NeuroImage
June 1, 2023
Rui Dai, Tony E Larkin, Zirui Huang et al.
49 citations
Three different psychedelics—nitrous oxide, ketamine, and lysergic acid diethylamide—produce a common pattern of brain network changes despite having distinct molecular mechanisms and delivery methods. Each drug reduced connectivity within brain networks and enhanced connectivity between networks. Specifically, all three increased connections between the right temporoparietal junction and bilateral intraparietal sulcus, and between the precuneus and left intraparietal sulcus. These regions lie within the posterior cortical "hot zone," an area thought to mediate the qualitative aspects of experience. The findings identify a biologically plausible candidate for the subjective effects of both classical and non-classical psychedelics.
Current Biology
December 1, 2023
Nicholas Kolbman, Tiecheng Liu, Peter Guzzo et al.
21 citations
A single intravenous dose of psilocybin reduces mechanical hypersensitivity for 28 days in a rat model of formalin-induced chronic pain, suggesting potential for treating chronic pain conditions. The study addresses a gap in research on psilocybin's effectiveness for chronic pain, as prior work focused on psychiatric disorders and substance abuse. No systematic investigation had previously examined psilocybin's impact on chronic pain indices.
Scientific reports
January 6, 2023
Nicolas G Glynos, Lily Carter, Soo Jung Lee et al.
17 citations
Indolethylamine N-methyltransferase (INMT) is an enzyme known for producing the psychedelic compound DMT in mammalian brains. Researchers created INMT-knockout rats to determine whether INMT is necessary for DMT production. Brain and lung tissues from both normal and INMT-knockout rats showed equal levels of tryptamine-dependent activity, but the resulting products were neither NMT nor DMT. Rat INMT alone was also insufficient for producing NMT or DMT. These findings indicate an alternative enzymatic pathway for DMT biosynthesis exists in rats, motivating further investigation into how mammals produce DMT naturally.
bioRxiv : the preprint server for biology
February 15, 2025
Nicolas G Glynos, Emma R Huels, Amanda Nelson et al.
11 citations
preprint
Intravenous DMT in rats caused dose-dependent increases in serotonin and dopamine in the medial prefrontal and somatosensory cortices, along with changes in brain wave patterns: reduced theta and low gamma power, increased delta, medium gamma, and high gamma power, and altered functional connectivity. All doses produced head twitch responses, most after the low dose. For the first time, endogenous DMT was measured in these cortical sites at levels comparable to serotonin and dopamine, suggesting a physiological role for the compound. The findings point to shared mechanisms with other psychedelics and support DMT's potential for treating psychiatric disorders.
Translational Psychiatry
March 25, 2025
Brian H Silverstein, Nicholas Kolbman, Amanda Nelson et al.
8 citations
Psilocybin alters brain network organization in rats in a dose-dependent manner. Using electroencephalography from 27 cortical sites in 12 rats, the study found that psilocybin disrupted theta-gamma coupling, increased frontal high gamma connectivity and network density, and increased posterior theta connectivity and density. Medium gamma frontoparietal connectivity and behavioral activity showed an inverted-U relationship with dose. These results suggest that high-frequency network organization, decoupled from local theta-phase, may be a key signature of psilocybin-induced altered states of consciousness.
Anesthesiology
June 1, 2024
George A Mashour, UnCheol Lee, Dinesh Pal et al.
8 citations
Near-death experiences have been reported since antiquity and often involve perceptions of light, interactions with entities, and life recall. After in-hospital cardiac arrest, such experiences occur in 10 to 20% of cases. Recent neurophysiologic evidence suggests a surge of gamma oscillations and increased cortical connectivity following cardiac and respiratory arrest, offering a biological basis for this conscious experience.
Sleep
May 26, 2025
Alejandra Mondino, Amir Jadidian, Brandon A Toth et al.
4 citations
The preoptic area of the hypothalamus, long thought to only promote sleep, contains glutamatergic neurons (MLPO_VGLUT2) that actually drive wakefulness and suppress REM sleep. Using fiber photometry in mice, these neurons were highly active during REM sleep, wakefulness, and brief arousals, but minimally active during non-REM sleep. Chemogenetic stimulation of MLPO_VGLUT2 inhibited REM sleep onset, independent of non-REM fragmentation caused by hypothermia, and blocked the REM sleep rebound normally seen after total sleep deprivation. Chemogenetic inhibition increased REM sleep time only during the light phase. Mapping showed these neurons project to brain regions that promote wakefulness and inhibit REM sleep. The authors conclude that MLPO_VGLUT2 powerfully suppress REM sleep, and their overactivation disrupts REM recovery.
bioRxiv (Cold Spring Harbor Laboratory)
February 12, 2024
Brian H Silverstein, Nicholas Kolbman, Amanda Nelson et al.
3 citations
preprint
Psilocybin disrupts the coupling between theta and gamma brain waves in rats and reorganizes brain networks in a dose-dependent manner. Using 27 electrodes across the cortex, the study found that psilocybin increased frontal high gamma connectivity and posterior theta connectivity, as well as network density in those regions. Medium gamma frontoparietal connectivity showed a nonlinear relationship with dose. Theta-gamma phase-amplitude coupling was disrupted. These changes suggest that high-frequency network organization, decoupled from local theta-phase, may be a signature of the altered state of consciousness induced by psilocybin.
JAMA psychiatry
June 1, 2026
Ben Deverett, Duan Li, Theresa R Lii et al.
1 citation
Ketamine produces distinct brain-wave patterns that may be linked to its therapeutic effects. General anesthesia selectively blocks one of these patterns—theta oscillations—while leaving another pattern, beta-gamma oscillations, intact. In 52 participants, ketamine given during anesthesia preserved beta-gamma power increases but eliminated the characteristic theta augmentation seen during awake administration. This suggests that different neurophysiologic effects of ketamine can be separated, offering a way to investigate which brain-wave changes underlie its antidepressant, analgesic, or dissociative properties.
Journal of psychopharmacology (Oxford, England)
May 1, 2025
Niloufar Pouyan, Jacob S Aday, Steven E Harte et al.
1 citation
People with treatment-resistant conditions often see their illness as part of their identity. The pictorial representation of illness and self measure (PRISM) gauges this self-condition enmeshment. In a survey of 297 individuals who used psychedelics therapeutically on their own, most reported symptom improvement: 95.4% with depression, 98.36% with posttraumatic stress disorder, and 94.87% with anxiety. PRISM scores dropped significantly after the most salient psychedelic experience, indicating reduced identification with the condition. The decrease in PRISM scores correlated with symptom improvement across all conditions. PRISM appears useful for tracking how psychedelics affect self-perception across diagnoses, though limitations include convenience sampling, potential positive bias, and retrospective reporting.
bioRxiv : the preprint server for biology
October 23, 2024
Rui Dai, Hyunwoo Jang, Anthony G Hudetz et al.
1 citation
preprint
Consciousness appears to depend on global interactions across multiple brain regions rather than on localized neural activity. Using fMRI data across psychedelic, sleep, and deep sedation states, the study found a mirror-image pattern: psychedelic states increased global functional connectivity and decreased local neural synchrony, while non-REM sleep and deep sedation showed the opposite pattern. This pattern was observed in anterior-posterior and posterior-posterior brain regions but not within the anterior brain alone. Anterior transmodal regions were key for anterior-posterior connectivity, while posterior transmodal and unimodal regions were critical for posterior-posterior connectivity. The findings support global theories of consciousness and bridge the Global Neuronal Workspace hypothesis and Integrated Information Theory by showing shared neural mechanisms.
bioRxiv : the preprint server for biology
June 1, 2026
Panagiotis Fotiadis, Hyunwoo Jang, Rui Dai et al.
Brain waves coordinate neural communication and shape conscious perception. Analyzing blood oxygen level-dependent activity from the Human Connectome Project and other datasets across sleep, propofol anesthesia, and psychedelic states (LSD, DMT, psilocybin, nitrous oxide, ketamine), four dominant wave propagation motifs were identified: a global synchronized wave, an anti-correlated unimodal-transmodal wave, an anti-correlated task-positive/task-negative wave, and an anti-correlated visual-somatomotor wave.
Current biology : CB
July 2, 2026
Youngjai Park, Younghwa Cha, Hyoungkyu Kim et al.
The human brain's information flow alternates between two dominant modes roughly every 200 milliseconds: a top-down mode where anterior brain regions drive posterior activity, and a bottom-up mode with reverse directionality. These sub-second alternations are most prominent during wakefulness, gradually diminish under anesthesia, and show pathological imbalance in attention-deficit/hyperactivity disorder (ADHD). Simultaneous EEG-fMRI recordings reveal that top-down dynamics coincide with increased activity in higher-order cognitive networks, while bottom-up dynamics correspond to heightened sensory network activity. A connectome-based coupled-oscillator model reproduces these transitions, suggesting they emerge naturally from structural connectivity. Relative phase analysis (RPA) enables tracking these whole-brain dynamics with millisecond precision in real time from electroencephalography.
Research square
January 12, 2026
Niloufar Pouyan, Chelsea M Kaplan, Tony E Larkin et al.
Subanesthetic nitrous oxide (N2O) alters visual experience by reconfiguring large-scale brain networks rather than changing early visual processing. In a placebo-controlled fMRI study with 13 healthy adults, participants viewed a flashing checkerboard and rated visual intensity and unpleasantness. Increased unpleasantness under N2O was linked to reduced connectivity between the right anterior insula and the anterior cingulate cortex and lateral occipital cortex. Network analyses revealed reduced modularity and a collapse of hierarchical organization, with sensorimotor connectivity redistributed toward salience and associative networks. These findings suggest that altered visual experience under N2O arises from disrupted salience integration and increased cross-network communication.
bioRxiv : the preprint server for biology
March 28, 2025
Youngjai Park, Younghwa Cha, Hyoungkyu Kim et al.
preprint
The human brain shifts between two directional modes on a sub-second timescale: a top-down mode where anterior regions drive posterior activity and a bottom-up mode with reverse directionality. These shifts are most distinct during full consciousness and become less pronounced as awareness fades. Simultaneous EEG-fMRI recordings show the top-down mode coincides with higher-order cognitive network activity, while the bottom-up mode aligns with sensory system activity. An inattentive ADHD cohort exhibited imbalances in these transition dynamics compared to typically developing individuals. A coupled-oscillator model of the structural brain network reproduced these patterns, suggesting they arise naturally from inter-regional neural interactions.
Nature communications
October 24, 2024
Hyunwoo Jang, George A Mashour, Anthony G Hudetz et al.
A metric called the integration-segregation difference (ISD), derived from fMRI data, captures two key brain network properties: efficiency (integration) and clustering (segregation). During anesthesia with propofol, brain networks shift profoundly toward segregation as consciousness is lost. A common sequence of disintegration and reintegration occurs in unimodal and transmodal networks during loss and return of responsiveness. Machine learning models using these measures accurately identify awake versus unresponsive states. Metastability is more closely linked to integration, while complexity is linked to segregation. Similar patterns appear in sleep. The ISD reliably indexes states of consciousness.
Brain sciences
August 30, 2024
Hyunwoo Jang, Rui Dai, George A Mashour et al.
A machine learning model that combines functional connectivity, graph-theoretic metrics, and cortical gradient features can classify brain states—including unconsciousness (NREM2 sleep, propofol sedation and anesthesia), psychedelic states (ketamine, LSD, nitrous oxide), and neuropsychiatric disorders (ADHD, bipolar disorder, schizophrenia)—with an average balanced accuracy of 79% (range 62–98%). The ensemble model outperformed individual feature-based models (70–76%). Transferability across datasets varied, and feature importance analysis indicated that different brain states rely on distinct neural mechanisms, suggesting that tailored approaches are needed for accurate classification. The findings highlight the value of integrating multiple feature types for robust brain-state classification, though further work is needed for broader generalizability.
Anesthesia and analgesia
June 1, 2022
Michael A Brito, Duan Li, Christopher W Fields et al.
Cortical acetylcholine levels correlate with neurophysiologic complexity and frontoparietal connectivity during altered states of consciousness. In rats under isoflurane anesthesia, subanesthetic ketamine (10 mg/kg/h) produced sustained increases in brain complexity and high gamma connectivity, accompanied by progressive rises in prefrontal (104%) and parietal (159%) acetylcholine. Nitrous oxide caused a transient increase in complexity and connectivity with smaller acetylcholine increases (prefrontal 56%, parietal 43%), followed by a later phase of decreased acetylcholine, reduced complexity, and weaker connectivity. These findings link cortical acetylcholine to changes in consciousness level.
eNeuro
January 1, 2021
Matthew S Willsey, Chrono S Nu, Samuel R Nason et al.
Inhaling 70% nitrous oxide (N2O) increases spiking rates and beta- and gamma-band power in the primary motor cortex of macaques while degrading the representation of somatosensory information. The proportion of correctly classified finger touches dropped from 0.50 to 0.34 during N2O inhalation, indicating impaired information transfer. The increased firing rate was not correlated with changes in neuronal tuning, suggesting a dissociation between overall activity and sensory processing.
Consciousness and cognition
December 1, 2008
George A Mashour, Eric LaRock
Philosophical p-zombies are imagined beings that behave like humans but lack consciousness, used to challenge physicalist theories of mind. Inverting this concept yields i-zombies: beings that appear unconscious but are actually conscious. A real-world approximation of i-zombies exists in anesthesia awareness, where 1-2 per 1000 patients under general anesthesia become conscious during surgery despite appearing unconscious due to paralysis and intubation. Additionally, 22% of patients in a recent study reported dreaming during anesthesia. P-zombies raise the hard problem of explaining qualia; i-zombies pose the practical problem of detecting qualia. The work compares these concepts and examines the hard problem of unconsciousness through anesthesia awareness.