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George A. Mashour

University of Michigan, Michigan Medicine

74 papers in the library · 2,172 citations · publishing 2006-2026

Papers

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Psilocybin induces dose-dependent changes in functional network organization in rat cortex

bioRxiv (Cold Spring Harbor Laboratory) February 12, 2024 Brian H Silverstein, Nicholas Kolbman, Amanda Nelson et al. 3 citations preprint

Abstract Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in brain networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on brain-wide network dynamics. Previous rodent studies of psychedelics, using electroencephalogram, have primarily been done...

Intravenous psilocybin attenuates mechanical hypersensitivity in a rat model of chronic pain

Current Biology December 1, 2023 Nicholas Kolbman, Tiecheng Liu, Peter R. Guzzo et al. 21 citations

There is a renewed interest in psychedelic drugs as potential therapeutic agents for the treatment of psychiatric disorders. In particular, psilocybin has shown promise for the treatment of refractory depression1 and major depressive disorder2, and has also been explored as a treatment for tobacco and alcohol abuse3,4. However, despite suggestive evidence5,6, there has been no systematic study...

Cellular rules underlying psychedelic control of prefrontal pyramidal neurons

bioRxiv (Cold Spring Harbor Laboratory) October 23, 2023 Tyler G. Ekins, Isla A. W. Brooks, Sameer Kailasa et al. 17 citations preprint

ABSTRACT Classical psychedelic drugs are thought to increase excitability of pyramidal cells in prefrontal cortex via activation of serotonin 2 A receptors (5-HT2 A Rs). Here, we instead find that multiple classes of psychedelics dose-dependently suppress intrinsic excitability of pyramidal neurons, and that extracellular delivery of psychedelics decreases excitability significantly more than...

Intravenous psilocybin administration attenuates mechanical hypersensitivity in a rat model of chronic pain

bioRxiv (Cold Spring Harbor Laboratory) August 28, 2023 Nicholas Kolbman, Tiecheng Liu, Peter R. Guzzo et al. preprint

Abstract There is a renewed interest in the therapeutic potential of psychedelics, including psilocybin, in treating mental health disorders. However, there are no data on the efficacy of psilocybin in alleviating chronic pain. In this study, we investigated the effect of psilocybin on mechanical hypersensitivity and thermal hyperalgesia in a rat model of formalin-induced chronic pain. Adult...

Classical and non-classical psychedelic drugs induce common network changes in human cortex.

Neuroimage June 1, 2023 Rui Dai, Tony E. Larkin, Zirui Huang et al. 49 citations

The neurobiology of the psychedelic experience is not fully understood. Identifying common brain network changes induced by both classical (i.e., acting at the 5-HT2 receptor) and non-classical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during...

Indolethylamine N-methyltransferase (INMT) is not essential for endogenous tryptamine-dependent methylation activity in rats.

Scientific Reports January 6, 2023 Nicolas G. Glynos, Lily Carter, Soo Jung Lee et al. 17 citations

Indolethylamine N-methyltransferase (INMT) is a transmethylation enzyme that utilizes the methyl donor S-adenosyl-L-methionine to transfer methyl groups to amino groups of small molecule acceptor compounds. INMT is best known for its role in the biosynthesis of N,N-Dimethyltryptamine (DMT), a psychedelic compound found in mammalian brain and other tissues. In mammals, biosynthesis of DMT is...

Functional geometry of the cortex encodes dimensions of consciousness

Nature Communications January 5, 2023 Zirui Huang, George A. Mashour, Anthony G. Hudetz

Consciousness is a multidimensional phenomenon, but key dimensions such as awareness and wakefulness have been described conceptually rather than neurobiologically. We hypothesize that dimensions of consciousness are encoded in multiple neurofunctional dimensions of the brain. We analyze cortical gradients, which are continua of the brain’s overarching functional geometry, to characterize these...

Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats.

Anesthesia and analgesia June 1, 2022 Michael A. Brito, Duan Li, Christopher W Fields et al.

Neurophysiologic complexity has been shown to decrease during states characterized by a depressed level of consciousness, such as sleep or anesthesia. Conversely, neurophysiologic complexity is increased during exposure to serotonergic psychedelics or subanesthetic doses of dissociative anesthetics. However, the neurochemical substrates underlying changes in neurophysiologic complexity are...

Ketamine Analgesia and Psychedelia: Can We Dissociate Dissociation?

Anesthesiology March 18, 2022 George A. Mashour 29 citations

Editorial| May 2022 Ketamine Analgesia and Psychedelia: Can We Dissociate Dissociation? George A. Mashour, M.D., Ph.D. George A. Mashour, M.D., Ph.D. Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan. Search for other works by this author on: This Site PubMed Google Scholar Author and Article Information Accepted for publication February 11, 2022....

Dynamic reconfiguration of frequency-specific cortical coactivation patterns during psychedelic and anesthetized states induced by ketamine

Neuroimage January 7, 2022 Duan Li, Phillip E. Vlisides, George A. Mashour 24 citations

Recent neuroimaging studies have demonstrated that spontaneous brain activity exhibits rich spatiotemporal structure that can be characterized as the exploration of a repertoire of spatially distributed patterns that recur over time. The repertoire of brain states may reflect the capacity for consciousness, since general anesthetics suppress and psychedelic drugs enhance such dynamics. However,...

Criticality Creates a Functional Platform for Network Transitions Between Internal and External Processing Modes in the Human Brain

Frontiers in Systems Neuroscience December 1, 2021 Minkyung Kim, Hyoungkyu Kim, Zirui Huang et al.

Continuous switching between internal and external modes in the brain appears important for generating models of the self and the world. However, how the brain transitions between these two modes remains unknown. We propose that a large synchronization fluctuation of brain networks, emerging only near criticality (i.e., a balanced state between order and disorder), spontaneously creates...

Differential classification of states of consciousness using envelope- and phase-based functional connectivity

Neuroimage May 14, 2021 Catherine Duclos, Charlotte Maschke, Yacine Mahdid et al.

The development of sophisticated computational tools to quantify changes in the brain's oscillatory dynamics across states of consciousness have included both envelope- and phase-based measures of functional connectivity (FC), but there are very few direct comparisons of these techniques using the same dataset. The goal of this study was to compare an envelope-based (i.e. Amplitude Envelope...

Anterior insula regulates brain network transitions that gate conscious access

Cell Reports May 1, 2021 Zirui Huang, Vijay Tarnal, Phillip E. Vlisides et al. 119 citations

Conscious access to sensory information is likely gated at an intermediate site between primary sensory and transmodal association cortices, but the structure responsible remains unknown. We perform functional neuroimaging to determine the neural correlates of conscious access using a volitional mental imagery task, a report paradigm not confounded by motor behavior. Titrating propofol to loss...

Neural Correlates of the Shamanic State of Consciousness

Frontiers in Human Neuroscience March 18, 2021 Emma R. Huels, Hyoungkyu Kim, UnCheol Lee et al. 51 citations

Psychedelics have been recognized as model interventions for studying altered states of consciousness. However, few empirical studies of the shamanic state of consciousness, which is anecdotally similar to the psychedelic state, exist. We investigated the neural correlates of shamanic trance using high-density electroencephalography (EEG) in 24 shamanic practitioners and 24 healthy controls...

Consciousness, Anesthesia, and Acetylcholine

Anesthesiology February 26, 2021 D. Pal, George A. Mashour

Although the precise neural correlates of consciousness have not yet been identified, there is one neurochemical marker that appears to track with our capacity to experience something: acetylcholine concentration in the cerebral cortex. Cortical acetylcholine concentration is high during wakefulness, decreases during slow-wave sleep, and increases again during rapid eye movement sleep, when we...

Brain network motifs are markers of loss and recovery of consciousness

Scientific Reports February 16, 2021 Catherine Duclos, Danielle Nadin, Yacine Mahdid et al. 28 citations

Motifs are patterns of inter-connections between nodes of a network, and have been investigated as building blocks of directed networks. This study explored the re-organization of 3-node motifs during loss and recovery of consciousness. Nine healthy subjects underwent a 3-h anesthetic protocol while 128-channel electroencephalography (EEG) was recorded. In the alpha (8-13 Hz) band, 5-min epochs...

Neural Dynamics in Primate Cortex during Exposure to Subanesthetic Concentrations of Nitrous Oxide.

eNeuro 2021 Matthew S Willsey, Chrono S Nu, Samuel R Nason et al.

Nitrous oxide (N2O) is a hypnotic gas with antidepressant and psychedelic properties at subanesthetic concentrations. Despite long-standing clinical use, there is insufficient understanding of its effect on neural dynamics and cortical processing, which is important for mechanistic understanding of its therapeutic effects. We administered subanesthetic (70%), inhaled N2O and studied the dynamic...

State-Dependent and Bandwidth-Specific Effects of Ketamine and Propofol on Electroencephalographic Complexity in Rats

Frontiers in Systems Neuroscience August 11, 2020 Michael A. Brito, Duan Li, George A. Mashour et al. 15 citations

There is an ongoing debate as to whether ketamine anesthesia suppresses neurophysiologic complexity at doses sufficient for surgical anesthesia, with previous human studies reporting surrogates of both suppressed and preserved levels of cortical complexity. However, these studies have not assessed cortical dynamics in higher gamma frequencies, which have previously been demonstrated to...

Temporal circuit of macroscale dynamic brain activity supports human consciousness

Science Advances March 1, 2020 Zirui Huang, Jun Zhang, Jinsong Wu et al.

Neuroimaging suggests that human consciousness relies on frequent access to default mode and dorsal attention brain networks. The ongoing stream of human consciousness relies on two distinct cortical systems, the default mode network and the dorsal attention network, which alternate their activity in an anticorrelated manner. We examined how the two systems are regulated in the conscious brain...

Cortical dynamics during psychedelic and anesthetized states induced by ketamine

Neuroimage April 5, 2019 Duan Li, George A. Mashour 103 citations

Ketamine is a unique drug that has psychedelic and anesthetic properties in a dose-dependent manner. Recent studies have shown that ketamine anesthesia appears to maintain the spatiotemporal complexity of cortical activation evoked by transcranial magnetic stimulation, while a psychedelic dose of ketamine is associated with increased spontaneous magnetoencephalographic signal diversity....

Relationship of critical dynamics, functional connectivity, and states of consciousness in large‐scale human brain networks

Neuroimage March 1, 2019 Heonsoo Lee, Daniel Golkowski, Denis Jordan et al.

ABSTRACT Recent modeling and empirical studies support the hypothesis that large‐scale brain networks function near a critical state. Similar functional connectivity patterns derived from resting state empirical data and brain network models at criticality provide further support. However, despite the strong implication of a relationship, there has been no principled explanation of how...

Opportunities and challenges for a maturing science of consciousness

Nature Human Behaviour February 1, 2019 M. Michel, Diane M Beck, Ned Block et al.

Scientific research on consciousness is critical to multiple scientific, clinical, and ethical issues. The growth of the field could also be beneficial to several areas including neurology and mental health research. To achieve this goal, we need to set funding priorities carefully and address problems such as job creation and potential media misrepresentation.

Mechanisms of hysteresis in human brain networks during transitions of consciousness and unconsciousness: Theoretical principles and empirical evidence

PLoS Computational Biology August 30, 2018 Hyoungkyu Kim, Joon-Young Moon, George A. Mashour et al. 79 citations

Hysteresis, the discrepancy in forward and reverse pathways of state transitions, is observed during changing levels of consciousness. Identifying the underlying mechanism of hysteresis phenomena in the brain will enhance the ability to understand, monitor, and control state transitions related to consciousness. We hypothesized that hysteresis in brain networks shares the same underlying...

Consciousness and Personhood in Medical Care

Frontiers in Human Neuroscience August 2, 2018 Stefanie Blain-Moraes, Eric Racine, George A. Mashour

Current paradigms in Western medicine often fail to differentiate clearly between consciousness, responsiveness and personhood. The growing number of individuals who exist with sustainable cardiopulmonary systems but who are behaviorally unresponsive has prompted a cultural reconsideration of the relationship between the presence of consciousness and what it means to be a person. This article...