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.

Focal hemolymphangioma of the rectum: A case report and literature review.

RATIONALE: Gastrointestinal hemolymphangiomas are very rare, especially in the rectum. Only 3 cases of rectal hemolymphangioma, all of which are diffuse lesions, have been reported in the English literature on PubMed. Our case is the first focal lesion of the rectum. It is important for radiologists to correctly identify the imaging features of rectal hemolymphangiomas. PATIENT CONCERNS: A 51-year-old woman visited our hospital because of intermittent constipation for 3 years. DIAGNOSES: Colonoscopy revealed a prominent lesion on the left anterior wall of the lower rectum. Transvaginal color Doppler ultrasonography showed that the posterior vaginal wall area had a mixed-echo mass, and blood flow signals of the dots and stripes could be seen. Pelvic magnetic resonance imaging showed that the cystic space-occupying lesion in the region between the left anterior wall of the lower rectum and the posterior wall of the middle and lower vagina had a clear boundary. INTERVENTIONS: The patient underwent surgery to remove the rectal lesions. The surgical specimen was finally diagnosed as local hemolymphangioma by pathological analysis. LESSONS: Localized hemolymphangioma of the rectum is very rare, and imaging examination is essential for the diagnosis and evaluation of the extent of lesion invasion.

Insomnia disorder with objective short sleep duration (ISS) phenotype and cognitive performance: a systematic review and meta-analysis.

OBJECTIVE: Insomnia disorder with objective short sleep duration (ISS) has been considered as a biologically severe subtype. The aim of this meta-analysis was to reveal the association of the ISS phenotype and cognitive performance. METHODS: We searched PubMed, EMBASE, and the Cochrane Library for studies that observed an association of cognitive performance and insomnia with objective short sleep duration (ISS) phenotype. The "metafor" and "MAd" packages in R software (version 4.2.0) were used to calculate the unbiased standardized mean difference (Hedge's g), which was adjusted so that a negative value indicated worse cognitive performance. RESULTS: The pooled analysis with 1339 participants revealed that the ISS phenotype was associated with overall cognitive impairments (Hedges' g = - 0.56 [- 0.89, - 0.23]), as well as specific cognitive domains including attention (Hedges' g = - 0.86 [- 1.25, - 0.47]), memory (Hedges' g = - 0.47 [- 0.82, - 0.12]), and executive function (Hedges' g = - 0.39 [- 0.76, - 0.02]). However, cognitive performance was not significantly different between insomnia disorder with objective normal sleep duration (INS) and good sleepers (p > .05). CONCLUSION: Insomnia disorder with the ISS phenotype, but not the INS phenotype, was associated with cognitive impairments, suggesting the possible utility of treating the ISS phenotype to improve cognitive performance.

Noninvasively evaluating the grade and IDH mutation status of gliomas by using mono-exponential, bi-exponential diffusion-weighted imaging and three-dimensional pseudo-continuous arterial spin labeling.

OBJECTIVES: To noninvasively assess the diagnostic performance of diffusion-weighted imaging (DWI), bi-exponential intravoxel incoherent motion imaging (IVIM) and three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) in differentiating lower-grade gliomas (LGGs) from high-grade gliomas (HGGs), and predicting the isocitrate dehydrogenase (IDH) mutation status. MATERIALS AND METHODS: Ninety-five patients with pathologically confirmed grade 2-4 gliomas with preoperative DWI, IVIM and 3D pCASL were enrolled in this study. The Student's t test and Mann-Whitney U test were used to evaluate differences in parameters of DWI, IVIM and 3D pCASL between LGG and HGG as well as between mutant and wild-type IDH in grade 2 and 3 diffusion astrocytoma; receiver operator characteristic (ROC) analysis was used to assess the diagnostic performance. RESULTS: The value of ADCmean, ADCmin, Dmean and Dmin in HGGs were lower than in LGGs, while the value of CBFmean and CBFmax in HGGs were higher than in LGGs. In ROC analysis, the AUC values of Dmean, Dmin and CBFmax were 0.827, 0.878 and 0.839, respectively. The combination of CBFmax and Dmin displayed the highest diagnostic performance to distinguish LGGs from HGGs, with AUC 0.906, sensitivity 82.4 %, and specificity 86.4 %. In grades 2 and 3 diffusion astrocytoma patients, ADCmin, Dmean, Dmin, CBFmean and CBFmax showed significant differences between IDHmut and IDHwt group (p < 0.05, 0.001, 0.001, 0.01 and 0.001, respectively) and the AUC values were 0. 709, 0.849, 0.919, 0.755 and 0.873, respectively. Similarly, the combination of CBFmax and Dmin demonstrated the highest AUC value (0.938) in prediction IDH mutation status, with sensitivity 92.9 %, and specificity 95.5 %. CONCLUSION: The combination of IVIM and 3D pCASL can be used in prediction histologic grade and IDH mutation status of glioma noninvasively.

Heart rate variability in patients with insomnia disorder: a systematic review and meta-analysis.

BACKGROUND: Though logical inference based on small studies suggests that patients with insomnia have a blunted heart rate variability (HRV), this condition not been clearly shown. This meta-analysis aimed to determine whether or not HRV was impaired in patients with insomnia. MATERIALS AND METHODS: We conducted a comprehensive literature search for studies that examined the association of HRV with insomnia disorder. HRV measures were extracted using the SDNN (time-domain measure, i.e., standard deviation of all NN intervals,) or the HF-norm (frequency-domain measure, i.e., high-frequency power normalized using total power). The effect size estimates of R_equivalent obtained from p values and sample size were synthesized. RESULTS: We identified 17 studies with 921 participants. The pooled R_equivalent was 0.19 with 95% CI of 0.12 and 0.25 (p < 0.001), and there was no significant heterogeneity (I2 = 0.0%, p = 0.809). A p value of 0.075 corresponding to the R_equivalent of 0.19 was obtained, suggesting that blunted HRV was not significant in patients with insomnia disorder. CONCLUSION: The current evidence did not confirm that HRV was reliably impaired in patients with insomnia disorder. Prospective studies using standard HRV measures are needed to clarify the HRV dynamics in different insomnia subtypes.

Cognitive-behavioral therapy for insomnia with objective short sleep duration phenotype: A systematic review with meta-analysis.

Cognitive-behavioral therapy for insomnia (CBT-I) has been recommended as the first-line therapy for this condition. However, insomnia disorder with objective short sleep duration (ISS) phenotype is a distinct subtype from insomnia with normal sleep duration (INS) phenotype, and it may have a differential therapeutic response. We searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov using the PICOS principle for studies that examined the efficacy of cognitive-behavioral therapy for those with the ISS phenotype versus the INS phenotype, and identified nine studies with 612 patients with insomnia disorder. This included 270 patients with the ISS phenotype and 342 patients with the INS phenotype. The main outcome was that CBT-I had a better efficacy for the INS phenotype compared with the ISS phenotype, with about 30% higher response and about 20% higher remission. Similar results were indicated in the secondary outcomes. The therapeutic response of the ISS phenotype was significantly different from that of the INS phenotype. In the future, research is needed to clarify how to optimally treat insomnia disorder with the ISS phenotype in prospective randomized clinical trials, and to understand whether decreasing physiologic arousal will be necessary to improve results.

Insomnia disorder diagnosed by resting-state fMRI-based SVM classifier.

BACKGROUND: The main classification systems of sleep disorders are based on the subjective self-reported criteria. Objective measures are essential to characterize the nocturnal sleep disturbance, identify daytime impairment, and determine the course of these symptoms. The aim of this study was to establish a resting-state fMRI-based support vector machine (SVM) classifier to diagnose insomnia disorder. METHODS: We enrolled 20 patients with insomnia disorder and 21 healthy controls, and obtained their simultaneous polysomnographic electroencephalography and functional magnetic resonance imaging (EEG-fMRI) recordings. The SVM classifiers were trained to capture insomnia. Classifier performance was quantified by a 5-fold cross validation and on independent test dataset. RESULTS: The fMRI-based SVM classifier was able to diagnose insomnia with an accuracy of 89.3% (sensitivity of 90.9%, specificity of 87.7%). The robustness of SVM classifier was encouraging. CONCLUSIONS: We established an encouraging resting-state fMRI-based SVM classifier to automatically diagnose insomnia disorder. As an objective measure for assessing insomnia disorder, it would be of additional value to the current self-reported subjective criteria.

Changes in white matter functional networks during wakefulness and sleep.

Blood oxygenation level-dependent (BOLD) signals in the white matter (WM) have been demonstrated to encode neural activities by showing structure-specific temporal correlations during resting-state and task-specific imaging of fiber pathways with various degrees of correlations in strength and time delay. Previous neuroimaging studies have shown state-dependent functional connectivity and regional amplitude of signal fluctuations in brain gray matter across wakefulness and nonrapid eye movement (NREM) sleep cycles. However, the functional characteristics of WM during sleep remain unknown. Using simultaneous electroencephalography and functional magnetic resonance imaging data during wakefulness and NREM sleep collected from 66 healthy participants, we constructed 10 stable WM functional networks using clustering analysis. Functional connectivity between these WM functional networks and regional amplitude of WM signal fluctuations across multiple low-frequency bands were evaluated. In general, decreased WM functional connectivity between superficial and middle layer WM functional networks was observed from wakefulness to sleep. In addition, functional connectivity between the deep and cerebellar networks was higher during light sleep and lower during both wakefulness and deep sleep. The regional fluctuation amplitude was always higher during light sleep and lower during deep sleep. Importantly, slow-wave activity during deep sleep negatively correlated with functional connectivity between WM functional networks but positively correlated with fluctuation strength in the WM. These observations provide direct physiological evidence that neural activities in the WM are modulated by the sleep-wake cycle. This study provided the initial mapping of functional changes in WM during sleep.

Repetitive Transcranial Magnetic Stimulation Induces Quantified Functional and Structural Changes in Subcortical Stroke: A Combined Arterial Spin Labeling Perfusion and Diffusion Tensor Imaging Study.

Purpose: To explore the changes of cerebral blood flow (CBF) and fractional anisotropy (FA) in stroke patients with motor dysfunction after repetitive transcranial magnetic stimulation (rTMS) treatment, and to better understand the role of rTMS on motor rehabilitation of subcortical stroke patients from the perfusion and structural level. Materials and Methods: In total, 23 first-episode acute ischemic stroke patients and sixteen healthy controls (HCs) were included. The patients were divided into the rTMS and sham group. The rehabilitation assessments and examination of perfusion and structural MRI were performed before and after rTMS therapy for each patient. Voxel-based analysis was used to detect the difference in CBF and FA among all three groups. The Pearson correlation analysis was conducted to evaluate the relationship between the CBF/FA value and the motor scales. Results: After rTMS, significantly increased CBF was found in the ipsilesional supplementary motor area, postcentral gyrus, precentral gyrus, pons, medulla oblongata, contralesional midbrain, superior cerebellar peduncle, and middle cerebellar peduncle compared to that during the prestimulation and in the sham group, these fasciculi comprise the cortex-pontine-cerebellum-cortex (CPC) loop. Besides, altered CBF in the ipsilesional precentral gyrus, postcentral gyrus, and pons was positively associated with the improved Fugl-Meyer assessment (FMA) scores. Significantly decreased FA was found in the contralesional precentral gyrus, increased FA was found in the ipsilesional postcentral gyrus, precentral gyrus, contralesional supplementary motor area, and bilateral cerebellum, these fasciculi comprise the corticospinal tract (CST). The change of FMA score was positively correlated with altered FA value in the ipsilesional postcentral gyrus and negatively correlated with altered FA value in the contralesional precentral gyrus. Conclusion: Our results suggested that rTMS could facilitate the motor recovery of stroke patients. High frequency could promote the improvement of functional activity of ipsilesional CPC loop and the recovery of the microstructure of CST.

Distinction of High- and Low-Frequency Repetitive Transcranial Magnetic Stimulation on the Functional Reorganization of the Motor Network in Stroke Patients.

Objective: To investigate the functional reorganization of the motor network after repetitive transcranial magnetic stimulation (rTMS) in stroke patients with motor dysfunction and the distinction between high-frequency rTMS (HF-rTMS) and low-frequency rTMS (LF-rTMS). Methods: Thirty-three subcortical stroke patients were enrolled and assigned to the HF-rTMS group, LF-rTMS group, and sham group. Each patient of rTMS groups received either 10.0 Hz rTMS over the ipsilesional primary motor cortex (M1) or 1.0 Hz rTMS over the contralesional M1 for 10 consecutive days. A resting-state functional magnetic resonance imaging (fMRI) scan and neurological examinations were performed at baseline and after rTMS. The motor network and functional connectivities intramotor network with the core brain regions including the bilateral M1, premotor area (PMA), and supplementary motor area (SMA) were calculated. Comparisons of functional connectivities and Pearson correlation analysis between functional connectivity changes and behavioral improvement were calculated. Results: Significant motor improvement was found after rTMS in all groups which was larger in two rTMS groups than in the sham group. The functional connectivities of the motor network were significantly increased in bilateral M1, SMA, and contralesional PMA after real rTMS. These changes were only detected in the regions of the ipsilesional hemisphere in the HF-rTMS group and in the regions of the contralesional hemisphere in the LF-rTMS group. Significantly changed functional connectivities of the intramotor network were found between the ipsilesional M1 and SMA and contralesional PMA, between contralesional M1 and contralesional SMA, between contralesional SMA and ipsilesional SMA and contralesional PMA in the HF-rTMS group in which the changed connectivity between ipsilesional M1 and contralesional PMA was obviously correlated with the motor improvement. In addition, the functional connectivity of the intramotor network between ipsilesional M1 and contralesional PMA was significantly higher in the HF-rTMS group than in the LF-rTMS group. Conclusion: Both HF-rTMS and LF-rTMS have a positive effect on motor recovery in patients with subcortical stroke and could promote the reorganization of the motor network. HF-rTMS may contribute more to the functional connectivity reorganization of the ipsilesional motor network and realize greater benefit to the motor recovery.

Placebo effect of rTMS on post-stroke motor rehabilitation: a meta-analysis.

Previous studies have shown that placebo repetitive transcranial magnetic stimulation (rTMS) was effective on post-stroke motor rehabilitation. However, the placebo effect has not been systematically assessed. Therefore, this meta-analysis was conducted to resolve this issue and explore potential influencing factors further. PubMed, Embase, web of science and the Cochrane Library were searched for published randomised controlled trials (RCTs) with placebo rTMS treatment of stroke recovery until May 2019. The placebo effect size (Hedges' g) was estimated using the motor outcome of pre- and post- placebo rTMS treatment. Meta-regression analysis was also performed to explore potential influencing factors for the placebo effect. Twenty-six placebo-controlled trials (including 381 patients in placebo group) were selected. Effect size results (Hedges' g = 0.466, 95% CI 0.207-0.726; P < 0.05) showed a medium and significant placebo rTMS effect on improving post-stroke motor recovery. The mean ratio of the effect size of sham to real stimulation was 56%. Meta-regression analysis did not find significant result except for the treatment sessions, which was significantly correlated with the placebo effect size (r = 0.465, p = 0.031). In the follow-up observations (1, 2 and 3 months), the sham rTMS groups manifested gradually increased motor improvement, which was similar to the real group, but the amplitude was lower, which was sustained for at least 3 months. Placebo effect of rTMS on post-stroke motor recovery was medium but significant. Regarding different sham styles, the number of stimulation sessions had an impact on the effect.

Insomnia Disorder Increases the Risk of Mortality: Pooled Analysis of Annual Cumulative Time-to-Event Data.

The association of mortality risk and insomnia disorder with daytime impairments has been plausible. The purpose of this study was to evaluate the strength of evidence for this relationship. We performed a comprehensive literature search for clinical Cohort trials including annual cumulative time-to-event data that evaluated the risk of mortality in insomnia disorder patients with daytime impairments. We used pooled hazard ratio (HR) as the main outcome measure and Kaplan-Meier survive curve to display outcome measures. The weighted cumulative mortality of 4.5% for patients with insomnia disorder was higher than that of 2.6% for those without insomnia (p<0.001). Higher risk of mortality presented in patients with insomnia disorder when compared to those without insomnia (HR = 1.66, 95% CI = 1.25-2.19, p<0.001). Patients with duration of more than 10 years were at a greater risk of annual cumulative mortality (R2 = 0.891, p<0.001). Insomnia disorder with daytime impairments increased the risk of mortality, and patients with duration of more than 10 years were at a greater risk of annual cumulative mortality.

Dynamic features of placebo effects addressing persistent insomnia disorder: A meta-analysis of placebo-controlled randomized clinical trials.

It has been accepted knowledge that placebo effects have been significant in insomnia clinical trials. However, the dynamic features of placebo effects have not been clarified. Our aim was therefore to conduct a meta-analysis of placebo-controlled randomized clinical trials to characterize the dynamic features of placebo effects addressing persistent insomnia disorder. We performed a comprehensive literature search for randomized, placebo-controlled, double-blind clinical trials evaluating the efficacy of therapeutic regimens addressing persistent insomnia disorder. We pooled separate effect size estimates (Hedge's g) of placebo and regimen conditions across trials for outcome measures, and multilevel mixed-effects models were used to explore potential sources of heterogeneity. The placebo effects were significant and robust to improve the symptoms of insomnia, and subjective measures were significantly smaller than objective measures (p < .001), but placebo response rates were nearly identical between subjective and objective measures. The overall placebo effects were influenced by publication year (p = .015), treatment duration (p = .010), sample size (p < .001) and therapeutic regimen (p < .001). Placebo effects showed a diphasic feature within treatment duration: initially a decrease and subsequently being stable; a sustained decline trend after withdrawals; and a steady-to-upward trend for a mixed therapeutic regimens in a large-scale period over decades. The dynamic features of placebo effects addressing persistent insomnia disorder may lead to the development and validation of dosing strategies that require less medication exposure to maintain clinical effects.

Effect-size seed-based d mapping of resting-state fMRI for persistent insomnia disorder.

BACKGROUND: Recently, several functional neuroimaging studies have been conducted in patients with persistent insomnia disorder, but these studies have yielded diverse findings. We aimed to identify convergence in function across the heterogeneity of patients, modalities, and methods for insomnia disorder by performing a quantitative coordinate-based meta-analysis. MATERIALS AND METHODS: We performed a quantitative, voxel-wise meta-analysis of resting-state fMRI studies using seed-based d mapping to find convergence of functional alterations in persistent insomnia disorder. RESULTS: We included 28 studies comprising 287 peak foci involving 951 patients with insomnia disorder and 884 healthy controls. Patients with persistent insomnia disorder showed that increased activity was more frequently reported in right parahippocampal gyrus (p < 0.001) and left median cingulate/paracingulate gyri (p < 0.001); while decreased activity was more frequently reported in right cerebellum (p < 0.001) and left superior frontal gyrus/medial orbital (p < 0.001). CONCLUSION: The altered functional networks in patients with persistent insomnia disorder converge in median cingulate/paracingulate gyri and right parahippocampal gyrus with increased activity, and cerebellum and superior frontal gyrus/medial orbital with reduced activity. As a potential target in future, the identification of these altered or unbalanced networks is very important because they may be noninvasively rebalanced to sleep homeostasis by noninvasive brain stimulation methods.

Biphasic feature of placebo response in primary insomnia: pooled analysis of data from randomized controlled clinical trials of orexin receptor antagonists.

OBJECTIVES: The placebo response to orexin receptor antagonists in primary insomnia is little-known. Our aim was, therefore, to conduct a systematic review of placebo-controlled randomized clinical trials to characterize placebo response. METHODS: We performed a comprehensive literature search for randomized, placebo-controlled, double-blind clinical trials evaluating the efficacy of orexin receptor antagonists addressing primary insomnia. To pool effect size estimates (Cohen's d) of placebo and orexin receptor antagonists across trials for outcome measures, a meta-analysis was done according to the Cochrane guideline. RESULTS: The placebo response was significant and robust to improve the symptoms of insomnia in terms of objective and subjective measures, and the effects (0.70 ± 0.51) in subjective measures were smaller than that (1.10 ± 1.14) in objective measures (p = 0.027). The biphasic feature of placebo response showed an initial short-term increase of placebo effect and subsequent changeless long-term effect. CONCLUSION: The biphasic feature of placebo response is clinically useful, and neuroimaging is essential to clarify the long-term mechanism in the future.

Efficacy and Placebo Response of Multimodal Treatments for Primary Insomnia: A Network Meta-Analysis.

BACKGROUND: Pharmacotherapy, psychotherapy, and complementary therapy have been used for primary insomnia. However, the efficacy and placebo response are not exactly clear because of limited clinical data. We therefore conducted a systematic review to examine the efficacy and placebo response of multimodal treatments. METHODS: We performed a comprehensive literature search for randomized placebo-controlled clinical trials evaluating the efficacy of multimodal treatments addressing primary insomnia. To pool effect size estimates (Hedges' g) of active and placebo conditions across studies for outcome measures, a meta-analysis was done according to the Cochrane guideline. RESULTS: The results of network meta-analysis for sleep efficiency showed that orexin receptor antagonists had the maximum effect size of 1.35 (95% confidence interval [CI], 0.88-1.82), followed by γ-aminobutyric acid agonists of 1.28 (95% CI, 0.85-1.71), cognitive behavioral therapy for insomnia of 1.07 (95% CI, 0.10-2.05), acupuncture of 0.64 (95% CI, -0.17 to 2.36), and repetitive transcranial magnetic stimulation of 0.61 (95% CI, -0.52 to 1.75), respectively. However, the placebo response was also significant and robust to improve insomnia symptoms, and 65.9% (95% CI, 49.3%-82.5%) of the effect size of multimodal treatments was actually produced by placebo conditions. CONCLUSIONS: The pharmacotherapy seems the most effective in improving sleep efficiency. However, the optimal therapeutic regimen is still uncertain. In addition, the placebo response is significant and robust in treatments of primary insomnia.

Efficacy and placebo response of repetitive transcranial magnetic stimulation for primary insomnia.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been considered a promising technique for the treatment of primary insomnia. However, its efficacy and placebo response remains unclear due to limited clinical data. Therefore, we conducted a systematic review to examine the efficacy and placebo response of rTMS. METHODS: We performed a comprehensive literature search for clinical trials evaluating the efficacy of rTMS addressing primary insomnia. To pool effect size estimates (Hedges' g) of active rTMS and sham rTMS across studies for outcome measures, a meta-analysis was done according to the Cochrane guideline. RESULTS: In sum, rTMS significantly improved insomnia symptoms in the active rTMS group, and the pooled effect size of Pittsburgh Sleep Quality Index (PSQI) was -0.98 (95% CI: -1.28, -0.68) for treatment duration of 10 days, -1.16 (95% CI: -1.51, -0.82) for 20 days, and -2.14 (95% CI: -2.45, -1.83) for 30 days, respectively. However, the placebo response was also significant, reducing insomnia symptoms in the sham rTMS group. Furthermore, 73.5% (95% CI: 50.8%, 96.2%) of the effect size of active rTMS was actually produced by sham rTMS. CONCLUSION: The rTMS was effective in the treatment of primary insomnia, yet, the placebo effect of sham stimulation was highly significant. This new evidence may alter rTMS regimen for insomnia from a clinical and methodological point of view. Finally, in future research more objective data and multicenter double-blinded controlled studies should be encouraged.

Repetitive transcranial magnetic stimulation (rTMS) fails to increase serum brain-derived neurotrophic factor (BDNF).

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity and in the pathophysiology of various brain disorders. Repetitive transcranial magnetic stimulation (rTMS) has been widely used in neuropsychiatric disease. It is presumed that BDNF mediates the therapeutic benefits of rTMS, but previous results are contradictory. We therefore conducted a meta-analysis to examine the efficacy of rTMS to increase serum BDNF. METHODS: We performed a comprehensive literature search for clinical trials evaluating the efficacy of rTMS and addressing serum BDNF level. To pool effect size estimate (Hedges' g) of serum BDNF across studies, a meta-analysis was performed according to the Cochrane guideline. RESULTS: rTMS failed to increase serum BDNF level with effect size of -0.12 (95% CI: -0.30, 0.06) (P=0.193). Multilevel mixed-effects models analysis showed that overall effect of rTMS on BDNF levels was influenced by group of participants (healthy vs. disease) (P<0.001), stimulation frequency (low-frequency vs. high-frequency) of rTMS (P=0.007), treatment duration (P<0.001) of rTMS, and population age (P<0.001). CONCLUSIONS: Repetitive rTMS fails to increase serum BDNF, and it seems that serum BDNF level is related to frequency and duration of rTMS, as well as age and health status of population.

Microwave ablation vs. parathyroidectomy for secondary hyperparathyroidism in maintenance hemodialysis patients.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) is a serious and common problem in patients undergoing maintenance hemodialysis. Minimally invasive microwave ablation (MWA) has been used to treat SHPT and shows some advantages. However, its efficacy is still undefined. The primary purpose of this study was to determine the efficacy and safety of MWA compared to total parathyroidectomy plus forearm autotransplantation. METHODS: The SHPT patients who were undergoing maintenance hemodialysis (follow-up for 6 to 24 months after treatments) were divided into a MWA group (n = 33) and a parathyroidectomy group (n = 48). The efficacy (serum intact parathyroid hormone [iPTH], calcium, and phosphorus levels) and safety (hoarseness, hypocalcaemia, and persistently low iPTH) were compared between the two groups. Additionally, the study explored potential predictors of response to MWA by a logistic regression analysis. FINDINGS: There were no significant differences in baseline characteristics between the two groups. The rates of achieving the recommended goal for iPTH were significantly higher in the MWA group than that in the parathyroidectomy group at all follow-up times: 57.58% vs. 12.50% at one-day (P < 0.001), 45.45% vs. 16.67% at 1-week (P = 0.005), 57.58% vs. 16.67% at 2-week (P < 0.001), 57.58% vs. 22.92% at 1-month (P = 0.002), and 69.70% vs. 35.42% at 3-month (P = 0.002), 76.47% vs. 28.57% at 6-month (P = 0.005), 87.50% vs. 47.37% at 12-month (P = 0.008), and 81.82% vs. 52.63% at 24-month (P = 0.015), respectively. However, there were no significant differences for phosphorus or calcium at any of the follow-up times (P > 0.05). The persistently low iPTH was more in the parathyroidectomy group (64.6%) than that in the MWA group (0%) (P < 0.001), but there was no significant difference in hoarseness or hypocalcaemia (P > 0.05). Baseline levels of iPTH (P = 0.021) and patient age (P = 0.011) were determined as predictors by univariate logistic regression analysis. CONCLUSION: The MWA could be an alternative to parathyroidectomy for SHPT but its eventual superiority has to be demonstrated by a proper study.

High-Frequency Repetitive Transcranial Magnetic Stimulation Could Improve Impaired Working Memory Induced by Sleep Deprivation.

Objective: To investigate whether and how the working memory impairment induced by sleep deprivation (SD) could be recovered by using repetitive transcranial magnetic stimulation (rTMS), as well as to clarify the corresponding brain activity changes. Methods: Seventeen healthy adults received one session of 5.0 Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) following 24 hours of SD. Resting state functional magnetic resonance imaging (fMRI) and working memory test were performed during a rested waking period, after SD and rTMS. The amplitude of low-frequency fluctuations (ALFF) was used to detect the spontaneous neural activity changes after both SD and rTMS. The relationship between ALFF and the performance of working memory was also assessed by using correlation analysis. Results: After SD, the participants exhibited lower response accuracies and longer reaction times on the working memory tests of letters and numbers. The decreased response accuracy of numbers was significantly improved after rTMS similarly to the state of the rested waking period after a normal night of sleep. ALFF values decreased from the rested waking period state to the state of SD in the brain regions involving the frontal gyrus, precuneus, angular gyrus, and parietal lobe which showed significantly increased ALFF after rTMS. Furthermore, significantly positive correlations were observed between changes of response accuracy and the changes of ALFF value of the inferior frontal gyrus and supramarginal gyrus. Conclusion: These results indicate that high-frequency rTMS applied over left DLPFC may contribute to the recovery of the impaired working memory after SD by modulating the neural activity of related brain regions.