This re-analysis pre-print (n=14) applies a receptor-informed network control theory framework to investigate the effects of DMT on the brain’s control energy landscape. It reveals that DMT, like LSD and psilocybin, reduces global control energy, with these trajectories correlating with EEG signal diversity and subjective intensity ratings. Furthermore, the regional effects of DMT correlate with serotonin 2a receptor density, demonstrating a potential proof-of-concept for predicting pharmacological intervention effects on brain dynamics using control models.
Abstract of Time-resolved network control analysis links reduced control energy under DMT
“Psychedelics offer a profound window into the functioning of the human brain and mind through their robust acute effects on perception, subjective experience, and brain activity patterns. In recent work using a receptor-informed network control theory framework, we demonstrated that the serotonergic psychedelics lysergic acid diethylamide (LSD) and psilocybin flatten the brain’s control energy landscape in a manner that covaries with more dynamic and entropic brain activity. Contrary to LSD and psilocybin, whose effects last for hours, the serotonergic psychedelic N,N-dimethyltryptamine (DMT) rapidly induces a profoundly immersive altered state of consciousness lasting less than 20 minutes, allowing for the entirety of the drug experience to be captured during a single resting-state fMRI scan. Using network control theory, which quantifies the amount of input necessary to drive transitions between functional brain states, we integrate brain structure and function to map the energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Consistent with previous work, we find that global control energy is reduced following injection with DMT compared to placebo. We additionally show longitudinal trajectories of global control energy correlate with longitudinal trajectories of EEG signal diversity (a measure of entropy) and subjective ratings of drug intensity. We interrogate these same relationships on a regional level and find that the spatial patterns of DMT’s effects on these metrics are correlated with serotonin 2a receptor density (obtained from separately acquired PET data). Using receptor distribution and pharmacokinetic information, we were able to successfully recapitulate the effects of DMT on global control energy trajectories, demonstrating a proof-of-concept for the use of control models in predicting pharmacological intervention effects on brain dynamics.”
Authors: S. Parker Singleton, Christopher Timmermann, Andrea I. Luppi, Emma Eckernäs, Leor Roseman, Robin L. Carhart-Harris & Amy Kuceyeski
Summary of Time-resolved network control analysis links reduced control energy under DMT
Serotonergic psychedelics such as LSD, psilocybin, and DMT are powerful neuromodulators that transiently alter the human experience. MAO enzymes metabolise DMT in the body and, therefore, must be combined with MAO inhibitors to be orally active.
Human neuroimaging studies with LSD and psilocybin have demonstrated that these compounds acutely decrease integrity within the brian’s functional sub-networks, while increasing integrity between functional sub-networks. This finding affords a unique opportunity to model and study the perturbation of brain dynamics using whole-brain computational models.
Network control theory is a linear dynamical systems approach that models state transitions occurring within a network. It has been applied to the brain in various cognitive states and neuropsychiatric/degenerative conditions, as well as throughout development and during neuromodulation and pharmacologically induced altered states.
Find this paper
Time-resolved network control analysis links reduced control energy under DMT with the serotonin 2a receptor, signal diversity, and subjective experience
Open Access | Google Scholar | Backup | 🕊
Cite this paper (APA)
Singleton, S. P., Timmermann, C., Luppi, A. I., Eckernas, E., Roseman, L., Carhart-Harris, R. L., & Kuceyeski, A. (2023). Time-resolved network control analysis links reduced control energy under DMT with the serotonin 2a receptor, signal diversity, and subjective experience. bioRxiv, 2023-05.
Neuroscience Healthy Subjects
Original Re-analysis Placebo-Controlled Single-Blind Within-Subject Randomized
Authors associated with this publication with profiles on BlossomChris Timmermann
Chris Timmerman is a postdoc at Imperial College London. His research is mostly focussed on DMT.
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.
Institutes associated with this publicationImperial College London
The Centre for Psychedelic Research studies the action (in the brain) and clinical use of psychedelics, with a focus on depression.
The psychedelics given at which dose and how many timesDMT 20 mg | 1x
Linked Research Papers
Notable research papers that build on or are influenced by this paperHuman brain effects of DMT assessed via EEG-fMRI
This neuroimaging study (n=20) aimed to understand the effects of DMT (20mg) on the human brain. The researchers used EEG-fMRI (electroencephalography-functional MRI) to measure brain activity before, during, and after administering DMT to healthy volunteers. They found that DMT increased global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient.