PLoS Computational Biology
October 16, 2014
Srivas Chennu, Paola Finoia, Evelyn Kamau et al.
249 citations
Consciousness is thought to require balanced integration and differentiation of brain activity, supported by efficient networks. Analyzing high-density EEG from 32 patients with chronic disorders of consciousness and healthy controls, the authors found that patient networks showed reduced local and global efficiency and fewer hubs in the alpha frequency band. A new metric, modular span, revealed that alpha network modules in patients were spatially limited, lacking the long-distance interactions seen in controls. However, delta and theta band networks were partially reversed and more similar to each other in patients. Alpha network efficiency correlated with behavioral awareness. Notably, some behaviorally unresponsive vegetative patients with covert awareness had well-preserved alpha networks resembling controls, suggesting network mechanisms that may support consciousness despite severe behavioral impairment.
Neuroimage
February 15, 2021
Andrea I. Luppi, Robin Carhart-Harris, Leor Roseman et al.
186 citations
LSD alters brain network dynamics non-uniformly over time, making globally segregated connectivity states more complex and weakening the link between functional and anatomical connectivity. The drug reduces functional connectivity in the anterior medial prefrontal cortex specifically during states of high segregation. Ego dissolution was predicted by increased small-world organization during a state of high global integration. These temporally-specific effects reveal a more nuanced picture of psychedelic-induced changes in brain connectivity and complexity than previously reported.
Communications Biology
January 28, 2023
Andrea I. Luppi, Jakub Vohryzek, Morten L. Kringelbach et al.
98 citations
Consciousness depends on how tightly brain function follows the brain's physical wiring. Using MRI scans, researchers measured structure-function coupling across spatial scales in people who were unconscious from anesthesia or brain injury and in people under psychedelics (LSD or ketamine). During loss of consciousness, function more closely tracked the brain's structural connections, a signature that could distinguish behaviorally similar brain-injured patients and detect covert consciousness. In contrast, psychedelics decoupled function from structure, and this decoupling correlated with physiological and subjective scores. The findings suggest that connectome harmonic decomposition reveals how neuromodulation and network architecture jointly shape consciousness.
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.
Scientific Reports
January 23, 2020
Thomas F. Varley, Andrea I. Luppi, Ioannis Pappas et al.
86 citations
Measures of algorithmic and process complexity, applied to functional MRI BOLD signals from individuals under propofol sedation, vary in their ability to distinguish sedation levels. Temporal complexity measures are more sensitive than topological ones. All measures strongly relate to a single underlying construct—termed 'overall complexity'—which explains most variance in the data, as assessed by principal component analysis. This overall complexity discriminates between sedation levels and propofol serum concentrations, supporting the idea that consciousness is linked to complexity, regardless of how complexity is measured.
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.
bioRxiv
November 26, 2020
Andrea I. Luppi, Pedro A. M. Mediano, Fernando E. Rosas et al.
49 citations
preprint
The brain coordinates information from many sources to create a unified conscious experience. Combining network science and information theory, the authors identify a “synergistic global workspace” where gateway regions gather synergistic information from specialized brain modules, integrate it, and then broadcast it widely via broadcaster regions. Functional MRI shows that gateway regions correspond to the default mode network and broadcasters to the executive control network. Loss of consciousness from general anesthesia or disorders of consciousness reduces the workspace’s ability to integrate information, which is restored upon recovery. This work reconciles aspects of the Global Neuronal Workspace and Integrated Information Theory.
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.
Trends in Neurosciences
May 31, 2024
Andrea I. Luppi, Fernando E. Rosas, Pedro A. M. Mediano et al.
23 citations
Unconsciousness increases the coupling between brain structure and function across scales, while psychedelics may decouple brain function from structure. Anaesthetics, psychedelics, and disorders of consciousness can produce similar reconfigurations along the brain's unimodal-transmodal functional axis. Decomposing brain function into fundamental constituents of time, space, and information has driven recent advances in understanding consciousness and the brain's functional organisation. Computational modelling offers a path toward mechanistic integration, and decomposition approaches may help translate discoveries across species.
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.
Elife
July 18, 2024
Andrea I. Luppi, Pedro A. M. Mediano, Fernando E. Rosas et al.
1 citation
Loss of consciousness significantly disrupts the brain's ability to integrate information. In a study involving functional MRI analysis, it was revealed that gateway regions in a 'synergistic global workspace' correspond to the default mode network, while broadcaster regions align with the executive control network. This integration breakdown occurs during general anaesthesia or disorders of consciousness, with recovery restoring functionality. The findings enhance understanding of consciousness by bridging Global Neuronal Workspace and Integrated Information Theory, highlighting the critical role of brain networks in maintaining conscious experience.
bioRxiv
December 17, 2024
Dian Lyu, Ram Adapa, Robin Carhart-Harris et al.
preprint
The default mode network (DMN) and frontoparietal control network (FPCN), typically anticorrelated at rest in healthy brains, show continuous rather than absolute anatomical boundaries in the posterior precuneus. Connectivity differences along the dorsal-ventral axis follow linear slopes, forming functional gradients that exist only within each network's territory. These gradients flatten in altered states of consciousness (ASC), with the gradient magnitude similarly impaired across different ASC types, while spatial entropy differs between psychedelic and sedative states. The findings suggest the DMN and FPCN, though appearing distinct, may originate from a single integrated mechanism, and the loss of functional differentiation between them characterizes altered conscious states.
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 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.
Brain Communications
January 1, 2026
Dorottya Szocs, Dian Lyu, Andrea I. Luppi et al.
The pulvinar nucleus of the thalamus shows the strongest functional connectivity change with loss of consciousness under anesthesia in healthy volunteers, while the ventral-latero-ventral nucleus shows the strongest change in patients with disorders of consciousness. These nuclei exhibit distinct connectivity patterns with higher-order brain networks such as the default mode and executive control networks. In patients, the neural connectivity biomarker mirrored behavioral changes, suggesting potential clinical relevance for targeted deep brain stimulation therapy.
Trends in Cognitive Sciences
March 1, 2024
Tim Bayne, Anil K. Seth, Marcello Massimini et al.
New tests for consciousness (C-tests) are urgently needed to resolve uncertainty about when consciousness arises in human development, when it is lost due to neurological disorders and brain injury, and how it is distributed in nonhuman species. This need is amplified by recent developments in AI, neural organoids, and xenobot technology. Existing C-tests are of limited use, and no tests exist for many critical populations. The paper identifies challenges facing any attempt to develop C-tests, proposes a multidimensional classification of such tests, and identifies strategies for validating them.
Neuroimage
February 11, 2023
Andrea I. Luppi, Pedro A. M. Mediano, Fernando E. Rosas et al.
High-level brain functions are thought to arise from coordinated activity across neural systems, but this has been hard to test empirically. Using a framework called Integrated Information Decomposition, which quantifies emergence in dynamical systems, the authors analyzed functional MRI data and found that emergent and hierarchical neural dynamics are significantly reduced in chronically unresponsive patients with severe brain injury. Emergence capacity was positively correlated with hierarchical organization in brain activity. Combining network control theory and whole-brain modeling, the authors show that reduced emergent and hierarchical dynamics in these patients can be explained by disruptions in the structural connectome. The results suggest that chronic unresponsiveness after severe brain injury may stem from structural damage to neural infrastructure needed for emergent brain dynamics.
Communications Biology
November 3, 2022
Peter Coppola, Judith Allanson, Lorina Naci et al.
Consciousness is associated with short-term brain connectivity transitions that are less predictable, quicker, but on average more constant than those in unconscious states. By combining modern consciousness theories with phenomenology and dynamical systems theory, the authors created an individual-specific landscape of brain connectivity dynamics as a proxy for the stream of consciousness. They found that temporally-specific connectivity states are less easily describable by network patterns distant in time, suggesting a richer space of possible states. The cortex, cerebellum, and subcortex all display consciousness-relevant dynamics.
Dian Lu, Adapa Ram, Robin Carhart-Harris et al.
The posterior precuneus, a key hub of the default mode network, sits at the boundary with the frontoparietal control network. Using a spatial-derivative approach across five pharmacological datasets including psychedelic and anaesthetic states, the authors show that measuring how functional connectivity changes along the precuneus's dorsal–ventral axis reveals the organization of these networks with greater anatomical specificity than connectivity alone. This functional gradient is systematically altered by consciousness level: its overall magnitude diminishes across all altered states of consciousness, while its spatial entropy increases under psychedelics but decreases under sedation. The findings suggest the precuneus embeds a continuous, anatomically constrained transition between large-scale networks sensitive to global brain-state dynamics.