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.
BJA Open
September 26, 2023
Javier Montupil, Paolo Cardone, Cécile Staquet et al.
32 citations
The source of consciousness is widely thought to be within the brain, and anesthesiologists have their own operational definition based on observations during anesthesia. The full functional correlates of consciousness remain unclear, but several theories have gained varying support from experiments, including those using anesthesia to reversibly alter aspects of consciousness. Understanding these mechanisms could improve patient management by enabling monitoring devices that detect different states during anesthesia: unconsciousness, internal awareness with or without conscious perception of the environment (connected or disconnected consciousness). Unresponsiveness does not guarantee absence of connectedness or consciousness. This narrative review presents current knowledge from a system-level perspective, highlighting anesthesia's contribution to theories of consciousness and proposing future research directions.
Journal of Psychopharmacology
July 29, 2023
Natalie Ertl, Will Lawn, Claire Mokrysz et al.
17 citations
Regular cannabis use is associated with localized increases in connectivity of the executive control network (ECN), which may reflect adaptive or compensatory changes in response to regular intoxication. Adolescents generally showed weaker connectivity than adults across multiple brain networks, consistent with normal developmental effects. However, there were no significant interactions between age group and cannabis user group, meaning the connectivity changes linked to cannabis use did not differ between adolescents and adults. No associations were found between cannabis use frequency and any connectivity measures.
Neurosci Conscious
June 15, 2024
Paolo Cardone, Naji Alnagger, Jitka Annen et al.
16 citations
Psychedelic substances, already being tested for psychiatric conditions like depression and PTSD, might also help people with disorders of consciousness caused by brain injury. The article discusses the rationale for using complexity-enhancing psychedelics in post-comatose patients, proposing an optimal level of brain complexity for recovery. It examines how psychedelics and disorders of consciousness may have counterintuitive effects on the default mode network and selfhood. Computational modeling could complement experimental studies to clarify treatment mechanisms and enable personalized medicine. The authors update ethical considerations for this clinical and scientific endeavor.
Journal of Cognitive Neuroscience
January 1, 2023
Rajanikant Panda, Audrey Vanhaudenhuyse, Andrea Piarulli et al.
15 citations
During hypnosis, brain connectivity changes in ways that suggest more efficient cognitive processing and less mind-wandering. In nine healthy participants, hypnosis increased delta-wave connections between frontal brain regions and between frontal and parietal regions. It decreased alpha and beta-2 connections among frontal, parietal, and midline areas. Network analysis showed greater segregation of short-range connections in delta and alpha bands and greater integration of long-range connections in beta-2 bands. Frontal and right parietal electrodes became central hubs. These altered dynamics may reflect a modified balance between internal and external awareness networks.
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.
Frontiers in Neuroscience
February 13, 2024
Benedetta Cecconi, Javier Montupil, Sepehr Mortaheb et al.
6 citations
Disconnected consciousness, where subjective experience persists but is cut off from the external world, often occurs during sleep or sedation but is difficult to study because unresponsive people may still be conscious and amnesia can erase memories of events. This research uses a serial awakening paradigm during mild propofol sedation: participants hear sounds and are interviewed while still sedated to determine whether they are connected or disconnected from the environment, bypassing the need for behavioral responses and amnesia. Functional MRI data reveal neural activity patterns during these states, testing whether sensory disconnection arises at the thalamus or from disrupted information flow to higher brain regions. Slow-wave activity's role is also explored via high-frequency BOLD oscillations. Findings could improve anesthesia monitoring and assessment of patients with reduced consciousness.
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.
Brain and Behavior
October 1, 2025
Pauline Fritz, Anaïs Pichelin, Aurore Ancion et al.
2 citations
A case of a near-death experience (NDE) occurring in a medical and pharmacological context is examined, highlighting the lasting transformations it can trigger. The account underscores the importance for clinicians to recognize NDEs because of their potential long-term effects on patients and their relevance to medical practice.
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.