Enhanced Instructed Fear Learning in Delusion-Proneness.

Psychosis is associated with distorted perceptions and deficient bottom-up learning such as classical fear conditioning. This has been interpreted as reflecting imprecise priors in low-level predictive coding systems. Paradoxically, overly strong beliefs, such as overvalued beliefs and delusions, are also present in psychosis-associated states. In line with this, research has suggested that patients with psychosis and associated phenotypes rely more on high-order priors to interpret perceptual input. In this behavioural and fMRI study we studied two types of , i.e., mediated by verbal suggestions about fear contingencies and mediated by low level associative learning, in delusion proneness-a trait in healthy individuals linked to psychotic disorders. Subjects were shown four faces out of which two were coupled with an aversive stimulation (CS+) while two were not (CS-) in a fear conditioning procedure. Before the conditioning, subjects were informed about the contingencies for two of the faces of each type, while no information was given for the two other faces. We could thereby study the effect of both classical fear conditioning and instructed fear learning. Our main outcome variable was evaluative rating of the faces. Simultaneously, fMRI-measurements were performed to study underlying mechanisms. We postulated that instructed fear learning, measured with evaluative ratings, is stronger in psychosis-related phenotypes, in contrast to classical fear conditioning that has repeatedly been shown to be weaker in these groups. In line with our hypothesis, we observed significantly larger instructed fear learning on a behavioural level in delusion-prone individuals ( = 20) compared to non-delusion-prone subjects ( = 23; = 20 in fMRI study). Instructed fear learning was associated with a bilateral activation of lateral orbitofrontal cortex that did not differ significantly between groups. However, delusion-prone subjects showed a stronger functional connectivity between right lateral orbitofrontal cortex and regions processing fear and pain. Our results suggest that psychosis-related states are associated with a strong instructed fear learning in addition to previously reported weak classical fear conditioning. Given the similarity between nocebo paradigms and instructed fear learning, our results also have an impact on understanding why nocebo effects differ between individuals.