Uncertainty and stress: Why it causes diseases and how it is mastered by the brain.
TL;DR: Based on the basic tenet that stress originates from uncertainty, an information‐theoretic approach – based on the ‘free energy principle’ – defining the essence of stress; namely, uncertainty is presented.
About: This article is published in Progress in Neurobiology.The article was published on 2017-09-01 and is currently open access. It has received 373 citations till now. The article focuses on the topics: Surprise.
Citations
More filters
TL;DR: A leading model of global brain function, hierarchical predictive coding, is integrated with an often-cited model of the acute action of psychedelics, the entropic brain hypothesis, which states that psychedelics work to relax high-level priors, sensitising them to liberated bottom-up information flow, which can help guide and cultivate the revision of entrenched pathological priors.
Abstract: This paper formulates the action of psychedelics by integrating the free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under psychedelics (REBUS) and the anarchic brain, founded on the principle that—via their entropic effect on spontaneous cortical activity—psychedelics work to relax the precision of high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as the limbic system. We assemble evidence for this model and show how it can explain a broad range of phenomena associated with the psychedelic experience. With regard to their potential therapeutic use, we propose that psychedelics work to relax the precision weighting of pathologically overweighted priors underpinning various expressions of mental illness. We propose that this process entails an increased sensitization of high-level priors to bottom-up signaling (stemming from intrinsic sources), and that this heightened sensitivity enables the potential revision and deweighting of overweighted priors. We end by discussing further implications of the model, such as that psychedelics can bring about the revision of other heavily weighted high-level priors, not directly related to mental health, such as those underlying partisan and/or overly-confident political, religious, and/or philosophical perspectives. Significance Statement Psychedelics are capturing interest, with efforts underway to bring psilocybin therapy to marketing authorisation and legal access within a decade, spearheaded by the findings of a series of phase 2 trials. In this climate, a compelling unified model of how psychedelics alter brain function to alter consciousness would have appeal. Towards this end, we have sought to integrate a leading model of global brain function, hierarchical predictive coding, with an often-cited model of the acute action of psychedelics, the entropic brain hypothesis. The resulting synthesis states that psychedelics work to relax high-level priors, sensitising them to liberated bottom-up information flow, which, with the right intention, care provision and context, can help guide and cultivate the revision of entrenched pathological priors.
361 citations
Cites background from "Uncertainty and stress: Why it caus..."
...…effect (CarhartHarris, 2018a), exemplified by findings of increased brain complexity/entropy (Schartner et al., 2017) and decreased modular differentiation (Petri et al., 2014), provides an iconic image of dysregulated global brain function under psychedelics, with the 5-HT2AR as the trigger point....
[...]
TL;DR: Older adults’ reports of what about the pandemic is stressful, and what brings joy and comfort in the midst of stress are explored, highlighting the importance of understanding the unique stress experience of each individual for effective distress intervention.
Abstract: Background and objectives The coronavirus disease 2019 (COVID-19) pandemic is experienced differently across individuals, and older adults' different life experiences lead to a variety of ways of coping. The present study explores older adults' reports of what about the pandemic is stressful, and what brings joy and comfort in the midst of stress. Research design and methods An online survey asked 825 U.S. adults aged 60 and older to complete questionnaires assessing 3 psychological well-being indicators: perceived stress, negative affect, and positive affect. Participants also responded to open-ended questions about what was stressful and what brought joy or comfort at the time of the survey. A mixed-method approach first qualitatively analyzed the open-ended responses, content analysis identified themes most frequently reported, and quantitative analysis examined the associations between various stressors and joys and the psychological well-being indicators. Results Qualitative analysis revealed 20 stress categories and 21 joy/comfort categories. The most commonly reported stressors were confinement/restrictions, concern for others, and isolation/loneliness; the most commonly reported sources of joy/comfort were family/friend relationships, digital social contact, and hobbies. Demographic comparisons revealed variations in experience. Independent t tests revealed stress from concern for others, the unknown future, and contracting the virus to be significantly associated with poorer psychological well-being; faith, exercise/self-care, and nature were associated with more positive psychological well-being. Discussion and implications Results are discussed in the context of stress and coping theory, highlighting the importance of understanding the unique stress experience of each individual for effective distress intervention.
145 citations
Cites background from "Uncertainty and stress: Why it caus..."
...The unpredictability of who will get sick, how long it will last, and its long-term effects—elevates feelings of uncertainty and uncontrollability, which serve to magnify one’s sense of distress (Peters et al., 2019; Wheaton & Montazer, 2009)....
[...]
...Recent work suggests that chronic uncertainty is the driving mechanism behind ―allostatic load,‖ a term referring to the cumulative effects of stress on the brain and the body (Peters et al., 2019)....
[...]
TL;DR: Central problems in understanding the link between early-life adversity and children’s brain development are discussed and alternative formulations that hold promise for advancing knowledge about the neurobiological mechanisms through which adversity affects human development are suggested.
Abstract: Discovering the processes through which early adverse experiences affect children's nervous-system development, health, and behavior is critically important for developing effective interventions. However, advances in our understanding of these processes have been constrained by conceptualizations that rely on categories of adversity that are overlapping, have vague boundaries, and lack consistent biological evidence. Here, we discuss central problems in understanding the link between early-life adversity and children's brain development. We conclude by suggesting alternative formulations that hold promise for advancing knowledge about the neurobiological mechanisms through which adversity affects human development.
144 citations
Cites background from "Uncertainty and stress: Why it caus..."
...This extended activation alters brain architecture in regions such as the PFC, amygdala, and hippocampus, which undermines adaptive regulation and coping (Peters et al., 2017)....
[...]
TL;DR: Insight in the role of stress in VTA-DA plasticity and connectivity, during reward processing and stress-coping, will be helpful to better understand the mechanism of resilience to breakdown of adaptation.
129 citations
TL;DR: It is suggested mood states act as (hyper) priors over uncertainty (i.e. emotions) in a hierarchical setting and reconciles several strands of research at multiple levels of enquiry.
Abstract: The neurobiological understanding of mood, and by extension mood disorders, remains elusive despite decades of research implicating several neuromodulator systems. This review considers a new approach based on existing theories of functional brain organisation. The free energy principle (a.k.a. active inference), and its instantiation in the Bayesian brain, offers a complete and simple formulation of mood. It has been proposed that emotions reflect the precision of – or certainty about – the predicted sensorimotor/interoceptive consequences of action. By extending this reasoning, in a hierarchical setting, we suggest mood states act as (hyper) priors over uncertainty (i.e. emotions). Here, we consider the same computational pathology in the proprioceptive and interoceptive (behavioural and autonomic) domain in order to furnish an explanation for mood disorders. This formulation reconciles several strands of research at multiple levels of enquiry.
115 citations
Cites background from "Uncertainty and stress: Why it caus..."
...This means that allostatic control is precluded – and is replaced by low-level homoeostatic responses (Barrett et al. 2016; Stephan et al. 2016; Peters et al. 2017)....
[...]
References
More filters
TL;DR: This final installment of the paper considers the case where the signals or the messages or both are continuously variable, in contrast with the discrete nature assumed until now.
Abstract: In this final installment of the paper we consider the case where the signals or the messages or both are continuously variable, in contrast with the discrete nature assumed until now. To a considerable extent the continuous case can be obtained through a limiting process from the discrete case by dividing the continuum of messages and signals into a large but finite number of small regions and calculating the various parameters involved on a discrete basis. As the size of the regions is decreased these parameters in general approach as limits the proper values for the continuous case. There are, however, a few new effects that appear and also a general change of emphasis in the direction of specialization of the general results to particular cases.
65,425 citations
16,176 citations
TL;DR: A summary of the layout of cortical areas associated with vision and with other modalities, a computerized database for storing and representing large amounts of information on connectivity patterns, and the application of these data to the analysis of hierarchical organization of the cerebral cortex are reported on.
Abstract: In recent years, many new cortical areas have been identified in the macaque monkey. The number of identified connections between areas has increased even more dramatically. We report here on (1) a summary of the layout of cortical areas associated with vision and with other modalities, (2) a computerized database for storing and representing large amounts of information on connectivity patterns, and (3) the application of these data to the analysis of hierarchical organization of the cerebral cortex. Our analysis concentrates on the visual system, which includes 25 neocortical areas that are predominantly or exclusively visual in function, plus an additional 7 areas that we regard as visual-association areas on the basis of their extensive visual inputs. A total of 305 connections among these 32 visual and visual-association areas have been reported. This represents 31% of the possible number of pathways if each area were connected with all others. The actual degree of connectivity is likely to be closer to 40%. The great majority of pathways involve reciprocal connections between areas. There are also extensive connections with cortical areas outside the visual system proper, including the somatosensory cortex, as well as neocortical, transitional, and archicortical regions in the temporal and frontal lobes. In the somatosensory/motor system, there are 62 identified pathways linking 13 cortical areas, suggesting an overall connectivity of about 40%. Based on the laminar patterns of connections between areas, we propose a hierarchy of visual areas and of somatosensory/motor areas that is more comprehensive than those suggested in other recent studies. The current version of the visual hierarchy includes 10 levels of cortical processing. Altogether, it contains 14 levels if one includes the retina and lateral geniculate nucleus at the bottom as well as the entorhinal cortex and hippocampus at the top. Within this hierarchy, there are multiple, intertwined processing streams, which, at a low level, are related to the compartmental organization of areas V1 and V2 and, at a high level, are related to the distinction between processing centers in the temporal and parietal lobes. However, there are some pathways and relationships (about 10% of the total) whose descriptions do not fit cleanly into this hierarchical scheme for one reason or another. In most instances, though, it is unclear whether these represent genuine exceptions to a strict hierarchy rather than inaccuracies or uncertainities in the reported assignment.
7,796 citations
"Uncertainty and stress: Why it caus..." refers background in this paper
...The brain’s architecture is hierarchically organized (Felleman and Van, 1991)....
[...]
...The anatomical correlates of hierarchical predictive coding The brain’s architecture is hierarchically organized (Felleman and Van, 1991)....
[...]
TL;DR: The long-term effect of the physiologic response to stress is reviewed, which I refer to as allostatic load, which is the ability to achieve stability through change.
Abstract: Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators. This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .
5,932 citations
"Uncertainty and stress: Why it caus..." refers background in this paper
...All of these long-lasting effects of persistently activated stress reactions are called ‘allostatic load’ (McEwen, 1998)....
[...]
...People living in a volatile and insecure environment (e.g., an insecure job, unhappy relationship, poverty, etc) have a high risk of depression, cognitive impairment, myocardial infarction, and stroke (McEwen, 1998; Peters and McEwen, 2015)....
[...]
...These pathologies include memory impairment, depression, myocardial infarction, stroke, visceral fat accumulation, type 2 diabetes, muscle loss, osteoporosis, disturbed growth and reproduction (McEwen, 1998)....
[...]
..., an insecure job, unhappy relationship, poverty, etc) have a high risk of depression, cognitive impairment, myocardial infarction, and stroke (McEwen, 1998; Peters and McEwen, 2015)....
[...]
Posted Content•
TL;DR: The information deviation between any two finite measures cannot be increased by any statistical operations (Markov morphisms) and is invarient if and only if the morphism is sufficient for these two measures as mentioned in this paper.
Abstract: The information deviation between any two finite measures cannot be increased by any statistical operations (Markov morphisms). It is invarient if and only if the morphism is sufficient for these two measures
5,228 citations
"Uncertainty and stress: Why it caus..." refers background in this paper
...From a theoretical perspective, the difference between attainable states and goal states can be formalized by the so-called ‘Kullback Leibler (KL) divergence’ (Kullback and Leibler, 1951)....
[...]
...‘Kullback Leibler (KL) divergence’ (Kullback and Leibler, 1951)....
[...]