This neuroscience reanalysis (n=25) of two earlier studies used connectome harmonic decomposition to analyse how DMT affects brain function across the structural connectome (white matter pathways), finding that DMT reshapes the connectome harmonic repertoire and increases repertoire entropy similarly to other psychedelics (psilocybin, LSD, ketamine), and importantly demonstrating for the first time that energy spectrum differences and repertoire entropy measures correlate with subjective experience intensity in a time-resolved manner, revealing close coupling between connectome harmonics and conscious experience under psychedelics.
Abstract of N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences
“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.“
Authors: Jakub Vohryzek, Andrea I. Luppi, Selen Atasoy, Gustavo Deco, Robin L. Carhart-Harris, Christopher Timmermann & Morten L. Kringelbach
Summary of N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences
Vohryzek and colleagues begin by outlining a central challenge in neuroscience: understanding how subjective experience arises from the interplay between the brain’s structure and function. Psychedelic compounds provide a unique opportunity to explore this relationship, as they act on specific neurotransmitter systems and alter brain dynamics in measurable ways. The researchers emphasise that such changes are not confined to local brain regions but spread throughout the brain along its structural wiring, also known as the connectome.
To study this interplay, the authors employ connectome harmonic decomposition (CHD). This mathematical framework represents brain activity in terms of “connectome harmonics,” which are patterns of neural activation linked to the brain’s structural network. The method is likened to a Fourier transform: just as sound can be broken down into component frequencies, brain activity can be decomposed into spatial frequencies defined by the connectome. Low-frequency harmonics reflect global brain organisation, whereas high-frequency harmonics capture more local, fine-grained patterns. This approach extends beyond earlier methods that examined brain function at only a single scale.
Previous research has shown that psychedelics such as LSD, psilocybin, and ketamine reduce the role of low-frequency harmonics while amplifying high-frequency ones. These shifts suggest a decoupling between brain activity and underlying structural connectivity. Psychedelics also broaden the brain’s harmonic repertoire, meaning a greater variety of activation patterns emerge during the altered state. Based on these findings, the authors hypothesise that DMT will induce similar changes. They predict a suppression of low-frequency harmonics, an enhancement of high-frequency harmonics, and an overall increase in entropy (a measure of diversity and unpredictability in brain activity).
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https://doi.org/10.1038/s41386-025-02190-4
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Cite this paper (APA)
Vohryzek, J., Luppi, A. I., Atasoy, S., Deco, G., Carhart-Harris, R. L., Timmermann, C., & Kringelbach, M. L. (2025). N, N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences. Neuropsychopharmacology, 1-9.
Study details
Topics studied
Neuroscience
Healthy Subjects
Study characteristics
Original Re-analysis
Placebo-Controlled
Single-Blind
Within-Subject
Randomized
Re-analysis
Bio/Neuro
Participants
25
Humans
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