Declined functional connectivity of white matter during rest and working memory tasks associates with cognitive impairments in schizophrenia

BACKGROUND: Schizophrenia, characterized by cognitive impairments, arises from a disturbance of brain network. Pathological changes in white matter (WM) have been indicated as playing a role in disturbing neural connectivity in schizophrenia. However, deficits of functional connectivity (FC) in individual WM bundles in schizophrenia have never been explored; neither have cognitive correlates with those deficits. METHODS: Resting-state and spatial working memory task fMRI images were acquired on 67 healthy subjects and 84 patients with schizophrenia. The correlations in blood-oxygenation-level-dependent (BOLD) signals between 46 WM and 82 gray matter regions were quantified, analyzed and compared between groups under three scenarios (i.e., resting state, retention period and entire time of a spatial working memory task). Associations of FC in WM with cognitive assessment scores were evaluated for three scenarios. RESULTS: FC deficits were significant (p<.05) in external capsule, cingulum, uncinate fasciculus, genu and body of corpus callosum under all three scenarios. Deficits were also present in the anterior limb of the internal capsule and cerebral peduncle in task scenario. Decreased FCs in specific WM bundles associated significantly (p<.05) with cognitive impairments in working memory, processing speed and/or cognitive control. CONCLUSIONS: Decreases in FC are evident in several WM bundles in patients with schizophrenia and are significantly associated with cognitive impairments during both rest and working memory tasks. Furthermore, working memory tasks expose FC deficits in more WM bundles and more cognitive associates in schizophrenia than resting state does.