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

Pharmacological Reviews, Journal Year: 2019, Volume and Issue: 71(3), P. 316 - 344

Published: June 20, 2019

This paper formulates the action of psychedelics by integrating free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under (REBUS) anarchic brain, founded on that—via their effect spontaneous cortical activity—psychedelics work to relax precision high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as limbic system. assemble evidence for model show how it can explain a broad range phenomena associated with psychedelic experience. With regard potential therapeutic use, we propose that weighting pathologically overweighted underpinning various expressions mental illness. process entails an increased sensitization signaling (stemming from sources), heightened sensitivity enables revision deweighting priors. end discussing further implications model, bring about other heavily weighted priors, not directly related health, those underlying partisan and/or overly-confident political, religious, philosophical perspectives.

Significance Statement

Psychedelics are capturing interest, efforts underway psilocybin therapy marketing authorisation legal access within decade, spearheaded findings series phase 2 trials. In climate, compelling unified how alter function consciousness would have appeal. Towards end, sought integrate leading global function, hierarchical predictive coding, often-cited acute psychedelics, the hypothesis. The resulting synthesis states sensitising them liberated which, right intention, care provision context, help guide cultivate entrenched pathological

Language: Английский

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Serotonin and brain function: a tale of two receptors

Journal of Psychopharmacology, Journal Year: 2017, Volume and Issue: 31(9), P. 1091 - 1120

Published: Aug. 31, 2017

Previous attempts to identify a unified theory of brain serotonin function have largely failed achieve consensus. In this present synthesis, we integrate previous perspectives with new and older data create novel bipartite model centred on the view that neurotransmission enhances two distinct adaptive responses adversity, mediated in large part by its most prevalent researched receptors: 5-HT1A 5-HT2A receptors. We propose passive coping (i.e. tolerating source stress) is postsynaptic 5-HT1AR signalling characterised stress moderation. Conversely, argue active actively addressing 5-HT2AR enhanced plasticity (defined as capacity for change). 5-HT1AR-mediated moderation may be brain’s default response adversity but an improved ability change one’s situation and/or relationship it via 5-HT2AR-mediated also important – increasingly so level reaches critical point. pathway conventional 5-HT reuptake blocking antidepressants such selective inhibitors (SSRIs), whereas 5-HT2AR-agonist psychedelics. This purports explain how different drugs (SSRIs psychedelics) modulate serotonergic system ways, can complementary potentially therapeutic outcomes.

Language: Английский

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The entropic brain - revisited

Neuropharmacology, Journal Year: 2018, Volume and Issue: 142, P. 167 - 178

Published: March 18, 2018

Language: Английский

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Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(11), P. 1569 - 1581

Published: Oct. 27, 2022

Abstract Neurotransmitter receptors support the propagation of signals in human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, there exists no comprehensive atlas receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative 19 transporters across nine different neurotransmitter systems. We found that profiles align with structural connectivity mediate function, including neurophysiological oscillatory dynamics resting-state hemodynamic functional connectivity. Using Neurosynth cognitive atlas, uncovered topographic gradient overlapping distributions separates extrinsic intrinsic psychological processes. Finally, both expected novel associations between cortical abnormality patterns 13 disorders. replicated all findings an independently collected autoradiography dataset. This work demonstrates chemoarchitecture shapes brain structure providing new direction for studying multi-scale organization.

Language: Английский

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Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels

Neuropsychopharmacology, Journal Year: 2019, Volume and Issue: 44(7), P. 1328 - 1334

Published: Jan. 26, 2019

Language: Английский

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Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin

Scientific Reports, Journal Year: 2017, Volume and Issue: 7(1)

Published: April 19, 2017

Abstract What is the level of consciousness psychedelic state? Empirically, measures neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than states with lower conscious like propofol-induced anesthesia. Here we compute these spontaneous magnetoencephalographic (MEG) signals from humans during altered induced by three substances: psilocybin, ketamine LSD. For all three, find reliably diversity, even when controlling spectral changes. This increase most pronounced single-channel LZ measure, hence temporal, opposed to spatial, diversity. We also uncover selective correlations between changes in phenomenological reports intensity experience. first time that have been applied state and, crucially, they yielded values exceeding those normal waking consciousness. These findings suggest sustained occurrence phenomenology constitutes an elevated - measured

Language: Английский

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Psychedelic Psychiatry’s Brave New World

Cell, Journal Year: 2020, Volume and Issue: 181(1), P. 24 - 28

Published: April 1, 2020

After a legally mandated, decades-long global arrest of research on psychedelic drugs, investigation psychedelics in the context psychiatric disorders is yielding exciting results. Outcomes neuroscience and clinical into 5-Hydroxytryptamine 2A (5-HT2A) receptor agonists, such as psilocybin, show promise for addressing range serious disorders, including depression addiction.

Language: Английский

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Dynamic coupling of whole-brain neuronal and neurotransmitter systems

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(17), P. 9566 - 9576

Published: April 13, 2020

Significance In a technical tour de force, we have created framework demonstrating the underlying fundamental principles of bidirectional coupling neuronal and neurotransmitter dynamical systems. Specifically, in present study, combined multimodal neuroimaging data to causally explain functional effects specific serotoninergic receptor (5-HT 2A R) stimulation with psilocybin healthy humans. Longer term, this could provide better understanding why is showing considerable promise as therapeutic intervention for neuropsychiatric disorders including depression, anxiety, addiction.

Language: Английский

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Comparing spatial null models for brain maps

NeuroImage, Journal Year: 2021, Volume and Issue: 236, P. 118052 - 118052

Published: April 19, 2021

Technological and data sharing advances have led to a proliferation of high-resolution structural functional maps the brain. Modern neuroimaging research increasingly depends on identifying correspondences between topographies these maps; however, most standard methods for statistical inference fail account their spatial properties. Recently, multiple been developed generate null distributions that preserve autocorrelation brain yield more accurate estimates. Here, we comprehensively assess performance ten published frameworks in analyses data. To test efficacy situations with known ground truth, first apply them series controlled simulations examine impact resolution family-wise error rates. Next, use each framework two empirical datasets, investigating when testing (1) correspondence (e.g., correlating activation maps) (2) distribution feature within partition quantifying specificity an map intrinsic network). Finally, investigate how differences implementation models may performance. In agreement previous reports, find naive do not consistently elevated false positive rates unrealistically liberal While spatially-constrained yielded realistic, conservative estimates, even suffer from inflated variable across analyses. Throughout our results, observe minimal parcellation model Altogether, findings highlight need continued development statistically-rigorous comparing maps. The present report provides harmonised benchmarking future advancements.

Language: Английский

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neuromaps: structural and functional interpretation of brain maps

Nature Methods, Journal Year: 2022, Volume and Issue: 19(11), P. 1472 - 1479

Published: Oct. 6, 2022

Abstract Imaging technologies are increasingly used to generate high-resolution reference maps of brain structure and function. Comparing experimentally generated these facilitates cross-disciplinary scientific discovery. Although recent data sharing initiatives increase the accessibility maps, often shared in disparate coordinate systems, precluding systematic accurate comparisons. Here we introduce neuromaps, a toolbox for accessing, transforming analyzing structural functional annotations. We implement functionalities generating high-quality transformations between four standard systems. The includes curated biological ontologies human brain, such as molecular, microstructural, electrophysiological, developmental ontologies. Robust quantitative assessment map-to-map similarity is enabled via suite spatial autocorrelation-preserving null models. neuromaps combines open-access with transparent functionality standardizing comparing providing workflow comprehensive annotation enrichment analysis brain.

Language: Английский

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