Neuropharmacology
December 27, 2022
Robin Carhart‐Harris, Shamil Chandaria, David Erritzøe et al.
106 citations
A theoretical model proposes that psychopathology arises from a defensive process called canalization, which narrows an individual's range of thoughts, feelings, and behaviors by increasing precision or reducing variance in neural responses. This contrasts with an early form of plasticity, TEMP (Temperature or Entropy Mediated Plasticity), which increases variance and learning rate. Canalization entrenches pathology as the agent develops expertise in their disorder, while TEMP, combined with gentle psychological support, may counter this entrenchment. The model distinguishes adaptive from maladaptive canalization and suggests concrete experiments to test its hypotheses.
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.
Neuroscience of Consciousness
November 1, 2021
Andrea I. Luppi, Pedro A. M. Mediano, Fernando E. Rosas et al.
42 citations
Consciousness can be better understood by decomposing it into distinct information-theoretic elements rather than measuring it as a single quantity of integrated information. The authors propose Integrated Information Decomposition (ΦID), which provides a formal argument that whether consciousness is an emergent phenomenon depends on its information-theoretic composition. Two organisms may have the same amount of integrated information yet differ in composition. A new measure, ΦR, and the ΦR-ing ratio quantify how efficiently information is used for conscious processing. This approach enables identification of qualitatively different 'modes of consciousness' and mapping them to phenomenology, starting with selfhood. ΦID offers new ways to explore the relationship between information, consciousness, and neural dynamics.
bioRxiv (Cold Spring Harbor Laboratory)
November 2, 2020
Pedro A. M. Mediano, Fernando E. Rosas, Christopher Timmermann et al.
39 citations
preprint
Psychedelics reliably increase brain entropy (neural signal diversity), an effect linked to psychological changes and opposite to the decrease seen during loss of consciousness. This study investigated how context—specifically stimulus manipulation—modulates that entropy increase. Participants under LSD or placebo experienced eyes-closed versus eyes-open conditions, or no stimulus, music, or video. Brain entropy rose with LSD across all conditions but was largest with eyes closed. Entropy changes consistently matched subjective ratings of the psychedelic experience, except during video viewing, suggesting competition between external stimuli and internal LSD-induced imagery. The findings provide quantitative evidence that context shapes neural dynamics during psychedelic experiences, supporting the practice of eyes-closed psychedelic psychotherapy, and challenge simplistic views of brain entropy as a direct measure of conscious level.
bioRxiv (Cold Spring Harbor Laboratory)
September 23, 2021
Pedro A. M. Mediano, Aleksi Ikkala, Rogier Kievit et al.
30 citations
preprint
Neural complexity measures, which can distinguish conscious from unconscious states, also detect meaningful fluctuations in conscious level during normal wakefulness. Using MEG and fMRI data from healthy adults, complexity decreased as participants became drowsy, validating the approach. Complexity changed within and between tasks, and higher complexity was associated with better performance and faster reaction times on an executive task. This offers a new way to explore the cognitive and neural basis of consciousness.
bioRxiv (Cold Spring Harbor Laboratory)
August 10, 2020
Andrea I. Luppi, Jakub Vohryzek, Morten L. Kringelbach et al.
26 citations
preprint
Consciousness arises from how the brain's structural wiring shapes its dynamic activity. By decomposing resting-state fMRI data into harmonic modes of the human structural connectome, a generalizable signature of lost consciousness emerges—whether from anesthesia or brain injury—while a reversed signature characterizes psychedelic states induced by LSD or ketamine, reflecting decoupling of function from structure. This connectome harmonic approach discriminates between behaviorally indistinguishable brain-injured patients and tracks covert consciousness, linking neurobiology to conscious experience.
Communications Biology
June 20, 2023
Joel Frohlich, Pedro A. M. Mediano, Francesco Bavato et al.
16 citations
Low-frequency delta-band neural activity is typically associated with loss of consciousness and cortical down states, especially when diffuse and high amplitude. However, several classes of pharmacological agents—including antiepileptic drugs, GABA B receptor activators, acetylcholine receptor blockers, and psychedelics—can produce neural activity resembling cortical down states while participants remain conscious. Among these substances safe for healthy volunteers, some may serve as valuable research tools for determining which neural activity patterns are sufficient for consciousness or its absence.
bioRxiv (Cold Spring Harbor Laboratory)
November 9, 2023
Fernando E. Rosas, Pedro A. M. Mediano, Christopher Timmermann et al.
14 citations
preprint
Autonomic signals can reveal aspects of subjective and neural states. A Bayesian framework estimated heart rate entropy under psychedelics. Across four drugs—LSD, DMT, psilocybin, and ketamine—mean heart rate, high-frequency heart rate variability, and heart rate entropy consistently increased during the psychedelic experience. These changes predicted various dimensions of the experience. Heart rate entropy increases correlated with brain entropy increases, while other autonomic markers did not. Cost-efficient autonomic measures can reveal detail about subjective and brain states, opening new research avenues in neuroscience.
July 7, 2022
Richard J. Zeifman, Meg J. Spriggs, Hannes Kettner et al.
13 citations
preprint
The Relaxed Beliefs Under pSychedelics (REBUS) model suggests that psychedelics reduce the strength of deeply held beliefs. In a preliminary test of this idea, 11 healthy adults received a low (1 mg) and a high (25 mg) dose of psilocybin four weeks apart. Confidence in negative self-beliefs decreased after the high dose but not after the low dose. Greater brain signal entropy and stronger subjective effects during the high dose correlated with larger decreases in negative belief confidence, both during the session and four weeks later. Reduced confidence in negative beliefs was strongly linked to improved well-being at the four-week follow-up. These findings provide initial psychological support for the REBUS model, though replication in larger and clinical samples is needed.
June 28, 2023
Daniel Andrew Atad, Pedro A. M. Mediano, Fernando E. Rosas et al.
11 citations
preprint
Meditation appears to increase the complexity of neural activity during practice, compared to resting or mind-wandering, but experienced meditators show lower baseline complexity as a lasting trait. This systematic review of studies on neural complexity in meditation examined different measurement approaches, short-term state effects, and long-term trait effects across meditation styles. The findings converge on a pattern where the meditative state enhances neural complexity, while trait effects in seasoned practitioners show reduced baseline complexity relative to novices and non-meditators. The review provides a framework to guide future research.
bioRxiv (Cold Spring Harbor Laboratory)
October 7, 2024
George Blackburne, Rosalind McAlpine, Marco S. Fabus et al.
8 citations
preprint
A high dose of the psychedelic drug 5-MeO-DMT radically reorganizes low-frequency brain activity in 29 healthy individuals. Inhaling 12 mg of vaporized synthetic 5-MeO-DMT caused neural activity flows to become incoherent, heterogeneous, viscous, fleeting, and nonrecurring, ceasing typical traveling waves across the cortex. This reorganization led to slower, more stable, low-dimensional broadband activity with increased energy barriers to rapid global shifts. The findings provide the first detailed empirical account of how 5-MeO-DMT alters human brain dynamics, revealing novel cortical slow wave behaviors.
medRxiv
September 11, 2024
M. Nikolič, Pedro A. M. Mediano, Tom Froese et al.
6 citations
preprint
Psilocybin, a classic psychedelic, alters perception, cognition, and emotion by activating 5-HT2A receptors and reducing serotonin reuptake. In a placebo-controlled crossover study with 20 healthy individuals, electroencephalography tracked brain activity changes over 24 hours after oral psilocybin (0.26 mg/kg). Acutely, absolute power decreased in alpha and beta bands but increased in delta and gamma frequencies; alpha power decreased occipitally between 1 and 3 hours, and beta decreased frontally at 3 hours. Global functional connectivity in the alpha band dropped acutely, while Lempel-Ziv complexity increased at 1 and 1.5 hours.
bioRxiv (Cold Spring Harbor Laboratory)
October 7, 2023
Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. Mediano et al.
2 citations
preprint
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and show therapeutic potential for depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—phenomenology, neuroimaging, and pharmacology—reveals that medium and high doses of LSD produce significantly stronger visionary restructuring than psilocybin. Neuroimaging shows psychedelics generally strengthen connectivity between brain networks while weakening connectivity within networks. Pharmacologically, LSD triggers more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, but no significant differences emerged in receptor selectivity among the drugs. The findings highlight high heterogeneity and risk of bias, underscoring the need for standardized methods.
October 1, 2025
Daniel Andrew Atad, Pedro A. M. Mediano, Fynn‐mathis Trautwein et al.
1 citation
preprint
The sense of being a bounded self can be attenuated or dissolved while awareness remains. Analyzing magnetoencephalography data from 46 long-term meditators, the study found that both meditation conditions (self-boundary dissolution and maintenance) increased broadband entropy rate and directed information transfer compared to rest, driven mainly by high-frequency activity. Localized reductions in information transfer from the anterior cingulate to posterior cingulate and in high-beta entropy rate in sensorimotor and posterior-medial cortices differentiated the two meditation conditions. Reduced orbitofrontal cortex entropy rate and reduced information transfer from occipital, cingulate, limbic, and subcortical areas correlated strongly with self-boundary dissolution phenomenology. Together with a previously reported neural correlate of reduced high-beta power in the posterior-medial cortex, these two neural correlates explained over half the variance in phenomenological dissolution scores (R² = 0.52).
bioRxiv (Cold Spring Harbor Laboratory)
Hanna M. Tolle, Andrea I Luppi, Timothy Lawn et al.
1 citation
preprint
A geometric deep learning model called graphTRIP predicts post-treatment depression severity from pretreatment clinical and brain imaging data. Trained on a clinical trial comparing psilocybin and escitalopram, it achieves strong predictive accuracy (r = 0.75) and generalizes to an independent dataset. The model links better outcomes to reduced functional coupling within serotonin systems and broader serotonergic integration with sensory-motor networks. Causal analysis shows a group-level advantage of psilocybin over escitalopram but identifies individuals with specific stress-related neuromodulatory profiles who may benefit more from escitalopram, advancing precision medicine and biomarker discovery in depression.
arXiv Preprint Archive
August 6, 2020
Rodrigo Cofré, Rubén Herzog, Pedro A. M. Mediano et al.
Altered states of consciousness, such as those experienced during dreaming or meditation, offer a way to study how large-scale brain activity relates to different subjective experiences. This paper advocates a research program that combines bottom-up generative models of whole-brain activity, based on known properties of neural tissue, with top-down signatures proposed by theories of consciousness. The authors define altered states, discuss relevant brain-activity signatures, and introduce whole-brain models to explore the mechanisms behind these states. They argue that systematically investigating altered states through bottom-up modeling can clarify the biophysical, informational, and dynamical foundations of consciousness.
arXiv Preprint Archive
February 12, 2019
Adam B. Barrett, Pedro A. M. Mediano
Integrated Information Theory (IIT) defines consciousness as a fundamental property of physical systems, measured by the quantity Phi. For IIT to be credible, Phi must be uniquely defined and always well-defined. This article identifies three ways in which the current formulation of Phi fails these standards, making the measure ambiguous or ill-defined in certain cases, and discusses potential solutions to address these foundational issues.