on morphine, but not saline sessions. Following acquisiton, rats were tested for generalization of the morphine stimulus to 0, 1.0, 3.2, and 5.4 mg/kg morphine. Female rats were monitored for estrous cyclicity using vaginal cytology throughout the study. RESULTS: Both sexes acquired stable drug discrimination. A gradient of generalization was measured across morphine doses and this behaviour did not differ by sex, nor did it differ across the estrous cycle in females. CONCLUSIONS: Morphine generalization is independent of fluctuations in levels of sex and endogenous gonadal hormones in females under these experimental conditions.

Interoceptive signals from the heart and coronary circulation in health and disease.

This review considers interoceptive signalling from the heart and coronary circulation. Vagal and cardiac sympathetic afferent sensory nerve endings are distributed throughout the atria, ventricles (mainly left), and coronary artery. A small proportion of cardiac receptors attached to thick myelinated vagal afferents are tonically active during the cardiac cycle. Dependent upon location, these mechanoreceptors detect fluctuations in atrial volume and coronary arterial perfusion. Atrial volume and coronary arterial signals contribute to beat-to-beat feedback control and physiological homeostasis. Most cardiac receptors are attached to thinly myelinated or nonmyelinated C fibres, many of which are unresponsive to the cardiac cycle. Of these, there are many chemically sensitive cardiac receptors which are activated during myocardial stress by locally released endogenous substances. In contrast, some tonically inactive receptors become activated by irregular ventricular wall mechanics or by distortion of the ischaemic myocardium. Furthermore, some are excited both by chemical mediators of ischaemia and wall abnormalities. Reflex responses arising from cardiac receptors attached to thinly myelinated or nonmyelinated are complex. Impulses that project centrally through vagal afferents elicit sympathoinhibition and hypotension, whereas impulses travelling in cardiac sympathetic afferents and spinal pathways elicit sympathoexcitation and hypertension. Two opposing cardiac reflexes may provide a mechanism for fine-tuning a composite haemodynamic response during myocardial stress. Sympathetic afferents provide the primary pathway for transmission of cardiac nociception to the central nervous system. However, activation of sympathetic afferents may increase susceptibility to life-threatening arrhythmias. Notably, the cardiac sympathetic afferent reflex predominates in pathophysiological states including hypertension and heart failure.

Hepatic interoception in health and disease.

The liver is a large organ with crucial functions in metabolism and immune defense, as well as blood homeostasis and detoxification, and it is clearly in bidirectional communication with the brain and rest of the body via both neural and humoral pathways. A host of neural sensory mechanisms have been proposed, but in contrast to the gut-brain axis, details for both the exact site and molecular signaling steps of their peripheral transduction mechanisms are generally lacking. Similarly, knowledge about function-specific sensory and motor components of both vagal and spinal access pathways to the hepatic parenchyma is missing. Lack of progress largely owes to controversies regarding selectivity of vagal access pathways and extent of hepatocyte innervation. In contrast, there is considerable evidence for glucose sensors in the wall of the hepatic portal vein and their importance for glucose handling by the liver and the brain and the systemic response to hypoglycemia. As liver diseases are on the rise globally, and there are intriguing associations between liver diseases and mental illnesses, it will be important to further dissect and identify both neural and humoral pathways that mediate hepatocyte-specific signals to relevant brain areas. The question of whether and how sensations from the liver contribute to interoceptive self-awareness has not yet been explored.

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.

From early relational experiences to non-suicidal self-injury in anorexia and bulimia nervosa: a structural equation model unraveling the role of impairments in interoception.

PURPOSE: Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) frequently exhibit Non-Suicidal Self-Injury (NSSI), yet their co-occurrence is still unclear. To address this issue, the aim of this study was to elucidate the role of impairments in interoception in explaining the NSSI phenomenon in AN and BN, providing an explanatory model that considers distal (insecure attachment/IA and traumatic childhood experiences/TCEs) and proximal (dissociation and emotional dysregulation) risk factors for NSSI. METHOD: 130 patients with AN and BN were enrolled and administered self-report questionnaires to assess the intensity of NSSI behaviors, interoceptive deficits, IA, TCEs, emotional dysregulation and dissociative symptoms. RESULTS: Results from structural equation modeling revealed that impairments in interoception acted as crucial mediators between early negative relational experiences and factors that contribute to NSSI in AN and BN, particularly emotional dysregulation and dissociation. Precisely, both aspects of IA (anxiety and avoidance) and various forms of TCEs significantly exacerbated interoceptive deficits, which in turn are associated to the emergence of NSSI behaviors through the increase in levels of dissociation and emotional dysregulation. CONCLUSIONS: The proposed model provided a novel explanation of the occurrence of NSSIs in patients with AN and BN by accounting for the significance of interoception. LEVEL OF EVIDENCE: Level V-Cross-sectional observational study.

Heart rate perception and expectation impact laboratory-induced perceived stress.

Previous studies have shown that the human capacity to gauge one's own physiological state is notoriously flawed. The cause for the mismatch between perceived and physiological stress has not yet been properly identified. In this study, we assumed that cardioceptive accuracy (CAc) is positively associated with cardiovascular reactivity, and CAc and expectation about stress might account for the discrepancy between perceived and physiological stress. In a crossover experiment, we assessed cardioceptive accuracy in two ways (mental heartbeat tracking task and perception of heart rate), and induced physiological (handgrip exercise) and mental (N-back task) stress in 64 university students (51 % male, mean age 22.2). We assessed cardiac and electrodermal activity, and expected and perceived stress. We found that indicators of cardioceptive accuracy were not associated with cardiovascular reactivity. However, heart rate perception moderated the association between the change in heart rate and perceived stress in the physical but not in the mental task. Whereas heartbeat tracking accuracy was not associated with perceived stress. Moreover, perceived stress was predicted by the expected stress but not by the change in heart rate and electrodermal activity in the mental stress task. In conclusion, heart rate perception and expectation of stress may shape perceived stress more than actual physiological changes in moderate acute stress.