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Psychedelic Resting-state Neuroimaging: A Review and Perspective on Balancing Replication and Novel Analyses

This paper (2022) by some of the most well-known authors in the field of psychedelics, reviews 42 studies where resting-state functional magnetic resonance imaging (fMRI) was used and assessed methodological variations across studies. Nearly all studies varied in data processing and analysis methodology. Guidelines are proposed to ensure consistency across the field.

Authors

  • Gitte Knudsen
  • Fernando Rosas
  • Felix Müller

Published

Neuroscience and Biobehavioral Reviews
meta Study

Abstract

Clinical research into serotonergic psychedelics is expanding rapidly, showing promising efficacy across myriad disorders. Resting-state functional magnetic resonance imaging (rs-fMRI) is a commonly used strategy to identify psychedelic-induced changes in neural pathways in clinical and healthy populations. Here we, a large group of psychedelic imaging researchers, review the 42 research articles published to date, based on the 17 unique studies evaluating psychedelic effects on rs-fMRI, focusing on methodological variation. Prominently, we observe that nearly all studies vary in data processing and analysis methodology, two datasets are the foundation of over half of the published literature, and there is lexical ambiguity in common outcome metric terminology. We offer guidelines for future studies that encourage coherence in the field. Psychedelic rs-fMRI will benefit from the development of novel methods that expand our understanding of the brain mechanisms mediating its intriguing effects; yet, this field is at a crossroads where we must also consider the critical importance of consistency and replicability to effectively converge on stable representations of the neural effects of psychedelics.

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Research Summary of 'Psychedelic Resting-state Neuroimaging: A Review and Perspective on Balancing Replication and Novel Analyses'

Introduction

Classical psychedelics such as psilocybin, LSD and ayahuasca have experienced a research resurgence since the early 2000s, with small clinical trials reporting preliminary efficacy across a range of psychiatric conditions and evidence of lasting psychological effects in healthy volunteers. At psychoactive doses these compounds act on multiple receptor targets but their subjective effects are thought to be driven primarily by agonism at the serotonin 2A (5-HT2A) receptor; pre-treatment with 5-HT2A antagonists attenuates these effects. Resting-state functional magnetic resonance imaging (fMRI) has become a widely used tool to probe brain function during psychedelic sessions because it captures intrinsic brain dynamics without imposing task demands that could disrupt introspective, often intense, psychedelic experiences. Functional connectivity, typically estimated as correlations in BOLD signal between brain regions over time, is a common endpoint in these studies. This paper reviews the resting-state fMRI literature on psychedelics with the explicit aim of characterising methodological variability across studies and highlighting areas where harmonisation and replication would improve the field’s ability to converge on robust neural markers. The review surveys the published resting-state work, summarises study- and analysis-level heterogeneity, identifies prominent explanatory models that have been tested (for example, default mode network disintegration and thalamic gating), and offers recommendations to increase coherence and reproducibility in future research. By emphasising both the need for novel models and the importance of consistency, the review positions the field at a methodological crossroads in which replication must be balanced with innovation.

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Psychedelic Resting-state Neuroimaging: A Review... — Research Summary & Context | Blossom