Psilocybin increases optimistic engagement over time: computational modelling of behavior in rats

Abstract

Psilocybin has shown promise as a novel pharmacological intervention for treatment of depression, where post-acute effects of psilocybin treatment have been associated with increased positive mood and decreased pessimism. Although psilocybin is proving to be effective in clinical trials for treatment of psychiatric disorders, the information processing mechanisms affected by psilocybin are not well understood. Here, we fit computational models of underlying decision-making mechanisms to behaviour in rats. The model revealed that rats treated with psilocybin achieve more rewards through increased task engagement, mediated by modification of forgetting rates and reduced loss aversion. These findings suggest that psilocybin may afford an optimism bias that arises through altered belief updating, with translational potential for clinical populations characterised by lack of optimism.

The Universal Optimism of the Self-Evidencing Mind

“…In fact, this is what we found in a study of optimism bias in rats, conceptualising the bias in terms of increased engagement and hypothesising that the animals would be more optimistic if treated with psilocybin [26]. Our further simulation modelling work with active inference adds to the face validity of this approach, capturing development, belief updating and behaviour with the same model of the bias [27].…”

“…( Bottom ) A graphical depiction of an active inference model and the expected free-energy equation formalised in terms of information seeking and reward seeking. For details, see [ 26 , 27 ].…”

An Active Inference Model of the Optimism Bias

“…UCB (Sutton & Barto, 2018)). We opted to use active inference for reasons of convenience as it is not necessary to include ad hoc terms in the objective function, and for congruence with a previous study, which used active inference models to fit to behavioural data on optimism bias (Fisher et al, 2024) Optimism Bias Model…”

“…Specifically, individuals suffering from depression have been shown to either have no optimism bias, or a pessimism bias where individuals overestimate the likelihood of negative outcomes (Garrett et al, 2014;Hobbs et al, 2022;Korn et al, 2014). Core symptoms of depression, such as anhedonia and apathy result in withdrawing from the world, the opposite behaviour that optimism promotes (Cooper et al, 2018;Fisher et al, 2024;Rizvi et al, 2016), and treatment of depression includes behavioural activation that reverses this behaviour by encouraging engagement with the world (Soucy Chartier & Provencher, 2013;Tindall et al, 2017).…”