Anesthesiology
September 30, 2010
Pierre Boveroux, Audrey Vanhaudenhuyse, Marie‐Aurélie Bruno et al.
645 citations
Propofol-induced unconsciousness is linked to decreased connectivity within frontoparietal networks (the default-mode and executive-control networks) and between the thalamus and these networks, with a negative correlation between thalamic and cortical activity emerging during unconsciousness. In contrast, connectivity in low-level sensory cortices (auditory and visual networks) is preserved, including their thalamocortical connections. Loss of consciousness is associated with a breakdown of cross-modal interactions between visual and auditory networks. These findings suggest that unconsciousness results from disrupted communication between sensory and higher-order frontoparietal cortices, preventing conscious perception.
Journal of The Royal Society Interface
January 1, 2016
Enzo Tagliazucchi, Dante R. Chialvo, Michael Siniatchkin et al.
210 citations
Loss of consciousness from propofol sedation reduces long-range temporal correlations in frontothalamic brain activity and weakens the link between functional connectivity and anatomical structure. A model based on phase transitions in complex systems reproduces these patterns and also explains the cortex's reduced sensitivity to external stimuli during unconsciousness. The findings suggest that these neural changes are universal across different causes of unconsciousness.
Anesthesiology
August 9, 2016
Vincent Bonhomme, Audrey Vanhaudenhuyse, Athena Demertzi et al.
206 citations
Ketamine alters consciousness by disrupting connectivity within and between specific resting-state brain networks, particularly the default mode network (DMn) and salience network (SALn), while leaving sensory and motor networks largely intact. In healthy volunteers given stepwise ketamine infusions until they lost responsiveness, DMn connectivity between the medial prefrontal cortex and other network regions decreased (from 0.20 to 0.07), and the normal anticorrelated activity between the DMn and sensory regions reversed (e.g., right sensory cortex shifted from -0.07 to 0.04). SALn connectivity was also suppressed but nonuniformly. These specific changes, including preserved sensory network connectivity, are shared with propofol-induced unconsciousness.
Nature Communications
February 25, 2022
Minji Lee, Leandro Sanz, Alice Barra et al.
120 citations
A deep-learning-based explainable consciousness indicator (ECI) uses EEG responses to transcranial magnetic stimulation and resting-state EEG to separately quantify arousal and awareness. Tested during sleep (n=6), general anesthesia (n=16), and severe brain injury (n=34), ECI distinguishes states such as ketamine-induced anesthesia and rapid eye movement sleep, which combine low arousal with high awareness. Parietal brain regions are most relevant for these measurements. The indicator offers a way to disentangle the two components of consciousness across physiological, pharmacological, and pathological conditions.
PLoS ONE
June 30, 2014
Enrico Amico, Francisco Gómez, Carol di Perri et al.
115 citations
Functional connectivity of brain areas fluctuates over time, even during anesthesia. By applying point process analysis to resting-state fMRI data from 18 healthy subjects during propofol-induced wakefulness, sedation, unconsciousness, and recovery, the study identified eight distinct co-activation patterns centered on the posterior cingulate cortex (PCC). The core of these patterns remained stable across consciousness levels, but propofol caused region-specific reductions in co-activation, including disconnections of the prefrontal cortex, thalamus, auditory cortex, motor cortex, and visual area. The methodology helps refine characterization of local functional brain changes associated with propofol-induced modulation of consciousness.
Frontiers in Systems Neuroscience
August 14, 2019
Vincent Bonhomme, Cécile Staquet, Javier Montupil et al.
109 citations
General anesthesia reversibly alters consciousness without globally shutting down the brain. Depending on the agent and dose, it can produce a complete absence of subjective experience (unconsciousness), a conscious experience without environmental perception (disconnected consciousness, like during dreaming), or oriented consciousness with environmental awareness (connected consciousness). Each state may be followed by explicit or implicit memories. Progress in brain function exploration has improved understanding of neural correlates of consciousness and their alterations during anesthesia, including changes in functional and effective brain connectivity, consciousness network topology, and spatio-temporal dynamics.
February 26, 2013
Vincent Bonhomme, P Boveroux, J. F. Brichant et al.
71 citations
Hypnotic anesthetic agents alter consciousness by targeting specific brain networks in a dose-dependent manner. Higher-order networks involved in mental content and sub-cortical networks regulating thalamic activity are affected first as concentrations increase and inhibitory neurotransmission is enhanced. Lower-order sensory networks, including thalamo-cortical connectivity within them, are preserved even at concentrations that suppress responsiveness, though cross-modal sensory interactions are inhibited. Thalamo-cortical connectivity into consciousness networks decreases with higher concentrations and becomes anti-correlated between thalamus and cortex at the deepest sedation levels when the subject is non-responsive. Whether these changes occur with agents that inhibit excitatory neurotransmission remains unknown, and the link between fMRI observations and biochemical targets is still unidentified.
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.
Scientific Reports
November 5, 2018
Matthieu Darracq, Chadd M. Funk, Daniel Polyakov et al.
49 citations
Sleep and anesthesia alter conscious experience, which can be absent (unconsciousness) or take the form of dreaming where sensory stimuli are not incorporated (disconnected consciousness). Using transcranial magnetic stimulation-electroencephalography over parietal regions, evoked alpha power (8-12 Hz) decreased during disconnected consciousness in rapid eye movement sleep and ketamine anesthesia compared to wakefulness. In unconscious states of propofol anesthesia and non-rapid eye movement sleep, evoked low-gamma power (30-40 Hz) decreased compared to wakefulness or disconnected consciousness. These findings, confirmed with dream reports from serial awakenings, suggest suppression of evoked alpha activity may mark sensory disconnection.
International Anesthesiology Clinics
January 1, 2008
Pierre Boveroux, Vincent Bonhomme, Melanie Boly et al.
44 citations
A peer-reviewed article examines the intersection of medicine, consciousness, and brain function, focusing on altered states such as those arising from cardiovascular syncope, autonomic disorders, hallucinations in medical conditions, and traumatic brain injury with neurovascular disturbances. The work discusses how these conditions affect cognitive science, psychology, and legal implications, without presenting a single empirical finding or specific numerical data. The argument integrates neuroscience and philately as a metaphor for collecting insights, suggesting that altered states of consciousness can inform understanding of brain function and autonomic regulation.
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.
NeuroImage
February 9, 2021
Riku Ihalainen, Olivia Gosseries, Frederik van de Steen et al.
30 citations
Using dynamic causal modelling of high-density EEG recordings from 10 people during propofol anaesthesia, the study evaluated how three resting state networks—the default mode network, the salience network, and the central executive network—contribute to consciousness. Loss of consciousness reduced inter-network connectivity in the parietal cortex, especially feed-forward frontoparietal and parietal connections at the precuneus node within the default mode network. Within the salience and central executive networks, unconsciousness generated small increases in bidirectional connectivity. The most consistent predictions of consciousness came from a key set of frontoparietal connections, supporting the importance of the posterior hot zone in explaining loss of consciousness.
Nature reviews. Neurology
June 1, 2025
Charlotte Martial, Pauline Fritz, Olivia Gosseries et al.
19 citations
Near-death experiences (NDEs) are episodes of disconnected consciousness with prototypical mystical features, often occurring during actual or perceived physical threat. Various explanatory theories have been proposed, but integration has been limited. Converging evidence from neuroscience—including non-human studies, psychedelic-induced mystical experiences, and research on the dying brain—now offers a comprehensive explanation. This Review discusses psychological and neurophysiological processes underlying NDEs, including cellular and electrophysiological brain network changes and neurotransmitter alterations. The authors propose a model encompassing a cascade of concomitant processes within an evolutionary framework and consider how NDE research informs debates on consciousness emergence near brain death.
Chaos An Interdisciplinary Journal of Nonlinear Science
September 1, 2021
Sofía Morena del Pozo, Helmut Laufs, Vincent Bonhomme et al.
13 citations
Consciousness is linked to brain regions that synchronize transiently in ways that are both integrated and differentiated. Using dynamic brain networks from fMRI data collected during deep sleep and propofol anesthesia, this study found that unconsciousness reduced the size and flexibility of the largest spatiotemporal module, identified as the dynamic core. These results support the dynamic core hypothesis of consciousness.
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.
The International journal of clinical and experimental hypnosis
January 1, 2024
Mélanie Louras, Audrey Vanhaudenhuyse, Rajanikant Panda et al.
8 citations
Combining virtual reality with mind-body therapies such as meditation, mindfulness, relaxation, and hypnosis can reduce pain in both healthy volunteers and patients. A scoping review of 43 studies found that the combination is feasible, well-tolerated, and potentially useful for decreasing pain, and also improves anxiety, mood, and relaxation. However, insufficient research and a lack of multidimensional studies limit full understanding of their potential. More randomized controlled trials with usability evaluations are needed to incorporate these approaches into routine clinical practice.
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.
OBM Integrative and Complementary Medicine
March 5, 2025
Gaëtan Collignon, Aminata Bicego, Marie-Elisabeth Faymonville et al.
2 citations
A 68-year-old man with chronic pain from an open Spina Bifida at L4-L5 used auto-induced cognitive trance (AICT) to manage his condition. After four days of training, pain intensity, anxiety, and depression slightly decreased; most attitudes and beliefs improved; the mental component of quality of life improved while the physical component decreased, and the patient reported his overall health had worsened. Qualitative analysis of his diary over two months revealed themes including trance characteristics, pain location, difficulties with practice, and medical history. The findings suggest AICT may alter subjective pain experience, but its effects on physical health and global well-being were mixed.
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.
bioRxiv Preprint Server
June 7, 2026
Andrea I. Luppi, Dragana Manasova, Justine Y. Hansen et al.
preprint
Functional connectivity in the awake human brain is shaped primarily by cognitive co-activation—the tendency of brain regions to work together during mental tasks—more than by structural or molecular constraints. This predominance is systematically lost across five datasets involving pharmacological and pathological perturbations of consciousness (chronic disorders of consciousness; anesthesia with sevoflurane, propofol, or ketamine), when cognition is disconnected from the environment or abolished. During such states, the predictors of functional architecture shift away from cognitive co-activation and toward anatomical and molecular constraints.
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.