Proceedings of the National Academy of Sciences of the United States of America
March 28, 2023
Christopher Timmermann, Leor Roseman, Sharad Haridas et al.
217 citations
Intravenous DMT, a potent psychedelic and serotonin 2A receptor agonist, profoundly alters brain function in healthy volunteers. In a placebo-controlled study with 20 participants, multimodal neuroimaging (EEG-fMRI) showed that DMT robustly increases global functional connectivity, disrupts and desegregates brain networks, and compresses the principal cortical gradient. These changes overlapped with brain regions rich in serotonin 2A receptors and associated with human-specific psychological functions. EEG and fMRI measures correlated, linking neurophysiological changes to network-level effects. The findings indicate DMT predominantly acts on the brain's transmodal association cortex, the evolutionarily recent area tied to advanced cognition and high 5-HT2A receptor density.
Neuropharmacology
December 27, 2022
Robin Carhart‐Harris, Shamil Chandaria, David Erritzøe et al.
106 citations
A theoretical model proposes that psychopathology arises from a defensive process called canalization, which narrows an individual's range of thoughts, feelings, and behaviors by increasing precision or reducing variance in neural responses. This contrasts with an early form of plasticity, TEMP (Temperature or Entropy Mediated Plasticity), which increases variance and learning rate. Canalization entrenches pathology as the agent develops expertise in their disorder, while TEMP, combined with gentle psychological support, may counter this entrenchment. The model distinguishes adaptive from maladaptive canalization and suggests concrete experiments to test its hypotheses.
Frontiers in Psychiatry
April 5, 2023
Sharday Mosurinjohn, Leor Roseman, Manesh Girn
54 citations
Research on psychedelics often measures 'mystical' effects using psychometric tools, and clinical studies link such experiences to better mental health. However, this research rarely engages with scholarship from religious studies or anthropology, which reveal that the concept of 'mysticism' in psychedelic science carries unacknowledged biases—particularly a perennialist and Christian bias that fails to historicize the term. The authors trace the concept's history in psychedelic research, propose more culturally sensitive operationalizations, and advocate for complementary 'non-mystical' approaches to study these phenomena, aiming to build interdisciplinary bridges for stronger theoretical and empirical work.
bioRxiv (Cold Spring Harbor Laboratory)
May 3, 2020
Manesh Girn, Leor Roseman, Boris C. Bernhardt et al.
27 citations
preprint
LSD and psilocybin flatten the brain's hierarchical organization, reducing the functional separation between sensory and higher-order cognitive networks. Using a non-linear dimensionality reduction technique on resting-state fMRI data, the authors found that both drugs compressed the principal gradient of cortical connectivity, which normally spans from unimodal (sensory) to transmodal (association) cortex. This flattening was driven by decreased differentiation at both ends of the hierarchy—default and frontoparietal networks at the upper end and somatomotor networks at the lower end—and was accompanied by increased crosstalk between unimodal and transmodal regions. Changes in the principal gradient under LSD tracked self-reported ego-dissolution. The findings support a mechanistic model of the psychedelic state and demonstrate that macroscale connectivity gradients are sensitive to serotonergic modulation.
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.
NeuroImage
June 10, 2026
Fran Hancock, Rachael Kee, Fernando Rosas et al.
Flow—a state of effortless immersion often experienced during video games—shows a moderate inverse relationship with global brain entropy, meaning the brain is less disordered during flow than during boredom or frustration. Synchronization and metastability do not explain flow. Boredom and frustration each display distinct patterns of brain dynamics. These findings integrate earlier observations about prefrontal activity and network synchrony into a single dynamical-systems framework, identifying complexity-based markers that could help map the neural basis of media-related benefits.
bioRxiv Preprint Server
July 11, 2025
Fran Hancock, Rachael Kee, Fernando Rosas et al.
preprint
Flow—the experience of effortless immersion—shows an inverse relationship with global brain entropy during a video game task, meaning less disorderly brain activity corresponds with more flow. Boredom and frustration each display distinct patterns of brain dynamics. These findings bring together earlier observations about prefrontal activity and network synchrony into a single framework and suggest complexity-based measures could help map the neural basis of media-related benefits.
October 14, 2024
Terence J. Lyons, Merle Spriggs, Leevi Kerkelä et al.
preprint
A single high dose of psilocybin (25 mg) produced lasting functional and anatomical brain changes in healthy, psychedelic-naive adults, detected from one hour to one month later. Diffusion imaging showed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity, which in turn correlated with improved well-being. Increased cortical signal entropy shortly after dosing predicted better psychological well-being at one month, with next-day psychological insight mediating this relationship. No such effects occurred with a 1 mg placebo dose. Cognitive flexibility, psychological insight, and well-being also increased at one month.
arXiv Preprint Archive
May 23, 2016
Kieran C. R. Fox, Manesh Girn, Cameron C. Parro et al.
Psychedelic substances produce radical psychological effects and have been surrounded by political and legal controversy since their widespread adoption about 50 years ago. This review examines functional neuroimaging studies that investigate the neural correlates of the psychedelic experience, highlighting connections with the psychological and neural bases of creativity, daydreaming, and dreaming. The authors synthesize findings from these imaging investigations to show how brain activity during psychedelic states overlaps with patterns seen during imaginative and creative thought processes.
arXiv Preprint Archive
March 21, 2016
Kieran C. R. Fox, Matthew L. Dixon, Savannah Nijeboer et al.
Meditation comprises diverse mental practices with distinct strategies. A meta-analysis of 78 neuroimaging studies (527 participants) found reliably different brain activation patterns for four common meditation styles—focused attention, mantra recitation, open monitoring, and compassion/loving-kindness—and suggestive differences for three others. Some brain regions (insula, pre/supplementary motor cortices, dorsal anterior cingulate cortex, frontopolar cortex) were recruited across multiple techniques, but convergence was the exception. Effect sizes were medium for both activations (d = .59) and deactivations (d = -.74), indicating potential practical significance. The findings support the neurophysiological dissociability of meditation practices while highlighting methodological concerns and future research directions.