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.
Communications Biology
September 30, 2024
Pablo Castro, Andrea I. Luppi, Enzo Tagliazucchi et al.
21 citations
Brain activity during unconsciousness, whether from general anaesthesia or slow wave sleep, is dominated by a recurrent functional connectivity pattern primarily mediated by structural connectivity and with a reduced capacity to transition to other patterns. Conscious awareness is characterized by richer brain dynamics measured by entropy and a greater repertoire of connectivity states. These findings suggest that the dynamic exploration of functional connectivity states provides robust and generalizable markers for the state of consciousness across different conditions.
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 L. 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 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.
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
October 1, 2023
Tim Bayne, Joel Frohlich, R. Cusack et al.
Evidence from studies of functional network connectivity, attention, multimodal integration, and cortical responses to global oddballs suggests that consciousness is likely present in early infancy and may even occur before birth. Recent research is beginning to provide clues about both the content and structure of infant consciousness.
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.
Alzheimer's & dementia (New York, N. Y.)
January 1, 2021
Jonathan D Huntley, Stephen M Fleming, Daniel C Mograbi et al.
People with Alzheimer's disease show a range of changes in consciousness, including reduced awareness of cognitive deficits, diminished self-awareness, and impaired introspection, which appear early and worsen as the disease progresses. These awareness impairments are linked to brain damage in areas that overlap with proposed neural correlates of consciousness. The authors argue that recognizing Alzheimer's disease as a disorder of consciousness is overdue and important for understanding patients' lived experience and improving care.