Frontiers in Human Neuroscience
January 1, 2014
Robin Carhart‐Harris, Robert Leech, Peter J. Hellyer et al.
1,289 citations
Entropy, a measure of uncertainty or disorder, is applied to brain function and consciousness, focusing on the psychedelic state induced by psilocybin. The psychedelic state is considered a primary or primitive state of consciousness, characterized by elevated entropy in brain function, including a greater repertoire of functional connectivity motifs that form and fragment over time. This suggests primary states may exhibit criticality, a transition zone between order and disorder. Normal waking consciousness suppresses entropy, operating just below criticality, which constrains cognition and enables metacognitive functions like reality-testing and self-awareness. Entry into primary states involves collapse of default-mode network activity and decoupling from medial temporal lobes. These hypotheses can be tested by comparing brain activity in REM sleep, early psychosis, normal waking consciousness, and anesthesia.
Proc Natl Acad Sci U S A
April 11, 2016
Robin L. Carhart-Harris, Suresh Muthukumaraswamy, Leor Roseman et al.
887 citations
LSD produces marked changes in brain activity that correlate with its psychological effects. Increased blood flow in the visual cortex, decreased alpha power there, and an expanded functional connectivity profile of the primary visual cortex strongly correlated with visual hallucinations, suggesting that intrinsic brain activity influences visual processing more during the psychedelic state. Decreased connectivity between the parahippocampus and retrosplenial cortex correlated strongly with ego-dissolution and altered meaning, indicating this circuit's role in maintaining the self and processing meaning. Different imaging metrics showed strong relationships, allowing firmer inferences about their functional significance.
Science Advances
February 1, 2019
Athena Demertzi, Enzo Tagliazucchi, Stanislas Dehaene et al.
545 citations
Consciousness depends on the brain's ability to sustain rich, dynamic patterns of signal coordination. Using functional magnetic resonance imaging, a complex pattern of coordinated and anticoordinated signals characterized healthy individuals and minimally conscious patients. Unresponsive patients showed low interareal phase coherence mainly mediated by structural connectivity, with fewer transitions between patterns. This complex pattern was also seen in patients with covert cognition who could perform mental imagery tasks, validating its link to consciousness. Anesthesia increased the probability of the less complex pattern to levels seen in unresponsive patients, confirming its role in unconsciousness. These results establish generalizable fingerprints of conscious and unconscious states after brain damage.
Curr Biol
April 13, 2016
Enzo Tagliazucchi, Leor Roseman, Mendel Kaelen et al.
531 citations
LSD, a potent serotonin-receptor agonist, increases global functional connectivity in the human brain, particularly in high-level association cortices and the thalamus, as shown by fMRI. These effects overlap with serotonin 2A receptor densities and correlate with subjective reports of ego dissolution. The drug also enhances communication between normally distinct brain networks, reducing the brain's modular and rich-club organization. This is the first modern human imaging study of LSD's acute effects on brain connectivity, demonstrating that LSD selectively expands global connectivity and blurs perceptual boundaries between self and environment.
Human Brain Mapping
July 3, 2014
Enzo Tagliazucchi, Robin Carhart‐Harris, Robert Leech et al.
423 citations
Psilocybin, the active compound in magic mushrooms, increases the variability and range of brain activity and connectivity. Using fMRI, fifteen healthy volunteers were scanned before, during, and after receiving psilocybin or a placebo. Psilocybin raised the variability of blood-oxygen-level-dependent signals in the hippocampi and anterior cingulate cortex. Changes in the spectral behavior of brain signals were limited to higher-order networks, including the default mode, executive control, and dorsal attention networks. The brain also explored a wider repertoire of connectivity states after psilocybin than under control conditions. These findings help explain the unconstrained, hyper-associative quality of consciousness in the psychedelic state.
Proceedings of the National Academy of Sciences
September 3, 2013
Enzo Tagliazucchi, Frederic von Wegner, Astrid Morzelewski et al.
278 citations
A conscious brain integrates information across segregated functional modules and also maintains long-term memory in its neural activity. This study examined temporal memory in blood oxygen level-dependent signals across the human nonrapid eye movement sleep cycle. Temporal dependence gradually decreased from wakefulness to deep nonrapid eye movement sleep, particularly in default mode and attention networks. Although spatial organization of spontaneous fluctuations remained nontrivial even during deep sleep, temporal complexity decreased in specific brain regions. These findings suggest that long-range temporal dependence may be a characteristic of the spontaneous conscious mentation that occurs during wakeful rest.
Proceedings of the National Academy of Sciences of the United States of America
March 28, 2023
Christopher Timmermann, Leor Roseman, Sharad Haridas et al.
217 citations
Intravenous DMT, a potent psychedelic and serotonin 2A receptor agonist, profoundly alters brain function in healthy volunteers. In a placebo-controlled study with 20 participants, multimodal neuroimaging (EEG-fMRI) showed that DMT robustly increases global functional connectivity, disrupts and desegregates brain networks, and compresses the principal cortical gradient. These changes overlapped with brain regions rich in serotonin 2A receptors and associated with human-specific psychological functions. EEG and fMRI measures correlated, linking neurophysiological changes to network-level effects. The findings indicate DMT predominantly acts on the brain's transmodal association cortex, the evolutionarily recent area tied to advanced cognition and high 5-HT2A receptor density.
Journal of The Royal Society Interface
January 1, 2016
Enzo Tagliazucchi, Dante R. Chialvo, Michael Siniatchkin et al.
210 citations
Loss of consciousness from propofol sedation reduces long-range temporal correlations in frontothalamic brain activity and weakens the link between functional connectivity and anatomical structure. A model based on phase transitions in complex systems reproduces these patterns and also explains the cortex's reduced sensitivity to external stimuli during unconsciousness. The findings suggest that these neural changes are universal across different causes of unconsciousness.
NeuroImage
October 3, 2017
Federico Cavanna, Martina G. Vilas, Matías Palmucci et al.
151 citations
A review of dynamic neuroimaging research suggests that the brain's spontaneous activity fluctuates in a non-trivial, structured way, compatible with exploring a discrete repertoire of states. This supports the hypothesis of a dynamic core—a constantly evolving but transiently stable set of coordinated neurons that forms the physical substrate for each conscious experience. Studies indicate that metastability in brain dynamics may underlie this repertoire and that it can be modified during altered states of consciousness. The review proposes that linking metastability to the level of consciousness could lead to a mechanistic understanding of altered states using dynamical systems theory and statistical physics.
Translational Psychiatry
August 2, 2022
Federico Cavanna, Stephanie Müller, Laura Alethia de la Fuente et al.
130 citations
A double-blind placebo-controlled trial tested the effects of a low (0.5 g) dose of dried psilocybin mushrooms on 34 individuals beginning a microdosing protocol. The active dose produced more intense acute subjective effects than placebo, but only among participants who correctly guessed their condition. These effects coincided with reduced EEG theta-band power and preserved Lempel-Ziv broadband signal complexity. No evidence was found for enhanced well-being, creativity, or cognitive function; instead, small changes toward cognitive impairment appeared. The findings suggest that expectation, not the drug itself, accounts for many anecdotal benefits attributed to psilocybin microdosing.
Neuroscience
February 4, 2020
Rocío Martínez Vivot, Carla Pallavicini, Federico Zamberlán et al.
116 citations
Long-term meditation practice can increase the entropy of brain oscillations, indicating a more flexible and diverse neural state. Among three traditions—focused attention (Himalayan Yoga), open monitoring (Vipassana), and open awareness (Isha Shoonya Yoga)—Vipassana produced the largest entropy increases, especially in alpha and gamma bands. All traditions increased global coherence in the gamma band while reducing metastability, stabilizing gamma dynamics. Machine learning classifiers distinguished between traditions based on gamma entropy scalp distributions. These findings show that meditation can endogenously induce high-entropy brain states, similar to those seen with serotonergic psychedelics, but achieved through prolonged practice.
Frontiers in Neuroscience
January 22, 2018
Camila Sanz, Federico Zamberlán, Earth Erowid et al.
112 citations
Subjective reports of experiences under hallucinogens like LSD are semantically most similar to reports of high-lucidity dreams, while Datura (a deliriant) resembles low-lucidity dreams. Sedatives, stimulants, antipsychotics, and antidepressants rank lowest in similarity to dream reports. Frequent words across both dreams and hallucinogen experiences include perception-related terms ("see," "visual," "color"), emotion ("fear"), setting ("inside," "outside"), and family members ("mom," "dad"). The analysis confirms that hallucinogens produce experiences with the highest semantic similarity to dreams among all psychoactive substances.
Consciousness and cognition
March 1, 2019
Charlotte Martial, Héléna Cassol, Vanessa Charland-Verville et al.
98 citations
Near-death experiences (NDEs) share consistent features across cultures, suggesting a common neurobiological basis. Analyzing semantic similarity between about 15,000 reports from 165 psychoactive substances and 625 NDE narratives, the NMDA receptor antagonist ketamine produced reports most similar to NDEs, followed by Salvia divinorum and serotonergic psychedelics like DMT. The similarity was driven by concepts of self and environmental consciousness, as well as therapeutic, ceremonial, and religious aspects of drug use. Ketamine may serve as a safe experimental model for NDE phenomenology, and endogenous NMDA antagonists might be released near death.
Physical review. E
July 28, 2021
Yonatan Sanz Perl, Hernan Bocaccio, Carla Pallavicini et al.
82 citations
Conscious wakefulness is characterized by brain dynamics far from thermodynamic equilibrium, while states of reduced consciousness—such as deep sleep and anesthesia induced by propofol, ketamine, or ketamine plus medetomidine—operate closer to equilibrium. This conclusion comes from analyzing electrocorticography data from nonhuman primates and functional magnetic resonance imaging data from humans. Entropy production and the curl of probability flux in phase space reliably distinguished conscious from unconscious states. The findings establish nonequilibrium macroscopic brain dynamics as a robust signature of consciousness and offer a statistical mechanics framework for studying cognition and awareness.
NeuroImage
April 11, 2020
Ignacio Pérez Ipiña, Patricio Donnelly Kehoe, Morten L. Kringelbach et al.
81 citations
A semi-empirical model combining fMRI data, structural connectivity, and anatomically-informed priors shows that brain states during the wake-sleep cycle are better described by multiple dimensions rather than a single continuum. The best fit used priors based on functionally coherent networks, dividing the cortex into regions with opposite dynamics: frontoparietal regions approached a noise-driven bifurcation from fixed-point dynamics, while sensorimotor regions approached a bifurcation from oscillatory dynamics. Sleep onset involved subcortical deactivation with low correlation, reversed in deeper stages. Periodic forcing simulating external perturbations identified key regions for wakefulness recovery. The model characterizes sleep as having diminished perceptual gating but latent capacity for rapid arousal.
Frontiers in Integrative Neuroscience
November 1, 2018
Camila Sanz, Carla Pallavicini, Carla Pallavicini et al.
78 citations
Classic psychedelics produce a wide range of subjective effects influenced by the user's mindset and environment, and their common mechanism involves activation of the serotonin 5-HT2A receptor. The diversity of effects across different compounds may also stem from their binding affinities for multiple neurotransmitter receptors and transporters. By analyzing two binding affinity datasets alongside natural language processing of thousands of trip reports from Erowid's Experience Vaults, preliminary evidence showed that similarity in binding profiles across phenethylamines and tryptamines correlates with similarity in the language used to describe experiences.
Frontiers in Integrative Neuroscience
November 1, 2018
Camila Sanz, Carla Pallavicini, Carla Pallavicini et al.
78 citations
Classic psychedelics produce a wide range of subjective effects influenced by the user's mindset and environment, and their common mechanism involves activation of the serotonin 5-HT2A receptor. The diversity of effects across different compounds may also stem from their binding affinities for multiple neurotransmitter receptors and transporters. By analyzing two binding affinity datasets alongside natural language processing of thousands of trip reports from Erowid's Experience Vaults, preliminary evidence showed that similarity in binding profiles across phenethylamines and tryptamines correlates with similarity in the language used to describe experiences.
Frontiers in Integrative Neuroscience
November 1, 2018
Camila Sanz, Carla Pallavicini, Carla Pallavicini et al.
78 citations
Classic psychedelics produce a wide range of subjective effects influenced by the user's mindset and environment, and their common mechanism involves activation of the serotonin 5-HT2A receptor. The diversity of effects across different compounds may also stem from their binding affinities for multiple neurotransmitter receptors and transporters. By analyzing two binding affinity datasets alongside natural language processing of thousands of trip reports from Erowid's Experience Vaults, preliminary evidence showed that similarity in binding profiles across phenethylamines and tryptamines correlates with similarity in the language used to describe experiences.
J Psychopharmacol
February 10, 2021
Carla Pallavicini, Federico Cavanna, Federico Zamberlán et al.
73 citations
Inhaled N,N-dimethyltryptamine (DMT) in natural settings reduces alpha brainwave power (8-12 Hz) across the scalp while increasing delta (1-4 Hz) and gamma (30-40 Hz) power. Gamma power increases correlate with reports of mystical-type experiences. DMT also raises global synchrony and metastability in the gamma band and lowers them in the alpha band. These findings align with prior lab-based psychedelic research and suggest EEG markers for mystical experiences in real-world contexts, underscoring the value of studying psychedelics in natural settings.
Communications Biology
June 29, 2022
Anira Escrichs, Yonatan Sanz Perl, Carme Uribe et al.
67 citations
Different brain states—resting, meditating, deep sleep, and disorders of consciousness after coma—are underpinned by distinct spatiotemporal dynamics that can be characterized using turbulence theory. Non-conscious states tend to be more synchronous, while conscious states are more asynchronous, but the work goes beyond this simple dichotomy. A model-free analysis of human neuroimaging data applied Kuramoto's turbulence framework with coupled oscillators and measured information cascades across spatial scales. A complementary model-based approach used exhaustive computer simulations of whole-brain models fitted to those measures to study information encoding. The framework shows that turbulence theory provides excellent tools for describing and differentiating between brain states.
Neuroimage
June 24, 2019
Carla Pallavicini, Martina G. Vilas, Mirta Villarreal et al.
66 citations
Classic serotonergic psychedelics and dissociative drugs like ketamine produce overlapping subjective effects despite different pharmacological mechanisms. Using source-localized magnetoencephalography, researchers found that LSD, psilocybin, and ketamine all caused widespread broadband reductions in spectral power. Machine learning classifiers trained on one pair of drugs could identify the third, confirming similarity. Functional connectivity analysis revealed decreases in low alpha and theta bands specific to LSD and psilocybin, linked to 5-HT2A agonism, while low beta band decreases were common to all three drugs. These findings quantify shared large-scale brain activity patterns across drug classes and suggest that beta band decoupling is an effect shared between NMDA antagonists and 5-HT2A agonists.
Scientific Reports
October 20, 2020
Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas et al.
60 citations
Psychedelic drugs such as lysergic acid diethylamide, which activate the serotonin 2A receptor, produce profound changes in consciousness and increase entropy in spontaneous neural activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonergic neuromodulation. The model reproduced the overall entropy rise seen in previous experiments. Entropy changes were not uniform: some brain regions showed increased entropy while others showed decreases, indicating a topographical reconfiguration driven by receptor activation. At the whole-brain level, this reconfiguration was not well explained by receptor density but was closely related to the brain's anatomical connectivity topology.
NeuroImage
November 1, 2020
Gerald J. Hahn, Gorka Zamora‐lópez, Lynn Uhrig et al.
55 citations
Brain-wide signal levels can reliably distinguish sleep and anesthesia from the awake state in human and monkey fMRI resting state data. A whole-brain computational model reproduces changes in global synchronization, functional connectivity, structure-function relationship, integration, and segregation across vigilance states. The awake brain operates near a Hopf bifurcation, which coincides with globally correlated fMRI signals. Simulated lesions of connectivity hubs in the posterior brain and subcortical nuclei disrupt the model's awake state, matching predictions from graph-theoretical analyses of structural data.
Scientific reports
April 17, 2023
Rubén Herzog, Pedro A M Mediano, Fernando E Rosas et al.
51 citations
Psychedelic drugs such as LSD, which activate the serotonin 2A receptor, produce profound changes in consciousness and are linked to increased entropy in spontaneous brain activity. This study provides the first model-based explanation for that entropy increase by extending a whole-brain model of serotonin neuromodulation. The model reproduced the overall rise in neural entropy seen in prior experiments. Entropy increased across all brain regions, with the largest effects in visuo-occipital areas. At the whole-brain level, this reconfiguration was not well explained by the density of serotonin 2A receptors but was closely related to the topological properties of the brain's anatomical connectivity.
Network Neuroscience
December 23, 2022
Gustavo Deco, Yonatan Sanz Perl, Laura de la Fuente et al.
43 citations
The default mode network (DMN) may coordinate the recruitment and scheduling of brain networks for solving cognitive tasks, supported by evidence that DMN regions are physically and functionally distant from sensorimotor areas. Using a thermodynamics-inspired, deep learning-based Temporal Evolution NETwork (TENET) framework to measure the 'arrow of time'—a marker of nonreversibility and hierarchy in brain signals—analysis of Human Connectome Project data from nearly a thousand participants suggests the DMN orchestrates hierarchy levels that shift between rest and seven cognitive tasks. This hierarchy differs significantly in health versus neuropsychiatric disorders, offering insights into brain dynamics for cognition.