NeuroImage
June 30, 2020
Thomas F. Varley, Robin Carhart‐Harris, Leor Roseman et al.
91 citations
Psychedelic drugs like psilocybin and LSD increase the fractal dimension of brain activity, suggesting that the brain moves toward a critical state between order and disorder. Using fMRI data from volunteers, the study tested two fractal measures: one for functional connectivity networks and one for BOLD time-series. Both drugs significantly increased the fractal dimension of functional connectivity networks. LSD also significantly increased the fractal dimension of BOLD signals, while psilocybin showed a non-significant trend in the same direction. Changes in the fractal dimension of BOLD signals were localized to brain areas in the dorsal attention network. These results indicate that psychedelic-induced changes in consciousness are associated with evolution toward a critical zone.
PLoS ONE
June 29, 2012
Laura Moreno-López, Emmanuel A. Stamatakis, María José Fernández-serrano et al.
73 citations
In a sample of 49 polysubstance users in residential treatment who had been abstinent for a prolonged period, the severity of use of heroin, alcohol, MDMA, and cannabis each showed negative correlations with brain metabolism in the dorsolateral prefrontal cortex and temporal cortex. Alcohol use was additionally linked to lower metabolism in the frontal premotor cortex and putamen, while stimulant use was associated with lower metabolism in the parietal cortex. These findings suggest that different drugs of abuse may produce overlapping and distinct patterns of brain dysfunction even after extended abstinence, which could inform targeted rehabilitation strategies.
Human Brain Mapping
March 19, 2021
Andrea I. Luppi, Daniel Golkowski, Andreas Ranft et al.
72 citations
The human brain alternates between states of high integration and segregation, which are thought to support consciousness. Using dynamic functional connectivity and graph theory on resting-state fMRI data from healthy volunteers, the authors show that the integrated state is especially vulnerable to the anaesthetic sevoflurane. At higher doses (3% vol and burst-suppression), anaesthesia reduces the complexity and small-world character of integrated brain states and disrupts the temporal balance between integration and segregation. These effects reverse upon recovery, linking them to consciousness. Reduced anticorrelations between the default mode and executive control networks also reconfigure dynamically depending on the brain's integration state. The breakdown of the integrated sub-state may serve as a generalisable biomarker of loss and recovery of consciousness.
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.
Neuroscience of Consciousness
November 1, 2021
Andrea I. Luppi, Pedro A. M. Mediano, Fernando E. Rosas et al.
42 citations
Consciousness can be better understood by decomposing it into distinct information-theoretic elements rather than measuring it as a single quantity of integrated information. The authors propose Integrated Information Decomposition (ΦID), which provides a formal argument that whether consciousness is an emergent phenomenon depends on its information-theoretic composition. Two organisms may have the same amount of integrated information yet differ in composition. A new measure, ΦR, and the ΦR-ing ratio quantify how efficiently information is used for conscious processing. This approach enables identification of qualitatively different 'modes of consciousness' and mapping them to phenomenology, starting with selfhood. ΦID offers new ways to explore the relationship between information, consciousness, and neural dynamics.
bioRxiv (Cold Spring Harbor Laboratory)
September 23, 2021
Pedro A. M. Mediano, Aleksi Ikkala, Rogier Kievit et al.
30 citations
preprint
Neural complexity measures, which can distinguish conscious from unconscious states, also detect meaningful fluctuations in conscious level during normal wakefulness. Using MEG and fMRI data from healthy adults, complexity decreased as participants became drowsy, validating the approach. Complexity changed within and between tasks, and higher complexity was associated with better performance and faster reaction times on an executive task. This offers a new way to explore the cognitive and neural basis of consciousness.
bioRxiv (Cold Spring Harbor Laboratory)
May 17, 2021
S. Parker Singleton, Andrea I. Luppi, Robin L. Carhart-Harris et al.
30 citations
preprint
LSD and psilocybin reduce the amount of energy the brain needs to transition between different activity states, as measured by functional MRI. This flattening of the brain's control energy landscape allows for more frequent state transitions and more diverse (entropic) brain activity. The effects are linked to the spatial distribution of serotonin 2a receptors, the main target of these psychedelics. The findings suggest that these compounds make brain state transitions more facile and temporally diverse, offering a mechanistic explanation for the altered subjective experience induced by psychedelics.
bioRxiv (Cold Spring Harbor Laboratory)
August 10, 2020
Andrea I. Luppi, Jakub Vohryzek, Morten L. Kringelbach et al.
26 citations
preprint
Consciousness arises from how the brain's structural wiring shapes its dynamic activity. By decomposing resting-state fMRI data into harmonic modes of the human structural connectome, a generalizable signature of lost consciousness emerges—whether from anesthesia or brain injury—while a reversed signature characterizes psychedelic states induced by LSD or ketamine, reflecting decoupling of function from structure. This connectome harmonic approach discriminates between behaviorally indistinguishable brain-injured patients and tracks covert consciousness, linking neurobiology to conscious experience.
bioRxiv (Cold Spring Harbor Laboratory)
January 11, 2019
Tf Varley, Robin Carhart‐Harris, Leor Roseman et al.
8 citations
preprint
Psychedelic drugs like LSD and psilocybin increase the fractal dimension of brain activity, indicating a shift toward a critical state between order and chaos. Using fMRI data, researchers measured the fractal dimension of functional connectivity networks and BOLD time-series. Both drugs significantly increased the fractal dimension of functional connectivity networks; LSD also significantly increased the fractal dimension of BOLD signals, while psilocybin showed a non-significant trend in the same direction. Changes localized to the dorsal-attentional network. These findings support the Entropic Brain Hypothesis, which proposes that psychedelics alter consciousness by moving the brain closer to a critical tipping point.
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.
Andrea I. Luppi, Pedro Mediano, Fernando Rosas et al.
5 citations
preprint
Consciousness can be understood not as a single unified thing but as composed of distinct information-theoretic elements. A new approach called Integrated Information Decomposition (ΦID) shifts from measuring how much integrated information a system has to analyzing its composition. This provides a formal way to determine whether consciousness is an emergent phenomenon based on that composition. Two organisms can have the same amount of integrated information yet differ in its composition. A new measure, ΦR, and the ΦR-ing rate quantify how efficiently an entity uses information for conscious processing. This decomposition identifies qualitatively different 'modes of consciousness,' enabling mapping between phenomenology and information-theoretic structure, starting with selfhood.
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
October 20, 2024
Peter Coppola, Adrian M. Owen, David K. Menon et al.
preprint
A new method captures the brain dynamics unique to each person's subjective experience. Using fMRI while people listened to a story awake and under different levels of anaesthesia, the approach tracks moment-to-moment changes in functional connectivity without assuming common brain states across individuals. The default mode network's dynamics were more dissimilar between conscious participants, reflecting personal engagement with the story. In contrast, the auditory and posterior dorsal attention networks showed higher similarity across conscious individuals, supporting more generalizable experiences. Conscious brain dynamics were more complex for individual-specific patterns but less complex for shared patterns.
bioRxiv Preprint Server
April 12, 2021
Peter Coppola, Lennart R.b. Spindler, Andrea I. Luppi et al.
preprint
The diversity of brain dynamics within small-world network topology, measured as sample entropy (dSW-E), consistently predicts levels of awareness across sedation and disorders of consciousness, even after accounting for underlying functional connectivity dynamics. Both subcortical and cortical areas show predictive value, but subcortical regions exhibit higher and more robust effect sizes. The dynamic reorganization of the functional information architecture, especially in the subcortex, emerges with awareness and offers explanatory power beyond the complexity of dynamic functional connectivity alone.
bioRxiv Preprint Server
June 12, 2026
Dante Sebastián Galván Rial, Gabriel A. Della Bella, Lorina Naci et al.
preprint
States of consciousness can be ordered along a single dimension defined by the entropy of spontaneous neural activity, as proposed by the Entropic Brain Theory. Applying the same analytical pipeline to pharmacological (psychedelics, modafinil, propofol anaesthesia) and clinical (schizophrenia) fMRI datasets, the temporal irregularity of brain network topology was quantified. Propofol anaesthesia occupied the low-entropy end; psychedelic states and schizophrenia occupied the high end. This ordering tracks combined modulations of the level and content of consciousness, from reduced awareness under anaesthesia to heightened arousal and expanded experience under psychedelics and disorganised processing in schizophrenia. The result was not reducible to fluctuations in mean functional connectivity and was supported by convergent reorganisation of higher-order association cortex.
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.