Increased global functional connectivity correlates with LSD-induced ego dissolution
Open accessAbstract
Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic [2]. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s [3]. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs [4]). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of "ego dissolution." The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain's modular and "rich-club" organization and, simultaneously, the perceptual boundaries between the self and the environment.
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The strongest specific correlation with ego dissolution was decoupling of the parahippocampal cortex (in the MTL) from the precuneus-a key DMN node anatomically adjacent to the PCC.
“The strongest specific correlation with ego dissolution was decoupling of the parahippocampal cortex (in the MTL) from the precuneus—a key DMN node anatomically adjacent to the PCC.”
From Self unbound: ego dissolution in psychedelic experience (2017) · cites this paper as Tagliazucchi et al. 2016
The Discussion (p. 6) reports correlations between ego dissolution and increased connectivity in the temporo-parietal junction and insula. It does not identify parahippocampal–precuneus decoupling as a correlate, let alone the strongest specific one. (LLM, conf=0.84)
Experimental — accuracy not yet measuredTagliazucchi et al. (2016) found that ego dissolution induced by LSD correlated with increased global functional connectivity, with these increases resulting from a breakdown in the integrity of resting-state networks.
“Most recently, Tagliazucchi et al. (2016) found that ego dissolution induced by LSD correlated with increased global functional connectivity, with these increases resulting from a breakdown in the integrity of resting-state networks.”
From Self unbound: ego dissolution in psychedelic experience (2017) · cites this paper as Tagliazucchi et al. 2016
The Highlights (p. 1) and Discussion (p. 7) report that increased global connectivity under LSD correlated with ego-dissolution ratings and coincided with decreased within-module integrity. But the paper does not establish that the connectivity increases resulted from a breakdown in resting-state network integrity; its Summary (p. 2) instead describes expanded connectivity as compromising modular organization. (LLM, conf=0.86)
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“Many consider it to be a typical effect of both LSD and psilocybin (Mason et al., 2020; Tagliazucchi et al., 2016), particularly at higher doses (Holze et al., 2021).”
BackgroundCultural Evolution of Religion, Spirituality and Ritual: Impacts On Human Cooperation
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“…associated with more top–down cortical control, leading those who enter these states to access parts of the body/mind that are otherwise inaccessible to conscious, alert awareness (Brewer et al. 2011; Danielson et al. 2011; Simon and Engström 2015; Smigielski et al. 2019; Tagliazucchi et al. 2016).”
Could psychedelics treat personality disorders
(2022) · Journal of Addiction Science · doi:10.17756/jas.2022-057 · Cited by 3 · see citing works
- Authors
- Tagliazucchi, E., Roseman, L., Kaelen, M., Orban, C., Muthukumaraswamy, S. D., Murphy, K., Laufs, H., Leech, R., McGonigle, J., Crossley, N., Bullmore, E., Williams, T., Bolstridge, M., Feilding, A., Nutt, D. J., & Carhart-Harris, R.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- Imperial College London (GB)
- University of Auckland (NZ)
- Cardiff University (GB)
- University Hospital Schleswig-Holstein (DE)
- King's College London (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- Beckley Foundation (GB)
- Corresponding author
- Tagliazucchi, Enzo
- Carhart-Harris, Robin
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 26
- Issue
- 8
- Pages
- 1043-1050
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2341558148
- Cited by
- 503
- References
- 42
- Citations by year
- 2026: 55 · 2025: 55 · 2024: 65 · 2023: 53 · 2022: 60 · 2021: 50 · 2020: 36 · 2019: 47 · 2018: 39 · 2017: 33 · 2016: 9
- FWCI
- 57.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, other-oa)
- Apollo (University of Cambridge) (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- GlaxoSmithKline
- Wellcome Trust (WT090199, 093875)
- National Institute for Health and Care Research
- Royal Society Te Apārangi
- AXA Research Fund
- Medical Research Council
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Keywords
- lysergic acid diethylamide, LSD, ego dissolution, intrinsic functional connectivity, 5-HT2A receptor, default mode network, salience network, frontoparietal attention network, thalamus, brain network integration, rich club, self-perception, psychedelics
- MeSH terms
- Brain, Consciousness, Ego, Hallucinogens, Humans, Lysergic Acid Diethylamide, Neural Pathways, Self Concept, Functional Neuroimaging
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