Abstract
Schizophrenia is a disorder of brain dysconnectivity, and both the connection strength and connection number are disrupted in patients with schizophrenia. The functional connectivity density (FCD) can reflect alterations in the connection number. Alterations in the global FCD (gFCD) in schizophrenia were previously demonstrated; however, alterations in two other indices of the pathological characteristics of the brain, local FCD (lFCD) and long-range FCD (lrFCD), have not been revealed. To investigate lFCD and lrFCD alterations in patients with schizophrenia, 95 patients and 93 matched healthy controls were examined using structural and resting-state functional magnetic resonance imaging scanning. lFCD and lrFCD were measured using FCD mapping, and differences were identified using a two-sample t-test in a voxel-wise manner, with age and gender considered to increase variability. Multiple comparisons were performed using a false discovery rate method with a corrected threshold of P<0.05. Our analysis showed that lFCD was primarily decreased in the postcentral gyrus, right calcarine sulcus, and inferior occipital gyrus lobule, but increased in the bilateral subcortical regions. The differences in lFCD were more pronounced and complicated than those in lrFCD. In summary, in contrast with previous studies that focused on the connection strength, our findings, from the perspective of connection number, indicate that schizophrenia is a disorder of brain dysconnectivity, particularly affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions.
Highlights
In the past two decades, several lines of evidence have converged to support that schizophrenia is a disorder associated with extensive disturbance of brain functional connectivity/activity [1,2,3,4,5]
In contrast with previous studies that focused on the connection strength, our findings, from the perspective of connection number, indicate that schizophrenia is a disorder of brain dysconnectivity, affecting the local functional connectivity network, and support the hypothesis that schizophrenia is associated with a widespread cortical functional connectivity/activity deficit, with hyper- and/or hypo-connectivity/activity coexisting in some cortical or subcortical regions
These findings suggest that the disturbance in local functional connection numbers was pronounced in schizophrenia patients, which is partially in agreement with a previous observation that local FCD (lFCD) was decreased in the primary sensorimotor area and increased in frontal areas [23]
Summary
In the past two decades, several lines of evidence have converged to support that schizophrenia is a disorder associated with extensive disturbance of brain functional connectivity/activity [1,2,3,4,5]. Most of the previous studies suggest that hyper-connectivity/activity is mainly located in subcortical regions and some cortical-subcortical circuits. Hypo-connectivity/activity is mainly located in the cortical regions, in the cortical regions of the frontal and parietal cortex [6,7,8,9,10,11,12]. As early as 2011, Fornito et al reviewed many previous studies and suggested that schizophrenia is associated with a widespread cortical functional connectivity deficit, and on this background, hyper- and/or hypo-connectivity was observed in some cortical or subcortical regions [13]. A few studies based on graph theory have suggested that the brain network appears to have only a few well-localized regions (hubs) for the fast integration of neural processing, and their dysfunction could contribute to neuropsychiatric diseases, including schizophrenia [14,15,16,17]. Even fewer studies have investigated alterations in functional hubs in schizophrenia [25]
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