Resistance to Extinction of Evaluative Fear Conditioning in Delusion Proneness.

Abstract

Delusional beliefs consist of strong priors characterized by resistance to change even when evidence supporting another view is overwhelming. Such bias against disconfirmatory evidence (BADE) has been experimentally demonstrated in patients with psychosis as well as in delusion proneness. In this fMRI-study, we tested for similar resistance to change and associated brain processes in extinction of fear learning, involving a well-described mechanism dependent of evidence updating. A social fear conditioning paradigm was used in which four faces had either been coupled to an unconditioned aversive stimulus (CS+) or not (CS-). For two of the faces, instructions had been given about the fear contingencies (iCS+/iCS-) while for two other faces no such instructions had been given (niCS+/niCS-). Interaction analysis suggested that individuals who score high on delusion-proneness (hDP; n = 20) displayed less extinction of evaluative fear compared to those with low delusion proneness (lDP; n = 23; n = 19 in fMRI-analysis) for non-instructed faces (F = 5.469, P = .024). The resistance to extinction was supported by a difference in extinction related activity between the two groups in medial prefrontal cortex and its connectivity with amygdala, as well as in a cortical network supporting fear processing. For instructed faces no extinction was noted, but there was a larger evaluative fear (F = 5.048, P = 0.03) and an increased functional connectivity between lateral orbitofrontal cortex and fear processing regions for hDP than lDP. Our study links previous explored BADE-effects in delusion associated phenotypes to fear extinction, and suggest that effects of instructions on evaluative fear learning are more pronounced in delusion prone subjects.