BibTex format
@article{Pasquini:2026:10.1002/hbm.70596,
author = {Pasquini, L and Vohryzek, J and Escrichs, A and Perl, YS and Ponce-Alvarez, A and Idesis, S and Girn, M and Roseman, L and Mitchell, JM and Gazzaley, A and Kringelbach, M and Nutt, DJ and Lyons, T and Carhart-Harris, RL and Deco, G},
doi = {10.1002/hbm.70596},
journal = {Hum Brain Mapp},
title = {Modeled Long-Term Effects of Psilocybin on Dynamic Activity and Effective Connectivity of Fronto-Striatal-Thalamic Circuits.},
url = {http://dx.doi.org/10.1002/hbm.70596},
volume = {47},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - 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.
AU - Pasquini,L
AU - Vohryzek,J
AU - Escrichs,A
AU - Perl,YS
AU - Ponce-Alvarez,A
AU - Idesis,S
AU - Girn,M
AU - Roseman,L
AU - Mitchell,JM
AU - Gazzaley,A
AU - Kringelbach,M
AU - Nutt,DJ
AU - Lyons,T
AU - Carhart-Harris,RL
AU - Deco,G
DO - 10.1002/hbm.70596
PY - 2026///
TI - Modeled Long-Term Effects of Psilocybin on Dynamic Activity and Effective Connectivity of Fronto-Striatal-Thalamic Circuits.
T2 - Hum Brain Mapp
UR - http://dx.doi.org/10.1002/hbm.70596
UR - https://www.ncbi.nlm.nih.gov/pubmed/42381187
VL - 47
ER -
