Neural mechanisms of imagery under psilocybin

Abstract

AbstractVisual alterations under classic psychedelics can include rich phenomenological accounts of eyes-closed 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 in healthy adults, we applied dynamic causal modelling to the resting state eyes-closed functional MRI scans of 24 subjects after administration of 0.2mg/kg of the serotonergic psychedelic drug, psilocybin (magic mushrooms), or placebo. The effective connectivity model included the early visual area, fusiform gyrus, intraparietal sulcus, and inferior frontal gyrus was modelled. We observed a pattern of increased self-inhibition of both early visual and higher visual-association regions under psilocybin that was consistent with preclinical findings. We also observed a pattern of reduced excitation and inhibition from visual-association regions to earlier visual areas that indicated top-down connectivity is enhanced during visual imagery. The results were associated with behavioural measures of complex and elementary imagery taken after the scans, suggesting psilocybin-induced deprivation of sensory activity amplifies endogenous neural activity associated with the perception of eyes-closed visual imagery. The findings inform our basic and clinical understanding of visual perception and identify neural mechanisms that contribute to psychedelic-induced eyes-closed visual imagery.Significance statementOur study is the first measurement of the effects of a 5-HT2A receptor agonist on synaptic gain of the visual system in humans and advances the understanding of the psychopharmacology of visual perception. Our findings are consistent with preclinical evidence and elucidate the effects of psychedelics on neural mechanisms of the visual system. Specifically, we identify manifestations of visual imagery in the absence of stimuli result from decreased self-connectivity of the visual system and increased reliance on top-down connectivity. The findings have relevance to understanding clinical hallucinations and offers avenues for exploring the neurology and utility of visual imagery in psychedelic-assisted-psychotherapy. Moreover, our study advances the broader field of neuroimaging by identifying the hierarchical organisation of brain connectivity underlying perception.