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.
Imaging Neurosci (Camb)
January 3, 2025
Kenneth Shinozuka, Prejaas K.b. Tewarie, Andrea Luppi et al.
9 citations
LSD weakens the brain's usual hierarchy of information flow by making neural communication more balanced between sending and receiving signals. Using magnetoencephalography (MEG) data from 16 healthy adults given 75 micrograms of LSD intravenously, researchers measured directed functional connectivity under four conditions (eyes-closed with or without music, eyes-open with or without video). Across the whole brain, LSD reduced the asymmetry of directed connectivity over time. Machine learning classifiers distinguished LSD from placebo more accurately using hierarchy metrics than traditional connectivity measures. These results indicate that LSD flattens the brain's hierarchical information processing by increasing the balance between senders and receivers of neural signals.
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)
April 28, 2024
Kenneth Shinozuka, Prejaas Tewarie, Andrea I. Luppi et al.
5 citations
preprint
LSD weakens the brain's directed connectivity hierarchy by increasing the balance between senders and receivers of neural signals. This finding supports the REBUS theory, which proposes that psychedelics flatten the hierarchy of information flow in the brain. Analyzing magnetoencephalography data from 16 healthy participants given 75 micrograms of intravenous LSD, the study found that LSD diminishes the asymmetry of directed connectivity averaged over time. Machine learning classifiers distinguished LSD from placebo more accurately when trained on hierarchy metrics than on traditional functional connectivity measures.
bioRxiv
August 29, 2022
Giulio Ruffini, Giada Damiani, Diego Lozano-Soldevilla et al.
5 citations
preprint
Using fMRI data from fifteen people who took LSD or a placebo, researchers modeled brain dynamics with an Ising spin model to test whether psychedelics push the brain into a more disordered state. LSD increased the Ising temperature of brain activity, moving it further away from a critical point (the edge between order and disorder) into a more disordered, paramagnetic phase. This shift was accompanied by a decrease in interhemispheric connectivity, especially between corresponding regions in the two hemispheres. Algorithmic complexity of brain signals also increased with LSD. The findings suggest LSD loosens homotopic connections, driving the brain into a more flexible, complex state, consistent with theories that psychedelics increase neural entropy.
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.
bioRxiv
March 24, 2025
Kenneth Shinozuka, Mattia Rosso, Clayton R. Coleman et al.
3 citations
preprint
LSD profoundly alters consciousness by reorganizing brain networks in specific frequency bands. Analyzing MEG data from 14 healthy participants, the substance enhances high alpha (12.1, 13.3 Hz) activity across all conditions and high beta (25.3 Hz) in three conditions, while suppressing low beta (18.1, 19.3 Hz) and low alpha (8.5 Hz). LSD also shifts network spatial distributions: low alpha moves anteriorly toward the motor cortex, high alpha becomes more localized to the visual cortex, and low beta expands over temporal and occipital cortices. These frequency- and region-specific changes add nuance to theories of network disintegration under psychedelics.
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.
bioRxiv (Cold Spring Harbor Laboratory)
October 7, 2023
Kenneth Shinozuka, Katarina Jerotic, Pedro A. M. Mediano et al.
2 citations
preprint
Serotonergic psychedelics such as LSD, psilocybin, and DMT alter consciousness and show therapeutic potential for depression and addiction, but their mechanisms remain unclear. A systematic review and meta-analysis across three levels—phenomenology, neuroimaging, and pharmacology—reveals that medium and high doses of LSD produce significantly stronger visionary restructuring than psilocybin. Neuroimaging shows psychedelics generally strengthen connectivity between brain networks while weakening connectivity within networks. Pharmacologically, LSD triggers more inositol phosphate formation at the 5-HT2A receptor than DMT or psilocin, but no significant differences emerged in receptor selectivity among the drugs. The findings highlight high heterogeneity and risk of bias, underscoring the need for standardized methods.
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.
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.
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
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.
Biological Psychiatry Global Open Science
May 14, 2026
Anne Maj van der Velden, Jakub Vohryzek, Paulina Clara Dagnino et al.
Mindfulness-based cognitive therapy (MBCT) alters brain network dynamics during depressive rumination in people with recurrent depression. In a randomized controlled trial with 48 participants, those who received MBCT plus treatment as usual showed changes in the occurrence frequency of a 'salience-somatomotor' brain state during rumination compared to those receiving treatment as usual alone. These neural changes were linked to reduced rumination after treatment and fewer depressive symptoms three months later. The findings suggest that MBCT may work by modifying how the brain's somatosensory and salience networks interact during rumination, offering clues about the brain mechanisms underlying treatment response.
Transl Psychiatry
November 13, 2025
Kenneth Shinozuka, Katarina Jerotic, Pedro Mediano et al.
correction
This correction notice addresses errors in a previously published article that presented three systematic reviews and meta-analyses examining the pharmacology, neuroimaging, and phenomenology of psychedelics. The correction does not provide new findings or data but serves to amend the original publication.
bioRxiv
September 25, 2025
Jakub Vohryzek, Edmundo Lopez-Sola, Winson F.z. Yang et al.
preprint
Advanced concentrative absorption meditation (jhāna) produces a shift in brain dynamics toward near-criticality, a state of heightened flexibility and integration. Using 7T fMRI and whole-brain modeling, the study found that later absorption states, considered minimal phenomenal experiences, show increased large-scale functional integration and a shift of the default mode network from a noise-driven regime to near-critical dynamics. This near-critical regime is interpreted as a form of openness, where constrained brain activity gives way to greater flexibility, correlating with broader attention and reduced narrative thought. The trajectory of these states is non-linear, with major reconfigurations at key meditative milestones.
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.
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.