Neuroimaging & Brain Measures

A complex systems perspective on psychedelic brain action

This commentary (2023) discusses the potential transdiagnostic efficacy of psychedelic-assisted therapy and its impact on brain function. It proposes that psychedelics induce a mode of brain function that is more dynamically flexible, diverse, integrated, and tuned for information sharing, which is consistent with greater criticality, and suggests that a complexity science perspective may help in understanding the inconsistencies in previous findings and guide towards compelling mechanistic models.

Authors

  • Fernando Rosas
  • Robin Carhart-Harris
  • Manesh Girn

Published

Trends in Cognitive Sciences
meta Study

Abstract

Recent findings suggesting the potential transdiagnostic efficacy of psychedelic-assisted therapy have fostered the need to deepen our understanding of psychedelic brain action. Functional neuroimaging investigations have found that psychedelics reduce the functional segregation of large-scale brain networks. However, beyond this general trend, findings have been largely inconsistent. We argue here that a perspective based on complexity science that foregrounds the distributed, interactional, and dynamic nature of brain function may render these inconsistencies intelligible. We propose that psychedelics induce a mode of brain function that is more dynamically flexible, diverse, integrated, and tuned for information sharing, consistent with greater criticality. This ‘meta’ perspective has the potential to unify past findings and guide intuitions toward compelling mechanistic models.

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Research Summary of 'A complex systems perspective on psychedelic brain action'

Introduction

Earlier neuroimaging work on serotonergic psychedelics (for example LSD, psilocybin, and DMT) has repeatedly reported a broad tendency toward reduced functional differentiation of large-scale brain networks — described here as increased global integration — yet attempts to identify consistent region- or network-specific correlates of the acute psychedelic state have produced heterogeneous and often contradictory results. Girn and colleagues note that conventional resting‑state fMRI analyses, which focus on time-averaged, location-specific functional connectivity (FC) within or between predefined networks, have yielded little spatial convergence across drugs, laboratories, or analytic pipelines. This inconsistency is further complicated by observations that some network changes attributed to psychedelics are not unique to them and by methodological factors such as differing parcellation strategies and individual variability in brain topography. To address this gap, the study proposes a ‘‘meta’’ perspective grounded in complexity science. Rather than seeking a canonical spatial fingerprint, the investigators aim to reinterpret existing findings through a whole-brain, dynamical-systems lens: they argue that psychedelics shift the brain into a distinct dynamical mode that is more flexible, diverse, integrated, and tuned for information sharing — a regime closer to criticality. The paper therefore reviews region- and network-focused fMRI results, presents didactic material on complexity approaches, surveys empirical studies that have applied such approaches to psychedelic datasets, and advances a theoretical framework that foregrounds spatiotemporal trajectories and individual variability as central to understanding psychedelic brain action.

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References (50)

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Show all 50 references
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The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

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Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology

Hartogsohn, I. · Journal of Psychopharmacology (2016)

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

Carhart-Harris, R. L., Erritzoe, D., Williams, T. et al. · PNAS (2012)

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Alonso, J. N., Romero, S., Mañanas, M. A. et al. · International Journal of Neuropsychopharmacology (2015)

Phenomenology, Structure, and Dynamic of Psychedelic States

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Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain’s control energy landscape

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Development of the Psychological Insight Questionnaire among a sample of people who have consumed psilocybin or LSD

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