Healthy VolunteersNeuroimaging & Brain MeasuresDMT

Human brain effects of DMT assessed via EEG-fMRI

In a within-subject, placebo-controlled EEG–fMRI study of 20 volunteers, IV DMT produced robust increases in global functional connectivity, network disintegration and desegregation, and a compression of the principal cortical gradient. These imaging changes tracked subjective intensity, correlated with PET-derived 5‑HT2A receptor maps and EEG alterations, supporting a predominant action of DMT on the transmodal association cortex rich in 5‑HT2A expression.

Authors

  • Fernando Rosas
  • Enzo Tagliazucchi
  • Robin Carhart-Harris

Published

PNAS
individual Study

Abstract

Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on brain function in 20 healthy volunteers. Simultaneous EEG-fMRI was acquired prior to, during, and after a bolus IV administration of 20 mg DMT, and, separately, placebo. At dosages consistent with the present study, DMT, a serotonin 2A receptor (5-HT2AR) agonist, induces a deeply immersive and radically altered state of consciousness. DMT is thus a useful research tool for probing the neural correlates of conscious experience. Here, fMRI results revealed robust increases in global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient under DMT. GFC × subjective intensity maps correlated with independent positron emission tomography (PET)-derived 5-HT2AR maps, and both overlapped with meta-analytical data implying human-specific psychological functions. Changes in major EEG-measured neurophysiological properties correlated with specific changes in various fMRI metrics, enriching our understanding of the neural basis of DMT’s effects. The present findings advance on previous work by confirming a predominant action of DMT—and likely other 5-HT2AR agonist psychedelics—on the brain’s transmodal association pole, i.e., the neurodevelopmentally and evolutionarily recent cortex that is associated with species-specific psychological advancements, and high expression of 5-HT2A receptors.

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Research Summary of 'Human brain effects of DMT assessed via EEG-fMRI'

Introduction

Earlier neuroimaging work on classic psychedelics has converged on a picture of disrupted large-scale cortical organisation, commonly implicating the brain's transmodal association cortex pole (TOP) at the upper end of a principal sensorimotor-to-association gradient. The TOP is linked to high-level cognitive functions, prolonged temporal integration, and expanded cortical development in primates, and prior studies suggest that psychedelic subjective effects reflect dysregulation of these association cortices with possible disinhibition of evolutionarily earlier systems such as limbic circuitry. However, most prior human work has treated electrophysiological and haemodynamic measures separately, which limits the ability to directly relate neuronal activity to fMRI-derived connectivity changes and leaves open concerns about vascular confounds. Timmermann and colleagues set out to address these gaps by performing simultaneous electroencephalography (EEG) and functional MRI (fMRI) in healthy volunteers during eyes-closed resting state, administering intravenous DMT (20 mg) versus placebo in a within-subject, counterbalanced design. The study aimed to characterise static and dynamic effects of DMT on spectral EEG metrics (power bands, signal diversity, travelling waves), on fMRI measures (within- and between-network connectivity, global functional connectivity, pairwise connectivity, and the brain's principal cortical gradient), and to link these multimodal changes to subjective intensity, plasma DMT levels, and an independent in vivo 5-HT2A receptor density map.

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Study Details

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