Autonomic regulation and vagal tone

Autonomy of autonomic dysfunction in major depression.: Objective: To investigate cardiac autonomic dysfunction in patients with major depressive disorder (MDD). Research in this area has faced several limitations because of the heterogeneity of the disease, the influence of medication, and methodological shortcomings. Methods: Participants were 75 patients suffering from an acute recurrent episode of MDD and 75 matched controls. All participants were assessed at baseline for linear and nonlinear parameters of heart rate variability, QT variability a

Non-invasive vagus nerve stimulation acutely improves spontaneous cardiac baroreflex sensitivity in healthy young men: A randomized placebo-controlled trial.: Background: Despite positive outcomes of transcutaneous vagus nerve stimulation (tVNS) via the auricular branch of the vagus nerve (ABVN), the mechanisms underlying these outcomes remain unclear. Additionally, previous studies have not been controlled the possible placebo effects of tVNS. Objective: To test the hypothesis that tVNS acutely improves spontaneous cardiac baroreflex sensitivity (cBRS) and autonomic modulation, and that these effects are specific to stimulation of ABVN. Methods: Thir

Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity.: Background: Vagus nerve stimulation (VNS) is currently used to treat refractory epilepsy and is being investigated as a potential therapy for a range of conditions, including heart failure, tinnitus, obesity and Alzheimer's disease. However, the invasive nature and expense limits the use of VNS in patient populations and hinders the exploration of the mechanisms involved. Objective: We investigated a non-invasive method of VNS through electrical stimulation of the auricular branch of the vagus n

Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation.: Ageing is associated with attenuated autonomic function. Transcutaneous vagal nerve stimulation (tVNS) improved autonomic function in healthy young participants. We therefore investigated the effects of a single session of tVNS (studies 1 and 2) and tVNS administered daily for two weeks (study 3) in volunteers aged ≥ 55 years. tVNS was performed using modified surface electrodes on the tragus and connected to a transcutaneous electrical nerve stimulation (TENS) machine. Study 1: participants (n=

Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity.: Background: The parasympathetic nervous system, whose main neural substrate is the vagus nerve, exerts a fundamental antinociceptive role and influences gastrointestinal sensori-motor function. Our research question was to whether combined electrical and physiological modulation of vagal tone, using transcutaneous electrical vagal nerve stimulation (t-VNS) and deep slow breathing (DSB) respectively, could increase musculoskeletal pain thresholds and enhance gastroduodenal motility in healthy sub

Sex differences in healthy human heart rate variability: A meta-analysis.: The present meta-analysis aimed to quantify current evidence on sex differences in the autonomic control of the heart, indexed by measures of heart rate variability (HRV) in healthy human subjects. An extensive search of the literature yielded 2020 titles and abstracts, of which 172 provided sufficient reporting of sex difference in HRV. Data from 63,612 participants (31,970 females) were available for analysis. Meta-analysis yielded a total of 1154 effect size estimates (k) across 50 different

Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk?

Background: Evidence exists linking major depressive disorder (MDD) with clinical cardiovascular events. The importance of the sympathetic nervous system in the generation of cardiac risk in other contexts is established. Objective: To examine the importance of the sympathetic nervous system in the generation of cardiac risk in patients with major depressive disorder (MDD). Methods: Studies were performed in 39 patients meeting the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for MDD and in 76 healthy subjects. Treatment for patients consisted of selective serotonin reuptake inhibition (SSRI) for 12 weeks. Whole body and cardiac sympathetic activity were examined using noradrenaline isotope dilution methodology and sympathetic nerve recording techniques. Measurement of the extraction of infused tritiated noradrenaline by the heart, and estimation of cardiac …

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Neurobio-logy of multiple myeloma and its therapeutical use - results of the pilot study with a control arm.

Background: Myeloma cells, occupying a bone marrow niche, are influenced not only by neighbouring stroma cells but also by signals from the axons of sympathetic nervous system. The nervous system is directly involved in the process of myeloma progression. Among other cancers, patients with myeloma suffer the most difficult distress generating intensive adrenergic signals, causing its further progression. There is a question arising from these facts regarding whether psychological interventions, modulating a function of the nervous system, can further improve outcomes of myeloma treatments. We focus on interactions between myeloma cells and the nervous system. Patients and methods: Twelve patients with monoclonal gamapathy of indetermined significance (MGUS) or myeloma have participated in this study; eight in the interventional arm with the intervention of forgiveness therapy and four in…

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The acute effects of continuous and intermittent whole-body passive heating on cardiovascular disease risk indicators in healthy and young males and females.

Purpose: Heat therapy is recognised to promote cardiovascular health, and whilst most recent heat therapy investigations have focussed on continuous heat exposure, traditional sauna use often includes recovery periods. This study compared the acute effects of continuous versus intermittent whole-body heating on cardiovascular function markers in males and females. Methods: Twenty healthy participants (25 ± 3 years; 10 males, 10 females) were exposed to 2 passive heating regimens: continuous heating (CH) for 60 min and intermittent heating (IH) comprised of 3 × 20-min blocks interspersed by 15-min cooling breaks. Skin perfusion, blood pressure (BP), plasma nitrite, interleukins, body temperature, and thermal perceptual responses were assessed. Results: Greater increases in rectal temperature (Trec) (CH: 1.2 ± 0.1 °C; IH: 0.5 ± 0.1 °C), skin perfusion, systolic blood pressure (SBP), heart …

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Examining the Impact of a Brief Compassion Focused Intervention on Everyday Experiences of Compassion in Autistic Adults Through Psychophysiology and Experience Sampling.

Autistic adults experience greater rates of anxiety and depression compared to the general population. Compassion-focused therapy interventions, aimed at promoting self-compassion capabilities, have shown efficacy in improving mental health outcomes in autistic and non-autistic samples suffering from self-criticism that contribute to difficulties in emotion regulation. We explored the experiences of autistic adults during a brief one-week online self-compassion exercise to evaluate it's feasibility and acceptability through self-report, experience sampling, and parasympathetic activity measured via HRV. Pre- to post-intervention comparisons showed significant improvement in trait self-compassion and fears of self-compassion, but this did not extend to acute measures of psychological distress (depression, anxiety, and stress) nor difficulties in emotion regulation. HRV measures displayed …

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Buffering effects of amusement and awe on stress responses: Behavioral, physiological, and neural response.

The experience of positive emotions plays a crucial role in promoting mental and physical health. Laboratory studies have suggested that induced positive emotions facilitate stress recovery. However, how recovery from stress by discrete positive emotions temporally changes in psychological and physiological measurements, and what neural mechanisms underlie these processes remains unclear. Therefore, we investigated the buffering effects of amusement and awe on stress responses from psychological, physiological, and neural perspectives using photoplethysmography and functional magnetic resonance imaging (fMRI). Sixty-seven college students completed the Montreal Imaging Stress Task and viewed emotion-inducing videos designed to elicit amusement, awe, or neutral emotional states inside an MRI scanner. Our findings demonstrate that amusement and awe had buffering effects on perceived stress…

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Transdiagnostic failure to adapt interoceptive precision estimates across affective, substance use, and eating disorders: A replication and extension of previous results.

Recent Bayesian theories of interoception suggest that perception of bodily states rests upon a precision-weighted integration of afferent signals and prior beliefs. In a previous study, we fit a computational model of perception to behavior on a heartbeat tapping task to test whether aberrant precision-weighting could explain misestimation of cardiac states in psychopathology. We found that, during an interoceptive perturbation designed to amplify afferent signal precision (inspiratory breath-holding), healthy individuals increased the precision-weighting assigned to ascending cardiac signals (relative to resting conditions), while individuals with anxiety, depression, substance use disorders, and/or eating disorders did not. In this pre-registered study, we aimed to replicate and extend our prior findings in a new transdiagnostic patient sample (N = 285) similar to the one in the origi…

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Thermosensation and emotion: Thermosensory accuracy in a dynamic thermal matching task is linked to depression and anxiety symptomatology.

Interoception is related to the generation of bodily feelings and the awareness of ourselves as 'sentient beings', informing the organism about its bodily needs to guarantee survival. Previous studies have reported links among interoception, emotion processing, and mental health. For example, the alignment of interoceptive dimensions (i.e., accuracy, sensibility, awareness) can predict emotional symptoms, such as anxiety. Here, we aimed to investigate the relationship between the perception of a certain type of skin-mediated interoceptive signal, i.e., thermosensation, and self-reported depression, anxiety, and stress. One hundred seventy participants completed the Depression Anxiety Stress Scale (DASS-21) and a dynamic thermal matching task, a static temperature detection task, and a heartbeat counting task. Our results revealed that self-reported anxiety and depression were related to …

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Cognitive performance during exposure to moderate normobaric hypoxia after sleep restriction: Relationship to physiological and stress biomarkers.

Introduction: Exposure to moderate levels of simulated hypoxia has subtle cognitive effects relative to ground level, in healthy individuals. However, there are few data on the cognitive consequences of the combination of hypoxia and partial sleep deprivation, which is a classic military or civilian operational context. In this study, we tested the hypothesis that exposure to moderate hypoxia while sleep-restricted impairs several domains of cognition, and we also assessed physiological parameters and salivary concentrations of cortisol and alpha-amylase. Method: Seventeen healthy males completed two sessions of cognitive tests (sustained attention using the PVT psychomotor vigilance task and executive functions using the Go-NoGo inhibition task and N-Back working memory task) after 30 min (T + 30') and 4 h (T + 240') of exposure in a normobaric hypoxic tent (FIO2 = 13.6 %, ≃ 3,500 m) (H…

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Do we need to accurately perceive our heartbeats? Cardioceptive accuracy and sensibility are independent from indicators of negative affectivity, body awareness, body image dissatisfaction, and alexithymia.

Assessment of the acuity of heartbeat perception, dubbed cardioceptive accuracy, as well as its association with various psychological characteristics are hot topics of interoception research. In this study, we aimed (1) to replicate previously reported findings on the association between the mental tracking task and a novel motor tracking task that eliminates disturbing tactile sensations; and (2) to explore associations between performance in the latter task and indicators of negative affectivity (anxiety, depression, anxiety sensitivity, somatic symptom distress), alexithymia, body focus, and dissatisfaction with body image. 102 young people (age = 20.8±5.08 yrs) participated in the study. Mental tracking score was significantly higher than motor tracking scores, although they were strongly associated. Frequentist correlation analysis showed no significant associations between indicat…

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A single oral dose of citalopram increases interoceptive insight in healthy volunteers.

Rationale: Interoception is the signalling, perception, and interpretation of internal physiological states. Many mental disorders associated with changes of interoception, including depressive and anxiety disorders, are treated with selective serotonin reuptake inhibitors (SSRIs). However, the causative link between SSRIs and interoception is not yet clear. Objectives: To ascertain the causal effect of acute changes of serotonin levels on cardiac interoception. Methods: Using a within-participant placebo-controlled design, forty-seven healthy human volunteers (31 female, 16 male) were tested on and off a 20 mg oral dose of the commonly prescribed SSRI, citalopram. Participants made judgements on the synchrony between their heartbeat and auditory tones and then expressed confidence in each judgement. We measured three types of interoceptive cognition. Results: Citalopram increased cardia…

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Acute physiological and psychophysical responses to different modes of heat stress.

New findings: What is the central question of this study? What are the profiles of acute physiological and psychophysical strain during and in recovery from different modes of heating, and to what extent do these diminish after repeated exposure? What is the main finding and its importance? Mode of heating affects the strain profiles during heat stress and recovery. Exercise in the heat incurred the greatest cardiovascular strain during heating and recovery. Humid heat was poorly tolerated despite heat strain being no greater than in other heating modes, and tolerance did not improve with multiple exposures. Abstract: Heat stress is common and arises endogenously and exogenously. It can be acutely hazardous while also increasingly advocated to drive health and performance-related adaptations. Yet, the nature of strain (deviation in regulated variables) imposed by different heating modes …

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Alteration of interoceptive sensitivity: expanding the spectrum of behavioural disorders in amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with progressive loss of upper and lower motor neurons. Non-motor-symptoms, such as cognitive, emotional, autonomic, and somatosensory alterations, have been also described. Interoception represents the link between the body and brain, since it refers to the ability to consciously perceive the physical condition of the inner body, including one's heartbeat (i.e., interoceptive sensitivity, IS). Objectives: To evaluate IS in ALS patients by means of a well-established task: the heartbeat perception task. Moreover, we evaluated possible correlations between IS and neuropsychological, affective, and disease-related characteristics. Methods: Fifty-five ALS patients (mean-age = 60.3 ± 12.5 years; mean disease-duration = 20.9 ± 18.8 months) and 41 caregivers (CG) underwent the heartbeat perception task and an exten…

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Towards a comprehensive assessment of interoception in a multi-dimensional framework.

Interoception has historically been assessed using behavioural tests of accuracy, self-report measures or through the characterisation of neural signals underlying interoceptive processing. More recent conceptualisations of interoception incorporate interoceptive attention and higher-order measures related to the interpretation of interoceptive signals. At present, these interoceptive dimensions are largely assessed in isolation, yet this fails to capture the complexity of interoception. Comprehensive assessment across interoceptive dimensions can determine the full operation of general interoceptive function. Current work suggests that these interoceptive processes may be dissociable across dimensions and bodily axes, with differential mapping to cognitive and emotion processing. To characterise differences in interoceptive profiles, all interoceptive dimensions can be assessed within i…

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Interoception is associated with anxiety and depression in pregnant women: A pilot study.

Pregnancy and postpartum are periods in which women develop psychosocially. However, becoming a mother is stressful, and mood disorders related to anxiety and depression often develop. In recent years, research on interoception-sensations related to the body's internal physiological state-has attracted attention. Interoception has multifaceted characteristics. It involves directly perceiving information in the body while also inferring and evaluating it. In this study, we examined interoception, anxiety, and depression in Japanese pregnant women. Empirical examinations and questionnaire surveys were used to measure interoception in 32 pregnant women not at high risk of pregnancy. A Japanese adaption of the Multidimensional Assessment of Interoceptive Awareness was used to measure interoceptive sensibility, and a heartbeat counting task performance was used to measure interoceptive accura…

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Individual differences in interoceptive accuracy and prediction error in motor functional neurological disorders: A DTI study.

In motor functional neurological disorders (mFND), relationships between interoception (a construct of high theoretical relevance to its pathophysiology) and neuroanatomy have not been previously investigated. This study characterized white matter in mFND patients compared to healthy controls (HCs), and investigated associations between fiber bundle integrity and cardiac interoception. Voxel-based analysis and tractography quantified fractional anisotropy (FA) in 38 mFND patients compared to 38 HCs. Secondary analyses compared functional seizures (FND-seiz; n = 21) or functional movement disorders (n = 17) to HCs. Network lesion mapping identified gray matter origins of implicated fiber bundles. Within-group mFND analyses investigated relationships between FA, heartbeat tracking accuracy and interoceptive trait prediction error (discrepancies between interoceptive accuracy and self-repor…

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Interoception and stress in patients with Functional Neurological Symptom Disorder.

Introduction: Research suggests that patients with Functional Neurological Symptom Disorder (pwFND) struggle to identify their own emotions and associated physiological cues (interoceptive sensitivity, IS). However, it is not known how this deficit interacts with stress. This study aimed to assess IS in pwFND at baseline and following stress induction, and relate the findings to self-reported emotion processing difficulties. Methods: Twenty-six pwFND and 27 healthy controls performed the Heart Beat Detection Task pre- and post-stress induction with the Cold Pressor Test. Participants also completed questionnaires assessing anxiety (GAD-7) and depressive symptomology (PHQ-9), as well as emotion processing (EPS-25). Results: Patients reported deficits in emotion processing (p < . 001) and had lower IS (p = .032) than healthy controls. IS improved following stress induction across both grou…

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Validity of differentiated ratings of perceived exertion for use during aquatic cycling.

Background: Although aquabiking has become widespread, the assessment of the intensity for aquatic cycling remains poorly defined. Methods: This study investigated the validity of differentiated ratings of perceived exertion (dRPE) recorded from the chest (RPE-chest) and legs (RPE-legs) during aquatic cycling and aimed to determine a simple and accurate estimate of dRPE to regulate aquabiking. Twelve active young subjects performed a pedaling task on an immersed ergocycle using randomly imposed cycling cadences ranging from 50 to 100 rpm in 3-minute steps interspersed by 3-minute active recovery periods. dRPE and cardiorespiratory responses (heart rate [HR]; percentage of heart rate peak value [%HRpeak]; oxygen uptake [V̇O2]; and percentage of peak oxygen uptake [%V̇O2peak]) were measured during the last minute of each level. Results: The data described three-step relationships between d…

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Photoplethysmography in Normal and Pathological Sleep.

This article presents an overview of the advancements that have been made in the use of photoplethysmography (PPG) for unobtrusive sleep studies. PPG is included in the quickly evolving and very popular landscape of wearables but has specific interesting properties, particularly the ability to capture the modulation of the autonomic nervous system during sleep. Recent advances have been made in PPG signal acquisition and processing, including coupling it with accelerometry in order to construct hypnograms in normal and pathologic sleep and also to detect sleep-disordered breathing (SDB). The limitations of PPG (e.g., oxymetry signal failure, motion artefacts, signal processing) are reviewed as well as technical solutions to overcome these issues. The potential medical applications of PPG are numerous, including home-based detection of SDB (for triage purposes), and long-term monitoring o…

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Effects of Twelve Sessions of High-Temperature Sauna Baths on Body Composition in Healthy Young Men.

The health benefits of sauna baths are attracting ever-increasing interest. Therefore, the purpose of this study was to evaluate the effects of 12 high-temperature (100 °C) sauna baths on body composition of 23 healthy young men, divided into a control group (CG) and a sauna group (SG). Both groups were initially evaluated by dual-energy X-ray absorptiometry (DXA), after which the SG experienced 12 sessions of sauna baths at high temperatures (100 °C). Initial measurements were carried out after the sauna sessions and after two weeks of decay in both groups. The muscle mass of the right leg (pre vs. decay: 9.50 (5.59) vs. 10.52 (5.15); p < 0.05; Δ 1.07%), bone mineral density (pre vs. post: 1.221 (0.35) vs. 1.315 (0.45); p < 0.05; Δ 7.7%) and bone mineral content (pre vs. post: 0.470 (0.21) vs. 0.499 (0.22); p < 0.05; Δ 6.17%) of the left leg increased in the SG after the sauna baths. It…

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Female sweet-likers have enhanced cross-modal interoceptive abilities.

There are well known phenotypic differences in sweet-liking across individuals, but it remains unknown whether these are related to broader underlying differences in interoceptive abilities (abilities to sense the internal state of the body). Here, healthy women (N = 64) classified as sweet likers (SLs) or sweet dislikers (SDs) completed a bimodal interoception protocol. A heartbeat tracking and a heartbeat discrimination task determined cardiac interoception; both were accompanied by confidence ratings. A water load task, where participants consumed water to satiation and then to maximum fullness was used to assess gastric interoceptive abilities. Motivational state, psychometric characteristics and eating behaviour were also assessed. SLs performed significantly better than SDs on both heartbeat tasks, independently of impulsivity, anxiety, depression, and alexithymia. No differences i…

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The utilization of advance telemetry to investigate critical physiological parameters including electroencephalography in cynomolgus macaques following aerosol challenge with eastern equine encephalitis virus.

Most alphaviruses are mosquito-borne and can cause severe disease in humans and domesticated animals. In North America, eastern equine encephalitis virus (EEEV) is an important human pathogen with case fatality rates of 30-90%. Currently, there are no therapeutics or vaccines to treat and/or prevent human infection. One critical impediment in countermeasure development is the lack of insight into clinically relevant parameters in a susceptible animal model. This study examined the disease course of EEEV in a cynomolgus macaque model utilizing advanced telemetry technology to continuously and simultaneously measure temperature, respiration, activity, heart rate, blood pressure, electrocardiogram (ECG), and electroencephalography (EEG) following an aerosol challenge at 7.0 log10 PFU. Following challenge, all parameters were rapidly and substantially altered with peak alterations from basel…

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Measuring interoception: The phase adjustment task.

Interoception, perception of one's bodily state, has been associated with mental health and socio-emotional processes. However, several interoception tasks are of questionable validity, meaning associations between interoception and other variables require confirmation with new measures. Here we describe the novel, smartphone-based Phase Adjustment Task (PAT). Tones are presented at the participant's heart rate, but out of phase with heartbeats. Participants adjust the phase relationship between tones and heartbeats until they are synchronous. Data from 124 participants indicates variance in performance across participants which is not affected by physiological or strategic confounds. Associations between interoception and anxiety, depression and stress were not significant. Weak associations between interoception and mental health variables may be a consequence of testing a non-clinical…

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Loneliness and the Social Brain: How Perceived Social Isolation Impairs Human Interactions.

Loneliness is a painful condition associated with increased risk for premature mortality. The formation of new, positive social relationships can alleviate feelings of loneliness, but requires rapid trustworthiness decisions during initial encounters and it is still unclear how loneliness hinders interpersonal trust. Here, a multimodal approach including behavioral, psychophysiological, hormonal, and neuroimaging measurements is used to probe a trust-based mechanism underlying impaired social interactions in loneliness. Pre-stratified healthy individuals with high loneliness scores (n = 42 out of a screened sample of 3678 adults) show reduced oxytocinergic and affective responsiveness to a positive conversation, report less interpersonal trust, and prefer larger social distances compared to controls (n = 40). Moreover, lonely individuals are rated as less trustworthy compared to controls…

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Interoception of breathing and its relationship with anxiety.

Interoception, the perception of internal bodily states, is thought to be inextricably linked to affective qualities such as anxiety. Although interoception spans sensory to metacognitive processing, it is not clear whether anxiety is differentially related to these processing levels. Here we investigated this question in the domain of breathing, using computational modeling and high-field (7 T) fMRI to assess brain activity relating to dynamic changes in inspiratory resistance of varying predictability. Notably, the anterior insula was associated with both breathing-related prediction certainty and prediction errors, suggesting an important role in representing and updating models of the body. Individuals with low versus moderate anxiety traits showed differential anterior insula activity for prediction certainty. Multi-modal analyses of data from fMRI, computational assessments of brea…

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Trait and state interoceptive abnormalities are associated with dissociation and seizure frequency in patients with functional seizures.

Objective: Dissociative traits represent a disturbance in selfhood that may predispose to, and trigger, functional seizures (FSs). The predictive representation and control of the internal physiological state of the body (interoception) are proposed to underpin the integrity of the sense of self ("minimal selfhood"). Therefore, discrepancies between objective and subjective aspects of interoception may relate to symptom expression in patients with FSs. Here, we tested whether individual differences in trait measures of interoception relate to dissociative symptoms, and whether state interoceptive deficits predict FS occurrence. Methods: Forty-one participants with FSs and 30 controls completed questionnaire ratings of dissociation, and measures of (1) interoceptive accuracy (IA)-objective performance on heartbeat detection tasks; (2) trait interoceptive sensibility-subjective sensitivity…

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