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.
Communications Biology
January 28, 2023
Andrea I. Luppi, Jakub Vohryzek, Morten L. Kringelbach et al.
98 citations
Consciousness depends on how tightly brain function follows the brain's physical wiring. Using MRI scans, researchers measured structure-function coupling across spatial scales in people who were unconscious from anesthesia or brain injury and in people under psychedelics (LSD or ketamine). During loss of consciousness, function more closely tracked the brain's structural connections, a signature that could distinguish behaviorally similar brain-injured patients and detect covert consciousness. In contrast, psychedelics decoupled function from structure, and this decoupling correlated with physiological and subjective scores. The findings suggest that connectome harmonic decomposition reveals how neuromodulation and network architecture jointly shape consciousness.
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.
ACS Chemical Neuroscience
February 7, 2024
Pedro A. M. Mediano, Fernando E. Rosas, Christopher Timmermann et al.
60 citations
LSD increases brain entropy (neural signal diversity) across all conditions, but the effect is strongest when eyes are closed. Brain entropy changes correlate with subjective psychedelic experience ratings, except when viewing a video, possibly because external stimuli compete with LSD-induced imagery. This shows context modulates neural dynamics during psychedelic experiences, highlighting the importance of environment in psychedelic psychotherapy.
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.
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.
bioRxiv
November 26, 2020
Andrea I. Luppi, Pedro A. M. Mediano, Fernando E. Rosas et al.
49 citations
preprint
The brain coordinates information from many sources to create a unified conscious experience. Combining network science and information theory, the authors identify a “synergistic global workspace” where gateway regions gather synergistic information from specialized brain modules, integrate it, and then broadcast it widely via broadcaster regions. Functional MRI shows that gateway regions correspond to the default mode network and broadcasters to the executive control network. Loss of consciousness from general anesthesia or disorders of consciousness reduces the workspace’s ability to integrate information, which is restored upon recovery. This work reconciles aspects of the Global Neuronal Workspace and Integrated Information Theory.
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.
Scientific Reports
January 29, 2025
Richard J. Zeifman, Meg J. Spriggs, Hannes Kettner et al.
26 citations
A preliminary test of the REBUS model found that a high dose of psilocybin (25 mg) reduced confidence in negative self-beliefs in 11 healthy individuals, both during the acute experience and four weeks later. Greater brain signal entropy and stronger subjective effects under psilocybin correlated with larger decreases in negative self-belief confidence. Decreases in negative self-belief confidence were linked to increases in well-being. The findings provide initial evidence that relaxing and revising negative self-beliefs may underlie psilocybin's positive psychological effects, with increased neuronal entropy as a possible mechanism. Replication in larger clinical samples is needed.
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.
Neuroimage
November 1, 2022
Hardik Rajpal, Pedro A. M. Mediano, Fernando E. Rosas et al.
23 citations
Schizophrenia and drug-induced states from LSD and ketamine both increase neural signal diversity, but they differ in brain connectivity: schizophrenia shows increased information flow from front to back of the brain, while the drugs reduce it. These differences can be modeled by altering Bayesian inference in a predictive processing framework: drug effects correspond to reduced precision of prior beliefs, whereas schizophrenia involves increased precision of sensory information. The findings clarify similarities and differences between these altered states, with implications for understanding consciousness and developing mental health treatments.
Translational Psychiatry
December 4, 2024
Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. Mediano et al.
17 citations
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and may help treat depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—subjective experience, neuroimaging, and molecular pharmacology—reveals that medium and high doses of LSD produce 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 exist in receptor selectivity among the drugs. The analysis finds high heterogeneity and risk of bias, calling for standardized methods and more research.
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.
The European journal of neuroscience
March 1, 2022
Claudia Pascovich, Santiago Castro-Zaballa, Pedro A. M. Mediano et al.
16 citations
Neural complexity, measured by the Lempel-Ziv (LZ) compression algorithm, is lowest during NREM sleep and similar during REM sleep and wakefulness in cats with intracranial electrodes. Under subanaesthetic doses of ketamine (5, 10, and 15 mg/kg), complexity follows an inverted U-shaped curve in some electrodes, primarily in prefrontal cortex, rising at low doses and falling as doses approach anaesthetic levels. The variability in the ketamine dose-response curve across cats and cortices was larger than across sleep stages, highlighting differential local dynamics. These results replicate findings in humans and other species, showing neural complexity is sensitive to changes in conscious state.
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.
Cell Reports
July 22, 2025
George Blackburne, Rosalind McAlpine, Marco S. Fabus et al.
10 citations
Inhaling a high dose of vaporized synthetic 5-MeO-DMT radically reorganizes low-frequency brain oscillations, making them heterogeneous, viscous, and nonrecurring, and halting their typical forward and backward travel across the cortex. This reorganization also causes broadband neural activity to become more stable and low-dimensional, with increased energy barriers for rapid global shifts. These findings, based on EEG data from 29 healthy individuals, provide a detailed account of how the drug sculpts human brain dynamics and reveal atypical cortical slow-wave behaviors relevant to neuroscientific models of serotonergic psychedelics.
Neuroscience of Consciousness
January 1, 2025
Daniel A Atad, Pedro A. M. Mediano, Fernando E. Rosas et al.
10 citations
A scoping review of neural complexity in meditation finds that, during meditation, brain activity shows higher complexity compared to waking rest or mind-wandering, while regular meditation practice is associated with decreased baseline complexity as a long-term trait. The review disentangles different families of complexity measures, distinguishes short-term state effects from long-term trait effects, and considers differences among meditation styles. It provides a framework to guide debates and offers practical guidelines for future research on complexity and consciousness.