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.
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
July 1, 2022
Fran Hancock, Joana Cabral, Andrea I. Luppi et al.
40 citations
Dynamic functional connectivity (dFC) in resting-state fMRI is promising for clinical biomarkers, but its reliability and interpretability are debated. This study combined phase-based dFC metrics from dynamical systems, stochastic processes, and information dynamics to assess their interrelationships and reliability. Novel relationships between metrics allowed building a predictive model for integrated information. Global metastability, reflecting simultaneous coupling and decoupling tendencies, was the most representative and stable metric in brain parcellations including cerebellar regions. Spatiotemporal patterns of phase-locking changed slowly and continuously over time. The findings suggest that most resting-state fMRI dynamics reflect an interrelated complexity profile unique to each acquisition, challenging cross-sectional designs for neuromarker discovery and indicating individual life-trajectories may be more informative.
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.
Preprints.org
July 21, 2023
Fran Hancock, Fernando E. Rosas, Mengsen Zhang et al.
16 citations
preprint
Healthy brain function requires a balance between stable integration across brain areas for coordinated activity and brief periods of desynchronization that allow subsystems to reconfigure and express specialized functions. Metastability, a concept from statistical physics and dynamical systems theory, has been proposed as a key signature of this balance. Neuroscience research has used markers of metastability to study cognitive performance, healthy aging, meditation, sleep, responses to drugs, and to characterize psychiatric conditions and disorders of consciousness. However, the term is often used heuristically or inaccurately, making the literature difficult to navigate. This paper provides a comprehensive review of metastability in neuroscience, covering its scientific and historical foundations, practical estimators, and a critical analysis of recent theoretical developments to clarify misconceptions.
National science review
May 1, 2024
Jakub Vohryzek, Joana Cabral, Christopher Timmermann et al.
13 citations
The human brain's activity constantly reorganizes across space and time, and decomposing whole-brain recordings into harmonic modes reveals gradient-like patterns linked to different functions. Using the HADES framework, researchers analyzed brain activity in healthy participants after taking the serotonergic psychedelic DMT. They found significant decreases in contributions across most low-frequency harmonic modes during the DMT state. Specifically, the second functional harmonic, which represents the uni- to transmodal functional hierarchy, decreased, supporting the hypothesis that psychedelics alter this hierarchy. Dynamic measures of fractional occupancy, lifetime, and latent space precisely described the changes in the brain's spacetime hierarchical organization during the psychedelic state.
Research Square
September 20, 2022
Jakub Vohryzek, Joana Cabral, Louis-David Lord et al.
10 citations
Psilocybin therapy for depression shows promise, but how it works is unclear. By comparing responders (those with >50% reduction in symptoms) to non-responders after 10mg and 25mg doses, whole-brain modeling identified specific brain regions whose dynamics shift from a depressive to a healthy state. These regions overlap with maps of serotonin 5-HT2A and 5-HT1A receptors, which psilocin—the active metabolite of psilocybin—activates. The findings provide causal evidence linking serotonergic transmission and recovery from depression via psilocybin.
bioRxiv (Cold Spring Harbor Laboratory)
July 25, 2018
Louis-David Lord, Paul Expert, Selen Atasoy et al.
10 citations
preprint
Brain activity can be viewed as exploring a landscape of different activity patterns over time, shifting between stable states of functional connectivity that support various mental processes. In a study using fMRI data from healthy participants given intravenous psilocybin (the active compound in magic mushrooms), researchers analyzed how this dynamical landscape changes during the psychedelic state. They found that a connectivity state linked to the fronto-parietal control system became strongly destabilized, while transitions toward a globally synchronized state increased. These changes suggest the psychedelic state biases the brain toward global integration at the cost of local network segregation, offering a mechanistic perspective on the subjective psychedelic experience and potential guidance for pharmacological interventions in neuropsychiatric disorders.
bioRxiv
August 21, 2023
Jakub Vohryzek, Joana Cabral, Christopher Timmermann et al.
7 citations
preprint
The brain's activity constantly reorganizes across space and time. A new framework called Harmonic Decomposition of Spacetime (HADES) was developed to track how spatial activity patterns (harmonic modes) change over time. As a proof-of-principle, HADES was applied to brain recordings from healthy participants under the psychedelic DMT and in a normal state. DMT significantly decreased contributions from most low-frequency harmonic modes. After normalizing by condition, a specific decrease appeared in the second functional harmonic, which represents the brain's hierarchy from unimodal to transmodal regions, supporting the hypothesis that psychedelics alter this functional hierarchy. Dynamic measures of fractional occupancy, lifetime, and latent space precisely described changes in the spacetime hierarchical organization of brain activity during the psychedelic state.
Front Hum Neurosci
January 6, 2025
Daniel Yochai Panitz, Avi Mendelsohn, Joana Cabral et al.
5 citations
Long-term mindfulness meditation practice shifts spontaneous brain activity toward states that synchronize sensory and perceptual cortical regions, while reducing time spent in frontal-lobe states linked to higher cognitive functions. Experienced meditators, compared to meditation-naïve participants, showed altered expression of resting-state networks during rest. These findings support a lasting effect of meditation on brain network dynamics and its therapeutic potential for disorders involving imbalanced network activity.