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

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-related from semantic control-related performance, we aimed to identify the preferential impairment in early psychosis and its structural correlates in the ventral and dorsal language streams. 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-related and semantic control-related 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. Compared to individuals with high and low schizotypy, individuals with early psychosis showed pronounced deficits in semantic control-related performance, while the semantic representation-related measure 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-related performance, but no DTI measure was associated with the semantic representation-related measure. These results underscore semantic control-related performance 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-related processes, indicating a more integrated interplay of dorsal and ventral streams in semantic language processing.