Psilocybin collapses visual change detection and drives cortical dynamics toward a state of surprise
Year: 2026
Type: preprint
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.
Authors: Roberto De Filippo, Ryan Gillis, David Wyrick, Mikayla Carlson, Severine Durand, R. Carter Peene, Ahad Bawany, Avalon Amaya, Hannah Belski, Conor Grasso, Warren Han, Jaimie Kenney, Carly Kiselycznyk, Henry Loeffler, Lydia C. Marks, Robyn Naidoo, Benjamin Ouellette, Lucas Suarez, Jackie Swapp, Tye Johnson, Julie Weber, Joshua Wilkes, Peter Groblewski, Allison Williford, Michael Buice, Christof Koch, Irene Rembado, Jérôme A. Lecoq, Torben Ott
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
OpenAlex ID: W7204201502