Navigating the chaos of psychedelic fMRI brain-entropy via multi-metric evaluations of acute psilocybin effects
Drummond E-Wen Mcculloch, Anders S. Olsen, Brice Ozenne, Dea Siggaard Stenbæk, Sophia Armand, M. Madsen, Gitte M. Knudsen, Patrick M. Fisher
medRxiv July 3, 2023 preprint DOI: 10.1101/2023.07.03.23292164 via OpenAlex
Summary
AI-generated from the abstractPsychedelics like psilocybin are thought to increase brain entropy, but previous findings have not been replicated. In 28 healthy participants with 121 fMRI scans taken before and after psilocybin, brain entropy was measured alongside plasma psilocin levels, serotonin 2A receptor occupancy, and subjective drug intensity. Shannon entropy of path-length and instantaneous correlation distributions showed significant positive associations with drug effects, while sample entropy showed divergent associations depending on time-scale. However, 8 of 13 entropy metrics showed no significant effects, and the metrics correlated poorly with each other. The results suggest a nuanced acute effect of psilocybin on brain entropy and highlight specific metrics that may mediate clinical effects.
Study at a glance
| Characteristics | Observational cohort |
|---|---|
| Sample size | 28 |
| Population | Healthy adults |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Sample entropy Artificial intelligence Mathematics Cognitive psychology |
| Citations | 20 |
| Key finding | Psilocybin had significant positive associations with some entropy metrics (Shannon entropy of path-length and instantaneous correlation distributions) but not with most metrics, indicating a nuanced effect on brain entropy. |
Abstract
A prominent theory of psychedelics is that they increase brain entropy. Twelve studies have evaluated psychedelic effects on fMRI brain entropy quantifications, 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 plasma psilocin, brain serotonin 2A receptor occupancy, and a subjective drug intensity rating using linear mixed-effects models. We observed significant positive associations for Shannon entropy of path-length, instantaneous correlation distributions, and divergent associations of sample entropy at varying time-scales. We did not observe significant effects for 8 of 13 entropy metrics. Brain entropy quantifications showed limited inter-measure correlations. Our observations support a nuanced acute psychedelic effect on brain entropy, underscoring the need for replication and that these metrics do not reflect a singular construct. Our findings highlight candidate brain entropy metrics that may mediate clinical effects of psychedelics.