Trends in Cognitive Sciences
June 1, 2022
Pedro A. M. Mediano, Fernando E. Rosas, Daniel Bor et al.
109 citations
The integrated information theory of consciousness (IIT) proposes a universal mathematical formula derived from fundamental properties of conscious experience to describe the quality of consciousness. The theory is ambitious in that it aims to derive a mathematical measure of integrated information from consciousness itself, using properties of conscious experience to characterize the quality of consciousness. The text repeatedly states that IIT is a theory of consciousness that proposes a mathematical formula derived from fundamental properties of conscious experience to describe the quality of consciousness, but it does not provide specific findings, numbers, or empirical results.
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.
Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences
May 23, 2022
Pedro A. M. Mediano, Fernando E. Rosas, Andrea I. Luppi et al.
73 citations
Emergence—how galaxies form or consciousness arises from neurons—lacks formal tools for rigorous study. This article summarizes, elaborates, and extends a recent formal theory of causal emergence based on information decomposition, which is quantifiable and empirically testable. The theory links emergence to information about a system's temporal evolution that cannot be obtained from its parts separately. The article provides an accessible but rigorous introduction to this framework, discussing its merits in various scenarios, interpretation issues, and potential misunderstandings, highlighting the distinctive benefits of this formalism.
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.
NeuroImage
July 1, 2022
Fran Hancock, Joana Cabral, Andrea I. Luppi et al.
40 citations
Dynamic functional connectivity (dFC) in resting-state fMRI is promising for clinical biomarkers, but its reliability and interpretability are debated. This study combined phase-based dFC metrics from dynamical systems, stochastic processes, and information dynamics to assess their interrelationships and reliability. Novel relationships between metrics allowed building a predictive model for integrated information. Global metastability, reflecting simultaneous coupling and decoupling tendencies, was the most representative and stable metric in brain parcellations including cerebellar regions. Spatiotemporal patterns of phase-locking changed slowly and continuously over time. The findings suggest that most resting-state fMRI dynamics reflect an interrelated complexity profile unique to each acquisition, challenging cross-sectional designs for neuromarker discovery and indicating individual life-trajectories may be more informative.
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.
Trends in Neurosciences
May 31, 2024
Andrea I. Luppi, Fernando E. Rosas, Pedro A. M. Mediano et al.
23 citations
Unconsciousness increases the coupling between brain structure and function across scales, while psychedelics may decouple brain function from structure. Anaesthetics, psychedelics, and disorders of consciousness can produce similar reconfigurations along the brain's unimodal-transmodal functional axis. Decomposing brain function into fundamental constituents of time, space, and information has driven recent advances in understanding consciousness and the brain's functional organisation. Computational modelling offers a path toward mechanistic integration, and decomposition approaches may help translate discoveries across species.
Preprints.org
July 21, 2023
Fran Hancock, Fernando E. Rosas, Mengsen Zhang et al.
16 citations
preprint
Healthy brain function requires a balance between stable integration across brain areas for coordinated activity and brief periods of desynchronization that allow subsystems to reconfigure and express specialized functions. Metastability, a concept from statistical physics and dynamical systems theory, has been proposed as a key signature of this balance. Neuroscience research has used markers of metastability to study cognitive performance, healthy aging, meditation, sleep, responses to drugs, and to characterize psychiatric conditions and disorders of consciousness. However, the term is often used heuristically or inaccurately, making the literature difficult to navigate. This paper provides a comprehensive review of metastability in neuroscience, covering its scientific and historical foundations, practical estimators, and a critical analysis of recent theoretical developments to clarify misconceptions.
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.
Sci Rep
September 15, 2022
Rubén Herzog, Pedro A. M. Mediano, Fernando E. Rosas et al.
3 citations
A scientific paper was retracted because a typo in the script used to calculate differential entropy made the reported entropy estimations invalid. The corrected calculations no longer show the expected increase in brain signal diversity or complexity that the original analysis had claimed.
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.
Hum Brain Mapp
January 1, 2026
Henrik Röhr, Daniel A. Atad, Fynn‐mathis Trautwein et al.
1 citation
Meditation can deliberately alter the sense of self, allowing comparison between an active and suspended self. In 41 experienced meditators, magnetoencephalography recordings distinguished a state of reduced sense of self (self-boundary dissolution) from rest and a control meditation state. Machine learning using source band power and Lempel-Ziv complexity features predicted mental states with above-chance accuracy. The best performance, classifying self-boundary dissolution versus rest using Lempel-Ziv complexity, achieved average accuracy of about 0.64 for within-participant prediction and about 0.57 for across-participant prediction. This neural marker could support decoded neurofeedback for clinical treatments of self disorders or meditation training.
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.
May 13, 2026
Robin Carhart-Harris, Richard Zeifman, Lorenzo Pasquini et al.
preprint
The paper argues that the term 'plasticity' in neuroscience refers to induced changes in brain function or structure, which differs from the dictionary definition of plasticity as the ability to be shaped or molded. Many biomarkers of neuroplasticity actually index processes that bias phenotypic canalization, the opposite of phenotypic plasticity, creating a paradox. The authors question extrapolating from these biomarkers to improved mental health, as the relationship is context dependent. They propose a new construct, 'mediational and recalibrative plasticity' (MR-P), which aligns with plasticity proper and can describe and predict phenotypic changes relevant to mental health.
arXiv (Cornell University)
August 6, 2020
Rodrigo Cofré, Rubén Herzog, Pedro A. M. Mediano et al.
Altered states of consciousness provide a key opportunity to understand how global brain activity changes relate to different subjective experiences. This paper advocates a research program that bridges bottom-up generative models of whole-brain activity with top-down signatures proposed by theories of consciousness. It defines altered states, discusses relevant brain-activity signatures, and introduces whole-brain models to explore the mechanisms of altered consciousness from the bottom-up. The authors argue that systematic investigation of altered states via bottom-up modeling may help clarify the biophysical, informational, and dynamical foundations of consciousness.
arXiv Preprint Archive
April 13, 2026
Adam B. Barrett, Borjan Milinkovic, Pedro A. M. Mediano et al.
The integrated information theory of consciousness (IIT) proposes a mathematical formula, derived from fundamental properties of conscious experience, to describe the quantity and quality of consciousness for any physical system. This article clarifies common misunderstandings. A high value of the measure Φ does not mean 'more consciousness'; Φ might be replaced with a suite of quantities for a multidimensional characterization. IIT implies a distinct panpsychism where space and time are tiled with substrates of proto-consciousness, which the authors find unproblematic. Φ is not well-defined for real physical systems and has never been computed on one; only proxies have been computed, not approximations. For IIT to align with fundamental physics, a reformulation in continuous fields would be needed.