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Effects of external stimulation on psychedelic state neurodynamics

View ORCID ProfilePedro A.M. Mediano, View ORCID ProfileFernando E. Rosas, View ORCID ProfileChristopher Timmermann, View ORCID ProfileLeor Roseman, David J. Nutt, Amanda Feilding, View ORCID ProfileMendel Kaelen, View ORCID ProfileMorten L. Kringelbach, Adam B. Barrett, View ORCID ProfileAnil K. Seth, View ORCID ProfileSuresh Muthukumaraswamy, View ORCID ProfileDaniel Bor, View ORCID ProfileRobin L. Carhart-Harris
doi: https://doi.org/10.1101/2020.11.01.356071
Pedro A.M. Mediano
aDepartment of Psychology, University of Cambridge, Cambridge CB2 3EB
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  • For correspondence: pam83@cam.ac.uk f.rosas@ic.ac.uk
Fernando E. Rosas
bPsychedelic Research Center, Department of Brain Science, Imperial College London, W12 0NN, UK
cData Science Institute, Imperial College London, London SW7 2RH
dCenter for Complexity Science, Imperial College London, London SW7 2RH
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  • For correspondence: pam83@cam.ac.uk f.rosas@ic.ac.uk
Christopher Timmermann
bPsychedelic Research Center, Department of Brain Science, Imperial College London, W12 0NN, UK
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Leor Roseman
bPsychedelic Research Center, Department of Brain Science, Imperial College London, W12 0NN, UK
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David J. Nutt
bPsychedelic Research Center, Department of Brain Science, Imperial College London, W12 0NN, UK
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Amanda Feilding
eThe Beckley Foundation, Beckley Park, OX3 9SY, Oxford, United Kingdom
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Mendel Kaelen
fWavepaths, London E1 5JL, UK
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Morten L. Kringelbach
gDepartment of Psychiatry, University of Oxford, Oxford OX3 7JX, UK
hCenter for Music in the Brain, Department of Clinical Medicine, Aarhus University, DK-8000 Aarhus C, Denmark
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Adam B. Barrett
iSackler Center for Consciousness Science and Department of Informatics, University of Sussex, Brighton BN1 9RH, UK
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Anil K. Seth
jCIFAR Program on Brain, Mind, and Consciousness, Toronto M5G 1M1, Canada
kSchool of Pharmacy and Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
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Suresh Muthukumaraswamy
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Daniel Bor
aDepartment of Psychology, University of Cambridge, Cambridge CB2 3EB
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Robin L. Carhart-Harris
bPsychedelic Research Center, Department of Brain Science, Imperial College London, W12 0NN, UK
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  • ORCID record for Robin L. Carhart-Harris
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Abstract

Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes such as personality changes. These findings are particularly intriguing given that a decrease of brain entropy is a robust indicator of loss of consciousness (e.g. from wakefulness to sleep). However, little is known about how context impacts the entropy-enhancing effect of psychedelics, which carries important implications for how it can be exploited in, for example, psychedelic psychotherapy. This article investigates how brain entropy is modulated by stimulus manipulation during a psychedelic experience, by studying participants under the effects of LSD or placebo, either with gross state changes (eyes closed vs. open) or different stimulus (no stimulus vs. music vs. video). Results show that while brain entropy increases with LSD in all the experimental conditions, it exhibits largest changes when subjects have their eyes closed. Furthermore, brain entropy changes are consistently associated with subjective ratings of the psychedelic experience, but this relationship is disrupted when participants are viewing video — potentially due to a “competition” between external stimuli and endogenous LSD-induced imagery. Taken together, our findings provide strong quantitative evidence for the role of context in modulating neural dynamics during a psychedelic experience, underlining the importance of performing psychedelic psychotherapy in a suitable environment. Additionally, our findings put into question simplistic interpretations of brain entropy as a direct neural correlate of conscious level.

Significance Statement The effects of psychedelic substances on conscious experience can be substantially affected by contextual factors, which play a critical role in the outcomes of psychedelic therapy. This study shows how context can modulate not only psychological, but also neurophysiological phenomena during a psychedelic experience. Our findings reveal distinctive effects of having eyes closed after taking LSD, including a more pronounced change on the neural dynamics, and a closer correspondence between brain activity and subjective ratings. Furthermore, our results suggest a competition between external stimuli and internal psychedelic-induced imagery, which supports the practice of carrying out psychedelic therapy with patients having their eyes closed.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • The authors declare no conflict of interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Effects of external stimulation on psychedelic state neurodynamics
Pedro A.M. Mediano, Fernando E. Rosas, Christopher Timmermann, Leor Roseman, David J. Nutt, Amanda Feilding, Mendel Kaelen, Morten L. Kringelbach, Adam B. Barrett, Anil K. Seth, Suresh Muthukumaraswamy, Daniel Bor, Robin L. Carhart-Harris
bioRxiv 2020.11.01.356071; doi: https://doi.org/10.1101/2020.11.01.356071
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Effects of external stimulation on psychedelic state neurodynamics
Pedro A.M. Mediano, Fernando E. Rosas, Christopher Timmermann, Leor Roseman, David J. Nutt, Amanda Feilding, Mendel Kaelen, Morten L. Kringelbach, Adam B. Barrett, Anil K. Seth, Suresh Muthukumaraswamy, Daniel Bor, Robin L. Carhart-Harris
bioRxiv 2020.11.01.356071; doi: https://doi.org/10.1101/2020.11.01.356071

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