Human brain effects of DMT assessed via EEG-fMRI

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.

Synergistic, Multi-level Understanding of Psychedelics: Three Systematic Reviews and Meta-analyses of Their Pharmacology, Neuroimaging and Phenomenology

“…This popular ‘meme’ likely has its origin in the first resting-state fMRI study of a psychedelic, where decreased blood flow, BOLD signal and altered FC were observed in a pattern of regions resembling the DMN (Carhart-Harris et al, 2012). Eleven years later, evidence continues to indicate that psychedelics potently affect the regularity of population brain activity in DMN regions (Timmermann et al, 2023). Since a commonly reported experience on psychedelics is the dissolution of the self, a phenomenon known as “ego death” (Moreton et al, 2020; Nour et al, 2016; Pahnke, 1969b), it would superficially make sense that psychedelics dysregulate the DMN.…”

“…While these latter findings about RSN disintegration and desegregation have been replicated across time, DMN-specific deactivation has not, and the initial focus on the DMN now seems unjustified. In more recent work by Carhart-Harris and colleagues, greater emphasis has been placed on the dysregulation of spontaneous activity across the high-level transmodal cortex, of which the DMN is a part (Girn et al, 2023; Timmermann et al, 2023).…”

“…When we initially looked at the pairwise FC matrices from the studies that we included in the meta-analysis, we were surprised to find that the increases in within-DMN FC outnumbered the decreases. This result was mostly driven by three studies that performed whole-brain seed-to-seed FC analyses (Bedford et al, 2023; Dai et al, 2023; Timmermann et al, 2023). However, we subsequently discovered that many of the regions in these studies overlapped with other Yeo networks besides the DMN.…”

“…Similarly, according to EBH, the brain would be more entropic if, for instance, individual regions were to exhibit a greater number of possible connectivity motifs. Tagliazucchi et al (2014) found that psychedelics raise entropy in this manner, and since then, ten other fMRI studies and several MEG and EEG studies have all shown that entropy increases during psychedelic use (Alonso et al, 2015; Atasoy et al, 2017; Lebedev et al, 2015, 2016; Lord et al, 2019; Luppi et al, 2023; Mediano et al, 2020; Pallavicini et al, 2021; Schartner et al 2017; Singleton et al, 2022; Timmermann et al, 2019, 2023; Varley et al, 2020; Viol et al, 2017, 2019).…”

Psychedelic Concentrations of Nitrous Oxide Reduce Functional Differentiation in Frontoparietal and Somatomotor Cortical Networks

“…As the scientific and clinical interest in psychedelics continues to grow, there is a pressing need for a deeper neurobiological understanding. Although there are extensive neuroimaging studies on the neural correlates of classical serotonergic psychedelics-such as lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT) (Carhart-Harris et al, 2012Timmermann et al, 2023)-nitrous oxide remains relatively understudied, despite the longstanding recognition of its psychedelic effects (Block et al, 1990;James, 1874).…”