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.

High-Frequency rTMS Could Improve Impaired Memory in Mild Cognitive Impairment Patients in China: A Randomized Controlled Study.

OBJECTIVE: The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on improving memory deficits in mild cognitive impairment (MCI), as well as to provide visualized evidence for neuronal specificity by using resting-state functional magnetic resonance imaging. MATERIALS AND METHODS: Forty MCI patients were enrolled to receive 10-session and sham-controlled 10Hz-rTMS over the left dorsolateral prefrontal cortex. The resting-state functional magnetic resonance imaging combined with memory scales assessment were performed before and after the intervention. To elucidate the therapeutic mechanism of rTMS, amplitude of low-frequency fluctuations (ALFF) and functional connectivity were calculated. The Pearson correlation was used to measure the relationship between ALFF and memory performance. RESULTS: Compared with the sham group, ALFF significantly increased in the right insula, right inferior frontal gyrus-opercular part, and decreased in the left middle occipital gyrus, left angular gyrus, and left lingual gyrus after rTMS. The change in Auditory Verbal Learning Test scores were negatively correlated with ALFF decreases in the left lingual gyrus. Functional connectivity significantly increased between the posterior cingulate cortex and right supramarginal gyrus, and decreased between the right frontoinsular cortex and right supramarginal gyrus after intervention. CONCLUSION: High-frequency rTMS over the left dorsolateral prefrontal cortex could facilitate improvement on impaired memory in patients with MCI via modulating the neuronal activity and brain network.

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.

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.

Effects of Noninvasive Brain Stimulation (NIBS) on Cognitive Impairment in Mild Cognitive Impairment and Alzheimer Disease: A Meta-analysis.

OBJECTIVE: The purpose of this meta-analysis was to evaluate the beneficial effects and optimal stimulation protocol of noninvasive brain stimulation (NIBS) including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on patients with mild cognitive impairment and Alzheimer disease. MATERIALS AND METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched until March 2020. The cognitive outcomes were extracted and the standardized mean difference with 95% confidence interval was calculated. RESULTS: Twenty-eight studies were included. The result of NIBS showed significant effect on global cognition (P<0.05). Low-frequency rTMS over right dorsolateral prefrontal cortex (DLPFC), high-frequency rTMS (HF-rTMS) over left DLPFC, and the tDCS over left DLPFC and temporal lobe can significantly improve the memory function (P<0.05). HF-rTMS over left, right, or bilateral DLPFC can significantly improve the language function (P<0.05). Both HF-rTMS and tDCS over left DLPFC can obviously improve the executive function (P<0.05). Multiple sessions of rTMS with 80% to 100% intensity and anode tDCS with 2 mA current density are more suitable for all these functions. CONCLUSIONS: NIBS has a beneficial effect on cognitive performance in both mild cognitive impairment and Alzheimer disease patients. Distinct optimal stimulation parameters were observed for different cognitive functions.

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.

White matter changes from mild cognitive impairment to Alzheimer's disease: a meta-analysis.

Previous diffusion tensor imaging (DTI) studies have reported that both mild cognitive impairment (MCI) and Alzheimer's disease (AD) revealed microstructural changes [fractional anisotropy (FA)]. However, these results were not conclusive. The purpose of this meta-analysis was to identify the consistent FA alterations and the differences between MCI and AD. Case-control studies investigating MCI and AD using FA were searched in the online databases. The quantitative FA value of cognition-related brain regions was extracted and the standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using fixed or random effect models. Twenty six studies with a total of 1,021 patients were included in this meta-analysis. Significantly decreased FA in patients with AD were identified in the left frontal lobe, corpus callosum (CC), fornix, hippocampus (HP), cingulate gyrus (CG), cingulate bundle (CB), uncinate fasciculus (UF), superior longitudinal fasciculus(SLF), the inferior fronto-occipital fascicles (IFOF), and the inferior longitudinal fasciculus(ILF) relative to MCI in this meta-analysis. This study provides objective and quantitative evidence that AD is associated with FA alteration within left frontal lobe, CC, FX, HP, CG, CB, and UF may suggest the key regions of the process from MCI to AD.

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.

Effect of rTMS on Parkinson's cognitive function: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effects and optimal parameters of repetitive transcranial magnetic stimulation (rTMS) on cognition function of patients with Parkinson's disease (PD) and to estimate which cognitive function may obtain more benefits from rTMS. METHOD: The articles dealing with rTMS on cognitive function of PD patients were retrieved from the databases until April 2019. Outcomes of global cognitive function and different cognitive domains were extracted. The standardized mean differences (SMDs) with 95% confidence interval (CI) of cognitive outcome for different parameters, scales, and cognitive functions were estimated. RESULTS: Fourteen studies involving 173 subjects were included in this meta-analysis. A significant effect size was observed with the mini-mental state examination (MMSE) for the global cognitive outcome based on the evidence of four published articles. Further subtests for different cognitive domains demonstrated prominent effect for the executive function. The significant effect sizes for executive function were found with multiple sessions of high-frequency rTMS over frontal cortex; especially over dorsolateral prefrontal cortex (DLPFC). All of the other cognitive domains, which included memory, attention, and language ability, did not obtain significant effects. CONCLUSIONS: Multiple sessions of high-frequency rTMS over the DLPFC may have positive effect on executive function in PD patients. Further well designed studies with large sample sizes are needed to verify our results and ascertain the long-term effects of rTMS.

Concordance of Chest CT and Nucleic Acid Testing in Diagnosing Coronavirus Disease Outside its District of Origin (Wuhan, China).

OBJECTIVES: This study aimed to determine the concordance between CT and nucleic acid testing in diagnosing coronavirus disease (COVID-19) outside its district of origin (Wuhan, China). METHODS: Twenty-three consecutive patients with COVID-19, confirmed by nucleic acid testing, were enrolled from two designated hospitals outside the district of disease origin. We collected clinical, laboratory, and CT data and assessed the concordance between CT manifestations and nucleic acid test results by comparing the percentage of patients with and without abnormal CT findings. Furthermore, using Chi-square tests, we analyzed the differences in CT manifestations between patients with and without an exposure history or symptoms. RESULTS: Multiple ground-glass opacities (GGOs), with or without consolidation, were observed on the initial CT scans of 19 patients (82.6%), whereas the remaining 4 (17.4%) showed no CT abnormalities, indicating that the initial chest CT findings were not entirely concordant with the nucleic acid test results in diagnosing COVID-19. Among the latter 4 patients, we observed multiple GGOs with and without consolidation in 2 patients on the follow-up chest CT scans taken on days 7 and 14 after admission, respectively. The remaining 2 patients showed no abnormalities on the follow-up CT scans. Furthermore, abnormal CT findings were found more frequently in patients who had been exposed to COVID-19 in its district of origin than in those who had not been exposed and in symptomatic patients than in asymptomatic patients (all p<0.05). CONCLUSIONS: Patients with positive results on nucleic acid testing may or may not have the abnormal CT manifestations that are frequently found in symptomatic patients with a history of exposure to the district of COVID-19 origin.

A radiomics model of liver CT to predict risk of hepatic encephalopathy secondary to hepatitis B related cirrhosis.

PURPOSE: To build a radiomics model of liver contrast-enhanced computed tomography (CT) to predict hepatic encephalopathy secondary to Hepatitis B related cirrhosis. MATERIALS AND METHODS: This study consisted of 304 consecutive patients with first-diagnosed hepatitis B related cirrhosis. 212 and 92 patients were randomly computer-generated into training and testing cohorts, among which 38 and 21 patients endured HE, respectively. 356 radiomics features of liver were extracted from portal venous-phase CT data, and 3 clinical features were collected from medical record. After data were standardized by Z-score, we used least absolute shrinkage and selection operator to choose useful radiomics features. Ultimately, three predictive models including a radiomics model, a clinical model and an integrated model of radiomics and clinical features were built by analysis of R-software. Predictive performance was tested by multivariable logistic regression, and evaluated by area under receiver-operating characteristic curve (AUC), and accuracy. RESULTS: 19 radiomics features of liver CT were selected. The selected radiomics features and 3 relevant clinical features were applied to develop a radiomics model, a clinical model, and an integrated model of both radiomics and clinical features. The integrated model showed better performance than the radiomics model or clinical model to predict HE (AUC = 0.94 vs. 0.91 or 0.76, and 0.87 vs. 0.86 or 0.73; accuracy = 0.93 vs. 0.89 or 0.83, and 0.83 vs. 0.84 or 0.77) in the training and testing cohorts, respectively. CONCLUSION: The integrated model of radiomics and clinical features could well predict HE secondary to hepatitis B related cirrhosis.

CT manifestations of the coronavirus disease 2019 of imported infection versus second-generation infection in patients outside the original district (Wuhan, China) of this disease: An observational study.

To explore the discrepancy in computed tomography (CT) manifestations of the coronavirus disease 2019 (COVID-19) in patients outside the original district (Wuhan, China) between cases with imported infection and second-generation infection, 22 patients with COVID-19 from 2 hospitals in Nanchong, China, 938 km away from the original district (Wuhan, China) of this disease were enrolled. All patients underwent initial and follow-up CT after admission during the treatment, and were divided into 2 groups. Group A and B were composed of 15 patients with a history of exposure to the original district (Wuhan, China) in short-term (i.e., imported infection), and 7 with a close contact with the patients with confirmed COVID-19 or with the healthy individuals from the original district (i.e., second-generation infection), respectively. Initial CT features including extent score and density score between groups were statistically compared. We found that all patients in group A and 3 of 7 patients in group B had abnormal CT findings while 4 of 7 patients in group B had not. Patients with abnormal CT findings were more frequent in group A than in group B (P < .05). On initial CT, pure ground glass opacity (GGO), and GGO with consolidation and/or other abnormalities were found in 20% (3/15) and 80% (12/15) patients in group A, respectively, while 1 (14.3%), 2 (28.6%), and 4 (57.1%) had pure GGOs, GGO with focal consolidation, and normal CT appearances in Group B, respectively. Patients with extent and density scores of ≥5 were more frequent in group A than in group B (all P-values < .01). Additionally, 3 of 4 (75%) patients with normal initial CT findings had focal pure GGO lesions on follow-up. In conclusion, COVID-19 in patients with a history of exposure to the original district can be severer than with the second-generation infection on CT.

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.

Concordance of chest ct and nucleic acid testing in diagnosing coronavirus disease outside its district of origin (Wuhan, China)

OBJECTIVES: This study aimed to determine the concordance between CT and nucleic acid testing in diagnosing coronavirus disease (COVID-19) outside its district of origin (Wuhan, China). METHODS: Twenty-three consecutive patients with COVID-19, confirmed by nucleic acid testing, were enrolled from two designated hospitals outside the district of disease origin. We collected clinical, laboratory, and CT data and assessed the concordance between CT manifestations and nucleic acid test results by comparing the percentage of patients with and without abnormal CT findings. Furthermore, using Chi-square tests, we analyzed the differences in CT manifestations between patients with and without an exposure history or symptoms. RESULTS: Multiple ground-glass opacities (GGOs), with or without consolidation, were observed on the initial CT scans of 19 patients (82.6%), whereas the remaining 4 (17.4%) showed no CT abnormalities, indicating that the initial chest CT findings were not entirely concordant with the nucleic acid test results in diagnosing COVID-19. Among the latter 4 patients, we observed multiple GGOs with and without consolidation in 2 patients on the follow-up chest CT scans taken on days 7 and 14 after admission, respectively. The remaining 2 patients showed no abnormalities on the follow-up CT scans. Furthermore, abnormal CT findings were found more frequently in patients who had been exposed to COVID-19 in its district of origin than in those who had not been exposed and in symptomatic patients than in asymptomatic patients (all p<0.05). CONCLUSIONS: Patients with positive results on nucleic acid testing may or may not have the abnormal CT manifestations that are frequently found in symptomatic patients with a history of exposure to the district of COVID-19 origin.

Different Therapeutic Effects of Transcranial Direct Current Stimulation on Upper and Lower Limb Recovery of Stroke Patients with Motor Dysfunction: A Meta-Analysis.

Objective: To explore the effects of transcranial direct current stimulation (tDCS) on the motor recovery of stroke patients and the effect differences between the upper limb and lower limb. Methods: Randomized control trials published until January 2019 were searched from PubMed, Embase, ScienceDirect, and Cochrane Library databases. The standardized mean difference (SMD) with 95% confidence interval (CI) was estimated separately for upper and lower limb motor outcomes to understand the mean effect size. Results: Twenty-nine studies with 664 subjects were included in this meta-analysis. The overall analyses of tDCS demonstrated significant effect size both for the upper limb (SMD = 0.26, P = 0.002) and the lower limb (SMD = 0.47, P = 0.002). Compared with acute and subacute stroke patients, chronic stroke patients obtained significant effects after tDCS (SMD = 0.25, P = 0.03) in upper limb function. Furthermore, both anode and cathode stimulations produced significant effect size for stroke patients after ≤10 sessions of tDCS (anode: SMD = 0.40, P = 0.001; cathode: SMD = 0.79, P < 0.0001) with >0.029 mA/cm2 of density (anode: SMD = 0.46, P = 0.002; cathode: SMD = 0.79, P < 0.0001). But for lower limb function, more prominent effects were found in subacute stroke patients (SMD = 0.56, P = 0.001) with bilateral tDCS (SMD = 0.59, p = 0.009). Conclusion: tDCS is effective for the recovery of stroke patients with motor dysfunction. In addition, upper limb and lower limb functions obtain distinct effects from different therapeutic parameters of tDCS at different stages, respectively.

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.

Effects of High-Frequency Transcranial Magnetic Stimulation for Cognitive Deficit in Schizophrenia: A Meta-Analysis.

Objective: Repetitive transcranial magnetic stimulation (rTMS) has been applied to dorsolateral prefrontal cortex (DLPFC) to improve cognitive function of patients with schizophrenia (SZs). The aim of this meta-analysis was to evaluate whether a high-frequency rTMS course could enhance cognitive function in SZs. Methods: Studies published in PubMed, Cochrane Library, Embase, ScienceDirect, and Web of science were searched until April 2018. The search terms included: "repetitive transcranial magnetic stimulation" or "Rtms," "SZ," or "schizophrenia," and "neuro-cognition" or "neurocognitive performance" or "cognitive effects" or "cognitive" or "cognition" or "working memory" or "executive function" or "language function" or "processing speed," After screening the literatures according to inclusion and exclusion criteria, extracting data, and evaluating the methodological quality of the included studies, a meta-analysis was performed using RevMan 5.3 software (The Cochrane Collaboration, USA). Results: A total of 9 studies on cognitive dysfunction of SZs were included and involved 351 patients. A significant efficacy of high-frequency rTMS on working memory in SZs was found compared to sham stimulation [p = 0.009, standardized mean difference (SMD) = 0.34]. Specifically, rTMS treatment positioned on the left DLPFC, with a total pluses <30,000 was more significantly more effective in improving the working memory (SMD = 0.33, p = 0.03). No improvement was found in other cognitive domains such as executive function, attention, processing speed, and language function. For the follow-up observations, high-frequency rTMS had long-lasting sustained effects on working memory (SMD = 0.45, p = 0.01) and language function (SMD = 0.77, p = 0.02) in SZs. Conclusions: High-frequency rTMS over the left DLPFC with a total pulses <30,000 stimulation could significantly improve working memory in SZs for an extended period of time.

Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A Meta-Analysis.

OBJECTIVE: The purpose of this meta-analysis was to evaluate the therapeutic effect of transcranial direct current stimulation (tDCS) on mild to moderate Alzheimer disease (AD) patients. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched until April 2018. The primary cognitive outcomes were extracted from included articles. A crude standardized mean difference with 95% CI was calculated by using fixed or random effect models. RESULTS: Seven studies with 146 patients were included in this meta-analysis. The pooled result showed that tDCS significantly improved cognitive function of AD patients (standardized mean difference=0.37; 95% CI, 0.09-0.65; P=0.01). Subgroup analyses showed that: a single session of tDCS was significantly effective (P<0.05) whereas repeated sessions of tDCS was not lower current density (0.06 mA/cm) (P>0.05) but not higher current density (0.08 mA/cm) significantly improved cognitive performance; stimulating the temporal cortex (P<0.05) but not the left dorsal lateral prefrontal cortex significantly improved cognitive function of AD patients; and improved cognitive function occurred in the group with higher education (P<0.05) but not in the group with lower education. CONCLUSIONS: Current evidence suggests that tDCS has a beneficial effect in mild to moderate AD patients. We must be cautious about the results of subgroup analysis given small sample sizes, and further well-designed studies with larger sample size are required to verify these results.

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.

Radiomics model of contrast-enhanced computed tomography for predicting the recurrence of acute pancreatitis.

OBJECTIVES: To predict the recurrence of acute pancreatitis (AP) by constructing a radiomics model of contrast-enhanced computed tomography (CECT) at AP first attack. METHODS: We retrospectively enrolled 389 first-attack AP patients (271 in the primary cohort and 118 in the validation cohort) from three tertiary referral centers; 126 and 55 patients endured recurrent attacks in each cohort. Four hundred twelve radiomics features were extracted from arterial and venous phase CECT images, and clinical characteristics were gathered to develop a clinical model. An optimal radiomics signature was chosen using a multivariable logistic regression or support vector machine. The radiomics model was developed and validated by incorporating the optimal radiomics signature and clinical characteristics. The performance of the radiomics model was assessed based on its calibration and classification metrics. RESULTS: The optimal radiomics signature was developed based on a multivariable logistic regression with 10 radiomics features. The classification accuracy of the radiomics model well predicted the recurrence of AP for both the primary and validation cohorts (87.1% and 89.0%, respectively). The area under the receiver operating characteristic curve (AUC) of the radiomics model was significantly better than that of the clinical model for both the primary (0.941 vs. 0.712, p = 0.000) and validation (0.929 vs. 0.671, p = 0.000) cohorts. Good calibration was observed for all the models (p > 0.05). CONCLUSIONS: The radiomics model based on CECT performed well in predicting AP recurrence. As a quantitative method, radiomics exhibits promising performance in terms of alerting recurrent patients to potential precautions. KEY POINTS: • The incidence of recurrence after an initial episode of acute pancreatitis is high, and quantitative methods for predicting recurrence are lacking. • The radiomics model based on contrast-enhanced computed tomography performed well in predicting the recurrence of acute pancreatitis. • As a quantitative method, radiomics exhibits promising performance in terms of alerting recurrent patients to the potential need to take precautions.