The flattening of spacetime hierarchy of the N,N-dimethyltryptamine brain state is characterized by harmonic decomposition of spacetime (HADES) framework.
Jakub Vohryzek, Joana Cabral, Christopher Timmermann, Selen Atasoy, Leor Roseman, David Nutt, Robin Carhart-Harris, Gustavo Deco, Morten L. Kringelbach
National Science Review May 1, 2024 DOI: 10.1093/nsr/nwae124 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Healthy participants |
| Interventions | N N-dimethyltryptamine (DMT) |
| Topics | DMT 5-MeO-DMT |
| Keywords | Harmonic modes Spatio-temporal brain dynamics Psychedelics hallucinogens Entheogens Psychoactive substances Neuroscience brain science Neural studies Cognitive science Consciousness awareness Perception Cognition Brain waves |
| Citations | 13 |
| Key findings | DMT decreases contributions across most low-frequency harmonic modes, particularly the second functional harmonic representing the uni- to transmodal functional hierarchy, supporting the hypothesis that psychedelics alter functional hierarchy. |
Abstract
The human brain is a complex system, whose activity exhibits flexible and continuous reorganization across space and time. The decomposition of whole-brain recordings into harmonic modes has revealed a repertoire of gradient-like activity patterns associated with distinct brain functions. However, the way these activity patterns are expressed over time with their changes in various brain states remains unclear. Here, we investigate healthy participants taking the serotonergic psychedelic N,N-dimethyltryptamine (DMT) with the Harmonic Decomposition of Spacetime (HADES) framework that can characterize how different harmonic modes defined in space are expressed over time. HADES demonstrates significant decreases in contributions across most low-frequency harmonic modes in the DMT-induced brain state. When normalizing the contributions by condition (DMT and non-DMT), we detect a decrease specifically in the second functional harmonic, which represents the uni- to transmodal functional hierarchy of the brain, supporting the leading hypothesis that functional hierarchy is changed in psychedelics. Moreover, HADES' dynamic spacetime measures of fractional occupancy, life time and latent space provide a precise description of the significant changes of the spacetime hierarchical organization of brain activity in the psychedelic state.
Comparable studies
Other experimental studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids | 2017 | Experimental study | |
| Bufo alvarius: a potent hallucinogen of animal origin. Bufo alvarius toad venom | 1994 | Experimental study | |
| Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment Volunteers | 2019 | Within-subjects experimental study | n = 11 |
| Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine. Adult cats | 1990 | Experimental study | n = 10 |
| Studies on the Mechanism of Action of Monoamine Oxidase: Metabolism of N,N-Dimethyltryptamine and N,N-Dimethyltryptamine-N-Oxide | 1962 | Experimental study |
Citations in the library
Cited by 8
- Neural Geometrodynamics, Complexity, and Plasticity: A Psychedelics Perspective Entropy January 22, 2024
- The Algorithmic Agent Perspective and Computational Neuropsychiatry: From Etiology to Advanced Therapy in Major Depressive Disorder Entropy November 6, 2024
- Time-resolved coupling between connectome harmonics and subjective experience under the psychedelic DMT bioRxiv (Cold Spring Harbor Laboratory) May 31, 2024
- Perturbing whole‐brain models of brain hierarchy: An application for depression following pharmacological treatment Annals of the New York Academy of Sciences July 21, 2025
- N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences. Neuropsychopharmacology September 12, 2025
and 3 more in the library
Cites 26
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Ongoing Cortical Activity at Rest: Criticality, Multistability, and Ghost Attractors Journal of Neuroscience March 7, 2012
and 21 more in the library