Navigating the chaos of psychedelic neuroimaging: A multi-metric evaluation of acute psilocybin effects on brain entropy
In a 28-participant, 121-scan fMRI study, acute psilocybin produced consistent increases on a subset of entropy measures (e.g. Shannon entropy of the spatial eigendistribution, path-length, instantaneous correlations, brain‑state switching and short-timescale sample entropy) while eight of 14 metrics showed no effect and Lempel‑Ziv complexity was inconsistently positive. Limited correlations across metrics indicate these entropy measures index distinct aspects of brain dynamics rather than a single unified construct.
Authors
- Gitte Knudsen
- Patrick Fisher
- Dea Stenbæk
Published
Abstract
A prominent theory of psychedelics is that they increase brain entropy. Thirteen studies have evaluated psychedelic effects on fMRI brain entropy; no findings have been replicated. Here we evaluated these metrics in an independent 28-participant healthy cohort with 121 pre- and post-psilocybin fMRI scans. We assessed relations between brain entropy and objective and subjective psychedelic drug effects using linear mixed-effects models. All metrics were evaluated using two parcellation strategies and 7 denoising pipelines. We observed consistent significant positive associations for Shannon entropy of the spatial eigendistribution of the time by voxel matrix, path-length, instantaneous correlations, brain-state switching, and sample entropy at short time-scales. We consistently did not observe significant effects for 8 of 14 entropy metrics and observe inconsistent positive effects for Lempel-Ziv complexity of the BOLD signal. Brain entropy quantifications showed limited inter-measure correlations. Our observations support a nuanced acute psychedelic effect on brain entropy, empirically demonstrating that these metrics do not reflect a singular construct.
Research Summary of 'Navigating the chaos of psychedelic neuroimaging: A multi-metric evaluation of acute psilocybin effects on brain entropy'
Introduction
Psychedelic drugs produce profound alterations of consciousness mediated largely by agonism at the serotonin 2A receptor, and clinical studies combined with psychological support have shown promising therapeutic effects in mood and behavioural disorders. Functional MRI studies have sought neural correlates of these altered states, and one prominent framework is the Entropic Brain Hypothesis (EBH), which proposes that the phenomenological richness of the acute psychedelic state reflects brain-wide increases in the entropy, or information complexity, of functional brain signals. Entropy here is operationalised in multiple ways (for example Shannon entropy, Lempel–Ziv complexity, and sample entropy) and can be applied to static connectivity matrices, dynamic connectivity profiles, or regional time-series. Drummond and colleagues note that twelve prior fMRI studies have each reported a distinct brain-entropy metric, none evaluated in an independent cohort, and that inter-metric correlations have not been systematically examined. To address this gap, the current study evaluated acute psilocybin effects on those 12 previously reported entropy metrics in an independent sample of 28 healthy participants. Scans were acquired before and multiple times after a single oral psilocybin dose and were accompanied by plasma psilocin levels and subjective drug intensity ratings; the investigators tested whether each entropy metric related to these measures and explored inter-metric correlations to assess whether 'brain entropy' behaves as a unified construct.
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Study Details
- Study Typeindividual
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McCulloch, D. E., Olsen, A. S., Ozenne, B., Stenbaek, D. S., Armand, S., Madsen, M. K., Knudsen, G. M., & Fisher, P. M. (2023). 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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