Altered resting state functional connectivity in a thalamo-cortico-cerebellar network in patients with schizophrenia

Schizophrenia is described as a disease in which complex psychopathology together with cognitive and behavioral impairments are related to widely disrupted brain circuitry causing a failure in coordinating information across multiple brain sites. This led to the hypothesis of schizophrenia as a network disease e.g. in the cognitive dysmetria model and the dysconnectivity theory. Nevertheless, there is no consensus regarding localized mechanisms, namely dysfunction of certain networks underlying the multifaceted symptomatology. In this study, we investigated potential functional disruptions in 35 schizophrenic patients and 41 controls using complex cerebral network analysis, namely network-based statistic (NBS) and graph theory in resting state fMRI. NBS can reveal locally impaired subnetworks whereas graph analysis characterizes whole brain network topology. Using NBS we observed a local hyperconnected thalamo-cortico-cerebellar subnetwork in the schizophrenia group. Furthermore, nodal graph measures retrieved from the thalamo-cortico-cerebellar subnetwork revealed that the total number of connections from/to (degree) of the thalamus is higher in patients with schizophrenia. Interestingly, graph analysis on the whole brain functional networks did not reveal group differences. Together, our results suggest that disruptions in the brain networks of schizophrenia patients are situated at the local level of the hyperconnected thalamo-cortico-cerebellar rather than globally spread in brain. Our results provide further evidence for the importance of the thalamus and cerebellum in schizophrenia and to the notion that schizophrenia is a network disease in line with the dysconnectivity theory and cognitive dysmetria model.