REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

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

Assessing the learning and transfer of gaze behaviours in immersive virtual reality

This is the final version. Available on open access from Springer via the DOI in this recordAvailability of data and materials: All data are available online from the Open Science Framework [https://osf.io/5n9j3/].Virtual reality (VR) has clear potential for improving simulation training in many industries. Yet, methods for testing the fidelity, validity and training efficacy of VR environments are, in general, lagging behind their adoption. There is limited understanding of how readily skills learned in VR will transfer, and what features of training design will facilitate effective transfer. Two potentially important elements are the psychological fidelity of the environment, and the stimulus correspondence with the transfer context. In this study, we examined the effectiveness of VR for training police room searching procedures, and assessed the corresponding development of perceptual-cognitive skill through eye-tracking indices of search efficiency. Participants (n = 54) were assigned to a VR rule-learning and search training task (FTG), a search only training task (SG) or a no-practice control group (CG). Both FTG and SG developed more efficient search behaviours during the training task, as indexed by increases in saccade size and reductions in search rate. The FTG performed marginally better than the CG on a novel VR transfer test, but no better than the SG. More efficient gaze behaviours learned during training were not, however, evident during the transfer test. These findings demonstrate how VR can be used to develop perceptual-cognitive skills, but also highlight the challenges of achieving transfer of training.Royal Academy of Engineering (RAE

Streams of data from drops of water: 21st century molecular microbial ecology

Microorganisms are ubiquitous and represent a taxonomically and functionally diverse component of freshwater environments of significant ecological importance. The bacteria, archaea, and microbial eukarya in freshwater systems support a range of ecosystem processes and functions, including mediating all major biogeochemical cycles, and therefore regulate the flow of multiple ecosystem services. Yet relative to conspicuous higher taxa, microbial ecology remains poorly understood. As the anthropocene progresses, the demand for freshwater–ecosystem services is both increasing with growing human population density, and by association, increasingly threatened from multiple and often interacting stressors, such as climate change, eutrophication, and chemical pollution. Thus, it is imperative to understand the ecology of microorganisms and their functional role in freshwater ecosystems if we are to manage the future of these environments effectively. To do this, researchers have developed a vast array of molecular tools that can illuminate the diversity, composition, and activity of microbial communities. Within this primer, we discuss the history of molecular approaches in microbial ecology, and highlight the scope of questions that these methods enable researchers to address. Using some recent case studies, we describe some exemplar research into the microbial ecology of freshwater systems, and emphasize how molecular methods can provide novel ecological insights. Finally, we detail some promising developments within this research field, and how these might shape the future research landscape of freshwater microbial ecology

Factors associated with alcohol reduction in harmful and hazardous drinkers following alcohol brief intervention in Scotland: a qualitative enquiry

Background: Alcohol Brief Intervention (ABI) uses a motivational counselling approach to support individuals to reduce excessive alcohol consumption. There is growing evidence on ABI’s use within various health care settings, although how they work and which components enhance success is largely unknown. This paper reports on the qualitative part of a mixed methods study. It explores enablers and barriers associated with alcohol reduction following an ABI. It focuses on alcohol’s place within participants’ lives and their personal perspectives on reducing consumption. There are a number of randomised controlled trials in this field though few ABI studies have addressed the experiences of hazardous/harmful drinkers. This study examines factors associated with alcohol reduction in harmful/hazardous drinkers following ABI. Methods: This qualitative study was underpinned by a realist evaluation approach and involved semistructured interviews with ten harmful or hazardous alcohol drinkers. Participants (n = 10) were from the intervention arm of a randomised controlled trial (n = 124). All had received ABI, a 20 min motivational counselling interview, six months previously, and had reduced their alcohol consumption. Interviews were recorded, transcribed verbatim and thematically analysed. Results: Participants described their views on alcohol, its’ place in their lives, their personal perspectives on reducing their consumption and future aspirations. Conclusions: The findings provide an insight into participants’ views on alcohol, ABI, and the barriers and enablers to change. Participants described a cost benefit analysis, with some conscious consideration of the advantages and disadvantages of reducing intake or abstaining from alcohol. Findings suggest that, whilst hospital admission can act as a catalyst, encouraging individuals to reflect on their alcohol consumption through ABI may consolidate this, turning this reflective moment into action. Sustainability may be enhanced by the presence of a ‘significant other’ who encourages and experiences benefit. In addition having a purpose or structure with activities linked to employment and/or social and leisure pursuits offers the potential to enhance and sustain reduced alcohol consumption. Trial registration: Trial registration number TRN NCT00982306 September 22nd 200

Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention

Development of a generic activities model of command and control

This paper reports on five different models of command and control. Four different models are reviewed: a process model, a contextual control model, a decision ladder model and a functional model. Further to this, command and control activities are analysed in three distinct domains: armed forces, emergency services and civilian services. From this analysis, taxonomies of command and control activities are developed that give rise to an activities model of command and control. This model will be used to guide further research into technological support of command and control activities

Hippocampal place cells encode global location but not connectivity in a complex space

Flexible navigation relies on a cognitive map of space, thought to be implemented by hippocampal place cells: neurons that exhibit location-specific firing. In connected environments, optimal navigation requires keeping track of one’s location and of the available connections between subspaces. We examined whether the dorsal CA1 place cells of rats encode environmental connectivity in four geometrically identical boxes arranged in a square. Rats moved between boxes by pushing saloon-type doors that could be locked in one or both directions. Although rats demonstrated knowledge of environmental connectivity, their place cells did not respond to connectivity changes, nor did they represent doorways differently from other locations. Place cells coded location in a global reference frame, with a different map for each box and minimal repetitive fields despite the repetitive geometry. These results suggest that CA1 place cells provide a spatial map that does not explicitly include connectivity

Determinants of muscle carnosine content

The main determinant of muscle carnosine (M-Carn) content is undoubtedly species, with, for example, aerobically trained female vegetarian athletes [with circa 13 mmol/kg dry muscle (dm)] having just 1/10th of that found in trained thoroughbred horses. Muscle fibre type is another key determinant, as type II fibres have a higher M-Carn or muscle histidine containing dipeptide (M-HCD) content than type I fibres. In vegetarians, M-Carn is limited by hepatic synthesis of β-alanine, whereas in omnivores this is augmented by the hydrolysis of dietary supplied HCD’s resulting in muscle levels two or more times higher. β-alanine supplementation will increase M-Carn. The same increase in M-Carn occurs with administration of an equal molar quantity of carnosine as an alternative source of β-alanine. Following the cessation of supplementation, M-Carn returns to pre-supplementation levels, with an estimated t1/2 of 5–9 weeks. Higher than normal M-Carn contents have been noted in some chronically weight-trained subjects, but it is unclear if this is due to the training per se, or secondary to changes in muscle fibre composition, an increase in β-alanine intake or even anabolic steroid use. There is no measureable loss of M-Carn with acute exercise, although exercise-induced muscle damage may result in raised plasma concentrations in equines. Animal studies indicate effects of gender and age, but human studies lack sufficient control of the effects of diet and changes in muscle fibre composition