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Interoceptive mismatch is a perceptual discrepancy between ascending bodily signals and higher-order representation of anticipated physiological state. This mismatch is implicated in emotion inference within predictive coding models. We present autonomic perceptual mismatch as a novel in vivo measure of the discrepancy between actual and perceived autonomic signals, for clinical application to brain-body interactions, specifically in the expression of anxiety. Joint hypermobility is disproportionately found in individuals with anxiety disorders, revealing an underexplored link between the mind and body. Atypical autonomic reactivity represents a likely mediating mechanism consequent of altered connective tissue within the vasculature and nervous system. The present fMRI study determined neural substrates of autonomic perceptual mismatch on affective processing in the hypermobility-anxiety interaction. We compared regional brain activity during emotional face processing in participants with and without hypermobility and generalized anxiety disorder diagnosis, then tested association with perceptual mismatch. In the brain, autonomic perceptual mismatch correlated with enhanced activation in emotion processing and autonomic control regions, notably anterior cingulate cortex. Anxious individuals exhibited increased mid-insula cortex activity in relation to perceptual mismatch. Activity was decreased within the inferior frontal gyrus, a region implicated in cognitive control. Dysautonomia mediated the link between hypermobility and anxiety. Together, these findings support a neural basis of an autonomic perceptual mismatch model in a clinical sample. This is supported by the engagement of neural systems for emotion-cognition and interoception. This work highlights convergent aspects of neurodiversity, mental health, connective tissue disorders and brain-body interactions relevant to precision healthcare.

Individuals vary in their ability to perceive, as conscious sensations, signals like the beating of the heart. Tests of such interoceptive ability are, however, constrained in nature and reliability. Performance of the heartbeat tracking task, a widely used test of cardiac interoception, often corresponds well with individual differences in emotion and cognition, yet is susceptible to reporting bias and influenced by higher-order knowledge, e.g., of expected heart rate. The present study introduces a new way of assessing cardiac interoceptive ability, focusing on sensitivity to short-term, naturalistic changes in frequency of heartbeats. At rest, such heart rate variability typically reflects the dominant influence of respiration on vagus parasympathetic control of the sinoatrial pacemaker. We observed an overall tendency of healthy participants to report feeling fewer heartbeats during increases in heart rate, which we speculate reflects a reduction in heartbeat strength and salience during inspiratory periods when heart rate typically increases to maintain a stable cardiac output. Within-participant performance was more variable on this measure of cardiac interoceptive sensitivity relative to the "classic" heartbeat tracking task. Our findings indicate that cardiac interoceptive ability, rather than reflecting the veridical monitoring of subtle variations in physiology, appears to involve more interpolation wherein interoceptive decisions are informed by dynamic working estimates derived from the integration of afferent signaling and higher-order predictions.

Background\ud The presence of auditory verbal hallucinations (AVH) 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 AVH which constitute a significant risk factor for suicide plans and attempts, and hospitalisation.\ud \ud Aim\ud This study addressed questions about the validity and phenomenology of AVH 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.\ud \ud Method\ud 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 AVH.\ud \ud Results\ud Participants gave ‘consistent’ reports on the measure of AVH phenomenology, suggesting that these experiences were legitimate. Similar to AVH in a psychosis context, AVH were experienced as distressing and appraised as persecutory. AVH were found to be weakly associated with BPD symptoms. AVH were also rated highly as a treatment priority by the majority of participants.\ud \ud Conclusion\ud The findings suggest that AVH is a legitimate and distressing symptom of BPD and a treatment priority for some patients. The relative independence of AVH from other BPD symptoms and emotional states suggests that psychological treatment may need to be targeted specifically at the symptom of AVH. This treatment could be adapted from Cognitive Behaviour Therapy, the psychological intervention that is recommended for the treatment of AVH in the context of psychosis.

In order to survive, organisms must effectively respond to the challenge of maintaining their physiological integrity in the face of an ever-changing environment. Preserving this homeostasis critically relies on adaptive behavior. In this review, we consider recent frameworks that extend classical homeostatic control via reflex arcs to include more flexible forms of adaptive behavior and that take interoceptive context, experiences and expectations into account. Specifically, we define a landscape for computational models of interoception, body regulation and forecasting, address these models’ unique challenges in relation to translational research efforts, and discuss what they can teach us about cognition as well as physical and mental health.

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.

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.

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.

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.

Autism symptomology has a profound impact on cognitive and affective functioning, yet we know relatively little about how it shapes patterns of ongoing thought. In an exploratory study in a large population of neurotypical individuals, we used experience sampling to characterise the relationship between ongoing cognition and self-reported autistic traits. We found that with increasing autistic symptom score, cognition was characterised by thinking more in words than images. Analysis of structural neuroimaging data found that autistic traits linked to social interaction were associated with greater cortical thickness in a region of lingual gyrus (LG) within the occipital cortex. Analysis of resting state functional neuroimaging data found autistic traits were associated with stronger connectivity between the LG and a region of motor cortex. Importantly, the strength of connectivity between the LG and motor cortex moderated the link between autistic symptoms and thinking in words: individuals showing higher connectivity showed a stronger association between autistic traits and thinking in words. Together we provide behavioural and neural evidence linking autistic traits to the tendency to think in words which may be rooted in underlying cortical organisation. These observations lay the groundwork for research into the form and content of self-generated thoughts in individuals with the established diagnosis of autism.

Objective: The current article discusses recent literature on perceptual processing in autism and aims to provide a critical review of existing theories of autistic perception and suggestions for future work. \ud \ud Method: We review findings detailing exteroceptive and interoceptive processing in autism and discuss their neurobiological basis as well as potential links and analogies between sensory domains. \ud \ud Results: Many atypicalities of autistic perception described in the literature can be explained either by weak neural synchronization or by atypical perceptual inference. Evidence for both mechanisms is found across the different sensory domains considered in this review. \ud \ud Conclusions: We argue that weak neural synchronization and atypical perceptual inference might be complementary neural mechanisms that describe the complex bottom-up and top-down differences of autistic perception, respectively. Future work should be sensitive to individual differences to determine if divergent patterns of sensory processing are observed within individuals, rather than looking for global changes at a group level. Determining whether divergent patterns of exteroceptive and interoceptive sensory processing may contribute to prototypical social and cognitive characteristics of autism may drive new directions in our conceptualization of autism

ObjectiveEmotional states are expressed in body and mind through subjective experience of physiological changes. In previous work, subliminal priming of anger prior to lexical decisions increased systolic blood pressure (SBP). This increase predicted the slowing of response times (RT), suggesting that baroreflex-related autonomic changes and their interoceptive (feedback) representations, influence cognition. Alexithymia is a subclinical affective dysfunction characterized by difficulty in identifying emotions. Atypical autonomic and interoceptive profiles are observed in alexithymia. Therefore, we sought to identify mechanisms through which SBP fluctuations during emotional processing might influence decision-making, including whether alexithymia contributes to this relationship.MethodsThirty-two male participants performed an affect priming paradigm and completed the Toronto Alexithymia Scale. Emotional faces were briefly presented (20ms) prior a short-term memory task. RT, accuracy and SBP were recorded on a trial-by-trial basis. Generalized mixed-effects linear models were used to evaluate the impact of emotion, physiological changes, alexithymia score, and their interactions, on performances.ResultsA main effect of emotion was observed on accuracy. Participants were more accurate on trials with anger primes, compared to neutral priming. Greater accuracy was related to increased SBP. An interaction between SBP and emotion was observed on RT: Increased SBP was associated with RT prolongation in the anger priming condition, yet this relationship was absent under the sadness priming. Alexithymia did not significantly moderate the above relationships.ConclusionsOur data suggest that peripheral autonomic responses during affective challenges guide cognitive processes. We discuss our findings in the theoretical framework proposed by Lacey and Lacey (1970).

Rates of loneliness are substantially higher among autistic individuals compared to the non-autistic population. This observation refutes the persistent stereotype that autistic individuals are not motivated to seek meaningful social relationships. In this two-part, mixed-methods study, we sought to quantify the level of distress associated with loneliness in autistic and non-autistic adults and gain qualitative insight into autistic experiences of loneliness. In Study A, N=209 participants completed questionnaire ratings of their level of loneliness, associated distress, trait anxiety, depression, and sensory sensitivity. In Study B, nine autistic adults took part in ten-minute, unstructured dyadic conversations around the topic of loneliness. We derived a qualitative understanding of autistic individuals’ experience of loneliness, enriched by inductive and deductive analyses. The autistic group scored significantly higher across all measures and both groups displayed strong correlations between loneliness and loneliness distress. The effect of loneliness on anxiety was mediated by increased sensory sensitivity in the autistic group. Our results oppose the ‘social motivation deficit’ hypothesis and we instead frame our findings within the larger context of ‘ethical loneliness’, concluding that to enable meaningful and inclusive social interaction, a societal effort is needed to create spaces that consider the sensory needs of all neurotypes.

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.To ascertain the causal effect of acute changes of serotonin levels on cardiac interoception.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.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.An acute change of serotonin levels can increase insight into the reliability of inferences made from cardiac interoceptive sensations.

Interoceptive processes in Tourette syndrome may foster the premonitory urges that commonly precede tics. Twenty-one adults with TS and 22 controls completed heartbeat tracking and discrimination tasks. Three dimensions of interoception were examined: objective accuracy, metacognitive awareness, and subjective (self-report) sensibility. Trait interoceptive prediction error was calculated as the discrepancy between accuracy and sensibility. Participants with TS had numerically lower interoceptive accuracy on the heartbeat tracking task, and increased self-reported interoceptive sensibility. While these group differences were not significant, the discrepancy between lower interoceptive accuracy and heightened sensibility, i.e. the trait interoceptive prediction error, was significantly greater in TS compared to controls. This suggests a heightened higher-order sensitivity to bodily sensations in TS, relative to a noisier perceptual representation of afferent bodily signals. Moreover, interoceptive sensibility predicted the severity of premonitory sensations and tics. This suggests interventions that work to align dimensions of interoceptive experience in TS hold therapeutic potential.

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.

Summary Rotten food, maggots, bodily waste—all elicit disgust in humans. Disgust promotes survival by encouraging avoidance of disease vectors1 but is also implicated in prejudice toward minority groups; avoidance of environmentally beneficial foods, such as insect protein; and maladaptive avoidance behavior in neuropsychiatric conditions.2, 3, 4, 5 Unlike fear, pathological disgust is not improved substantially by exposure therapy clinically,6 nor in experimental work does behavioral avoidance of disgusting images habituate following prolonged exposure.7,8 Under normal physiological conditions, perception of disgusting stimuli disrupts myoelectrical rhythms in the stomach,9, 10, 11, 12, 13 inducing gastric dysrhythmias that correlate with neural signatures of disgust.11 However, the causal role of gastric rhythm in disgust avoidance is unknown. We manipulated gastric rhythm using domperidone, a peripheral dopamine D2/D3 antagonist and common anti-emetic, at a dose (10 mg) that acts to convert gastric dysrhythmias to normal rhythms.9 In a preregistered, randomized, double-blind, placebo-controlled crossover design in 25 healthy volunteers (aged 18–25), we measured the effects of domperidone on core disgust avoidance, using eye tracking to measure implicit (oculomotor) avoidance of disgusting images (feces) before and after an “exposure” intervention (monetary reinforcement for looking at disgusting images).7,8 We find that domperidone significantly reduces oculomotor disgust avoidance following incentivized exposure. This suggests that domperidone may weaken the “immunity” of disgust to habituation, putatively by reducing gastric dysrhythmias during incentivized engagement with disgusting stimuli. This indicates a causal role for disgust-related visceral changes in disgust avoidance, supporting the hypothesis that physiological homeostasis contributes to emotional experience., Highlights • Healthy volunteers were given domperidone to normalize gastric rhythm or placebo • We measured the effect of an exposure paradigm on oculomotor disgust avoidance • Domperidone reduced oculomotor disgust avoidance after the exposure intervention • This suggests gastric rhythm has a causal role in disgust avoidance, It is unknown whether gastric dysrhythmias contribute to disgust avoidance. By normalizing gastric state with domperidone and measuring oculomotor avoidance of disgusting images, Nord et al. discover that domperidone reduces oculomotor disgust avoidance following an exposure task. This suggests that gastric rhythm is one cause of disgust avoidance.

The study of the brain’s processing of sensory inputs from within the body (‘interoception’) has been gaining rapid popularity in neuroscience, where interoceptive disturbances are thought to exist across a wide range of chronic physiological and psychological conditions. Here we present a task and analysis procedure to quantify specific dimensions of breathing-related interoception, including interoceptive sensitivity, decision bias, metacognitive bias, and metacognitive performance. Two major developments address some of the challenges presented by low trial numbers in interoceptive experiments: (i) a novel adaptive algorithm to maintain task performance at 70–75% accuracy; (ii) an extended hierarchical metacognitive model to estimate regression parameters linking metacognitive performance to relevant (e.g. clinical) variables. We demonstrate the utility of the task and analysis developments, using both simulated data and three empirical datasets. This methodology represents an important step towards accurately quantifying interoceptive dimensions from a simple experimental procedure that is compatible with clinical settings., Biological Psychology, 165, ISSN:0301-0511, ISSN:1873-6246

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.

Interoception is the signalling, perception, and interpretation of internal physiological states. Much of the psychopharmacology of interoception is still undiscovered. However, psychiatric disorders associated with changes of interoception, including depressive, anxiety, and eating disorders are often treated with selective serotonin reuptake inhibitors (SSRIs). The causal effect of acute changes of serotonergic signaling on interoceptive cognition was tested by a within-participant, crossover, placebo-controlled study. Forty-seven healthy human volunteers (31 female, 16 male) were tested both on and off a 20mg oral dose of the commonly prescribed SSRI citalopram. For each randomly ordered session, participants made judgments on the synchrony of their heartbeat to auditory tones and expressed confidence in each of these judgments. Citalopram enhanced insight into the likelihood that one's interoceptive judgment had been correct, driven primarily by enhanced confidence for correct responses. This effect was independent of measured cardiac and subjective effects of the drug. This novel result is evidence that acute serotonin changes can alter metacognitive insight into the reliability of inferences based on interoceptive information, which is a foundation for considering effects of serotonin on cognition and emotion in terms of effective top-down regulation of interoceptive influence on mental states.

The majority of interoceptive tasks (i.e. measuring the sensitivity to bodily signals) are based upon the heartbeat sensations perception. However, temporal perception of heartbeats varies among individuals and confidence and spatial perception of heartbeats in relation to temporal judgements have not yet been systematically investigated. This study examined the perception of heartbeat sensations in both time and spatial domains, using a multi-interval heartbeat discrimination task. The relationship between these domains was investigated, as well as the contribution of mental health conditions and cardiovascular parameters. Heartbeat sensations occurred on average ~250ms after the ECG R-wave and were more frequently sampled from the left part of the chest. Participants’ confidence in their experience of heartbeat sensations was maximal for the 0 ms interval. Interestingly, higher confidence was related to reduced dispersion of sampling locations but we found evidence toward the absence of relationship between temporal and spatial heartbeat sensations perception, using Bayesian statistics. Finally, we found evidence toward a relationship between spatial precision of heartbeat sensations and state anxiety score, which seems independent from the cardiovascular parameters. This systematic investigation of heartbeat sensations perception provides important fresh insights, informing the mechanistic understanding of the interoceptive signaling contribution to emotion, cognition and behaviour.

Mental processes are recognized to be embodied, hence dependent upon functions of the body. Interoception (i.e., the sense of the internal bodily physiology) underpinning motivational states and emotional feelings, however, are mostly ignored within present sensory-motor accounts of embodiment. The inclusion of interoception within models of embodiment is important both for health psychology and for theories of cognition. Here, we deduce that reference to visceral organs, in language describing emotion concepts, should be viewed as metonymy (i.e., the mental mapping wherein a component is used to describe the whole), rather than metaphor (i.e., one familiar and concrete concept used to describe another unfamiliar and/or abstract concept that shares some similarities). This view contrasts with a dominant assumption within cognitive linguistics. We further argue that conceptual differences in the assumption about the body-mind-emotion relationship or emotional somatization, evident when comparing Chinese to standard English, is culturally and cognitively determined (e.g., by divergent Western and Chinese philosophical, medical traditions and meaning systems). We propose a new model in which two contending variables, bodily transparency and cognitive granularity, define cultural differences in emotion conceptualization, capturing the dynamic multidimensional interaction between body, mind, brain, language, and society.

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 in metacognitive awareness and subjective interoceptive measures were found. With gastric interoception, SLs were more sensitive to stomach distention, and they ingested less water than SDs to reach satiety when accounting for stomach capacity. SLs also scored higher on mindful and intuitive eating scales and on emotional eating particularly in response to negative stimuli; emotional overeating was fully mediated via interoceptive performance. Overall, our data suggest the SL phenotype may reflect enhanced responsiveness to internal cues more broadly.

Tourette syndrome is characterized by ‘unvoluntary’ tics, which are compulsive, yet often temporarily suppressible. The inferior frontal gyrus is implicated in motor control, including inhibition of pre-potent actions through influences on downstream subcortical and motor regions. Although tic suppression in Tourette syndrome also engages the inferior frontal gyrus, it is unclear whether such prefrontal control of action is also dysfunctional: Tic suppression studies do not permit comparison with control groups, and neuroimaging studies of motor inhibition can be confounded by the concurrent expression or suppression of tics. Here, patients with Tourette syndrome were directly compared to control participants when performing an intentional inhibition task during functional MRI. Tic expression was recorded throughout for removal from statistical models. Participants were instructed to make a button press in response to Go cues, withhold responses to NoGo cues, and decide whether to press or withhold to ‘Choose’ cues. Overall performance was similar between groups, for both intentional inhibition rates (% Choose-Go) and reactive NoGo inhibition commission errors. A subliminal face prime elicited no additional effects on intentional or reactive inhibition. Across participants, the task activated prefrontal and motor cortices and subcortical nuclei, including pre-supplementary motor area, inferior frontal gyrus, insula, caudate nucleus, thalamus and primary motor cortex. In Tourette syndrome, activity was elevated in the inferior frontal gyrus, insula and basal ganglia, most notably within the right inferior frontal gyrus during voluntary action and inhibition (Choose-Go and Choose-NoGo), and reactive inhibition (NoGo-correct). Anatomically, the locus of this inferior frontal gyrus hyperactivation during control of voluntary action matched that previously reported for tic suppression. In Tourette syndrome, activity within the caudate nucleus was also enhanced during both intentional (Choose-NoGo) and reactive (NoGo-correct) inhibition. Strikingly, despite the absence of overt motor behaviour, primary motor cortex activity increased in patients with Tourette syndrome but decreased in controls during both reactive and intentional inhibition. Additionally, severity of premonitory sensations scaled with functional connectivity of the pre-supplementary motor area to the caudate nucleus, globus pallidus and thalamus when choosing to respond (Choose-Go). Together, these results suggest that patients with Tourette syndrome use equivalent prefrontal mechanisms to suppress tics and withhold non-tic actions, but require greater inferior frontal gyrus engagement than controls to overcome motor drive from hyperactive downstream regions, notably primary motor cortex. Moreover, premonitory sensations may cue midline motor regions to generate tics through interactions with the basal ganglia., On an intentional inhibition task, in which participants choose whether to move or not, patients with Tourette syndrome show greater prefrontal engagement to prevent movements. This is accompanied by hyperactivity in downstream motor regions, in particular primary motor cortex, explaining the reason why volitional Tic suppression is effortful., Graphical Abstract

Avolitional tics in Tourette syndrome may be worsened by stress and triggered by social cues such as the facial expressions of others. Rae et al. show that during viewing of emotional faces, the insula is hyperactive in Tourette syndrome and displays increased functional connectivity with cortical and subcortical motor regions., Tourette syndrome is a neurodevelopmental disorder, characterized by motor and phonic tics. Tics are typically experienced as avolitional, compulsive, and associated with premonitory urges. They are exacerbated by stress and can be triggered by external stimuli, including social cues like the actions and facial expressions of others. Importantly, emotional social stimuli, with angry facial stimuli potentially the most potent social threat cue, also trigger behavioural reactions in healthy individuals, suggesting that such mechanisms may be particularly sensitive in people with Tourette syndrome. Twenty-one participants with Tourette syndrome and 21 healthy controls underwent functional MRI while viewing faces wearing either neutral or angry expressions to quantify group differences in neural activity associated with processing social information. Simultaneous video recordings of participants during neuroimaging enabled us to model confounding effects of tics on task-related responses to the processing of faces. In both Tourette syndrome and control participants, face stimuli evoked enhanced activation within canonical face perception regions, including the occipital face area and fusiform face area. However, the Tourette syndrome group showed additional responses within the anterior insula to both neutral and angry faces. Functional connectivity during face viewing was then examined in a series of psychophysiological interactions. In participants with Tourette syndrome, the insula showed functional connectivity with a set of cortical regions previously implicated in tic generation: the presupplementary motor area, premotor cortex, primary motor cortex, and the putamen. Furthermore, insula functional connectivity with the globus pallidus and thalamus varied in proportion to tic severity, while supplementary motor area connectivity varied in proportion to premonitory sensations, with insula connectivity to these regions increasing to a greater extent in patients with worse symptom severity. In addition, the occipital face area showed increased functional connectivity in Tourette syndrome participants with posterior cortical regions, including primary somatosensory cortex, and occipital face area connectivity with primary somatosensory and primary motor cortices varied in proportion to tic severity. There were no significant psychophysiological interactions in controls. These findings highlight a potential mechanism in Tourette syndrome through which heightened representation within insular cortex of embodied affective social information may impact the reactivity of subcortical motor pathways, supporting programmed motor actions that are causally implicated in tic generation. Medicinal and psychological therapies that focus on reducing insular hyper-reactivity to social stimuli may have potential benefit for tic reduction in people with Tourette syndrome.

Fear is coupled to states of physiological arousal. We tested how learning and memory of threat, specifically conditioned fear, is influenced by interoceptive signals. Forty healthy individuals were exposed to two threat (conditioned stimuli [CS+], paired with electrocutaneous shocks) and two safety (CS-) stimuli, time-locked to either cardiac ventricular systole (when arterial baroreceptors signal cardiovascular arousal to brainstem), or diastole (when these afferent signals are quiescent). Threat learning was indexed objectively using skin conductance responses (SCRs). During acquisition of threat contingencies, cardiac effects dominated: Stimuli (both CS+ and CS-) presented at systole evoked greater SCR responses, relative to stimuli (both CS+ and CS-) presented at diastole. This difference was amplified in more anxious individuals. Learning of conditioned fear was established by the end of the acquisition phase, which was followed by an extinction phase when unpaired CSs were presented at either the same or switched cardiac contingencies. One day later, electrocutaneous shocks triggered the reinstatement of fear responses. Subsequent presentation of stimuli previously encoded at systole evoked higher SCRs. Moreover, only those participants for whom stimuli had the same cardiac-contingency over both acquisition and extinction phases retained conditioned fear memory (i.e., CS+ > CS-). Our findings reveal two important cardiac afferent effects on threat learning and memory: 1) Cardiac signals bias processing toward threat; and 2) cardiac signals are a context for fear memory; altering this context can disrupt the memory. These observations suggest how threat reactivity may be reinforced and maintained by both acute and enduring states of cardiac arousal. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Interoception is the sensing of internal bodily sensations. Interoception is an umbrella term that encompasses (1) the afferent (body-to-brain) signaling through distinct neural and humoral (including immune and endocrine) channels; (2) the neural encoding, representation, and integration of this information concerning internal bodily state; (3) the influence of such information on other perceptions, cognitions, and behaviors; (4) and the psychological expression of these representations as consciously accessible physical sensations and feelings. Interoceptive mechanisms ensure physiological health through the cerebral coordination of homeostatic reflexes and allostatic responses that include motivational behaviors and associated affective and emotional feelings. Furthermore, the conscious, unitary sense of self in time and space may be grounded in the primacy and lifelong continuity of interoception. Body-to-brain interactions influence physical and mental well-being. Consequently, we show that systematic investigation of how individual differences, and within-individual changes, in interoceptive processing can contribute to the mechanistic understanding of physical and psychological disorders. We present a neurobiological overview of interoception and describe how interoceptive impairments at different levels relate to specific physical and mental health conditions, including sickness behaviors and fatigue, depression, eating disorders, autism, and anxiety. We frame these findings in an interoceptive predictive processing framework and highlight potential new avenues for treatments.

Threat learning elicits robust changes across multiple affective domains, including changes in autonomic indices and subjective reports of fear and anxiety. It has been argued that the underlying causes of such changes may be dissociable at a neural level, but there is currently limited evidence to support this notion. To address this, we examined the neural mediators of trial-by-trial skin conductance responses (SCR), and subjective reports of anxious arousal and valence in participants (n = 27; 17 females) performing a threat reversal task during ultra-high field functional magnetic resonance imaging. This allowed us to identify brain mediators during initial threat learning and subsequent threat reversal. Significant neural mediators of anxious arousal during threat learning included the dorsal anterior cingulate, anterior insula cortex (AIC), and ventromedial prefrontal cortex (vmPFC), subcortical regions including the amygdala, ventral striatum, caudate and putamen, and brain-stem regions including the pons and midbrain. By comparison, autonomic changes (SCR) were mediated by a subset of regions embedded within this broader circuitry that included the caudate, putamen and thalamus, and two distinct clusters within the vmPFC. The neural mediators of subjective negative valence showed prominent effects in posterior cortical regions and, with the exception of the AIC, did not overlap with threat learning task effects. During threat reversal, positive mediators of both subjective anxious arousal and valence mapped to the default mode network; this included the vmPFC, posterior cingulate, temporoparietal junction, and angular gyrus. Decreased SCR during threat reversal was positively mediated by regions including the mid cingulate, AIC, two sub-regions of vmPFC, the thalamus, and the hippocampus. Our findings add novel evidence to support distinct underlying neural processes facilitating autonomic and subjective responding during threat learning and threat reversal. The results suggest that the brain systems engaged in threat learning mostly capture the subjective (anxious arousal) nature of the learning process, and that appropriate responding during threat reversal is facilitated by participants engaging self- and valence-based processes. Autonomic changes (SCR) appear to involve distinct facilitatory and regulatory contributions of vmPFC sub-regions.

Biological Psychiatry, 3 (6), ISSN:0006-3223, ISSN:1873-2402

Background This trial tested if a novel therapy, Aligning Dimensions of Interoceptive Experience (ADIE), reduces anxiety in autistic adults. ADIE targets the association of anxiety with mismatch between subjective and behavioral measures of an individual's interoceptive sensitivity to bodily signals, including heartbeats. Methods In this superiority randomized controlled trial, autistic adults (18–65 years) from clinical and community settings in Southern England were randomly assigned (1:1) to receive six sessions of ADIE or an active ‘exteroceptive’ control therapy (emotional prosody identification). Researchers conducting outcome assessments were blind to allocation. ADIE combines two modified heartbeat detection tasks with performance feedback and physical activity manipulation that transiently increases cardiac arousal. Participants were followed-up one-week (T1) and 3-months post-intervention (T2). The primary outcome was Spielberger Trait Anxiety Score (STAI-T) at T2. Outcomes were assessed on an intention-to-treat basis using multiple imputation for dealing with missing values. This trial was registered at International Standard Randomized Controlled Trial Registry, ISRCTN14848787. Findings Between July 01, 2017, and December 31, 2019, 121 participants were randomly allocated to ADIE (n = 61) or prosody (n = 60) intervention groups. Data at T1 was provided by 85 (70%) participants (46 [75%] ADIE; 39 [65%] prosody). Data at T2 was provided by 61 (50%) participants (36 [59%] ADIE; 25 [42%] prosody). One adverse event (cardiac anxiety following ADIE) was recorded. A statistically significant group effect of ADIE on trait anxiety continued at T2 (estimated mean difference 3•23 [95% CI 1•13 to 5•29]; d = 0•30 [95% CI 0•09 to 0•51]; p = 0•005) with 31% of ADIE group participants meeting trial criteria for recovery (compared to 16% in the control group). Interpretation ADIE can reduce anxiety in autistic adults, putatively improving regulatory control over internal stimuli. With little reliance on language and emotional insight, ADIE may constitute an inclusive intervention. Funding: MQ Transforming Mental Health PsyImpact Grant.

Interoceptive signals concerning the internal physiological state of the body influence motivational feelings and action decisions. Cardiovascular arousal may facilitate inhibition to mitigate risks of impulsive actions. Baroreceptor discharge at ventricular systole underpins afferent signalling of cardiovascular arousal. In a modified Go/NoGo task, decisions to make or withhold actions on ‘Choose’ trials were not influenced by cardiac phase, nor individual differences in heart rate variability. However, cardiac interoceptive awareness and insight predicted how frequently participants chose to act, and their speed of action: Participants with better awareness and insight tended to withhold actions and respond slower, while those with poorer awareness and insight tended to execute actions and respond faster. Moreover, self-reported trait urgency correlated negatively with intentional inhibition rates. These findings suggest that lower insight into bodily signals is linked to urges to move the body, putatively by engendering noisier sensory input into motor decision processes eliciting reactive behaviour.

The dynamic embodiment of psychological processes is evident in the association of health outcomes, behavioural traits and psychological functioning with Heart Rate Variability (HRV). The dominant high-frequency component of HRV is an index of the central neural control of heart rhythm, mediated via the parasympathetic vagus nerve. HRV provides a potential objective measure of action policies for the adaptive and predictive allostatic regulation of homeostasis within the cardiovascular system. In its support, a network of brain regions (referred to as the 'central autonomic network') maps internal state, and controls autonomic responses. This network includes regions of prefrontal cortex, anterior cingulate cortex, insula, amygdala, periaqueductal grey, pons and medulla. Human neuroimaging studies of neural activation and functional connectivity broadly endorse this architecture, and its link with cardiac regulation at rest and dysregulation in clinical states that include affective disorders. In this review, we appraise neuroimaging research and related evidence for HRV as an informative marker of autonomic integration with affect and cognition, taking a perspective on function and organisation. We consider evidence for the utility of HRV as a metric to inform targeted interventions to improve autonomic and affective dysregulation, and suggest research questions for further investigation.

Background: Interoception, the sense of internal bodily physiology, influences our thoughts and feelings. Interoceptive dysfunction is implicated in some psychiatric disorders. We undertook a systematic characterisation to determine if abnormalities in cardiac interoception underlie symptoms and diagnoses in patients accessing mental health services. Methods: This cross-sectional study recruited 306 patients (clinical diagnoses spanning affective disorders, personality disorder, and psychoses) and 67 controls. We recorded measures of cardiac physiology (heart rate and heart rate variability; HRV); objective interoceptive influences on perception, and subjective (self-report) sensitivity to interoceptive signals. Outcomes: Patients differed from controls in; 1) HRV (RMSSD ms, patients vs controls mean ± SD: 51.6; ± 42.6 vs 70.19 ± 58.4, [F(1,341)=8.8, P=0.003]); 2) cardiac afferent effects on processing emotional stimuli ([fear - neutral] x [systole - diastole] %intensity change: 5.2 ± 16.1 vs 10.5 ± 16.1, [F(1,324)=4.8, P

IntroductionPain, fatigue and anxiety are common features of fibromyalgia and ME/CFS and significantly impact quality of life. Aetiology is poorly defined but dysfunctional inflammatory, autonomic and interoceptive (sensing of internal bodily signals) processes are implicated.ObjectivesTo investigate how altered interoception relates to baseline expression of pain, fatigue and anxiety symptoms in fibromyalgia and ME/CFS and in response to an inflammatory challenge.MethodsSixty-five patients with fibromyalgia and/or ME/CFS diagnosis and 26 matched controls underwent baseline assessment: pressure-pain thresholds and self-report questionnaires assessing pain, fatigue and anxiety severity. Participants received injections of typhoid (inflammatory challenge) or saline (placebo) in a randomised, double-blind, crossover design, before completing heartbeat tracking tasks. Three interoception dimensions were examined: subjective sensibility, objective accuracy and metacognitive awareness. Interoceptive trait prediction error was calculated as discrepancy between accuracy and sensibility.ResultsPatients with fibromyalgia and ME/CFS had significantly higher interoceptive sensibility and trait prediction error, despite no differences in interoceptive accuracy. Interoceptive sensibility and trait prediction error correlated with all self-report pain, fatigue and anxiety measures, and with lower pain thresholds. Anxiety mediated the positive-predictive relationships between pain (Visual Analogue Scale and Widespread Pain Index), fatigue impact and interoceptive sensibility. After inflammatory challenge, metacognitive awareness correlated with baseline self-reported symptom measures and lower pain thresholds.ConclusionsThis is the first study investigating interoceptive dimensions in patients with fibromyalgia and ME/CFS, which were found to be dysregulated and differentially influenced by inflammatory mechanisms. Interoceptive processes may represent a new potential target for diagnostic and therapeutic investigation in these poorly understood conditions.DisclosureNo significant relationships.

Taste hedonics and interoception (sense of internal state of the body; IC) drive ingestive decision-making while the same brain areas mediate both gustatory and IC processes. Yet, no research has tested whether individual variation in IC abilities relates to sweet liking. Here, young female sweet likers (SLs; n=32) and sweet dislikers (SDs; n=34) completed a bimodal IC protocol. Cardiac IC was determined by a heartbeat detection (HDe) and a heartbeat discrimination (HDi) task accompanied by confidence ratings. To test gastric IC, a water load task was used. Participants’ motivational state and behavioural characteristics were also assessed. SLs performed better than SDs on both HDe and HDi tasks independently of anxiety, depression, and alexithymia. No differences in IC awareness and subjective IC measures were found. With gastric IC, SLs were more sensitive to stomach distention, ingesting less water than SDs to reach satiety but more for fullness. SLs scored higher on mindful and intuitive eating. Our data suggest that SL phenotype may reflect enhanced responsiveness to internal cues. Using sweet liking phenotypes to identify predisposition to poorer IC abilities and hence to food choices beyond internal needs seems promising.

Background Generalized anxiety disorder (GAD) is characterized by the core symptom of uncontrollable worry. Functional magnetic resonance imaging studies link this symptom to aberrant functional connectivity between the amygdala and prefrontal cortex. Patients with GAD also display a characteristic pattern of autonomic dysregulation. Although frontolimbic circuitry is implicated in the regulation of autonomic arousal, no previous study to our knowledge combined functional magnetic resonance imaging with peripheral physiologic monitoring in these patients to test the hypothesis that core symptoms of worry and autonomic dysregulation in GAD arise from a shared underlying neural mechanism. Methods We used resting-state functional magnetic resonance imaging and the measurement of parasympathetic autonomic function (heart rate variability) in 19 patients with GAD and 21 control subjects to define neural correlates of autonomic and cognitive responses before and after induction of perseverative cognition. Seed-based analyses were conducted to quantify brain changes in functional connectivity with the right and left amygdala. Results Before induction, patients showed relatively lower connectivity between the right amygdala and right superior frontal gyrus, right paracingulate/anterior cingulate cortex, and right supramarginal gyrus than control subjects. After induction, such connectivity patterns increased in patients with GAD and decreased in control subjects, and these changes tracked increases in state perseverative cognition. Moreover, decreases in functional connectivity between the left amygdala and subgenual cingulate cortex and between the right amygdala and caudate nucleus predicted the magnitude of reduction in heart rate variability after induction. Conclusions Our results link functional brain mechanisms underlying worry and rumination to autonomic dyscontrol, highlighting overlapping neural substrates associated with cognitive and autonomic responses to the induction of perseverative cognitions in patients with GAD.

In grapheme-colour synaesthesia (GCS), the presentation of letters or numbers induces an additional ‘concurrent’ experience of colour. Early functional MRI (fMRI) investigations of GCS reported activation in colour-selective area V4 during the concurrent experience. However, others have failed to replicate this key finding. We reasoned that individual differences in synaesthetic phenomenology might explain this inconsistency in the literature. To test this hypothesis, we examined fMRI BOLD responses in a group of grapheme-colour synaesthetes (n=20) and matched controls (n=20) while characterising the individual phenomenology of the synaesthetes along dimensions of ‘automaticity’ and ‘localisation’. We used an independent functional localiser to identify colour-selective areas in both groups. Activations in these areas were then assessed during achromatic synaesthesia-inducing, and non-inducing conditions; we also explored whole brain activations, where we sought to replicate the existing literature regarding synaesthesia effects. Controls showed no significant activations in the contrast of inducing > non-inducing synaesthetic stimuli, in colour-selective ROIs or at the whole brain level. In the synaesthete group, we correlated activation within colour-selective ROIs with individual differences in phenomenology using the Coloured Letters and Numbers (CLaN) questionnaire which measures, amongst other attributes, the subjective automaticity/attention in synaesthetic concurrents, and their spatial localisation. Supporting our hypothesis, we found significant correlations between individual measures of synaesthetic phenomenology and BOLD responses in colour-selective areas, when contrasting inducing against non-inducing stimuli. Specifically, left-hemisphere colour area responses were stronger for synaesthetes scoring high on phenomenological localisation and automaticity/attention, while right-hemisphere colour area responses showed a relationship with localisation only. In exploratory whole brain analyses, the BOLD response within several other areas was also correlated with these phenomenological factors, including the intra-parietal sulcus, insula, precentral and supplementary motor areas. Our findings reveal a network of regions underlying synaesthetic phenomenology and they help reconcile the diversity of previous results regarding colour-selective BOLD responses during synaesthesia, by establishing a bridge between neural responses and individual synaesthetic phenomenology.

Mental processes depend upon a dynamic integration of brain and body. Emotions encompass internal physiological changes which, through interoception (sensing bodily states), underpin emotional feelings, for example, cardiovascular arousal can intensify feelings of fear and anxiety. The brain is informed about how quickly and strongly the heart is beating by signals from arterial baroreceptors. These fire in bursts after each heartbeat, and are quiet between heartbeats. The processing of fear stimuli is selectively enhanced by these phasic signals, and these inhibit the processing of other types of stimuli including physical pain. Behavioural and neuroimaging studies detail this differential impact of heart signals on the processing of salient stimuli, and add to knowledge linking rhythmic activity in brain and body to perceptual consciousness.

Objective: Spider phobia is a common form of anxiety disorder for which exposure therapy is an effective first-line treatment. Motivated by the observed modulation of threat processing by afferent cardiac signals; we tested the hypothesis that interoceptive information concerning cardiovascular arousal can influence the outcomes of computerised exposure therapy for spider phobia.\ud \ud Method: Fifty-three normal healthy participants with high spider phobia scores underwent one of three modified computerised exposure protocols, defined by the timing of exposure to brief spider stimuli within the cardiac cycle: Systole (during afferent baroreceptor firing); Diastole (during baroreceptor-quiescent interbeat interval); Random (non-contingent on cardiac cycle). Outcomes were judged on phobic and anxiety measures and physiological data (skin conductance). Subjects were also rated on interoceptive accuracy.\ud \ud Results: Mancova analysis showed that timing group affected the outcome measures (F(10,80)=2.405, p=0.015) and there was a group interaction with interoception ability (F(15,110)=1.808, p=0.045). Subjective symptom reduction (SPQ) was greatest in the Systolic group relative to the other two groups (Diastolic (t=3.115, ptukey=0.009); Random (t=2.438, ptukey=0.048), with greatest reductions in those participants with lower interoceptive accuracy. Behavioural aversion (BAT) reduced more in cardiac-contingent groups than the non-contingent (Random) group (Diastolic (t=3.295, ptukey=0.005); Systolic (t=2.602, ptukey=0.032). Physiological (SCR) responses remained strongest for spider stimuli presented at cardiac systole.\ud \ud Conclusion: Interoceptive information influences exposure benefit. The reduction in the subjective expression of fear/phobia is facilitated by ‘bottom-up’ afferent signals; while improvement in the behavioural expression is further dependent on ‘top-down’ representation of\ud Interoceptive effects in spider phobia treatment\ud self-related physiology (heart rhythm). Individual interoceptive differences moderate these effects, suggesting means to personalise therapy.

Interoception is the body-to-brain axis of sensation concerning the state of the internal body. Interoceptive signals from the heart can modulate emotional processing. Moreover, the degree to which people accurately detect their own heart beating at rest can predict their emotional responsivity. Here we determine how interoceptive signals can modulate the perception of faces by exploiting phasic cardiac activity within a binocular onset rivalry paradigm. We demonstrate that afferent cardiac signals facilitate the early processing of fearful face images in individuals with high interoceptive (heartbeat detection) accuracy: The contraction of heart at cardiac systole enhanced the detection of fearful faces (during initial image selection in rivalrous presentations), and shortened reaction times for subsequent emotional judgements. However, cardiac systole does not lead to an overall bias in increased fear categorisation. Our findings highlight interactive contributions of interoception in shaping perceptual and behavioural aspects of emotional processing. Our results thereby add to empirical data regarding mechanisms of body-brain integration underpinning emotional experience. (Preprint of manuscript under review)