N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences.
Jakub Vohryzek, Andrea I. Luppi, Selen Atasoy, Gustavo Deco, Robin L. Carhart-Harris, Christopher Timmermann, Morten L. Kringelbach
Neuropsychopharmacology September 12, 2025 DOI: 10.1038/s41386-025-02190-4 via PubMed Central
Summary
AI-generated from the abstractThe brain's function depends on its structural wiring, and psychedelics alter this relationship. Using connectome harmonic decomposition, a method linking brain activity to the network of white matter pathways, the authors show that under N,N-dimethyltryptamine (DMT), the brain's harmonic repertoire shifts similarly to that seen with psilocybin, LSD, and ketamine. Repertoire entropy—a measure of the diversity of brain states—increases under DMT. For the first time, the energy spectrum difference and repertoire entropy of connectome harmonics track the intensity of subjective experience in real time, indicating a close coupling between brain network dynamics and conscious experience.
Study at a glance
| Characteristics | Observational study Peer reviewed |
|---|---|
| Interventions | N N-dimethyltryptamine (DMT) |
| Topics | 5-MeO-DMT Altered states of consciousness DMT |
| Keywords | Psychedelic Hallucinogen Neuroscience |
| Citations | 2 |
| Key finding | Connectome harmonic repertoire entropy increases under DMT, and measures of energy spectrum difference and repertoire entropy index the intensity of subjective experience in a time-resolved manner. |
Abstract
Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome - a network of white matter pathways linking different regions. To comprehensively grasp the effects of psychedelic compounds on brain function, we used a theoretically rigorous framework known as connectome harmonic decomposition. This framework provides a robust method to characterize how brain function intricately depends on the organized network structure of the human connectome. We show that the connectome harmonic repertoire under N,N-dimethyltryptamine (DMT) is reshaped in line with other reported psychedelic compounds - psilocybin, lysergic acid diethylamide (LSD) and ketamine. Furthermore, we show that the repertoire entropy of connectome harmonics increases under DMT, as with those other psychedelics. Importantly, we demonstrate for the first time that measures of energy spectrum difference and repertoire entropy of connectome harmonics index the intensity of subjective experience of the participants in a time-resolved manner reflecting close coupling between connectome harmonics and subjective experience.