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Address correspondence to Sahib S. Khalsa, M.D., Ph.D., Laureate Institute for Brain Research, Oxley College of Health Sciences, University of Tulsa, 6655 S. Yale Ave., Tulsa, OK 74136.
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California
Interoception refers to the process by which the nervous system senses, interprets, and integrates signals originating from within the body, providing a moment-by-moment mapping of the body’s internal landscape across conscious and unconscious levels. Interoceptive signaling has been considered a component process of reflexes, urges, feelings, drives, adaptive responses, and cognitive and emotional experiences, highlighting its contributions to the maintenance of homeostatic functioning, body regulation, and survival. Dysfunction of interoception is increasingly recognized as an important component of different mental health conditions, including anxiety disorders, mood disorders, eating disorders, addictive disorders, and somatic symptom disorders. However, a number of conceptual and methodological challenges have made it difficult for interoceptive constructs to be broadly applied in mental health research and treatment settings. In November 2016, the Laureate Institute for Brain Research organized the first Interoception Summit, a gathering of interoception experts from around the world, with the goal of accelerating progress in understanding the role of interoception in mental health. The discussions at the meeting were organized around four themes: interoceptive assessment, interoceptive integration, interoceptive psychopathology, and the generation of a roadmap that could serve as a guide for future endeavors. This review article presents an overview of the emerging consensus generated by the meeting.
Interoception refers collectively to the processing of internal bodily stimuli by the nervous system. Parcellation of the nervous system’s processing of sensory signals into interoception, proprioception, and exteroception began more than 100 years ago (
). Scientific interest in interoception has fluctuated (Figure 1A). During the 1980s, biological psychiatry was inundated with observations of interoceptive disturbances in panic disorder (
Carbon dioxide sensitivity in panic anxiety: Ventilatory and anxiogenic response to carbon dioxide in healthy subjects and patients with panic anxiety before and after alprazolam treatment.
). Recent years have witnessed a surge of interest on the topic of interoception due in part to findings highlighting its integral role in emotional experience, self-regulation, decision making, and consciousness. Importantly, interoception is not limited to conscious perception or even unique to the human species. From this perspective, interdisciplinary efforts to understand different features of interoception have been essential for advancing progress in cognitive and clinical neuroscience (Figure 1B).
Figure 1(A) Number of English language publications per year on interoception from PubMed, PsycINFO, and Institute for Science Information Web of Knowledge. The timeline starts in 1905, one year before the publication of Charles Sherrington’s book, The Integrative Action of the Nervous System, which first defined the concept of interoception. Key historical events relevant to interoception science are superimposed. (B) Publications per year on interoception vs. those investigating features of interoception that do not specifically refer to the term. These latter publications are more numerous and arise mainly from basic neuroscience, physiology, and subspecialty disciplines within the biomedical field. Note the use of a logarithmic scale in the second panel.
[Figure reproduced and modified with permission from Khalsa and Lapidus (
Visceroception has classically referred to the perception of bodily signals arising specifically from visceral organs, such as the heart, lungs, stomach, intestines, and bladder, along with other internal organs in the trunk of the body (
). It did not include organs such as the skin and skeletal muscle, in contrast to contemporary definitions of interoception that typically encompasses signals from both the viscera and all other tissues that relay a signal to the central nervous system about the current state of the body, including the skin and skeletal/smooth muscle fibers, via lamina I spinothalamic afferents (
) (Table 1). There has been relatively little focus overall on the integration across bodily systems; thus, it is not surprising that most investigations of the topic have been siloed within distinct research areas or scientific disciplines [see (
Several key distinctions are that interoceptive sensing 1) may be painful or nonpainful, 2) occurs across the spectra of high/low arousal and negative/positive valence, 3) usually occurs outside of conscious awareness (with the exception of pain sensations), and 4) is often (but not always) consciously experienced during instances of homeostatic perturbation.
). The act of sensing, interpreting, and integrating information about the state of inner body systems can be related to different elements such as interoceptive attention, detection, discrimination, accuracy, insight, sensibility, and self-report (Table 2). However, most interoceptive processes occur outside the realm of conscious awareness. Consciously experienced elements are measured clinically via subjective report, and there are few observable interoceptive signs (e.g., heart rate, respiration rate, pupillary dilation, flushing, perspiration, piloerection, nociceptive reflexes) (Table 3). Experimental approaches can quantify different body systems and features of interoceptive processing. Nevertheless, these measures are only partially overlapping and likely reflect somewhat distinct neural processes (
). Access to the full range of interoceptive signals often involves invasive approaches, which tend to elicit physiological perturbations and index more objectively measurable features (
Physiological changes during carbon dioxide inhalation in patients with panic disorder, major depression, and premenstrual dysphoric disorder: Evidence for a central fear mechanism.
High and low threshold for startle reactivity associated with PTSD symptoms but not PTSD risk: Evidence from a prospective study of active duty Marines.
How do you feel when you can’t feel your body? Interoception, functional connectivity and emotional processing in depersonalization-derealization disorder.
Altered patterns of heartbeat-evoked potentials in depersonalization/derealization disorder: Neurophysiological evidence for impaired cortical representation of bodily signals.
There is no generally agreed-on taxonomy for interoception science. Variable definitions have made it difficult to identify the features under investigation, let alone evaluate the quality of the findings. Based on the number of physiological systems involved, it could be questioned whether the terms “interoception” and “interoceptive awareness” are too broad. Interoceptive awareness is an umbrella term that was first used to describe a self-report subscale (
), but it has subsequently been used to encompass any (or all) of the different interoception features accessible to conscious self-report. Researchers from different fields developed definitions that only partially overlapped, reflecting the need for operationalization in neuroscience (
While interoception research to date has typically focused on single organ systems, an expanded approach that assesses multiple interoceptive organ systems and/or elements is needed. Examples include targeting numerous interoceptive features simultaneously and employing different tasks that converge on the same feature (e.g., combining top-down assessments of interoceptive attention with bottom-up perturbation approaches in the same individual) (Figure 2A).
Figure 2(A) Cardiac interoceptive processing measures and feature loading. This illustrates how the most commonly used heartbeat perception tasks differentially measure interoceptive features. [Figure reproduced and modified with permission from Khalsa and Lapidus
.] (B) Multisystem interoceptive processing measures and feature loadings: Example of hypothetical approaches to measuring interoceptive processing across multiple systems. Approaches that perturb the state of the body are recommended, as are convergent approaches such as combined assessments of interoceptive attention and perturbation. (C) Central neural integration of interoceptive rhythms. Interoceptive rhythms vary considerably across the different systems of the body. They exhibit complex characteristics and are hierarchically integrated within discrete regions of the central nervous system. [Figure modified, with permission, from Petzschner et al.
.] (D) Interoceptive rhythms vary in both amplitude and frequency. The top trace illustrates a hypothetical example of an amplitude modulation signal superimposed on a static frequency. The middle trace illustrates a hypothetical frequency modulation signal superimposed on a static amplitude. The bottom trace illustrates a hypothetical signal change involving both amplitude and frequency modulations that are temporally correlated. GI, gastrointestinal; GU, genitourinary.
The inner and outer worlds of the body constantly fluctuate. The nervous system monitors these environmental changes and responds adaptively in order to maintain a homeostatic balance and promote survival. Because psychiatric disorders often promote or reflect the development of chronic homeostatic and allostatic disturbances (
), there is a need for methods capable of eliciting homeostatic perturbations in controlled settings, especially those assessing subjective and behavioral responses to valence and arousal deviations. However, interoception is not simply about afferent processing. The brain’s constant monitoring of the body occurs in service of optimizing homeostatic regulation. This efferent limb is understudied (
), and paradigms that can effectively measure visceromotor outputs will be critical to establish sensitive assays of dysfunctional interoception and homeostatic regulation (e.g., detection of visceromotor-efferent neural signals controlling baroreflex sensitivity during modulation of visceral-afferent input by sympathetic drugs). The reliability and validity of methods should be rigorously established.
Integration
Interoception and Domain Specificity Within the Brain
There are fundamentally differing ways to interpret the evolution of brain and body signaling in humans. The processing of interoceptive input could be domain specific, with modular processing occurring in specialized, encapsulated neural circuits [e.g., cardiac, respiratory, urinary, genital, chemical, hormonal; see (
) for a review of domain specificity] or functionally coupled (e.g., cardiorespiratory, genitourinary, chemohormonal) and integrated within a single neural circuit. Understanding the adaptive origins and functions of interoceptive domain specificity (if present) could tell us how the implementation and deployment of interoceptive signals by the nervous system contributes to disordered mental health. Because interoceptive signaling involves afferent and efferent inputs across multiple hierarchies within the autonomic and central nervous systems, identifying where and how information processing dysfunctions negatively affect mental health represents a challenging problem.
Neural Pathways of Interoception
Several pathways have been implicated in the neural processing of interoceptive signals, beginning with a rich interface between autonomic afferents and the central nervous system. Relay pathways involve primarily spinal, vagal, and glossopharyngeal afferents, with multiple levels of processing and integration in autonomic ganglia and spinal cord (
). Several brainstem (nucleus of the solitary tract, parabrachial nucleus, and periaqueductal gray), subcortical (thalamus, hypothalamus, hippocampus, and amygdala), and cortical regions (insula and somatosensory cortices) represent key afferent processing regions (
). A complementary set of regions involved in visceromotor actions represents key efferent processing regions, including the anterior insula, anterior cingulate, subgenual cingulate, orbitofrontal, ventromedial prefrontal, supplementary motor, and premotor areas (
). It is noteworthy that these neural regions coincide closely with other sensory processing systems, especially the nociceptive and affective systems. The degree to which these represent distinct or overlapping systems is currently unclear.
Linking Paradigms Across Units of Analysis
A particular challenge when examining interoception is the fact that afferent sensory signals are integrated on several levels (peripherally, within the spinal cord, and supraspinally) to form sets of interoceptive maps across different body systems. The brain appears to integrate information representing particular states of multiple systems simultaneously (cardiac, respiratory, chemical, hormonal, nociceptive, etc.) (
), and it is imperative to be able to model and comparatively evaluate such mappings (Figure 2B). This poses many challenges. One approach might be to apply measures that assess multiple organ systems or interoceptive features simultaneously [see (
). However, it is also possible that multisystem assessments may reduce specificity for certain disorders and therefore may be unnecessary. For example, some patients with panic disorder may experience dyspnea but not palpitations. Localizing and then targeting the dysfunctional interoceptive domain would become more useful than broad multisystem interventions.
Timing and Rhythm in Interoceptive Circuits
The physiological timescales and amplitudes of interoceptive signaling vary dramatically (e.g., heart rate [0.5–3.3 Hz], respiratory rate [0.08–1 Hz], gastric contractility [0.05–0.1 Hz], urinary frequency [0.000045–0.00012 Hz]), with even slower changes in humoral mediators (
) (Figure 2C, D). They also vary across individuals, and over the life span (e.g., increased heart rates in infants/children). Despite the variance, the brain tracks such changes in similar subregions, including the insula, somatosensory cortices, cingulate, amygdala, thalamus, and brainstem (
). Temporal synchrony or dyssynchrony between these systems may affect interoceptive experiences, affect, and behavior, although the exact mechanisms require further study (
). Repetitive events are another important element for learning, and while there are numerous classic studies on visceral learning at the peripheral organ system level (
How Can Animal Research Improve the Understanding of Human Interoceptive Processing?
Although the inability to measure the subjective state of animals results in indirect inferences, well-established tasks exist [e.g., conditioned interoceptive place preference (
)]. The principal utility of animal models is the hypothesis testing of mechanistic processes at the biological level independent of appraisal and cognition. These include examining effects of peripheral or central nervous system lesions on physiology/behavior, or mapping of peripheral/central interactions via stimulation of selective neurons/circuits using optogenetic methods (
). Animal models are advantageous in that they allow for identification of neural mechanisms that may be distinct from higher cognitive processes (e.g., nonmammalian [reptiles/birds] vs. mammalian [mice/rats/monkeys/apes/chimpanzees], invertebrate [octopus] vs. vertebrate [fish/monkeys]). The study of interoception in nonhuman primates offers intriguing opportunities. Investigations in this area have been centered primarily on neural encoding of baroreceptor afferent stimulation (
). Fewer studies have examined relationships between mechanistic manipulation of interoceptive experiences and neural representation in these animals [see (
). Listening in on this process requires different approaches. Peripheral perturbations are often used to stimulate the afferent bottom-up transfer of information, usually of mechanical (
Cortisol rapidly affects amplitudes of heartbeat-evoked brain potentials—Implications for the contribution of stress to an altered perception of physical sensations?.
) origin (Supplemental Table S1). Central perturbations to probe efferent top-down processes have most typically involved selective regulation of attentional focus (
) have provided the primary means of assessing neural circuitry. However, a host of novel tools are capable of inhibiting, stimulating, or modulating the activity of interoceptive brain networks. Noninvasive methods include the application of transcranial magnetic stimulation (
). An important point is that many of the critical brain structures are difficult to modulate noninvasively because they are located deep within the brain or near the midline. Invasive measures do not share this limitation, and while their implementation is driven by clinical concerns, they can provide important insights. These include implanted vagus nerve stimulation (
). Beyond these perturbation tools, the use of experimental methods to modulate expectancies, such as placebo and sham interventions, is key. These methods will help to determine how sensitive psychiatric and other clinical patients’ afferent/efferent feedback loops are to processes requiring integrations of environmental context with body–brain signals (illustrated in the next section). Finally, neurofeedback (e.g., functional magnetic resonance imaging, electroencephalogram) represents an exciting opportunity to participate in the brain–body conversation by simultaneously measuring and modulating brain regions during treatment [for a noninteroceptive example, see (
)]. Equipped with these tools, the future looks promising, but to advance progress they need to be paired with better models of brain function.
Computational Theories of Interoception
Identifying the state of the body represents a problem that cannot be solved by pure sensing because afferent signals from body sensors (interosensations) are not only noisy but often ambiguous (
) (Figures 3 and 4). Specifically, the brain is assumed to construct a so-called generative model of interosensations that combines a predictive mapping (from hidden bodily states to interosensations) with prior information (beliefs or expectations about bodily states represented as probability distributions). This view is supported by findings that interoceptive perception is strongly shaped by expectations (
Figure 3(A) Example of one possible form of a general inference–control loop illustrated within a hierarchical Bayesian model. (B) Highly schematic example of illustrating that both interoceptive information and exteroceptive information are concurrently integrated to inform perceptual representations and action selection with respect to internally directed (e.g., visceromotor, autonomic) and externally directed (e.g., skeletomotor) actions. (C) General nodes that comprise a peripheral and central neural circuit for hierarchically integrating afferent interoceptive information into homeostatic reflexes, sensory and metacognitive representations, and allostatic regulators (predictions). ACC, anterior cingulate cortex; AIC, anterior insular cortex; MC, metacognitive layer; MIC, midinsular cortex; OFC, orbitofrontal cortex; PE, prediction error; PIC, posterior insular cortex; SGC, subgenual cortex.
[Panels (A) and (B) reproduced, with permission, from Petzschner et al. (
Figure 4(A) Active inference implementation according to the Embodied Predictive Interoception Coding model. Agranular visceromotor cortices, including the cingulate cortex, posterior ventral medial prefrontal cortex, posterior orbitofrontal cortex, and ventral anterior insula, estimate the balance among autonomic, metabolic, and immunological resources available to the body and its predicted requirements. These agranular visceromotor cortices issue allostatic predictions to hypothalamus, brainstem, and spinal cord nuclei to maintain a homeostatic internal milieu and simultaneously to the primary interoceptive sensory cortex in the mid and posterior insula. The interoceptive sensory cortex in the granular mid and posterior insula sends reciprocal prediction error signals back to the agranular visceromotor regions to modify the predictions. Under usual circumstances, these agranular regions are relatively insensitive to such feedback, which explains why interoceptive predictions are fairly stable in the face of body fluctuations. One hypothesis of the role of interoception in mental illness is that interoceptive input (i.e., posteriors) becomes increasingly decoupled from interoceptive predictions issued by the agranular visceromotor cortex (priors), leading to increased interoceptive prediction error signals. This decoupling may present in the brain as “noisy afferent interoceptive inputs”
. (B) Proposed intracortical architecture and intercortical connectivity for interoceptive predictive coding. The granular cortex contains six cell layers including granule cells, which are excitatory neurons that amplify and distribute thalamocortical inputs throughout the column. The granular cortex is structurally similar to the neocortex and therefore more recently evolved than the agranular and dysgranular cortices. Within the insula, the granular cortex is present in the mid and posterior sectors. AC, anterior cingulate; PL, prelimbic cortex.
[Figures reproduced, with permission, from Barrett and Simmons (
Another argument supporting a Bayesian view on interoception is its relation to what constitutes arguably the brain’s most fundamental task: the regulation (or control) of bodily states. Put simply, if the brain were unable to resolve the ambiguity of interosensations, it would face difficulties in choosing appropriate actions to protect homeostasis. In information-theoretic terms, the challenge of keeping bodily states within narrow homeostatic ranges corresponds to choosing actions that minimize the long-term average Shannon surprise (entropy) of interosensations (
). Solving this control problem requires knowledge or estimations of current and/or future bodily states and hence inference and predictions/forecasts—two natural domains of generative models.
Eliciting surprise-minimizing (homeostasis-restoring) actions changes the bodily state and thus interosensations. This means that inference and control of bodily states form a closed loop. Inference–control loops that minimize interoceptive surprise can be cast as hierarchical Bayesian models (HBMs). Anatomically, HBMs are plausible candidates given that interoceptive circuitry is structured hierarchically (
). These quantities can support surprise minimization in two ways: by adjusting beliefs (probability distributions) throughout the hierarchy [predictive coding (
HBMs support both homeostatic (reactive) and allostatic (prospective) control. Reconsidering classical homeostatic set points as beliefs (i.e., probabilistic representations of expected/desired bodily states) enables reactive regulation at the bottom of the hierarchy (
); here, prediction errors elicit reflex-like actions that minimize momentary interoceptive surprise. Allostatic regulation at longer time scales is achieved through modulation of homeostatic beliefs by inferred or forecast states signaled from higher hierarchical levels (
). Importantly, belief precision determines the force/pace of corrective actions—that is, the tighter the expected range of bodily state, the more vigorous the elicited regulatory action. This offers a novel explanation for psychosomatic phenomena and placebo effects (
In summary, a hierarchical Bayesian perspective unifies interoception and homeostatic/allostatic control under the same computational principles. This provides a conceptual foundation for computational psychosomatics and supports a taxonomy of disease processes (
). One caveat is that the empirical evidence for hierarchical Bayesian principles of interoception and homeostatic/allostatic control is indirect so far. Studies designed to probe hierarchical Bayesian processes under experimentally controlled homeostatic perturbations will be crucial for finessing (or refuting) current computational concepts of interoception.
Psychopathology
Interoceptive Psychopathology
Several conceptual and heuristic models have linked dysfunctions of interoception to mental health conditions. Specifically, mood and anxiety disorders have been linked to failures to appropriately anticipate changes in interoceptive states (
), although it remains unclear whether this is due to altered afferent signaling, altered central sensory processing, abnormal temperament, and/or metacognition. Drug addiction, another condition marked by interoceptive disturbances, has an overlapping neural circuitry and abnormal responses to interoceptive cues (
). Other disorders also have interoceptive symptom overlap; however, the specific feature involved may differ according to the disorder or affected individual [e.g., chronic pain (
Do interoceptive sensations provoke fearful responses in adolescents with chronic headache or chronic abdominal pain? A preliminary experimental study.
)]. Table 3 lists diagnostic symptoms and clinical signs indicative of interoceptive dysfunction in several psychiatric disorders. Conditions that have a psychiatric component include fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and functional disorders within medicine (e.g., noncardiac chest pain, functional dysphagia) as well as certain medical disorders (e.g., gastroesophageal reflux, asthma).
Alternatively, one can use a dimensional psychopathology approach to link processes underlying interoceptive dysfunction to psychiatric disorders. Transdiagnostic perspectives such as those provided by the Research Domain Criteria (
) may be particularly helpful in identifying the potential role played by various interoceptive processes because several of these might not be readily identified at the symptom report level relied on by clinicians and, accordingly, might not have entered into the diagnostic specifications for DSM. This would allow for identification of mechanistic dysfunctions across units of analyses and might bridge the biological gap in current diagnostic classification frameworks by directly probing the links between physiological and psychological dysfunctions. Interoceptive investigations in mental health populations might reveal evidence of 1) attentional bias (e.g., hypervigilance), 2) distorted physiological sensitivity (e.g., blunted or heightened magnitude estimation in response to a perturbation), 3) cognitive bias (e.g., catastrophizing in response to an anticipated stimulus), 4) abnormal sensibility (e.g., tendency to label one’s experiences in a particular way), and 5) impaired insight (e.g., poor confidence–accuracy correspondence on a task).
Determining whether interoceptive processes are a cause or consequence of developmental psychopathology, and which factors might affect this development (such as early life stress or pain), will be an important area for future research. Such studies may benefit from the examination of younger (
). Investigating the role of social cognition/theory of mind in clinically relevant interoceptive inference generation represents another ripe opportunity (
Because interoception is fundamentally a process linking body and brain, it is conceivable that objective measures of this process could serve as biological indicators of disease states. However, there is currently limited evidence for interoceptive predictors of diagnostic, prognostic, or treatment status (
Support vector machine analysis of functional magnetic resonance imaging of interoception does not reliably predict individual outcomes of cognitive behavioral therapy in panic disorder with agoraphobia.
). Biomarkers, such as those derived from neuroimaging or blood measurements, should be sensitive, specific, and unaffected by cognitive and emotional influences. However, it seems conceivable that the most clinically sensitive interoceptive measures might derive from probes that perturb physiological functions to engage specific metacognitive beliefs and/or expectations about bodily states. Such measures could facilitate differential diagnosis testing by revealing the presence of interoceptive dysfunction of biological (within a physiological system or systems), psychological (e.g., overly precise expectations about bodily states), or metacognitive (e.g., discrepant self-efficacy beliefs with regard to homeostatic/allostatic regulation) origin (
). This approach could be seen as analogous to a cardiac stress test, such that adequate engagement of the system under ecologically valid conditions is required in order to measure its dysfunction.
The most common application of interoceptive evaluation in current clinical practice occurs during interoceptive exposure psychotherapy for panic disorder (
). During this procedure, patients self-induce varieties of interoceptive symptoms via low-arousal manipulations (e.g., hyperventilation, performing jumping jacks, spinning in a chair, breathing through a straw) while the clinician monitors their subjective distress level. Unfortunately these manipulations often fail to adequately reproduce the fear response, possibly because the patient retains full control over the stimulation (the patient can quit at any time) and the perturbation remains predictable with minimal uncertainty, raising the question of whether modulating both physiological homeostasis and the perception of controllability might further improve the ecological validity and efficacy of interoceptive exposures (
). In this setting, the degree of tolerance to being enclosed in a small dark chamber for 10 minutes might provide behavioral evidence verifying tolerance to triggers of interoceptive dysregulation. There is also experimental evidence that pharmacological interoceptive exposure therapy can reduce anxiety disorder symptom severity either as monotherapy (
). However, there are few studies of these procedures to date, the impact of such interventions on longer term outcomes (e.g., 6 months or beyond) are unknown, and none of these approaches has translated into clinical practice.
Current Treatments Relevant to Interoception
Among the currently available therapies with an interoceptive basis are pharmacotherapies directly modulating interoceptive physiology. Examples include adrenergic blockade (e.g., propranolol) or agonism (e.g., yohimbine), stimulants (e.g., methylphenidate), benzodiazepines, muscle relaxants, and opioids. A second example is cognitive behavioral therapy with exposure and response prevention to reverse or attenuate conditioned fears or form new learned associations. It is helpful in ameliorating cognitive biases in numerous disorders, including depression, obsessive-compulsive disorder, posttraumatic stress disorder (specifically prolonged exposure therapy), irritable bowel syndrome, and chronic pain. Interoceptive exposure is a special example demonstrated to be effective in specific disorders (especially panic disorder). Behavioral activation therapy for depression sometimes includes exposure to experiences with positive interoceptive value. A third example is capnometry-assisted respiratory training. Based on the assumption that sustained hypocapnia resulting from hyperventilation is a key mechanism in the production and maintenance of panic, carbon dioxide capnography-assisted therapy aims to help patients voluntarily increase end-tidal partial pressure of carbon dioxide and tolerate physiological variability associated with panic attacks (
). As a fourth example, mindfulness-based stress reduction, yoga, and other meditation/movement-based treatments may be aimed at improving metacognitive awareness of mind–body connections by systematically attending to sensations of breathing, cognitions, and/or other modulated body states (e.g., muscle stretching) (
Several emerging technologies may have relevance for interoception and mental health, including Floatation-REST (reduced environmental stimulation therapy) and perturbation approaches.
Floatation-REST
This intervention, which systematically attenuates exteroceptive sensory input to the nervous system, also appears to noninvasively enhance exposure to interoceptive sensations such as the breath and heartbeat (
). Preliminary data suggest that a single 1-hour session has a short-term anxiolytic and antidepressant effect in patients with comorbid anxiety and depression (
), are several approaches awaiting further investigation. Given the hypothesis of noisy baseline afferent signaling, these approaches may systematically enhance the signal-to-noise ratio and facilitate interoceptive learning. A key aspect in discerning clinical efficacy of any perturbation may be the extent to which the patient perceives controllability over the intervention and is willing/able to surrender this parameter in treatment. Interventions in which escape or active avoidance behaviors are directly measurable may provide especially meaningful information (
Beyond the issues outlined previously, progress in determining the relevance of interoception for mental health relies on emphasizing the features that distinguish it from other sensory modalities. Interoception seemingly involves a high degree of connectivity within the brain (
). It appears to be tightly linked to the self and survival through homeostatic maintenance of the body, and by helping us to represent how things are going in the present with respect to the experienced past and the anticipated future. These computations may depend on what has occurred to shape the body’s internal landscape, and it is in this regard that learning, and malleability of representations over time, could play important roles.
The conceptual framework for investigating interoception may overlap with other processes, including emotion (
), because each is integral for maintaining bodily homeostasis. An important endeavor may involve the identification of which neural systems for interoception, emotion, cognition, and pain are overlapping, interdigitating, or even possibly identical. Additional effort is needed to define the neurophysiological nomenclature, core criteria, common features, developmental aspects, modulating factors, functional consequences, and putative pathophysiologic mechanisms of interoception in mental health disorders.
The current work offers some conceptual distinctions and some mutually agreed-on terminology, with many others still needed. Several low-hanging fruits, as well as promising emerging technologies and tools, have been mentioned. Further empirical work will be critical to delineate how interoception can be mapped to mental health measures, models, and approaches, and benchmarks for success/failure need to be established. Models of interoceptive processing that improve on the traditional stimulus, sensorimotor processing, and response function concepts have been described, but these models remain theoretical and await further testing. Therefore, the current document is best viewed as a work in progress.
Acknowledgments and Disclosures
We express our sincere appreciation to the William K. Warren Foundation for supporting the Interoception Summit 2016 and to all of the Laureate Institute for Brain Research staff members for their assistance with facilitating the meeting.
AEM reports the following disclosures: research/grant: National Institutes of Health (NIH) Grant No. 1U01EB021952-01; scientific advisory board: Anxiety and Depression Association of America. AvL reports the following disclosures: research/grants: Research Fund KU Leuven, Belgium (Grant Nos. STRT/13/002 and DBOF/14/021), an infrastructure grant from the Herculesstichting, Belgium (Grant No. AKUL/13/07), “Asthenes” long-term structural funding Methusalem grant (Grant No. METH/15/011) by the Flemish Government, Belgium. CBN reports the following disclosures: research/grant: NIH, Stanley Medical Research Institute; consulting (last 3 years): Xhale, Takeda, Taisho Pharmaceutical, Inc., Prismic Pharmaceuticals, Bracket (Clintara), Total Pain Solutions, Gerson Lehrman Group Healthcare & Biomedical Council, Fortress Biotech, Sunovion Pharmaceuticals, Inc., Sumitomo Dainippon Pharma, Janssen Research & Development, LLC, Magstim, Inc., Navitor Pharmaceuticals, Inc., TC MSO, Inc.; stockholder: Xhale, Celgene, Seattle Genetics, Abbvie, OPKO Health, Inc., Bracket Intermediate Holding Corporation, Network Life Sciences, Inc., Antares; scientific advisory boards: American Foundation for Suicide Prevention (AFSP), Brain and Behavior Research Foundation (formerly National Alliance for Research on Schizophrenia and Depression [NARSAD]), Xhale, Anxiety and Depression Association of America (ADAA), Skyland Trail, Bracket (Clintara), RiverMend Health, LLC, Laureate Institute for Brain Research, Inc.; board of directors: AFSP, Gratitude America, ADAA; income sources or equity of $10,000 or more: American Psychiatric Publishing, Xhale, Bracket (Clintara), CME Outfitters, Takeda; patents: method and devices for transdermal delivery of lithium (Patent No. US 6,375,990B1), method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (Patent No. US 7,148,027B2). HDC reports the following disclosures: research/grants: European Research Council Horizon 2020 Proof of Concept Grant “HeartRater: Tools for the systematic evaluation of interoceptive ability,” Medical Research Council (UK) MRC Confidence in Concept Grant “Identifying neural, cognitive, and phenomenological markers of auditory verbal hallucinations in borderline personality,” MQ (Mental Health) PsyImpact “Aligning Dimensions of Interoceptive Experience (ADIE) to prevent development of anxiety disorders in autism,” Dr. Mortimer and Theresa Sackler Foundation Sackler Centre for Consciousness Science, University of Sussex, BIAL Foundation Bursary “Microneurography as a tool for consciousness science”; scientific advisory boards: Emteq, Ltd., unpaid governor on board of charity “Reflecting nature in art & science”; board of directors: Codirector of Sackler Centre for Consciousness Science, University of Sussex. KES reports the following disclosures: research/grants: Deutsche Forschungsgemeinschaft, Transregional Collaborative Research Centre, “Ingestive Behaviour: Homeostasis and Reward,” René and Susanne Braginsky Foundation. LPS reports the following disclosures: scientific advisory board: Laureate Institute for Brain Research, Inc. JDF reports the following disclosures: research/grants: NIH Grant Nos. R01MH105662, R21MH110865, and R01HD087712; scientific advisory boards: International Obsessive-Compulsive Disorder Foundation Clinical and Scientific Advisory Board. JLR reports the following disclosures: research/grants: NIH Grant No. R01MD007807 and Oklahoma Center for the Advancement of Science and Technology Grant No. HR15-079. JSF reports the following disclosures: research/grants: NIH/National Institute of General Medical Sciences (NIGMS) Grant No. P20GM121312, Brain and Behavior Research Foundation (formerly NARSAD) Young Investigator Award. MBS reports the following disclosures: scientific advisory board: Laureate Institute for Brain Research, Inc.; editorial board: Depression and Anxiety, Biological Psychiatry. MPP reports the following disclosures: research/grants: the William K. Warren Foundation and NIH Grant No. R01DA016663, NIH/NIGMS Grant No. P20DA027834, and NIH Grant Nos. R01DA027797, R01DA018307, U01DA041089, and 1R01MH101453; consulting (last 3 years): has received royalties for an article about methamphetamine use disorder from UpToDate. OVdB reports the following disclosures: scientific advisory boards: Research Training Group 2271 of the Deutsche Forschungsgemeinschaft on “Expectation maintenance vs. change in the context of expectation violations: Connecting different approaches,” University of Marburg. RDL reports the following disclosures: research/grant: NIH. SSK reports the following disclosures: research/grants: NIH/National Institute of Mental Health Grant No. K23MH112949, NIH/NIGMS Grant No. P20GM121312, William K. Warren Foundation, Brain and Behavior Foundation (formerly NARSAD) Young Investigator Award. WEM reports the following disclosures: research/grants: NCIRE (Veterans Health Research Institute, San Francisco, California), Alzheimer’s Association, Mental Insight Foundation, the Pepper Foundation, University of California, San Francisco, Resource Allocation Program. WKS reports the following disclosures: research/grants: NIH Grant No. P20GM121312, Brain and Behavior Foundation (formerly NARSAD) Young Investigator Award. The remaining authors report no biomedical financial interests or potential conflicts of interest.
Carbon dioxide sensitivity in panic anxiety: Ventilatory and anxiogenic response to carbon dioxide in healthy subjects and patients with panic anxiety before and after alprazolam treatment.
Cortisol rapidly affects amplitudes of heartbeat-evoked brain potentials—Implications for the contribution of stress to an altered perception of physical sensations?.
Do interoceptive sensations provoke fearful responses in adolescents with chronic headache or chronic abdominal pain? A preliminary experimental study.
Support vector machine analysis of functional magnetic resonance imaging of interoception does not reliably predict individual outcomes of cognitive behavioral therapy in panic disorder with agoraphobia.
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