Language-network connectivity and cortical glutamate and their associations with overweighted semantic prior beliefs, schizotypy and task-based hallucinations

BackgroundImpairments in language comprehension and production are core symptoms of schizophrenia spectrum disorders (SSD). Predictive processing, a Bayesian framework of brain function, provides an explanatory account of both language processing and psychotic symptom formation. Within SSD, neurobiological correlates of alterations in predictive language processing are poorly understood. Here, we investigate if glutamatergic neurotransmission and functional connectivity (FC) within the language network are associated with (1) altered predictive language processing, (2) task-based hallucinations (TBH), and (3) schizotypy. MethodsIn 53 healthy individuals (26 women), we combined a predictive language task analyzed using a Bayesian belief update model to estimate the individuals reliance on prior knowledge versus sensory input depending on the their schizotypal trait expression, resting-state functional MRI, and MR spectroscopy to measure glutamate levels in the anterior cingulate cortex (ACC) and left dorsolateral prefrontal cortex (DLPFC). Seed-based FC analysis focused on the language network including the left inferior frontal gyrus (IFG), posterior superior temporal gyrus (pSTG), and posterior middle temporal gyrus (pMTG). ResultsIncreased FC between left IFG and frontal areas predicted schizotypy-informed prior overweighting. Enhanced left pSTG-medial frontal FC was associated with the frequency of TBH. Finally, schizotypy was predicted by interactions between ACC/DLPFC Glx and left pSTG-frontal FC. ConclusionsThese results provide novel insights into neurobiological and computational mechanisms underlying altered language-related predictive processing and subclinical symptom formation. They highlight potential early indicators of schizotypal symptom development and underscore the value of multimodal approaches in elucidating pathophysiology of SSD.