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.
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.
Hum Brain Mapp
July 1, 2026
Lorenzo Pasquini, Jakub Vohryzek, Anira Escrichs et al.
A computational model predicts that a single dose of psilocybin can produce lasting changes in the dynamic activity and effective connectivity of fronto-striatal-thalamic brain circuits. The modeling suggests that psilocybin may strengthen connectivity between the prefrontal cortex and striatum while altering thalamic gating, effects that persist beyond the acute drug experience. These changes could underlie the sustained therapeutic benefits observed in clinical settings, such as reduced depressive symptoms and increased psychological flexibility. The findings provide a mechanistic framework for understanding how psilocybin induces long-term neural plasticity and highlight potential circuit targets for treating psychiatric disorders.
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.
arXiv (Cornell University)
May 15, 2026
Jonas Mago, Edmundo Lopez-Sola, Jakub Vohryzek et al.
States of consciousness with minimal phenomenal content, such as those induced by certain meditation practices, show increased brain entropy similar to high-content psychedelic states, challenging the Entropic Brain Hypothesis that links entropy to phenomenal richness. The Complex Brain Hypothesis resolves this by proposing that brain complexity, not entropy, better indexes the richness of experience. Complexity is modulated by the grain of inference the brain uses to resolve uncertainty: fine-grained inference loosens constraints and proliferates content, as in psychedelic states; coarse-grained inference simplifies experience into contentless awareness, as in minimal phenomenal experiences. Both regimes can elevate entropy but differ in phenomenology and perturbational signatures, refining the Entropic Brain Hypothesis and highlighting minimal phenomenal experiences as a test case for computational theories of consciousness.
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.
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
June 7, 2026
Andrea I. Luppi, Dragana Manasova, Justine Y. Hansen et al.
preprint
Functional connectivity in the awake human brain is shaped primarily by cognitive co-activation—the tendency of brain regions to work together during mental tasks—more than by structural or molecular constraints. This predominance is systematically lost across five datasets involving pharmacological and pathological perturbations of consciousness (chronic disorders of consciousness; anesthesia with sevoflurane, propofol, or ketamine), when cognition is disconnected from the environment or abolished. During such states, the predictors of functional architecture shift away from cognitive co-activation and toward anatomical and molecular constraints.