Brain
October 22, 2021
Manoj K Doss, Maxwell B Madden, Andrew Gaddis et al.
196 citations
Classic psychedelic drugs like psilocybin and LSD may help treat psychiatric disorders by altering brain circuits. Two existing models—the cortico-striatal thalamo-cortical (CSTC) model and the relaxed beliefs under psychedelics (REBUS) model—highlight different subcortical structures in mediating these effects. This paper introduces a third circuit-level model, the cortico-claustro-cortical (CCC) model, focusing on the claustrum, a thin strip of grey matter that densely expresses serotonin 2A receptors. The CCC model proposes that the claustrum entrains canonical cortical network states, and psychedelic drugs disrupt 5-HT2A-mediated coupling between claustrum and cortex, attenuating these networks. Together, the three models may explain many phenomena of the psychedelic experience.
NeuroImage
October 15, 2022
Andrew Gaddis, Daniel E Lidstone, Mary Beth Nebel et al.
38 citations
Psilocybin alters the functional organization of distinct thalamic subregions and their connections to cortical networks, particularly the mediodorsal and pulvinar nuclei. Using a novel ICA-based approach in 18 healthy meditators, psilocybin-induced changes in intrathalamic spatial organization correlated with subjective drug effects. Thalamocortical connectivity predominantly decreased with visual and default mode networks. In contrast, treating the thalamus as a single unit showed a non-significant numerical increase in connectivity, suggesting that whole-thalamus analyses may mask focal decreases in specific nuclei that express serotonin 2A receptors.
bioRxiv (Cold Spring Harbor Laboratory)
March 2, 2022
Andrew Gaddis, Daniel E. Lidstone, Mary Beth Nebel et al.
2 citations
preprint
Psilocybin, a classic psychedelic, alters perception and cognition by affecting connectivity between the thalamus and cortex. Using a novel analysis of resting-state fMRI data, this study found that psilocybin changes the functional organization within specific thalamic nuclei—primarily the mediodorsal and pulvinar nuclei—and alters their connections with visual and default mode networks. These changes correlated with subjective drug effects. When the thalamus was treated as a single unit, a numerical but not statistically significant increase in thalamocortical connectivity was observed, suggesting that psilocybin causes widespread modest increases offset by strong focal decreases in relevant nuclei.