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In this paper, we integrate recent theoretical and empirical developments in predictive coding and active inference accounts of interoception (including the Embodied Predictive Interoception Coding model) with working hypotheses from the theory of constructed emotion to propose a biologically plausible unified theory of the mind that places metabolism and energy regulation (i.e. allostasis), as well as the sensory consequences of that regulation (i.e. interoception), at its core. We then consider the implications of this approach for understanding depression. We speculate that depression is a disorder of allostasis, whose myriad symptoms result from a ‘locked in’ brain that is relatively insensitive to its sensory context. We conclude with a brief discussion of the ways our approach might reveal new insights for the treatment of depression. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’.

Large-scale intrinsic brain systems have been identified for exteroceptive senses (such as sight, hearing and touch). We introduce an analogous system for representing sensations from within the body, called interoception, and demonstrate its relation to regulating peripheral systems in the body, called allostasis. Employing the recently introduced Embodied Predictive Interoception Coding (EPIC) model, we used tract-tracing studies of macaque monkeys, followed by two intrinsic functional magnetic resonance imaging samples ( N  = 280 and N  = 270) to evaluate the existence of an intrinsic allostatic–interoceptive system in the human brain. Another sample ( N  = 41) allowed us to evaluate the convergent validity of the hypothesized allostatic–interoceptive system by showing that individuals with stronger connectivity between system hubs performed better on an implicit index of interoceptive ability related to autonomic fluctuations. Implications include insights for the brain’s functional architecture, dissolving the artificial boundary between mind and body, and unifying mental and physical illness. Kleckner et al. use monkey and human data to identify an intrinsic brain system that supports interoception (that is, sensations from within the body) and allostasis (that is, the process by which the brain maintains energy regulation in the body).

This paper integrates emerging evidence from two broad streams of scientific literature into one common framework: (a) hierarchical gradients of functional connectivity that reflect the brain’s large-scale structural architecture (e.g., a lamination gradient in the cerebral cortex); and (b) approaches to predictive processing and one of its specific instantiations called (i.e., the predictive regulation of energetic resources in the service of coordinating the body’s internal systems). This synthesis begins to sketch a coherent, neurobiologically inspired framework suggesting that predictive energy regulation is at the core of human brain function, and by extension, psychological and behavioral phenomena, providing a shared vocabulary for theory building and knowledge accumulation. Allostasis refers to the process by which the brain anticipates the needs of the body and attempts to meet those needs before they arise, and is one specific instantiation of a broader predictive processing framework. In this perspective article, we propose that allostasis is a basic function of the human brain subserved by an intrinsic architecture composed of two hierarchical functional gradients. Our framework, based on a synthesis of multimodal and multiscale evidence across species, begins to sketch a coherent, neurobiologically inspired research program suggesting that predictive energy regulation is at the core of human brain function, and by extension, psychological and behavioral phenomena, providing a shared vocabulary for theory building and knowledge accumulation.

Medically unexplained syndromes (MUS), also termed persistent physical symptoms, are both prevalent and disabling. Yet treatments for MUS are marked by high rates of patient dissatisfaction, as well as disagreement between patients and providers on the management of persistent physical symptoms. A better understanding of patient-generated goals could increase collaborative goal setting and promote person-centered care, a critical component of MUS treatment; yet research in this area is lacking. This paper aimed to develop a typology of treatment and life goals among Gulf War veterans with a medically unexplained syndrome (Gulf War Illness). We examined participants’ responses to open-ended questions about treatment and life goals using Braun and Clarke’s thematic analysis methodology. Results showed that treatment goals could be categorized into four overarching themes: 1) Get better/healthier, 2) Improve quality of life, 3) Improve or seek additional treatment, and 4) Don’t know/Don’t have any. Life goals were categorized into six overarching themes: 1) Live a fulfilling life, 2) Live a happy life, 3) Live a healthy life, 4) Be productive/financially successful, 5) Manage GWI, and 6) Don’t know/Don’t have any. Treatment goals were largely focused on getting better/healthier (e.g., improving symptoms), whereas life goals focused on living a fulfilling life. Implications for the treatment of Gulf War Illness and patient-provider communication are discussed. ClinicalTrials.gov Identifier: NCT02161133.

Gradient mapping is an important technique to summarize high dimensional biological features as low dimensional manifold representations in exploring brain structure-function relationships at various levels of the cerebral cortex. While recent studies have characterized the major gradients of functional connectivity in several brain structures using this technique, very few have systematically examined the correspondence of such gradients across structures under a common systems-level framework. Using resting-state functional magnetic resonance imaging, here we show that the organizing principles of the isocortex, and those of the cerebellum and hippocampus in relation to the isocortex, can be described using two common functional gradients. We suggest that the similarity in functional connectivity gradients across these structures can be meaningfully interpreted within a common computational framework based on the principles of predictive processing. The present results, and the specific hypotheses that they suggest, represent an important step toward an integrative account of brain function. Analysis of functional MRI data from the Human Connectome Project and Brain Genomics Superstruct Project reveals common functional gradients among the human isocortex, cerebellum, and hippocampus.

Conditions defined by persistent \"medically unexplained\" physical symptoms and syndromes (MUS) are common and disabling. Veterans from the Gulf War (deployed 1990-1991) have notably high prevalence and disability from MUS conditions. Individuals with MUS report that providers do not recognize their MUS conditions. Our goal was to determine if Veterans with MUS receive an ICD-10 diagnosis for a MUS condition or receive disability benefits available to them for these conditions. A chart review was conducted with US Veterans who met case criteria for Gulf War Illness, a complex MUS condition (N = 204, M = 53 years-old, SD = 7). Three coders independently reviewed Veteran's medical records for MUS condition diagnosis or service-connection along with comorbid mental and physical health conditions. Service-connection refers to US Veterans Affairs disability benefits eligibility for conditions or injuries experienced during or exacerbated by military service. Twenty-nine percent had a diagnosis of a MUS condition in their medical record, the most common were irritable colon/irritable bowel syndrome (16%) and fibromyalgia (11%). Slightly more Veterans were service-connected for a MUS condition (38%) as compared to diagnosed. There were high rates of diagnoses and service-connection for mental health (diagnoses 76% and service-connection 74%), musculoskeletal (diagnoses 86%, service-connection 79%), and illness-related conditions (diagnoses 98%, service-connection 49%). Given that all participants were Gulf War Veterans who met criteria for a MUS condition, our results suggest that MUS conditions in Gulf War Veterans are under-recognized with regard to clinical diagnosis and service-connected disability. Veterans were more likely to be diagnosed and service-connected for musculoskeletal-related and mental health conditions than MUS conditions. Providers may need education and training to facilitate diagnosis of and service-connection for MUS conditions. We believe that greater acknowledgement and validation of MUS conditions would increase patient engagement with healthcare as well as provider and patient satisfaction with care.

Exposure to media coverage of mass violence has been shown to predict poorer mental health symptomology. However, it is unknown whether such media coverage can have ubiquitous effects on average community members, extending to biological and perceptual processes that underlie everyday decision making and behavior. Here, we used a repeated-measures design over the first anniversary of the Boston Marathon bombings to track participants' self-reported distress, their eye blink startle reactivity while viewing images of the bombings, and their ability to perceptually distinguish armed from unarmed individuals in a behavioral shooting task. We leveraged a computational linguistics method in which we sampled news content from the sources our participants most commonly self-reported reading, and then quantified both the extent of news coverage about the marathon and the affective tone of that news coverage. Results revealed that participants experienced greater current distress, greater physiological reactivity to threats, and poorer perceptual sensitivity when recent news coverage of the marathon contained more affectively negative words. This is the first empirical work to examine relationships between the media's affective tone in its coverage of mass violence and individuals' threat perception and physiological threat reactivity.

[...]all subsequent references are misnumbered. Changes in Affective Tone of Recent Marathon-related Coverage Predicts Distress, Startle Reactivity, Perceptual Sensitivity, and Shooting Behavior. https://doi.org/10.1371/journal.pone.0250756.t002 thumbnail Download: * PPT PowerPoint slide * PNG larger image * TIFF original image Table 3. Variance components. r0 and r1 refer, respectively, to the participant-level variability in the intercept and slope values (i.e., across-participant variability). r2 refers to the participant-level variability in the slope value for the control variable (i.e., bias or sensitivity) in models relating to threat perception. e refers to the estimated Level-1 error for each model (i.e., wave-level error). *p < .05 https://doi.org/10.1371/journal.pone.0250756.s003 (DOCX) S3 Table. Variance components. r0 and r1 refer, respectively, to the participant-level variability in the intercept and slope values (i.e., across-participant variability). r2 refers to the participant-level variability in the slope value for the control variable (i.e., bias or sensitivity) in models relating to threat perception. e refers to the

Background: The mutual maintenance model proposes that post-traumatic stress disorder (PTSD) symptoms and chronic physical symptoms have a bi-directional temporal relationship. Despite widespread support for this model, there are relatively few empirical tests of the model and these have primarily examined patients with a traumatic physical injury. Objective: To extend the assessment of this model, we examined the temporal relationship between PTSD and physical symptoms for military personnel deployed to combat (i.e., facing the risk of death) who were not evacuated for traumatic injury. Methods: The current study used a prospective, longitudinal design to understand the cross-lagged relationships between PTSD and physical symptoms before, immediately after, 3 months after, and 1 year after combat deployment. Results: The cross-lagged results showed physical symptoms at every time point were consistently related to greater PTSD symptoms at the subsequent time point. PTSD symptoms were related to subsequent physical symptoms, but only at one time-point with immediate post-deployment PTSD symptoms related to physical symptoms at three months after deployment. Conclusion: The findings extend prior work by providing evidence that PTSD and physical symptoms may be mutually maintaining even when there is not a severe traumatic physical injury. * We followed soldiers from before to after combat and found a high comorbidity of PTSD and physical symptoms.* PTSD and physical symptoms were mutually maintaining among soldiers who did not experience a traumatic injury resulting in hospitalization.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.