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BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been increasingly used as a treatment modality for chronic insomnia disorder (CID). However, our understanding of the mechanisms underlying the efficacy of rTMS is limited.ObjectiveThis study aimed to investigate rTMS-induced alterations in resting-state functional connectivity and to find potential connectivity biomarkers for predicting and tracking clinical outcomes after rTMS.MethodsThirty-seven patients with CID received a 10-session low frequency rTMS treatment applied to the right dorsolateral prefrontal cortex. Before and after treatment, the patients underwent resting-state electroencephalography recordings and a sleep quality assessment using the Pittsburgh Sleep Quality Index (PSQI).ResultsAfter treatment, rTMS significantly increased the connectivity of 34 connectomes in the lower alpha frequency band (8–10 Hz). Additionally, alterations in functional connectivity between the left insula and the left inferior eye junction, as well as between the left insula and medial prefrontal cortex, were associated with a decrease in PSQI score. Further, the correlation between the functional connectivity and PSQI persisted 1 month after the completion of rTMS as evidenced by subsequent electroencephalography (EEG) recordings and the PSQI assessment.ConclusionBased on these results, we established a link between alterations in functional connectivity and clinical outcomes of rTMS, which suggested that EEG-derived functional connectivity changes were associated with clinical improvement of rTMS in treating CID. These findings provide preliminary evidence that rTMS may improve insomnia symptoms by modifying functional connectivity, which can be used to inform prospective clinical trials and potentially for treatment optimization.

Chronic insomnia disorder is one of the most common problems in postmenopausal women, exacerbated by underdiagnosis and improper treatment. This double-blinded, randomized, placebo-controlled trial was conducted to evaluate the potential of vitamin E to treat chronic insomnia as an alternative to sedative drugs and hormonal therapy. The study enrolled 160 postmenopausal women with chronic insomnia disorder, divided randomly into two groups. The vitamin E group received 400 units of mixed tocopherol daily, while the placebo group received an identical oral capsule. The primary outcome of this study was sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI), a self-evaluated and standardized questionnaire. The secondary outcome was the percentage of participants using sedative drugs. There were no significant differences in baseline characteristics between the study groups. However, the median PSQI score at baseline was slightly higher in the vitamin E group compared with the placebo (13 (6, 20) vs. 11 (6, 20); p-value 0.019). After one month of intervention, the PSQI score was significantly lower (indicating better sleep quality) in the vitamin E group compared with the placebo (6 (1, 18) vs. 9 (1, 19); p-value 0.012). Moreover, the improvement score was significantly higher in the vitamin E group compared with the placebo (5 (−6, 14) vs. 1 (−5,13); p-value < 0.001). In addition, there was a significant reduction in the percentage of patients using sedative drugs in the vitamin E group (15%; p-value 0.009), while this reduction was not statistically significant in the placebo group (7.5%; p-value 0.077). This study demonstrates vitamin E’s potential as an excellent alternative treatment for chronic insomnia disorder that improves sleep quality and reduces sedative drug use.

Background Many patients with chronic insomnia disorder (CID) have gastrointestinal (GI) symptoms. First-line insomnia medications do not treat GI problems. Acupuncture has a comprehensive regulative action on both CID and GI disorder and is receiving increasing attention. Recent studies indicate that both CID and GI diseases may cause abnormal brain activity. However, the neurological mechanism underlying the effect of acupuncture on such diseases is still unclear. The aim of this study is to explore the pathological mechanisms of CID with GI discomfort, as well as the main response characteristics of acupuncture treatment from multiple perspectives using multimodal magnetic resonance imaging (MRI). Methods A total of 60 participants with CID and GI disorders will be randomly divided into two groups (real acupuncture group and sham acupuncture group; ratio of 1:1). Patients will receive 20 sessions (five sessions per week) of real acupuncture treatment or sham acupuncture treatment. The primary outcome is the aggregate score on the Pittsburgh Sleep Quality Index. Secondary outcomes are scores on the Gastrointestinal Symptom Rating Scale, Self-Rating Anxiety Scale, and Self-Rating Depression Scale. Multimodal MRI scans and clinical assessments will be performed both at baseline and post-treatment. Another 30 age-, sex-, and education-matched healthy subjects will be recruited as controls and will receive MRI scans and clinical evaluations. Discussion This study aims to provide scientific evidence for the mechanism of acupuncture in treating CID with GI disorder using multimodal MRI imaging data on brain structure, function, and metabolism. Trial registration Chinese Clinical Trial Registry, ChiCTR1800017092 (URL: http://www.chictr.org.cn/showproj.aspx?proj=27173). Registered on July 11, 2018.

Jing-Jing Sun,1,2 Xiao-Min Liu,2 Chen-Yu Shen,2 Xiao-Qian Zhang,1,2 Gao-Xiang Sun,2 Kun Feng,2 Bo Xu,2 Xia-Jin Ren,1,2 Xiang-Yun Ma,1,2 Po-Zi Liu2 1Medical Center, Tsinghua University, Beijing, China, 2Department of Psychiatry, YuQuan Hospital, Tsinghua University, Beijing, China Purpose: Daytime complaints such as memory and attention deficits and failure to accomplish daily tasks are common in insomnia patients. However, objective psychological tests to detect cognitive impairment are equivocal. Neural function associated with cognitive performance may explain the discrepancy. The aim of this study was to investigate the hemodynamic response patterns of patients with chronic insomnia disorder (CID) using the noninvasive and low-cost functional neuroimaging technique of multichannel near-infrared spectroscopy (NIRS) in order to identify changes of neural function associated with cognitive performance.Patients and methods: Twenty-four CID patients and twenty-five healthy controls matched for age, right-hand dominance, educational level, and gender were examined during verbal fluency tasks (VFT) using NIRS. A covariance analysis was conducted to analyze differences of oxygenated hemoglobin (oxy-Hb) changes in prefrontal cortex (PFC) between the two groups and reduce the influence of the severity of depression. Pearson correlation coeffcients were calculated to examine the relationship between the oxy-Hb changes, with the severity of insomnia and depressive symptoms assessed by the Pittsburgh Sleep Quality Index (PSQI) and the Hamilton Rating Scale for Depression (HAMD).Results: The number of words generated during the VFT in CID groups showed no statistical differences with healthy controls. CID patients showed hypoactivation in the PFC during the cognitive task. In addition, we found that the function of left orbitofrontal cortex (OFC) during the VFT was significantly negatively correlated with the PSQI scores and the function of right dorsolateral PFC (DLPFC) was significantly negatively correlated with the HAMD scores.Conclusion: The present study detected dysfunctions in PFC in spite of intact performance which indicates the role of PFC in the neurophysiological underpinnings. Left OFC function is associated with insomnia symptoms and right DLPFC function is associated with depressive symptoms. Keywords: chronic insomnia disorder, near-infrared spectroscopy, NIRS, prefrontal cortex, verbal fluency task, depressive symptoms

Background Insomnia disorder is defined as a combination of dissatisfaction with sleep quantity or quality and a significant negative impact on daytime functioning. Chronic insomnia disorder refers to clinical symptoms of persistent insomnia at least three nights a week for at least 3 months. Prevalence estimates of insomnia disorder range from 12% to 20% in the adult population, with approximately 50% having a chronic course. The potential side effects of hypnotic medications hinder their clinical application. Thus, traditional Chinese medicine is considered as an alternative option for treating insomnia. Objective To evaluate the efficacy and safety of suanzaoren decoction (SZRD), a classic Chinese herbal prescription, for adult chronic insomnia disorder. Methods/analysis This is a randomised, double-blind, double-dummy, placebo-controlled clinical trial. A total of 150 patients with chronic insomnia disorder are randomised, allocated in a ratio of 1:1:1 to three groups: intervention group, control group and placebo group. The intervention group receives SZRD granule plus zolpidem tartrate (ZT) placebo; the control group receives ZT tablet plus SZRD granule placebo; and the placebo group receives ZT placebo and SZRD granule placebo. The patients receive medicine or placebo for 5 weeks and are followed up at 20 weeks. The primary outcome measures are polysomnography and Pittsburgh Sleep Quality Index. Secondary outcome measures are the Insomnia Severity Index, sleep diary and safety assessment. Outcomes will be assessed at baseline and after treatment. Trial registration number ChiCTR-IOR-16009198. pre-results.