Functional MRI-based biomarkers of insomnia with objective short sleep duration phenotype.

BACKGROUND: Insomnia disorder with objective short sleep duration (ISS) phenotype is a more serious biological subtype than insomnia with objective normal sleep duration (INS) phenotype, and the neuroimaging data is helpful to understand the pathophysiology of the ISS phenotype. This study was to compare the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) between the ISS phenotype and the INS phenotype. METHODS: In this cross-sectional study, 55 patients with insomnia disorder were recruited, and 22 of them were defined as the ISS phenotype by the objective cardiopulmonary coupling (CPC) technique. The blood oxygen level-dependent (BOLD) sequences of all participants were obtained using the 3.0 T magnetic resonance imaging system. We analyzed and compared the ALFF, ReHo, and FC between the ISS phenotype and the INS phenotype. We also conducted Pearson's correlation analysis between significant neuroimaging biomarkers and the CPC parameters. RESULTS: The differences were not significant in ALFF (PFWE-corr＞0.05) or ReHo (PFWE-corr＞0.05) between the ISS phenotype and the INS phenotype. For the FC analysis, the ISS phenotype had a Hub-node of the left inferior occipital gyrus (IOG.L), with significantly decreased connections (p＜0.001) in the bilateral occipital, parietal, and temporal regions. The significant FCs were closely related to sleep parameters. CONCLUSION: The left inferior occipital gyrus (IOG.L), as a Hub-node with decreased functional connections, may be a potential fMRI-based biomarker of the ISS phenotype.

The brain in chronic insomnia and anxiety disorder: a combined structural and functional fMRI study.

Background: Chronic insomnia disorder (CID) is usually associated with Generalized Anxiety Disorder (GAD), which may change brain structure and function. However, the possible brain markers, imaging characteristics, and pathophysiology are unknown. Objective: To look at the probable brain markers, imaging characteristics, and pathogenesis of CID in combination with GAD. Methods: A total of 57 patients with CID concomitant GAD and 57 healthy controls (HC) were enrolled. Voxel-based morphometry (VBM) and functional connectivity (FC) were utilized to measure gray matter volume (GMV) and functional changes. Correlation analysis was utilized to identify relationships between brain changes and clinical characteristics. Results: Patients had decreased GMV in the left cerebellum, right cerebellar peduncle, and left insula; increased FC between the left cerebellum and right angular gyrus, as well as between the left insula and anterior left cingulate gyrus; and decreased FC in several areas, including the left cerebellum with the middle left cingulate gyrus and the left insula with the left superior postcentral gyrus. These brain changes related to CID and GAD. These data could be used to identify relevant brain markers, imaging features, and to better understand the etiology. Conclusion: The intensity of insomnia in patients was strongly related to the severity of anxiety. The lower GMV in the cerebellum could be interpreted as an imaging characteristic of CID. Reduced GMV in the insula, as well as aberrant function in the cingulate gyrus and prefrontal lobe, may contribute to the pathophysiology of CID and GAD. Abnormal function in the postcentral gyrus and angular gyrus may be associated with patients' clinical complaints.

Effectiveness of repetitive transcranial magnetic stimulation for insomnia disorder on fear memory extinction: study protocol for a randomised controlled trial.

BACKGROUND: Fear memory extinction is closely related to insomnia. Repetitive transcranial magnetic stimulation (rTMS) is safe and effective for treating insomnia disorder (ID), and it has been shown to be an efficient method for modulating fear extinction. However, whether rTMS can improve fear extinction memory in ID patients remains to be studied. In this study, we specifically aim to (1) show that 1 Hz rTMS stimulation could improve fear extinction memory in ID patients and (2) examine whether changes in sleep mediate this impact. METHODS AND DESIGN: We propose a parallel group randomised controlled trial of 62 ID participants who meet the inclusion criteria. Participants will be assigned to a real rTMS group or a sham rTMS group. The allocation ratio will be 1:1, with 31 subjects in each group. Interventions will be administered five times per week over a 4-week period. The assessments will take place at baseline (week 0), post-intervention (week 4), and 8-week follow-up (week 8). The primary outcome measure of this study will be the mean change in the Pittsburgh Sleep Quality Index (PSQI) scores from baseline to post-intervention at week 4. The secondary outcome measures include the mean change in skin conductance response (SCR), fear expectation during fear extinction, Insomnia Severity Index (ISI), Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). DISCUSSION: This study will be the first examination of the impact of rTMS on fear memory extinction in ID patients. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2300076097. Registered on 25 September 2021.

Clinico-demographic factors associated with the treatment response to cognitive behavioral therapy for insomnia.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is among the recommended non-pharmacological treatments for patients with insomnia. While there are multiple reports on the effects of CBT-I treatment, few studies evaluating the factors associated with the treatment response to CBT-I have been reported. The present study aimed to confirm the effects of CBT-I in patients with insomnia and to examine the clinico-demographic factors that can predict the outcomes of CBT-I in these patients. METHODS: Overall, 62 patients were included in the present study. To confirm the effectiveness of CBT-I, we compared the pre- and post-CBT-I therapy values of several sleep parameters. Furthermore, to identify the clinico-demographic factors that could be predictive of the treatment response to CBT-I, we performed generalized linear model (GLM) analysis. RESULTS: The values of several sleep parameters were significantly lower after treatment than at baseline. The results of the GLM analysis revealed that sex and occupation were significantly associated with the treatment response to CBT-I. CONCLUSIONS: The present results suggest that several clinico-demographic factors should be considered in the treatment of patients with insomnia.

Rasch analysis of the pre-sleep arousal scale in patients with acute insomnia disorder.

BACKGROUND: Hyperarousal plays an essential role in the initiation and maintenance of insomnia, highlighting the need for a tool that measure the hyperarousal state during the early course of insomnia. Pre-sleep Arousal Scale (PSAS) is a self-report questionnaire to evaluate subjective pre-sleep arousal of insomnia. The aim of this study was to examine the psychometric properties of the PSAS among patients with acute insomnia disorder (AID) using Rasch analysis. METHODS: Totally 170 patients with AID from 31 public hospitals in China were recruited and completed the test. The psychometric properties of the PSAS were tested using Rasch analysis by Winsteps v5.4.1.0, including unidimensionality, local item independence, item fit, category diagnostics, reliability, item-person maps and differential item functioning (DIF) by age and gender. RESULTS: According to Rasch analysis, somatic and cognitive subscales were unidimensional and basically demonstrated good item-fit statistics. 4-point Likert scale may be more appropriate for PSAS. All items have a good reliability and separation. No gender and age bias were detected for the scale. However, the person arousal level is not well matched to item difficulty. CONCLUSION: The present study further reveals appropriate psychometric properties of the PSAS in patients with AID and provides suggestions for refinements and supplements to the PSAS.

Daridorexant for patients with chronic insomnia disorder: number needed to treat, number needed to harm, and likelihood to be helped or harmed.

OBJECTIVES: Appraise the evidence for daridorexant 50 mg and 25 mg versus placebo when treating chronic insomnia disorder in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). METHODS: NNT, NNH, and LHH were calculated from a 3-month pivotal Phase 3 study (N = 930; randomized 1:1:1 to daridorexant 50 mg, daridorexant 25 mg, or placebo once nightly). Wakefulness after sleep onset, latency to persistent sleep, self-reported total sleep time, Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), and Insomnia Severity Index were used for the NNT efficacy analysis. NNH safety analysis was performed using rates of adverse events (AEs) occurring in >1% of the participants in any arm. LHH was assessed for all NNT estimates, contrasting them with NNH estimates for somnolence, headache, and fatigue AEs. RESULTS: NNT estimates for daridorexant 50 mg versus placebo were <10 for clinically meaningful thresholds across all outcomes. NNT estimates for daridorexant 25 mg versus placebo were not as robust as those observed for daridorexant 50 mg, with many values exceeding 10. NNH estimates for daridorexant 50 mg and 25 mg versus placebo did not show a statistically significant treatment difference except for falls, where NNH was negative for the daridorexant 50 mg group (-44 [95% CI -328; -21]; rate of falls was greater with placebo than for daridorexant 50 mg). All LHH ratios at Months 1 and 3 were >1 (except for daridorexant 25 mg for the IDSIQ alert/cognition domain), indicating that patients were more likely to respond to daridorexant 50 mg and 25 mg than to experience an AE of somnolence, headache, or fatigue. CONCLUSION: Daridorexant 50 mg and 25 mg have a favorable benefit-risk ratio over 3 months. Daridorexant 50 mg demonstrated more robust (lower) NNT estimates versus placebo than daridorexant 25 mg.

Daridorexant, a dual orexin receptor antagonist, is a new treatment for chronic insomnia disorder. This analysis examined the effect and safety of daridorexant 50 and 25 mg, using data from a 3-month Phase 3 study (NCT03545191) to measure 'number needed to treat' (NNT) and 'number needed to harm' (NNH).NNT estimates how many patients need to be treated over a specific period to see one more beneficial response. Estimates versus placebo <10 indicate an effective treatment. Daridorexant 50 mg estimates were <10 for all objective and subjective measurements of insomnia assessed in this analysis, including evaluation of daytime functioning. NNT estimates for daridorexant 25 mg versus placebo were not as robust as daridorexant 50 mg, with values >10.NNH is calculated in the same way as NNT but estimates harmful outcomes rather than benefits. Estimates versus placebo >10 means the treatment is reasonably well tolerated.Using NNT and NNH, the 'likelihood to be helped or harmed' (LHH) ratio was calculated, determining how more likely a patient is to benefit versus experiencing harm from a treatment (LHH of >1 denotes a positive benefit­risk ratio). Both daridorexant doses had a favorable benefit­risk ratio over 3 months with LHH > 1.This analysis supports daridorexant 50 mg as the optimal dose to treat insomnia in adults, offering improved effectiveness compared with daridorexant 25 mg, with a similarly good safety profile.

Serum levels of neurotensin, pannexin-1, and sestrin-2 and the correlations with sleep quality or/and cognitive function in the patients with chronic insomnia disorder.

Objectives: To examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, and their correlations with subjective and objective sleep quality and cognitive function in the patients with chronic insomnia disorder (CID). Methods: Sixty-five CID patients were enrolled continuously and fifty-six good sleepers in the same period were served as healthy controls (HCs). Serum levels of neurotensin, pannexin-1 and sestrin-2 were measured by enzyme-linked immunosorbent assays. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and polysomnography, and mood was evaluated by 17-item Hamilton Depression Rating Scale. General cognitive function was assessed with the Chinese-Beijing Version of Montreal Cognitive Assessment and spatial memory was evaluated by Blue Velvet Arena Test (BVAT). Results: Relative to the HCs, the CID sufferers had higher levels of neurotensin (t=5.210, p<0.001) and pannexin-1 (Z=-4.169, p<0.001), and lower level of sestrin-2 (Z=-2.438, p=0.015). In terms of objective sleep measures, pannexin-1 was positively associated with total sleep time (r=0.562, p=0.002) and sleep efficiency (r=0.588, p=0.001), and negatively with wake time after sleep onset (r=-0.590, p=0.001) and wake time (r=-0.590, p=0.001); sestrin-2 was positively associated with percentage of rapid eye movement sleep (r=0.442, p=0.016) and negatively with non-rapid eye movement sleep stage 2 in the percentage (r=-0.394, p=0.034). Adjusted for sex, age and HAMD, pannexin-1 was still associated with the above objective sleep measures, but sestrin-2 was only negatively with wake time (r=-0.446, p=0.022). However, these biomarkers showed no significant correlations with subjective sleep quality (PSQI score). Serum concentrations of neurotensin and pannexin-1 were positively associated with the mean erroneous distance in the BVAT. Adjusted for sex, age and depression, neurotensin was negatively associated with MoCA score (r=-0.257, p=0.044), pannexin-1 was positively associated with the mean erroneous distance in the BVAT (r=0.270, p=0.033). Conclusions: The CID patients had increased neurotensin and pannexin-1 and decreased sestrin-2 in the serum levels, indicating neuron dysfunction, which could be related to poor sleep quality and cognitive dysfunction measured objectively.

Cardiovascular Outcome in Patients with Major Depression: Role of Obstructive Sleep Apnea Syndrome, Insomnia Disorder, and COMISA.

In this study, the 10-year cardiovascular risk associated with comorbid sleep disorders (insomnia disorder, obstructive sleep apnea syndrome, and COMISA [comorbid insomnia and sleep apnea]) was investigated for patients with major depression. To enable our analysis, 607 patients with major depression were selected from the data register of the Sleep Unit. High 10-year cardiovascular risk was considered present when the Framingham Risk Score was ≥10%. The 10-year cardiovascular risk associated with comorbid sleep disorders has been assessed using logistic regression analyzes. High 10-year cardiovascular risk is significant (40.4%) in patients with major depression. After successive introduction of the different confounders, multivariate logistic regressions showed that for patients with major depression high 10-year cardiovascular risk was significantly associated with COMISA but was not significantly associated with insomnia disorder or obstructive sleep apnea syndrome alone. Thus, these results highlight the existence of a negative synergistic action between insomnia disorder and obstructive sleep apnea syndrome on the 10-year cardiovascular risk in patients with major depression, which demonstrates the importance of researching and treating COMISA to improve the prognosis of this specific population subgroup characterized by higher cardiovascular morbidity and mortality.

Multimodal transformer graph convolution attention isomorphism network (MTCGAIN): a novel deep network for detection of insomnia disorder.

Background: In clinic, the subjectivity of diagnosing insomnia disorder (ID) often leads to misdiagnosis or missed diagnosis, as ID may have the same symptoms as those of other health problems. Methods: A novel deep network, the multimodal transformer graph convolution attention isomorphism network (MTGCAIN) is proposed in this study. In this network, graph convolution attention (GCA) is first employed to extract the graph features of brain connectivity and achieve good spatial interpretability. Second, the MTGCAIN comprehensively utilizes multiple brain network atlases and a multimodal transformer (MT) to facilitate coded information exchange between the atlases. In this way, MTGCAIN can be used to more effectively identify biomarkers and arrive at accurate diagnoses. Results: The experimental results demonstrated that more accurate and objective diagnosis of ID can be achieved using the MTGCAIN. According to fivefold cross-validation, the accuracy reached 81.29% and the area under the receiver operating characteristic curve (AUC) reached 0.8760. A total of nine brain regions were detected as abnormal, namely right supplementary motor area (SMA.R), right temporal pole: superior temporal gyrus (TPOsup.R), left temporal pole: superior temporal gyrus (TPOsup.L), right superior frontal gyrus, dorsolateral (SFGdor.R), right middle temporal gyrus (MTG.R), left middle temporal gyrus (MTG.L), right inferior temporal gyrus (ITG.R), right median cingulate and paracingulate gyri (DCG.R), left median cingulate and paracingulate gyri (DCG.L). Conclusions: The brain regions in the default mode network (DMN) of patients with ID show significant impairment (occupies four-ninths). In addition, the functional connectivity (FC) between the right middle occipital gyrus and inferior temporal gyrus (ITG) has an obvious correlation with comorbid anxiety (P=0.008) and depression (P=0.005) among patients with ID.

Analysis of functional connectivity changes in attention networks and default mode networks in patients with depression and insomnia.

PURPOSE: Major Depressive Disorder (MDD) and Insomnia Disorder (ID) are prevalent psychiatric conditions often occurring concurrently, leading to substantial impairment in daily functioning. Understanding the neurobiological underpinnings of these disorders and their comorbidity is crucial for developing effective interventions. This study aims to analyze changes in functional connectivity within attention networks and default mode networks in patients with depression and insomnia. METHODS: The functional connectivity alterations in individuals with MDD, ID, comorbid MDD and insomnia (iMDD), and healthy controls (HC) were assessed from a cohort of 174 participants. They underwent rs-fMRI scans, demographic assessments, and scale evaluations for depression and sleep quality. Functional connectivity analysis was conducted using region-of-interest (ROI) and whole-brain methods. RESULTS: The MDD and iMDD groups exhibited higher Hamilton Depression Scale (HAMD) scores compared to HC and ID groups (P < 0.001). Both ID and MDD groups displayed enhanced connectivity between the left and right orbital frontal cortex compared to HC (P < 0.05), while the iMDD group showed reduced connectivity compared to HC and ID groups (P < 0.05). In the left insula, reduced connectivity with the right medial superior frontal gyrus was observed across patient groups compared to HC (P < 0.05), with the iMDD group showing increased connectivity compared to MDD (P < 0.05). Moreover, alterations in functional connectivity between the left thalamus and left temporal pole were found in iMDD compared to HC and MDD (P < 0.05). Correlation analyses revealed associations between abnormal connectivity and symptom severity in MDD and ID groups. CONCLUSIONS: Our findings demonstrate distinct patterns of altered functional connectivity in individuals with MDD, ID, and iMDD compared to healthy controls. These findings contribute to a better understanding of the pathophysiology of depression and insomnia, which could be used as a reference for the diagnosis and treatments of these patients.

Markers of intestinal barrier damage in patients with chronic insomnia disorder.

Objective: Insomnia disorder stands out as one of the prevalent clinical sleep and psychiatric disorders. Prior research has unequivocally demonstrated variations in the diversity and abundance of gut microbiota among individuals with insomnia disorder. These alterations may play a direct or indirect role in the onset and progression of insomnia disorder by compromising the integrity of the intestinal barrier. This study aims to evaluate the impairment of the intestinal barrier in individuals with insomnia disorder by scrutinizing the serum functionality of this barrier. Materials and methods: 45 patients with chronic insomnia disorder and 30 matched healthy volunteers were meticulously selected based on inclusion criteria. ELISA technology was employed to measure serum levels of diamine oxidase (DAO), D-lactic acid (D-LA), intestinal fatty acid binding protein (I-FABP), and endothelin (ET). Spearman correlation analysis was used to explore the relationship between intestinal mucosal markers and clinical characteristics. Data were analyzed using SPSS 26.0. Results: Compared to the healthy control group, the insomnia disorder group exhibited significantly elevated scores on subjective mood and sleep scales (GAD-7, PHQ-9, HAMA, HAMD, PSQI, and ISI) (P < 0.05). Overnight PSG indicated a notable increase in bed time, total wake time, sleep onset latency, and wake after sleep onset in individuals with insomnia disorder. Additionally, there was a decrease in sleep efficiency and alterations in sleep structure (increased proportion of N1 and N3 stages, prolonged N1 stage) (P < 0.05). The chronic insomnia disorder group displayed significantly reduced concentrations of serum DAO, D-LA, I-FABP, and ET (P < 0.05). Furthermore, significant positive correlations were identified between intestinal epithelial barrier markers and sleep efficiency, while negative correlations were found with wake after sleep onset, total wake time, PSQI, HAMA, and HAMD. Additionally, D-LA levels were significantly positively correlated with ET concentrations. Conclusion: Individuals with chronic insomnia disorder manifest disruptions in sleep structure, heightened susceptibility to anxiety and depressive moods, and impaired intestinal barrier function. These findings suggest that the occurrence and development of insomnia disorder may be linked to the impairment of the intestinal barrier.

Wavelet Entropy Analysis of Electroencephalogram Signals During Wake and Different Sleep Stages in Patients with Insomnia Disorder.

Objective: To investigate the changes in the wavelet entropy during wake and different sleep stages in patients with insomnia disorder. Methods: Sixteen patients with insomnia disorder and sixteen normal controls were enrolled. They underwent scale assessment and two consecutive nights of polysomnography (PSG). Wavelet entropy analysis of electroencephalogram (EEG) signals recorded from all participants in the two groups was performed. The changes in the integral wavelet entropy (En) and individual-scale wavelet entropy (En(a)) during wake and different sleep stages in the two groups were observed, and the differences between the two groups were compared. Results: The insomnia disorder group exhibited lower En during the wake stage, and higher En during the N3 stage compared with the normal control group (all P < 0.001). In terms of En(a), patients with insomnia disorder exhibited lower En(a) in the ß and α frequency bands during the wake stage compared with normal controls (ß band, P < 0.01; α band, P < 0.001), whereas they showed higher En(a) in the ß and α frequency bands during the N3 stage than normal controls (ß band, P < 0.001; α band, P < 0.001). Conclusion: Wavelet entropy can reflect the changes in the complexity of EEG signals during wake and different sleep stages in patients with insomnia disorder, which provides a new method and insights about understanding of pathophysiological mechanisms of insomnia disorder. Wavelet entropy provides an objective indicator for assessing sleep quality.

Assessment and management of chronic insomnia disorder: an algorithm for primary care physicians.

BACKGROUND: Primary care physicians often lack resources and training to correctly diagnose and manage chronic insomnia disorder. Tools supporting chronic insomnia diagnosis and management could fill this critical gap. A survey was conducted to understand insomnia disorder diagnosis and treatment practices among primary care physicians, and to evaluate a diagnosis and treatment algorithm on its use, to identify ways to optimize it specifically for these providers. METHODS: A panel of experts developed an algorithm for diagnosing and treating chronic insomnia disorder, based on current guidelines and experience in clinical practice. An online survey was conducted with primary care physicians from France, Germany, Italy, Spain, and the United Kingdom, who treat chronic insomnia patients, between January and February 2023. A sub-sample of participants provided open-ended feedback on the algorithm and gave suggestions for improvements. RESULTS: Overall, 106 primary care physicians completed the survey. Half (52%, 55/106) reported they did not regularly screen for insomnia and half (51%, 54/106) felt they did not have enough time to address patients' needs in relation to insomnia or trouble sleeping. The majority (87%,92/106) agreed the algorithm would help diagnose chronic insomnia patients and 82% (87/106) agreed the algorithm would help improve their clinical practice in relation to managing chronic insomnia. Suggestions for improvements were making the algorithm easier to read and use. CONCLUSION: The algorithm developed for, and tested by, primary care physicians to diagnose and treat chronic insomnia disorder may offer significant benefits to providers and their patients through ensuring standardization of insomnia diagnosis and management.

Acupuncture for reducing the south to reinforce the north on executive function and sleep structure in patients with chronic insomnia disorder of heart-kidney disharmony. / æ³»å—è¡¥åŒ—æ³•é’ˆåˆºå¯¹å¿ƒè‚¾ä¸äº¤åž‹æ ¢æ€§å¤±çœ éšœç¢æ‚£è€ æ‰§è¡ŒåŠŸèƒ½åŠç¡çœ ç»“æž„çš„å½±å“.

OBJECTIVES: To observe the efficacy of acupuncture for reducing the south to reinforce the north on executive function, sleep structure and sleep quality in patients with chronic insomnia disorder of heart-kidney disharmony. METHODS: A total of 100 patients with chronic insomnia disorder of heart-kidney disharmony were randomized into an acupuncture group (50 cases, 1 case dropped out) and a western medication group (50 cases, 2 cases dropped out). Acupuncture for reducing the south to reinforce the north was applied at Baihui (GV 20) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6), Shenmai (BL 62), Zhaohai (KI 6), Xinshu (BL 15), Shenshu (BL 23) in the acupuncture group, once a day, 5 days a week. Lorazepam tablet was given orally in the western medication group, 0.5-1 mg a time, once a day. Both groups were treated for 4 weeks. The Stroop color-word test (SCWT) indexes (the time consuming and the correct number of card A, B, C and the Stroop interference effect [SIE]), sleep structure indexes (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], non-rapid eye movement period 1 [N1], non-rapid eye movement period 2 [N2], non-rapid eye movement period 3 [N3], rapid eye movement period [REM]) and Pittsburgh sleep quality index (PSQI) score were observed before and after treatment in the two groups. RESULTS: After treatment, the time consuming of card B and C, the time consuming and the correct number of SIE, SL, WASO, N1, N2, as well as the sub-item scores and total score of PSQI were decreased (P<0.05, P<0.01), the correct number of card A, B and C, TST, SE, N3 and REM were increased (P<0.01) compared with those before treatment in the acupuncture group; the time consuming of card C and SIE, the correct number of card A and SIE, TST, SE, REM were increased (P<0.05, P<0.01), SL, WASO, N1, as well as the sub-item scores of sleep quality, sleep latency, sleep duration, sleep efficiency, daytime function and total score of PSQI were decreased (P<0.01) compared with those before treatment in the western medication group. After treatment, in the acupuncture group, the time consuming of card C, the time consuming and the correct number of SIE, N1, N2, as well as the sub-item scores of sleep quality, sleep dysfunction, daytime function and total score of PSQI were lower than those in the western medication group (P<0.01), the correct number of card B and C, N3, REM were higher than those in the western medication group (P<0.01). CONCLUSIONS: Acupuncture for reducing the south to reinforce the north can improve the executive function of patients with chronic insomnia disorder of heart-kidney disharmony, adjust the sleep structure, and improve the night sleep quality and daytime body function.

Insomnia disorder characterized by probabilistic metastable substates using blood-oxygenation-level-dependent (BOLD) phase signals.

PURPOSE: From a clinical point of view, how to force a transition from insomnia brain state to healthy brain state by external driven stimulation is of great interest. This needs to define brain state of insomnia disorder as metastable substates. The current study was to identify recurrent substates of insomnia disorder in terms of probability of occurrence, lifetime, and alternation profiles by using leading eigenvector dynamics analysis (LEiDA) method. METHODS: We enrolled 32 patients with insomnia disorder and 30 healthy subjects. We firstly obtained the BOLD phase coherence matrix from Hilbert transform of BOLD signals and then extracted all the leading eigenvectors from the BOLD phase coherence matrix for all subjects across all time points. Lastly, we clustered the leading eigenvectors using a k-means clustering algorithm to find the probabilistic metastable substates (PMS) and calculate the probability of occurrence and associated lifetime for substates. RESULTS: The resulting 3 clusters were optimal for brain state of insomnia disorder and healthy brain state, respectively. The occurred probabilities of the PMS were significantly different between the patients with insomnia disorder and healthy subjects, with 0.51 versus 0.44 for PMS-1 (p < 0.001), 0.25 versus 0.27 for PMS-2 (p = 0.051), and 0.24 versus 0.29 for PMS-3 (p < 0.001), as well as the lifetime (in TR) of 36.65 versus 33.15 for PMS-1 (p = 0.068), 14.36 versus 15.43 for PMS-2 (p = 0.117), and 14.80 versus 16.34 for PMS-3 (p = 0.042). The values of the diagonal of the transition matrix were much higher than the probabilities of switching states, indicating the metastable nature of substates. CONCLUSION: The resulted probabilistic metastable substates hint the characteristic brain dynamics of insomnia disorder. The results may lay a foundation to help determine how to force a transition from insomnia brain state to healthy brain state by external driven stimulation.

Electroencephalography connectome changes in chronic insomnia disorder are correlated with neurochemical signatures.

STUDY OBJECTIVES: This study aimed to investigate the alterations in resting-state electroencephalography (EEG) global brain connectivity (GBC) in patients with chronic insomnia disorder (CID) and to explore the correlation between macroscale connectomic variances and microscale neurotransmitter distributions. METHODS: We acquired 64-channel EEG from 35 female CID patients and 34 healthy females. EEG signals were source-localized using individual brain anatomy and orthogonalized to mitigate volume conduction. Correlation coefficients between band-limited source-space power envelopes of the DK 68 atlas were computed and averaged across regions to determine specific GBC values. A support vector machine (SVM) classifier utilizing GBC features was employed to differentiate CID patients from controls. We further used Neurosynth and a 3D atlas of neurotransmitter receptors/transporters to assess the cognitive functions and neurotransmitter landscape associated with CID cortical abnormality maps, respectively. RESULTS: CID patients exhibited elevated GBC within the medial prefrontal cortex and limbic cortex, particularly at the gamma carrier frequency, compared to controls (pFDR < .05). GBC patterns were found to effectively distinguish CID patients from controls with a precision of 90.8% in the SVM model. The cortical abnormality maps were significantly correlated with meta-analytic terms like "cognitive control" and "emotion regulation." Notably, GBC patterns were associated with neurotransmitter profiles (pspin < .05), with neurotransmitter systems such as norepinephrine, dopamine, and serotonin making significant contributions. CONCLUSIONS: This work characterizes the EEG connectomic profile of CID, facilitating the cost-effective clinical translation of EEG-derived markers. Additionally, the linkage between GBC patterns and neurotransmitter distribution offers promising avenues for developing targeted treatment strategies for CID.

Prenatal insomnia disorder may predict concurrent and postpartum psychopathology: A longitudinal study.

While insomnia symptoms may be a risk factor for mental disturbances, few studies evaluated "Insomnia Disorder" and its relationship with perinatal psychopathology. Pregnant women were recruited during their last routine assessment before being hospitalized for delivery during the 3rd trimester at the Gynaecological Unit of the University Hospital of Ferrara and Udine, Italy, from January 2022 to January 2023. Our assessment included baseline evaluation (T0), and evaluations at 1 month (T1) and 3 months (T2) in the postpartum period, with specific questionnaires for insomnia disorder, such as Sleep Condition Indicator, mood and anxiety symptoms and psychosocial functioning, such as Edinburgh Postnatal Depression Scale, Mood Disorder Questionnaire, State-Trait Anxiety Inventory, Work and Social Adjustment Scale. At T0, 181 pregnant women were included. Insomnia disorder affected 22.3% at T0, 23.5% at T1 and 16.2% at T2. Women with insomnia disorder at baseline were significantly more affected by concurrent anxiety and depressive symptoms, had higher bipolar diathesis and poorer psychosocial functioning in the perinatal period. Prenatal insomnia disorder predicted anxiety (T0: odds ratio 4.44, p << 0.001; T1: odds ratio 4.009, p = 0.042) and depressive symptoms (T0: odds ratio 2.66, p = 0.015; T1: odds ratio 11.20, p = 0.001; T2: odds ratio 12.50 p = 0.049) in both the prenatal and postnatal period. It also predicted poor psychosocial function during the prenatal (odds ratio 3.55, p = 0.003) and postpartum periods (T1: odds ratio 2.33, p = 0.004). Insomnia disorder is emerging as an important prenatal factor that may contribute to concurrent and postpartum psychopathology.

Relationships between rumination and different types of rapid eye movement sleep in patients with chronic insomnia disorder.

BACKGROUND AND OBJECTIVE: Rumination, a common factor of chronic insomnia disorder (CID) caused by cognitive-emotional arousal, is associated with an increased amount of rapid eye movement (REM) sleep. However, the specific subtypes, such as phasic REM and tonic REM, that contribute to the increased REM sleep have not been reported. This study aimed to determine the association between rumination and different REM sleep subtypes in patients with CID. METHODS: This study enrolled 35 patients with CID and 27 age- and sex-matched healthy controls. The Immersion-Rumination Questionnaire evaluated participants' rumination, and the Insomnia Severity Index was used to assess insomnia severity. Finally, polysomnography was used to monitor objective sleep quality and quantification of different types of REM. RESULTS: The CID patients had higher rumination scores than the healthy controls. They had a shorter REM sleep duration, less phasic REM, a lower percentage of phasic REM time, and a higher percentage of tonic REM time. Spectral analysis revealed that the patients affected by insomnia had higher ß power during REM sleep, higher ß and σ power during phasic REM sleep, and higher ß, and γ power during tonic REM sleep. Partial correlation analysis showed that rumination in the CID patients correlated negatively with the duration of phasic REM sleep. Additionally, rumination correlated negatively with δ power in REM sleep and positively with ß power in REM sleep, tonic REM sleep, phasic REM sleep, N3and N2 sleep in the patients with CID. CONCLUSION: The CID patients had stronger rumination, reduced total and phasic REM sleep, and the stronger rumination was, the shorter phasic REM was and the higher fast (ß) wave power in REM sleep.

Changed nocturnal levels of stress-related hormones couple with sleep-wake states in the patients with chronic insomnia disorder: A clinical pilot study.

OBJECTIVES: To explore the relationship between nocturnal levels of stress-related hormones and different sleep-wake states in chronic insomnia disorder (CID) patients. METHODS: Thirty-three CID patients and 34 good sleepers were enrolled and completed assessment of sleep log, Pittsburgh Sleep Quality Index and Insomnia Severity Index. During a-overnight polysomnography monitoring, the patients' vein bleeds were continually collected at different time points (pre-sleep, deep-sleep, 5-min or 30-min waking, and morning waking-up). The control subjects' bleeds were collected only at 22:00 and morning waking-up. The serum hormones were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with at pre-sleep, the level of cortisol was significantly higher at morning waking-up respectively in two-group subjects (Ps < 0.001), with insignificant inter-group differences in cortisol, corticotropin releasing hormone and copeptin at the two time-points. In the patients, the nocturnal secretion curves of three hormones were similar, with the highest concentration at morning waking-up, followed by 30-min waking, 5-min waking, pre-sleep, and deep-sleep. The patients' cortisol (Z = 79.192, P < 0.001) and copeptin (Z = 12.333, P = 0.015) levels were statistically different at different time-points, with higher cortisol at morning waking-up relative to deep-sleep, pre-sleep and 5-min waking (Ps < 0.05), and at 30-min waking relative to deep-sleep and pre-sleep (Ps < 0.05), and higher copeptin at morning waking-up relative to deep-sleep (P < 0.05). CONCLUSIONS: In CID, the nocturnal wakes were instantaneously accompanied by high level, and deep sleep was accompanied by the lowest levels, of stress-related hormones, especially in cortisol, supporting the insomniac hypothesis of increased nocturnal pulse-release of cortisol.

Increased functional connectivity within the salience network in patients with insomnia.

BACKGROUND: Insomnia is a common sleep disorder with significant negative impacts on emotional states; however, the underlying mechanism of insomnia with comorbid emotional dysregulation remains largely unknown. The salience network (SN) plays an important role in both sleep and emotional regulation. The study aimed to explore the specific alterations in functional connectivity (FC) within the SN in insomnia patients. METHODS: A total of 30 eligible patients with insomnia disorder (ID group) and 30 healthy controls (HC group) underwent resting-state functional magnetic resonance imaging (fMRI) scanning and psychometric assessments. Differences in FC within the SN were examined using seed-based region-to-region connectivity analysis. RESULTS: Compared with healthy controls, patients with insomnia showed increased FC within the SN, mainly between the anterior cingulate cortex (ACC) and right superior frontal gyrus (SFG), the right SFG and right supramarginal gyrus (SMG), and between the right insular (INS) and left SMG (P<0.05). Additionally, significant correlations were observed between increased FC and the Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), and Hamilton Anxiety Rating Scale (HAMA) scores (P<0.05, after Bonferroni correction). CONCLUSIONS: These results suggest that increased FC within the SN may be related to poor sleep quality and negative emotions, highlighting the importance of the SN in the pathophysiological mechanisms of insomnia with comorbid emotional dysregulation.