Altered Functional Connectivity of Striatum Based on the Integrated Connectivity Model in First-Episode Schizophrenia

Background: The human striatum is a heterogeneous structure involved in diverse functional domains that related to distinct striatum subregions. Striatal dysfunction was thought to be a fundamental element in schizophrenia. However, the connectivity pattern of striatum solely based on functional or structural characteristics leads to inconsistent findings in healthy adult and also schizophrenia. This study aims to develop an integrated striatal model and reveal the altered functional connectivity pattern of the striatum in schizophrenia. Methods: Two data-driven approaches, task-dependent meta-analytic connectivity modeling (MACM) and task-independent resting-state functional connectivity (RSFC), were used for seven anatomical connectivity-based striatum subregions to provide an integrated striatal model. Then, RSFC analyses of seven striatal subregions were applied to 45 first-episode schizophrenia (FES) and 27 healthy controls to examine the difference, based on the integrated model, of functional connectivity pattern of striatal subregions. Results: MACM and RSFC results showed that striatum subregions were associated with discrete cortical regions and involved in distinct cognitive processes. Besides, RSFC results overlapped with MACM findings but showed broader distributions. Importantly, significantly reduced functional connectivity was identified between limbic subregion and thalamus, medial prefrontal cortex, anterior cingulate cortex, and insula and also between executive subregions and thalamus, supplementary motor area, and insula in FES. Conclusions: Combing functional and structural connectivity information, this study provides the integrated model of corticostriatal subcircuits and confirms the abnormal functional connectivity of limbic and executive striatum subregions with different networks and thalamus, supporting the important role of the corticostriatal-thalamic loop in the pathophysiology of schizophrenia

Sex Differences of Uncinate Fasciculus Structural Connectivity in Individuals with Conduct Disorder

Conduct disorder (CD) is one of the most common behavior disorders in adolescents, such as impulsivity, aggression, and running from school. Males are more likely to develop CD than females, and two previous diffusion tensor imaging (DTI) studies have demonstrated abnormal microstructural integrity in the uncinate fasciculus (UF) in boys with CD compared to a healthy control group. However, little is known about changes in the UF in females with CD. In this study, the UF was illustrated by tractography; then, the fractional anisotropy (FA), axial diffusivity, mean diffusion, radial diffusivity (RD), and the length and number of the UF fiber bundles were compared between male and female patients with CD and between female patients with CD and female healthy controls, as well as between males with CD and healthy males. We found that males with CD showed significantly higher FA of the bilateral UF and significantly lower RD of the left UF when comparing with females with CD. Meanwhile, significantly higher FA and lower RD of the bilateral UF were also found in boys with CD relative to the male healthy controls. Our results replicated previous reports that the microstructural integrity of the UF was abnormal in boys with CD. Additionally, our results demonstrated significant gender effects on the UF of patients with CD, which may indicate why boys have higher rates of conduct problems than girls