N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic, known to rapidly induce short-lasting alterations in conscious experience, characterized by a profound and immersive sense of physical transcendence alongside rich and vivid auditory distortions and visual imagery. Multimodal neuroimaging data paired with dynamic analysis techniques offer a valuable approach for identifying unique signatures of brain activity—and linked autonomic physiology—naturally unfolding during the altered state of consciousness induced by DMT. We leveraged simultaneous fMRI and EKG data acquired in 14 healthy volunteers prior to, during, and after intravenous administration of DMT, and, separately, placebo. fMRI data were preprocessed to derive individual dynamic activity matrices, reflecting the similarity of brain activity in time, and community detection algorithms were applied on these matrices to identify brain activity substates; EKG data were used to derive continuous heart rate. We identified a brain substate occurring immediately after DMT injection, characterized by hippocampal and medial parietal deactivations and increased superior temporal lobe activity under DMT. Deactivations in the hippocampus and medial parietal cortex correlated with alterations in the usual sense of time, space, and self-referential processes, reflecting a deconstruction of essential features of ordinary consciousness. Superior lobe activations, instead, correlated with audio/visual hallucinations and experience of “ entities ”, reflecting the emergence of altered sensory experiences under DMT. Finally, increased heart rate under DMT correlated positively with hippocampus/medial parietal deactivation and the experience of “ entities ”, and negatively with altered self-referential processes. These results suggest a chain of influence linking sympathetic regulation to hippocampal and medial parietal deactivations under DMT, which, combined, may contribute to positive mental health outcomes related to self-referential processing following psychedelic administration.

Psychedelics are serotonergic drugs that profoundly alter consciousness, yet their neural mechanisms are not fully understood. A popular theory, RElaxed Beliefs Under pSychedelics (REBUS), posits that psychedelics flatten the hierarchy of information flow in the brain. Here, we investigate hierarchy based on the imbalance between sending and receiving brain signals, as determined by directed functional connectivity. We measure properties of directed functional hierarchy in a magnetoencephalography (MEG) dataset of 16 healthy human participants who were administered a psychedelic dose (75 micrograms, intravenous) of lysergic acid diethylamide (LSD) under four different conditions: eyes-closed with or without music and eyes-open with or without a video stimulus. Across the whole brain, LSD diminishes the asymmetry of directed connectivity when averaged across time. Additionally, we demonstrate that machine learning classifiers distinguish between LSD and placebo more accurately when trained on one of our hierarchy metrics than when trained on traditional measures of functional connectivity. Taken together, these results indicate that LSD weakens the hierarchy of directed connectivity in the brain by increasing the balance between senders and receivers of neural signals.