Psilocybin and predictive coding in the visual system
Predictive processing theory describes the brain as actively generating conscious perception by continually optimizing internally-generated predictions about its sensory inputs. In visual processing, priors are signals that are informed by previous visual experiences that disambiguate the brain’s perceptual interpretations of inherently noisy visual stimuli. Psychedelics may alter perception, cognition, and emotions by reducing the strength of top-down priors (Carhart-Harris and Friston, 2019), thereby allowing new interpretations of the world around us and ourselves. We will employ psilocybin, functional magnetic resonance imaging (fMRI), and visual stimuli that elicit multiple possible perceptual interpretations to rigorously test the hypothesis that the psychedelic experience is characterized by reduced influence of priors on the brain’s construction of conscious visual perception.
Characterizing the effects of psilocybin on visual feature representations in the brain with voxelwise encoding models
Many psychedelic drugs elicit profound alterations in visual perception, but little is known about the brain mechanisms the underlie these effects. In collaboration with Jack Gallant’s lab, we will employ fMRI and voxelwise encoding models to fully characterize the brain’s representations of visual features at high spatial resolution with whole-brain coverage. The acute effects of psilocybin on these feature representations and their tuning will be systematically quantified. In addition, we will relate changes in these feature representations to subjective reports of the perceptual experiences subjects report during acquisition of the fMRI data. This project will provide a comprehensive description of changes in the brain’s representations of the visual environment following psilocybin administration. The vast knowledge base regarding visual cortical function and representation allows the effects of psilocybin to be quantified with high precision, and this can then be used as a scaffold to characterize higher-order effects on processes such as memory, emotion, and social cognition.
Enduring effects of the psychedelic experience on cognition, emotion, and stress and associated neural correlates in older and younger adults
Although thousands of doses of psilocybin have been administered in controlled scientific settings over the past few decades, very few of these participants have been older adults (>60 years), and there has been no systematic study of the effects of psilocybin on cognitive function and associated brain mechanisms in older adults. This work is being carried out in collaboration with Bill Jagust’s and Dacher Keltner’s laboratories.
We will administer psilocybin to groups of both older and younger adults to determine its feasibility as an intervention in healthy aging. Our experimental measures will include cognitive testing to quantify memory performance, structural MRI (hippocampal volume), fMRI (resting-state to characterize whole-brain dynamics as well as a memory task to measure functional activity in the hippocampus that is associated with encoding information into memory).
We will also collect survey data to determine which aspects of the psychedelic experience best predict enduring beneficial effects on cognition and its neural correlates, emotional regulation, prosocial behaviors, and stress levels. In particular, we hypothesize that the subjective experience of awe is critical for psychedelics to induce long-lasting improvements in well-being.