Altered white matter microstructure of language pathways and semantic cognition deficiencies in early psychosis

ABSTRACT Background Semantic language dysfunction is a hallmark of early psychosis, yet the underlying brain structural correlates are largely unexplored. In particular, it is unclear whether core deficits arise from disruptions to semantic representation, which refers to the stored knowledge of word meanings, or to semantic control, which entails top-down mechanisms that guide the retrieval and selection of context-appropriate semantic information. By dissociating semantic representation from semantic control, we aimed to clarify which aspect of semantic processing is preferentially impaired in early psychosis and how these deficits map onto structural properties of the ventral and dorsal language streams. Methods We investigated N = 120 individuals across the psychosis spectrum: N = 40 individuals with early psychosis, N = 40 individuals with high schizotypy and N = 40 individuals with low schizotypy. Participants with high and low schizotypy constituted the non-clinical comparison group. All participants completed tasks designed to isolate semantic representation and semantic control processes. Given the importance of accurate delineation, this study employed meticulous manual fiber tractography of diffusion tensor imaging (DTI) data to ensure reliable evaluation of ventral and dorsal pathway microstructure. Findings Compared to individuals with high and low schizotypy, individuals with early psychosis showed pronounced deficits in semantic control while semantic representation remained largely intact. Mean diffusivity in the left inferior fronto-occipital fasciculus and left uncinate fasciculus was lower in the early psychosis group than in individuals with schizotypy. In the early psychosis group, fractional anisotropy in the left arcuate fasciculus was negatively correlated with semantic control but no DTI measure was associated with semantic representation. Conclusion These results underscore semantic control as a core deficit in early psychosis and extend the conventional view that semantic processing is subserved primarily by ventral pathways. The arcuate fasciculus appears implicated in semantic control, indicating a more integrated interplay of dorsal and ventral streams in semantic language processing.