Functional connectivity between interoceptive brain regions is associated with distinct health-related domains: A population-based neuroimaging study.

Interoception is the sensation, perception, and integration of signals from within the body. It has been associated with a broad range of physiological and psychological processes. Further, interoceptive variables are related to specific regions and networks in the human brain. However, it is not clear whether or how these networks relate empirically to different domains of physiological and psychological health at the population level. We analysed a data set of 19,020 individuals (10,055 females, 8965 males; mean age: 63 years, age range: 45-81 years), who have participated in the UK Biobank Study, a very large-scale prospective epidemiological health study. Using canonical correlation analysis (CCA), allowing for the examination of associations between two sets of variables, we related the functional connectome of brain regions implicated in interoception to a selection of nonimaging health and lifestyle related phenotypes, exploring their relationship within modes of population co-variation. In one integrated and data driven analysis, we obtained four statistically significant modes. Modes could be categorised into domains of arousal and affect and cardiovascular health, respiratory health, body mass, and subjective health (all p < .0001) and were meaningfully associated with distinct neural circuits. Circuits represent specific neural "fingerprints" of functional domains and set the scope for future studies on the neurobiology of interoceptive involvement in different lifestyle and health-related phenotypes. Therefore, our research contributes to the conceptualisation of interoception and may lead to a better understanding of co-morbid conditions in the light of shared interoceptive structures.

In the Body's Eye: The computational anatomy of interoceptive inference.

A growing body of evidence highlights the intricate linkage of exteroceptive perception to the rhythmic activity of the visceral body. In parallel, interoceptive inference theories of affective perception and self-consciousness are on the rise in cognitive science. However, thus far no formal theory has emerged to integrate these twin domains; instead, most extant work is conceptual in nature. Here, we introduce a formal model of cardiac active inference, which explains how ascending cardiac signals entrain exteroceptive sensory perception and uncertainty. Through simulated psychophysics, we reproduce the defensive startle reflex and commonly reported effects linking the cardiac cycle to affective behaviour. We further show that simulated 'interoceptive lesions' blunt affective expectations, induce psychosomatic hallucinations, and exacerbate biases in perceptual uncertainty. Through synthetic heart-rate variability analyses, we illustrate how the balance of arousal-priors and visceral prediction errors produces idiosyncratic patterns of physiological reactivity. Our model thus offers a roadmap for computationally phenotyping disordered brain-body interaction.

Psilocybin Induces Aberrant Prediction Error Processing of Tactile Mismatch Responses-A Simultaneous EEG-FMRI Study.

As source of sensory information, the body provides a sense of agency and self/non-self-discrimination. The integration of bodily states and sensory inputs with prior beliefs has been linked to the generation of bodily self-consciousness. The ability to detect surprising tactile stimuli is essential for the survival of an organism and for the formation of mental body representations. Despite the relevance for a variety of psychiatric disorders characterized by altered body and self-perception, the neurobiology of these processes is poorly understood. We therefore investigated the effect of psilocybin (Psi), known to induce alterations in self-experience, on tactile mismatch responses by combining pharmacological manipulations with simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) recording. Psi reduced activity in response to tactile surprising stimuli in frontal regions, the visual cortex, and the cerebellum. Furthermore, Psi reduced tactile mismatch negativity EEG responses at frontal electrodes, associated with alterations of body- and self-experience. This study provides first evidence that Psi alters the integration of tactile sensory inputs through aberrant prediction error processing and highlights the importance of the 5-HT2A system in tactile deviancy processing as well as in the integration of bodily and self-related stimuli. These findings may have important implications for the treatment of psychiatric disorders characterized by aberrant bodily self-awareness.

The seductive allure of cargo cult computationalism.

Bruineberg and colleagues report a striking confusion, in which the formal Bayesian notion of a "Markov blanket" has been frequently misunderstood and misapplied to phenomena of mind and life. I argue that misappropriation of formal concepts is pervasive in the "predictive processing" literature, and echo Richard Feynman in suggesting how we might resist the allure of cargo cult computationalism.

Deeply Felt Affect: The Emergence of Valence in Deep Active Inference.

The positive-negative axis of emotional valence has long been recognized as fundamental to adaptive behavior, but its origin and underlying function have largely eluded formal theorizing and computational modeling. Using deep active inference, a hierarchical inference scheme that rests on inverting a model of how sensory data are generated, we develop a principled Bayesian model of emotional valence. This formulation asserts that agents infer their valence state based on the expected precision of their action model-an internal estimate of overall model fitness ("subjective fitness"). This index of subjective fitness can be estimated within any environment and exploits the domain generality of second-order beliefs (beliefs about beliefs). We show how maintaining internal valence representations allows the ensuing affective agent to optimize confidence in action selection preemptively. Valence representations can in turn be optimized by leveraging the (Bayes-optimal) updating term for subjective fitness, which we label affective charge (AC). AC tracks changes in fitness estimates and lends a sign to otherwise unsigned divergences between predictions and outcomes. We simulate the resulting affective inference by subjecting an in silico affective agent to a T-maze paradigm requiring context learning, followed by context reversal. This formulation of affective inference offers a principled account of the link between affect, (mental) action, and implicit metacognition. It characterizes how a deep biological system can infer its affective state and reduce uncertainty about such inferences through internal action (i.e., top-down modulation of priors that underwrite confidence). Thus, we demonstrate the potential of active inference to provide a formal and computationally tractable account of affect. Our demonstration of the face validity and potential utility of this formulation represents the first step within a larger research program. Next, this model can be leveraged to test the hypothesized role of valence by fitting the model to behavioral and neuronal responses.

Emotional metacognition: stimulus valence modulates cardiac arousal and metamemory.

Emotion alters how we feel, see, and experience the world. In the domain of memory, the emotional valence and arousal of memorised stimuli can modulate both the acuity and content of episodic recall. However, no experiment has investigated whether arousal and valence also influence metacognition for memory (i.e. the process of self-monitoring memories). In a pre-registered study, we applied a novel psychophysiological design together with computational models of metacognition to assess the influence of stimulus valence and arousal on the sensitivity, bias, and efficiency of metamemory. To estimate the role of physiological arousal in mediating these effects, we recorded cardiac measures through pulse oximetry. We found that negative valence substantially decreased both memory performance and subjective confidence, in particular for low arousal words. Simultaneously, we found that emotional valence modulated both heart rate and heart-rate variability (HRV) during recognition memory. Exploratory trial-level analyses further revealed that subjective confidence was encoded in instantaneous heart-rate fluctuations and that this relationship was also modulated by emotional valence. Our results demonstrate that recognition memory and metacognition are influenced by the emotional valence of encoded items and that this correlation is in part related to cardiac activity.

Thinking through prior bodies: autonomic uncertainty and interoceptive self-inference.

The Bayesian brain hypothesis, as formalized by the free-energy principle, is ascendant in cognitive science. But, how does the Bayesian brain obtain prior beliefs? Veissière and colleagues argue that sociocultural interaction is one important source. We offer a complementary model in which "interoceptive self-inference" guides the estimation of expected uncertainty both in ourselves and in our social conspecifics.

Quantitative MRI provides markers of intra-, inter-regional, and age-related differences in young adult cortical microstructure.

Measuring the structural composition of the cortex is critical to understanding typical development, yet few investigations in humans have charted markers in vivo that are sensitive to tissue microstructural attributes. Here, we used a well-validated quantitative MR protocol to measure four parameters (R1, MT, R2*, PD*) that differ in their sensitivity to facets of the tissue microstructural environment (R1, MT: myelin, macromolecular content; R2*: myelin, paramagnetic ions, i.e., iron; PD*: free water content). Mapping these parameters across cortical regions in a young adult cohort (18-39 years, N = 93) revealed expected patterns of increased macromolecular content as well as reduced tissue water content in primary and primary adjacent cortical regions. Mapping across cortical depth within regions showed decreased expression of myelin and related processes - but increased tissue water content - when progressing from the grey/white to the grey/pial boundary, in all regions. Charting developmental change in cortical microstructure cross-sectionally, we found that parameters with sensitivity to tissue myelin (R1 & MT) showed linear increases with age across frontal and parietal cortex (change 0.5-1.0% per year). Overlap of robust age effects for both parameters emerged in left inferior frontal, right parietal and bilateral pre-central regions. Our findings afford an improved understanding of ontogeny in early adulthood and offer normative quantitative MR data for inter- and intra-cortical composition, which may be used as benchmarks in further studies.

From cognitivism to autopoiesis: towards a computational framework for the embodied mind.

Predictive processing (PP) approaches to the mind are increasingly popular in the cognitive sciences. This surge of interest is accompanied by a proliferation of philosophical arguments, which seek to either extend or oppose various aspects of the emerging framework. In particular, the question of how to position predictive processing with respect to enactive and embodied cognition has become a topic of intense debate. While these arguments are certainly of valuable scientific and philosophical merit, they risk underestimating the variety of approaches gathered under the predictive label. Here, we first present a basic review of neuroscientific, cognitive, and philosophical approaches to PP, to illustrate how these range from solidly cognitivist applications-with a firm commitment to modular, internalistic mental representation-to more moderate views emphasizing the importance of 'body-representations', and finally to those which fit comfortably with radically enactive, embodied, and dynamic theories of mind. Any nascent predictive processing theory (e.g., of attention or consciousness) must take into account this continuum of views, and associated theoretical commitments. As a final point, we illustrate how the Free Energy Principle (FEP) attempts to dissolve tension between internalist and externalist accounts of cognition, by providing a formal synthetic account of how internal 'representations' arise from autopoietic self-organization. The FEP thus furnishes empirically productive process theories (e.g., predictive processing) by which to guide discovery through the formal modelling of the embodied mind.

Active inference, enactivism and the hermeneutics of social cognition.

We distinguish between three philosophical views on the neuroscience of predictive models: predictive coding (associated with internal Bayesian models and prediction error minimization), predictive processing (associated with radical connectionism and 'simple' embodiment) and predictive engagement (associated with enactivist approaches to cognition). We examine the concept of active inference under each model and then ask how this concept informs discussions of social cognition. In this context we consider Frith and Friston's proposal for a neural hermeneutics, and we explore the alternative model of enactivist hermeneutics.

Expectation violation and attention to pain jointly modulate neural gain in somatosensory cortex.

The neural processing and experience of pain are influenced by both expectations and attention. For example, the amplitude of event-related pain responses is enhanced by both novel and unexpected pain, and by moving the focus of attention towards a painful stimulus. Under predictive coding, this congruence can be explained by appeal to a precision-weighting mechanism, which mediates bottom-up and top-down attentional processes by modulating the influence of feedforward and feedback signals throughout the cortical hierarchy. The influence of expectation and attention on pain processing can be mapped onto changes in effective connectivity between or within specific neuronal populations, using a canonical microcircuit (CMC) model of hierarchical processing. We thus implemented a CMC within dynamic causal modelling for magnetoencephalography in human subjects, to investigate how expectation violation and attention to pain modulate intrinsic (within-source) and extrinsic (between-source) connectivity in the somatosensory hierarchy. This enabled us to establish whether both expectancy and attentional processes are mediated by a similar precision-encoding mechanism within a network of somatosensory, frontal and parietal sources. We found that both unexpected and attended pain modulated the gain of superficial pyramidal cells in primary and secondary somatosensory cortex. This modulation occurred in the context of increased lateralized recurrent connectivity between somatosensory and fronto-parietal sources, driven by unexpected painful occurrences. Finally, the strength of effective connectivity parameters in S1, S2 and IFG predicted individual differences in subjective pain modulation ratings. Our findings suggest that neuromodulatory gain control in the somatosensory hierarchy underlies the influence of both expectation violation and attention on cortical processing and pain perception.

Metacognitive ability correlates with hippocampal and prefrontal microstructure.

The ability to introspectively evaluate our experiences to form accurate metacognitive beliefs, or insight, is an essential component of decision-making. Previous research suggests individuals vary substantially in their level of insight, and that this variation is related to brain volume and function, particularly in the anterior prefrontal cortex (aPFC). However, the neurobiological mechanisms underlying these effects are unclear, as qualitative, macroscopic measures such as brain volume can be related to a variety of microstructural features. Here we leverage a high-resolution (800µm isotropic) multi-parameter mapping technique in 48 healthy individuals to delineate quantitative markers of in vivo histological features underlying metacognitive ability. Specifically, we examined how neuroimaging markers of local grey matter myelination and iron content relate to insight as measured by a signal-theoretic model of subjective confidence. Our results revealed a pattern of microstructural correlates of perceptual metacognition in the aPFC, precuneus, hippocampus, and visual cortices. In particular, we extend previous volumetric findings to show that right aPFC myeloarchitecture positively relates to metacognitive insight. In contrast, decreased myelination in the left hippocampus correlated with better metacognitive insight. These results highlight the ability of quantitative neuroimaging to reveal novel brain-behaviour correlates and may motivate future research on their environmental and developmental underpinnings.

Delta and gamma oscillations in operculo-insular cortex underlie innocuous cold thermosensation.

Cold-sensitive and nociceptive neural pathways interact to shape the quality and intensity of thermal and pain perception. Yet the central processing of cold thermosensation in the human brain has not been extensively studied. Here, we used magnetoencephalography and EEG in healthy volunteers to investigate the time course (evoked fields and potentials) and oscillatory activity associated with the perception of cold temperature changes. Nonnoxious cold stimuli consisting of Δ3°C and Δ5°C decrements from an adapting temperature of 35°C were delivered on the dorsum of the left hand via a contact thermode. Cold-evoked fields peaked at around 240 and 500 ms, at peak latencies similar to the N1 and P2 cold-evoked potentials. Importantly, cold-related changes in oscillatory power indicated that innocuous thermosensation is mediated by oscillatory activity in the range of delta (1-4 Hz) and gamma (55-90 Hz) rhythms, originating in operculo-insular cortical regions. We suggest that delta rhythms coordinate functional integration between operculo-insular and frontoparietal regions, while gamma rhythms reflect local sensory processing in operculo-insular areas.NEW & NOTEWORTHY Using magnetoencephalography, we identified spatiotemporal features of central cold processing, with respect to the time course, oscillatory profile, and neural generators of cold-evoked responses in healthy human volunteers. Cold thermosensation was associated with low- and high-frequency oscillatory rhythms, both originating in operculo-insular regions. These results support further investigations of central cold processing using magnetoencephalography or EEG and the clinical utility of cold-evoked potentials for neurophysiological assessment of cold-related small-fiber function and damage.

Anterior insula coordinates hierarchical processing of tactile mismatch responses.

The body underlies our sense of self, emotion, and agency. Signals arising from the skin convey warmth, social touch, and the physical characteristics of external stimuli. Surprising or unexpected tactile sensations can herald events of motivational salience, including imminent threats (e.g., an insect bite) and hedonic rewards (e.g., a caressing touch). Awareness of such events is thought to depend upon the hierarchical integration of body-related mismatch responses by the anterior insula. To investigate this possibility, we measured brain activity using functional magnetic resonance imaging, while healthy participants performed a roving tactile oddball task. Mass-univariate analysis demonstrated robust activations in limbic, somatosensory, and prefrontal cortical areas previously implicated in tactile deviancy, body awareness, and cognitive control. Dynamic Causal Modelling revealed that unexpected stimuli increased the strength of forward connections along a caudal to rostral hierarchy-projecting from thalamic and somatosensory regions towards insula, cingulate and prefrontal cortices. Within this ascending flow of sensory information, the AIC was the only region to show increased backwards connectivity to the somatosensory cortex, augmenting a reciprocal exchange of neuronal signals. Further, participants who rated stimulus changes as easier to detect showed stronger modulation of descending PFC to AIC connections by deviance. These results suggest that the AIC coordinates hierarchical processing of tactile prediction error. They are interpreted in support of an embodied predictive coding model where AIC mediated body awareness is involved in anchoring a global neuronal workspace.

Neurocognitive evidence for mental imagery-driven hypoalgesic and hyperalgesic pain regulation.

Mental imagery has the potential to influence perception by directly altering sensory, cognitive, and affective brain activity associated with imagined content. While it is well established that mental imagery can both exacerbate and alleviate acute and chronic pain, it is currently unknown how imagery mechanisms regulate pain perception. For example, studies to date have been unable to determine whether imagery effects depend upon a general redirection of attention away from pain or focused attentional mechanisms. To address these issues, we recorded subjective, behavioral and ERP responses using 64-channel EEG while healthy human participants applied a mental imagery strategy to decrease or increase pain sensations. When imagining a glove covering the forearm, participants reported decreased perceived intensity and unpleasantness, classified fewer high-intensity stimuli as painful, and showed a more conservative response bias. In contrast, when imagining a lesion on the forearm, participants reported increased pain intensity and unpleasantness, classified more low-intensity stimuli as painful, and displayed a more liberal response bias. Using a mass-univariate approach, we further showed differential modulation of the N2 potentials across conditions, with inhibition and facilitation respectively increasing and decreasing N2 amplitudes between 122 and 180 ms. Within this time window, source localization associated inhibiting vs. facilitating pain with neural activity in cortical regions involved in cognitive inhibitory control and in the retrieval of semantic information (i.e., right inferior frontal and temporal regions). In contrast, the main sources of neural activity associated with facilitating vs. inhibiting pain were identified in cortical regions typically implicated in salience processing and emotion regulation (i.e., left insular, inferior-middle frontal, supplementary motor and precentral regions). Overall, these findings suggest that the content of a mental image directly alters pain-related decision and evaluative processing to flexibly produce hypoalgesic and hyperalgesic outcomes.

Domain-specific updating of metacognitive self-beliefs.

Metacognitive self-monitoring is thought to be largely domain-general, with numerous prior studies providing evidence of a metacognitive g-factor. The observation of shared inter-individual variance across different measures of metacognition does not however preclude the possibility that some aspects may nevertheless be domain-specific. In particular, it is unknown the degree to which explicit metacognitive beliefs regarding one's own abilities may exhibit domain generality. Similarly, little is known about how such prior self-beliefs are maintained and updated in the face of new metacognitive experiences. In this study of 330 healthy individuals, we explored metacognitive belief updating across memory, visual, and general knowledge domains spanning nutritional and socioeconomic facts. We find that across all domains, participants strongly reduced their self-belief (i.e., expressed less confidence in their abilities) after completing a multi-domain metacognition test battery. Using psychological network and cross-correlation analyses, we further found that while metacognitive confidence exhibited strong domain generality, metacognitive belief updating was highly domain-specific, such that participants shifted their confidence specifically according to their performance on each domain. Overall, our findings suggest that metacognitive experiences prompt a shift in self-priors from a more general to a more specific focus.

Brain-body states embody complex temporal dynamics.

We propose a computational framework for high-dimensional brain-body states as transient embodiments of nested internal and external dynamics governed by interoception. Unifying recent theoretical work, we suggest ways to reduce arbitrary state complexity to an observable number of features in order to accurately predict and intervene in pathological trajectories.

Aberrant Cardiac Interoception in Psychosis.

BACKGROUND AND HYPOTHESIS: There is mounting evidence that cardiac interoception, the perception of one's heartbeat, is central to affective experiences. It has been proposed that symptoms of psychosis could arise from interoceptive dysfunction. Here we hypothesized that people with psychotic disorders would have a specific impairment in cardiac interoception, over and above broader perceptual deficits. STUDY DESIGN: 43 adults with a history of psychosis (31 schizophrenia, 12 schizoaffective disorder) and 41 matched control participants completed a heart rate discrimination task. Participants responded to whether they perceived a sequence of auditory tones to be faster or slower than their heart rate. By trialing a range of auditory tone rates, we estimated a threshold for each participant, the difference between perceived heart rate and actual heart rate. To test whether differences were specific to interoception, participants completed an exteroceptive control condition, testing their discrimination of the rate of 2 sets of audible sounds instead of heart rate. STUDY RESULTS: Participants with a history of psychosis had greater absolute differences between perceived and actual heart rate, indicating over- or under-estimation of heart rate compared to healthy controls. This difference was specific to the interoceptive condition, and not explained by group differences in exteroceptive perception. CONCLUSIONS: Psychotic disorders are associated with misestimation of heart rate. Further research may elucidate whether interoceptive abnormalities contribute to specific symptoms such as somatic delusions or affective features, and whether interoception could be a treatment target in psychotic disorders.

Thermal contrast enhancement predicts paradoxical heat sensation.

Paradoxical Heat Sensation (PHS) is the remarkable feeling of warmth or heat pain while the skin is cooling. Despite its initial documentation over 100 years ago, a unified explanation for this perplexing experience remains elusive. Here we apply contrast enhancement principles, known for their instrumental role in understanding visual illusions, to the domain of thermosensation. Contrast enhancement describes the amplification of two contrasting visual features, such as the enhanced perception of an edge between a light and dark bar. In thermosensation, this encompasses an enhancement of the difference between sequential warming and cooling of the skin, and is defined as the normalised difference between successive temporal warm and cold temperatures. Remarkably, thermal contrast predicts the occurrence of PHS. Our findings reveal compelling evidence supporting the role of thermal contrast in the generation of PHS, shedding light on its underlying mechanism and offering a framework for broader encoding principles in thermosensation and pain.

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.