Abnormal Topology of the Structural Connectome in the Limbic Cortico-Basal-Ganglia Circuit and Default-Mode Network Among Primary Insomnia Patients.

Yunfan Wu,Guomin Li,Shaoqing Zeng,Shishun Fu,Jianhao Yan,Xiaofen Ma,Yi Yin,Guang Xu,Chao Li,Cheng Li,Tianyue Wang,Mengchen Liu,Chulan Lin,Kelei Hua,Guihua Jiang

doi:10.3389/fnins.2018.00860

Yunfan Wu, Guomin Li + Show 13 more

Open Access

https://doi.org/10.3389/fnins.2018.00860

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Abstract

Purpose: Primary insomnia (PI) is the second most common mental disorder. However, the topologic alterations in structural brain connectome in patients with PI remain largely unknown.Methods: A total of 44 PI patients and 46 age-, gender-, and education level matched healthy control (HC) participants were recruited in this study. Diffusion tensor imaging (DTI) and resting state MRI were used to construct structural connectome for each participant, and the network parameters were employed by non-parametric 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: PI patients demonstrated small-world architecture with lower global (P = 0.005) and local (P = 0.035) efficiencies compared with the HC group. The unique hub nodal properties in PI patients were mainly in the right limbic cortico-basal-ganglia circuit. Five disrupted subnetworks in PI patients were observed in the limbic cortico-basal-ganglia circuit and left default-mode networks (DMN) (P < 0.05, NBS corrected). Moreover, most unique hub nodal properties in the right limbic cortico-basal-ganglia circuit were significantly correlated with disease duration, and clinical characteristics (SAS, SDS, ISI scores) in PI processing.Conclusion: These findings suggested the abnormal anatomical network architecture may be closely linked to clinical characteristics in PI. The study provided novel insights into the neural substrates underlying symptoms and neurophysiologic mechanisms of PI.

Highlights

Primary insomnia is the second most common mental disorder (Wittchen et al, 2011)
primary insomnia (PI) patients were enrolled in this study according to the following criteria: (a) patients were diagnosed and confirmed as PI based on the criteria of Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-V) (American Psychiatric Association, 2013); (b) patients with a selfcomplaint of difficulty falling asleep, maintaining sleep or early awakening for at least 3 months; (c) patients with no other sleep disorders, such as hypersomnia, parasomnia, obstructive sleep apnea, or sleep-related movement disorder; (d) patients with no serious organic diseases or no severe mental diseases, such as brain stroke, depression (SDS < 70), and anxiety (SAS < 70); (e) all participants were right-handed according to the Edinburgh handedness inventory; (f) all subjects were aged 18–60 years
Five unique regions of nodal properties (Ne, degree centrality (Dc), and betweenness centrality (Bc)) in PIs were located in ORBsupmed.R, HIP.R, bilateral THA and CAU.R compared with healthy control (HC) (Figure 2)

Summary

Introduction

Primary insomnia is the second most common mental disorder (Wittchen et al, 2011). PI is characterized by difficulty in initiating and maintaining sleep and early morning awakening for at least 3 months (American Psychiatric Association, 2013). Two positron emission tomography studies (Nofzinger et al, 2004, 2006) have demonstrated that compared with healthy control participants (HCs), 18-fluorodeoxyglucose metabolism was lower in the prefrontal cortex while awake, and higher in the thalamus (THA), anterior cingulate gyrus, temporal region and pontine tegmentum during non-rapid eye movement sleep in PI patients (PIs). Wang T. et al (2016) found that regional homogeneity values were higher in the left insula (INS.L), right anterior cingulate gyrus (ACG.R), left insula, bilateral precentral gyrus and left cuneus (CUN.L) in PIs than in HCs. Two positron emission tomography studies (Nofzinger et al, 2004, 2006) have demonstrated that compared with healthy control participants (HCs), 18-fluorodeoxyglucose metabolism was lower in the prefrontal cortex while awake, and higher in the thalamus (THA), anterior cingulate gyrus, temporal region and pontine tegmentum during non-rapid eye movement sleep in PI patients (PIs).

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Conclusion