CoChat
Sign Up
Cited by 1,252Psychedelics and Drug StudiesParanormal Experiences and BeliefsPhilosophy and Theoretical Science

The DOI matches its Crossref record; 243 of the 255 references it cites were found in a registry or an index.

The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs.

Open access
Carhart-Harris, Robin L., Leech, Robert, Hellyer, Peter J., Shanahan, Murray, Feilding, Amanda, Tagliazucchi, Enzo, Chialvo, Dante R., Nutt, David·2014·Frontiers in Human Neuroscience
DOI 10.3389/fnhum.2014.00020PMC PMC3909994
Open this paper in CoChat — free accountOpen PDF

Abstract

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of "primary states" is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit "criticality," i.e., the property of being poised at a "critical" point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fnhum.2014.00020

Cites

243 of 243 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Relative publications on psychoanalysis and cognitive psychology. Annual publications in major medical science journals referenced in the leading database, PubMed. Articles were retrieved by entering the search terms “psychoanalysis” and “cognitive psychology” in separate searches using the default search parameters of PubMed. It is worth noting that psychoanalysis has a different publication culture to cognitive neuroscience. Articles on psychoanalysis are not always available via PubMed and many psychoanalytic writings are published in books rather than academic journals. With these caveats entered however, the publication count shown above still helps to illustrate the general point that psychoanalysis has failed to gain a significant foothold in mainstream analytical science.
Figure 1 Relative publications on psychoanalysis and cognitive psychology. Annual publications in major medical science journals referenced in the leading database, PubMed. Articles were retrieved by entering the search terms “psychoanalysis” and “cognitive psychology” in separate searches using the default search parameters of PubMed. It is worth noting that psychoanalysis has a different publication culture to cognitive neuroscience. Articles on psychoanalysis are not always available via PubMed and many psychoanalytic writings are published in books rather than academic journals. With these caveats entered however, the publication count shown above still helps to illustrate the general point that psychoanalysis has failed to gain a significant foothold in mainstream analytical science.CC BY · PubMed Central
Figure 2 The effect of psilocybin on fMRI and MEG measures of brain activity. (A) Decreased CBF post-psilocybin. (B) Ventromedial PFC (red) resting state functional connectivity (RSFC) at baseline (top, orange) and decreases post-psilocybin (bottom, blue). (C) Dorsolateral PFC (red) RSFC at baseline (top, orange) and decreases post-psilocybin (bottom, blue). (D) Hippocampal (red) RSFC at baseline (top, orange) and decreases post-psilocybin (bottom, blue). (E) Decreases in oscillatory power (purple) post-psilocybin measured with MEG. All spatial maps were whole-brain cluster corrected Z > 2.3. p < 0.05.
Figure 2 The effect of psilocybin on fMRI and MEG measures of brain activity. (A) Decreased CBF post-psilocybin. (B) Ventromedial PFC (red) resting state functional connectivity (RSFC) at baseline (top, orange) and decreases post-psilocybin (bottom, blue). (C) Dorsolateral PFC (red) RSFC at baseline (top, orange) and decreases post-psilocybin (bottom, blue). (D) Hippocampal (red) RSFC at baseline (top, orange) and decreases post-psilocybin (bottom, blue). (E) Decreases in oscillatory power (purple) post-psilocybin measured with MEG. All spatial maps were whole-brain cluster corrected Z > 2.3. p < 0.05.CC BY · PubMed Central
Figure 3 Increased variance/amplitude fluctuations in the hippocampus post-psilocybin. The charts on the left show the complete time series from the hippocampus (left in blue, right in green) in 3 different individual subjects during the 12 min scan in which they received psilocybin. The transparent red vertical line indicates the beginning and duration of the 60 s infusion of psilocybin. The images on the right show the right hippocampal region where the increases in variance were especially marked.
Figure 3 Increased variance/amplitude fluctuations in the hippocampus post-psilocybin. The charts on the left show the complete time series from the hippocampus (left in blue, right in green) in 3 different individual subjects during the 12 min scan in which they received psilocybin. The transparent red vertical line indicates the beginning and duration of the 60 s infusion of psilocybin. The images on the right show the right hippocampal region where the increases in variance were especially marked.CC BY · PubMed Central
Figure 4 Decreased PCC alpha power predicts ego-disintegration and magical thinking after psilocybin. Top: Decreased PCC alpha power v ratings of ego-disintegration. Bottom: Decreased PCC alpha power vs. ratings of magical/supernatural thinking. Both correlations were significant after correction for multiple comparisons (0.05/23 = 0.002). These charts are derived from data discussed in Muthukumaraswamy et al. (2013).
Figure 4 Decreased PCC alpha power predicts ego-disintegration and magical thinking after psilocybin. Top: Decreased PCC alpha power v ratings of ego-disintegration. Bottom: Decreased PCC alpha power vs. ratings of magical/supernatural thinking. Both correlations were significant after correction for multiple comparisons (0.05/23 = 0.002). These charts are derived from data discussed in Muthukumaraswamy et al. (2013).CC BY · PubMed Central
Figure 5 Psilocybin promotes unconstrained thinking and decreases blood flow, venous oxygenation and oscillatory power in the DMN. This chart shows the average (+SE) ratings for the item “my thoughts wandered freely” in 3 neuroimaging studies, each involving the administration of psilocybin and placebo to 15 healthy volunteers. Ratings were given within 30 min of the end of the relevant resting state scans. This particular item was one of the highest rated items in all 3 studies and nicely communicates the quality of cognition that predominates in the psychedelic state. The brain image on the left displays the mean regional decreases in CBF post-psilocybin in the ASL study; the central image displays the mean regional decreases in BOLD signal post-psilocybin in the BOLD study; and the image on the right displays the mean regional decreases in alpha power post-psilocybin in the MEG study. All images were derived using a whole brain corrected threshold of p < 0.05.
Figure 5 Psilocybin promotes unconstrained thinking and decreases blood flow, venous oxygenation and oscillatory power in the DMN. This chart shows the average (+SE) ratings for the item “my thoughts wandered freely” in 3 neuroimaging studies, each involving the administration of psilocybin and placebo to 15 healthy volunteers. Ratings were given within 30 min of the end of the relevant resting state scans. This particular item was one of the highest rated items in all 3 studies and nicely communicates the quality of cognition that predominates in the psychedelic state. The brain image on the left displays the mean regional decreases in CBF post-psilocybin in the ASL study; the central image displays the mean regional decreases in BOLD signal post-psilocybin in the BOLD study; and the image on the right displays the mean regional decreases in alpha power post-psilocybin in the MEG study. All images were derived using a whole brain corrected threshold of p < 0.05.CC BY · PubMed Central
Figure 6 Changes in network metastability and entropy post-infusion of psilocybin. (A) This chart displays the mean variance of the internal synchrony of 9 brain networks for the sample of 15 healthy volunteers, as a percentage change post vs. pre-infusion. A post-infusion increase in metastability for a specific network indicates that the mean signal in that network is a poor model of the activity in its constituent voxels, implying that the network is behaving more “chaotically” post-infusion than pre. Bonferonni correction gave a revised statistical threshold of p < 0.006 (0.05/9). One-sample (2-tailed) t-tests were performed, comparing the % change against zero. The significant networks are labeled with an asterisk. (B,C) These probability distributions were derived from data from the same single subject, by discretizing a measure of the internal synchrony of the DMN across time into bins. These bins reflect the distance a data point is from the mean and this gives a probability distribution of the variance of internal synchrony within a network for a given time period (e.g., a 5 min period of scanning). The probability distributions shown in Chart B were produced from placebo data where it is clear that prediction of internal network synchrony of the DMN across time is similar before and after infusion (i.e., the blue and green curves). The probability distributions shown in Chart C were derived using psilocybin data and here it is evident that following infusion of psilocybin (i.e., the green curve), prediction of internal network synchrony within the DMN is more difficult compared to pre infusion (the blue curve). When the entropy change was calculated for the group, significantly greater increases in entropy were found in the same networks highlighted in (A) (post-psilocybin vs. pre) vs. (post-placebo vs. pre).
Figure 6 Changes in network metastability and entropy post-infusion of psilocybin. (A) This chart displays the mean variance of the internal synchrony of 9 brain networks for the sample of 15 healthy volunteers, as a percentage change post vs. pre-infusion. A post-infusion increase in metastability for a specific network indicates that the mean signal in that network is a poor model of the activity in its constituent voxels, implying that the network is behaving more “chaotically” post-infusion than pre. Bonferonni correction gave a revised statistical threshold of p < 0.006 (0.05/9). One-sample (2-tailed) t-tests were performed, comparing the % change against zero. The significant networks are labeled with an asterisk. (B,C) These probability distributions were derived from data from the same single subject, by discretizing a measure of the internal synchrony of the DMN across time into bins. These bins reflect the distance a data point is from the mean and this gives a probability distribution of the variance of internal synchrony within a network for a given time period (e.g., a 5 min period of scanning). The probability distributions shown in Chart B were produced from placebo data where it is clear that prediction of internal network synchrony of the DMN across time is similar before and after infusion (i.e., the blue and green curves). The probability distributions shown in Chart C were derived using psilocybin data and here it is evident that following infusion of psilocybin (i.e., the green curve), prediction of internal network synchrony within the DMN is more difficult compared to pre infusion (the blue curve). When the entropy change was calculated for the group, significantly greater increases in entropy were found in the same networks highlighted in (A) (post-psilocybin vs. pre) vs. (post-placebo vs. pre).CC BY · PubMed Central
Figure 7 Spectrum of cognitive states. This schematic is intended to summarize much of what this paper has tried to communicate. It shows an “inverted u” relationship between entropy and cognition such that too high a value implies high flexibility but high disorder, whereas too low a value implies ordered but inflexible cognition. It is proposed that normal waking consciousness inhabits a position that is close to criticality but slightly sub-critical and primary states move brain activity and associated cognition toward a state of increased system entropy i.e., brain activity becomes more random and cognition becomes more flexible. It is proposed that primary states may actually be closer to criticality proper than secondary consciousness/normal waking consciousness.
Figure 7 Spectrum of cognitive states. This schematic is intended to summarize much of what this paper has tried to communicate. It shows an “inverted u” relationship between entropy and cognition such that too high a value implies high flexibility but high disorder, whereas too low a value implies ordered but inflexible cognition. It is proposed that normal waking consciousness inhabits a position that is close to criticality but slightly sub-critical and primary states move brain activity and associated cognition toward a state of increased system entropy i.e., brain activity becomes more random and cognition becomes more flexible. It is proposed that primary states may actually be closer to criticality proper than secondary consciousness/normal waking consciousness.CC BY · PubMed Central
Figure 8 Gas expansion post-release of constraints as a metaphor for increased entropy in primary states. (A) Entropy is low while the gas is constrained. (B) Entropy increases once constraints are released. In an information theoretical sense, entropy/uncertainty is increased post-expansion because it is more difficult to predict the spatial location of a single molecule. In primary vs. secondary states, it is hypothesized that the biological parameters known to define key brain states (e.g., the default-mode) become more variant or less predictable, thus causing the subject to become less certain in themselves and their experience of the world.
Figure 8 Gas expansion post-release of constraints as a metaphor for increased entropy in primary states. (A) Entropy is low while the gas is constrained. (B) Entropy increases once constraints are released. In an information theoretical sense, entropy/uncertainty is increased post-expansion because it is more difficult to predict the spatial location of a single molecule. In primary vs. secondary states, it is hypothesized that the biological parameters known to define key brain states (e.g., the default-mode) become more variant or less predictable, thus causing the subject to become less certain in themselves and their experience of the world.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 4

  1. Freud S. (1949). An Outline of Psycho-Analysis. Hogarth Press, [S.l.].
  2. Hutson M. (2012). The 7 Laws of Magical Thinking: How Irrational Beliefs Keep Us Happy, Healthy, and Sane. New York, NY: Hudson Street Press
  3. Jung C. G. (1982a). Dreams. London: Routledge and Kegan Paul
  4. Monroe R. R. Heath R. G. (1961). Effects of lysergic acid and various derivatives on depth and cortical electrograms. J. Neuropsychiatr. 3, 75– 82 14475431

Cited by

Sorted by citations

See all 1,252

Related

See all

Metadata

Authors
Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., Chialvo, D. R., & Nutt, D.
Affiliations
  • Imperial College London (GB)
  • Beckley Foundation (GB)
  • Goethe University Frankfurt (DE)
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
Corresponding author
Carhart-Harris, Robin L.
ORCID
Venue
Frontiers in Human Neuroscience
Publisher
Frontiers Media SA
Published
2014
Volume
8
Pages
20-20
ISSN
1662-5161 (ISSN-L)
DOI
10.3389/fnhum.2014.00020
PMC
PMC3909994
OpenAlex
W2109543774
Cited by
1,252
References
255
Citations by year
2026: 145 · 2025: 169 · 2024: 169 · 2023: 157 · 2022: 152 · 2021: 112 · 2020: 85 · 2019: 71 · 2018: 59 · 2017: 54 · 2016: 42 · 2015: 17 · 2014: 13
FWCI
49.32
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Human Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
  • Americanae (AECID Library) (submittedVersion, cc-by-nc-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Greater South Information System
Funders
Medical Research Council (MR/J00460X/1)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Social Sciences › Psychology › Social Psychology › Paranormal Experiences and Beliefs
  • Social Sciences › Arts and Humanities › Philosophy › Philosophy and Theoretical Science
Keywords
entropy (information theory), states of consciousness, psychedelic states, psilocybin, criticality, power-law scaling, default mode network, medial temporal lobe, self-awareness, reality testing, metacognition, REM sleep, early psychosis, anesthesia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review