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.
Trends Cogn Sci
February 3, 2023
Manesh Girn, Fernando E. Rosas, Richard E. Daws et al.
76 citations
Psychedelics reduce the functional segregation of large-scale brain networks, but findings have been largely inconsistent. A complexity-science perspective that emphasizes the distributed, interactional, and dynamic nature of brain function may explain these inconsistencies. The authors propose that psychedelics induce a mode of brain function that is more dynamically flexible, diverse, integrated, and tuned for information sharing, consistent with greater criticality. This 'meta' perspective can unify past findings and guide intuitions toward compelling mechanistic models.
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.
Neuroscience of Consciousness
January 1, 2023
Inês Hipólito, Jonas Mago, Fernando E. Rosas et al.
60 citations
Psychedelic therapy shows promise for mental health, but the psychological mechanisms behind its benefits are unclear. This paper proposes that psychedelics act as destabilizers, both psychologically and neurophysiologically, drawing on the 'entropic brain' hypothesis and the 'RElaxed Beliefs Under pSychedelics' model. Using complex systems theory, it suggests that psychedelics disrupt fixed points or attractors, breaking reinforced patterns of thinking and behavior. The approach explains how increased brain entropy destabilizes neurophysiological set points, leading to new understandings of psychedelic psychotherapy. These insights have implications for reducing risks and optimizing treatment during both the peak experience and the subacute recovery period.
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.
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.
Journal of Psychopharmacology
March 22, 2024
Tommaso Barba, David Erritzøe, Meg J. Spriggs et al.
26 citations
In a clinical trial comparing psilocybin plus psychological support to escitalopram plus psychological support for major depressive disorder, patients who discontinued their SSRI or SNRI medication before receiving psilocybin showed a reduced treatment effect on all depression severity and well-being measures compared with those who were unmedicated at trial entry. Discontinuation did not affect the intensity of the acute psychedelic experience. The findings are exploratory and hypothesis-generating, not confirmatory, and the study did not test SSRI/SNRI continuation. A controlled trial comparing discontinuation versus continuation before psilocybin is needed.
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.
Psychedelic Medicine
October 28, 2022
Bruna Giribaldi, Sandeep M. Nayak, Bilal A. Bari et al.
15 citations
A Bayesian reanalysis of a trial comparing psilocybin (25 mg) to escitalopram (20 mg) over 6 weeks in 59 patients with major depressive disorder found that psilocybin outperformed escitalopram on three of four depression scales, though evidence was not uniformly clinically meaningful. Using skeptical priors that bias results toward zero, the analysis showed strong to extremely strong evidence favoring psilocybin on the BDI-1A, MADRS, and HAMD-17, while evidence on the primary outcome (QIDS SR-16) was indeterminate. For clinically meaningful superiority, evidence was moderate against it for the QIDS SR-16 but moderate to strong for the MADRS and HAMD-17. Psilocybin showed extremely strong evidence of noninferiority to escitalopram across all scales. The findings support further research on psilocybin's relative efficacy.
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.
June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
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.
Pedro A.M. Mediano, Fernando E. Rosas, Andrea I. Luppi et al.
10 citations
A new method called Complexity via State-space Entropy Rate (CSER) estimates neural signal complexity with better temporal resolution and spectral decomposition than the standard Lempel-Ziv complexity (LZ) approach. CSER matches LZ in distinguishing conscious states but offers two key advantages: it can break complexity down by frequency bands, and it provides temporal resolution about 100 times finer. Using MEG, EEG, and ECoG data from humans and monkeys, CSER revealed that gamma-band activity primarily drives complexity changes across states of consciousness. In an auditory mismatch negativity experiment, CSER detected early entropy increases roughly 20 milliseconds before the standard event-related potential. This method enables finer-grained study of how signal complexity relates to cognitive processes and conscious states.
Research Square
October 26, 2022
Rubén Herzog, Pedro A.M Mediano, Fernando E. Rosas et al.
6 citations
Psychedelic drugs like LSD, which activate serotonin 2A receptors, dramatically alter subjective experience and offer a window into the neurobiology of consciousness. A key signature of these drugs is increased entropy—or randomness—in spontaneous brain activity, but why this occurs was unclear. Using a computational model of serotonin's effects on the whole brain, researchers reproduced the entropy increase seen in living brains, providing the first model-based explanation. Entropy rose across all brain regions but was most pronounced in visual and occipital areas. Surprisingly, this pattern was not tied to the density of serotonin receptors but instead linked to the brain's structural connectivity network. The findings clarify how psychedelics reconfigure brain activity.
bioRxiv
March 20, 2024
Valerie Bonnelle, Amanda Feilding, Fernando E. Rosas et al.
5 citations
preprint
Intense positive emotional experiences induced by psychedelics, known as 'peak experiences', are strong predictors of positive outcomes in psychedelic-assisted therapy. This study investigated how the autonomic nervous system (ANS) relates to such experiences. Analyzing electrocardiogram data from 17 participants who received DMT or placebo, researchers found that coactivation of the sympathetic and parasympathetic branches of the ANS during the DMT experience was strongly correlated with ratings of 'Spiritual Experience' and 'Insightfulness', and also linked to improved wellbeing two weeks later. Additionally, the balance between these branches before DMT injection predicted 'Insightfulness' scores. These findings demonstrate the ANS's involvement in psychedelic-induced peak experiences and suggest potential for biofeedback tools to enhance therapy.
bioRxiv
August 29, 2022
Giulio Ruffini, Giada Damiani, Diego Lozano-Soldevilla et al.
5 citations
preprint
Using fMRI data from fifteen people who took LSD or a placebo, researchers modeled brain dynamics with an Ising spin model to test whether psychedelics push the brain into a more disordered state. LSD increased the Ising temperature of brain activity, moving it further away from a critical point (the edge between order and disorder) into a more disordered, paramagnetic phase. This shift was accompanied by a decrease in interhemispheric connectivity, especially between corresponding regions in the two hemispheres. Algorithmic complexity of brain signals also increased with LSD. The findings suggest LSD loosens homotopic connections, driving the brain into a more flexible, complex state, consistent with theories that psychedelics increase neural entropy.
bioRxiv
February 1, 2022
Hardik Rajpal, Pedro A.M. Mediano, Fernando E. Rosas et al.
5 citations
preprint
Schizophrenia and drug-induced states from LSD and ketamine both increase neural signal diversity, but they differ in how information flows in the brain. In schizophrenia, transfer entropy from the front to the back of the brain is increased, whereas under both drugs it is reduced overall. These differences can be modeled by altering Bayesian inference within a predictive processing framework: drug effects correspond to reduced precision of prior beliefs, while schizophrenia corresponds to increased precision of sensory information. The findings clarify similarities and differences between these altered states, with potential implications for understanding consciousness and developing mental health treatments.
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.
September 2, 2025
Zefan Zheng, Robert Chis-Ciure, Peter Thestrup Waade et al.
1 citation
preprint
Consciousness science is fragmented, with theories operating orthogonally and accumulating anomalies. The principle of recurrency—functional and architectural feedback loops—offers a unifying scaffold. All theories tacitly invoke feedback loops and can be re-expressed along a single axis of recursion. Four nested levels (cellular, local inter-areal, global, and lateral) map onto state, phenomenal content, manipulative access, and experiential similarity, tying evolved anatomy to phenomenon. The phenomenal-versus-access distinction dissolves into a graded cascade where deeper recursion expands reportable variables. Recurrence is evolutionarily favored, rebutting feed-forward objections, while brain-body loops ground selfhood. Clinically, targeting recurrent pathways promises new biomarkers and alleviation in disorders of consciousness.