Psilocybin collapses visual change detection and drives cortical dynamics toward a state of surprise
Roberto De Filippo, Ryan Gillis, David G Wyrick, Mikayla Carlson, Séverine Durand, Carter R. Peene, Ahad Bawany, Avalon Amaya, Hannah Belski, Conor Grasso, Warren Han, Jaimie Kenney, Carly Kiselycznyk, Henry Loeffler, Lydia C. Marks, R. Naidoo, Ben Ouellette, Lucas Suarez, Jackie Swapp, Tye Johnson, Julie Weber, Joshua Wilkes, Peter A. Groblewski, Allison Williford, Michael A. Buice, Christof Koch, Irene Rembado, Jérôme Lecoq, Torben Ott
bioRxiv (Cold Spring Harbor Laboratory) August 25, 2026 preprint DOI: 10.64898/2026.08.21.745777 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study (with optogenetics and Neuropixels recordings in mice) |
|---|---|
| Population | Head-fixed mice performing a visual change-detection task |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Key findings | Psilocybin impaired task performance and imposed a 4-Hz oscillation on visually evoked activity, preferentially affecting change-encoding neurons. Expected image repetitions under psilocybin recruited change-encoding ensembles, shifting cortical dynamics toward genuine change trajectories, with strongest effects in somatostatin-expressing interneurons. |
Abstract
Abstract Psilocybin profoundly alters visual perception, yet the neuronal mechanisms underlying these effects remain unclear. Here we combined large-scale Neuropixels recordings with cell-type-specific optogenetics in head-fixed mice performing a visual change-detection task. Psilocybin severely impaired task performance without overt motor deficits. In cortex, the drug modestly suppressed activity of layer 5 neurons while preserving representations of image identity. By contrast, psilocybin imposed a 4-Hz oscillation on visually evoked activity that preferentially affected neurons encoding image change rather than image identity. Under psilocybin, expected image repetitions aberrantly recruited change-encoding ensembles and shifted cortical population dynamics towards trajectories normally evoked by genuine stimulus changes. These effects were strongest in somatostatin-expressing (SST) interneurons in visual cortex. The strength of this modulation depended on image structure and was greatest for images with clear, continuous contours, which preferentially recruited change-encoding ensembles. These findings demonstrate that psilocybin drives internally generated cortical surprise signals, providing a circuit mechanism for altered perception in the acute psychedelic state.