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.

Dissociative Symptoms and Interoceptive Integration.

Dissociative symptoms and disorders of dissociation are characterised by disturbances in the experience of the self and the surrounding world, manifesting as a breakdown in the normal integration of consciousness, memory, identity, emotion, and perception. This paper aims to provide insights into dissociative symptoms from the perspective of interoception, the sense of the body's internal physiological state, adopting a transdiagnostic framework.Dissociative symptoms are associated with a blunting of autonomic reactivity and a reduction in interoceptive precision. In addition to the central function of interoception in homeostasis, afferent visceral signals and their neural and mental representation have been shown to shape emotional feeling states, support memory encoding, and contribute to self-representation. Changes in interoceptive processing and disrupted integration of interoceptive signals into wider cognition may contribute to detachment from the body and the world, blunted emotional experience, and altered subjective recall, as experienced by individuals who suffer from dissociation.A better understanding of the role of altered interoceptive integration across the symptom areas of dissociation could thus provide insights into the neurophysiological mechanisms underlying dissociative disorders. As new therapeutic approaches targeting interoceptive processing emerge, recognising the significance of interoceptive mechanisms in dissociation holds potential implications for future treatment targets.

Effects of stress on pain in females using a mobile health app in the Russia-Ukraine conflict.

The chronic and acute effects of stress can have divergent effects on health; long-term effects are associated with detrimental physical and mental health sequelae, while acute effects may be advantageous in the short-term. Stress-induced analgesia, the attenuation of pain perception due to stress, is a well-known phenomenon that has yet to be systematically investigated under ecological conditions. Using Flo, a women's health and wellbeing app and menstrual cycle tracker, with a world-wide monthly active usership of more than 57 million, women in Ukraine were monitored for their reporting of stress, pain and affective symptoms before, and immediately after, the onset of the Russian-Ukrainian conflict. To avoid potential selection (attrition) or collider bias, we rely on a sample of 87,315 users who were actively logging multiple symptoms before and after the start of the war. We found an inverse relationship between stress and pain, whereby higher reports of stress predicted lower rates of pain. Stress did not influence any other physiological symptoms with a similar magnitude, nor did any other symptom have a similar effect on pain. This relationship generally decreased in magnitude in countries neighbouring and surrounding Ukraine, with Ukraine serving as the epicentre. These findings help characterise the relationship between stress and health in a real-world setting.

Evidence that pupil dilation and cardiac afferent signalling differentially impact the processing of emotional intensity and racial bias.

Interoceptive cardiac arousal signals (e.g., from baroreceptor firing at ventricular systole compared to diastole) have been found to enhance perception of fearful versus neutral faces. They have also been found to amplify racially biased misidentification of tools as weapons when preceded by facial images of Black versus White individuals. Since pupil size is strongly coupled to arousal, we tested if experimental manipulation of pupil size influences fear processing in emotional judgement and racial bias tasks involving measurement of cardiac signals. In a sample of 22 non-clinical participants in an emotional intensity judgement task, pupil size did not affect emotional intensity ratings. Nor did it interact with differential effects of cardiac systole versus diastole on intensity judgements of fearful and neutral faces, replicated here. In a sample of 25 non-clinical participants in a weapons identification task, larger pupil size resulted in faster response times and lower accuracy when identifying tools and weapons. However, pupil size did not interact with weapon versus tool identification, race of prime, or cardiac timing. We nevertheless replicated the observed increase in racially biased misidentification of tools as weapons following Black face primes presented at cardiac systole. Together our findings indicate that pupil dilation does not directly influence the processing of fear cues or perceived threat (as in racial bias) yet affects task performance by decreasing response times and accuracy. These findings contrast with the established effect of cardiac arousal signals on threat processing and may help focus interventions to mitigate related decision errors in high-pressure occupations.

Impaired cardiac modulation in patients with functional seizures: Results from a face intensity judgment task.

OBJECTIVE: Although interoceptive abnormality in patients with functional seizure (FSs) has been demonstrated using explicit tasks, implicit measurements of interoception such as the effect of interoception on perceptual brain processes have not been investigated. It has been shown that perception is normally modulated by interoceptive signals related to the different phases (systole vs diastole) of the cardiac cycle (cardiac modulation effect). Given our previous findings using explicit measures of interoception, we hypothesized that cardiac modulation would be impaired in FSs. METHODS: Thirty-two patients with FSs and 30 age- and sex-matched non-clinical individuals conducted a face intensity judgment task, in which their intensity rating when fearful or neutral faces was presented was compared between systolic and diastolic phases. They also conducted the heartbeat discrimination task as a measure of their capacity to integrate both interoceptive and exteroceptive information. RESULTS: Patients with FSs had impaired cardiac modulation of the perception of neutral faces (corrected p = .044). Individual differences in the heartbeat discrimination task predicted the degree to which cardiac modulation occurred across the whole group (p = .028). This cardiac modulation effect was significantly associated with seizure severity (p = .021). Regardless of cardiac phase, patients rated fearful facial expressions as less intense compared to control participants (p = .006). SIGNIFICANCE: These findings highlight impaired implicit cardiac modulation effects in patients with FSs. This reflects interoceptive dysfunction in patients with FSs, and an inability of the brain to integrate interoceptive signaling with perceptual processing. This may have implications for our understanding of the pathophysiology in FSs and inform novel diagnostic approaches.

"Mom said it in quotation marks!" Irony comprehension and metapragmatic awareness in 8-year-olds.

This study investigated links between the development of children's understanding of ironic comments and their metapragmatic knowledge. Forty-six 8-year-olds completed the short version of the Irony Comprehension Task, during which they were presented with ironic comments in three stories and asked to provide reasons for why the speaker in a story uttered an ironic comment. We coded their responses and compared the results to similar data collected previously with 5-year-olds. Results showed that compared to younger children, 8-year-olds frequently refer to interlocutors' emotions, intentions, and to metapragmatics. These results support the view that comprehension of verbal irony is an emerging skill in children.

Changes in the heartbeat-evoked potential are associated with functional seizures.

BACKGROUND: Patients with functional seizures (FS) can experience dissociation (depersonalisation) before their seizures. Depersonalisation reflects disembodiment, which may be related to changes in interoceptive processing. The heartbeat-evoked potential (HEP) is an electroencephalogram (EEG) marker of interoceptive processing. AIM: To assess whether alterations in interoceptive processing indexed by HEP occur prior to FS and compare this with epileptic seizures (ES). METHODS: HEP amplitudes were calculated from EEG during video-EEG monitoring in 25 patients with FS and 19 patients with ES, and were compared between interictal and preictal states. HEP amplitude difference was calculated as preictal HEP amplitude minus interictal HEP amplitude. A receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of HEP amplitude difference in discriminating FS from ES. RESULTS: The FS group demonstrated a significant reduction in HEP amplitude between interictal and preictal states at F8 (effect size rB=0.612, false discovery rate (FDR)-corrected q=0.030) and C4 (rB=0.600, FDR-corrected q=0.035). No differences in HEP amplitude were found between states in the ES group. Between diagnostic groups, HEP amplitude difference differed between the FS and ES groups at F8 (rB=0.423, FDR-corrected q=0.085) and C4 (rB=0.457, FDR-corrected q=0.085). Using HEP amplitude difference at frontal and central electrodes plus sex, we found that the ROC curve demonstrated an area under the curve of 0.893, with sensitivity=0.840 and specificity=0.842. CONCLUSION: Our data support the notion that aberrant interoception occurs prior to FS. Changes in HEP amplitude may reflect a neurophysiological biomarker of FS and may have diagnostic utility in differentiating FS and ES.

Cardiac interoception in patients accessing secondary mental health services: A transdiagnostic study.

BACKGROUND: Abnormalities in the regulation of physiological arousal and interoceptive processing are implicated in the expression and maintenance of specific psychiatric conditions and symptoms. We undertook a cross-sectional characterisation of patients accessing secondary mental health services, recording measures relating to cardiac physiology and interoception, to understand how physiological state and interoceptive ability relate transdiagnostically to affective symptoms. METHODS: Participants were patients (n = 258) and a non-clinical comparison group (n = 67). Clinical diagnoses spanned affective disorders, complex personality presentations and psychoses. We first tested for differences between patient and non-clinical participants in terms of cardiac physiology and interoceptive ability, considering interoceptive tasks and a self-report measure. We then tested for correlations between cardiac and interoceptive measures and affective symptoms. Lastly, we explored group differences across recorded clinical diagnoses. RESULTS: Patients exhibited lower performance accuracy and confidence in heartbeat discrimination and lower heartbeat tracking confidence relative to comparisons. In patients, greater anxiety and depression predicted greater self-reported interoceptive sensibility and a greater mismatch between performance accuracy and sensibility. This effect was not observed in comparison participants. Significant differences between patient groups were observed for heart rate variability (HRV) although post hoc differences were not significant after correction for multiple comparisons. Finally, accuracy in heartbeat tracking was significantly lower in schizophrenia compared to other diagnostic groups. CONCLUSIONS: The multilevel characterisation presented here identified certain physiological and interoceptive differences associated with psychiatric symptoms and diagnoses. The clinical stratification and therapeutic targeting of interoceptive mechanisms is therefore of potential value in treating certain psychiatric conditions.

The relationship between interoception and agency and its modulation by heartbeats: an exploratory study.

Interoception, the sense of the internal physiological state of the body, theoretically underpins aspects of self-representation. Experimental studies link feelings of body ownership to interoceptive perception, yet few studies have tested for association between the sense of agency and interoceptive processing. Here, we combined an intentional binding paradigm with cardiac measures of interoceptive processing (behavioural performance on a heartbeat discrimination task, and effects of timing within the cardiac cycle) in twenty-six non-clinical participants as an exploratory study. We found performance accuracy on the heartbeat discrimination task correlated positively with the intentional binding effect, an index of sense of agency (ß = 0.832, p = 0.005), even after controlling for effects of age, sex, educational level, heart rate, heart rate variability and time accuracy. The intentional binding effect was enhanced during cardiac systole (compared to diastole) in individuals with greater heartbeat discrimination accuracy (ß = 0.640, p = 0.047). These findings support the proposal that interoception contributes to mechanisms underlying the emergence of sense of agency.

Hypermobility in patients with functional seizures: Toward a pathobiological understanding of complex conditions.

BACKGROUND: Functional seizures (FS), otherwise known as psychogenic nonepileptic seizures (PNES), are a common symptom presenting to neurology and epilepsy clinics. There is a pressing need for further research to understand the neurobiology of FS to develop mechanistically targeted treatments. Joint hypermobility is an expression of variation in connective tissue structure along a spectrum, and it has received increasing attention in functional neurological disorders, but there is lack of evidence of its relevance in FS. METHODS: In the present study, forty-two patients with FS and a non-clinical comparison group of 34 age/sex-matched controls were recruited. Joint hypermobility of all participants was quantified using the Beighton scale. RESULTS: In our sample, 24 (57%) patients with FS, and 7 (21%) of the comparison group met criteria for joint hypermobility (p = 0.002). Our statistical model revealed that patients with FS showed a significant degree of hypermobility compared to the comparison group (odds ratio = 11.1; Confidence interval: 2.1-78.0, p = 0.008), even after controlling age, sex, anxiety, and depression. CONCLUSION: We found a significant association between FS and joint hypermobility, which was independent of anxiety and depression.

Interoceptive pathways to understand and treat mental health conditions.

An increasing recognition that brain and body are dynamically coupled has enriched our scientific understanding of mental health conditions. Peripheral signals interact centrally to influence how we think and feel, generating our sense of the internal condition of the body, a process known as interoception. Disruptions to this interoceptive system may contribute to clinical conditions, including anxiety, depression, and psychosis. After reviewing the nature of interoceptive disturbances in mental health conditions, this review focuses on interoceptive pathways of existing and putative mental health treatments. Emerging clinical interventions may target novel peripheral treatment mechanisms. Future treatment development requires forward- and back-translation to uncover and target specific interoceptive processes in mental health to elucidate their efficacy relative to interventions targeting other factors.

Cardiac deceleration following positive and negative feedback is influenced by competence-based social status.

Previous studies indicate that neurophysiological signatures of feedback processing might be enhanced when participants are assigned a low-status position. Error commission and negative feedback can evoke responses in the peripheral (autonomic) nervous system including heart rate deceleration. We conducted an exploratory study to investigate whether such activity can be modulated by the participant's social status in a competence-based hierarchy. Participants were engaged in a cooperative time estimation task with two same-gender confederates. On each trial, they were provided with positive or negative feedback depending on their time estimation performance. Their social status varied during the task, so that they were either at the top (high-status) or at the bottom (low-status) of the hierarchy in different blocks. Results showed that cardiac deceleration was significantly modulated by feedback valence in the high-status but not in the low-status condition. We interpret this result as an increased activation of the performance monitoring system elicited by the desire to maintain a high-status position in an unstable hierarchy. In this vein, negative feedback might be processed as an aversive stimulus that signals a threat to the acquired status.

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 cardiac interoceptive insight, measured as correspondence of self-reported confidence to the likelihood that interoceptive judgements were actually correct. This effect was driven by enhanced confidence for correct interoceptive judgements and was independent of measured cardiac and reported subjective effects of the drug. CONCLUSIONS: An acute change of serotonin levels can increase insight into the reliability of inferences made from cardiac interoceptive sensations.

Addressing the need for new interoceptive methods.

Internal bodily signals are dynamically coupled to brain dynamics; interoception, the 'sensing' of internal signals, can influence cognition, emotion and perception. An appreciation of the wide-ranging implications of interoceptive processing has surpassed the range and breadth of available interoceptive methods. New techniques are required to support the scientific study of interoception and this special issue brings together a diverse array of novel interoceptive methods and assessments, spanning psychophysiology, experimental psychology, affective neuroscience and computational approaches, divided into 5 core sections. Section 1 presents novel theoretical and computational models of interoception, while section two brings together a range of perspectives on questionnaire measures of interoception. Section 3 is devoted to the development of novel methods to assess interoception in behavioral tasks and section 4 focuses on the validity and confounds present in a range of methods used to assess interoception. Finally, section 5 details new methodological insights of interoception in the domains of emotion, cognition and health. Improved interoceptive methods are needed to progress this field; greater precision in techniques and core interoceptive constructs will aid in the mapping of interoceptive measures to cognition and emotion factors, as well as help to elucidate precise interoceptive alterations observed in clinical conditions.

RapidHRV: an open-source toolbox for extracting heart rate and heart rate variability.

Heart rate and heart rate variability have enabled insight into a myriad of psychophysiological phenomena. There is now an influx of research attempting using these metrics within both laboratory settings (typically derived through electrocardiography or pulse oximetry) and ecologically-rich contexts (via wearable photoplethysmography, i.e., smartwatches). However, these signals can be prone to artifacts and a low signal to noise ratio, which traditionally are detected and removed through visual inspection. Here, we developed an open-source Python package, RapidHRV, dedicated to the preprocessing, analysis, and visualization of heart rate and heart rate variability. Each of these modules can be executed with one line of code and includes automated cleaning. In simulated data, RapidHRV demonstrated excellent recovery of heart rate across most levels of noise (>=10 dB) and moderate-to-excellent recovery of heart rate variability even at relatively low signal to noise ratios (>=20 dB) and sampling rates (>=20 Hz). Validation in real datasets shows good-to-excellent recovery of heart rate and heart rate variability in electrocardiography and finger photoplethysmography recordings. Validation in wrist photoplethysmography demonstrated RapidHRV estimations were sensitive to heart rate and its variability under low motion conditions, but estimates were less stable under higher movement settings.

The Cardiac Timing Toolbox (CaTT): Testing for physiologically plausible effects of cardiac timing on behaviour.

There is a long history of, and renewed interest in, cardiac timing effects on behaviour and cognition. Cardiac timing effects may be identified by expressing events as a function of their location in the cardiac cycle, and applying circular (i.e. directional) statistics to test cardiac time-behaviour associations. Typically this approach 'stretches' all points in the cardiac cycle equally, but this is not necessarily physiologically valid. Moreover, many tests impose distributional assumptions that are not met by such data. We present a set of statistical techniques robust to this, instantiated within our new Cardiac Timing Toolbox (CaTT) for MATLAB: A physiologically-motivated method of wrapping behaviour to the cardiac cycle; and a set of non-parametric statistical tests that control for common confounds and distributional characteristics of these data. Using a reanalysis of previously published data, we guide readers through analyses using CaTT, aiding researchers in identifying physiologically plausible associations between heart-timing and cognition.

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 individuals, both within a single bodily axis (e.g., cardiac) or across bodily axes. Future work can better delineate how these interoceptive measures correspond to different types of processing. Comprehensive interoceptive assessment can help isolate selective interoceptive disruptions in different clinical conditions.

A cross-sectional study of auditory verbal hallucinations experienced by people with a diagnosis of borderline personality disorder.

BACKGROUND: The presence of auditory verbal hallucinations (AVHs) does not currently feature in the main diagnostic criteria for borderline personality disorder (BPD). However, there is accumulating evidence that a high proportion of BPD patients report longstanding and frequent AVHs which constitute a significant risk factor for suicide plans and attempts, and hospitalization. AIM: This study addressed questions about the validity and phenomenology of AVHs in the context of BPD. The longer-term aim is to facilitate the development and translation of treatment approaches to address the unmet need of this population. METHOD: This was a cross-sectional study, combining phenomenological and psychological assessments administered in person and online. We explored the experiences of 48 patients with a diagnosis of BPD who were hearing AVHs. RESULTS: Participants gave 'consistent' reports on the measure of AVH phenomenology, suggesting that these experiences were legitimate. Similar to AVHs in a psychosis context, AVHs were experienced as distressing and appraised as persecutory. AVHs were found to be weakly associated with BPD symptoms. AVHs were also rated highly as a treatment priority by the majority of participants. CONCLUSION: The findings suggest that AVH is a legitimate and distressing symptom of BPD and a treatment priority for some patients. The relative independence of AVHs from other BPD symptoms and emotional states suggests that psychological treatment may need to be targeted specifically at the symptom of AVHs. This treatment could be adapted from cognitive behaviour therapy, the psychological intervention that is recommended for the treatment of AVHs in the context of psychosis.

Voice Hearing in Borderline Personality Disorder Across Perceptual, Subjective, and Neural Dimensions.

BACKGROUND: Auditory verbal hallucinations (AVH) commonly occur in the context of borderline personality disorder (BPD) yet remain poorly understood. AVH are often perceived by patients with BPD as originating from inside the head and hence viewed clinically as "pseudohallucinations," but they nevertheless have a detrimental impact on well-being. METHODS: The current study characterized perceptual, subjective, and neural expressions of AVH by using an auditory detection task, experience sampling and questionnaires, and functional neuroimaging, respectively. RESULTS: Perceptually, reported AVH correlated with a bias for reporting the presence of a voice in white noise. Subjectively, questionnaire measures indicated that AVH were significantly distressing and persecutory. In addition, AVH intensity, but not perceived origin (i.e., inside vs outside the head), was associated with greater concurrent anxiety. Neurally, fMRI of BPD participants demonstrated that, relative to imagining or listening to voices, periods of reported AVH induced greater blood oxygenation level-dependent activity in anterior cingulate and bilateral temporal cortices (regional substrates for language processing). AVH symptom severity was associated with weaker functional connectivity between anterior cingulate and bilateral insular cortices. CONCLUSION: In summary, our results indicate that AVH in participants with BPD are (1) underpinned by aberrant perceptual-cognitive mechanisms for signal detection, (2) experienced subjectively as persecutory and distressing, and (3) associated with distinct patterns of neural activity that inform proximal mechanistic understanding. Our findings are like analogous observations in patients with schizophrenia and validate the clinical significance of the AVH experience in BPD, often dismissed as "pseudohallucinations." These highlight a need to reconsider this experience as a treatment priority.