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.

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.

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.

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.

The neuroscience of sadness: A multidisciplinary synthesis and collaborative review.

Sadness is typically characterized by raised inner eyebrows, lowered corners of the mouth, reduced walking speed, and slumped posture. Ancient subcortical circuitry provides a neuroanatomical foundation, extending from dorsal periaqueductal grey to subgenual anterior cingulate, the latter of which is now a treatment target in disorders of sadness. Electrophysiological studies further emphasize a role for reduced left relative to right frontal asymmetry in sadness, underpinning interest in the transcranial stimulation of left dorsolateral prefrontal cortex as an antidepressant target. Neuroimaging studies - including meta-analyses - indicate that sadness is associated with reduced cortical activation, which may contribute to reduced parasympathetic inhibitory control over medullary cardioacceleratory circuits. Reduced cardiac control may - in part - contribute to epidemiological reports of reduced life expectancy in affective disorders, effects equivalent to heavy smoking. We suggest that the field may be moving toward a theoretical consensus, in which different models relating to basic emotion theory and psychological constructionism may be considered as complementary, working at different levels of the phylogenetic hierarchy.

Altered interoceptive processing in smokers: Evidence from the heartbeat tracking task.

Neuroimaging evidence suggests that interoceptive processing might be altered in nicotine addiction, however this has not yet been confirmed with behavioural measures. Therefore, we investigated the perception of internal bodily states in smokers (n = 49) and people who had never smoked (n = 51), by measuring interoceptive accuracy (IAcc) and interoceptive sensibility (IS). IAcc was measured with a heartbeat tracking task and a heartbeat discrimination task. Performance on the heartbeat tracking task may be influenced by one's ability to estimate an elapsed time interval so this was controlled by also administering a time-estimation (TE) task. IS was measured using two sub-scales from the Multidimensional Assessment of Interoceptive Awareness (MAIA). All smokers completed the Revised Fagerström Test for Nicotine Dependence (FTND-R) to measure addiction severity. Non-smokers performed significantly better than smokers on the heartbeat tracking task. There were no significant group differences observed for the remaining variables. Furthermore, none of the variables predicted addiction severity. This is the first demonstration of behavioural differences in interoception between smokers and non-smokers.

Difficulties in emotion regulation and deficits in interoceptive awareness in moderate and severe obesity.

PURPOSE: Difficulties in emotion regulation and deficits in interoceptive awareness may be responsible for overeating and weight gain in obesity by increasing the risks of problematic eating behaviors. This study aimed to: (1) examine emotion regulation difficulties and interoceptive deficits in obesity; (2) compare the emotion regulation and interoceptive abilities of moderately and severely obese patients. METHODS: Participants were recruited through the university, diabetology centers and bariatric surgery departments. A total of 165 participants were categorized in three groups, matched by age and gender, according to their Body Mass Index (BMI). The severely obese (SO), moderately obese (MO) and normal weight (NW) groups were constituted of 55 participants each. Self-report questionnaires were used to assess emotion regulation difficulties (CERQ-DERS) and interoceptive awareness (MAIA-FFMQ). RESULTS: Overall, obese participants reported more emotion regulation difficulties and less interoceptive awareness than NW participants did. They also reported a lack of planning strategies and emotional awareness, as well as less ability to observe, notice and trust body sensations. No differences in emotion regulation and interoceptive abilities were found between MO and SO participants. CONCLUSIONS: Emotion regulation and interoceptive awareness should be targeted in the psychotherapeutic care of obese people, regardless of their BMI. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Immediate biomechanical, systemic, and interoceptive effects of myofascial release on the thoracic spine: A randomised controlled trial.

BACKGROUND: Myofascial release (MFR) is used to restore tissue extensibility of the fascia tissue and is considered to be useful in a number of clinical settings such as low back pain, ankle injuries, fibromyalgia, and headaches. There is, however, despite the popularity of MFR in manual therapy, little consensus on whether it leads to biomechanical, systemic or interoceptive outcomes. AIMS: This study aimed to explore the immediate biomechanical (increased elasticity for increased range of motion), systemic (local vs. distal areas of pain threshold) and bodily awareness effects (interoception) of a myofascial release technique on the thoracic spine. METHOD: Twelve healthy participants took part in this triple-bind, repeated measures, cross-over design study, and were randomised into counterbalanced sequences of three conditions; a control, a sham, and the MFR condition. The outcome measures used were; range of motion (ROM), pain pressure thresholds (PPT), and interoceptive sensitivity (IS) to assess biomechanical, systemic, and interoceptive effects of MFR. RESULTS: There were significant increases in ROM and PPT (both local and distal) post MFR intervention. There was also a positive correlation between baseline interoceptive sensitivity and post-MFR ROM and a negative correlation for baseline interoceptive sensitivity and post-MRF PPT. Interoceptive sensitivity did increase post-MFR but this was non-significant. CONCLUSIONS: The increase in ROM suggests that the MFR may have caused a biomechanical change in tissue elasticity creating an increase in tissue flexibility. The increase in both local and distal sites of the PPT suggest an overall systemic response to the therapy. The correlation between baseline IS and post-MFR ROM and PPT suggest that IS may be usefully applied as a predictor for ROM and PPT post-MFR.

Interoception and respiratory sinus arrhythmia in gambling disorder.

Gambling has longstanding links with excitement and physiological arousal, but prior research has not considered (a) gamblers' ability to detect internal physiological signals, or (b) markers of parasympathetic functioning. The present study measured interoception in individuals with gambling disorder, using self-report measures and a heartbeat counting task administered at rest. Resting state respiratory sinus arrhythmia (RSA), an index of heart rate variability, was measured as a proxy for parasympathetic control and emotional regulation capacity. In a case-control design, 50 individuals with gambling disorder were compared against 35 controls without gambling problems. Participants completed two self-report measures of bodily awareness and a behavioral test of heartbeat counting. A resting state electrocardiogram (5 min) was used to calculate RSA. There were no significant differences on the self-report or behavioral interoception probes. The group with gambling disorder displayed significantly reduced RSA, which at face value is consistent with reduced parasympathetic control. However, the group difference in RSA did not survive controlling for age and smoking status, as established predictors of heart rate variability. Our findings do not support any changes in interoceptive processing in people with gambling disorder, at least under resting conditions. Our observation that group differences in RSA are partly explained by smoking behavior highlights the importance of controlling for nicotine use in future research characterizing physiological functioning and emotional regulation in disordered gambling.

Emotional orienting during interoceptive threat in orthostatic intolerance: Dysautonomic contributions to psychological symptomatology in the postural tachycardia syndrome and vasovagal syncope.

Cognitive and emotional processes are influenced by interoception (homeostatic somatic feedback), particularly when physiological arousal is unexpected and discrepancies between predicted and experienced interoceptive signals may engender anxiety. Due to the vulnerability for comorbid psychological symptoms in forms of orthostatic intolerance (OI), this study investigated psychophysiological contributions to emotional symptomatology in 20 healthy control participants (13 females, mean age 36 ±â€¯8 years), 20 postural tachycardia syndrome (PoTS) patients (18 females, mean age 38 ±â€¯13 years) and 20 vasovagal syncope (VVS) patients (15 females, mean age 39 ±â€¯12 years). We investigated indices of emotional orienting responses (OR) to randomly presented neutral, pleasant and unpleasant images in the supine position and during the induced interoceptive threat of symptom provocation of head-up tilt (HUT). PoTS and VVS patients produced greater indices of emotional responsivity to unpleasant images and, to a lesser degree, pleasant images, during interoceptive threat. Our findings are consistent with biased deployment of response-focused emotion regulation (ER) while patients are symptomatic, providing a mechanistic underpinning of how pathological autonomic overexcitation predisposes to anxiogenic traits in PoTS and VVS patients. This hypothesis may improve our understanding of why orthostasis exacerbates cognitive symptoms despite apparently normal cerebral autoregulation, and offer novel therapeutic targets for behavioural interventions aimed at reducing comorbid cognitive-affective symptoms in PoTS and VVS.

Investigating the relationship between cardiac interoception and autonomic cardiac control using a predictive coding framework.

Predictive coding models, such as the 'free-energy principle' (FEP), have recently been discussed in relation to how interoceptive (afferent visceral feedback) signals update predictions about the state of the body, thereby driving autonomic mediation of homeostasis. This study appealed to 'interoceptive inference', under the FEP, to seek new insights into autonomic (dys)function and brain-body integration by examining the relationship between cardiac interoception and autonomic cardiac control in healthy controls and patients with forms of orthostatic intolerance (OI); to (i) seek empirical support for interoceptive inference and (ii) delineate if this relationship was sensitive to increased interoceptive prediction error in OI patients during head-up tilt (HUT)/symptom provocation. Measures of interoception and heart rate variability (HRV) were recorded whilst supine and during HUT in healthy controls (N = 20), postural tachycardia syndrome (PoTS, N = 20) and vasovagal syncope (VVS, N = 20) patients. Compared to controls, interoceptive accuracy was reduced in both OI groups. Healthy controls' interoceptive sensibility positively correlated with HRV whilst supine. Conversely, both OI groups' interoceptive awareness negatively correlated with HRV during HUT. Our pilot study offers initial support for interoceptive inference and suggests OI cohorts share a central pathophysiology underlying interoceptive deficits expressed across distinct cardiovascular autonomic pathophysiology. From a predictive coding perspective, OI patients' data indicates a failure to attenuate/modulate ascending interoceptive prediction errors, reinforced by the concomitant failure to engage autonomic reflexes during HUT. Our findings offer a potential framework for conceptualising how the human nervous system maintains homeostasis and how both central and autonomic processes are ultimately implicated in dysautonomia.

How the Brain Wants What the Body Needs: The Neural Basis of Positive Alliesthesia.

Discontinuing unhealthy behaviors, such as overeating or drug use, depends upon an individual's ability to overcome the influence of environmental reward cues. The strength of that influence, however, varies greatly depending upon the internal state of the body. Characterizing the relationship between interoceptive signaling and shifting drug cue valuation provides an opportunity for understanding the neural bases of how changing internal states alter reward processing more generally. A total of 17 cigarette smokers rated the pleasantness of cigarette pictures when they were nicotine sated or nicotine abstinent. On both occasions, smokers also underwent functional magnetic resonance imaging (fMRI) scanning while performing a visceral interoceptive attention task and a resting-state functional connectivity scan. Hemodynamic, physiological, and behavioral parameters were compared between sated and abstinent scans. The relationships between changes in these parameters across scan sessions were also examined. Smokers rated cigarette pictures as significantly more pleasant while nicotine abstinent than while nicotine sated. Comparing abstinent with sated scans, smokers also exhibited significantly decreased mid-insula, amygdala, and orbitofrontal activity while attending to interoceptive signals from the body. Change in interoceptive activity within the left mid-insula predicted the increase in smoker's pleasantness ratings of cigarette cues. This increase in pleasantness ratings was also correlated with an increase in resting-state functional connectivity between the mid-insula and the ventral striatum and ventral pallidum. These findings support a model wherein interoceptive processing in the mid-insula of withdrawal signals from the body potentiates the motivational salience of reward cues through the recruitment of hedonic 'hot spots' within the brain's reward circuitry.

Differential brain responses to gradual intragastric nutrient infusion and gastric balloon distension: A role for gut peptides?

BACKGROUND: Rapid gastric balloon distension to discomfort threshold activates the "pain neuromatrix" and deactivates exteroceptive sensory and "default mode network" regions. However, little is known about brain mechanisms underlying tolerance of meal-induced gastric distension. We aimed to directly compare brain responses to gradual balloon distension and intragastric nutrient infusion and to explore the role of differential gut peptide release in these responses. MATERIALS AND METHODS: Brain responses to balloon- and nutrient-induced distension (to individually titrated pain or maximal satiation threshold) were measured in 15 healthy volunteers using H215O-PET on 2 separate days in counterbalanced order. The effects of increasing gastric distension and plasma levels of ghrelin and peptide YY3-36 (PYY3-36) on neural activity were assessed. RESULTS: Balloon distension progressively activated pain-responsive regions and deactivated exteroceptive sensory and "default mode network" areas. During nutrient infusion, "pain neuromatrix" regions and the orbitofrontal cortex were progressively deactivated, while the midbrain was activated. Plasma levels of PYY3-36 and ghrelin increased and decreased, respectively, during nutrient infusion only; decreasing ghrelin levels correlated with increasing midbrain activity. CONCLUSION: Different brain responses to gastric balloon distension and intragastric nutrient infusion are associated with nutrient-induced gut-brain signals, particularly to the midbrain, where these signals may interfere with both descending pain modulatory and mesolimbic reward processes. Deactivation of the "pain neuromatrix" during nutrient infusion may constitute the neurophysiological mechanism underlying the tolerance of normal meal volumes in health without induction of (painful) symptoms. Nutrient-induced deactivation of the orbitofrontal cortex may represent a key interoceptive meal termination signal.

Diminished Interoceptive Awareness in Fibromyalgia Syndrome.

Sensitivity to signals arising within the body (interoceptive awareness) has been implicated in emotion processing; interindividual differences in interoceptive awareness modulate both subjective and physiological indicators of emotional experience and the regulation of emotion-related behaviors. This study investigated interoceptive awareness in patients with fibromyalgia syndrome (FMS), a chronic pain condition accompanied by various affective symptoms. Interoceptive awareness was assessed in 45 FMS patients and 31 healthy individuals using a heartbeat perception task. Cognitive performance, comorbid psychiatric disorders and medication use were assessed as possible confounding variables. Concerning the primary outcome, patients exhibited markedly reduced heartbeat perception compared to healthy individuals. Moreover, there was an inverse relationship between interoceptive awareness and FMS symptom severity. Reduced interoceptive awareness may be involved in the affective aspects of FMS pathology. Poor access to bodily signals may restrict patients´ ability to integrate these signals during emotional processing, which, by extension, may preclude optimal emotional self-regulation.

Neurofisiología de la empatía: una revisión de investigaciones / Neurophysiology of empathy: a review of investigations

La empatía es un constructo con múltiples definiciones y modelos explicativos, los cuales se han conformado a partir de observaciones e investigaciones en humanos y otros animales. En el presente, se revisaron estudios en humanos sanos, que vincula empatía con conducta motora, sistema nervioso autónomo y central. La evidencia presentada apoya la asociación entre empatía y el sistema de neuronas en espejo, la imitación facial, el contagio pupilar, el sistema autonómico, la interocepción, la conectividad neuronal, la ínsula, el cíngulo, entre otras. Finalmente, esta revisión incentiva el estudio, investigación y desarrollo de las múltiples áreas y disciplinas que tratan con la empatía.