Investigating cognitive flexibility deficit in schizophrenia using task-based whole-brain functional connectivity.

Background: Cognitive flexibility is a core cognitive control function supported by the brain networks of the whole-brain. Schizophrenic patients show deficits in cognitive flexibility in conditions such as task-switching. A large number of neuroimaging studies have revealed abnormalities in local brain activations associated with deficits in cognitive flexibility in schizophrenia, but the relationship between impaired cognitive flexibility and the whole-brain functional connectivity (FC) pattern is unclear. Method: We investigated the task-based functional connectivity of the whole-brain in patients with schizophrenia and healthy controls during task-switching. Multivariate pattern analysis (MVPA) was utilized to investigate whether the FC pattern can be used as a feature to discriminate schizophrenia patients from healthy controls. Graph theory analysis was further used to quantify the degrees of integration and segregation in the whole-brain networks to interpret the different reconfiguration patterns of brain networks in schizophrenia patients and healthy controls. Results: The results showed that the FC pattern classified schizophrenia patients and healthy controls with significant accuracy. Moreover, the altered whole-brain functional connectivity pattern was driven by a lower degree of network integration and segregation in schizophrenia, indicating that both global and local information transfers at the entire-network level were less efficient in schizophrenia patients than in healthy controls during task-switching processing. Conclusion: These results investigated the group differences in FC profiles during task-switching and not only elucidated that FC patterns are changed in schizophrenic patients, suggesting that task-based FC could be used as a potential neuromarker to discriminate schizophrenia patients from healthy controls in cognitive flexibility but also provide increased insight into the brain network organization that may contribute to impaired cognitive flexibility.