NeuroImage
April 5, 2019
Duan Li, George A. Mashour
103 citations
Ketamine produces dose-dependent effects on the brain's spatiotemporal complexity. At a subanesthetic dose, ketamine elevates complexity relative to baseline, while an anesthetic dose initially causes alternating low and high complexity levels before stabilizing at a high level comparable to baseline. These findings reveal that ketamine-induced state transitions blend features of general anesthesia, normal consciousness, and altered states, advancing understanding of its pharmacological and neurophysiological properties.
Frontiers in Systems Neuroscience
March 23, 2017
Duan Li, Viviane S. Hambrecht‐Wiedbusch, George A. Mashour
33 citations
High-frequency gamma connectivity across the cortex is present during consciousness and depressed during unconsciousness. Subanesthetic ketamine (25 mg/kg) administered during isoflurane anesthesia accelerates recovery upon discontinuation of the primary anesthetic and increases gamma power during emergence. In rodents, ketamine reduced emergence time by 44%. During accelerated emergence, frontal-parietal coherence and normalized symbolic transfer entropy in high-frequency gamma bandwidth were increased compared with saline-treated controls. Surrogates of cortical information exchange in high-frequency gamma are increased in association with accelerated recovery from anesthesia, suggesting a functional significance of high-gamma information transfer in consciousness.
NeuroImage
January 7, 2022
Duan Li, Phillip E. Vlisides, George A. Mashour
24 citations
Spontaneous brain activity explores a repertoire of recurring spatial patterns, and the richness of this repertoire may reflect the capacity for consciousness. Ketamine, which has both psychedelic and anesthetic properties depending on dose, was used to examine brain dynamics across a continuum of consciousness. Analyzing EEG data from source-localized cortical activity, researchers identified frequency-specific spatial coactivation patterns. Ketamine anesthesia shifted brain states toward those with low spatial variability. Subanesthetic ketamine was associated with a richer repertoire of brain states, while anesthetic ketamine initially reduced repertoire richness, which then evolved to a level comparable to normal wakefulness before recovery of consciousness. These findings describe ketamine's modulation of cortical dynamics across spatial, temporal, and spectral dimensions.
Frontiers in Systems Neuroscience
August 11, 2020
Michael A. Brito, Duan Li, George A. Mashour et al.
15 citations
Ketamine and propofol anesthesia both reduce cortical complexity, but in different frequency bands. Using Lempel-Ziv complexity (LZc) to analyze electroencephalographic data from rats, the study found that ketamine anesthesia significantly reduced complexity in the high gamma range (65–175 Hz), while propofol anesthesia reduced complexity in lower frequencies (0.5–55 Hz). During emergence from ketamine anesthesia, complexity increased in broadband and low-frequency ranges. After normalizing for spectral influences, the reductions during anesthesia remained significant, indicating they are genuine neurophysiological features. The findings suggest that reduced high gamma complexity is a specific marker of ketamine anesthesia.
Anesthesiology
May 1, 2024
Zhenhu Liang, Bo Tang, Yu Chang et al.
13 citations
Two new measures of EEG microstate complexity—type I, quantifying randomness, and type II, quantifying fluctuation complexity—track anesthetic-induced unconsciousness independently of the drug used (propofol or esketamine). In 20 patients, type I complexity increased from wakefulness to unconsciousness and decreased upon recovery, while type II complexity showed the opposite pattern. Both measures changed significantly under both anesthetics, suggesting they reflect the state of consciousness rather than the specific drug. These complexity measures may serve as state-related neural correlates of consciousness during general anesthesia.
British journal of anaesthesia
March 1, 2024
Zhenhu Liang, Yu Chang, Xiaoge Liu et al.
10 citations
Information integration and brain network measures derived from EEG can distinguish conscious from unconscious states induced by three different anaesthetics. In 72 participants given propofol, dexmedetomidine, or ketamine until they lost responsiveness, permutation cross mutual information (PCMI) within frontal, parietal, and occipital regions decreased during unresponsiveness—for example, frontal within-area PCMI fell from 0.54 to 0.46. Alpha-band PCMI in the frontal region and gamma-band PCMI in posterior areas also dropped. Network analyses showed reduced clustering coefficients and nodal efficiency in frontal, parietal, and occipital areas, while normalized path length increased in delta, theta, and gamma bands, indicating impaired global integration. The three drugs produced similar changes, suggesting a common EEG signature of anaesthesia-induced unconsciousness.
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.
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.
NeuroImage
July 18, 2025
Xin Wen, Yu Chang, Sijie Li et al.
1 citation
A new measure called Φcopula, which uses a Gaussian copula approach to estimate integrated information, outperforms common estimators by maintaining the lowest bias and mean squared error even in non-Gaussian high-dimensional systems. Applied to electroencephalographic data across awake, propofol-induced unresponsive, and NREM sleep states, alpha-band Φcopula significantly decreased during both anesthesia and sleep. Φcopula-based classifiers distinguished arousal states more accurately than functional connectivity and network efficiency measures. The dorsal attention network and default mode network contributed most to Φcopula, with the cingulate and posterior cortices showing the greatest contributions. The posterior cortex, especially the posterior cingulate cortex, appears critical for arousal-related information integration and consciousness.
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.
medRxiv
August 7, 2025
Ben Deverett, Duan Li, Theresa R. Lii et al.
preprint
Ketamine produces dissociative, analgesic, and antidepressant effects, but it is unclear whether its underlying neurophysiological signatures can be separated. In this observational cohort study, 52 participants (healthy volunteers, elective surgery patients, and patients with depression) received a subanesthetic infusion of ketamine or placebo, with or without general anesthesia. When ketamine was given under general anesthesia, its characteristic low-frequency brain wave augmentation was absent, while high-frequency power modulation was preserved. This selective modulation suggests a method for investigating the distinct roles of high- and low-frequency neural activity in ketamine's behavioral effects.
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.