Guided by Expectations: Overweighted Semantic Priors in Schizotypy and Their Links to Glutamate.

BACKGROUND: An imbalance in the weighting of prior beliefs and sensory evidence is thought to contribute to the development of psychotic symptoms, such as hallucinations and delusions. We investigated 1) how much individuals with schizotypal traits, a subclinical expression of psychosis proneness, use high-level semantic priors and sensory evidence to understand noise-degraded language; 2) whether an imbalance would potentially result in task-based hallucinations-perceptions that match expectations but not the input; and finally, 3) whether a potential imbalance was linked to altered levels of cortical glutamate.

METHODS: In a language comprehension task, we simultaneously manipulated semantic predictability, sensory degradation, and surprisal to estimate the prior weight using a Bayesian belief updating model. We conducted 2 studies. Study 1 (N = 109) tested the language comprehension task behaviorally; study 2 (N = 55) was used to replicate the findings of study 1, but was also combined with proton magnetic resonance spectroscopy to assess cortical levels of glutamate.

RESULTS: Study 1 showed that high-level priors were overweighted, with increasing schizotypy providing a potential explanation for the increased number of task-based hallucinations observed in the same individuals. Importantly, replicating the results of study 1, study 2 revealed that an overweighting of priors was associated with increased cingulate glutamate, providing a neurobiological basis for overreliance on top-down predictions.

CONCLUSIONS: These results offer a mechanistic and neurobiological understanding of how predictive coding alterations contribute to symptom development along the psychosis spectrum.