Affected White Matter Structural Network Im Patients With Primary Insomnia:A Diffusion-Tensor Imaging Study

Objective:Primary insomnia is the second most common mental disorder.We aimed to assess whether there are topological changes in the white matter structure brain network of patients with primary insomnia,and to explore the relationship between abnormal network topological changes and clinical features by diffusion tensor imaging(DTI)and graph theory analysis methods.We hoped to provide objective imaging evidences for the neuropathological mechanism of-primary insomnia.Materials and Methods:This prospective study was approved by the review ethics committee of Guangdong Second Provincial General Hospital.Written informed consent was obtained from each participant.MRI images for all primary insomnia patients(PI)and healthy control participants(HC)were acquired on a Philips 1.5T MRI system(Achieva Nova-Dual;Philips).In total,this study analyzed 44 PI participants and 46 age-,sex-,and years of education matched healthy control participants.Using the PANDA software,90 network nodes were defined by the automated anatomical labeling(AAL)atlas to construct brain networks for each subject.All global and nodal metrics were determined with the GRETNA toolbox and MATLAB 2014 software.All participants underwent a standardized clinical evaluation protocol before MRI.The network parameters were employed by nonparametric permutations to evaluate the significant differences between the two groups.Relationships between abnormal network metrics and clinical characteristics,including the disease duration,the Pittsburgh Sleep Quality Index(PSQI),the Insomnia Severity Index(ISI),the Self-Rating Anxiety Scale(SAS)and the Self-Rating Depression Scale(SDS),were investigated with Spearman’s correlation analysis in PI patients.Results:(1)No significant differences were found in age,gender,and education between the PI and HC groups.(2)Both PI and HC showed characteristic small-world topology in the brain structural connectome across all selected thresholds(γ>1,λ≈1,and σ>1)compared with 1000 matched random networks.Compared with HCs,PIs exhibited significantly lower global efficiency and local efficiency.(3)The topological alterations of abnormal hub nodes,disrupted subnetworks and rich club of the brain network in PI patients were mostly involved in the limbic cortico-basal-ganglia circuit and default-mode networks.(4)There were significant correlations between clinical characteristics(SAS,SDS scores and disease duration)and abnormal hub nodal properties in PI patients.(5)This study revealed a significant decrease in rich club density and feeder density,a significantly lower proportion of densities between rich club and feeder connections(rich club/feeder)and between rich club and local connections in PI patients compared with HC participants.(6)The PI group has weaker ability to divide the module than the HC group.(7)At the group level,there were negative correlations between the modular Q value(Qfc),SDS scores and the rich club connections,while the positive correlations between the Qfc and rich club connection,and between the average module index Q(Qi)and individual-level rich club connections.Conclusion:The study showed that there were extensive damages to the bain white matter structure network in PI patients.The topological alterations of abnormal hub nodes,disrupted subnetworks and rich club of the brain network in PI patients were mostly involved in the limbic cortico-basal-ganglia circuit and default-mode networks,which associated with the underlying symptoms of PI,especially sleep-dependent emotional abnormalities.The decrease of rich club metrics may be a characteristic manifestation of abnormal anatomical structure in insomnia procession.The PI group has decreased ability to divide the module than the HC group.This study deepens our understanding of the neuropathological mechanism of PI.This study discovered that the changes in the topological alterations of the rich club and module structure were associated with the severity of clinical manifestations in PI patients.The present study may provide a novel insight into the basic symptoms and neuropathological mechanisms of PI patients.