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Attending to heartbeats for interoceptive awareness initiates distinct electrophysiological responses synchronized with the R-peaks of an electrocardiogram (ECG), such as the heartbeat-evoked potential (HEP). Beyond HEP, this study proposes heartbeat-related spectral perturbation (HRSP), a time–frequency map of the R-peak locked electroencephalogram (EEG), and explores its characteristics in identifying interoceptive attention states using a classification approach. HRSPs of EEG brain components specified by independent component analysis (ICA) were used for the offline and online classification of interoceptive states. A convolutional neural network (CNN) designed specifically for HRSP was applied to publicly available data from a binary-state experiment (attending to self-heartbeats and white noise) and data from our four-state classification experiment (attending to self-heartbeats, white noise, time passage, and toe) with diverse input feature conditions of HRSP. From the dynamic state perspective, we evaluated the primary frequency bands of HRSP and the minimal number of averaging epochs required to reflect changing interoceptive attention states without compromising accuracy. We also assessed the utility of group ICA and models for classifying HRSP in new participants. The CNN for trial-by-trial HRSP with actual R-peaks demonstrated significantly higher classification accuracy than HRSP with sham, i.e., randomly positioned, R-peaks. Gradient-weighted class activation mapping highlighted the prominent role of theta and alpha bands between 200–600 ms post-R-peak—features absent in classifications using sham HRSPs. Online classification benefits from employing a group ICA and classification model, ensuring reliable accuracy without individual EEG precollection. These results suggest HRSP’s potential to reflect interoceptive attention states, proposing transformative implications for clinical applications.

Real-time fMRI (rt-fMRI) neurofeedback (NF) training is a novel non-invasive technique for volitional brain modulation. Given the important role of the anterior insula (AI) in human cognitive and affective processes, it has become one of the most investigated regions in rt-fMRI studies. Most rt-fMRI insula studies employed emotional recall/imagery as the regulation strategy, which may be less effective for psychiatric disorders characterized by altered emotional processing. The present study thus aimed to examine the feasibility of a novel interoceptive strategy based on heartbeat detection in rt-fMRI guided AI regulation and its associated behavioral changes using a randomized double-blind, sham feedback-controlled between-subject design. 66 participants were recruited and randomly assigned to receive either NF from the left AI (LAI) or sham feedback from a control region while using the interoceptive strategy. N = 57 participants were included in the final data analyses. Empathic and interoceptive pre-post training changes were collected as behavioral measures of NF training effects. Results showed that participants in the NF group exhibited stronger LAI activity than the control group with LAI activity being positively correlated with interoceptive accuracy following NF training, although there were no significant increases of LAI activity over training sessions. Importantly, ability of LAI regulation could be maintained in a transfer session without feedback. Successful LAI regulation was associated with strengthened functional connectivity of the LAI with cognitive control, memory and learning, and salience/interoceptive networks. The present study demonstrated for the first time the efficacy of a novel regulation strategy based on interoceptive processing in up-regulating LAI activity. Our findings also provide proof of concept for the translational potential of this strategy in rt-fMRI AI regulation of psychiatric disorders characterized by altered emotional processing.

Every day we constantly observe other people receiving rewards. Theoretical accounts posit that vicarious reward processing might be linked to people's sensitivity to internal body states (interoception) and facilitates a tendency to act prosocially. However, the neural processes underlying the links between vicarious reward processing, interoception, and prosocial behaviour are poorly understood. Previous research has linked vicarious reward processing to the anterior cingulate gyrus (ACCg) and the anterior insula (AI). Can we predict someone's propensity to be prosocial or to be aware of interoceptive signals from variability in how the ACCg and AI process rewards? Here, participants monitored rewards being delivered to themselves or a stranger during functional magnetic resonance imaging. Later, they performed a task measuring their willingness to exert effort to obtain rewards for others, and a task measuring their propensity to be aware and use interoceptive respiratory signals. Using multivariate similarity analysis, we show that people's willingness to be prosocial is predicted by greater similarity between self and other representations in the ACCg. Moreover, greater dissimilarity in self-other representations in the AI is linked to interoceptive propensity. These findings highlight that vicarious reward is linked to bodily signals in AI, and foster prosocial tendencies through the ACCg.

Feeling happy, or judging whether someone else is feeling happy are two distinct facets of emotions that nevertheless rely on similar physiological and neural activity. Differentiating between these two states, also called Self/Other distinction, is an essential aspect of empathy, but how exactly is it implemented? In non-emotional cognition, the transient neural response evoked at each heartbeat, or heartbeat evoked response (HER), indexes the self and signals Self/Other distinction. Here, using electroencephalography (n = 32), we probe whether HERs’ role in Self/Other distinction extends also to emotion – a domain where brain-body interactions are particularly relevant. We asked participants to rate independently validated affective scenes, reporting either their own emotion (Self) or the emotion expressed by people in the scene (Other). During the visual cue indicating to adopt the Self or Other perspective, before the affective scene, HERs distinguished between the two conditions, in visual cortices as well as in the right frontal operculum. Physiological reactivity (facial electromyogram, skin conductance, heart rate) during affective scene co-varied as expected with valence and arousal ratings, but also with the Self- or Other- perspective adopted. Finally, HERs contributed to the subjective experience of valence in the Self condition, in addition to and independently from physiological reactivity. We thus show that HERs represent a trans-domain marker of Self/Other distinction, here specifically contributing to experienced valence. We propose that HERs represent a form of evidence related to the ‘I’ part of the judgement ‘To which extent do I feel happy’. The ‘I’ related evidence would be combined with the affective evidence collected during affective scene presentation, accounting at least partly for the difference between feeling an emotion and identifying it in someone else.

Attending to heartbeats for interoceptive awareness initiates distinct electrophysiological responses synchronized with the R-peaks of an electrocardiogram (ECG), such as the heartbeat-evoked potential (HEP). Beyond HEP, this study proposes heartbeat-related spectral perturbation (HRSP), a time–frequency map of the R-peak locked electroencephalogram (EEG), and explores its characteristics in identifying interoceptive attention states using a classification approach. HRSPs of EEG brain components specified by independent component analysis (ICA) were used for the offline and online classification of interoceptive states. A convolutional neural network (CNN) designed specifically for HRSP was applied to publicly available data from a binary-state experiment (attending to self-heartbeats and white noise) and data from our four-state classification experiment (attending to self-heartbeats, white noise, time passage, and toe) with diverse input feature conditions of HRSP. From the dynamic state perspective, we evaluated the primary frequency bands of HRSP and the minimal number of averaging epochs required to reflect changing interoceptive attention states without compromising accuracy. We also assessed the utility of group ICA and models for classifying HRSP in new participants. The CNN for trial-by-trial HRSP with actual R-peaks demonstrated significantly higher classification accuracy than HRSP with sham, i.e., randomly positioned, R-peaks. Gradient-weighted class activation mapping highlighted the prominent role of theta and alpha bands between 200–600 ms post-R-peak—features absent in classifications using sham HRSPs. Online classification benefits from employing a group ICA and classification model, ensuring reliable accuracy without individual EEG precollection. These results suggest HRSP's potential to reflect interoceptive attention states, proposing transformative implications for clinical applications. • Heartbeat-related spectral perturbations (HRSP) is proposed for interoception. • HRSP is a time–frequency EEG characteristic tied to heartbeats. • CNN model effectively classifies interoceptive attention states using HRSP. • Group models enhance the individual classification of interoceptive states. [ABSTRACT FROM AUTHOR]

• Visual stimuli encountering stronger cardiac signals were selectively suppressed. • Frequent cardio-visual coincidences lead to a larger heartbeat evoked potential. • Frequent cardio-visual coincidences lead to reduced visual sensitivity. • Internal cardiac processing trades-off with external visual processing. • Bodily signals adjust resource allocation along the internal-external axis. Internal bodily signals, such as heartbeats, can influence conscious perception of external sensory information. Spontaneous shifts of attention between interoception and exteroception have been proposed as the underlying mechanism, but direct evidence is lacking. Here, we used steady-state visual evoked potential (SSVEP) frequency tagging to independently measure the neural processing of visual stimuli that were concurrently presented but varied in heartbeat coupling in healthy participants. Although heartbeat coupling was irrelevant to participants' task of detecting brief color changes, we found decreased SSVEPs for systole-coupled stimuli and increased SSVEPs for diastole-coupled stimuli, compared to non-coupled stimuli. These results suggest that attentional and representational resources allocated to visual stimuli vary according to fluctuations in cardiac-related signals across the cardiac cycle, reflecting spontaneous and immediate competition between cardiac-related signals and visual events. Furthermore, frequent coupling of visual stimuli with stronger cardiac-related signals not only led to a larger heartbeat evoked potential (HEP) but also resulted in a smaller color change evoked N2 component, with the increase in HEP amplitude associated with a decrease in N2 amplitude. These findings indicate an overall or longer-term increase in brain resources allocated to the internal domain at the expense of reduced resources available for the external domain. Our study highlights the dynamic reallocation of limited processing resources across the internal-external axis and supports the trade-off between interoception and exteroception. [ABSTRACT FROM AUTHOR]

Emotional experiences are proposed to arise from contextualized perception of bodily responses, also referred to as interoceptive inferences. The recognition of emotions benefits from adequate access to one's own interoceptive information. However, direct empirical evidence of interoceptive inferences and their neural basis is still lacking. In the present fMRI study healthy volunteers performed a probabilistic emotion classification task with videotaped dynamically unfolding facial expressions. In a first step, we aimed to determine functional areas involved in the processing of dynamically unfolding emotional expressions. We then tested whether individuals with higher interoceptive accuracy (IAcc), as assessed by the Heartbeat detection task (HDT), or higher interoceptive sensitivity (IS), as assessed by the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2), benefit more from the contextually given likelihood of emotional valence and whether brain regions reflecting individual IAcc and/or IS play a role in this. Individuals with higher IS benefitted more from the biased probability of emotional valence. Brain responses to more predictable emotions elicited a bilateral activity pattern comprising the inferior frontal gyrus and the posterior insula. Importantly, individual IAcc scores positively covaried with brain responses to more surprising and less predictable emotional expressions in the insula and caudate nucleus. We show for the first time that IAcc score is associated with enhanced processing of interoceptive prediction errors, particularly in the anterior insula. A higher IS score seems more likely to be associated with a stronger weighting of attention to interoceptive changes processed by the posterior insula and ventral prefrontal cortex.

Many studies have elucidated the multisensory processing of different exteroceptive signals (e.g., auditory-visual stimuli), but less is known about the multisensory integration of interoceptive signals with exteroceptive information. Here, we investigated the perceptual outcomes and electrophysiological brain mechanisms of cardio-visual integration by using participants’ electrocardiogram signals to control the color change of a visual target in dynamically changing displays. Reaction times increased when the target change coincided with strong cardiac signals concerning the state of cardiovascular arousal (i.e., presented at the end of ventricular systole), compared to when the target change occurred at a time when cardiac arousal was relatively low (i.e., presented at the end of ventricular diastole). Moreover, the concurrence of the target change and cardiac arousal signals modulated the event-related potentials and the beta power in an early period (~100 ms after stimulus onset), and decreased the N2pc and the beta lateralization in a later period (~200 ms after stimulus onset). Our results suggest that the multisensory integration of anticipated cardiac signals with a visual target negatively affects its detection among multiple visual stimuli, potentially by suppressing sensory processing and reducing attention toward the visual target. This finding highlights the role of cardiac information in visual processing and furthers our understanding of the brain dynamics underlying multisensory perception involving both interoception and exteroception.

Respiration and heartbeat continuously interact within the living organism at many different levels, representing two of the main oscillatory rhythms of the body and providing major sources of interoceptive information to the brain. Despite the modulatory effect of respiration on exteroception and cognition has been recently established in humans, its role in shaping interoceptive perception has been scarcely investigated so far.In two independent studies, we investigated the effect of spontaneous breathing on cardiac interoception by assessing the Heartbeat Evoked Potential (HEP) in healthy humans. In Study 1, we compared HEP activity for heartbeats occurred during inhalation and exhalation in 40 volunteers at rest. We found higher HEP amplitude during exhalation, compared to inhalation, over fronto-centro-parietal areas. This suggests increased brain-heart interactions and improved cortical processing of the heartbeats during exhalation. Further analyses revealed that this effect was moderated by heart rate changes. In Study 2, we tested the respiratory phase-dependent modulation of HEP activity in 20 volunteers during Exteroceptive and Interoceptive conditions of the Heartbeat Detection (HBD) task. In these conditions, participants were requested to tap at each heartbeat, either listened to or felt, respectively. Results showed higher HEP activity and higher detection accuracy at exhalation than inhalation in the Interoceptive condition only. Direct comparisons of Interoceptive and Exteroceptive conditions confirmed stronger respiratory phase-dependent modulation of HEP and accuracy when attention was directed towards the interoceptive stimuli. Moreover, HEP changes during the Interoceptive condition were independent of heart physiology, but were positively correlated with higher detection accuracy at exhalation than inhalation. This suggests a link between optimization of cortical processing of cardiac signals and detection of heartbeats across the respiratory cycle.Overall, we provide data showing that respiration shapes cardiac interoception at the neurophysiological and behavioural levels. Specifically, exhalation may allow attentional shift towards the internal bodily states.

Prominent theories propose that interoception modulates our behavioral and emotional responses involving decision-making and emotion regulation. Are the regions implicated in interoception also spatially related to and possibly nested within the networks of decision making and emotion regulation? Addressing this question, we performed three meta-analyses of functional magnetic resonance imaging studies to identify the regions that are commonly activated by the three domains using activation likelihood estimation (ALE). Additionally, we assessed the coactivation pattern of identified common regions using meta-analytic connectivity modeling (MACM). The results showed major overlaps of interoception with both decision making and emotion regulation in specifically the right dorsal anterior insula. The pairwise contrast analyses confirmed this finding and revealed conjunction-based activities in decision making and emotion regulation in the dorsal anterior cingulate cortex (dACC). MACM based on the identified insula revealed a widespread convergent coactivation pattern with the left anterior insula, dACC, and bilateral thalamus which, together, constitute the salience network. Among these co-activated regions, bilateral insula and the dACC were shared among all three domains. These results suggest that the regions mediating interoception including intero-exteroceptive integration and salience attribution are contained and thus spatially nested within the more extensive networks recruited during decision making and emotion regulation.

Neuroscientific studies have mainly focused on the way humans perceive and interact with the external world. Recent work in the interoceptive domain indicates that the brain predictively models information from inside the body such as the heartbeat and that the efficiency with which this is executed can have implications for exteroceptive processing. However, to date direct evidence underpinning these hypotheses is lacking. Here, we show how the brain predictively refines neural resources to process afferent cardiac feedback and uses these interoceptive cues to enable more efficient processing of external sensory information. Participants completed a repetition-suppression paradigm consisting of a neutral repeating face. During the first face presentation, they heard auditory feedback of their heartbeat which either coincided with the systole of the cardiac cycle, the time at which cardiac events are registered by the brain or the diastole during which the brain receives no internal cardiac feedback. We used electroencephalography to measure the heartbeat evoked potential (HEP) as well as auditory (AEP) and visual evoked potentials (VEP). Exteroceptive cardiac feedback which coincided with the systole produced significantly higher HEP amplitudes relative to feedback timed to the diastole. Elevation of the HEP in this condition was followed by significant suppression of the VEP in response to the repeated neutral face and a stepwise decrease of AEP amplitude to repeated heartbeat feedback. Our results hereby show that exteroceptive heartbeat feedback coinciding with interoceptive signals at systole enhanced interoceptive cardiac processing. Furthermore, the same cue facilitating interoceptive integration enabled efficient suppression of a visual stimulus, as well as repetition suppression of the AEP across successive auditory heartbeat feedback. Our findings provide evidence that the alignment of external to internal signals can enhance the efficiency of interoceptive processing and that cues facilitating this process in either domain have beneficial effects for internal as well as external sensory processing.

Our perception of the external world is influenced by internal bodily signals. For example, we recently showed that timing of stimulation along the cardiac cycle and spontaneous fluctuations of heartbeat-evoked potential (HEP) amplitudes influence somatosensory perception and the associated neural processing (Al et al., 2020). While cardiac phase affected detection sensitivity and late components of the somatosensory-evoked potentials (SEPs), HEP amplitudes affected detection criterion and both early and late SEP components. In a new EEG study, we investigate whether these results are replicable in a modified paradigm, which includes two succeeding temporal intervals. In one of the intervals, subjects received a weak electrical finger stimulation and reported first whether they detected any stimulation and then allocated the stimulus to one of the two intervals. Our results confirm the previously reported cardiac cycle and prestimulus HEP effects on somatosensory perception and evoked potentials. In addition, we obtained two new findings. Source analyses in this and our original study show that the increased likelihood of conscious perception goes along with HEP fluctuations in parietal and posterior cingulate regions, known to play important roles in interoceptive processes. Furthermore, HEP amplitudes were shown to decrease when subjects engaged in the somatosensory task compared to a resting state condition. Our findings are consistent with the view that HEP amplitudes are a marker of interoceptive (versus exteroceptive) attention and provide a neural underpinning for this view.

Whereas impaired multisensory processing of bodily stimuli and distorted body representation are well-established in various chronic pain disorders, such research has focused on exteroceptive bodily cues and neglected bodily signals from the inside of the body (or interoceptive signals). Extending existing basic and clinical research, we investigated for the first time interoception and its neurophysiological correlates in patients with complex regional pain syndrome (CRPS). In three different experiments, including a total of 36 patients with CRPS and 42 aged-gender matched healthy controls, we measured interoceptive sensitivity (heart beat counting task, HBC) and neural responses to heartbeats (heartbeat evoked potentials, HEPs). As hypothesized, we observed reduced sensitivity in perceiving interoceptive bodily stimuli, i.e. their heartbeat, in two independent samples of CRPS patients (studies 1 and 2). Moreover, the cortical processing of their heartbeat, i.e. the HEP, was reduced compared to controls (study 3) and reduced interoceptive sensitivity and HEPs were related to CRPS patients’ motor impairment and pain duration. By providing consistent evidence for impaired processing of interoceptive bodily cues in CRPS, this study shows that the perceptual changes occurring in chronic pain include signals originating from the visceral organs, suggesting changes in the neural body representation, that includes next to exteroceptive, also interoceptive bodily signals. By showing that impaired interoceptive processing is associated with clinical symptoms, our findings also encourage the use of interoceptive-related information in future rehabilitation for chronic pain.

The hypothalamus and insular cortex play an essential role in the integration of endocrine and homeostatic signals and their impact on food intake. Resting-state functional connectivity alterations of the hypothalamus, posterior insula (PINS) and anterior insula (AINS) are modulated by metabolic states and caloric intake. Nevertheless, a deeper understanding of how these factors affect the strength of connectivity between hypothalamus, PINS and AINS is missing. This study investigated whether effective (directed) connectivity within this network varies as a function of prandial states (hunger vs. satiety) and energy availability (glucose levels and/or hormonal modulation). To address this question, we measured twenty healthy male participants of normal weight twice: once after 36 ​h of fasting (except water consumption) and once under satiated conditions. During each session, resting-state functional MRI (rs-fMRI) and hormone concentrations were recorded before and after glucose administration. Spectral dynamic causal modeling (spDCM) was used to assess the effective connectivity between the hypothalamus and anterior and posterior insula. Using Bayesian model selection, we observed that the same model was identified as the most likely model for each rs-fMRI recording. Compared to satiety, the hunger condition enhanced the strength of the forward connections from PINS to AINS and reduced the strength of backward connections from AINS to PINS. Furthermore, the strength of connectivity from PINS to AINS was positively related to plasma cortisol levels in the hunger condition, mainly before glucose administration. However, there was no direct relationship between glucose treatment and effective connectivity. Our findings suggest that prandial states modulate connectivity between PINS and AINS and relate to theories of interoception and homeostatic regulation that invoke hierarchical relations between posterior and anterior insula.

Following the interoceptive inference framework, we set out to replicate our previously reported association of self-control and interoceptive prediction and strived to investigate the neural underpinnings subserving the relationship between self-control and aversive interoceptive predictive models. To this end, we used fMRI and a within-subject design including an inspiratory breathing-load task to examine the prediction of aversive interoceptive perturbation and a craving-regulation for palatable foods task to measure self-control. In this current study, we could successfully replicate previous effects with an independent sample (n ​= ​39) and observed that individuals who ‘over-estimated’ their upcoming interoceptive state with respect to experienced dyspnea (i.e., anticipated versus experienced) were more effective in the down-regulation of craving using negative future-thinking strategies. These individuals, again, obtained higher scores on a measure of trait self-control, i.e. self-regulation to achieve long-term goals. On a neural level, we found evidence that the anterior insula (AI) and the presupplementary motor area (preSMA), which were recruited in both tasks, partly accounted for these effects. Specifically, levels of AI activation during the anticipation of the aversive interoceptive state (breathing restriction) were associated with self-controlled behavior in the craving task, whereas levels of interoceptive prediction during the breathing task were conversely associated with activation in preSMA during the down-regulation of craving, whose anticipatory activity was correlated with self-control success. Moreover, during the self-control task, levels of interoceptive prediction were associated with connectivity in a spatially distributed network including among other areas the insula and regions of cognitive control, while during the interoceptive prediction task, levels of self-control were associated with connectivity in a spatially distributed network including among other regions the insula and preSMA. In sum, these findings consolidate the notion that self-control is directly linked to interoceptive inference and highlight the contribution of AI and preSMA as candidate regions underlying this relationship possibly creating processing advantages in self-control situations referring to the prediction of future internal states.

Interoception (the sensing of inner-body signals) is a multi-faceted construct with major relevance for basic and clinical neuroscience research. However, the neurocognitive signatures of this domain (cutting across behavioral, electrophysiological, and fMRI connectivity levels) are rarely reported in convergent or systematic fashion. Additionally, various controversies in the field might reflect the caveats of standard interoceptive accuracy (IA) indexes, mainly based on heartbeat detection (HBD) tasks. Here we profit from a novel IA index (md) to provide a convergent multidimensional and multi-feature approach to cardiac interoception. We found that outcomes from our IA-md index are associated with –and predicted by– canonical markers of interoception, including the hd-EEG-derived heart-evoked potential (HEP), fMRI functional connectivity within interoceptive hubs (insular, somatosensory, and frontal networks), and socio-emotional skills. Importantly, these associations proved more robust than those involving current IA indexes. Furthermore, this pattern of results persisted when taking into consideration confounding variables (gender, age, years of education, and executive functioning). This work has relevant theoretical and clinical implications concerning the characterization of cardiac interoception and its assessment in heterogeneous samples, such as those composed of neuropsychiatric patients.

• Self-regulation of insula activity via real-time fMRI neurofeedback. • Interoceptive-based strategy is efficient in regulating insula activity. • Successful regulation of insula activity was associated with interoceptive accuracy. • Successful regulation was associated with increased LAI connectivity with cognitive control and memory/learning networks. • Regulation ability could be maintained in a transfer session without feedback. Real-time fMRI (rt-fMRI) neurofeedback (NF) training is a novel non-invasive technique for volitional brain modulation. Given the important role of the anterior insula (AI) in human cognitive and affective processes, it has become one of the most investigated regions in rt-fMRI studies. Most rt-fMRI insula studies employed emotional recall/imagery as the regulation strategy, which may be less effective for psychiatric disorders characterized by altered emotional processing. The present study thus aimed to examine the feasibility of a novel interoceptive strategy based on heartbeat detection in rt-fMRI guided AI regulation and its associated behavioral changes using a randomized double-blind, sham feedback-controlled between-subject design. 66 participants were recruited and randomly assigned to receive either NF from the left AI (LAI) or sham feedback from a control region while using the interoceptive strategy. N = 57 participants were included in the final data analyses. Empathic and interoceptive pre-post training changes were collected as behavioral measures of NF training effects. Results showed that participants in the NF group exhibited stronger LAI activity than the control group with LAI activity being positively correlated with interoceptive accuracy following NF training, although there were no significant increases of LAI activity over training sessions. Importantly, ability of LAI regulation could be maintained in a transfer session without feedback. Successful LAI regulation was associated with strengthened functional connectivity of the LAI with cognitive control, memory and learning, and salience/interoceptive networks. The present study demonstrated for the first time the efficacy of a novel regulation strategy based on interoceptive processing in up-regulating LAI activity. Our findings also provide proof of concept for the translational potential of this strategy in rt-fMRI AI regulation of psychiatric disorders characterized by altered emotional processing. [ABSTRACT FROM AUTHOR]

Aberrant patterns of brain functional connectivity in the default mode network (DMN) have been observed across different classes of substance use disorder (SUD) and are associated with craving and relapse. In addicted individuals resting functional connectivity (RSFC) of the anterior DMN, which participates in attribution of personal value and emotional regulation, tends to be decreased, whereas RSFC of the posterior DMN, which directs attention to the internal world, tends to be increased. Aberrant RSFC within the DMN is believed to contribute to impaired self-awareness, negative emotions and to ruminations in addiction. Additionally, the disrupted connectivity between DMN and cortical regions involved with executive function, memory and emotion could be critical to drug-taking regardless of negative consequences and to stress-triggered relapse. At the system level, the dynamics of DMN interactions with the executive control and the salience networks are also disturbed in addiction. The DMN is prominently engaged during the withdrawal and preoccupation phases of the addiction cycle at the expense of the executive control network and with an enhanced participation of the salience network. In contrast, DMN prominence appears to be transitorily decreased during the intoxication phases. There is also growing evidence that disruption of the DMN in addiction reflects in part changes in dopaminergic, glutamatergic, and GABAergic signaling associated with acute and chronic drug use. Findings are starting to reveal DMN RSFC as a potential biomarker for predicting clinical outcomes in SUD and identify the DMN as a promising target for the treatment of addiction. • Drug abuse alters DMN connectivity affecting cognitive and emotional processing. • Acute and chronic drug use have different effects on DMN. • Aberrant connectivity of DMN to other regions affects self-related decisions. • DMN loses dynamic interaction with other networks facilitating craving and relapse. • DA dysfunction in drug abusers contributes to DMN dysfunction. [ABSTRACT FROM AUTHOR]

The heart continuously and cyclically communicates with the brain. Beyond homeostatic regulation and sensing, recent neuroscience research has started to shed light on brain-heart interactions in diverse cognitive and emotional processes. In particular, neural responses to heartbeats, as measured with the so-called heartbeat-evoked potential, have been shown to be useful for investigating cortical activity processing cardiac signals. In this review, we first overview and discuss the basic properties of the HEP such as underlying physiological pathways, brain regions, and neural mechanisms. We then provide a systematic review of the mental processes associated with cortical HEP activations, notably heartbeat perception, emotional feelings, perceptual awareness, and self-consciousness, in healthy subjects and clinical populations. Finally, we discuss methodological issues regarding the experimental design and data analysis for separating genuine HEP components from physiological artifacts (e.g., cardiac field artifact, pulse artifact) or other neural activities that are not specifically associated with the heartbeat. Findings from this review suggest that when intrinsic limitations (e.g., artifacts) are carefully controlled, the HEP could provide a reliable neural measure for investigating brain-viscera interactions in diverse mental processes. [ABSTRACT FROM AUTHOR]

Abstract Previous functional neuroimaging studies provided evidence for a specific supraspinal network involved in lower urinary tract (LUT) control. However, data on the reliability of blood oxygenation level-dependent (BOLD) signal changes during LUT task-related functional magnetic resonance imaging (fMRI) across separate measurements are lacking. Proof of the latter is crucial to evaluate whether fMRI can be used to assess supraspinal responses to LUT treatments. Therefore, we prospectively assessed task-specific supraspinal responses from 20 healthy participants undergoing two fMRI measurements (test-retest) within 5–8 weeks. The fMRI measurements, conducted in a 3T magnetic resonance (MR) scanner, comprised a block design of repetitive bladder filling and drainage using an automated MR-compatible and MR-synchronized infusion-drainage device. Following transurethral catheterization and bladder pre-filling with body warm saline until participants perceived a persistent desire to void (START condition), fMRI was recorded during repetitive blocks (each 15 s) of INFUSION and WITHDRAWAL of 100 mL body warm saline into respectively from the bladder. BOLD signal changes were calculated for INFUSION minus START. In addition to whole brain analysis, we assessed BOLD signal changes within multiple 'a priori' region of interest (ROI), i.e. brain areas known to be involved in the LUT control from previous literature. To evaluate reliability of the fMRI results between visits, we applied different types of analyses: coefficient of variation (CV), intraclass correlation coefficient (ICC), Sørensen-Dice index, Bland-Altman method, and block-wise BOLD signal comparison. All participants completed the study without adverse events. The desire to void was rated significantly higher for INFUSION compared to START or WITHDRAWAL at both measurements without any effect of visit. At whole brain level, significant (p < 0.05, cluster corrected, k ≥ 41 voxels) BOLD signal changes were found for the contrast INFUSION compared to START in several brain areas. Overlap of activation maps from both measurements were observed in the orbitofrontal cortex, insula, ventrolateral prefrontal cortex (VLPFC), and inferior parietal lobe. The two highest ICCs, based on a ROI's mean beta weight, were 0.55 (right insular cortex) and 0.47 (VLPFC). Spatial congruency (Sørensen-Dice index) of all voxels within each ROI between measurements was highest in the insular cortex (left 0.55, right 0.44). In addition, the mean beta weight of the right insula and right VLPFC demonstrated the lowest CV and narrowest Bland and Altman 95% limits of agreement. In conclusion, the right insula and right VLPFC were revealed as the two most reliable task-specific ROIs using our automated, MR-synchronized protocol. Achieving high reliability using a viscero-sensory/interoceptive task such as repetitive bladder filling remains challenging and further endeavour is highly warranted to better understand which factors influence fMRI outcomes and finally to assess LUT treatment effects on the supraspinal level. Highligths • First multisession fMRI study on reliability of supraspinal bladder control. • Reliability of supraspinal response is prerequisite to assess LUT treatment effects. • Right insular cortex and VLPFC show most reliable response to bladder filling task. • Automated, MR-synchronized protocol facilitates reliable viscero-sensory tasks. [ABSTRACT FROM AUTHOR]

Abstract Interoceptive signalling has been shown to contribute to action regulation and action experience. Here, we assess whether motor behaviour can be influenced by anticipated homeostatic feeling states induced through different predictable contexts. Participants performed a reward incentive paradigm in which accurate responses increased (gain) or avoided the depletion (averted loss) of a credit score. Across two types of blocks, we varied the predictability of the outcome state. In predictable blocks, a cue signaled a gain, loss or control trial (motor response did not affect the credit score). This allowed participants to anticipate the interoceptive feeling state associated with the outcome. In unpredictable blocks, the cue had no relation to the type of outcome. Thus, participants were unable to anticipate the feeling state it produced. Via EEG, we measured the Heartbeat Evoked Potential (HEP) and the Contingent Negative Variation (CNV) as indices of interoceptive and motor processing respectively. In addition, we measured feedback P3 amplitude following outcome presentation and accuracy and reaction times of the required motor response. We observed higher HEP and CNV amplitudes as well as faster and more accurate motor responses in predictable compared to unpredictable outcome blocks. Similarly, feedback-related P3 amplitudes were significantly lower for predictable relative to unpredictable outcomes. Crucially, HEP amplitudes measured prior to feedback predicted feedback-related P3 amplitudes for anticipated outcome events. Results suggest that accurate anticipation of homeostatic feeling states associated with gain, loss or control outcomes facilitates motor execution and outcome evaluation. Findings are hereby the first to empirically assess the link between interoceptive and motor domains and provide primary evidence for a joint processing structure. Highlights • Heartbeat-evoked responses are higher for predictable affective outcomes. • This effect coincides with enhanced motor performance and outcome evaluation. • Interoceptive signals could have a direct functional relevance for motor actions. [ABSTRACT FROM AUTHOR]

Abstract Imagination is an internally-generated process, where one can make oneself or other people appear as protagonists of a scene. How does the brain tag the protagonist of an imagined scene as being oneself or someone else? Crucially, during imagination, neither external stimuli nor motor feedback are available to disentangle imagining oneself from imagining someone else. Here, we test the hypothesis that an internal mechanism based on the neural monitoring of heartbeats could distinguish between self and other. 23 participants imagined themselves (from a first-person perspective) or a friend (from a third-person perspective) in various scenarios, while their brain activity was recorded with magnetoencephalography and their cardiac activity was simultaneously monitored. We measured heartbeat-evoked responses, i.e. transients of neural activity occurring in response to each heartbeat, during imagination. The amplitude of heartbeat-evoked responses differed between imagining oneself and imagining a friend, in the precuneus and posterior cingulate regions bilaterally. Effect size was modulated by the daydreaming frequency scores of participants but not by their interoceptive abilities. These results could not be accounted for by other characteristics of imagination (e.g., the ability to adopt the perspective, valence or arousal), nor by cardiac parameters (e.g., heart rate) or arousal levels (e.g. arousal ratings, pupil diameter). Heartbeat-evoked responses thus appear as a neural marker distinguishing self from other during imagination. Highlights • Heartbeat-evoked responses differentiate self from other during imagination. • These effects were located in the precuneus and posterior cingulate. • The neural monitoring of the heart could be a mechanism for self/other distinction. [ABSTRACT FROM AUTHOR]

Abstract Theoretical frameworks such as predictive coding suggest that the perception of the body and world – interoception and exteroception – involve intertwined processes of inference, learning, and prediction. In this framework, attention is thought to gate the influence of sensory information on perception. In contrast to exteroception, there is limited evidence for purely attentional effects on interoception. Here, we empirically tested if attentional focus modulates cortical processing of single heartbeats, using a newly-developed experimental paradigm to probe purely attentional differences between exteroceptive and interoceptive conditions in the heartbeat evoked potential (HEP) using EEG recordings. We found that the HEP is significantly higher during interoceptive compared to exteroceptive attention, in a time window of 524–620 ms after the R-peak. Furthermore, this effect predicted self-report measures of autonomic system reactivity. Our study thus provides direct evidence that the HEP is modulated by pure attention and suggests that this effect may provide a clinically relevant readout for assessing interoception. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract The error-related negativity (ERN) is an event-related potential in the electroencephalogram (EEG) observed within the first 100 ms after commission of an error. Increased ERN amplitudes have been observed in several psychological disorders characterized by high negative affect. While the ERN has extensively been studied in tasks using exteroceptive stimuli, its relation to interoceptive stimuli is unknown. Since errors related to interoception might be particularly relevant for survival and negative affect, this study aimed to explore the ERN for errors related to interoceptive, respiratory sensations (intERN). Moreover, we compared the intERN with a commonly observed ERN related to exteroceptive, visual stimuli (extERN) and examined their associations with interoception-related negative affect. We studied the ERN using a respiratory occlusion task (intERN) and a visual flanker task (extERN) in 40 healthy volunteers during continuous 129 channel EEG recordings. In the occlusion task, participants received inspiratory occlusions of two different durations and indicated whether each occlusion was short or long. In the Flanker task, participants indicated the direction of arrowheads. Interoception-related negative affect was assessed with the Anxiety Sensitivity Index. Comparable with the extERN, the intERN was observed at fronto-central scalp positions after error commission in the occlusion task, but it peaked significantly earlier than the extERN. Mean amplitudes of the intERN and extERN showed no significant difference and were not correlated. Moreover, higher levels of anxiety sensitivity were correlated with significantly greater amplitudes of the intERN, but with lower amplitudes of the extERN. The present results firstly demonstrate an error-related negativity EEG-potential that is related to interoceptive sensations (intERN). This intERN is not associated with a commonly observed ERN elicited by exteroceptive stimuli and is distinctly linked to higher levels of interoception-related negative affect. The intERN might be a promising neural marker for future studies on interoception, negative affect and error processing. Highlights • An error-related negativity (ERN) potential for interoceptive sensations is presented • The interoceptive respiratory ERN is not associated with an exteroceptive visual ERN • The interoceptive ERN is linked to higher levels of anxiety sensitivity • The exteroceptive ERN is related to lower levels of anxiety sensitivity [ABSTRACT FROM AUTHOR]

• The hypothalamus regulates sleep-wake cycle and motivated behavior. • Sleep deficit is associated with negative emotions. • Sleep deficit alters hypothalamic rest-state connectivity with the right insula in men. • Anxiety-depression symptom severity and hypothalamic-insula rsFC are related via sleep deficit in men. • Sex differences in hypothalamic dysfunction vs. sleep deficit need more research. The hypothalamus plays a crucial role in regulating sleep-wake cycle and motivated behavior. Sleep disturbance is associated with impairment in cognitive and affective functions. However, how hypothalamic dysfunction may contribute to inter-related sleep, cognitive, and emotional deficits remain unclear. We curated the Human Connectome Project dataset and investigated how hypothalamic resting state functional connectivities (rsFC) were associated with sleep dysfunction, as evaluated by the Pittsburgh Sleep Quality Index (PSQI), cognitive performance, and subjective mood states in 687 young adults (342 women). Imaging data were processed with published routines and evaluated with a corrected threshold. We examined the inter-relationship amongst hypothalamic rsFC, PSQI score, and clinical measures with mediation analyses. In whole-brain regressions with age and drinking severity as covariates, men showed higher hypothalamic rsFC with the right insula in correlation with PSQI score. No clusters were identified in women at the same threshold. Both hypothalamic-insula rsFC and PSQI score were significantly correlated with anxiety and depression scores in men. Further, mediation analyses showed that PSQI score mediated the relationship between hypothalamic-insula rsFC and anxiety/depression symptom severity bidirectionally in men. Sleep dysfunction is associated with negative emotions and hypothalamic rsFC with the right insula, a core structure of the interoceptive circuits. Notably, anxiety-depression symptom severity and altered hypothalamic-insula rsFC are related bidirectionally by poor sleep quality. These findings are specific to men, suggesting potential sex differences in the neural circuits regulating sleep and emotional states that need to be further investigated. [ABSTRACT FROM AUTHOR]

Athletes regularly endure large increases in ventilation and accompanying perceptions of breathlessness. Whilst breathing perceptions often correlate poorly with objective measures of lung function in both healthy and clinical populations, we have previously demonstrated closer matching between subjective breathlessness and changes in ventilation in endurance athletes, suggesting that athletes may be more accurate during respiratory interoception. To better understand the link between exercise and breathlessness, we sought to identify the mechanisms by which the brain processing of respiratory perception might be optimised in athletes. Twenty endurance athletes and twenty sedentary controls underwent 7 T functional magnetic resonance imaging. Inspiratory resistive loading induced conscious breathing perceptions (breathlessness), and a delay-conditioning paradigm was employed to evoke preceding periods of breathlessness-anticipation. Athletes demonstrated anticipatory brain activity that positively correlated with resulting breathing perceptions within key interoceptive areas, such as the thalamus, insula and primary sensorimotor cortices, which was negatively correlated in sedentary controls. Athletes also exhibited altered connectivity between interoceptive attention networks and primary sensorimotor cortex. These functional differences in athletic brains suggest that exercise may alter anticipatory representations of respiratory sensations. Future work may probe whether these brain mechanisms are harnessed when exercise is employed to treat breathlessness within chronic respiratory disease. [ABSTRACT FROM AUTHOR]

• Anticipatory interoceptive signals increase during unexpected social rejection. • Negative HEP modulations reflect larger interoceptive signals in uncertainty. • Key brain allostatic-interoceptive network hubs found via intracranial recordings. • Exteroceptive signals are modulated by anticipation of reward-related outcomes. • Findings inform models of allostatic interoception in social stress. Anticipating social stress evokes strong reactions in the organism, including interoceptive modulations. However, evidence for this claim comes from behavioral studies, often with inconsistent results, and relates almost solely to the reactive and recovery phase of social stress exposure. Here, we adopted an allostatic-interoceptive predictive coding framework to study interoceptive and exteroceptive anticipatory brain responses using a social rejection task. We analyzed the heart-evoked potential (HEP) and task-related oscillatory activity of 58 adolescents via scalp EEG, and 385 human intracranial recordings of three patients with intractable epilepsy. We found that anticipatory interoceptive signals increased in the face of unexpected social outcomes, reflected in larger negative HEP modulations. Such signals emerged from key brain allostatic-interoceptive network hubs, as shown by intracranial recordings. Exteroceptive signals were characterized by early activity between 1-15 Hz across conditions, and modulated by the probabilistic anticipation of reward-related outcomes, observed over distributed brain regions. Our findings suggest that the anticipation of a social outcome is characterized by allostatic-interoceptive modulations that prepare the organism for possible rejection. These results inform our understanding of interoceptive processing and constrain neurobiological models of social stress. [ABSTRACT FROM AUTHOR]

Multiple neuroimaging studies have now linked emotional awareness (EA), as measured by the Levels of Emotional Awareness Scale (LEAS), with activation in regions of neural networks associated with both conceptualization (i.e., default mode network [DMN] regions) and interoception (i.e., salience network [SN] regions) – consistent with the definition of EA as one's ability to appropriately recognize, conceptualize, and articulate the emotions of self and other in fine-grained, differentiated ways. However, no study has yet tested the hypothesis that greater LEAS scores are associated with greater resting state functional connectivity (FC) within these networks. Twenty-six adults (13 female) underwent resting state functional magnetic resonance imaging, and also completed the LEAS. Using pre-defined functional ROIs from the DMN and SN, we observed that LEAS scores were significantly positively correlated with FC between several regions of both of these networks, even when controlling for differences in general intelligence (IQ). These results suggest that higher EA may be associated with more efficient information exchange between brain regions involved in both interoception- and conceptualization-based processing, which could plausibly contribute to more differentiated bodily feelings and more fine-grained conceptualization of those feelings. [ABSTRACT FROM AUTHOR]

Multisensory perception research has largely focused on exteroceptive signals, but recent evidence has revealed the integration of interoceptive signals with exteroceptive information. Such research revealed that heartbeat signals affect sensory (e.g., visual) processing: however, it is unknown how they impact the perception of body images. Here we linked our participants' heartbeat to visual stimuli and investigated the spatio-temporal brain dynamics of cardio-visual stimulation on the processing of human body images. We recorded visual evoked potentials with 64-channel electroencephalography while showing a body or a scrambled-body (control) that appeared at the frequency of the on-line recorded participants' heartbeat or not (not-synchronous, control). Extending earlier studies, we found a body-independent effect, with cardiac signals enhancing visual processing during two time periods (77–130 ms and 145–246 ms). Within the second (later) time-window we detected a second effect characterised by enhanced activity in parietal, temporo-occipital, inferior frontal, and right basal ganglia-insula regions, but only when non-scrambled body images were flashed synchronously with the heartbeat (208–224 ms). In conclusion, our results highlight the role of interoceptive information for the visual processing of human body pictures within a network integrating cardio-visual signals of relevance for perceptual and cognitive aspects of visual body processing. [ABSTRACT FROM AUTHOR]

Neural responses in striatal, limbic and somatosensory brain regions track individual differences in loss aversion, i.e. the higher sensitivity to potential losses compared with equivalent gains in decision-making under risk. The engagement of structures involved in the processing of aversive stimuli and experiences raises a further question, i.e. whether the tendency to avoid losses rather than acquire gains represents a transient fearful overreaction elicited by choice-related information, or rather a stable component of one's own preference function, reflecting a specific pattern of neural activity. We tested the latter hypothesis by assessing in 57 healthy human subjects whether the relationship between behavioral and neural loss aversion holds at rest, i.e. when the BOLD signal is collected during 5 minutes of cross-fixation in the absence of an explicit task. Within the resting-state networks highlighted by a spatial group Independent Component Analysis (gICA), we found a significant correlation between strength of activity and behavioral loss aversion in the left ventral striatum and right posterior insula/supramarginal gyrus, i.e. the very same regions displaying a pattern of neural loss aversion during explicit choices. Cross-study analyses confirmed that this correlation holds when voxels identified by gICA are used as regions of interest in task-related activity and vice versa. These results suggest that the individual degree of (neural) loss aversion represents a stable dimension of decision-making, which reflects in specific metrics of intrinsic brain activity at rest possibly modulating cortical excitability at choice. [ABSTRACT FROM AUTHOR]

• Vicarious rewards processing is linked to prosociality and interoception. • Anterior cingulate reward representations can predict prosocial behaviour. • Anterior insula reward representations can predict interoceptive propensity. • More prosocial people are more propense to use interoceptive signals. Every day we constantly observe other people receiving rewards. Theoretical accounts posit that vicarious reward processing might be linked to people's sensitivity to internal body states (interoception) and facilitates a tendency to act prosocially. However, the neural processes underlying the links between vicarious reward processing, interoception, and prosocial behaviour are poorly understood. Previous research has linked vicarious reward processing to the anterior cingulate gyrus (ACCg) and the anterior insula (AI). Can we predict someone's propensity to be prosocial or to be aware of interoceptive signals from variability in how the ACCg and AI process rewards? Here, participants monitored rewards being delivered to themselves or a stranger during functional magnetic resonance imaging. Later, they performed a task measuring their willingness to exert effort to obtain rewards for others, and a task measuring their propensity to be aware and use interoceptive respiratory signals. Using multivariate similarity analysis, we show that people's willingness to be prosocial is predicted by greater similarity between self and other representations in the ACCg. Moreover, greater dissimilarity in self-other representations in the AI is linked to interoceptive propensity. These findings highlight that vicarious reward is linked to bodily signals in AI, and foster prosocial tendencies through the ACCg. [ABSTRACT FROM AUTHOR]

• HERs distinguish between self and other in emotions. • Neural sources in frontal operculum and visual cortices. • Physiological reactivity also encodes perspective. • HERs uniquely contribute to the valence ratings of one's own emotion. Feeling happy, or judging whether someone else is feeling happy are two distinct facets of emotions that nevertheless rely on similar physiological and neural activity. Differentiating between these two states, also called Self/Other distinction, is an essential aspect of empathy, but how exactly is it implemented? In non-emotional cognition, the transient neural response evoked at each heartbeat, or heartbeat evoked response (HER), indexes the self and signals Self/Other distinction. Here, using electroencephalography (n = 32), we probe whether HERs' role in Self/Other distinction extends also to emotion – a domain where brain-body interactions are particularly relevant. We asked participants to rate independently validated affective scenes, reporting either their own emotion (Self) or the emotion expressed by people in the scene (Other). During the visual cue indicating to adopt the Self or Other perspective, before the affective scene, HERs distinguished between the two conditions, in visual cortices as well as in the right frontal operculum. Physiological reactivity (facial electromyogram, skin conductance, heart rate) during affective scene co-varied as expected with valence and arousal ratings, but also with the Self- or Other- perspective adopted. Finally, HERs contributed to the subjective experience of valence in the Self condition, in addition to and independently from physiological reactivity. We thus show that HERs represent a trans-domain marker of Self/Other distinction, here specifically contributing to experienced valence. We propose that HERs represent a form of evidence related to the 'I' part of the judgement 'To which extent do I feel happy'. The 'I' related evidence would be combined with the affective evidence collected during affective scene presentation, accounting at least partly for the difference between feeling an emotion and identifying it in someone else. [ABSTRACT FROM AUTHOR]

• Previous research revealed that the breathing system is involved in diverse motor processes including running, orofacial movements, and even voluntary motor action. • In this study, we investigated whether the breathing system is associated with voluntary initiation of mental actions (i.e., motor and visual imagery) which are not accompanied by any overt movement. • We found that the breathing cycle is synchronized with the onset of self-initiated mental imagery performance which was preceded by the cortical readiness potential. • Our findings suggest breathing-action coupling is involved in more general action preparation processing, regardless of any subsequent motor process. Previous research has suggested that bodily signals from internal organs are associated with diverse cortical and subcortical processes involved in sensory-motor functions, beyond homeostatic reflexes. For instance, a recent study demonstrated that the preparation and execution of voluntary actions, as well as its underlying neural activity, are coupled with the breathing cycle. In the current study, we investigated whether such breathing-action coupling is limited to voluntary motor action or whether it is also present for mental actions not involving any overt bodily movement. To answer this question, we recorded electroencephalography (EEG), electromyography (EMG), and respiratory signals while participants were conducting a voluntary action paradigm including self-initiated motor execution (ME), motor imagery (MI), and visual imagery (VI) tasks. We observed that the voluntary initiation of ME, MI, and VI are similarly coupled with the respiration phase. In addition, EEG analysis revealed the existence of readiness potential (RP) waveforms in all three tasks (i.e., ME, MI, VI), as well as a coupling between the RP amplitude and the respiratory phase. Our findings show that the voluntary initiation of both imagined and overt action is coupled with respiration, and further suggest that the breathing system is involved in preparatory processes of voluntary action by contributing to the temporal decision of when to initiate the action plan, regardless of whether this culminates in overt movements. [ABSTRACT FROM AUTHOR]

Emotions have been shown to exert influences on decision making during economic exchanges. Here we investigate the underlying neural mechanisms of a training regimen which is hypothesized to promote emotional awareness, specifically mindfulness training (MT). We test the hypothesis that MT increases cooperative economic decision making using fMRI in a randomized longitudinal design involving 8 weeks of either MT or active control training (CT). We find that MT results in an increased willingness to cooperate indexed by higher acceptance rates to unfair monetary offers in the Ultimatum Game. While controlling for acceptance rates of monetary offers between intervention groups, subjects in the MT and CT groups show differential brain activation patterns. Specifically, a subset of more cooperative MT subjects displays increased activation in the septal region, an area linked to social attachment, which may drive the increased willingness to express cooperative behavior in the MT cohort. Furthermore, MT resulted in attenuated activity in anterior insula compared with the CT group in response to unfair monetary offers post-training, which may suggest that MT enables greater ability to effectively regulate the anterior insula and thereby promotes social cooperation. Finally, functional connectivity analyses show a coupling between the septal region and posterior insula in the MT group, suggesting an integration of interoceptive inputs. Together, these results highlight that MT may be employed in contexts where emotional regulation is required to promote social cooperation. [ABSTRACT FROM AUTHOR]

There are continuing uncertainties regarding whether performance monitoring recruits the anterior insula (aI) and/or the frontal operculum (fO). The proximity and morphological complexity of these two regions make proper identification and isolation of the loci of activation extremely difficult. The use of group averaging methods in human neuroimaging might contribute to this problem. The result has been heterogeneous labeling of this region as aI, fO, or aI/fO, and a discussion of results oriented towards either cognitive or interoceptive functions depending on labeling. In the present article, we adapted the spatial preprocessing of functional magnetic resonance imaging data to account for group averaging artifacts and performed a subject-by-subject analysis in three performance monitoring tasks. Results show that functional activity related to feedback or action monitoring consistently follows local morphology in this region and demonstrate that the activity is located predominantly in the fO rather than in the aI. From these results, we propose that a full understanding of the respective role of aI and fO would benefit from increased spatial resolution and subject-by-subject analysis. [ABSTRACT FROM AUTHOR]

The Pain and Interoception Imaging Network (PAIN) repository (painrepository.org) is a newly created NIH (NIDA/NCCAM) funded neuroimaging data repository that aims to accelerate scientific discovery regarding brain mechanisms in pain and to provide more rapid benefits to pain patients through the harmonization of efforts and data sharing. The PAIN Repository consists of two components, an Archived Repository and a Standardized Repository . Similar to other ‘open’ imaging repositories, neuroimaging researchers can deposit any dataset of chronic pain patients and healthy controls into the Archived Repository . Scans in the Archived Repository can be very diverse in terms of scanning procedures and clinical metadata, complicating the merging of datasets for analyses. The Standardized Repository overcomes these limitations through the use of standardized scanning protocols along with a standardized set of clinical metadata, allowing an unprecedented ability to perform pooled analyses. The Archived Repository currently includes 741 scans and is rapidly growing. The Standardized Repository currently includes 433 scans. Pain conditions currently represented in the PAIN repository include: irritable bowel syndrome, vulvodynia, migraine, chronic back pain, and inflammatory bowel disease. Both the PAIN Archived and Standardized Repositories promise to be important resources in the field of chronic pain research. The enhanced ability of the Standardized Repository to combine imaging, clinical and other biological datasets from multiple sites in particular make it a unique resource for significant scientific discoveries. [ABSTRACT FROM AUTHOR]

Whilst external events trigger emotional responses, interoception (the perception of internal physiological states) is fundamental to core emotional experience. By combining high resolution functional neuroimaging with concurrent physiological recordings, we investigated the neural mechanisms of interoceptive integration during free listening to an emotionally salient audio film. We found that cardiac activity, a key interoceptive signal, was robustly synchronised across participants and centrally represented in the posterior insula. Effective connectivity analysis revealed that the anterior insula, specifically tuned to the emotionally salient moments of the audio stream, serves as an integration hub of interoceptive processing: interoceptive states represented in the posterior insula are integrated with exteroceptive representations by the anterior insula to highlight these emotionally salient moments. Our study for the first time demonstrates the insular hierarchy for interoceptive processing during natural emotional experience. These findings provide an ecologically-valid framework for elucidating the neural underpinnings of emotional deficits in neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Many studies have elucidated the multisensory processing of different exteroceptive signals (e.g., auditory-visual stimuli), but less is known about the multisensory integration of interoceptive signals with exteroceptive information. Here, we investigated the perceptual outcomes and electrophysiological brain mechanisms of cardio-visual integration by using participants' electrocardiogram signals to control the color change of a visual target in dynamically changing displays. Reaction times increased when the target change coincided with strong cardiac signals concerning the state of cardiovascular arousal (i.e., presented at the end of ventricular systole), compared to when the target change occurred at a time when cardiac arousal was relatively low (i.e., presented at the end of ventricular diastole). Moreover, the concurrence of the target change and cardiac arousal signals modulated the event-related potentials and the beta power in an early period (~100 ms after stimulus onset), and decreased the N2pc and the beta lateralization in a later period (~200 ms after stimulus onset). Our results suggest that the multisensory integration of anticipated cardiac signals with a visual target negatively affects its detection among multiple visual stimuli, potentially by suppressing sensory processing and reducing attention toward the visual target. This finding highlights the role of cardiac information in visual processing and furthers our understanding of the brain dynamics underlying multisensory perception involving both interoception and exteroception. [ABSTRACT FROM AUTHOR]

Respiration and heartbeat continuously interact within the living organism at many different levels, representing two of the main oscillatory rhythms of the body and providing major sources of interoceptive information to the brain. Despite the modulatory effect of respiration on exteroception and cognition has been recently established in humans, its role in shaping interoceptive perception has been scarcely investigated so far. In two independent studies, we investigated the effect of spontaneous breathing on cardiac interoception by assessing the Heartbeat Evoked Potential (HEP) in healthy humans. In Study 1, we compared HEP activity for heartbeats occurred during inhalation and exhalation in 40 volunteers at rest. We found higher HEP amplitude during exhalation, compared to inhalation, over fronto-centro-parietal areas. This suggests increased brain-heart interactions and improved cortical processing of the heartbeats during exhalation. Further analyses revealed that this effect was moderated by heart rate changes. In Study 2, we tested the respiratory phase-dependent modulation of HEP activity in 20 volunteers during Exteroceptive and Interoceptive conditions of the Heartbeat Detection (HBD) task. In these conditions, participants were requested to tap at each heartbeat, either listened to or felt, respectively. Results showed higher HEP activity and higher detection accuracy at exhalation than inhalation in the Interoceptive condition only. Direct comparisons of Interoceptive and Exteroceptive conditions confirmed stronger respiratory phase-dependent modulation of HEP and accuracy when attention was directed towards the interoceptive stimuli. Moreover, HEP changes during the Interoceptive condition were independent of heart physiology, but were positively correlated with higher detection accuracy at exhalation than inhalation. This suggests a link between optimization of cortical processing of cardiac signals and detection of heartbeats across the respiratory cycle. Overall, we provide data showing that respiration shapes cardiac interoception at the neurophysiological and behavioural levels. Specifically, exhalation may allow attentional shift towards the internal bodily states. [ABSTRACT FROM AUTHOR]

• This study provides new insights into how interoceptive accuracy (IAcc), as assessed by the Heartbeat detection task (HDT), and interoceptive sensibility (IS), as assessed by the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2), shape emotion recognition and interoceptive predictions at the behavioral and the brain level. • Higher IS involves more precise adaptation to biased probabilities of emotion. • Brain responses to more predictable emotions elicited a bilateral activity pattern comprising the inferior frontal gyrus and the posterior insula. • Individual IAcc scores positively covaried with brain responses to more surprising and less predictable emotional expressions in the insula and caudate nucleus. • Higher IS might be associated with a stronger weighting of attention to interoceptive changes processed by the posterior insula and ventral prefrontal cortex. Emotional experiences are proposed to arise from contextualized perception of bodily responses, also referred to as interoceptive inferences. The recognition of emotions benefits from adequate access to one's own interoceptive information. However, direct empirical evidence of interoceptive inferences and their neural basis is still lacking. In the present fMRI study healthy volunteers performed a probabilistic emotion classification task with videotaped dynamically unfolding facial expressions. In a first step, we aimed to determine functional areas involved in the processing of dynamically unfolding emotional expressions. We then tested whether individuals with higher interoceptive accuracy (IAcc), as assessed by the Heartbeat detection task (HDT), or higher interoceptive sensitivity (IS), as assessed by the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2), benefit more from the contextually given likelihood of emotional valence and whether brain regions reflecting individual IAcc and/or IS play a role in this. Individuals with higher IS benefitted more from the biased probability of emotional valence. Brain responses to more predictable emotions elicited a bilateral activity pattern comprising the inferior frontal gyrus and the posterior insula. Importantly, individual IAcc scores positively covaried with brain responses to more surprising and less predictable emotional expressions in the insula and caudate nucleus. We show for the first time that IAcc score is associated with enhanced processing of interoceptive prediction errors, particularly in the anterior insula. A higher IS score seems more likely to be associated with a stronger weighting of attention to interoceptive changes processed by the posterior insula and ventral prefrontal cortex. [ABSTRACT FROM AUTHOR]

Prominent theories propose that interoception modulates our behavioral and emotional responses involving decision-making and emotion regulation. Are the regions implicated in interoception also spatially related to and possibly nested within the networks of decision making and emotion regulation? Addressing this question, we performed three meta-analyses of functional magnetic resonance imaging studies to identify the regions that are commonly activated by the three domains using activation likelihood estimation (ALE). Additionally, we assessed the coactivation pattern of identified common regions using meta-analytic connectivity modeling (MACM). The results showed major overlaps of interoception with both decision making and emotion regulation in specifically the right dorsal anterior insula. The pairwise contrast analyses confirmed this finding and revealed conjunction-based activities in decision making and emotion regulation in the dorsal anterior cingulate cortex (dACC). MACM based on the identified insula revealed a widespread convergent coactivation pattern with the left anterior insula, dACC, and bilateral thalamus which, together, constitute the salience network. Among these co-activated regions, bilateral insula and the dACC were shared among all three domains. These results suggest that the regions mediating interoception including intero-exteroceptive integration and salience attribution are contained and thus spatially nested within the more extensive networks recruited during decision making and emotion regulation. [ABSTRACT FROM AUTHOR]

• Comprehensive microstructural mapping of the posterior and dorsal anterior human insula performed. • New areas Ig3, Ia1, Id2, Id3, Id4, Id5, Id6 identified and characterized. • Areas grouped into three superordinated cytoarchitectonic clusters. • Probabilistic cytoarchitectonic maps of 7 areas added to Julich-brain atlas. • Publicly available maps can be used to establish structure-function relationships. The human insular cortex supports multifunctional integration including interoceptive, sensorimotor, cognitive and social-emotional processing. Different concepts of the underlying microstructure have been proposed over more than a century. However, a 3D map of the cytoarchitectonic segregation of the insula in standard reference space, that could be directly linked to neuroimaging experiments addressing different cognitive tasks, is not yet available. Here we analyzed the middle posterior and dorsal anterior insula with image analysis and a statistical mapping procedure to delineate cytoarchitectonic areas in ten human postmortem brains. 3D-probability maps of seven new areas with granular (Ig3, posterior), agranular (Ia1, posterior) and dysgranular (Id2-Id6, middle to dorsal anterior) cytoarchitecture have been calculated to represent the new areas in stereotaxic space. A hierarchical cluster analysis based on cytoarchitecture resulted in three distinct clusters in the superior posterior, inferior posterior and dorsal anterior insula, providing deeper insights into the structural organization of the insula. The maps are openly available to support future studies addressing relations between structure and function in the human insula. [ABSTRACT FROM AUTHOR]

• Steady-state visually evoked potentials are modulated by internal attention. • Internal attention increases alpha-band activity and the heartbeat evoked potential. • Low-level visual processing trades-off with cardiac signal processing. • A limited cortical capacity is shared between sensory and interoceptive processing. While attention to external visual stimuli has been extensively studied, attention directed internally towards mental contents (e.g., thoughts, memories) or bodily signals (e.g., breathing, heartbeat) has only recently become a subject of increased interest, due to its relation to interoception, contemplative practices and mental health. The present study aimed at expanding the methodological toolbox for studying internal attention, by examining for the first time whether the steady-state visual evoked potential (ssVEP), a well-established measure of attention, can differentiate between internally and externally directed attention. To this end, we designed a task in which flickering dots were used to generate ssVEPs, and instructed participants to count visual targets (external attention condition) or their heartbeats (internal attention condition). We compared the ssVEP responses between conditions, along with alpha-band activity and the heartbeat evoked potential (HEP) - two electrophysiological measures associated with internally directed attention. Consistent with our hypotheses, we found that both the magnitude and the phase synchronization of the ssVEP decreased when attention was directed internally, suggesting that ssVEP measures are able to differentiate between internal and external attention. Additionally, and in line with previous findings, we found larger suppression of parieto-occipital alpha-band activity and an increase of the HEP amplitude in the internal attention condition. Furthermore, we found a trade-off between changes in ssVEP response and changes in HEP and alpha-band activity: when shifting from internal to external attention, increase in ssVEP response was related to a decrease in parieto-occipital alpha-band activity and HEP amplitudes. These findings suggest that shifting between external and internal directed attention prompts a re-allocation of limited processing resources that are shared between external sensory and interoceptive processing. [ABSTRACT FROM AUTHOR]

Abstract: Opening and closing the eyes are fundamental behaviors for directing attention to the external versus internal world. However, it remains unclear whether the states of eyes-open (EO) relative to eyes-closed (EC) are associated with different topological organizations of functional neural networks for exteroceptive and interoceptive processing (processing the external world and internal state, respectively). Here, we used resting-state functional magnetic resonance imaging and neural network analysis to investigate the topological properties of functional networks of the human brain when the eyes were open versus closed. The brain networks exhibited higher cliquishness and local efficiency, but lower global efficiency during the EO state compared to the EC state. These properties suggest an increase in specialized information processing along with a decrease in integrated information processing in EO (vs. EC). More importantly, the “exteroceptive” network, including the attentional system (e.g., superior parietal gyrus and inferior parietal lobule), ocular motor system (e.g., precentral gyrus and superior frontal gyrus), and arousal system (e.g., insula and thalamus), showed higher regional nodal properties (nodal degree, efficiency and betweenness centrality) in EO relative to EC. In contrast, the “interoceptive” network, composed of visual system (e.g., lingual gyrus, fusiform gyrus and cuneus), auditory system (e.g., Heschl's gyurs), somatosensory system (e.g., postcentral gyrus), and part of the default mode network (e.g., angular gyrus and anterior cingulate gyrus), showed significantly higher regional properties in EC vs. EO. In addition, the connections across sensory modalities were altered by volitional eye opening. The synchronicity between the visual system and the motor, somatosensory and auditory systems, characteristic of EC, was attenuated in EO. Further, the connections between the visual system and the attention, arousal and subcortical systems were increased in EO. These results may indicate that EO leads to a suppression of sensory modalities (other than visual) to allocate resources to exteroceptive processing. Our findings suggest that the topological organization of human brain networks dynamically switches corresponding to the information processing modes as we open or close our eyes. [Copyright &y& Elsevier]

Abstract: The insula has been identified as a key region involved in interoceptive awareness. Whilst imaging studies have investigated the neural activation patterns in this region involved in intero- and exteroceptive awareness, the underlying biochemical mechanisms still remain unclear. In order to investigate these, a well-established fMRI task targeting interoceptive awareness (heartbeat counting) and exteroceptive awareness (tone counting) was combined with magnetic resonance spectroscopy (MRS). Controlling for physiological noise, neural activity in the insula during intero- and exteroceptive awareness was confirmed in an independent data sample using the same fMRI design. Focussing on MRS values from the left insula and combining them with neural activity during intero- and exteroceptive awareness in the same healthy individuals, we demonstrated that GABA concentration in a region highly involved in interoceptive processing is correlated with neural responses to interoceptive stimuli, as opposed to exteroceptive stimuli. In addition, both GABA and interoceptive signal changes in the insula predicted the degree of depressed affect, as measured by the Beck Hopelessness Scale. On the one hand, the association between GABA concentration and neural activity during interoceptive awareness provides novel insight into the biochemical underpinnings of insula function and interoception. On the other, through the additional association of both GABA and neural activity during interoception with depressed affect, these data also bear potentially important implications for psychiatric disorders like depression and anxiety, where GABAergic deficits, altered insula function and abnormal affect coincide. [Copyright &y& Elsevier]