The psychedelic DOI decreases the modularity of the cortical network by increasing cortico-cortical and thalamo-cortical functional influence
Roman Doronin, Eduard Stroukov, Georg B. Keller
bioRxiv (Cold Spring Harbor Laboratory) July 24, 2026 preprint DOI: 10.64898/2026.07.20.739656 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Awake mice |
| Intervention | DOI |
| Key findings | DOI acutely decreased cortical network modularity by increasing correlations between anterolateral and posteromedial cortical domains, dependent on 5-HT2A receptors, and increased thalamo-cortical and long-range cortico-cortical functional influence onto the anterolateral domain. |
Abstract
SUMMARY Psychedelics are powerful modulators of conscious perception, hypothesized to exert their effects by reorganizing large-scale brain functional connectivity. The circuit mechanisms underlying this reorganization remain unknown. Here, using widefield calcium imaging in awake mice, we found that the psychedelic DOI, in a 5-HT2A-dependent manner, acutely decreased the modularity of the cortical network by increasing correlations between anterolateral (AL) and posteromedial (PM) cortical domains. Functional influence measurements revealed that DOI increased both thalamo-cortical and long-range cortico-cortical influence onto the AL domain. We speculate that these increases in functional influence are driving the DOI-induced increase in the coupling between cortical domains. Our results provide a mouse correlate of the network reorganization seen under psychedelics in human neuroimaging and identify thalamo-cortical and cortico-cortical changes as candidate circuit mechanisms for this reorganization.