Interoceptive technologies for psychiatric interventions: From diagnosis to clinical applications.

Interoception-the perception of internal bodily signals-has emerged as an area of interest due to its implications in emotion and the prevalence of dysfunctional interoceptive processes across psychopathological conditions. Despite the importance of interoception in cognitive neuroscience and psychiatry, its experimental manipulation remains technically challenging. This is due to the invasive nature of existing methods, the limitation of self-report and unimodal measures of interoception, and the absence of standardized approaches across disparate fields. This article integrates diverse research efforts from psychology, physiology, psychiatry, and engineering to address this oversight. Following a general introduction to the neurophysiology of interoception as hierarchical predictive processing, we review the existing paradigms for manipulating interoception (e.g., interoceptive modulation), their underlying mechanisms (e.g., interoceptive conditioning), and clinical applications (e.g., interoceptive exposure). We suggest a classification for interoceptive technologies and discuss their potential for diagnosing and treating mental health disorders. Despite promising results, considerable work is still needed to develop standardized, validated measures of interoceptive function across domains and before these technologies can translate safely and effectively to clinical settings.

The bodily self from psychosis to psychedelics.

The sense of self is a foundational element of neurotypical human consciousness. We normally experience the world as embodied agents, with the unified sensation of our selfhood being nested in our body. Critically, the sense of self can be altered in psychiatric conditions such as psychosis and altered states of consciousness induced by psychedelic compounds. The similarity of phenomenological effects across psychosis and psychedelic experiences has given rise to the "psychotomimetic" theory suggesting that psychedelics simulate psychosis-like states. Moreover, psychedelic-induced changes in the sense of self have been related to reported improvements in mental health. Here we investigated the bodily self in psychedelic, psychiatric, and control populations. Using the Moving Rubber Hand Illusion, we tested (N = 75) patients with psychosis, participants with a history of substantial psychedelic experiences, and control participants to see how psychedelic and psychiatric experience impacts the bodily self. Results revealed that psychosis patients had reduced Body Ownership and Sense of Agency during volitional action. The psychedelic group reported subjective long-lasting changes to the sense of self, but no differences between control and psychedelic participants were found. Our results suggest that while psychedelics induce both acute and enduring subjective changes in the sense of self, these are not manifested at the level of the bodily self. Furthermore, our data show that bodily self-processing, related to volitional action, is disrupted in psychosis patients. We discuss these findings in relation to anomalous self-processing across psychedelic and psychotic experiences.

Attachment Reminders Trigger Widespread Synchrony across Multiple Brains.

Infant stimuli elicit widespread neural and behavioral response in human adults, and such massive allocation of resources attests to the evolutionary significance of the primary attachment. Here, we examined whether attachment reminders also trigger cross-brain concordance and generate greater neural uniformity, as indicated by intersubject correlation. Human mothers were imaged twice in oxytocin/placebo administration design, and stimuli included four ecological videos of a standard unfamiliar mother and infant: two infant/mother alone (Alone) and two mother-infant dyadic contexts (Social). Theory-driven analysis measured cross-brain synchrony in preregistered nodes of the parental caregiving network (PCN), which integrates subcortical structures underpinning mammalian mothering with cortical areas implicated in simulation, mentalization, and emotion regulation, and data-driven analysis assessed brain-wide concordance using whole-brain parcellation. Results demonstrated widespread cross-brain synchrony in both the PCN and across the neuroaxis, from primary sensory/somatosensory areas, through insular-cingulate regions, to temporal and prefrontal cortices. The Social context yielded significantly more cross-brain concordance, with PCNs striatum, parahippocampal gyrus, superior temporal sulcus, ACC, and PFC displaying cross-brain synchrony only to mother-infant social cues. Moment-by-moment fluctuations in mother-infant social synchrony, ranging from episodes of low synchrony to tightly coordinated positive bouts, were tracked online by cross-brain concordance in the preregistered ACC. Findings indicate that social attachment stimuli, representing evolutionary-salient universal cues that require no verbal narrative, trigger substantial interbrain concordance and suggest that the mother-infant bond, an icon standing at the heart of human civilization, may function to glue brains into a unified experience and bind humans into social groups.SIGNIFICANCE STATEMENT Infant stimuli elicit widespread neural response in human adults, attesting to their evolutionary significance, but do they also trigger cross-brain concordance and induce neural uniformity among perceivers? We measured cross-brain synchrony to ecological mother-infant videos. We used theory-driven analysis, measuring cross-brain concordance in the parenting network, and data-driven analysis, assessing brain-wide concordance using whole-brain parcellation. Attachment cues triggered widespread cross-brain concordance in both the parenting network and across the neuroaxis. Moment-by-moment fluctuations in behavioral synchrony were tracked online by cross-brain variability in ACC. Attachment reminders bind humans' brains into a unitary experience and stimuli characterized by social synchrony enhance neural similarity among participants, describing one mechanism by which attachment bonds provide the neural template for the consolidation of social groups.

Multisensory decisions from self to world.

Classic Bayesian models of perceptual inference describe how an ideal observer would integrate 'unisensory' measurements (multisensory integration) and attribute sensory signals to their origin(s) (causal inference). However, in the brain, sensory signals are always received in the context of a multisensory bodily state-namely, in combination with other senses. Moreover, sensory signals from both interoceptive sensing of one's own body and exteroceptive sensing of the world are highly interdependent and never occur in isolation. Thus, the observer must fundamentally determine whether each sensory observation is from an external (versus internal, self-generated) source to even be considered for integration. Critically, solving this primary causal inference problem requires knowledge of multisensory and sensorimotor dependencies. Thus, multisensory processing is needed to separate sensory signals. These multisensory processes enable us to simultaneously form a sense of self and form distinct perceptual decisions about the external world. In this opinion paper, we review and discuss the similarities and distinctions between multisensory decisions underlying the sense of self and those directed at acquiring information about the world. We call attention to the fact that heterogeneous multisensory processes take place all along the neural hierarchy (even in forming 'unisensory' observations) and argue that more integration of these aspects, in theory and experiment, is required to obtain a more comprehensive understanding of multisensory brain function. This article is part of the theme issue 'Decision and control processes in multisensory perception'.

Disentangling the neural correlates of agency, ownership and multisensory processing.

The experience of the self as an embodied agent in the world is an essential aspect of human consciousness. This experience arises from the feeling of control over one's bodily actions, termed the Sense of Agency, and the feeling that the body belongs to the self, Body Ownership. Despite longstanding philosophical and scientific interest in the relationship between the body and brain, the neural systems involved in Body Ownership and Sense of Agency, and especially their interactions, are not yet understood. In this preregistered study using the Moving Rubber Hand Illusion inside an MR-scanner, we aimed to uncover the relationship between Body Ownership and Sense of Agency in the human brain. Importantly, by using both visuomotor and visuotactile stimulations and measuring online trial-by-trial fluctuations in the illusion magnitude, we were able to disentangle brain systems related to objective sensory stimulation and subjective judgments of the bodily-self. Our results indicate that at both the behavioral and neural levels, Body Ownership and Sense of Agency are strongly interrelated. Multisensory regions in the occipital and fronto-parietal regions encoded convergence of sensory stimulation conditions. The subjective judgments of the bodily-self were related to BOLD fluctuations in the Somatosensory cortex and in regions not activated by the sensory conditions, such as the insular cortex and precuneus. Our results highlight the convergence of multisensory processing in specific neural systems for both Body Ownership and Sense of Agency with partially dissociable regions for subjective judgments in regions of the Default Mode Network.

ChillsDB: A Gold Standard for Aesthetic Chills Stimuli.

We introduce ChillsDB the first validated database of audiovisual stimuli eliciting aesthetic chills (goosebumps, psychogenic shivers) in a US population. To discover chills stimuli "in the wild", we devised a bottom-up, ecologically-valid method consisting in searching for mentions of the emotion' somatic markers in user comments throughout social media platforms (YouTube and Reddit). We successfully captured 204 chills-eliciting videos of three categories: music, film, and speech. We then tested the top 50 videos in the database on 600+ participants and validated a gold standard of 10 stimuli with a 0.9 probability of generating chills. All ChillsDB tools and data are fully available on GitHub for researchers to be able to contribute and perform further analysis.

The Scientific Study of Consciousness Cannot and Should Not Be Morally Neutral.

A target question for the scientific study of consciousness is how dimensions of consciousness, such as the ability to feel pain and pleasure or reflect on one's own experience, vary in different states and animal species. Considering the tight link between consciousness and moral status, answers to these questions have implications for law and ethics. Here we point out that given this link, the scientific community studying consciousness may face implicit pressure to carry out certain research programs or interpret results in ways that justify current norms rather than challenge them. We show that because consciousness largely determines moral status, the use of nonhuman animals in the scientific study of consciousness introduces a direct conflict between scientific relevance and ethics-the more scientifically valuable an animal model is for studying consciousness, the more difficult it becomes to ethically justify compromises to its well-being for consciousness research. Finally, in light of these considerations, we call for a discussion of the immediate ethical corollaries of the body of knowledge that has accumulated and for a more explicit consideration of the role of ideology and ethics in the scientific study of consciousness.

Impaired sense of agency and associated confidence in psychosis.

The Sense of Agency (SoA), our sensation of control over our actions, is a fundamental mechanism for delineating the Self from the environment and others. SoA arises from implicit processing of sensorimotor signals as well as explicit higher-level judgments. Psychosis patients suffer from difficulties in the sense of control over their actions and accurate demarcation of the Self. Moreover, it is unclear if they have metacognitive insight into their aberrant abilities. In this pre-registered study, we examined SoA and its associated confidence judgments using an embodied virtual reality paradigm in psychosis patients and controls. Our results show that psychosis patients not only have a severely reduced ability for discriminating their actions but they also do not show proper metacognitive insight into this deficit. Furthermore, an exploratory analysis revealed that the SoA capacities allow for high levels of accuracy in clinical classification of psychosis. These results indicate that SoA and its metacognition are core aspects of the psychotic state and provide possible venues for understanding the underlying mechanisms of psychosis, that may be leveraged for novel clinical purposes.

The dynamic boundaries of the Self: Serial dependence in the Sense of Agency.

The feeling of control over one's actions, termed the Sense of Agency (SoA), delineates one's experience as an embodied self. Although this embodied experience is typically perceived as stable over time, recent theoretical accounts highlight the experience-dependent and dynamic nature of the embodied self. In this study we examined how recent experiences modulate SoA (i.e., serial dependence), and disambiguated the unique contributions of previous stimuli and choices on subsequent SoA judgments. In addition, we examined whether these effects persist across different domains of perceptual alteration. We analyzed two independent datasets of the Virtual Hand (VH) task (N = 100 participants) in which a sensorimotor conflict is introduced between the presented visual feedback and the actual movement performed. In Dataset 1, which included only temporal alterations, we found that previous stimuli recalibrate current perception, increasing the likelihood of the current choice to be different than the previous choice. Whereas previous choices induce a repetition bias increasing the likelihood to repeat choices across trials. Thus, previous external stimuli and self-generated choices exert opposing influences on SoA. We replicated these findings in Dataset 2, in which the VH task was tested with alterations in both temporal and spatial domains. In addition, we discovered that previous stimuli from a different perceptual domain exert a recalibration effect similar to stimuli from the same domain. Thus, SoA is constantly shaped by our previous subjective choices and objective stimuli experienced even across different perceptual domains. This highlights how SoA may act as unifying construct organizing our experience of the self over time and across perceptual experiences.

Judgments of agency are affected by sensory noise without recruiting metacognitive processing.

Acting in the world is accompanied by a sense of agency, or experience of control over our actions and their outcomes. As humans, we can report on this experience through judgments of agency. These judgments often occur under noisy conditions. We examined the computations underlying judgments of agency, in particular under the influence of sensory noise. Building on previous literature, we studied whether judgments of agency incorporate uncertainty in the same way that confidence judgments do, which would imply that the former share computational mechanisms with metacognitive judgments. In two tasks, participants rated agency, or confidence in a decision about their agency, over a virtual hand that tracked their movements, either synchronously or with a delay and either under high or low noise. We compared the predictions of two computational models to participants' ratings and found that agency ratings, unlike confidence, were best explained by a model involving no estimates of sensory noise. We propose that agency judgments reflect first-order measures of the internal signal, without involving metacognitive computations, challenging the assumed link between the two cognitive processes.

Agency Deficits in a Human Genetic Model of Schizophrenia: Insights From 22q11DS Patients.

Schizophrenia is a chronic and disabling mental illness characterized by a disordered sense of self. Current theories suggest that deficiencies in the sense of control over one's actions (Sense of Agency, SoA) may underlie some of the symptoms of schizophrenia. However, it is not clear if agency deficits are a precursor or a result of psychosis. Here, we investigated full body agency using virtual reality in a cohort of 22q11 deletion syndrome participants with a genetic propensity for schizophrenia. In two experiments employing virtual reality, full body motion tracking, and online feedback, we investigated SoA in two separate domains. Our results show that participants with 22q11DS had a considerable deficit in monitoring their actions, compared to age-matched controls in both the temporal and spatial domain. This was coupled with a bias toward erroneous attribution of actions to the self. These results indicate that nonpsychotic 22q11DS participants have a domain general deficit in the conscious sensorimotor mechanisms underlying the bodily self. Our data reveal an abnormality in the SoA in a cohort with a genetic predisposition for schizophrenia, but without psychosis, providing evidence that deficits in delineation of the self may be a precursor rather than a result of the psychotic state.

Neural representation of the parent-child attachment from infancy to adulthood.

Attachment theory is built on the assumption of consistency; the mother-infant bond is thought to underpin the life-long representations individuals construct of attachment relationships. Still, consistency in the individual's neural response to attachment-related stimuli representing his or her entire relational history has not been investigated. Mothers and children were followed across two decades and videotaped in infancy (3-6 months), childhood (9-12 years) and young adulthood (18-24 years). In adulthood, participants underwent functional magnetic resonance imaging while exposed to videos of own mother-child interactions (Self) vs unfamiliar interactions (Other). Self-stimuli elicited greater activations across preregistered nodes of the human attachment network, including thalamus-to-brainstem, amygdala, hippocampus, anterior cingulate cortex (ACC), insula and temporal cortex. Critically, self-stimuli were age-invariant in most regions of interest despite large variability in social behavior, and Bayesian analysis showed strong evidence for lack of age-related differences. Psycho-physiological interaction analysis indicated that self-stimuli elicited tighter connectivity between ACC and anterior insula, consolidating an interface associating information from exteroceptive and interceptive sources to sustain attachment representations. Child social engagement behavior was individually stable from infancy to adulthood and linked with greater ACC and insula response to self-stimuli. Findings demonstrate overlap in circuits sustaining parental and child attachment and accord with perspectives on the continuity of attachment across human development.

Aesthetic chills cause an emotional drift in valence and arousal.

Aesthetic chills are an embodied peak emotional experience induced by stimuli such as music, films, and speeches and characterized by dopaminergic release. The emotional consequences of chills in terms of valence and arousal are still debated and the existing empirical data is conflicting. In this study, we tested the effects of ChillsDB, an open-source repository of chills-inducing stimuli, on the emotional ratings of 600+ participants. We found that participants experiencing chills reported significantly more positive valence and greater arousal during the experience, compared to participants who did not experience chills. This suggests that the embodied experience of chills may influence one's perception and affective evaluation of the context, in favor of theoretical models emphasizing the role of interoceptive signals such as chills in the process of perception and decision-making. We also found an interesting pattern in the valence ratings of participants, which tended to harmonize toward a similar mean after the experiment, though initially disparately distributed. We discuss the significance of these results for the diagnosis and treatment of dopaminergic disorders such as Parkinson's, schizophrenia, and depression.

Trust as Extended Control: Human-Machine Interactions as Active Inference.

In order to interact seamlessly with robots, users must infer the causes of a robot's behavior-and be confident about that inference (and its predictions). Hence, trust is a necessary condition for human-robot collaboration (HRC). However, and despite its crucial role, it is still largely unknown how trust emerges, develops, and supports human relationship to technological systems. In the following paper we review the literature on trust, human-robot interaction, HRC, and human interaction at large. Early models of trust suggest that it is a trade-off between benevolence and competence; while studies of human to human interaction emphasize the role of shared behavior and mutual knowledge in the gradual building of trust. We go on to introduce a model of trust as an agent' best explanation for reliable sensory exchange with an extended motor plant or partner. This model is based on the cognitive neuroscience of active inference and suggests that, in the context of HRC, trust can be casted in terms of virtual control over an artificial agent. Interactive feedback is a necessary condition to the extension of the trustor's perception-action cycle. This model has important implications for understanding human-robot interaction and collaboration-as it allows the traditional determinants of human trust, such as the benevolence and competence attributed to the trustee, to be defined in terms of hierarchical active inference, while vulnerability can be described in terms of information exchange and empowerment. Furthermore, this model emphasizes the role of user feedback during HRC and suggests that boredom and surprise may be used in personalized interactions as markers for under and over-reliance on the system. The description of trust as a sense of virtual control offers a crucial step toward grounding human factors in cognitive neuroscience and improving the design of human-centered technology. Furthermore, we examine the role of shared behavior in the genesis of trust, especially in the context of dyadic collaboration, suggesting important consequences for the acceptability and design of human-robot collaborative systems.

Fronto-Temporal Disconnection Within the Presence Hallucination Network in Psychotic Patients With Passivity Experiences.

Psychosis, characterized by hallucinations and delusions, is a common feature of psychiatric disease, especially schizophrenia. One prominent theory posits that psychosis is driven by abnormal sensorimotor predictions leading to the misattribution of self-related events. This misattribution has been linked to passivity experiences (PE), such as loss of agency and, more recently, to presence hallucinations (PH), defined as the conscious experience of the presence of an alien agent while no person is actually present. PH has been observed in schizophrenia, Parkinson's disease, and neurological patients with brain lesions and, recently, the brain mechanisms of PH (PH-network) have been determined comprising bilateral posterior middle temporal gyrus (pMTG), inferior frontal gyrus (IFG), and ventral premotor cortex (vPMC). Given that the experience of an alien agent is a common feature of PE, we here analyzed the functional connectivity within the PH-network in psychotic patients with (N = 39) vs without PE (N = 26). We observed reduced fronto-temporal functional connectivity in patients with PE compared to patients without PE between the right pMTG and the right and left IFG of the PH-network. Moreover, when seeding from these altered regions, we observed specific alterations with brain regions commonly linked to auditory-verbal hallucinations (such as Heschl's gyrus). The present connectivity findings within the PH-network extend the disconnection hypothesis for hallucinations to the specific case of PH and associates the PH-network with key brain regions for frequent psychotic symptoms such as auditory-verbal hallucinations, showing that PH are relevant to the study of the brain mechanisms of psychosis and PE.

Mother brain is wired for social moments.

Reorganization of the maternal brain upon childbirth triggers the species-typical maternal social behavior. These brief social moments carry profound effects on the infant's brain and likely have a distinct signature in the maternal brain. Utilizing a double-blind, within-subject oxytocin/placebo administration crossover design, mothers' brain was imaged twice using fMRI while observing three naturalistic maternal-infant contexts in the home ecology; 'unavailable', 'unresponsive', and 'social', when mothers engaged in synchronous peek-a-boo play. The social condition elicited greater neural response across the human caregiving network, including amygdala, VTA, hippocampus, insula, ACC, and temporal cortex. Oxytocin impacted neural response primarily to the social condition and attenuated differences between social and non-social stimuli. Greater temporal consistency emerged in the 'social' condition across the two imaging sessions, particularly in insula, amygdala, and TP. Findings describe how mother's brain varies by caregiving experiences and gives salience to moments of social synchrony that support infant development and brain maturation.

Modulation of Bodily Self-Consciousness by Self and External Touch.

The full body illusion (FBI) is a bodily illusion based on the application of multisensory conflicts that induce changes in bodily self-consciousness (BSC). This has been used to study cognitive brain mechanisms underlying body ownership and related aspects of self-consciousness. Typically, such paradigms employ external passive multisensory stimulation, thus neglecting the possible contributions of self-generated action and haptic cues to body ownership. In this article, the effects of both external and voluntary self-touch on BSC were examined with a robotics-based FBI paradigm. We compared the effects of classical passive visuotactile stimulation and active self-touch (in which experimental participants had a sense of agency over the tactile stimulation) on the FBI. We evaluated these effects using a questionnaire, crossmodal congruency task, and measurements of changes in self-location. The results indicated that both synchronous passive visuotactile stimulation and synchronous active self-touch induced illusory ownership over a virtual body, without significant differences in their magnitudes. However, the FBI induced by active self-touch was associated with a larger drift in self-location towards the virtual body. These results show that movement-related signals arising from self-touch impact the BSC not only for hand ownership but also for torso-centered body ownership and related aspects of BSC.

Synchronous caregiving from birth to adulthood tunes humans' social brain.

Mammalian young are born with immature brain and rely on the mother's body and caregiving behavior for maturation of neurobiological systems that sustain adult sociality. While research in animal models indicated the long-term effects of maternal contact and caregiving on the adult brain, little is known about the effects of maternal-newborn contact and parenting behavior on social brain functioning in human adults. We followed human neonates, including premature infants who initially lacked or received maternal-newborn skin-to-skin contact and full-term controls, from birth to adulthood, repeatedly observing mother-child social synchrony at key developmental nodes. We tested the brain basis of affect-specific empathy in young adulthood and utilized multivariate techniques to distinguish brain regions sensitive to others' distinct emotions from those globally activated by the empathy task. The amygdala, insula, temporal pole (TP), and ventromedial prefrontal cortex (VMPFC) showed high sensitivity to others' distinct emotions. Provision of maternal-newborn contact enhanced social synchrony across development from infancy and up until adulthood. The experience of synchrony, in turn, predicted the brain's sensitivity to emotion-specific empathy in the amygdala and insula, core structures of the social brain. Social synchrony linked with greater empathic understanding in adolescence, which was longitudinally associated with higher neural sensitivity to emotion-specific empathy in TP and VMPFC. Findings demonstrate the centrality of synchronous caregiving, by which infants practice the detection and sharing of others' affective states, for tuning the human social brain, particularly in regions implicated in salience detection, interoception, and mentalization that underpin affect sharing and human attachment.

Thought consciousness and source monitoring depend on robotically controlled sensorimotor conflicts and illusory states.

Thought insertion (TI) is characterized by the experience that certain thoughts, occurring in one's mind, are not one's own, but the thoughts of somebody else and suggestive of a psychotic disorder. We report a robotics-based method able to investigate the behavioral and subjective mechanisms of TI in healthy participants. We used a robotic device to alter body perception by providing online sensorimotor stimulation, while participants performed cognitive tasks implying source monitoring of mental states attributed to either oneself or another person. Across several experiments, conflicting sensorimotor stimulation reduced the distinction between self- and other-generated thoughts and was, moreover, associated with the experimentally generated feeling of being in the presence of an alien agent and subjective aspects of TI. Introducing a new robotics-based approach that enables the experimental study of the brain mechanisms of TI, these results link TI to predictable self-other shifts in source monitoring and specific sensorimotor processes.