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Objective: To assess efficacy of Chinese medicine (CM) on insomnia considering characteristics of treatment based on syndrome differentiation. Methods: A total of 116 participants aged 18 to 65 years with moderate and severe primary insomnia were randomized to the placebo (n=20) or the CM group (n=96) for a 4-week treatment and a 4-week follow-up. Three CM clinicians independently prescribed treatments for each patient based on syndromes differentiation. The primary outcome was change in total sleep time (TST) from baseline. Secondary endpoints included sleep onset latency (SOL), wake time after sleep onset (WASO), sleep efficiency, Pittsburgh Sleep Quality Index (PSQI) and CM symptoms. Results: The CM group had an average 0.6 h more (95% confidence interval (CI): 0.3–0.9, P<0.001) TST and 34.1% (10.3%–58.0%, P=0.005) more patients beyond 0.5 h TST increment than that of the placebo group. PSQI was changed −3.3 (−3.8 to −2.7) in the CM group, a −2.0 (−3.2 to −0.8, P<0.001) difference from the placebo group. The CM symptom score in the CM group decreased −2.0 (−3.3 to −0.7, P=0.003) more than the placebo group. SOL and WASO changes were not significantly different between groups. The analysis of prescriptions by these clinicians revealed blood deficiency and Liver stagnation as the most common syndromes. Prescriptions for these clinicians displayed relative stability, while the herbs varied. All adverse events were mild and were not related to study treatment. Conclusion: CM treatment based on syndrome differentiation can increase TST and improve sleep quality of primary insomnia. It is effective and safe for primary insomnia. In future studies, the long-term efficacy validation and the exploratory of eutherapeutic clinicians' fixed herb formulas should be addressed (Registration No. NCT01613183). [ABSTRACT FROM AUTHOR]

Background: The neuropathologic mechanism of primary insomnia (PI) of females remains unclear. This study aims to investigate the features of amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in females with PI using functional magnetic resonance imaging (fMRI), and then explore the abnormalities of functional connectivity (FC). Materials and methods: A total of 39 female PI patients and 31 female healthy controls (HC) were enrolled in the study. The sleep condition was assessed using the Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI), and their depressive symptom was evaluated using the Hamilton Depression Scale (HAMD-24). The rs-fMRI was once conducted for every subject. ReHo, ALFF, and ROI-based FC were used to analyze the changes of brain function. Results: ALFF values were increased in the Cerebelum_4_5_L, as well as decreased ALFF in the bilateral Frontal_Sup_Medial (SFGmed), Angular_L (ANG.L), Parietal_ Inf_R (IPL.R), SupraMarginal_R (SMG.R), and Postcentral_R (PoCG.R). ReHo values were increased in the Temporal_Pole_Mid_R (TPOsup.R), as well as decreased ReHo in the Insula_R (INS.R), Frontal_Inf_Oper_R (ORBinf.R), Putamen_R (PUT.R), Rolandic_Oper_R (ROL.R), bilateral Cingulum_Post (PCG), bilateral Frontal_Sup_ Medial (SFGmed), bilateral anterior cingulate and paracingulate gyri (ACG), and the bilateral precuneus (PCUN). Across the entire brain, there was a decline in the FC between Angular_R and Frontal_Sup_Medial_L. Conclusion: Alterations in brain regions of female patients with PI involved multiple functional networks, including the default mode network, the salience network, the central executive network, and the limbic network. Reduced coordination between functional networks may be an important mechanism for insomnia and may lead to reduced cognitive function and decision-making ability. [ABSTRACT FROM AUTHOR]

Chronic insomnia has the potential to significantly impact physical well-being, occupational performance, and overall quality of life. This review summarizes the clinical and basic research on the central regulatory mechanism of acupuncture in treating primary insomnia (PI), aiming to explore the clinical effectiveness and possible mechanism of acupuncture in treating PI. The currently available drugs for insomnia exhibit notable adverse effects and tend to induce dependence. Empirical evidence from clinical investigations has demonstrated that acupuncture has a favorable safety profile while substantially enhancing the sleep quality of individuals diagnosed with PI. The combination of acupuncture and medication has been shown to augment the therapeutic efficacy of medication while reducing the dosage and mitigating the occurrence of unwanted effects. A review of the current clinical and basic research on the effects of acupuncture on central alterations in PI patients revealed that acupuncture exerts a regulatory influence on the functional activity of brain regions implicated in cognitive and emotional processes. Additionally, acupuncture has been found to impact metabolite levels and circadian clock gene expression and enhance inflammatory responses and energy metabolism. Notably, a single acupuncture intervention had a modulatory effect on functional brain regions similar to that of cumulative acupuncture. The current clinical trials on acupuncture have been limited in scale, and basic research has focused on a single objective. With the continuous progress of brain research, extensive clinical randomized controlled trials of high quality can be combined with various neuroimaging technology modalities. Moreover, different targets and pathways can be explored through basic research. This may serve to enhance the understanding of the fundamental central nervous system mechanisms involved in the efficacy of acupuncture in treating PI.

Objective: The study retrospectively evaluated the effects of quetiapine on sleep in primary insomnia and neurodegenerative diseases using polysomnographic data. Materials and Methods: Between January 1, 2010, and June 1, 2023, the records of 49 patients who were followed up in the sleep outpatient clinic of the neurology department of our hospital and who underwent polysomnography examination were retrospectively reviewed. Patients aged between 18 and 65 years with primary insomnia and neurodegenerative diseases were included in the study. Results: The mean age of 49 patients (26 females and 23 males) were 56.67 years. The mean quetiapine dose was 59.37. Sleep latency, stage 1 (N1) duration, stage 2 (N2) duration, mean and minimum SO2 and apnea-hypopnea index were similar. Total sleep duration, stage 3 (N3) duration and rapid eye movement (REM) sleep duration were higher in neurodegenerative patients. N3 duration was shorter in patients with primary insomnia on quetiapine. Sleep duration and REM duration were longer in the neurodegenerative group and sleep latency was longer in primary insomnia in quetiapine users. Among quetiapine users, the N2 sleep percentage was higher and the nonREM 3 sleep percentage was lower in primary insomnia, whereas there was no difference in sleep percentages in neurodegenerative patients. Conclusion: Quetiapine is an atypical antipsychotic agent. It shortens sleep latency and decreases the percentage of REM sleep and wake time. It increases total sleep time, sleep efficiency, and N2 sleep. In this study, in primary insomnia patients using quetiapine, N3 sleep duration was shorter and sleep percentage was lower, whereas N2 sleep percentage was longer. There has been no placebo-controlled study of any antipsychotic drug for treating insomnia.

Objective: The study retrospectively evaluated the effects of quetiapine on sleep in primary insomnia and neurodegenerative diseases using polysomnographic data. Materials and Methods: Between January 1, 2010, and June 1, 2023, the records of 49 patients who were followed up in the sleep outpatient clinic of the neurology department of our hospital and who underwent polysomnography examination were retrospectively reviewed. Patients aged between 18 and 65 years with primary insomnia and neurodegenerative diseases were included in the study. Results: The mean age of 49 patients (26 females and 23 males) were 56.67 years. The mean quetiapine dose was 59.37. Sleep latency, stage 1 (N1) duration, stage 2 (N2) duration, mean and minimum SO2 and apnea-hypopnea index were similar. Total sleep duration, stage 3 (N3) duration and rapid eye movement (REM) sleep duration were higher in neurodegenerative patients. N3 duration was shorter in patients with primary insomnia on quetiapine. Sleep duration and REM duration were longer in the neurodegenerative group and sleep latency was longer in primary insomnia in quetiapine users. Among quetiapine users, the N2 sleep percentage was higher and the nonREM 3 sleep percentage was lower in primary insomnia, whereas there was no difference in sleep percentages in neurodegenerative patients. Conclusion: Quetiapine is an atypical antipsychotic agent. It shortens sleep latency and decreases the percentage of REM sleep and wake time. It increases total sleep time, sleep efficiency, and N2 sleep. In this study, in primary insomnia patients using quetiapine, N3 sleep duration was shorter and sleep percentage was lower, whereas N2 sleep percentage was longer. There has been no placebo-controlled study of any antipsychotic drug for treating insomnia. [ABSTRACT FROM AUTHOR]

Insomnia is very common in psychiatric disorders, but the polysomnographic (PSG) characteristics of insomnia in various psychiatric disorders are still not agreed upon. This study aimed to investigate the characteristics of PSG and its relationship with metabolic indicators in insomnia patients with affective disorders and primary insomnia (PI) patients. A total of 38 patients with PI, 44 major depressive disorder patients with insomnia (DI), 49 generalized anxiety disorder patients with insomnia (GI), and 19 bipolar mania patients with insomnia (BI) were included. PSG was used to detect sleep problems in subjects, and biochemical indicators were also collected. The results of this study found that subjects with BI were lower on REM sleep latency (RL), awakenings number (AN), number of microarousals (NM), and apnea–hypopnea index (AHI) than those with DI and GI, and lower on RL and AN than those with PI. Subjects with PI had lower NM and AHI than those with DI and GI. Patients with DI had a higher RL than those with GI. All results passed Bonferroni correction (p < 0.00078). No differences in biochemical indices were found among the four groups of subjects. Also, AHI was found to be positively correlated with free triiodothyronine (FT3) and fasting blood glucose in subjects. This study suggests that various psychiatric disorders may have their characteristics in terms of PSG parameters, which prompted us to focus on the PSG characteristics of these disorders when assessing them, as well as to focus on their biochemical indicators. • The study aimed to investigate the PSG characteristics of insomnia in four psychiatric disorders. • Patients with BI had lower REM sleep latency, AN, NM, and AHI than those with other disorders studied. • Patients with PI had lower NM and AHI compared to patients with MI and GI. • Patients with MI had a higher REM sleep latency than those with GI. • FT3 and FBG correlated positively with AHI in all insomnia patients, indicating the importance of biochemical assessment. [ABSTRACT FROM AUTHOR]

Study objectives: Primary insomnia (PI) triggers a decline in cognitive function, and the thalamus plays an integral role in this process; however, the mechanisms are unclear. The purpose of this study was to investigate the altered functional connectivity (FC) of the thalamus in PI patients with mild cognitive impairment (MCI) and to explore the potential neural mechanisms of thalamic involvement in these patients. Methods: This case–control study was conducted in older adults from various communities in Fuzhou, China with a PI diagnosis. These participants underwent neuropsychological assessment and were matched in a 1:2 ratio to the healthy control (HC) group and the PI group according to sex, age, and education level. Resting‐state functional magnetic resonance imaging was used to explore changes in thalamic FC in PI patients. To further compare changes in thalamic and whole‐brain FC, we further divided the PI group into cognitively normal patients and patients with MCI according to the diagnostic criteria for MCI. The relationship between abnormal FC and cognitive function was investigated. Results: The 28 HCs and 58 participants with PI showed significant differences in Montreal Cognitive Assessment (MoCA) scores (p =.044). In comparison to the HC group, the PI group showed enhanced FC of the occipital thalamus with the left inferior occipital gyrus, right lingual gyrus, left middle temporal gyrus, left superior marginal gyrus, left dorsolateral superior frontal gyrus, and right anterior central gyrus. The MoCA total score and the executive function, attention, and abstraction scores of PI patients with MCI (PI–MCI) were worse than those of PI patients without MCI. In comparison to the simple PI group, FC was enhanced in the PI–MCI group between the left occipital thalamus and the middle occipital gyrus, and between the right occipital thalamus and the right superior frontal gyrus, left middle frontal gyrus, right superior occipital gyrus, and orbital inferior frontal gyrus. There was a significant negative correlation between the MoCA total score and the enhanced FC between the right occipital thalamus and right superior occipital gyrus (r = −.419, p =.042). Conclusion: The early onset of cognitive impairment in patients with PI is associated with altered FC between the thalamus and the cortex. Enhanced FC between the thalamus and the visual cortex, that is, the superior occipital gyrus, which is involved in attentional processing, may play a role in the early onset of cognitive impairment in insomnia patients. Moreover, due to the fact that PI patients "overdraw" the compensatory capacity of these brain regions earlier, the PI–MCI may fall into the abyss of "decompensation" faster and face more severe cognitive impairments. [ABSTRACT FROM AUTHOR]

Background and Objectives: Adults aged 18?60 years are recommended to have a sound sleep of 7 or more hours per night. Lack of sleep due to sleep disturbances, such as insomnia, causes significant impairment in an individual's quality of life. Insomnia shares many similarities with the condition mentioned in Ayurveda as nidranasha. The general Ayurvedic approach to insomnia includes a combination of therapies and internal medications. Ayurvedic therapies such as shirodhara (oil-dripping therapy), takradhara (buttermilk-dripping therapy), shirobasti (retention of oil on the head), and shirolepa (application of medicated paste over the head) are commonly used in the treatment of insomnia. However, no studies have been conducted to evaluate the role of shirolepa although it is widely practiced by Ayurvedic practitioners. Therefore, this study aims to evaluate the effect of shirolepa in adults with primary insomnia using subjective and objective parameters. Design: Two group pretest post-test design with randomization and waitlist control with 1:1 allocation ratio. Methods: The protocol adheres to Standard Protocol Items: Recommendations for Interventional Trials guidelines. Thirty-eight adults aged between 18 and 60 years with primary insomnia will be randomly assigned to intervention and waitlist control groups in 1:1 allocation ratio. The intervention group will receive shirolepa (application of medicinal herbal paste on the head) for 7 consecutive days. The control group will receive shirolepa after the post-test assessment. Our primary outcome is insomnia severity, which is evaluated using the Insomnia Severity Index. Secondary outcome measures will be evaluated using Pittsburgh Sleep Quality Index, Sleep Diary, Epworth Sleepiness Scale, and wrist actigraphy. Ethics and Dissemination: Ethical clearance was obtained from the Institutional Ethics Committee (01/PK/IEC/2021), and the trial was registered in the Clinical Trials Registry of India (CTRI/2022/09/045226). The study results will be reported and published in peer-reviewed journals.

Abstract Background Benzodiazepines, such as flunitrazepam, may be at risk of disinhibition, leading to aggressiveness, impulsivity, self‐harm, and possibly suicide attempts, whereas ramelteon may be far from disinhibition. Case Presentation In a 43‐year‐old female with primary insomnia, flunitrazepam alone did not induce any type of disinhibition, but the addition of ramelteon to flunitrazepam brought about disinhibition, leading to aggressiveness and finally to her suicide attempt. Her disinhibition rapidly subsided as soon as ramelteon alone was discontinued. Conclusion These findings suggest that a suicide attempt may occur during ramelteon and flunitrazepam combination in a susceptible patient.

Background: Primary insomnia (PI) refers to syndromes of difficulty falling asleep, poor sleep quality, early awakening, and difficulty falling asleep after waking up. Although there have been numerous studies, the specific etiology and pathogenesis of PI are still misunderstanding. In recent years, the gut microbiota has been proved to be involved in the metabolism of many mental disorders. But the specific mechanisms of its involvement in PI have not been fully elucidated. This study aims to explore the relationship between the gut microbiota and the symptoms, cognitive function changes in PI. Methods: In this study, the gut microbiota of PI patients and healthy controls was profiled by performing stool 16s rRNA gene sequencing. The co-occurrence network was constructed by using Weight Gene Co-expression Network Analysis (WGCNA) algorithm. The correlation between gut microbiota associated pathways and traits in PI were predicted. Results: WGCNA results demonstrated several Operational Taxonomic Units (OTU) modules are correlated to symptoms. By using PICRUSt2 software, we predicted the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of microbiota in modules. For instance, sleep efficiency may be correlated with the presence of Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane and chlorobenzene degradation. Total sleep time may be correlated with the presence of Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation and Biosynthesis of unsaturated fatty acids. The severity of insomnia may be correlated with Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism and RNA polymerase. Change of name score in Montreal Cognitive Assessment (MoCA) may be correlated with Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation in Gut Microbiota (GM). Conclusion: This study revealed the potential relationships between gut microbiota and PI. By using pathway prediction and enrichment analysis, we concluded many metabolic pathways may associated with some important traits of insomnia patients, including sleep efficiency, severe insomnia, total sleep time and change of name score in MoCA. The metabolic pathways include Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane, chlorobenzene degradation, Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation.Our study demonstrated that PI patients demonstrate significant changes in gut microbiota, which will help delineate the relationship between gut microbiota and syndromes of PI.

Abstract Study objectives Primary insomnia (PI) triggers a decline in cognitive function, and the thalamus plays an integral role in this process; however, the mechanisms are unclear. The purpose of this study was to investigate the altered functional connectivity (FC) of the thalamus in PI patients with mild cognitive impairment (MCI) and to explore the potential neural mechanisms of thalamic involvement in these patients. Methods This case–control study was conducted in older adults from various communities in Fuzhou, China with a PI diagnosis. These participants underwent neuropsychological assessment and were matched in a 1:2 ratio to the healthy control (HC) group and the PI group according to sex, age, and education level. Resting‐state functional magnetic resonance imaging was used to explore changes in thalamic FC in PI patients. To further compare changes in thalamic and whole‐brain FC, we further divided the PI group into cognitively normal patients and patients with MCI according to the diagnostic criteria for MCI. The relationship between abnormal FC and cognitive function was investigated. Results The 28 HCs and 58 participants with PI showed significant differences in Montreal Cognitive Assessment (MoCA) scores (p = .044). In comparison to the HC group, the PI group showed enhanced FC of the occipital thalamus with the left inferior occipital gyrus, right lingual gyrus, left middle temporal gyrus, left superior marginal gyrus, left dorsolateral superior frontal gyrus, and right anterior central gyrus. The MoCA total score and the executive function, attention, and abstraction scores of PI patients with MCI (PI–MCI) were worse than those of PI patients without MCI. In comparison to the simple PI group, FC was enhanced in the PI–MCI group between the left occipital thalamus and the middle occipital gyrus, and between the right occipital thalamus and the right superior frontal gyrus, left middle frontal gyrus, right superior occipital gyrus, and orbital inferior frontal gyrus. There was a significant negative correlation between the MoCA total score and the enhanced FC between the right occipital thalamus and right superior occipital gyrus (r = −.419, p = .042). Conclusion The early onset of cognitive impairment in patients with PI is associated with altered FC between the thalamus and the cortex. Enhanced FC between the thalamus and the visual cortex, that is, the superior occipital gyrus, which is involved in attentional processing, may play a role in the early onset of cognitive impairment in insomnia patients. Moreover, due to the fact that PI patients “overdraw” the compensatory capacity of these brain regions earlier, the PI–MCI may fall into the abyss of “decompensation” faster and face more severe cognitive impairments.

Summary: This study examined the integrity of white matter tracts in 25 participants with primary insomnia (PI), 50 participants with major depressive disorder (MDD), and 25 healthy controls. Seven white matter tracts, selected based on prior research, were quantified by fractional anisotropy (FA) as well as by related measures of diffusivity using diffusion tensor imaging (DTI) on a 3‐T scanner. All 100 participants were free of significant medical, psychiatric (excluding the MDD group) and sleep disorders (excluding the PI group), were free of central nervous system medications, and completed an extensive clinical assessment. Subjective and objective sleep measures revealed significant sleep disruption in both the PI and MDD groups. Relative to the controls, both the PI and MDD groups demonstrated impaired integrity in three of the seven white matter tracts: the genu of the corpus callosum (GenuCC), the superior longitudinal fasciculus (SLF), and the inferior longitudinal fasciculus (ILF). We demonstrated reduced FA in the GenuCC, reduced FA and reduced axial diffusivity (AD) in the SLF, as well as reduced AD and radial diffusivity in the ILF. Finally, in an exploratory analysis of the combined cohorts, FA in the GenuCC and FA in the SLF were negatively correlated with depression severity and positively correlated with total sleep time. Abnormalities documented in the GenuCC, SLF and ILF, and present in both the PI and MDD groups may suggest some shared neurobiology. [ABSTRACT FROM AUTHOR]

Background: Insomnia is the second most commonly presenting symptom, after pain, in clinics. Insomnia prevalence in India is 28.1 %. Objective: This study explores the effect of Mamsyadi Kwatha in the management of primary insomnia. Materials and methods: Fifty patients attending KLE Ayurveda hospital meeting the diagnostic criteria of primary insomnia (DSM IV TR) were enrolled. Patients were randomly divided into two groups: group MK and TK. Intervention in group MK was 24 ml of Mamsyadi Kwatha twice a day and in group TK was 24 ml of Tagaradi Kwatha twice a day for 30 days. Assessment was done through primary outcome measures like Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), insomnia severity index (ISI). Secondary outcome measures were sleep diary recordings of past 15 days and depression anxiety and stress scale (DASS). Follow ups were at base line, 15th and 30th day of interventions. Laboratory assessments of liver function test, haemoglobin, and serum creatinine levels were carried at base line and 30th day of intervention. Results: Effect on primary and secondary outcomes showed that both the drugs were comparable. = Within group comparison of both the drugs showed that they produced significant improvement in PSQI, ESS, ISI, sleep diary variables, and DASS. However, Mamsyadi kwath has additional benefit of early recovery in total sleep. Both the drugs showed good safety profile evaluated through serum creatinine and liver function tests. Conclusion: The effects of Mamsyadi Kwatha is comparable to Tagaradi Kwatha. Both drugs produced significant improvement in clinical assessments of insomnia, anxiety, depression, and stress.

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Introduction: The brain waves pattern in primary insomniacs is different from healthy subjects. Studies have shown that binaural beats can alter the pattern of brain waves in healthy individuals; however, the efficacy of binaural beats in altering the pattern of brain waves in primary insomniacs has not yet been investigated. This study aims to evaluate the efficacy of theta binaural beat on the absolute power of theta activity in primary insomniacs. Methods: This study was a randomized clinical trial with experimental and control groups. The primary insomniacs received theta binaural beats in the experimental group while the control group received white noise. Their brain waves were recorded by electroencephalogram for 25 min; the first 5 min was without stimulus (first block), the next was followed by 15 min of receiving stimulus (binaural beat or white noise), and the last 5 min without stimulus (fifth block). The Matlab software, version R2019a, EEGLAB toolbox, and SPSS software, version 24 were used to analyze the data. Results: The absolute power of theta activity in the experimental group was significantly higher in the last block compared to the first block in all brain lobes (P<0.05). The largest changes in theta activity were in the temporal and parietal lobes, and the last one was in the prefrontal lobe. In the control group, none of the brain lobes showed significant differences in the last block compared to the first block. Conclusion: Theta binaural beat can alter the absolute power of theta activity in primary insomniacs. The implications of the study are discussed. [ABSTRACT FROM AUTHOR]

Objectives: To quantitatively measure the T1 value, T2 value, proton density (PD) value, and cerebral blood flow (CBF) in young and middle-aged primary insomnia (PI) patients, and analyze the correlations between relaxation times, PD, and CBF to explore potential brain changes. Methods: Cranial magnetic resonance (MR) images of 44 PI patients and 30 healthy subjects were prospectively collected for analysis. The T1, T2, PD, and CBF values of the frontal lobe, parietal lobe, temporal lobe, and occipital lobe were independently measured using three-dimensional arterial spin labeling (3D-ASL), synthetic magnetic resonance imaging (syMRI) and a whole-brain automatic segmentation method. The differences of these imaging indices were compared between PI patients and healthy subjects. Follow-up MR images were obtained from PI patients after 6 months to compare with pre-treatment images. The Wilcoxon signed rank test and Spearman rank were used for statistical analysis. Results: Bilateral CBF asymmetry was observed in 38 patients, with significant differences in both the T2 value and CBF between the four lobes of the brain (p < 0.01). However, no significant difference was found in the T1 and PD values between the bilateral lobes. A negative correlation was found between CBF and T2 values in the right four lobes of patients with primary insomnia (PI). During follow-up examinations, five PI patients showed a disappearance of insomnia symptoms and a decrease in CBF in both brain lobes. Conclusion: Insomnia symptoms may be associated with high CBF, and most PI patients have higher CBF and lower T2 values in the right cerebral hemispheres. The right hemisphere appears to play a critical role in the pathophysiology of PI. The 3D-ASL and syMRI technologies can provide a quantitative imaging basis for investigating the brain conditions and changes in young and middle-aged PI patients. [ABSTRACT FROM AUTHOR]

Bin Ji,1 Min Dai,2 Zhongwei Guo,3 Jiapeng Li,4 Yulin Cao,4 Zhenzhong Zhang,3 Yan Zhang,3 Xiaozheng Liu2 1Department of Anesthesiologyand Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2Department of Radiology of the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 3The Sleep Medical Center of Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310012, People’s Republic of China; 4Department of Radiology of Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310012, People’s Republic of ChinaCorrespondence: Yan ZhangThe Sleep Medical Center of Tongde Hospital of Zhejiang Province, No. 234 Gucui Road, Hangzhou, Zhejiang, 310012, People’s Republic of ChinaEmail zhyan73@163.comXiaozheng LiuDepartment of Radiology of the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, No. 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, People’s Republic of ChinaEmail lxz_2088@hotmail.comObjective: It is unclear whether the patterns of functional connectivity density (FCD) differ between patients with primary insomnia (PI) and healthy subjects. In the present study, we investigated the features of FCD in patients with PI using resting-state functional MRI (rsfMRI).Methods: rsfMRI datasets of 32 patients with PI and 34 healthy controls (HCs) were obtained using a 3-Tesla scanner. FCD analysis was performed to compare voxels with abnormal whole-brain functional connectivity with other voxels among patients with PI and HCs. Abnormal brain regions were then used as seed points for FC analysis.Results: Compared with HCs, patients with PI exhibited significantly decreased FCD in the left medial frontal gyrus and increased FCD in the left supplementary motor area (SMA). With the left medial frontal gyrus as the seed point, patients with PI showed decreased FC between the left medial frontal gyrus and the left fusiform gyrus compared with HCs. With the left SMA as the seed point, patients with PI exhibited increased FC between the left SMA and the right anterior cingulate gyrus. Correlation analysis revealed that the increased FCD values in the left SMA were positively correlated with sleep latency in patients with PI.Conclusion: Default-mode network and SMA dysfunctions may be related to the pathophysiology of PI.Keywords: primary insomnia, resting-state functional magnetic resonance imaging, functional connectivity density

(1) Background: The purpose of this study was to investigate the efficacy and safety of transcutaneous vagus nerve stimulation (t-VNS) in the treatment of primary insomnia. (2) Methods: This is a single center, randomized, double-blind study. A total of 30 patients diagnosed with primary insomnia were randomly divided into two groups to receive 20 Hz t-VNS in either the auricular concha area (treatment group) or periauricular area (control group), twice a day for 20 min during a one-month study period. The effective rate of treatment, defined as a ≥50% reduction of the Pittsburgh Sleep Index Scale (PSQI) after treatment, was compared between the two groups as the primary outcome. Response rate (defined as ≥10% change in the PSQI score), and changes in the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores were also assessed. (3) Results: After one month of treatment, the PSQI score of the treatment group decreased significantly (p = 0.001). The effective rate of the treatment group (73% vs. 27%, p = 0.027) was significantly higher than that of the control group. No statistical differences in changes of HAMA and HAMD scores were detected between the two groups. There were no complications in all patients. (4) Conclusion: T-VNS appeared to be a safe and effective treatment for primary insomnia. [ABSTRACT FROM AUTHOR]

Cognitive behavioral therapy for insomnia (CBT-I) is effective for not only primary insomnia (PI) but also comorbid insomnia (CI; insomnia associated with psychiatric/physical diseases or other types of sleep disorders). This study aimed to compare the outcomes of CBT-I implemented in the same manner between patients with PI and CI. In total, 41 adult patients who had completed CBT-I were enrolled in this retrospective analysis and divided into a PI group and a CI group. The authors then examined and compared the significance of changes after therapy between the two groups. The magnitude of improvement on the Japanese version of the Insomnia Severity Index (ISI-J) was analyzed as the primary endpoint. In the PI group (n = 24), both the ISI-J score and the dose of hypnotics decreased significantly following CBT-I. On the other hand, in the CI group (n = 17), only the dose of hypnotics decreased significantly; no statistically significant improvement was seen in the ISI-J score. Sleep onset latency and sleep quality rating in recorded sleep diaries were significantly correlated with improved ISI-J scores in the CI group only. CBT-I was shown to be effective for CI, but its efficacy for CI was inferior to that for PI in terms of impact on sleep and mental condition. These results suggest that in addition to the basic components of CBT-I, treatment for CI, especially when accompanied by severe insomnia symptoms, should include approaches targeting the comorbid disease. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of acupuncture with mind regulating method on heart rate variability in patients with primary insomnia. Methods: A total of 120 patients with primary insomnia treated in the Insomnia Clinic of Acupuncture Center of Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical University from July 2014 to May 2017 were enrolled. The patients were randomly divided into the treatment group and the sham acupuncture group with 60 cases in each group. Patients in the treatment group were treated by acupuncture with mind regulating method. Patients in the sham acupuncture group were treated with acupuncture at ineffective points. The treatment should be given 3 times in a week, and continuous 4 weeks of treatment was needed. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the changes of sleep quality. Fatigue Scale-14 (FS-14) was used to evaluate the changes of fatigue degree. In addition, the changes of heart rate variability (HRV) before and after treatment were detected respectively, in order to analyze the regulating effect of acupuncture on sympathetic and parasympathetic function of primary insomnia. Results: After 4 weeks of treatment and during the follow-up period, (1) PSQI score: Compared with the sham acupuncture group, the PSQI score of the treatment group decreased significantly, and the difference was statistically significant (P < 0.01). (2) FS-14 score: Compared with the sham acupuncture group, the difference in the treatment group at the fourth week of treatment was statistically significant (P < 0.05). (3) Low-frequency power (LF) and LF/HF index of heart rate variability: LF and LF/HF in the treatment group after treatment were significantly lower than those before treatment. High-frequency power (HF) in the treatment group after treatment increased compared with that before treatment, but there was no significant difference (P > 0.05). LF and LF/HF in the treatment group were significantly lower than those in the sham acupuncture group at the fourth week of treatment, and the difference was statistically significant (P < 0.05). After treatment, HF in the treatment group was higher than that in the sham acupuncture group, but there was no statistical significance (P > 0.05). Conclusions: The acupuncture with mind regulating method can improve sleep quality, reduce fatigue degree, improve heart rate variability, and reduce sympathetic excitability in patients with primary insomnia, as well as balance the excitability of sympathetic and parasympathetic nerves. [ABSTRACT FROM AUTHOR]

Background: Acupuncture has been widely practiced for primary insomnia (PI). However, the relative benefit and harm among acupuncture therapies remain uncertain.Objectives: To compare and evaluate the effect differences of multiple acupuncture therapies for patients with PI.Methods: Systematic literature search for randomized controlled trials (RCTs). Pairs of reviewers independently conducted literature screening, data extraction, and risk of bias assessment. Meta-analysis was conducted using R and Stata software. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to assess certainty of evidence and interpret results.Results: Fifty-seven RCTs with 4678 patients were included. Compared with usual treatment, multiple acupuncture therapies showed a better effect for Pittsburgh sleep quality index score. And acupoints catgut embedding (ACE) was proved to be the most effective with a moderate certainty of evidence; auricular acupressure or auricular acupuncture plus manual acupuncture (AP + MA), electroacupuncture plus acupoint application (EA + APA), and intradermal needle (IN) might be also the most effective with low certainty of evidence. ACE, ACE + MA, AP + MA, EA, EA + APA, HPN, MA and PBN + MA showed significantly improvement in effective rate when compared with usual treatment. Insufficient evidence reported on Epworth Sleepiness Scale, Athens Insomnia Scale, and recurrence rate. The most common slight adverse events mainly included hematoma, pain, headache, and bleeding.Conclusions: With moderate to low certainty of evidence, multiple acupuncture therapies showed impressive insomnia improvement, especially ACE, AP + MA, and EA + APA. Differences between therapies were small or insignificant and based-on low or very low certainty of evidence. [ABSTRACT FROM AUTHOR]

Primary insomnia (PI) is among the most prevalent sleep-related disorders and has a far-reaching impact on daytime functioning. Repetitive transcranial magnetic stimulation (rTMS) has drawn attention because of its effectiveness and safety. The purpose of the current study was to detect changes in the topological organization of whole-brain functional networks and to determine their associations with the clinical treatment effects of rTMS. Resting-state functional magnetic resonance imaging (rsfMRI) data from 32 patients with PI were collected and compared with findings from 32 age- and gender-matched healthy controls (HCs). The patients were treated with Stanford accelerated intelligent neuromodulation therapy, which is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation protocol. Graph theoretical analysis was used to construct functional connectivity matrices and to extract the attribute features of small-world networks in insomnia. Scores on the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the associations between these clinical characteristics and functional metrics, were the primary outcomes. At baseline, the patients with PI showed inefficient small-world property and aberrant functional segregation and functional integration compared with the HCs. These properties showed renormalization after individualized rTMS treatment. Furthermore, low functional connectivity between the right insula and left medial frontal gyrus correlated with improvement in ISI scores. We highlight functional network dysfunctions in PI patients and provide evidence into the pathophysiological mechanisms involved and the possible mode of action of rTMS. [ABSTRACT FROM AUTHOR]

Insomnia is a common problem, affecting individuals' health and quality of life. Among several therapies used to treat this condition, spiritual interventions are suggested to have beneficial outcomes on sleep disturbances. Nevertheless, a systematic compilation of the evidence available is still needed in the literature in order to scientifically investigate the topic. To examine the most common spiritual interventions proposed to treat sleep disorders and to assess the scientific evidence of these interventions. This is a scoping literature review conducted by independent researchers on the following databases: PubMed, SCOPUS, Web of Science, Cochrane Library and OpenGrey. A boolean expression was used, and all studies published in the last 5 years investigating the role of spiritual or religious interventions on insomnia were included. From a total of 3257 articles retrieved in our search, ten studies were included in the final analysis. There is a wide array of techniques used to treat insomnia or the mental disorders associated with insomnia, such as mantra, yoga, mindfulness, praying/meditation, daily spiritual experiences, psycho-religious training and intervention. The included studies showed a positive influence of spiritual/religious interventions on insomnia directly and indirectly. However, there is a scarcity of clinical trials and most studies have small sample sizes and used only subjective measures, resulting in a low evidence. The results of the present review point to a promising role of spirituality and religion on better sleep outcomes, particularly in the improvement in insomnia. However, the heterogeneity and the quality of these studies suggest caution while interpreting these findings. More clinical trials are needed in this area to provide a recommendation of these methods in clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Background Primary insomnia (PI) is characterized by difficulties in initiating sleep or maintaining sleep, which lead to many serious diseases. Acupuncture for PI has drawn attention with its effectiveness and safety. However, the operation of choosing acupoints lacks scientific suggestion. Our trial aims to provide reference and scientific basis for the selection of acupoints and to explore its possible mechanism. Methods A patient-assessor-blinded, randomized and sham controlled trial was designed to compare the efficacy of 5-weeks acupuncture at a single acupoint, the combination of multi-acupoints, and a sham point. The Pittsburgh sleep quality index and Athens Insomnia Scale questionnaire were used for the primary clinical outcomes, while polysomnography was performed for the secondary clinical outcomes. The resting state functional MRI was employed to detect the cerebral responses to acupuncture. The brain activity in resting state was measured by calculating the fractional amplitude of low-frequency fluctuations (fALFF), which reflected the idiopathic activity level of neurons in the resting state. These results were analyzed by two factorial ANOVA test and post-hoc t-tests. Results The clinical outcomes suggest that acupuncture could improve clinical symptoms, and the combination of multi-acupoints might lead to a better clinical efficacy. The rs-fMRI results suggested that the brain activity of certain regions was related to the sleep experience, and acupuncture could regulate the activity of these regions. Furthermore, the combination of multi-acupoints could impact more regions which were influenced by the sleep experience. Conclusions Acupuncture has been proven to be beneficial for PI patients, and the combination of multi-acupoints might improve its efficacy. Trial registration This trial has been registered on the U.S. National Library of Medicine (https://clinicaltrials.gov) ClinicalTrials.gov Identifier: NCT02448602 . Registered date: 14/04/2015.

Primary insomnia (PI) is among the most prevalent sleep-related disorders and has a far-reaching impact on daytime functioning. Repetitive transcranial magnetic stimulation (rTMS) has drawn attention because of its effectiveness and safety. The purpose of the current study was to detect changes in the topological organization of whole-brain functional networks and to determine their associations with the clinical treatment effects of rTMS. Resting-state functional magnetic resonance imaging (rsfMRI) data from 32 patients with PI were collected and compared with findings from 32 age- and gender-matched healthy controls (HCs). The patients were treated with Stanford accelerated intelligent neuromodulation therapy, which is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation protocol. Graph theoretical analysis was used to construct functional connectivity matrices and to extract the attribute features of small-world networks in insomnia. Scores on the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the associations between these clinical characteristics and functional metrics, were the primary outcomes. At baseline, the patients with PI showed inefficient small-world property and aberrant functional segregation and functional integration compared with the HCs. These properties showed renormalization after individualized rTMS treatment. Furthermore, low functional connectivity between the right insula and left medial frontal gyrus correlated with improvement in ISI scores. We highlight functional network dysfunctions in PI patients and provide evidence into the pathophysiological mechanisms involved and the possible mode of action of rTMS.

Objectives: Primary insomnia is a substantial public health burden, but current treatments for this disorder have limited effectiveness and adherence. Herein, we aimed to investigate the efficacy and safety of continuous theta burst stimulation (cTBS) for the treatment of primary insomnia., Methods: This two-armed, randomized, sham-controlled trial was conducted at Peking University Sixth Hospital and local community clinics. A total of 46 patients with primary insomnia were recruited and randomly allocated to either the cTBS group or sham group. Forty-one patients completed 10 sessions of cTBS or sham intervention and follow-up assessments., Results: After the intervention, the severity of insomnia was significantly lower in the cTBS group than in the sham group, with a large effect size (Cohen's d = -1.938). Additionally, 52.4 % of patients in the cTBS group achieved a response (Insomnia Severity Index score reduction ≥8), whereas only 4 % of patients in the sham group achieved a response. The duration of objective total sleep time and slow-wave sleep were higher in the cTBS group than in the sham group. The degree of anxiety was lower in the cTBS group than in the sham group. There were no significant differences in depression, sleepiness, or cognitive function between the cTBS and sham groups. During follow-up, the sleep quality of the cTBS group significantly improved and remained stable at the 6-month follow-up., Conclusion: In this randomized clinical trial, cTBS improved insomnia symptoms and was generally well tolerated, thus supporting the further development of cTBS for the treatment of primary insomnia., Competing Interests: Declaration of competing interest The authors report that they have no financial conflicts of interest with respect to the content of this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

Background: The neuropathologic mechanism of primary insomnia (PI) of females remains unclear. This study aims to investigate the features of amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in females with PI using functional magnetic resonance imaging (fMRI), and then explore the abnormalities of functional connectivity (FC)., Materials and Methods: A total of 39 female PI patients and 31 female healthy controls (HC) were enrolled in the study. The sleep condition was assessed using the Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI), and their depressive symptom was evaluated using the Hamilton Depression Scale (HAMD-24). The rs-fMRI was once conducted for every subject. ReHo, ALFF, and ROI-based FC were used to analyze the changes of brain function., Results: ALFF values were increased in the Cerebelum&#95;4&#95;5&#95;L, as well as decreased ALFF in the bilateral Frontal&#95;Sup&#95;Medial (SFGmed), Angular&#95;L (ANG.L), Parietal&#95;Inf&#95;R (IPL.R), SupraMarginal&#95;R (SMG.R), and Postcentral&#95;R (PoCG.R). ReHo values were increased in the Temporal&#95;Pole&#95;Mid&#95;R (TPOsup.R), as well as decreased ReHo in the Insula&#95;R (INS.R), Frontal&#95;Inf&#95;Oper&#95;R (ORBinf.R), Putamen&#95;R (PUT.R), Rolandic&#95;Oper&#95;R (ROL.R), bilateral Cingulum&#95;Post (PCG), bilateral Frontal&#95;Sup&#95;Medial (SFGmed), bilateral anterior cingulate and paracingulate gyri (ACG), and the bilateral precuneus (PCUN). Across the entire brain, there was a decline in the FC between Angular&#95;R and Frontal&#95;Sup&#95;Medial&#95;L., Conclusion: Alterations in brain regions of female patients with PI involved multiple functional networks, including the default mode network, the salience network, the central executive network, and the limbic network. Reduced coordination between functional networks may be an important mechanism for insomnia and may lead to reduced cognitive function and decision-making ability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Jie, Liu, Wu, Wang, Zhang, Fang, Wang, Zhao and Liu.)

To investigate the effect of escitalopram combined with zolpidem on sleep quality, anxiety and depression state and serum neurotransmitter in patients with primary insomnia. 100 cases of primary insomnia admitted to our hospital from January 2018 to December 2020 were selected as the study object. The above patients were divided into control group (treated with zolpidem, n=50) and study group (treated with escitalopram on the basis of the control group, n=50,) according to the random number table method. The sleep quality, anxiety and depression state, serum neurotransmitter and adverse reactions of the two groups were compared. 4 weeks after treatment, the sleep efficiency of the study group were higher than those of the control group, the total sleep time were longer than those of the control group, while the wake-up time and sleep time of the study group were shorter than those of the control group (P<0.05). 4 weeks after treatment, the pittsburgh sleep quality index (PSQI), hamilton Depression Rating Scale (HAMD) and hamilton Anxiety Rating Scale (HAMA) of the study group were lower than those of the control group (P<0.05). 4 weeks after treatment, the levels of 5-hydroxytryptamine (5-HT), r-aminobutyric acid (GABA) in the study group were higher than those in the control group, and the levels of norepinephrine(NE) in the study group were lower than those in the control group (P<0.05). There was no difference in adverse reactions between the two groups (P>0.05). Esmcitalopram combined with zolpidem can effectively improve the sleep quality, anxiety and depression of patients with primary insomnia, and improve the serum 5-HT, NE, CRH, with good safety. [ABSTRACT FROM AUTHOR]

Background: Cognitive behavioral therapy for insomnia (CBT-I) is a first-line therapy for insomnia disorders. We assessed changes in discrepancies between subjective and objective sleep measures and correlations between discrepancy changes and clinical insomnia severity for CBT-I in patients with primary insomnia Methods: Fifty-two outpatients (mean age, 60.3 years; 26 women) with primary insomnia were treated by individual CBT-I (50 min, maximum six sessions, once every 1–2 weeks). One week before and after CBT-I, patients recorded a sleep log and wore an actigraphy device. Subjective and objective time in bed (TIB), total sleep time (TST), sleep-onset latency (SOL), wake time after sleep onset (WASO), and sleep efficiency (SE) were evaluated by averaging 1-week records. Relative values of sleep discrepancy in TIB, TST, SOL, WASO, and SE were calculated for estimating effects of CBT-I. The therapeutic effects were also evaluated using psychological scales before and after CBT-I. Results: Subjective and objective discrepancies in sleep measures decreased by 36, 25, and 37 min in TST, SOL, and WASO, respectively, and 7% in SE (all P < 0.001) after CBT-I. Seven patients transitioned from underestimating SE before CBT-I to overestimating SE after CBT-I. Although CBT-I improved relative values of discrepancy in WASO and SE, alongside ISI, the improvement in insomnia severity only correlated with SOL discrepancy. Conclusions: CBT-I may reduce the discrepancy between subjective and objective sleep measures in patients with primary insomnia. However, a greater therapeutic effect of CBT-I was observed in reducing the ISI, which was slightly influenced by improvements in sleep discrepancies. [ABSTRACT FROM AUTHOR]

Dysfunction of the sleep-wake transition is considered to be associated with the pathology of patients with primary insomnia (PI). Previous animal study had reported that brain circuits between the striatum and cortex can regulate sleep-wake transitions. So far, few studies have systematically explored the structural connectivity of the striatum-centered circuits and their potential roles in patients with PI. In this study, we chosen the striatum as the seed and 10 priori target regions as masks to assess the structural connectivity by using seed-based classification with a diffusion tensor imaging (DTI) probabilistic tractography method. Track strengths of the striatum-centered circuits were compared between 22 patients with PI (41.27 ± 9.21 years) and 30 healthy controls (HC) (35.2 ± 8.14 years). Pittsburgh Sleep Quality Index (PSQI) was used to measure the sleep quality in all participants. Lower track strengths (left striatum- anterior cingulate cortex (ACC), left striatum- dorsal anterior cingulate cortex (dACC), left striatum-Hippocampus, and right striatum-Hippocampus) were observed in patients with PI compared to HC. Additionally, the lower track strengths of brain circuits mentioned above were negatively correlated with PSQI. Taken together, our findings revealed the lower tract strength of frontostriatal circuits in patients with PI and HC, which provided the implications of the system-level structural connections of frontostriatal circuits in the pathology of PI. We suggested that the track strengths of the frontostriatal circuits calculated from DTI can be the potential neuroimaging biomarkers of the sleep quality in patients with PI. [ABSTRACT FROM AUTHOR]

Devon A Hansen,1,2 Matthew E Layton,1–3 Samantha M Riedy,1,2 Hans PA Van Dongen1,2 1Sleep and Performance Research Center, Washington State University, Spokane, WA, USA; 2Department of Medical Education and Clinical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA; 3Program of Excellence in Addictions Research, College of Nursing, Washington State University, Spokane, WA, USACorrespondence: Devon A HansenSleep and Performance Research Center, Washington State University Spokane, 412 E. Spokane Falls Blvd., Spokane, WA 99202, USATel +1-509-358-7754Fax +1-509-358-7810Email devon.hansen@wsu.eduPurpose: Individuals with primary insomnia frequently report cognitive impairment as a next-day consequence of disrupted sleep. Studies attempting to quantify daytime impairment objectively in individuals with insomnia have yielded mixed results, with evidence suggesting impairments in aspects of executive functioning but not psychomotor vigilance. It has been suggested that persons with insomnia may have latent performance deficits for which they would be able to compensate effectively under normal daytime circumstances – suggesting that any such deficits may be exposed through perturbation. In this context, we used a laboratory-based total sleep deprivation (TSD) paradigm to investigate psychomotor vigilance performance in individuals with chronic sleep-onset insomnia as compared to healthy normal controls.Participants and methods: Fourteen participants, seven individuals with chronic sleep-onset insomnia (ages 24–40y) and seven age-matched, healthy normal sleepers completed a highly controlled in-laboratory study involving 38 h of TSD. A 10 min and a 3 min version of the psychomotor vigilance test (PVT) were administered every 3 h during TSD.Results: In both the individuals with sleep-onset insomnia and the age-matched normal sleepers, lapses of attention and false starts on the PVT were relatively infrequent during the first 16 h of the TSD period, but increased significantly when wakefulness was extended beyond 16 h. However, the effects of TSD on PVT performance were considerably exacerbated in the sleep-onset insomnia group, which showed about twice as many lapses of attention, more than twice as many false starts, and approximately twice as big a time-on-task effect on the 10 min PVT as the age-matched normal sleepers group, with similar findings on the 3 min PVT.Conclusion: These findings indicate that daytime impairment reported by individuals with sleep-onset insomnia has an objective performance component that is exposed during TSD. Thus, persons with sleep-onset insomnia could be at increased risk of performance impairment in settings that involve extended wakefulness. This underscores the importance of treating insomnia and suggests that laboratory sleep deprivation studies could serve to document the effectiveness of treatment approaches.Keywords: bedtime-specific hyperarousal, chronic insomnia, cognitive performance, extended wakefulness, primary insomnia, vulnerability to sleep loss

Purpose: To investigate the intervention effects of using traditional Chinese Guqin music and Chinese Calligraphy handwriting (CCH) for patients with Primary Insomnia. Methods: A total of ninety patients were assigned to control group, Guqin group, and calligraphy group for 8 weeks. For 5 days a week, patients' heart rate variability (HRV) and frontal midline (FZ) electroencephalographic signals were recorded in a clinic during interventional period while either listening to Guqin music or writing calligraphy. Patients in the control group remained in rest condition. Results: For the Guqin group, the higher low-frequency-range HRV of coherence was found with marginal significance (P = 0.055), and heart rate was significantly reduced (P < 0.05) during the 4th week in listening to Guqin music compared to the prerest period. For listening to Guqin music or calligraphy intervention, FZ δ, FZ θ, and FZ α waves in the 8th week compared to the 0th week (Pre Intervention) showed a significantly enhanced effect (P < 0.05). Between the three groups, for heart rate and FZ δ and FZ θ waves, calligraphy group showed significantly increased heart rate than the Guqin group (P < 0.001)and the control group (P = 0.004); increased FZ δ wave than the Guqin group (P < 0.001) and the control group (P < 0.001); and increased FZ θ wave than the Guqin group (P = 0.024) and the control group (P = 0.008) respectively. Conclusion: Positive intervention effects on HRV coherence of Guqin music; FZ δ, FZ θ, and FZ α waves of Guqin music and calligraphy proved that Guqin music together with calligraphy training helping to promote physical and mental health, thereby it contributes to the clinical application of TCM Psychology for patients with insomnia syndrome.

(1) Background: The purpose of this study was to investigate the efficacy and safety of transcutaneous vagus nerve stimulation (t-VNS) in the treatment of primary insomnia. (2) Methods: This is a single center, randomized, double-blind study. A total of 30 patients diagnosed with primary insomnia were randomly divided into two groups to receive 20 Hz t-VNS in either the auricular concha area (treatment group) or periauricular area (control group), twice a day for 20 min during a one-month study period. The effective rate of treatment, defined as a ≥50% reduction of the Pittsburgh Sleep Index Scale (PSQI) after treatment, was compared between the two groups as the primary outcome. Response rate (defined as ≥10% change in the PSQI score), and changes in the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores were also assessed. (3) Results: After one month of treatment, the PSQI score of the treatment group decreased significantly (p = 0.001). The effective rate of the treatment group (73% vs. 27%, p = 0.027) was significantly higher than that of the control group. No statistical differences in changes of HAMA and HAMD scores were detected between the two groups. There were no complications in all patients. (4) Conclusion: T-VNS appeared to be a safe and effective treatment for primary insomnia.

Background: Primary insomnia is a worldwide problem and it has a considerable negative impact on one's physical and mental health. Studies have shown that non‐synonymous Single‐nucleotide polymorphisms in 5‐hydroxytryptamine (serotonin or 5‐HT) are related to primary insomnia. Previous studies have shown that 5‐HT polymorphism (rs140700) is related to depression, and insomnia is often accompanied by depression and anxiety. The relationship between this site and primary insomnia is unknown. We speculated that this site may be related to primary insomnia, so we investigated the relationship between rs140700 and primary insomnia. Aims: To explore the relationship between the 5‐HT gene polymorphism rs140700 and primary insomnia. Methods: In this study, we included 57 patients with primary insomnia and 54 age‐ and gender‐matched normal controls. The subjects who belonged to the Chinese population were subjected to polysomnography for three consecutive nights. Their sleep quality was assessed, and the genotypes of the 5‐hydroxytryptamine (5‐HT) gene polymorphism rs140700 were determined by the flight mass spectrometry. Results: The genotype distributions of the 5‐HT gene polymorphism rs140700 were in Hardy–Weinberg equilibrium in both patients and controls (P > 0.05). The allele and genotype distributions of this variant were comparable between the patients and controls in all subjects and between genders (all P > 0.05). The influence of rs140700 on percentage of stage 1 (P = 0.015) change and arousal index (P = 0.028) of primary insomnia was statistically significant. The logistic multi‐factor regression analysis results revealed that 5‐HT gene polymorphism rs140700 was not a risk factor for primary insomnia in the Chinese population (P = 0.589). Conclusions: The 5‐HT gene polymorphism rs140700 may not be a susceptibility locus for primary insomnia in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: The neural mechanisms of sleep beliefs and attitudes in primary insomnia (PI) patients at resting state remain unclear. The aim of this study was to investigate the features of regional homogeneity (ReHo) in PI using resting-state functional magnetic resonance imaging (rsfMRI).Methods: Thirty-two PI patients and 34 normal controls (NC) underwent rsfMRI using a 3 T scanner at Tongde Hospital of Zhejiang Province. Participants were assessed with the Dysfunctional Beliefs and Attitudes about Sleep scale (DBAS-16) and Pittsburgh Sleep Quality Index (PSQI). Statistical analyses were performed to determine the regions in which ReHo differed between the two groups. Correlation analyses were performed between the ReHo index of each of these regions and DBAS-16 in PI patients.Results: PI patients showed increased ReHo values in the right superior frontal gyrus, and decreased ReHo values in the left cerebellar gyrus, left inferior occipital gyrus (IOG) and left amygdala compared with those of NC. ReHo values in the left IOG were negatively correlated with total DBAS-16 scores, and scores for "consequences of insomnia" and"worry/helplessness about sleep"in PI patients.Conclusions: These results suggest that ReHo alterations in the left IOG may play an important role in the dysfunctional beliefs and attitudes about sleep in PI. [ABSTRACT FROM AUTHOR]

Background: The efficacy of acupuncture for treating primary insomnia (PI) has been explored in several meta-analyses where the outcomes measures were based on subjective self-reported sleep rating scales. Sleep state misperception is common in PI and self-reports underestimate sleep duration and quality. No systematic reviews or meta-analyses have investigated the efficacy of acupuncture in improving objective sleep measures in PI.Objective: To perform a systematic review to determine whether objective sleep parameters are improved by acupuncture in patients with PI.Methods: Randomized controlled trials treating PI via verum-acupuncture versus sham-/placebo-acupuncture or waitlist control were searched for in English [MEDLINE (via PubMed), Sciverse ScienceDirect, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, Springer, EMBASE (Elsevier), Ebsco Medline, and PsycINFO (ProQuest)] and Chinese (SinoMed, CNKI, Wanfang and CQVIP) databases, from the dates of the databases' inception to January 2020. The parameters of polysomnography (PSG), actigraphy, or micromovement sensitive mattress/pillow sleep monitoring systems were considered as the primary outcome measures. Revman 5.3 and Stata 16.0 software were used to conduct the meta-analysis. Heterogeneity was examined by using I2 statistics and publication bias was assessed via Egger's test.Results: Eleven studies involving 775 patients met the inclusion criteria. The results of meta-analysis suggested that acupuncture can increase total sleep time [MD = 55.29, 95%CI (29.16, 81.42), p < 0.01], increase sleep efficiency [MD = 8.96, 95%CI (3.97, 13.95), p < 0.01], decrease wake after sleep onset [MD = -49.54, 95%CI (-82.98, -16.09), p < 0.01], and reduce number of awakening times [MD = -6.29, 95%CI (-10.75, -1.82), p < 0.01] compared with either sham-/placebo-acupuncture or waitlist control. Subsequent analysis indicated a superior effect for verum-acupuncture in comparison with sham-/placebo-acupuncture or waitlist-control when the recommended lowest threshold dosage (12 sessions) was met. Despite positive outcomes, most studies reviewed were heterogeneous and at risk of bias due to methodological issues.Conclusions: Despite limited evidence, acupuncture was significantly associated with improvements in several objective sleep parameters (increases in total sleep time and sleep efficiency, and reductions in wake after sleep onset and number of awakening times) as well as subjective sleep quantity and quality in patients with PI. A minimum therapeutic threshold dosage (≥12 sessions) is recommended. Well-designed RCTs using PSG are required to clarify the influence of acupuncture on sleep architecture/structure and to promote better application of acupuncture as a treatment for PI. [ABSTRACT FROM AUTHOR]

Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective in the treatment of primary insomnia (PI); however, its efficacy varies considerably across individuals for reasons that are unclear. In order to clarify the underlying mechanisms, this study investigated the effects of taVNS on spontaneous neuronal activity and autonomic nervous system function by functional magnetic resonance imaging (fMRI) and measurement of heart rate variability (HRV), respectively, in patients with PI. Forty patients with PI were divided into effective (group A) and ineffective (group B) groups based on their response to taVNS as determined by Pittsburgh Sleep Quality Index score reduction rate (group A ≥ 25% and group B < 25%). Spontaneous neuronal activity was measured by fractional amplitude of low-frequency fluctuations (fALFF) and HRV values and was compared between the two groups as well as before vs after taVNS. We then analyzed the correlations among efficacy of taVNS for 4 weeks, the fALFF and HRV values during continuous taVNS state. The results showed that the HRV parameter values (i.e., root mean square of successive differences, percentage of adjacent NN intervals differing by >50 ms, and high frequency) of group A were higher than those of group B during continuous taVNS state. In the fMRI scan, the fALFF values of the right cerebellum, right medial superior frontal gyrus, and bilateral supplementary motor area—which belong to the sensorimotor network (SMN)—were lower in group A than in group B during continuous taVNS state. The correlation analysis revealed that the efficacy of continuous taVNS and HRV and fALFF values were interrelated. These findings demonstrate that differential regulation of the SMN by the autonomic nervous system may be responsible for inter-individual variations in the efficacy of taVNS and suggest that HRV and fALFF are potential biomarkers for predicting PI patients’ response to taVNS treatment.

Abstract Background Primary insomnia (PI) is defined as a sleep disorder with no definite cause or inducement. Electroacupuncture, a treatment of inserting needles into specific points on the body surface and applying electrical stimulation, has been proved effective in treating PI with minimal adverse effects. However, the influence of gender difference on the clinical treatment efficacy of electroacupuncture for PI patients remains unclear. Therefore, we designed a clinical trial to compare the clinical treatment efficacy of electroacupuncture for PI patients with different genders. The research on the mechanism of electroacupuncture suggested it could modulate the sleep and wakefulness by activating or deactivating brain regions via a needling/tactile somatosensory specific stimulus. Therefore, we also designed a resting‐state functional magnetic resonance imaging (rs‐fMRI) study to detect the spontaneous brain activity of PI patients before and after the electroacupuncture treatment. Method Thirty PI patients were recruited to accept 5‐week electroacupuncture treatment on HT‐7. Athens Insomnia Scale (AIS) and Pittsburgh sleep quality index (PSQI) questionnaires were used to evaluate the clinical treatment efficacy. Rs‐fMRI was employed to observe the spontaneous brain activity in the resting state at the baseline and after 5 weeks of electroacupuncture treatment, which was measured by the fractional amplitude of low‐frequency fluctuations (fALFF). Result The AIS and PSQI scores were significantly decreased both in the female PI group and the male PI group after treatment. The decreased PSQI of female patients was significantly more than that of male patients (p

ObjectiveTo examine the association between physiological hyperarousal and response accuracy on reaction time tasks among individuals with insomnia.Design and settingThis study was conducted at affiliated Veterans Administration (VA) and academic medical centers using a matched-group, cross-sectional research design.ParticipantsEighty-nine individuals (48 women) with primary insomnia, PI (MAge = 49.8 ± 17.2 y) and 95 individuals (48 women) who were well-screened normal sleepers, NS (MAge = 46.9 ± 17.0 y).Methods and measuresParticipants underwent 3 nights of polysomnography followed by daytime testing with a four-trial Multiple Sleep Latency Test (MSLT). Before each MSLT nap, they rated their sleepiness and completed computer-administered reaction time tasks. The mean number of correct and error responses made by each participant across testing trials served as dependent measures. The PI and NS groups were each subdivided into alert (e.g., MSLT mean onset latency > 8 min) and sleepy (e.g., MSLT mean onset latency ≤ 8 min) subgroups to allow for testing the main and interaction effects of participant type and level of alertness.ResultsAlert participants had longer MSLT latencies than sleepy participants (12.7 versus 5.4 min), yet both alert and sleepy individuals with PI reported greater sleepiness than NS. Alert participants also showed lower sleep efficiencies (83.5% versus 86.2%, P = 0.03), suggesting 24-h physiological hyperarousal particularly in the PI group. Individuals with PI had fewer correct responses on performance testing than did NS, whereas a significant group × alertness interaction (P = 0.0013) showed greater error rates among alert individuals with PI (mean = 4.5 ± 3.6 errors per trial) than among alert NS (mean = 2.6 ± 1.9 errors per trial).ConclusionsPhysiological hyperarousal in insomnia may lead to more apparent daytime alertness yet dispose individuals with insomnia to higher error rates on tasks requiring their attention.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective in the treatment of primary insomnia (PI); however, its efficacy varies considerably across individuals for reasons that are unclear. In order to clarify the underlying mechanisms, this study investigated the effects of taVNS on spontaneous neuronal activity and autonomic nervous system function by functional magnetic resonance imaging (fMRI) and measurement of heart rate variability (HRV), respectively, in patients with PI. Forty patients with PI were divided into effective (group A) and ineffective (group B) groups based on their response to taVNS as determined by Pittsburgh Sleep Quality Index score reduction rate (group A ≥ 25% and group B < 25%). Spontaneous neuronal activity was measured by fractional amplitude of low-frequency fluctuations (fALFF) and HRV values and was compared between the two groups as well as before vs after taVNS. We then analyzed the correlations among efficacy of taVNS for 4 weeks, the fALFF and HRV values during continuous taVNS state. The results showed that the HRV parameter values (i.e., root mean square of successive differences, percentage of adjacent NN intervals differing by >50 ms, and high frequency) of group A were higher than those of group B during continuous taVNS state. In the fMRI scan, the fALFF values of the right cerebellum, right medial superior frontal gyrus, and bilateral supplementary motor area—which belong to the sensorimotor network (SMN)—were lower in group A than in group B during continuous taVNS state. The correlation analysis revealed that the efficacy of continuous taVNS and HRV and fALFF values were interrelated. These findings demonstrate that differential regulation of the SMN by the autonomic nervous system may be responsible for inter-individual variations in the efficacy of taVNS and suggest that HRV and fALFF are potential biomarkers for predicting PI patients' response to taVNS treatment. [ABSTRACT FROM AUTHOR]

Purpose: According to the cognitive processing perspectives, patients with insomnia have insufficient neural management of expressional information. In this study, we compared the pre-attentive processing function of task-irrelevant facial expressions in patients with primary insomnia (PI) and matched healthy controls, with expression-related mismatch negativity (EMMN) elicited by emotional faces as the indicator. Methods: Using three schematic facial expressions (neutral, happy, and sad) as task-irrelevant stimuli, we investigated the visual processing of PI patients (n = 22) and healthy subjects (n = 22) in an expression-related oddball paradigm designed to elicit the visual N170 and EMMN component. After recording and analyzing the electroencephalogram of all participants, amplitude analysis of N170 and EMMN was eventually conducted under corresponding time window. Results: Compared with control group, the amplitude of sad-EMMN component was significantly attenuated in patients with PI, while no remarkable difference was observed under the happy condition. In addition, negative cognitive bias was further validated in the control group, but not presented in the PI group. Conclusion: The current data suggest dysfunctional expressional information processing in PI patients, accompanied by the disorganization of high level perceptual strategy of processing facial emotional expression. [ABSTRACT FROM AUTHOR]

Background: Primary insomnia (PI) is defined as a sleep disorder with no definite cause or inducement. Electroacupuncture, a treatment of inserting needles into specific points on the body surface and applying electrical stimulation, has been proved effective in treating PI with minimal adverse effects. However, the influence of gender difference on the clinical treatment efficacy of electroacupuncture for PI patients remains unclear. Therefore, we designed a clinical trial to compare the clinical treatment efficacy of electroacupuncture for PI patients with different genders. The research on the mechanism of electroacupuncture suggested it could modulate the sleep and wakefulness by activating or deactivating brain regions via a needling/tactile somatosensory specific stimulus. Therefore, we also designed a resting‐state functional magnetic resonance imaging (rs‐fMRI) study to detect the spontaneous brain activity of PI patients before and after the electroacupuncture treatment. Method: Thirty PI patients were recruited to accept 5‐week electroacupuncture treatment on HT‐7. Athens Insomnia Scale (AIS) and Pittsburgh sleep quality index (PSQI) questionnaires were used to evaluate the clinical treatment efficacy. Rs‐fMRI was employed to observe the spontaneous brain activity in the resting state at the baseline and after 5 weeks of electroacupuncture treatment, which was measured by the fractional amplitude of low‐frequency fluctuations (fALFF). Result: The AIS and PSQI scores were significantly decreased both in the female PI group and the male PI group after treatment. The decreased PSQI of female patients was significantly more than that of male patients (p <.05). The gender‐related difference in the cerebral response to electroacupuncture was mainly in posterior cingulate and supramarginal gyrus. Conclusion: There is a gender‐related difference in the clinical treatment efficacy of electroacupuncture for PI patients, and female patients may benefit more from electroacupuncture. Gender‐related differences in the cerebral response to electroacupuncture may be one of the factors affecting clinical treatment efficacy. [ABSTRACT FROM AUTHOR]

ObjectivesThe present study examined the abnormal resting state functional connections (RSFCs) in structural deficit brain regions of primary insomnia (PI) patients.MethodsThirty-three PI patients and 38 well-matched healthy controls participated in our study. We used voxel-based morphometry and RSFC to study functional connectivity abnormalities of brain regions with structural deficits in PI patients.ResultsPI patients showed decreased gray matter (GM) volume in the left dorsolateral prefrontal cortex, left orbitofrontal cortex (OFC), bilateral middle frontal gyrus (MFC), right inferior frontal gyrus (IFG), and left inferior temporal gyrus. Gray matter volume in the right MFC negatively correlated with Self-Rating Scale of Sleep (SRSS) scores, and GM volume in the right IFG negatively correlated with SRSS and Insomnia Severity Index (ISI) scores. Therefore, the right MFC and right IFG were selected as regions of interest for RSFC analysis. PI patients had weakened RSFC between the right inferior parietal gyrus (IPC) and the right MFC compared to the healthy controls and between the left OFC and right IFG. The RSFC between the right MFC and right IPC negatively correlated with SRSS scores. The RSFC between the right IFG and left OFC negatively correlated with SRSS, ISI, SAS, and SDS scores.ConclusionsThe present study found structural changes in the right MFC and right IFG accompanied by RSFC changes. This finding may provide novel insights into the neural mechanisms of PI via combining structural and functional modality information.