Cognitive effects of placebo antipsychotics: Investigating their mechanisms using event-related potentials (ERPs) in a cognitive test and a self-referential task

Placebos modulate neurocognitive processes. We examined whether a fully deceptive antipsychotic-placebo changes cognition not only by enhancing arousal and attention but also by changing self-representations, namely, by adding that of being under a treatment related to psychosis and by weakening the binding of experience to reality. Drug-naive healthy participants (N = 83) were split into a group (N = 40) who took a pill described as an antipsychotic and a no-pill control group (N = 43). Participants performed a cognitive test (CogTest), that is, a semantic categorization task and a self-referential role judgment task (SRT). Behavioral responses and event-related potentials (ERPs) were recorded. In the CogTest, placebos showed faster response times and higher accuracy than no-pills. This cognitive improvement was associated with more negative occipito-temporal early ERPs (OTEEs), larger central P2s (CentP2s), and larger late positive potentials (LPPs), with the latter correlating with response times. As in the literature, CentP2s were maximal in the SRT, possibly because it maximally stimulates the binding of the stimulus to long-term self-representations. The larger CentP2s and LPPs for placebos than for no-pills in the CogTest were thus tentatively related to the binding of the stimulus with egocentric self-representations, temporarily enriched by the addition of the representation of being on drug. On the contrary, the more negative OTEEs were related to a weaker binding to allocentric ones, preventing a strong binding of experience with reality. The smaller N400s observed for placebos than for no-pills in both tasks were related to greater openness to new experiences.