Background: Mental syndromes such as anxiety and depression are common comorbidities in patients with chronic insomnia disorder (CID). The locus coeruleus noradrenergic (LC-NE) system is considered to be crucial for modulation of emotion and sleep/wake cycle. LC-NE system is also a critical mediator of the stress-induced anxiety. However, whether the LC-NE system contributes to the underlying mechanism linking insomnia and these comorbidities remain unclear. This study aimed to investigate the LC-NE system alterations in patients with insomnia and its relationship with depression and anxiety symptoms.Materials and Methods: Seventy patients with CID and 63 matched good sleep control (GSC) subjects were recruited and underwent resting-state functional MRI scan. LC-NE functional network was constructed by using seed-based functional connectivity (FC) analysis. The alterations in LC-NE FC network in patients with CID and their clinical significance was explored.Results: Compared with GSC group, the CID group showed decreased left LC-NE FC in the left inferior frontal gyrus, while they had increased LC-NE FC in the left supramarginal gyrus and the left middle occipital gyrus (MOG). For the right LC-NE FC network, decreased FC was found in left dorsal anterior cingulate cortex (dACC). Interesting, the increased LC-NE FC was located in sensory cortex, while decreased LC-NE FC was located in frontal control cortex. In addition, the FC between the left LC and left MOG was associated with the duration of the disease, while abnormal FC between right LC and left dACC was associated with the anxiety scores in patients with CID.Conclusion: The present study found abnormal LC-NE functional network in patients with CID, and the altered LC-NE function in dACC was associated with anxiety symptoms in CID. The present study substantially extended our understanding of the neuropathological basis of CID and provided the potential treatment target for CID patients who also had anxiety.

Insomnia is a common comorbidity symptom in patients with major depressive disorder (MDD). However, the brain functional alteration in MDD with higher level insomnia (MDD-HI) and lower level insomnia (MDD-LI) remains unclear. Here, we investigated the association of insomnia with global functional connectivity density (gFCD) in patients with MDD. A total of 148 participants were recruited and underwent resting-state functional magnetic resonance imaging. A voxel-wise analysis of covariance was employed to explore group differences in gFCD among the MDD-HI, MDD-LI and healthy control (HC) groups. The gFCD in the bilateral parahippocampal/hippocampal gyri (PHG/HIP) was higher in the two MDD than in the HC group, and it was higher in the MDD-LI than in the MDD-HI group; the gFCD in the left fusiform area was lower in the MDD than in the HC group. The gFCD in the left inferior temporal gyrus (ITG) was higher in the MDD-HI than in the MDD-LI and HC groups. The gFCD in the left ITG and posterior PHG/HIP was associated with insomnia, while the gFCD in the left anterior PHG/HIP was correlated with non-insomnia depressive symptoms in the MDD group. The cross-sectional design and the use of brief/subjective insomnia assessments. The present study showed that the abnormal brain features of MDD with different insomnia symptom. Importantly, the posterior and anterior parts of the hippocampus may play different roles in the presence or absence of insomnia in patients with MDD.

Empathy, including cognitive and emotional empathy, refers to the ability to infer the mental states of others and to the capacity to share emotions. The neural mechanisms involved in empathy are complex and not yet fully understood, and previous studies have shown that both cognitive and emotional empathy are closely associated with the inferior frontal gyrus (IFG). In this study, we examined whether empathy can be modulated by high-definition transcranial direct current stimulation (HD-tDCS) of the right IFG. Twenty-three healthy participants took part in all three experimental conditions (i.e., anodal, cathodal and sham stimulation) in a randomized order. Participants then completed the Chinese version of the Multifaceted Empathy Test (MET), which assesses both cognitive and emotional empathy. The results show that scores obtained for cognitive empathy following cathodal stimulation are significantly lower than those obtained following sham stimulation. In addition, scores obtained for cognitive empathy following anodal stimulation are higher than those obtained following sham stimulation, though the difference is only marginally significant. However, the results fail to show whether the stimulation of the right IFG via HD-tDCS plays a role in emotional empathy. Our results suggest that the right IFG plays a key role in cognitive empathy and indicate that HD-tDCS can regulate cognitive empathy by inducing excitability changes in the right IFG.

The ascending arousal system plays a crucial role in individuals' consciousness. Recently, advanced functional magnetic resonance imaging (fMRI) has made it possible to investigate the ascending arousal network (AAN) in vivo. However, the role of AAN in the neuropathology of human insomnia remains unclear. Our study aimed to explore alterations in AAN and its connections with cortical networks in chronic insomnia disorder (CID). Resting‐state fMRI data were acquired from 60 patients with CID and 60 good sleeper controls (GSCs). Changes in the brain's functional connectivity (FC) between the AAN and eight cortical networks were detected in patients with CID and GSCs. Multivariate pattern analysis (MVPA) was employed to differentiate CID patients from GSCs and predict clinical symptoms in patients with CID. Finally, these MVPA findings were further verified using an external data set (32 patients with CID and 33 GSCs). Compared to GSCs, patients with CID exhibited increased FC within the AAN, as well as increased FC between the AAN and default mode, cerebellar, sensorimotor, and dorsal attention networks. These AAN‐related FC patterns and the MVPA classification model could be used to differentiate CID patients from GSCs with 88% accuracy in the first cohort and 77% accuracy in the validation cohort. Moreover, the MVPA prediction models could separately predict insomnia (data set 1, R² = .34; data set 2, R² = .15) and anxiety symptoms (data set 1, R² = .35; data set 2, R² = .34) in the two independent cohorts of patients. Our findings indicated that AAN contributed to the neurobiological mechanism of insomnia and highlighted that fMRI‐based markers and machine learning techniques might facilitate the evaluation of insomnia and its comorbid mental symptoms.

Repetitive transcranial magnetic stimulation (rTMS) offers a promising approach for the treatment of insomnia; however, the precise targets and underlying neural mechanisms remain unclear. This randomized, wait-controlled trial aimed to evaluate the clinical efficacy of neuronavigated rTMS targeting the right dorsolateral prefrontal cortex (DLPFC) in chronic insomnia disorder (CID) and to identify potential neural mechanisms associated with therapeutic outcomes. Fifty patients with CID were randomized to receive 20 sessions of 1 Hz rTMS targeting the right DLPFC or to a waitlist control group. Stimulation coordinates were selected (MNI: 40,39,11) based on our previous neuroimaging meta-analysis, and were precisely localized using MRI-guided neuronavigation. Clinical assessments and resting-state fMRI were conducted before and after the intervention, respectively. Target-based functional connectivity (FC) analysis was used to map rTMS-associated network changes, while causal mediation analysis was used to examine the relationships between neural changes and clinical improvements. Compared to waitlist controls, the rTMS group showed greater improvements in insomnia and mood symptoms (all p < 0.001), with higher response rates (54.55 % vs. 9.09 %) and remission rates (68.18 % vs. 13.64 %). FC analysis showed significant group × time effects on the bilateral DLPFC, middle cingulate cortex, and right anterior cerebellar vermis. Mediation analysis indicated that FC changes in the right DLPFC mediated 24 % of the improvement in insomnia severity (Insomnia Severity Index, p = 0.048). These preliminary findings suggest that precision neuronavigated rTMS targeting the right DLPFC may alleviate insomnia symptoms, with the observed clinical improvements potentially related to the reorganization of the DLPFC network. While these results are encouraging, further research based on placebo-controlled study designs is required to confirm these effects and better understand the underlying mechanisms. This study provides preliminary evidence supporting the integration of precision targeting with neuroimaging to explore the mechanisms underlying the effects of rTMS in insomnia treatment.