Subcortical-cortical structural connectivity alternations and their application in cognitive impairments of schizophrenia

Background It has been suggested that white matter involves in regulation of various cognitive activities of schizophrenia(SZ). The complexity of SZ along with the lack of specific brain abnormalities indicates widespread systemic structural foundations in schizophrenia. To detect and visualize the abnormal patterns of whole-brain white matter network and their significance in cognitive impairment of SZ through diffusion-weighted magnetic resonance imaging (DWI) and tractography. Methods This cross-sectional study progressively recruited 61 SZ and 63 matched healthy controls(HC) from August 2019 and December 2022 at the Shanghai Mental Health Center. Probabilistic tractography was conducted, and a full-cortex connectomes of 82 brain regions based on Desikan-Killiany atlas were created to depict the number of streamlines between brain regions. Network-based statistic (NBS) analysis was performed to test between-group differences in brain subnetwork connectivity. Graph theoretical metrics were assessed to characterize the topological organization of structural networks. Pearson correlation analysis was conducted to explore the correlation between general data, clinical features, and significant network features. Results The NBS analysis indicated one component with stronger connectivity (p < 0.001) containing 53 connections among HC individuals compared with patients with SZ. These connections mainly located in the subcortical regions including thalamus, hippocampus, putamen as well as accumbens, and cortical regions mainly consisting of Insula, media lorbito-frontal, and anterior cingulate (threshold edge t > 3.10, component p < 0.001, NBS corrected). Further graph theoretical analysis revealed that SZ patients exhibited impairments in global efficiency and local topological properties, indicating disruptions in the ability of transiting and integrating information in the brain network. Correlation analysis shows that these structural network abnormalities were significantly associated with cognitive dysfunction in SZ. Conclusions： These findings here provided a new perspective for understanding the mechanisms behind the core symptoms of schizophrenia and emphasize the important pathological role of the white matter pathway in schizophrenia.