Neural mechanisms of imagery under psilocybin

This pre-print follow-up analysis (n=24) of an RCT with psilocybin (up to 22mg/70kg) finds that self-inhibition of visual areas of the brain (EVA, FG) leads to complex imagery, as seen by participants. The results align with the REBUS model and highlight (again) how the bottoms-up processes of the brain are amplified under the influence of psychedelics.


“Visual alterations under classic psychedelics can include rich phenomenological accounts of eyes-closed imagery. Bottom-up connectivity of the visual pathway underpins sensory perception, with top-down connectivity enhanced during intentional imagery. Preclinical evidence suggests agonism of the 5-HT2A receptor may reduce synaptic gain to produce psychedelic induced-imagery. However, this has not been investigated in humans. To infer the directed connectivity changes to visual sensory connectivity underlying psychedelic visual imagery, we applied dynamic causal modelling to the resting state eyes-closed functional MRI scans of healthy adults after administration of psilocybin or placebo. The model included early visual regions, fusiform gyrus, intraparietal sulcus, and inferior frontal gyrus. We observed a pattern of increased self-inhibition of both early visual and higher visual-associative regions under psilocybin. The increased self-inhibition was associated with behavioural measures of complex and elementary imagery, and a pattern of reduced excitation and inhibition from visual-associative regions to earlier visual areas. The results are consistent with preclinical findings, inform our understanding of clinical hallucinations and perception, and suggest deprivation of sensory activity may amplify endogenous associative neural activity. The findings inform the neurobiology of psychedelic-induced changes to sensory connectivity and the neural mechanisms associated with closed-eyes visual imagery.”

Authors: Devon Stoliker, Katrin H. Preller, Alan Anticevic, Gary Egan, Franz X. Vollenweider & Adeel Razi

Study details

Compounds studied

Topics studied

Study characteristics

24 Humans


Institutes associated with this publication

Monash University
The Clinical Psychedelic Research Lab at Monash University is Australia's first research group dedicated to the study of psychedelics.

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