Dose-dependent modulation of visual imagery by Ayahuasca and dampening of visual processing away from external input: a placebo-controlled pharmacoimaging study

Abstract Ayahuasca, an amazonian brew containing the serotonergic psychedelic substance N,N-dimethyltryptamine (DMT), induces distinctive visual perceptual phenomenology, yet the neural mechanisms underlying the interplay between external visual drive and internal imagery remain unknown. Using a placebo-controlled, within-subject fMRI design, the present study investigated the impact of multiple doses of Ayahuasca upon strong bottom-up visual drive using high contrast periodic dynamic stimuli processing in 11 participants. Subjective ratings indicated psychedelic effects regarding visual perception and imagery, with dose-dependent increases in simple and complex visual imagery and intensity ratings. At the neural level, high-dose Ayahuasca attenuated this strong stimulus-evoked activation in ventral visual regions and reduced stimulus-evoked deactivation in the precuneus, while early visual cortex responses remained unaffected at this high stimulus drive level. Functional connectivity analyses revealed that Ayahuasca decreased the de-coupling between early visual cortex and a midline associative region, spanning the cuneal cortex and precuneus. These findings support the view that Ayahuasca biases visual processing away from externally driven input toward internally oriented processing, consistent with predictive coding and the REBUS model of psychedelic action.