Science Advances
June 14, 2023
Leor Roseman, Christopher Timmermann, Daniel Golkowski et al.
65 citations
The effects of mind-altering drugs on brain function arise from complex interactions with multiple neurotransmitter systems, not just one. By linking the distribution of 19 neurotransmitter receptors and transporters (measured with PET) to changes in functional connectivity (measured with fMRI) caused by 10 drugs—anesthetics (propofol, sevoflurane, ketamine), psychedelics (LSD, psilocybin, DMT, ayahuasca), and others (MDMA, modafinil, methylphenidate)—the work shows a many-to-many mapping between drug effects and neurotransmitter systems. The drugs' impacts follow hierarchical gradients of brain structure and function, and regional susceptibility to drug-induced changes mirrors susceptibility to structural alterations from brain disorders.
iScience
January 17, 2025
Paolo Cardone, Arthur Bonhomme, Vincent Bonhomme et al.
9 citations
In a small double-blind, placebo-controlled, cross-over trial with three adults who had prolonged disorders of consciousness after a coma, an intravenous sub-anesthetic dose of the atypical psychedelic ketamine increased brain complexity as measured by Lempel-Ziv complexity, but did not change the explainable consciousness indicator. Patients showed reduced spastic paresis and spent more time with their eyes open, yet their diagnosis of consciousness did not improve. No adverse effects occurred. The findings suggest a potential therapeutic role for ketamine in disorders of consciousness and support a link between brain complexity and conscious states.
bioRxiv (Cold Spring Harbor Laboratory)
July 13, 2022
Andrea I. Luppi, Justine Y. Hansen, R. Adapa et al.
5 citations
preprint
Psychoactive drugs reshape brain function by engaging multiple neurotransmitter systems simultaneously. By mapping the distribution of 19 neurotransmitter receptors and transporters (via PET) and the connectivity changes caused by 10 drugs (anesthetics, psychedelics, and stimulants), the study shows that drug effects are organized along hierarchical gradients of brain structure and function. Additionally, brain regions susceptible to drug-induced changes are also vulnerable to structural alterations from brain disorders. These findings reveal systematic links between molecular neurochemistry and large-scale functional reorganization.
British journal of anaesthesia
April 1, 2025
Milan Van Maldegem, Jakub Vohryzek, Selen Atasoy et al.
3 citations
Ketamine, at anesthetic doses, produces a state where people are unresponsive yet often report vivid inner experiences, separating conscious awareness from behavioral responsiveness. Using connectome harmonic decomposition on fMRI data, researchers found that brain signals during ketamine-induced unresponsiveness show increased fine-grained spatial patterns, indicating higher neural granularity. This harmonic signature aligned with those of LSD-induced and ketamine-induced psychedelic states, but misaligned with signatures from unconscious individuals due to propofol sedation or brain injury. The method can track changes in conscious awareness even when behavior is absent, offering a tool for consciousness and anesthesia research.
bioRxiv (Cold Spring Harbor Laboratory)
August 19, 2024
Naji Alnagger, Paolo Cardone, Charlotte Martial et al.
3 citations
preprint
Disorders of consciousness, such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have few treatments. Using whole-brain computational models built from individual patients' fMRI and diffusion-weighted imaging data, this virtual clinical trial simulated the effects of LSD and psilocybin. The psychedelics shifted the brains of patients with disorders of consciousness closer to a critical dynamical state, with a larger effect in MCS patients. In UWS patients, the treatment response depended on structural connectivity, whereas in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for considering psychedelics in treating disorders of consciousness and highlight the role of computational modeling in drug discovery and personalized medicine.
Advanced Science
November 20, 2025
Paolo Cardone, Charlotte Martial, Yonatan Sanz Perl et al.
2 citations
Simulated administration of LSD and psilocybin in computational models of patients with disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), shifted brain activity closer to criticality—the phase transition between order and chaos. The effect was greater in MCS patients. In UWS patients, the treatment response correlated with structural connectivity, while in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for using psychedelics in DoC treatment and highlight the potential role of computational modeling in drug discovery and personalized medicine.
bioRxiv (Cold Spring Harbor Laboratory)
June 25, 2024
Milan van Maldegem, Jakub Vohryzek, Selen Atasoy et al.
2 citations
preprint
Ketamine, a dissociative anesthetic, produces different brain dynamics at anesthetic versus sub-anesthetic doses. Using connectome harmonic decomposition (CHD) to analyze resting-state fMRI data from volunteers during ketamine-induced unresponsiveness, the study found increased prevalence of localized harmonics, similar to patterns seen in psychedelic states induced by LSD or psilocybin. This contrasts with traditional GABAergic sedation (e.g., propofol), where global harmonics increase with higher doses. The results indicate that ketamine-induced unresponsiveness does not necessarily suppress conscious experience and influences connectome harmonics oppositely to GABAergic hypnotics. CHD may track alterations in conscious awareness rather than behavioral responsiveness.
The International journal of clinical and experimental hypnosis
January 1, 2025
Aminata Bicego, Naji Alnagger, Etzel Cardeña et al.
1 citation
Auto-induced cognitive trance (AICT) can produce mystical-type experiences in healthy individuals, with 29% of participants reporting such experiences during AICT compared to none during a rest condition. The study examined twenty-seven people who could self-induce AICT, measuring their religious and spiritual practices and paranormal beliefs beforehand. Participants completed five conditions including rest, imagination, and AICT with or without auditory stimulation. The intensity of the AICT experience and features resembling near-death experiences were linked to mystical-type experiences only during AICT. This is the first demonstration that AICT, a technique distinct from hypnosis or meditation, can induce mystical-type experiences outside life-threatening situations.
bioRxiv Preprint Server
September 28, 2022
Yonatan Sanz Perl, Carla Pallavicini, Juan Piccinini et al.
preprint
Brain states are often described on a single scale from full consciousness to unconsciousness, but this ignores the complex, high-dimensional nature of brain activity. By combining whole-brain modeling, data augmentation, and deep learning, researchers mapped states of consciousness into a low-dimensional space where distances reflect similarities between states. They found an orderly trajectory from wakefulness to brain-injured patients, with coordinates related to functional modularity and structure-function coupling, both increasing as consciousness is lost. Model perturbations provided a geometric interpretation of state stability and reversibility. The work suggests conscious awareness depends on functional patterns encoded as a low-dimensional trajectory within the vast space of brain configurations.