Navigating the chaos of psychedelic neuroimaging: A multi-metric evaluation of acute psilocybin effects on brain entropy

This brain imaging study (n=28) evaluated the acute effects of psilocybin on 12 previously reported brain entropy metrics in healthy participants. It found a positive association for Shannon entropy of path-length and instantaneous correlation distributions, while no significant effects were observed for seven of the 12 metrics, and concluded that the acute effects of psychedelics on brain entropy are nuanced and that ‘brain entropy’ is not a singular construct.

Abstract of Navigating the chaos of psychedelic neuroimaging

“Investigations into the acute effects of psychedelics on brain imaging have emphasised increased ‘brain entropy’ as a potential neural correlate. To date, 12 previous studies have reported brain entropy effects, each reporting a single and unique metric, none of which have been examined in an independent cohort. Here we evaluated acute psilocybin effects on these 12 brain entropy metrics in an independent cohort of 28 healthy participants. Following a single psilocybin dose, participants completed pre/post resting-state BOLD fMRI scans (28 pre-drug, 93 post-drug scans during the acute drug effects). Each scan was accompanied by a plasma sample to quantify plasma drug levels and estimate brain serotonin 2A receptor occupancy, as well as a rating of subjective drug intensity. We assessed relations between brain entropy and these measures with linear mixed-effects models. There was a significantly positive association for Shannon entropy of path-length and instantaneous correlation distributions and divergent associations of network-wise sample entropy at varying time-scales. We did not observe significant psilocybin effects for seven of 12 brain-entropy metrics. Whole-brain entropy metrics showed limited correlations between each other. Our observations suggest a nuanced acute effect of psychedelics on brain entropy, underscoring the need for reproducing effects. The variable effects and limited inter-metric correlation undermines the generalisability of ‘brain entropy’ as a singular construct. Future studies in clinical cohorts are crucial to elucidate the link between these metrics and therapeutic effects of psychedelics.”

Authors: Drummond E-W. McCulloch, Anders S. Olsen, Brice Ozenne, Dea S. Stenbaek, Sophia Armand, Martin K. Madsen, Gitte M. Knudsen & Patrick M. Fisher

Summary of Navigating the chaos of psychedelic neuroimaging

Psychedelic drugs induce profoundly altered states of consciousness and may be used to treat various disorders. Human brain functional magnetic resonance imaging has begun to shed light on the neural pathways affected by psychedelics.

The Entropic Brain Hypothesis

The Entropic Brain Hypothesis (EBH) posits that the ‘richness’ of the phenomenology of the acute psychedelic state reflects brain-wide increases in the entropy of functional brain signals. Entropy is a metric of information content commonly referred to by the eponymous name “Shannon entropy”.

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Find this paper

Navigating the chaos of psychedelic neuroimaging: A multi-metric evaluation of acute psilocybin effects on brain entropy

https://doi.org/10.1101/2023.07.03.23292164

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Cite this paper (APA)

Drummond, E., McCulloch, W., Olsen, A. S., Ozenne, B., Stenbaek, D. S., Armand, S., ... & Fisher, P. M. (2023). Navigating the chaos of psychedelic neuroimaging: A multi-metric evaluation of acute psilocybin effects on brain entropy. medRxiv.

Study details

Compounds studied
Psilocybin

Topics studied
Neuroscience

Study characteristics
Original Re-analysis Active Placebo Single-Blind Within-Subject

Participants
28 Humans

Institutes

Institutes associated with this publication

Copenhagen University Hospital Rigshospitalet
The university hospital in Copenhagen, the Rigshospitalet, is Denmark's most prestigious (and largest) hospital. Literally translated, the name stands for 'Hospital of the Realm.' Researchers here are working on at least three psychedelic trials with psilocybin.

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 14 - 21
mg | 1x

Linked Clinical Trial

The Neurobiological Effect of 5-HT2AR Modulation
The investigators wish to investigate neurobiological effects of serotonin 2A receptor modulation in healthy volunteers, contrasting effects of an agonist (psilocybin) and an antagonist (ketanserin). Magnetic resonance imaging (MRI) and positron emission tomography (PET) will be used as neuroimaging tools.

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