Journal of Neuroscience
March 7, 2012
Gustavo Deco, Viktor Jirsa
778 citations
The brain's ongoing activity at rest, in the absence of tasks or stimulation, is highly structured into spatiotemporal patterns known as resting state networks, which exhibit low-frequency fluctuations below 0.1 Hz. Using a global spiking attractor network model that incorporates realistic neuroanatomical connectivity from diffusion tensor imaging, the authors demonstrate that resting state functional connectivity quantitatively matches human experimental data when the brain network operates at the edge of instability. Under these conditions, slow fluctuations emerge as structured noise around a stable low firing equilibrium, shaped by latent multistable attractors inherent in the neuroanatomical connectivity.
Science Advances
February 1, 2019
Athena Demertzi, Enzo Tagliazucchi, Stanislas Dehaene et al.
545 citations
Consciousness depends on the brain's ability to sustain rich, dynamic patterns of signal coordination. Using functional magnetic resonance imaging, a complex pattern of coordinated and anticoordinated signals characterized healthy individuals and minimally conscious patients. Unresponsive patients showed low interareal phase coherence mainly mediated by structural connectivity, with fewer transitions between patterns. This complex pattern was also seen in patients with covert cognition who could perform mental imagery tasks, validating its link to consciousness. Anesthesia increased the probability of the less complex pattern to levels seen in unresponsive patients, confirming its role in unconsciousness. These results establish generalizable fingerprints of conscious and unconscious states after brain damage.
Proceedings of the National Academy of Sciences
April 13, 2020
Morten L. Kringelbach, Josephine Cruzat, Joana Cabral et al.
326 citations
By combining multimodal neuroimaging data, a framework was developed that demonstrates the fundamental principles of bidirectional coupling between neuronal and neurotransmitter dynamical systems. The work causally explains the functional effects of stimulating specific serotoninergic receptors (5-HT2AR) with psilocybin in healthy humans. This could lead to a better understanding of why psilocybin shows promise as a therapeutic intervention for neuropsychiatric disorders such as depression, anxiety, and addiction.
Neuroimage
May 25, 2019
Louis-David Lord, Paul Expert, Selen Atasoy et al.
249 citations
Brain function can be understood as the exploration of a repertoire of metastable connectivity patterns that underlie different mental processes. Intravenous infusion of psilocybin rapidly modulates how the brain dynamically explores these resting-state networks. Using a data-driven approach focused on the leading eigenvector of BOLD phase coherence at single-TR resolution, recurrent BOLD phase-locking patterns were assessed pre- and post-infusion. A frontoparietal subsystem pattern was strongly destabilized after psilocybin, while a pattern characterized by global BOLD phase coherence became more probable. These results demonstrate network-specific neuromodulation by psilocybin, bridging molecular pharmacodynamics and whole-brain network dynamics.
Curr Biol
September 27, 2018
Gustavo Deco, Josephine Cruzat, Joana Cabral et al.
246 citations
A whole-brain model integrating anatomical, functional, and neurotransmitter data explains how serotonin 2A receptor stimulation with LSD alters brain dynamics. The model combines diffusion MRI, functional MRI, and PET scans of serotonin 2A receptor density to simulate resting-state activity and music listening effects. It shows that LSD's effects arise from non-linear interactions between anatomical connectivity, the brainwide distribution of 5-HT2A receptors, and neuromodulation of neuronal gain. Accounting for neuromodulatory activity in brain models can yield insights into brain function and aid drug discovery for neuropsychiatric disorders.
Sci Rep
December 15, 2017
Selen Atasoy, Leor Roseman, Mendel Kaelen et al.
225 citations
LSD alters the energy and power of individual harmonic brain states in a frequency-selective manner, leading to an expansion of the repertoire of active brain states. This expansion is non-random, suggesting a general re-organization of brain dynamics. The frequency distribution of active brain states under LSD closely follows power-laws, indicating a re-organization of dynamics at the edge of criticality. These findings provide insight into how LSD affects brain function and open new methods for understanding complex brain dynamics in health and disease.
PLoS Computational Biology
November 7, 2007
Marco Loh, Edmund T. Rolls, Gustavo Deco
172 citations
Reduced depth in the basins of attraction of cortical attractor states destabilizes neural activity at the network level due to constant statistical fluctuations from stochastic spiking of neurons. In integrate-and-fire network simulations, decreasing NMDA receptor conductances reduces attractor basin depth, destabilizes short-term memory states, and increases distractibility. Cognitive symptoms of schizophrenia—distractibility, working memory deficits, poor attention—could stem from this instability in prefrontal cortical networks. Lower firing rates in orbitofrontal and anterior cingulate cortex may account for negative symptoms like reduced emotions. Decreasing both GABA and NMDA conductances causes switches between attractor states and jumps from spontaneous activity into attractors, linked to positive symptoms such as delusions, paranoia, and hallucinations from shallow basins in temporal lobe semantic memory networks.
Nature communications
October 3, 2022
S Parker Singleton, Andrea I Luppi, Robin L Carhart-Harris et al.
156 citations
Psychedelics like LSD and psilocybin temporarily alter subjective experience by acting on serotonin 2a (5-HT2a) receptors, increasing the diversity (entropy) of brain activity. This increase may arise from a flattening of the brain's control energy landscape. Using fMRI data, the authors show that these compounds reduce the control energy needed for transitions between brain states compared to placebo. Across individuals, lower control energy correlates with more frequent state transitions and higher entropy. Incorporating PET data on 5-HT2a receptor distribution under non-drug conditions, the analysis links these receptors to reduced control energy. The findings demonstrate that receptor-informed network control theory can model how neuropharmacological manipulation affects brain dynamics.
The Neuroscientist
September 1, 2017
Selen Atasoy, Gustavo Deco, Morten L. Kringelbach et al.
131 citations
Spontaneous brain activity exhibits coherent oscillations across a wide range of frequencies, with temporal patterns highly correlated across distributed cortical areas, forming resting state networks. This work introduces harmonic brain modes as fundamental building blocks of complex spatiotemporal neural activity, defined as harmonic modes of structural connectivity (connectome harmonics) that yield fully synchronous activity patterns with different frequency oscillations constrained by brain structure. This framework links space and time in brain dynamics. The authors show how harmonic brain modes explain neurophysiological, temporal, and network-level changes across mental states (wakefulness, sleep, anesthesia, psychedelic). Spatial and temporal characteristics emerge from the interplay between excitation and inhibition, fitting changes associated with different mental states, offering tools for understanding brain dynamics in various states of consciousness.
Current Biology
February 20, 2016
Raphael Kaplan, Mohit H. Adhikari, Rikkert Hindriks et al.
127 citations
Hippocampal sharp-wave ripples, brief high-frequency oscillations linked to memory consolidation, are followed by a dramatic increase in fMRI signal within the default mode network (DMN) of anesthetized monkeys. This effect was specific to ripples and did not occur after other hippocampal events or in other resting-state networks. The findings link circuit-level neural dynamics—ripples—to network-level fluctuations in the DMN, providing mechanistic support for the DMN's role in memory consolidation.
Cerebral Cortex
July 10, 2013
Gustavo Deco, P. Hagmann, Anthony G. Hudetz et al.
99 citations
The transition from wakefulness to sleep involves gradual neural changes rather than an abrupt shift. Local slow waves appear during wakefulness and increase as arousal-promoting neuromodulation decreases, while resting-state brain networks maintain their overall organization. Only when neuromodulation drops to very low levels do slow waves become global and resting-state networks merge into a single synchronized network.
Physical review. E
July 28, 2021
Yonatan Sanz Perl, Hernan Bocaccio, Carla Pallavicini et al.
82 citations
Conscious wakefulness is characterized by brain dynamics far from thermodynamic equilibrium, while states of reduced consciousness—such as deep sleep and anesthesia induced by propofol, ketamine, or ketamine plus medetomidine—operate closer to equilibrium. This conclusion comes from analyzing electrocorticography data from nonhuman primates and functional magnetic resonance imaging data from humans. Entropy production and the curl of probability flux in phase space reliably distinguished conscious from unconscious states. The findings establish nonequilibrium macroscopic brain dynamics as a robust signature of consciousness and offer a statistical mechanics framework for studying cognition and awareness.
NeuroImage
April 11, 2020
Ignacio Pérez Ipiña, Patricio Donnelly Kehoe, Morten L. Kringelbach et al.
81 citations
A semi-empirical model combining fMRI data, structural connectivity, and anatomically-informed priors shows that brain states during the wake-sleep cycle are better described by multiple dimensions rather than a single continuum. The best fit used priors based on functionally coherent networks, dividing the cortex into regions with opposite dynamics: frontoparietal regions approached a noise-driven bifurcation from fixed-point dynamics, while sensorimotor regions approached a bifurcation from oscillatory dynamics. Sleep onset involved subcortical deactivation with low correlation, reversed in deeper stages. Periodic forcing simulating external perturbations identified key regions for wakefulness recovery. The model characterizes sleep as having diminished perceptual gating but latent capacity for rapid arousal.
Communications Biology
June 29, 2022
Anira Escrichs, Yonatan Sanz Perl, Carme Uribe et al.
67 citations
Different brain states—resting, meditating, deep sleep, and disorders of consciousness after coma—are underpinned by distinct spatiotemporal dynamics that can be characterized using turbulence theory. Non-conscious states tend to be more synchronous, while conscious states are more asynchronous, but the work goes beyond this simple dichotomy. A model-free analysis of human neuroimaging data applied Kuramoto's turbulence framework with coupled oscillators and measured information cascades across spatial scales. A complementary model-based approach used exhaustive computer simulations of whole-brain models fitted to those measures to study information encoding. The framework shows that turbulence theory provides excellent tools for describing and differentiating between brain states.
Prog Brain Res
October 25, 2018
Selen Atasoy, Jakub Vohryzek, Gustavo Deco et al.
67 citations
Psychedelics produce distinct brain activity patterns characterized by frequency-specific energy changes and an expanded repertoire of functional states, as revealed through connectome-harmonic decomposition. These neural signatures suggest that psychedelics increase the brain's flexibility and diversity of activity, which may underlie their therapeutic benefits for mental health.
Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences
May 23, 2022
Jakub Vohryzek, Joana Cabral, Peter Vuust et al.
62 citations
The brain balances order and disorder in its activity patterns to adapt to a complex environment. Depression involves excessively rigid, ordered brain states, while psychedelics induce more disordered, overly flexible states. This review uses dynamical system theory and neuroimaging to characterize how different healthy and altered brain states correspond to distinct spacetime dynamics, potentially guiding new treatments for rebalancing brain states in disease.
NeuroImage
November 1, 2020
Gerald J. Hahn, Gorka Zamora‐lópez, Lynn Uhrig et al.
55 citations
Brain-wide signal levels can reliably distinguish sleep and anesthesia from the awake state in human and monkey fMRI resting state data. A whole-brain computational model reproduces changes in global synchronization, functional connectivity, structure-function relationship, integration, and segregation across vigilance states. The awake brain operates near a Hopf bifurcation, which coincides with globally correlated fMRI signals. Simulated lesions of connectivity hubs in the posterior brain and subcortical nuclei disrupt the model's awake state, matching predictions from graph-theoretical analyses of structural data.
Network Neuroscience
December 23, 2022
Gustavo Deco, Yonatan Sanz Perl, Laura de la Fuente et al.
43 citations
The default mode network (DMN) may coordinate the recruitment and scheduling of brain networks for solving cognitive tasks, supported by evidence that DMN regions are physically and functionally distant from sensorimotor areas. Using a thermodynamics-inspired, deep learning-based Temporal Evolution NETwork (TENET) framework to measure the 'arrow of time'—a marker of nonreversibility and hierarchy in brain signals—analysis of Human Connectome Project data from nearly a thousand participants suggests the DMN orchestrates hierarchy levels that shift between rest and seven cognitive tasks. This hierarchy differs significantly in health versus neuropsychiatric disorders, offering insights into brain dynamics for cognition.
Nature Mental Health
August 5, 2024
Gustavo Deco, Yonatan Sanz Perl, Samuel Johnson et al.
39 citations
Two serotonergic interventions—psilocybin therapy and the antidepressant escitalopram—rebalance brain dynamics in major depressive disorder through opposite hierarchical reconfigurations. In a double-blind phase II trial, 22 patients received two 25 mg doses of psilocybin plus daily placebo, while 20 patients received two 1 mg doses of psilocybin plus daily escitalopram. Resting-state fMRI scans before and after treatment, analyzed with generative effective connectivity models, showed that the two treatments produced significantly different and opposite changes in whole-brain hierarchy. Machine learning predicted treatment response with 85% accuracy. The findings suggest that depression may involve disrupted function of brain regions that orchestrate dynamics from the top of the hierarchy.
Neuroimage
January 29, 2021
Beatrice M. Jobst, Selen Atasoy, Adrián Ponce-Alvarez et al.
37 citations
After taking LSD, the brain's dynamics become less stable and more diverse in response to perturbations. Using a whole-brain computational model fitted to fMRI data from individuals under LSD or placebo, researchers simulated external disruptions to different brain regions. They measured recovery time with the Perturbational Integration Latency Index (PILI). Globally, LSD caused consistently higher PILI values, indicating a shift further from stable equilibrium. Locally, the largest differences appeared in the limbic, visual, and default mode networks. LSD also increased variability of PILI across brain regions, suggesting greater response diversity. These findings reveal brain-wide dynamical changes underlying the psychedelic state and suggest potential clinical applications for psychiatric disorders.
Interface Focus
April 14, 2023
Elvira G-Guzmán, Yonatan Sanz Perl, Jakub Vohryzek et al.
34 citations
Living systems must constantly work against equilibrium to survive, a property that can be measured through temporal asymmetry in brain signals. Using statistical physics, researchers analyzed reversibility in functional magnetic resonance imaging data from patients with disorders of consciousness. They found that decreased asymmetry and reduced non-stationarity in brain signals characterize impaired consciousness states, consistent with previous findings in sleep and anesthesia. The work aims to identify biomarkers for patient improvement and classification, and to deepen mechanistic understanding of consciousness disorders.
Brain communications
January 1, 2024
Jakub Vohryzek, Joana Cabral, Louis-David Lord et al.
33 citations
Psilocybin therapy for depression shows promise, but its causal mechanisms are unknown. By comparing brain dynamics in treatment responders (those with >50% symptom reduction) and non-responders before treatment, researchers used large-scale brain modeling to identify brain regions whose perturbation could shift a depressive brain state to a healthy one. The identified regions correlated with density maps of serotonin receptors 5-HT2a and 5-HT1a, where psilocin (psilocybin's active metabolite) acts as an agonist. These findings provide causal mechanistic evidence linking specific brain regions and serotonergic transmission to recovery from depression via psilocybin.
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.
PLoS computational biology
February 1, 2023
Giulio Ruffini, Giada Damiani, Diego Lozano-Soldevilla et al.
28 citations
Brain dynamics under LSD become more disordered and complex, moving further from the critical point that characterizes healthy brain function. Using Ising spin models fitted to fMRI data from fifteen participants, the authors show that LSD reduces interhemispheric connectivity, especially between corresponding regions in opposite hemispheres. Ising temperatures were significantly higher under LSD than placebo, indicating a shift into a more disordered (paramagnetic) state. Algorithmic complexity of brain activity, measured by block decomposition, correlated with both Ising temperature and condition, supporting the entropic brain hypothesis that psychedelics increase neural disorder.
Network Neuroscience
January 1, 2022
Josephine Cruzat, Yonatan Sanz Perl, Anira Escrichs et al.
28 citations
Psychedelic drugs like LSD and psilocybin may treat neuropsychiatric disorders by dose-dependently altering the brain's functional hierarchy—the organization of neural activity across regions. Using a turbulence framework that measures local synchronization (vorticity) in both space and time, researchers found that both drugs produce consistent and distinct effects, particularly compressing the default mode network, a higher-level network. These findings support the hypothesis that psychedelics modulate the functional hierarchy and provide a quantitative comparison of how LSD and psilocybin change brain dynamics, with implications for therapeutic use.