Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience

2462 

Abstract Submission 

Lorenzo Pasquini¹, Alexander Simon², Courtney Gallen¹, Hannes Kettner¹, Leor Roseman³, Adam Gazzaley¹, Robin Carhart-Harris¹, Christian Timmermann⁴

¹Department of Neurology, Neuroscape, University of California, San Francisco, San Francisco, CA, ²Yale University, Interdepartmental Neuroscience Program, New Haven, CT, ³Division of Psychiatry, Department of Brain Sciences, Centre for Psychedelic Research, Imperial Coll, London, UK, ⁴Division of Psychiatry, Department of Brain Sciences, Centre for Psychedelic Research, Imperial Col, London, UK

Lorenzo Pasquini  
Department of Neurology, Neuroscape, University of California, San Francisco
San Francisco, CA

Alexander Simon  
Yale University, Interdepartmental Neuroscience Program
New Haven, CT

Courtney Gallen  
Department of Neurology, Neuroscape, University of California, San Francisco
San Francisco, CA

Hannes Kettner  
Department of Neurology, Neuroscape, University of California, San Francisco
San Francisco, CA

Leor Roseman  
Division of Psychiatry, Department of Brain Sciences, Centre for Psychedelic Research, Imperial Coll
London, UK

Adam Gazzaley  
Department of Neurology, Neuroscape, University of California, San Francisco
San Francisco, CA

Robin Carhart-Harris  
Department of Neurology, Neuroscape, University of California, San Francisco
San Francisco, CA

Christian Timmermann  
Division of Psychiatry, Department of Brain Sciences, Centre for Psychedelic Research, Imperial Col
London, UK

One's sense of self results from the integration of visceral and autonomic bodily functions into a distributed interoceptive brain network (1) and from the representation of autobiographical memories in midline parietal and medial temporal cortices (2). N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic, known to rapidly induce short-lasting disruptions in the ordinary sense of self, characterized by auditory distortions, amplification of emotional states, and feelings of ego dissolution (3). Multimodal neuroimaging work has started elucidating the impact of DMT on the human brain, by revealing brain network disintegration, heightened global connectivity, and increased EEG-based signal entropy after DMT administration (3). Novel methods enable the identification of functional substates that emerge over the course of an entire scan (4–6), a valuable approach for identifying unique signatures of brain activity – and linked autonomic physiology – naturally evolving during the altered state of consciousness induced by DMT.

We leveraged neuroimaging data acquired in 14 healthy volunteers as part of a within-subject study assessing the effects of DMT on brain function3. Simultaneous fMRI and ECG data were acquired prior to, during, and after an intravenous bolus administration of 20 mg of DMT fumarate, and, separately, placebo. ECG data was used to derive continuous heart rate; fMRI data was preprocessed to derive nodal activity time series. Cosine similarity was applied on the nodal activity time series to derive individual dynamic activity matrices, reflecting the similarity of brain activity in time. Group-averaged dynamic activity matrices were subtracted, revealing periods of homogeneous brain activity under DMT and community detection methods were applied on this subtraction matrix to identify brain activity substates. Brain activity substate maps were compared across DMT and placebo and significant activity changes were linked to scores of auditory distortions, meaningfulness of the experience, and heart rate alterations.

We identified three brain activity substates, one occurring before the injection of DMT and towards the end of the scanning session, a second directly following the injection of DMT, and a third state immediately following the previous post-injection substate. Only the second substate (i.e., the first occurring post-injection) showed significant brain activity changes when comparing the DMT to the placebo condition, revealing increased right superior temporal pole activity and decreased left hippocampal and medial parietal deactivations under DMT. Increased activation in the right superior temporal lobe correlated with the intensity of the auditory distortion, while deactivation of the hippocampus/medial parietal cortex correlated with scores of meaningfulness of the experience. During the first post-injection state, heart rate was increased during DMT, which correlated negatively with meaningfulness of the experience and positively with hippocampus/medial parietal deactivation.

Dynamic analyses and community detection algorithms applied to neuroimaging data acquired under DMT administration revealed a brain substate emerging during the peak effects, which was characterized by superior temporal lobe hyperactivity, and hippocampus and medial parietal cortex deactivation (7). While hyperactivity correlated with altered sensory perception, deactivations related to the self-referential attribution of meaning to the psychedelic experience. Although the acute DMT experience is accompanied by increased heart rate (8), lower heart rate changes predicted meaningfulness of the experience and stronger hippocampal/medial parietal deactivation. These results indicate that sympathetic regulation (9) and deactivation of hippocampal and medial parietal regions, which are associated with ego-dissolution under psychedelics, may contribute to fostering positive mental health outcomes in the context of psychedelic therapy.

Higher Cognitive Functions Other

Activation (eg. BOLD task-fMRI)

Anatomy and Functional Systems

Consciousness and Awareness ¹

Physiology, Metabolism and Neurotransmission Other ²

Autonomics

Cognition

Computational Neuroscience

Consciousness

Data analysis

Design and Analysis

FUNCTIONAL MRI

Seretonin

Treatment

Other - psychedelic