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.
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.
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.
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.
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.
Entropy
January 22, 2024
Giulio Ruffini, Edmundo Lopez-Sola, Jakub Vohryzek et al.
15 citations
A framework called neural geometrodynamics, inspired by general relativity, describes how neural dynamics unfold at three timescales: fast (momentary activity), slow (synaptic plasticity), and ultraslow (metaplasticity). Psychedelics flatten the neural landscape, increasing entropy and complexity of fast dynamics, which disrupts functional integration. This destabilization counteracts pathological, rigid neural patterns by promoting fluid, adaptable states. The plasticity-enhancing effects of psychedelics amplify this shift, leading to acute systemic disorder and potentially longer-lasting increases in complexity that affect both short-term dynamics and long-term plastic processes, offering a holistic view of psychedelics' acute and lasting impacts.
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.
Entropy
November 6, 2024
Giulio Ruffini, Francesca Castaldo, Edmundo Lopez-Sola et al.
10 citations
Major Depressive Disorder (MDD) is a complex condition that computational neuropsychiatry can help model mechanistically. Using the Kolmogorov theory of consciousness, a model was developed in which algorithmic agents interact with the world to maximize an Objective Function evaluating affective valence. Depression—defined as persistently low valence—may arise from inaccurate world models (cognitive biases), a dysfunctional Objective Function (anhedonia, anxiety), deficient planning (executive deficits), or unfavorable environments. The model maps to brain circuits and functional networks, linking with depression biotypes. Brain stimulation, psychotherapy, and psychedelics may synergistically repair neural circuits, with therapies optimized using personalized computational models.
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)
March 19, 2025
Giulio Ruffini, Edmundo Lopez-Sola, Raul P. Aristides et al.
8 citations
preprint
Cross-frequency coupling (CFC), where brain rhythms at different speeds interact, may be the mechanism the brain uses to compare sensory input with internal predictions. Using a laminar neural mass model, the authors show that two forms of CFC—signal-envelope coupling and envelope-envelope coupling—can implement hierarchical prediction-error computation and precision-weighting. In Alzheimer's disease, disruptions in fast-spiking interneurons lead to aberrant prediction errors: inflated early on, then attenuated. Serotonergic psychedelics reduce the influence of predictions, increasing prediction-error signals. These findings suggest that CFC across multiple timescales is a key computational mechanism supporting predictive coding, with disruptions central to certain disorders.
bioRxiv (Cold Spring Harbor Laboratory)
May 31, 2024
Jakub Vohryzek, Selen Atasoy, Gustavo Deco et al.
8 citations
preprint
Psychedelic substances like DMT, psilocybin, LSD, and ketamine alter brain function by reshaping the repertoire of connectome harmonics—patterns of neural activity that depend on the brain's structural network of white matter pathways. Under DMT, the entropy of these harmonics increases, indicating a more diverse range of brain states. For the first time, changes in the energy spectrum and entropy of connectome harmonics were shown to track the intensity of subjective experience in real time, suggesting a close link between the brain's harmonic activity and conscious experience.
bioRxiv (Cold Spring Harbor Laboratory)
December 16, 2024
Jan C. Gendra, Edmundo Lopez-Sola, Francesca Castaldo et al.
7 citations
preprint
Classical serotonergic psychedelics may help treat neurodegenerative disorders like Alzheimer's disease by altering pathological brain dynamics. Using multimodal neuroimaging data from thirty subjects with mild to moderate Alzheimer's disease, a personalized whole-brain model based on a laminar neural mass framework simulated the effects of serotonin 2A receptor activation. Modulating the excitability of layer 5 pyramidal neurons reproduced hallmark EEG changes seen under psychedelics, including alpha power suppression and gamma power enhancement. These spectral shifts correlated strongly with regional serotonin 2A receptor distribution. Simulated EEG also showed increased complexity and entropy, suggesting restored network function, offering mechanistic insights into potential therapeutic effects in early Alzheimer's disease.
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.
Entropy (Basel, Switzerland)
January 19, 2025
Giulio Ruffini, Francesca Castaldo, Jakub Vohryzek
6 citations
Tracking natural data forces an agent to mirror the symmetry properties of the generative world model, enforcing a hierarchical organization in the agent's neural network consistent with the manifold hypothesis. Using Lie pseudogroups to formalize invariance in natural data and drawing parallels to Noether's theorem, the study shows that data tracking constrains both the agent's constitutive parameters and dynamical repertoire. This bridges algorithmic information theory, symmetry, and dynamics, offering insights into neural correlates of agenthood and structured experience, as well as AI and brain model design.
bioRxiv (Cold Spring Harbor Laboratory)
November 7, 2024
Lorenzo Pasquini, Jakub Vohryzek, Anira Escrichs et al.
4 citations
preprint
Psilocybin induces fast and sustained improvements in mental well-being, yet its long-term mechanisms are not fully understood. Four weeks after a full dose, fronto-striatal-thalamic (FST) circuitry—involved in goal-directed behavior and motivation—shows increased dynamic activity and flexibility in healthy volunteers. Computational modeling indicates that reduced structural constraints on functional dynamics cause this increased flexibility. Long-term changes include increased bottom-up and reduced top-down information flow, mediated by serotonergic (5-HT2A) and dopaminergic (D2) receptor systems. This functional re-organization of FST circuits may represent a common mechanism underlying clinical improvements across neuropsychiatric disorders such as substance abuse, major depression, and anorexia.
Annals of the New York Academy of Sciences
July 21, 2025
Marcel Socoró-garrigosa, Yonatan Sanz Perl, Morten L Kringelbach et al.
3 citations
The scale at which the brain represents information remains a key question in neuroscience. Evidence shows that information is encoded not just in localized areas but across distributed, hierarchical networks. The hierarchy of causal influences shaping brain activity patterns is a signature of different brain states, relevant to neuropsychiatric disorders. Using whole-brain models guided by the thermodynamics of mind framework, researchers estimated brain hierarchy and studied in-silico transitions in static functional connectivity. Applying this to major depressive disorder, they built resting-state whole-brain models of depressed patients before and after treatment with psilocybin or escitalopram.
British journal of anaesthesia
April 1, 2025
Milan Van Maldegem, Jakub Vohryzek, Selen Atasoy et al.
3 citations
Ketamine, at anesthetic doses, produces a state where people are unresponsive yet often report vivid inner experiences, separating conscious awareness from behavioral responsiveness. Using connectome harmonic decomposition on fMRI data, researchers found that brain signals during ketamine-induced unresponsiveness show increased fine-grained spatial patterns, indicating higher neural granularity. This harmonic signature aligned with those of LSD-induced and ketamine-induced psychedelic states, but misaligned with signatures from unconscious individuals due to propofol sedation or brain injury. The method can track changes in conscious awareness even when behavior is absent, offering a tool for consciousness and anesthesia research.
August 30, 2022
Giulio Ruffini, Edmundo Lopez-Sola, Jakub Vohryzek
3 citations
preprint
The unfolding argument challenges causal structure theories of consciousness by requiring that a theory specify which physical systems are conscious and which are not. This paper examines how the algorithmic information theory of consciousness (KT), which links subjective experience to the structure of a computational system, is affected by this argument. Considering computational hierarchies and limited physical resources, the authors introduce novel considerations that may extend the unfolding argument, suggesting that the argument's requirements may be more complex when applied to theories that rely on algorithmic information and computational structure.
Neuropsychopharmacology
September 12, 2025
Jakub Vohryzek, Andrea I. Luppi, Selen Atasoy et al.
2 citations
The brain's function depends on its structural wiring, and psychedelics alter this relationship. Using connectome harmonic decomposition, a method linking brain activity to the network of white matter pathways, the authors show that under N,N-dimethyltryptamine (DMT), the brain's harmonic repertoire shifts similarly to that seen with psilocybin, LSD, and ketamine. Repertoire entropy—a measure of the diversity of brain states—increases under DMT. For the first time, the energy spectrum difference and repertoire entropy of connectome harmonics track the intensity of subjective experience in real time, indicating a close coupling between brain network dynamics and conscious experience.
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.
Philosophy and the Mind Sciences
May 27, 2026
Edmundo Lopez-Sola, Roser Sanchez-Todo, Jakub Vohryzek et al.
1 citation
A computational framework rooted in algorithmic information theory, the algorithmic agent model, is used to investigate the phenomenon of pure awareness central to contemplative traditions. The framework proposes that agents build compressive models of the world, and structured experience arises from running such models. Pure awareness may correspond to experiences with minimal structure achieved through meditation, psychedelics, or other deconstructive practices, such as jhāna meditation. A key hypothesis is that the phenomenology of pure awareness arises from the agent's model of its own modeling process, and this recognition can occur alongside other phenomenal content, as in non-dual awareness. These ideas can be explored through whole-brain computational models based on predictive processing, grounded in meditation and psychedelic research.
bioRxiv (Cold Spring Harbor Laboratory)
October 3, 2025
Marian Martínez-Marín, Jakub Vohryzek, Anira Escrichs et al.
1 citation
preprint
Consciousness levels after coma can be assessed by measuring how far the brain's dynamics are from equilibrium. Using fMRI data and individualized whole-brain models, researchers found that patients with disorders of consciousness—those in a minimally conscious state or unresponsive wakefulness syndrome—show brain activity closer to equilibrium than healthy controls, with the shift increasing as consciousness decreases. Disruptions in hierarchical drive were identified in default-mode network regions and subcortical hubs like the thalamus. Recovery of near-control hierarchy in the visual network distinguished minimally conscious from unresponsive patients, while limbic areas showed similar abnormalities in both groups. Deviation from the fluctuation-dissipation theorem offers a model-based biomarker for clinical stratification.
medRxiv
February 7, 2025
Jakub Vohryzek, Anne Maj van der Velden, Willem Kuyken et al.
1 citation
preprint
Mindfulness-based cognitive therapy (MBCT) alters brain network dynamics during depressive rumination in people with recurrent depression. In a randomized trial, 27 patients received MBCT plus treatment as usual, while 21 received treatment as usual alone. Using fMRI, researchers analyzed brain substates during an induced rumination state before and after treatment. MBCT changed the probability of a specific 'Salience-somatomotor' brain substate occurring during rumination, compared to the control group. These dynamic network changes were linked to reduced depressive symptoms after treatment and at three months follow-up, suggesting a candidate brain mechanism for how mindfulness training improves clinical outcomes.