Modeled Long-Term Effects of Psilocybin on Dynamic Activity and Effective Connectivity of Fronto-Striatal-Thalamic Circuits.

Overview

1. Department of Neurology, University of California, San Francisco, California, San Francisco, USA
2. Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona, Spain
3. Centre for Eudaimonia and Human Flourishing, Linacre College, University of Oxford, Oxford, UK
4. Department of Mathematics, Polytechnic University of Catalonia, Barcelona, Spain
5. Centre for Psychedelic Research, Imperial College London, London, UK
6. Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, California, USA
7. Department of Psychiatry, University of Oxford, Oxford, UK
8. Institució Catalana de la Recerca i Estudis Avançats (ICREA), Barcelona, Spain

Abstract

Psilocybin has been shown to induce fast and sustained symptoms improvements across various psychiatric conditions, yet its long‐term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto‐striatal‐thalamic (FST) circuitry, a broad system involved in goal‐directed behavior and motivational states. Here, we performed secondary analyses and applied computational modeling to resting‐state fMRI data from a within‐subject longitudinal psilocybin trial in psychedelic‐naïve healthy volunteers. We first showed that dynamic FST activity increased 4 weeks after a full dose of psilocybin. We then proceeded to mechanistically account for these changes by providing tentative model‐based support that reductions in the structure–function coupling contribute to increased dynamic FST activity postpsilocybin. Finally, we used computational approaches to show that psilocybin induces longitudinal increases in bottom‐up and reduced top‐down modulation of FST circuits. We then used publicly available receptor maps to show that cortical reductions in top‐down modulation are linked to regional 5‐HT2A receptor availability, while increased information outflow via subcortical and limbic regions relates to local D2 receptor availability. Together, these findings suggest that increased FST flexibility weeks after a high dose of psilocybin is linked to serotonergic‐mediated decreases in top‐down information flow and dopaminergic‐mediated increases in bottom‐up information flow. This long‐term functional re‐organization of FST circuits may represent a common mechanism contributing to the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia nervosa.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

• 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
• 0 scripts, each with its path and the digest of its content;
• no match between paragraphs and code yet;
• neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data Availability Statement

Data is available from R.L.C.‐H. or L.R. after reasonable request. Scripts used to generate the data are publicly available on GitHub (https://github.com/lollopasquini).

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 6 keywords, 16 MeSH terms, 3 funders, 56 references.

Cite

This paper

Pasquini, L., Vohryzek, J., Escrichs, A., Perl, Y. S., Ponce‐Alvarez, A., Idesis, S., Girn, M., Roseman, L., Mitchell, J. M., Gazzaley, A., Kringelbach, M., Nutt, D. J., Lyons, T., Carhart‐Harris, R. L., & Deco, G. (2026). Modeled Long-Term Effects of Psilocybin on Dynamic Activity and Effective Connectivity of Fronto-Striatal-Thalamic Circuits. Human brain mapping, 47(10), e70596. https://doi.org/10.1002/hbm.70596

The tracing map gets a citation of its own once an author has validated it and it has a DOI.

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s41591-026-04287-9 [code]

An international mega-analysis of psychedelic drug effects on brain circuit function.

Journal: Nature medicine

In common: systems, 10 references, author David J Nutt

[2] doi:10.1038/s41586-026-10910-z [code]

Psychedelics align brain activity with context.

Journal: Nature

In common: 8 references, author Gustavo Deco

[3] doi:10.1038/s41467-026-74215-5 [code]

Multi-metric evaluations of acute psychedelic effects on fMRI brain entropy.

Journal: Nature communications

In common: 11 references

[4] doi:10.64898/2026.06.21.26356048

Changes in hierarchical brain dynamics of rumination following mindfulness-based cognitive therapy for depression

Journal: medRxiv (preprint)

In common: 3 references, 2 authors

[5] doi:10.64898/2026.06.08.26355206

A canary in the mind: A single baseline brain scan predicts adolescent depression and anxiety one year later

Journal: medRxiv (preprint)

In common: 3 references, 2 authors

[6] doi:10.1038/s41467-026-75890-0

Serotonergic psychedelics induce distinct patterns of metabolic activity and covariance within biologically informed rat brain networks.

Journal: Nature communications

In common: 8 references

[7] doi:10.64898/2026.06.26.26356643

Complex harmonic manifolds in mindfulness-based cognitive therapy for major depressive disorder

Journal: medRxiv (preprint)

In common: 1 reference, 2 authors

[8] doi:10.3389/fnhum.2026.1874178

Longitudinal neural and psychological changes following psilocybin under compassion imagery priming.

Journal: Frontiers in human neuroscience

In common: 7 references

[9] doi:10.1016/j.xcrm.2026.102867

Psilocybin restores behavior and 5-HT<sub>2A</sub> signaling while reducing microglial density after chronic traumatic brain injury in rats.

Journal: Cell reports. Medicine

In common: 6 references

[10] doi:10.1371/journal.pcbi.1013463 [code]

A multi-frequency whole-brain neural mass model with homeostatic feedback inhibition.

Journal: PLoS computational biology

In common: 6 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.