Human brain effects of DMT assessed via EEG-fMRI

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(13)

Published: March 20, 2023

Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the of intravenous (IV) N,N-Dimethyltryptamine (DMT) in 20 healthy volunteers. Simultaneous was prior to, during, and after bolus IV administration mg DMT, and, separately, placebo. At dosages consistent with present study, serotonin 2A receptor (5-HT2AR) agonist, induces deeply immersive radically altered state consciousness. DMT is thus useful research tool for probing neural correlates conscious experience. Here, fMRI results revealed robust increases global functional connectivity (GFC), network disintegration desegregation, compression principal cortical gradient under DMT. GFC × subjective intensity maps correlated independent positron emission tomography (PET)-derived 5-HT2AR maps, both overlapped meta-analytical implying human-specific psychological functions. Changes major EEG-measured neurophysiological properties specific changes various metrics, enriching our understanding basis DMT’s effects. The findings advance previous work by confirming predominant action DMT—and likely other agonist psychedelics—on brain’s transmodal association pole, i.e., neurodevelopmentally evolutionarily recent cortex that associated species-specific advancements, high expression 5-HT2A receptors.

Language: Английский

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Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 3, 2022

Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise part from a flattening of the brain's control energy landscape, which can be observed using network theory to quantify required transition between recurrent states. Using states derived existing functional magnetic resonance imaging (fMRI) datasets, we show LSD reduce for state transitions compared placebo. Furthermore, across individuals, reduction correlates frequent increased dynamics. Through analysis incorporates spatial distribution 5-HT2a receptors (obtained publicly available positron emission tomography (PET) data under non-drug conditions), demonstrate an association reduced energy. Our findings provide evidence agonist allow facile temporally More broadly, receptor-informed model impact neuropharmacological manipulation on activity

Language: Английский

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Psychedelic resting-state neuroimaging: A review and perspective on balancing replication and novel analyses

Neuroscience & Biobehavioral Reviews, Journal Year: 2022, Volume and Issue: 138, P. 104689 - 104689

Published: May 16, 2022

Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) a commonly used strategy to identify psychedelic-induced changes in neural pathways clinical and healthy populations. Here we, large group of psychedelic researchers, review the 42 articles published date, based on 17 unique studies evaluating effects rs-fMRI, focusing methodological variation. Prominently, we observe that nearly all vary data processing analysis methodology, two datasets are foundation over half literature, there lexical ambiguity common outcome metric terminology. We offer guidelines for future encourage coherence field. Psychedelic rs-fMRI will benefit from development novel methods expand our understanding brain mechanisms mediating its intriguing effects; yet, this field at crossroads where must also consider critical importance consistency replicability effectively converge stable representations psychedelics.

Language: Английский

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New and emerging approaches to treat psychiatric disorders

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(2), P. 317 - 333

Published: Feb. 1, 2023

Language: Английский

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A complex systems perspective on psychedelic brain action

Trends in Cognitive Sciences, Journal Year: 2023, Volume and Issue: 27(5), P. 433 - 445

Published: Feb. 3, 2023

Language: Английский

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Canalization and plasticity in psychopathology

Neuropharmacology, Journal Year: 2022, Volume and Issue: 226, P. 109398 - 109398

Published: Dec. 27, 2022

This theoretical article revives a classical bridging construct, canalization, to describe new model of general factor psychopathology. To achieve this, we have distinguished between two types plasticity, an early one that call 'TEMP' for 'Temperature or Entropy Mediated Plasticity', and another, 'canalization', which is close Hebbian plasticity. These forms plasticity can be most easily by their relationship 'precision' inverse variance; TEMP relates increased variance decreased precision, whereas the opposite true canalization. also subsumes learning rate, (Ising) temperature entropy. Dictionary definitions 'plasticity' it as property being shaped molded; better match this. Importantly, propose 'pathological' phenotypes develop via mechanisms canalization defensive response adversity associated distress dysphoria. Our states entrenches in psychopathology, narrowing phenotypic state-space agent develops expertise pathology. We suggest - combined with gently guiding psychological support counter address questions whether when adaptive versus maladaptive, furnish our references basic human neuroscience, offer concrete experiments measures test its main hypotheses implications. part Special Issue on "National Institutes Health Psilocybin Research Speaker Series".

Language: Английский

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Pattern breaking: a complex systems approach to psychedelic medicine

Neuroscience of Consciousness, Journal Year: 2023, Volume and Issue: 2023(1)

Published: Jan. 1, 2023

Recent research has demonstrated the potential of psychedelic therapy for mental health care. However, psychological experience underlying its therapeutic effects remains poorly understood. This paper proposes a framework that suggests psychedelics act as destabilizers, both psychologically and neurophysiologically. Drawing on 'entropic brain' hypothesis 'RElaxed Beliefs Under pSychedelics' model, this focuses richness experience. Through complex systems theory perspective, we suggest destabilize fixed points or attractors, breaking reinforced patterns thinking behaving. Our approach explains how psychedelic-induced increases in brain entropy neurophysiological set lead to new conceptualizations psychotherapy. These insights have important implications risk mitigation treatment optimization medicine, during peak subacute period recovery.

Language: Английский

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In vivo mapping of pharmacologically induced functional reorganization onto the human brain’s neurotransmitter landscape

Science Advances, Journal Year: 2023, Volume and Issue: 9(24)

Published: June 14, 2023

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to they engage the brain's rich neurotransmitter landscape. Here, bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating regional distribution of 19 receptors transporters obtained from positron emission tomography, changes in magnetic resonance imaging connectivity 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs' function multiple systems. The both anesthetics psychedelics are organized along hierarchical gradients structure function. Last, show that co-susceptibility recapitulates disorder-induced structural alterations. Collectively, these highlight statistical patterns drug-induced reorganization architecture.

Language: Английский

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The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity

Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 48(8), P. 1175 - 1183

Published: April 25, 2023

Abstract Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), novel technique assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomised, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100 μg LSD placebo fMRI sessions. compared EC against (FC) classical statistics machine learning methods. Multivariate analyses parameters revealed predominantly stronger interregional reduced self-inhibition under placebo, with notable exception weakened increased occipital brain regions well subcortical regions. Together, these findings suggests perturbs Excitation/Inhibition balance brain. Notably, did not only provide additional mechanistic insight into effects on brain, but also correlated global subjective discriminated experimental conditions learning-based analysis high accuracy (91.11%), highlighting potential decode or predict future.

Language: Английский

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Intensive whole-brain 7T MRI case study of volitional control of brain activity in deep absorptive meditation states

Cerebral Cortex, Journal Year: 2023, Volume and Issue: 34(1)

Published: Nov. 6, 2023

Abstract Jhanas are profound states of mind achieved through advanced meditation, offering valuable insights into the nature consciousness and tools to enhance well-being. Yet, its neurophenomenology remains limited due methodological difficulties rarity meditation practitioners. We conducted a highly exploratory study investigate jhanas in an intensively sampled adept meditator case (4 hr 7T fMRI collected 27 sessions) who performed jhana rated specific aspects experience immediately thereafter. Linear mixed models correlations were used examine relations among brain activity phenomenology. identified distinctive patterns cortical, subcortical, brainstem, cerebellar regions associated with jhana. Furthermore, we observed between phenomenological qualities attention, jhanic qualities, narrative processing, highlighting distinct compared non-meditative states. Our presents most rigorous evidence yet that practice deconstructs consciousness, unique significant implications for mental health

Language: Английский

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