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.
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.
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.
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.
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.
June 30, 2022
Sandeep M. Nayak, Bilal A. Bari, David B. Yaden et al.
1 citation
preprint
A Bayesian reanalysis of a trial comparing psilocybin (COMP360) to escitalopram for major depressive disorder found that psilocybin outperformed escitalopram, but not by a clinically meaningful amount. The analysis also found extremely strong evidence that psilocybin is non-inferior to escitalopram. Evidence for psilocybin's superiority varied by depression scale: indeterminate for one, strong for two, and extremely strong for another. For a clinically meaningful difference, evidence was moderate against it on one scale, indeterminate on two, and moderate supporting it on one. These results provide a more nuanced interpretation and support further research.
December 11, 2020
Balázs Szigeti, Laura Kärtner, Allan Blemings et al.
1 citation
A self-blinding citizen science study tested whether psychedelic microdosing improves well-being and cognition beyond placebo. 191 participants who already planned to microdose were randomly assigned to receive four weeks of microdoses, placebos, or a mix. All psychological outcomes—including well-being, mindfulness, and life satisfaction—improved from baseline in the microdose group, but the placebo group also improved, and no significant differences emerged between groups. Small acute differences in mood, energy, and creativity were observed, but these could be explained by participants correctly guessing whether they took a microdose. The findings suggest that the anecdotal benefits of microdosing are likely due to the placebo effect.
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.