Disruption of structure-function coupling in the schizophrenia connectome.

Abstract

Neuroimaging studies have demonstrated that the phenomenology of schizophrenia maps onto diffuse alterations in large-scale functional and structural brain networks. However, the relationship between structural and functional deficits remains unclear. To answer this question, patients with established schizophrenia and matched healthy controls underwent resting-state functional and diffusion weighted imaging. The network-based statistic was used to characterize between-group differences in whole-brain functional connectivity. Indices of white matter integrity were then estimated to assess the structural correlates of the functional alterations observed in patients. Finally, group differences in the relationship between indices of functional and structural brain connectivity were determined. Compared to controls, patients with schizophrenia showed decreased functional connectivity and impaired white matter integrity in a distributed network encompassing frontal, temporal, thalamic, and striatal regions. In controls, strong interregional coupling in neural activity was associated with well-myelinated white matter pathways in this network. This correspondence between structure and function appeared to be absent in patients with schizophrenia. In two additional disrupted functional networks, encompassing parietal, occipital, and temporal cortices, the relationship between function and structure was not affected. Overall, results from this study highlight the importance of considering not only the separable impact of functional and structural connectivity deficits on the pathoaetiology of schizophrenia, but also the implications of the complex nature of their interaction. More specifically, our findings support the core nature of fronto-striatal, fronto-thalamic, and fronto-temporal abnormalities in the schizophrenia connectome.