bioRxiv (Cold Spring Harbor Laboratory)
June 16, 2026
Paulina Clara Dagnino, Irene Acero-Pousa, Gorka Zamora‐lópez et al.
1 citation
Psilocybin and the conventional antidepressant escitalopram produce opposite changes in the brain's hierarchical non-equilibrium dynamics when treating major depressive disorder. Using resting-state fMRI before and after treatment, researchers built whole-brain models and measured how much each patient's brain activity deviated from the fluctuation-dissipation theorem. Baseline measures distinguished treatment responders from non-responders within each group. The deviation from the fluctuation-dissipation theorem may serve as a marker to differentiate the brain effects of psilocybin and escitalopram, contributing to understanding how these treatments work for depression.
Biological psychiatry global open science
March 1, 2026
Noam Goldway, Taly Markovits, Naomi Fine et al.
1 citation
Dissociation—feeling detached from one's body, environment, or self—often accompanies posttraumatic stress disorder (PTSD), but its neural basis is poorly understood. Using network control theory on resting-state functional MRI data, researchers examined brain dynamics during dissociative states in healthy volunteers given ketamine (n=30) and in PTSD patients (n=78) before and after treatment. Ketamine induced brain dynamics similar to those in untreated PTSD patients: increased dominance of the default mode network (DMN) meta-state and decreased dominance of the somatomotor network (SOM) meta-state. After treatment, reduced DMN meta-state dominance correlated with fewer dissociative symptoms. Treated patients also showed more organized, less entropic brain states, though ketamine did not significantly alter entropy indices. Dissociative states, whether drug-induced or clinical, involve increased DMN and reduced SOM dominance.
bioRxiv (Cold Spring Harbor Laboratory)
December 22, 2024
Jakub Vohryzek, Morten L. Kringelbach, Edmundo Lopez-Sola et al.
1 citation
preprint
Both psychedelic states and reduced states of consciousness flatten the brain's functional hierarchy, yet their behavioral and phenomenological profiles differ. To resolve this paradox, researchers defined hierarchy by the brain's proximity to thermodynamic equilibrium and examined changes induced by three serotonergic psychedelics: psilocybin, LSD, and DMT. All three consistently reduced the functional hierarchy globally. Unlike loss of consciousness, psychedelics moved the brain toward equilibrium while increasing neural activity complexity, indicating a distinct mechanism involving altered configuration and differentiation of resting-state networks. This work demonstrates how statistical mechanics metrics can characterize different global brain states, advancing understanding of consciousness as an emergent collective process.
bioRxiv Preprint Server
July 27, 2023
Paulina Clara Dagnino, Javier A. Galadí, Estela Càmara et al.
1 citation
preprint
Meditation produces distinct whole-brain dynamics compared to rest, particularly in the triple-network model (executive control, salience, and default-mode networks). Using a causal mechanistic framework, researchers defined probabilistic metastable substates from dynamic brain patterns and adjusted a whole-brain model of the resting state to simulate transitions to meditation. They successfully induced the meditative state through localized artificial perturbations, primarily shifting areas in the somatomotor and dorsal attention networks. The work suggests meditation can be studied as a practice for health and as a potential therapy for brain disorders.
bioRxiv Preprint Server
January 5, 2021
Beatrice M. Jobst, Selen Atasoy, Adrián Ponce-Alvarez et al.
1 citation
preprint
LSD alters brain dynamics by shifting the brain's global working point further from a stable equilibrium, as shown by consistently higher Perturbational Integration Latency Index (PILI) values after intake. Using a whole-brain computational model perturbed in silico, the largest differences were found in the limbic, visual, and default mode networks. Greater variability of PILI values across brain regions under LSD indicates higher response diversity to external perturbations. These findings provide insights into the brain-wide dynamical changes underlying the psychedelic state and suggest possible clinical applications for psychiatric disorders.
medRxiv
July 8, 2026
Paulina Clara Dagnino, Anne Maj van der Velden, Yonatan Sanz Perl et al.
In people with major depressive disorder, mindfulness-based cognitive therapy (MBCT) plus treatment as usual, compared to treatment as usual alone, alters whole-brain dynamics in ways that may reduce rumination. Using a novel method called complex harmonics decomposition on fMRI data from 80 patients, the study identified low-dimensional spatiotemporal manifolds that capture both local and long-range brain interactions. After MBCT, during rumination, brain regions involved in bodily and interoceptive processing became more consistently integrated across these manifolds. The latent configurations shifted with clinical and behavioral improvements, and the brain showed greater flexibility within the reduced space. These changes may reflect reduced 'stickiness' of ruminative thinking patterns following mindfulness training.
bioRxiv (Cold Spring Harbor Laboratory)
June 26, 2026
Paulina Clara Dagnino, Irene Acero-Pousa, Robin Carhart‐Harris et al.
A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after intervention with psilocybin and escitalopram. First, we built whole-brain models of pre- and post-treatment resting-state functional magnetic resonance imaging (fMRI) and obtained an initial generative effective connectivity (GEC) matrix for each individual.
medRxiv
June 23, 2026
Paulina Clara Dagnino, Anne Maj van der Velden, Henricus G. Ruhé et al.
In people with major depressive disorder, mindfulness-based cognitive therapy (MBCT) plus treatment as usual, compared to treatment as usual alone, increased the hierarchical organization of brain activity during rumination but not at rest. Greater hierarchy—meaning more directional information flow and less recurrent looping—was linked to improvements in clinical and behavioral outcomes. This shift away from self-reinforcing negative mental loops toward more differentiated cognitive and bodily cycles may help explain how MBCT interrupts ruminative thought patterns. Hierarchical brain dynamics could serve as a treatment-sensitive marker and potential mechanism of therapeutic change in MBCT for depression.
bioRxiv (Cold Spring Harbor Laboratory)
June 9, 2026
Morten L Kringelbach, Gustavo Deco
Brain dynamics can be described in three mathematical languages—connectome harmonics, turbulence, and complex harmonics (CHARM)—which are unified as a single self-adjoint operator and its spectral measure. The connectome Laplacian carries this measure; harmonics are its spectral projections, the turbulence smoothing kernel is its resolvent, and CHARM form is its unitary propagator. A shared control parameter, the spectral gap, yields cortical hierarchy, turbulent information cascade, and structured interference. Testing this with a pharmacological perturbation by LSD showed that one scalar coupling simultaneously predicts multi-scale turbulence shifts and macroscale harmonic energy redistribution, supporting the unified operator structure.
bioRxiv (Cold Spring Harbor Laboratory)
January 2, 2025
Marcel Socoró Garrigosa, Yonatan Sanz Perl, Morten L. Kringelbach et al.
preprint
Using whole-brain models guided by the Thermodynamics of Mind framework, the authors estimated the brain hierarchy of specific brain states and simulated transitions between states. Applying this to major depressive disorder, they built models of depressed patients before and after psilocybin and escitalopram treatments. Dynamic sensitivity analysis showed that susceptibility to change was on average reduced by escitalopram and increased by psilocybin, and both treatments promoted healthier transitions. These results align with the post-treatment plasticity window opened by serotonergic psychedelics and with the similar clinical efficacy of both drugs observed in clinical trials.
Neuroscience and biobehavioral reviews
July 1, 2022
Drummond E-Wen Mcculloch, Gitte Moos Knudsen, Frederick Streeter Barrett et al.
A large group of psychedelic imaging researchers reviewed 42 articles from 17 unique studies that used resting-state functional magnetic resonance imaging (rs-fMRI) to examine psychedelic effects. They found that nearly all studies varied in data processing and analysis methods, two datasets underpin over half of the published literature, and key outcome terms are used ambiguously. The authors recommend guidelines to improve consistency and replicability in future research, arguing that the field must balance novel methods with standardized approaches to reliably understand the neural mechanisms of psychedelics.
Noam Goldway, Taly Markovits, Naomi Fine et al.
preprint
Dissociation—feeling detached from one's body, surroundings, or self—is common in PTSD but its neural basis is poorly understood. Using network control theory, researchers examined brain dynamics during dissociative states in two contexts: ketamine-induced dissociation in 30 healthy volunteers and therapeutic interventions in 78 PTSD patients. Ketamine produced brain dynamics similar to those seen in PTSD patients before treatment, with increased dominance of a default mode network meta-state and decreased dominance of a somatomotor meta-state. Ketamine did not significantly alter the brain's energetic landscape, but transition energies increased after PTSD treatment, suggesting more organized, less entropic brain dynamics.
bioRxiv Preprint Server
December 9, 2025
Tomas Berjaga-Buisan, Juan Manuel Monti, Martina Cortada et al.
preprint
A non-invasive framework using generative whole-brain models of non-equilibrium dynamics reveals that violations of the Fluctuation-Dissipation Theorem (FDT) in spontaneous brain signals are reduced in unresponsive disorders of consciousness and anesthesia compared to conscious states, mirroring patterns seen with the Perturbational Complexity Index (PCI). This links PCI to fundamental physics principles and offers new objective, model-based tools for assessing consciousness loss and recovery.
bioRxiv Preprint Server
September 28, 2022
Yonatan Sanz Perl, Carla Pallavicini, Juan Piccinini et al.
preprint
Brain states are often described on a single scale from full consciousness to unconsciousness, but this ignores the complex, high-dimensional nature of brain activity. By combining whole-brain modeling, data augmentation, and deep learning, researchers mapped states of consciousness into a low-dimensional space where distances reflect similarities between states. They found an orderly trajectory from wakefulness to brain-injured patients, with coordinates related to functional modularity and structure-function coupling, both increasing as consciousness is lost. Model perturbations provided a geometric interpretation of state stability and reversibility. The work suggests conscious awareness depends on functional patterns encoded as a low-dimensional trajectory within the vast space of brain configurations.
bioRxiv Preprint Server
September 2, 2021
Laura De la Fuente, Federico Zamberlan, Hernán Bocaccio et al.
preprint
The laws of physics are time-symmetric, but dissipative systems like the brain show a preferred temporal direction. Using a deep learning framework inspired by stochastic thermodynamics, researchers analyzed electrocorticography signals from non-human primates. Brain activity during conscious wakefulness could be distinguished from its time-reversed version with high accuracy, using both frequency and phase information. This ability was reduced during deep sleep and ketamine-induced anesthesia. Transitions between slow (≈20 Hz) and fast frequencies (> 40 Hz) mainly contributed to the temporal asymmetry seen during wakefulness. The findings suggest that a preferred temporal direction in neural activity correlates with conscious awareness, linking brain processes to the subjective experience of time's passage.
arXiv Preprint Archive
December 19, 2020
Yonatan Sanz Perl, Hernan Bocaccio, Ignacio Perez-Ipina et al.
Consciousness depends on brain activity that is far from thermodynamic equilibrium. Analyzing electrocorticography data from non-human primates during sleep and various anesthetics, and fMRI data from humans during deep sleep and propofol anesthesia, all states of reduced consciousness showed dynamics closer to equilibrium than conscious wakefulness. This was measured by entropy production and the curl of probability flux in phase space. Non-equilibrium macroscopic brain dynamics therefore serve as a robust signature of consciousness, offering a statistical mechanics approach to studying cognition and awareness.
bioRxiv Preprint Server
July 2, 2020
Yonatan Sanz Perl, Carla Pallavicini, Ignacio Pérez Ipiña et al.
preprint
The level of consciousness—how conscious someone is—is often measured by how similar their brain activity is to normal wakefulness. However, this approach misses important information about how stable that state is. Using computer models of the whole brain, the authors show that the stability of a conscious state—how easily it can be disrupted—provides additional, complementary information. They propose a new framework that sorts brain states by both their similarity to wakefulness and their stability, which helps distinguish between different types of unconsciousness: natural sleep, anesthesia, and brain injury. This framework offers a more complete way to characterize and differentiate states of consciousness.
bioRxiv Preprint Server
June 4, 2020
Camilo Miguel Signorelli, Lynn Uhrig, Morten Kringelbach et al.
preprint
Anesthesia disrupts the brain's hierarchical organization, which may be a key mechanism behind loss of consciousness. By analyzing resting-state fMRI data from awake and anesthetized macaques, the authors found that anesthesia reduces the flexibility and richness of brain dynamics, making them more rigid and driven by brain structure. The depth of anesthesia and the specific anesthetic agent used both modulate these effects. Spatial and temporal aspects of cortical hierarchy are affected differently, involving distinct brain networks. The findings suggest that a breakdown in brain hierarchy is a new signature of unconsciousness.