The brain and body need to adapt constantly to changing social and physical environments. A key mechanism for this adaptation is the ‘stress response’, which is necessary and not negative in and of itself. The term ‘stress’, however, is ambiguous and has acquired negative connotations. We argue that the concept of allostasis can be used instead to describe the mechanisms employed to achieve stability of homeostatic systems through active intervention (adaptive plasticity). In the context of allostasis, resilience denotes (...) the ability of an organism to respond to stressors in the environment by means of the appropriate engagement and efficient termination of allostatic responses. In this review, we discuss the neurobiological and organismal factors that modulate resilience, such as growth factors, chaperone molecules and circadian rhythms, and highlight its consequences for cognition and behavior. (shrink)

Early life adversity, such as child maltreatment or child poverty, engenders problems with emotional and behavioral regulation. In the quest to understand the neurobiological sequelae and mechanisms of risk, the amygdala has been of major focus. While the basic functions of this region make it a strong candidate for understanding the multiple mental health issues common after ELA, extant literature is marked by profound inconsistencies, with reports of larger, smaller, and no differences in regional volumes of this area. We believe (...) integrative models of stress neurodevelopment, grounded in “allostatic load,” will help resolve inconsistencies in the impact of ELA on the amygdala. In this review, we attempt to connect past research studies to new findings with animal models of cellular and neurotransmitter mediators of stress buffering to extreme fear generalization onto testable research and clinical concepts. Drawing on the greater impact of inescapability over unpredictability in animal models, we propose a mechanism by which ELA aggravates an exhaustive cycle of amygdala expansion and subsequent toxic-metabolic damage. We connect this neurobiological sequela to psychosocial mal/adaptation after ELA, bridging to behavioral studies of attachment, emotion processing, and social functioning. Lastly, we conclude this review by proposing a multitude of future directions in preclinical work and studies of humans that suffered ELA. (shrink)

Open peer commentary on the article “Interactivity and Enaction in Human Cognition” by Matthew Isaac Harvey, Rasmus Gahrn-Andersen & Sune Vork Steffensen. Upshot: In contrasting an interactivity account alternative to variants on the enactive approach, the authors discuss the role of sense-making. They claim that their interactivity perspective, unlike enactive approaches, accounts for a dependency on “non-local” resources characteristic of many organisms. I draw attention to the cybernetic-enactivist perspective on homeostatic sense-making, which may fundamentally fail to explain the operationally open (...) nature of organismic regulatory processes better captured by Sterling’s notion of “allostasis.” This sense-making model appears to be more in line with Harvey et al.’s interactivity framework, focusing as it does on the regulatory effect of extrinsic “norms” rather than the cybernetic-enactivist focus on intrinsic “norms.”. (shrink)

This is the penultimate and peer-reviewed version of Chapter 5 from Elpidorou, A., The Anatomy of Boredom, to be published by Oxford University Press in late 2024/early 2025. Please note that this version may differ from the final published version. All rights to this work, including but not limited to rights of reproduction and distribution, are reserved by the publisher, Oxford University Press.

This is the penultimate and peer-reviewed version of Chapter 5 from The Anatomy of Boredom, to be published by Oxford University Press in late 2024/early 2025. Please note that this version may differ from the final published version. All rights to this work, including but not limited to rights of reproduction and distribution, are reserved by the publisher, Oxford University Press.

There are two main paradigms for brain-related science, with different implications for brain-focused intervention or advancement. The paradigm of homeostasis (“stability through constancy,” Walter Cannon), originating from laboratory-based experimental physiology pioneered by Claude Bernard, shows that living systems tend to maintain system functionality in the direction of constancy (or similitude). The aim of physiology is elucidate the factors that maintain homeostasis, and therapeutics aim to correct abnormal factor functions. The homeostasis paradigm does not formally recognize influences outside its controlled experimental (...) frames and it is variable in its modelling of neural contributions. The paradigm of allostatic orchestration (PAO) extends the principle of allostasis (“stability through change”) as originally put forth by Peter Sterling. The PAO originates from an evolutionary perspective and recognizes that biological set points change in anticipation of changing environments. The brain is the organ of central command, orchestrating cross-system operations to support optimal behavior at the level of the whole organism. Alternative views of blood pressure regulation and posttraumatic stress disorder illustrate differences between the paradigms. For the PAO, complexities of top-down neural effects and environmental context are foundational (not to be “factored out”), and anticipatory regulation is the principle of their interface. The allostatic state represents the integrated totality of brain-body interactions. Health itself is an allostatic state of optimal anticipatory oscillation, hypothesized to relate to the state of criticality, a mathematical point of poise between phases, on the border between order and disorder (or the “edge of chaos”). Diseases are allostatic states of impaired anticipatory oscillations, demonstrated as rigidifications of set points across the brain and body (disease comorbidity). Conciliation of the paradigms is possible, with “reactive homeostasis” resolved as an illusion stemming from anticipation of environmental monotony. Considerations are presented with respect to implications of the two paradigms for brain-focused intervention or advancement; the hypothesis that the state of criticality is a vehicle for evolutionary processes; concordance with a philosophy of freedom based on ethical individualism as well as self-creativity, non-obsolescence, empowerment, and citizenship; and concluding reflections on the science and ethics of the placebo, and the potential for virtuous cycles of brain-Anthropocene interactions. (shrink)

Physiologists and historians are still debating what conceptually differentiates each of the three major modern theories of regulation: the constancy of the milieu inte´rieur, homeostasis and allostasis. Here I propose that these models incarnate two distinct regimes of politization of the life sciences.This perspective leads me to suggest that the historicization of physiological norms is intrinsic to the allostatic model, which thus divides it fundamentally from the two others. I analyze the allostatic model in the light of the Canguilhemian (...) theory, showing how the former contributed to the development of a critical epistemology immune to both naturalist essentialism and social constructivism. With a unique clarity in the history of physiology, allostasis gives us a model of the convergence of historical epistemology and scientific practice. As such it played a key role in codifying the epistemological basis of certain current research programs that, in the fields of social epidemiology and feminist neuroscience, promote what we name here a critical physiology. (shrink)

Our culture and its scientific endeavor direly need a holistic characterization of mind and body. Many phenomena attest to the profound effects of beliefs on bodily function (e.g., open-label placebo's effects on chronic pain) and interoceptive systems’ role in mental processes (e.g., the emerging role of gut microbiomes in the mood). We need a mechanistic, integrative framework to account for these phenomena and generate novel predictions. Major advances have been made in understanding how the nervous system senses and regulates the (...) body and in modeling how the brain implements the computations that subserve such activities. However, the vestiges of Cartesianism have entrained a style of thinking in which systems from the brainstem downward exist as the implementation layer of computational processes supporting sensation and behavior, rather than a complementary locus of information processing. As speakers and microphones, rather than other members of the chorus. We are thus forced to perceive well-documented, belief-driven phenomena like placebo, ritual, and psychosomatic disorders as mysterious obstacles or dubious allies rather than as a wellspring of potential. (shrink)

Psychedelic drugs such as psilocybin, LSD and DMT are known to induce powerful alterations in phenomenology. Perhaps of most philosophical and scientific interest is their capacity to disrupt and even “dissolve” one of the most primary features of normal experience: that of being a self. Such “peak” or “mystical” experiences are of increasing interest for their potentially transformative therapeutic value. While empirical research is underway, a theoretical conception of the mechanisms underpinning these experiences remains elusive. In the following paper, psychedelic-induced (...) ego-dissolution is accounted for within an active inference framework, as a collapse in the “temporal thickness” of an agent’s deep temporal model, as a result of lowered precision on high-level priors. The argument here is composed of three moves: first, a view of the self-model is proposed as arising within a temporally deep generative model of an embodied organism navigating an affordance landscape in the service of allostasis. Next, a view of the action of psychedelics as lowering the precision of high-level priors within the generative model is unpacked in terms of a high Bayesian learning rate. Finally, the relaxation of high-level priors is argued to cause a “collapse” in the temporal thickness of the generative model, resulting in a collapse in the self-model and a loss of the ordinary sense of being a self. This account has implications for our understanding of ordinary self-consciousness and disruptions in self-consciousness present in psychosis, autism, depression, and dissociative disorders. The philosophical, theoretical and therapeutic implications of this account are touched upon. (shrink)

Emotion is critical for cultural dynamics, that is, for the formation, maintenance, and transformation of culture over time. We outline the component micro- and macro-level processes of cultural dynamics, and argue that emotion not only facilitates the transmission and retention of cultural information, but also is shaped and crafted by cultural dynamics. Central to this argument is our understanding of emotion as a complete information package that signals the adaptive significance of the information that the agent is processing. It captures (...) an agent’s appraisal about the relationship between themself and the object of emotional focus, as well as action orientation and allostasis in context. We discuss implications of this perspective in the context of the changing natural and geopolitical environment, and future cultural dynamics into the 21st century. (shrink)

This paper aims to offer an account of affective experiences within Predictive Processing, a novel framework that considers the brain to be a dynamical, hierarchical, Bayesian hypothesis-testing mechanism. We begin by outlining a set of common features of affective experiences that a PP-theory should aim to explain: feelings are conscious, they have valence, they motivate behaviour, and they are intentional states with particular and formal objects. We then review existing theories of affective experiences within Predictive Processing and delineate two families (...) of theories: Interoceptive Inference Theories and Error Dynamics Theories. We highlight the strengths and shortcomings of each family of theories and develop a synthesis: the Affective Inference Theory. Affective Inference Theory claims that valence corresponds to the expected rate of prediction error reduction. In turn, the particular object of a feeling is the object predicted to be the most likely cause of expected changes in prediction error rate, and the formal object of a feeling is a predictive model of the expected changes in prediction error rate caused by a given particular object. Finally, our theory shows how affective experiences bias action selection, directing the organism towards allostasis and towards optimal levels of uncertainty in order to minimise prediction error over time. (shrink)

We articulate a conception of resilience via allostasis and the free energy principle to augment Nassim Nicholas Taleb’s conception of antifragility. Creative resilience is resilience 3.0, after robustness (1.0) and antifragility (2.0), because creative resilience is the deliberate effort to construct ecological niches toward a more caring and thus more viable world for more people – what Dewey proffered as the moral ideal of creative democracy. Viability is understood as the healthy tension between stability and precarity. Viability is related (...) to regulatory mechanisms of homeostasis and allostasis. Along with discussion of the free energy principle, we situate these processes of the internal milieu within the external milieu. Ecological niche construction and ecological psychological affordances are related to human practices as means of generating culture. Culture is both a product and producer of the process of valuation, which originates in evolution but is further developed by the free energy principle and social allostasis. The collective languishing exacerbated by the Covid-19 pandemic can be ameliorated through creative resilience so conceived as social allostasis writ large. (shrink)

We present a hierarchical integrated model of self-regulation in which executive function is the cognitive component of the model, together with emotional, behavioral, physiological, and genetic components. These five components in the model are reciprocally and recursively related. The model is supported by empirical evidence, primarily from a single longitudinal study with good measurement at each level of the model. We also find that the model is consistent with current thinking on related topics such as cybernetic theory, the theory of (...) allostasis and allostatic load, and the theory of skill development in harsh and unpredictable environments, referred to as “hidden talents.” Next, we present literature that the integrative processes are susceptible to environmental adversity, poverty-related risk in particular, while positive social interactions with caregivers would promote self-regulatory processes or mitigate the adverse effect of early risk on the processes. A hierarchical integrative model of self-regulation advances our understanding of self-regulatory processes. Future research may consider broader social contexts of the integrative self-regulation system, such as neighborhood/community contexts and structural racism. This can be an integral step to provide children with equitable opportunities to thrive, even among children living in socioeconomically and psychosocially disadvantaged environments. (shrink)

Osteopathy is a person-centred healthcare discipline that emphasizes the body’s structure-function interrelationship—and its self-regulatory mechanisms—to inform a whole-person approach to health and wellbeing. This paper aims to provide a theoretical framework for developing an integrative hypothesis in osteopathy, which is based on the enactivist and active inference accounts. We propose that osteopathic care can be reconceptualised under active inference as a unifying framework. Active inference suggests that action-perception cycles operate to minimize uncertainty and optimize an individual’s internal model of the (...) lived world and, crucially, the consequences of their behaviour. We argue that active inference offers an integrative framework for osteopathy, which can evince the mechanisms underlying dyadic and triadic exchanges and osteopathic care outcomes. We propose that this theoretical framework can underpin osteopathic care across the lifespan, from preterm infants to the elderly and those with persistent pain and other physical symptoms. In situations of chronicity, as an ecological niche, the patient-practitioner dyad provides the osteopath and the patient with a set of affordances, i.e., possibilities for action provided by the environment, that through shared intentionally, can promote adaptations and restoration of productive agency. Through a dyadic therapeutic relationship, as they engage with their ecological niche’s affordances—a structured set of affordances shared by agents—osteopath and patient actively construct a shared sense-making narrative and realise a shared generative model of their relation to the niche. In general, touch plays a critical role in developing a robust therapeutic alliance, mental state alignment, and biobehavioural synchrony between patient and practitioner. However, its role is particularly crucial in the fields of neonatology and paediatrics, where it becomes central in regulating allostasis and restoring homeostasis. We argue that from an active inference standpoint, the dyadic shared ecological niche underwrites a robust therapeutic alliance, which is crucial to the effectiveness of osteopathic care. Considerations and implications of this model—to clinical practice and research, both within- and outside osteopathy—are critically discussed. (shrink)

The well-replicated observation that many people maintain mental health despite exposure to severe psychological or physical adversity has ignited interest in the mechanisms that protect against stress-related mental illness. Focusing on resilience rather than pathophysiology in many ways represents a paradigm shift in clinical-psychological and psychiatric research that has great potential for the development of new prevention and treatment strategies. More recently, research into resilience also arrived in the neurobiological community, posing nontrivial questions about ecological validity and translatability. Drawing on (...) concepts and findings from transdiagnostic psychiatry, emotion research, and behavioral and cognitive neuroscience, we propose a unified theoretical framework for the neuroscientific study of general resilience mechanisms. The framework is applicable to both animal and human research and supports the design and interpretation of translational studies. The theory emphasizes the causal role of stimulus appraisal (evaluation) processes in the generation of emotional responses, including responses to potential stressors. On this basis, it posits that a positive (non-negative) appraisal style is the key mechanism that protects against the detrimental effects of stress and mediates the effects of other known resilience factors. Appraisal style is shaped by three classes of cognitive processes – positive situation classification, reappraisal, and interference inhibition – that can be investigated at the neural level. Prospects for the future development of resilience research are discussed. (shrink)

Neuropragmatism offers a non-dualistic conception of experience from which scientific inquiries can provide resources for sociocultural critique. This reconstructive effort addresses what Emma Dowling calls the care crisis without succumbing to what Mike W. Martin calls therapeutic tyranny. This tyranny relies on problematic dualisms, between mind/body, mind/world, and fact/value, that are also found in neuropsychoanalysis. While pragmatism and psychoanalysis more generally share an evolutionary perspective and can overlap in therapeutic approaches, neuropsychoanalysis diverges from this effort in its dual-aspect monism and (...) positivistic conception of science. Where neuropsychoanalysis seeks to reconcile the first-person subjectivity of lived experience with the third-person objectivity of science, neuropragmatism offers reconstruction. In taking the neuropragmatic turn, neuropsychoanalysts can better utilize Freudian therapies in conjunction with active inference principles, such as the free-energy principle and allostasis. Along with neuropragmatism’s conception of experience as organism-environment dynamic engagement, neuropsychoanalysis can benefit from allostatic approaches to experience and inquiry without reducing experience to brute mechanism or denying the utility of such mechanisms for prediction and intervention. Understanding the value-ladenness of experience, primary and secondary, in everyday waking life and in reflective inquiry, empowers people to better care for themselves without succumbing to merely coping with neoliberal oppression. (shrink)

“Iatrophilosophy” is defined as the translational discipline between medicine and philosophy that has a double objective, theoretical and practical. It is presented a model of practical iatrophilosophy applied to chronic pain associated with depression and stress—depresalgia—, that expands Phenomenologic, Hermeneutic, Dynamic Psychotherapy (PHD) to the general medical field. It starts from the general model of the medical triad - disease, illness, and sickness- and, in the horizon of Ortega's anthropology, five nuclear metaphors are proposed: greed of the body, anguish of (...) circumstance, personal tear, personal knots, and personal expropriation. These are related to the neurobiological mechanisms of central sensitization, allostasis, and alteration of the hypothalamic-pituitary-adrenal axis. A personal recovery process based on therapeutic concord is proposed. The analysis of chronic pain and other complex health problems can benefit from philosophical methodologies such as clinical hermeneutics. (shrink)

What is the relationship between pain and the body? I claim that pain is best explained as a type of personal experience and the bodily response during pain is best explained in terms of a type of mechanical neurophysiologic operation. I apply the radical philosophy of identity theory from philosophy of mind to the relationship between the personal experience of pain and specific neurophysiologic mechanism and argue that the relationship between them is best explained as one of type identity. Specifically, (...) pain is a specific type of personal experience identical to a specific type of allostatic stress response comprised of interdependent nervous, endocrine and immune mechanical operations. (shrink)

This article derives from the Buddhist Nikāya Suttas the idea that fear has an intentional object that is best analysed in anticipatory terms. Something is feared, I argue, if construed as dangerous, where to construe something as dangerous is to anticipate it will cause certain unwanted effects. To help explain what this means, I appeal to the concept of formal objects in the philosophy of emotions and to predictive processing accounts of perception. I demonstrate how this analysis of fear can (...) do exegetical work in the context of the Nikāya Suttas, and respond to philosophical issues concerning the relation between the intentional and anticipatory dimensions of fear; the relevant anticipated effects of feared objects; and whether fearing subjects necessarily know they anticipate unwanted effects. I also draw an analogy to allostatic sensations to engage issues concering how the anticipatory dimension of fear relates to the motivational. (shrink)

This renin‐angiotensin system (RAS) interpretation is focused on differences in tissue dependence on RAS and on the topological hierarchy that allows mediators to act only on downstream tissues.Dependence of tissues on RAS: Tested by expectation maximization clustering of the RNA human tissue expression (https://biogps.org/). ACE and vasoconstrictive AT1R clustered with the prorenin receptor. ACE2 and dilatory MAS1 clustered with nine RAS‐related genes, highly expressed in: Liver; Cardiac_Myocytes; Skeletal_Muscle; Uterus; Kidney; Lung; Small_Intestine; Smooth_Muscle.RAS and stress accumulation: While prorenin is active after (...) binding to its receptor, binding of soluble renin increases its enzymatic activity several times. Increased renin secretion multiplies the overall capacity for producing Ang I, leading to hypertension and increased vascular resistance.Coronavirus infection and comorbidities: Cardiorespiratory failure during infection is linked to the previously altered RAS role in lungs and myocardium. Reduced vasodilation by ACE2 lead to vasoconstriction and suboptimal tissue perfusion patterns. Also see the video abstract here https://www.youtube.com/watch?v=Jf0Iped-Mws. (shrink)