Characteristics of disrupted topological organization in white matter functional connectome in schizophrenia

Background Neuroimaging characteristics have demonstrated disrupted functional organization in schizophrenia (SZ), involving large-scale networks within grey matter (GM). However, previous studies have ignored the role of white matter (WM) in supporting brain function. Methods Using resting-state functional MRI and graph theoretical approaches, we investigated global topological disruptions of large-scale WM and GM networks in 93 SZ patients and 122 controls. Six global properties [clustering coefficient (C-p), shortest path length (L-p), local efficiency (E-loc), small-worldness (sigma), hierarchy (beta) and synchronization (S) and three nodal metrics [nodal degree (K-nodal), nodal efficiency (E-nodal) and nodal betweenness (B-nodal)] were utilized to quantify the topological organization in both WM and GM networks. Results At the network level, both WM and GM networks exhibited reductions in E-loc, C-p and S in SZ. The SZ group showed reduced sigma and beta only for the WM network. Furthermore, the C-p, E-loc and S of the WM network were negatively correlated with negative symptoms in SZ. At the nodal level, the SZ showed nodal disturbances in the corpus callosum, optic radiation, posterior corona radiata and tempo-occipital WM tracts. For GM, the SZ manifested increased nodal centralities in frontoparietal regions and decreased nodal centralities in temporal regions. Conclusions These findings provide the first evidence for abnormal global topological properties in SZ from the perspective of a substantial whole brain, including GM and WM. Nodal centralities enhance GM areas, along with a reduction in adjacent WM, suggest that WM functional alterations may be compensated for adjacent GM impairments in SZ.

Automated summary

This study examined the global topological disruptions of large-scale white matter (WM) and grey matter (GM) networks in patients with schizophrenia (SZ) using resting-state functional MRI and graph theoretical approaches. The results showed abnormal global topological properties in both WM and GM networks in SZ. Moreover, specific regions in WM and GM exhibited nodal disturbances. The findings suggest compensatory functional alterations in WM may occur in response to impairments in adjacent GM in SZ.