S-ketamine, suggestibility, and spontaneous thought: a double-blind randomized crossover EEG study extending the ESKOP protocol

Abstract

The NMDA-receptor antagonist ketamine is widely used as an anaesthetic and has recently attracted considerable interest due to its rapid antidepressant effects. Beyond its clinical applications, ketamine reliably induces marked alterations in bodily awareness and self-experience, including dissociation, disembodiment and perceptual distortions. Contemporary neurocognitive accounts increasingly interpret these phenomena within predictive processing frameworks, according to which conscious experience emerges from the dynamic integration of prior beliefs and incoming sensory signals. Within this perspective, ketamine is thought to modify the precision-weighting of interoceptive and exteroceptive information, thereby shifting the balance between internally generated predictions (priors) and sensory evidence. Such changes may increase the influence of contextual factors on perceptual inference and expriential reports. Understanding these alterations therefore requires a multimodal approach that combines behavioral, neurophysiological and expriential measures. The aim of this study is to characterise how (S+)-ketamine vs. placebo alters precision-weighting accross multimodal interoceptive, perceptual and cognitive tasks using a within-subjects double-blind cross-over experimental design. This preregistration is for a direct extension of a previously registered study, the ESKOP study (Effect of S-Ketamine on Body Perception in Healthy Adults - ESKOP; OSF: https://osf.io/8u9az/files/u84jd). The ESKOP study investigated the acute effects of intravenous s-ketamine on implicit body and self-perception using EEG and cognitive experimental tasks in healthy volunteers (N = 24). The present study extends the ESKOP study by recruiting an additional independent sample of 24 healthy participants who complete a partially overlapping but distinct set of tasks. Specifically, the present study introduces two new tasks not included in the original ESKOP study, the Mind Wandering task and the Brief Suggestibility Scale, while retaining tasks from the original protocol (EEG Resting State, Sensory Suppression task, and Heart Rate Discrimination task) to allow for replication and assessment of robustness across samples. The experimental protocol, drug administration procedure, inclusion and exclusion criteria, and double-blind randomized crossover design are identical to those of the original ESKOP study. Data from the shared task will be combined across both studies (total N = 48) for replication and individual difference analyses, as detailed in the Sample Size Rationale section.

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