Neural correlates of uncertainty processing in psychosis spectrum disorder.

Psychotic beliefs are typically held with high certainty. Altered computation of uncertainty about a belief and about environmental dynamics may be an underlying mechanism of psychotic symptoms. We set out to shed light on behavioural and neural correlates of uncertainty processing and how it drives belief updating in psychosis. This cross-sectional study included 19 participants with psychosis spectrum disorder (5 female and 14 male) and 40 healthy control participants (21 female and 19 male) between 18 and 65 years of age. Participants performed a predictive inference task that required belief updating of a noisy outcome in a suddenly changing environment during functional magnetic resonance imaging. Behavioural and imaging data were analysed with a computational model that approximates an ideal Bayesian observer. The model expects beliefs to be updated based on the relative belief uncertainty and environmental change point probability. Task performance, model parameters and associated neural activation were compared between groups and associated with self-reported delusional ideation and cognitive functioning. While the belief updating speed overall did not differ between groups, the psychosis group showed lower task performance. Lower performance was associated with higher self-reported delusional ideation, even when controlling for cognitive functioning. Persons with psychosis spectrum disorder tended to persevere on beliefs after large prediction errors that signal environmental changes. They informed belief updates less by the probability of environmental change points, although this capacity seemed to depend on general cognitive functioning. The psychosis group also encoded the change point probability less in the superior occipital and fusiform gyrus, as well as a cluster comprising pre-central to middle frontal gyrus. Activity in these clusters was associated with lower self-reported delusional ideation across the whole sample and lower general and negative symptoms in the clinical sample. Persons with psychosis spectrum disorder did not seem to overestimate environmental volatility in general. Instead, they showed altered processing of information that occurred after environmental change points, whose probability was less well represented in brain regions encoding visual surprise and motor responses. Possibly, persons with psychosis spectrum disorder inadequately integrated visual surprise signals, leading to ineffective transmission to motor regions that eventually guide behaviour. Summarizing, our study suggests that delusions could result from a tendency to stick to old beliefs even in the light of contrary evidence, due to a failure to integrate uncertainty information based on inferred environmental dynamics.