Reduced precision underwrites ego dissolution and therapeutic outcomes under psychedelics

Introduction

Classic psychedelics can induce a range of subjective effects, including visual alterations, altered perception of time, and shifts in attention and perspective that reframe the relationship of self with the world. Ego dissolution is a validated independent and measurable construct, and is thought to be linked to therapeutic outcomes. The 5HT2A receptor is a serotonergic receptor involved in attention, especially in the prediction of the cause of sensory impressions and the consequences of self-initiated actions. Predictive processing describes the interplay between ascending neuronal signals and descending predictions that embody internal world models. Surprise is minimised by updating predictions or by initiation of actions on the world to align sensory evidence with predictions. The cortical hierarchy maintains a generative model of the world by updating beliefs about the causes and consequences of exogenous and endogenous sensations. Belief updating is a unifying principle in neural computation.

Predictive processing uses a signal to noise ratio to update predictions across the predictive hierarchy, and acts as a neural implementation of attention between layers of the cortical hierarchy. The generative model encodes causes of sensory states and confidence of predictions in predictive processes, which are more or less independent of high level beliefs. When a prediction error requires an update, it is attended and granted access to higher levels where prediction errors are resolved. Predictive processing suggests a means to examine and understand cognition, and the analysis of large-scale resting state network connectivity may aid the interpretation of predictive processes in consciousness and attention. Precision, the inverse of the variance of a signal, is explored in this work as a bridge between predictive processing and large-scale brain connectivity. Precision can be modelled as a probabilistic range of prior alternate hypotheses about the causes of sensory information. A high level of belief in a generative model can inhibit updating of conscious beliefs based on contradictory sensory evidence. Despite being closely related to the self, precision is significantly dependent on and modulated by neurotransmitter systems. Agonism of serotonergic 5HT2A receptors by psychedelics is thought to reduce the precision of belief updating and reduce the ‘confidence’ in the selection of any one channel of attention.