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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.

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

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.

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.

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.

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.

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

Background and Purpose. This meta-analysis aimed to evaluate the therapeutic potential of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional hemisphere on upper limb motor recovery and cortex plasticity after stroke.Methods. Databases of PubMed, Medline, ScienceDirect, Cochrane, and Embase were searched for randomized controlled trials published before Jun 31, 2017. The effect size was evaluated by using the standardized mean difference (SMD) and a 95% confidence interval (CI). Resting motor threshold (rMT) and motor-evoked potential (MEP) were also examined.Results. Twenty-two studies of 1 Hz LF-rTMS over the contralesional hemisphere were included. Significant efficacy was found on finger flexibility (SMD = 0.75), hand strength (SMD = 0.49), and activity dexterity (SMD = 0.32), but not on body function (SMD = 0.29). The positive changes of rMT (SMD = 0.38 for the affected hemisphere and SMD = −0.83 for the unaffected hemisphere) and MEP (SMD = −1.00 for the affected hemisphere and SMD = 0.57 for the unaffected hemisphere) were also significant.Conclusions. LF-rTMS as an add-on therapy significantly improved upper limb functional recovery especially the hand after stroke, probably through rebalanced cortical excitability of both hemispheres. Future studies should determine if LF-rTMS alone or in conjunction with practice/training would be more effective.Clinical Trial Registration Information. This trial is registered with unique identifierCRD42016042181.

Background: To evaluate the effects and optimal parameters of repetitive transcranial magnetic stimulation (rTMS) on cognition improvement of Parkinson's disease (PD) patients with cognitive deficit and to estimate which cognitive function may obtain more benefit from rTMS. Method: The articles dealing with rTMS on cognitive deficit of PD patients were retrieved from the databases until December 2018. Two researchers selected research papers, evaluated their quality, extracted data, and cross-checked them according to the inclusion and exclusion criteria. 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 163 subjects were included in the study. A significant effect size was observed for the mini-mental state examination (MMSE) global cognitive outcome. Further subtests for different cognitive domains demonstrated prominent effect for the executive function. The significant effect sizes were respectively found with multiple sessions of high-frequency rTMS over frontal cortex, especially with over dorsolateral prefrontal cortex (DLPFC), based on subgroup analysis of the executive function. All of the other cognitive domains including working 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 with cognitive deficit. Further well designed studies with large sample sizes are needed to verify our results and ascertain the long-term effects of rTMS.

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.

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.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.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 (P0.05) whereas repeated sessions of tDCS was not lower current density (0.06 mA/cm) (P0.05) but not higher current density (0.08 mA/cm) significantly improved cognitive performance; stimulating the temporal cortex (P0.05) 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 (P0.05) but not in the group with lower education.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.

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.

Background: It has been accepted knowledge that placebo effects have been significant in insomnia randomized 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 primary insomnia. Methods: We performed a comprehensive literature search for randomized, placebo-controlled, double-blind clinical trials evaluating the efficacy of therapeutic regimens addressing primary insomnia. We pooled separate effect size estimates (Hedge's g) of placebo and regimen conditions across trials for outcome measures, and multilevel mixed-effects models was used to explore potential sources of heterogeneity. Findings: The placebo effects were significant and robust to reduce the symptoms of insomnia, and subjective measures were significantly smaller than objective measures (p

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.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment tool for the recovery of cerebral palsy (CP). This report describes the modulation effect of rTMS to functional connectivity, functional network connectivity, motor, and cognitive ability following treatment in a child with mild ataxia CP. After receiving 8 months of 0.5 Hz rTMS treatment over the right dorsolateral prefrontal cortex, the child showed a gradual improvement in motor and cognitive-related functional connectivity and functional network connectivity following treatment as well as improved motor, cognitive functions. These pilot results provide the first evidence of the efficiency of 0.5 Hz of rTMS on a child with CP. Further large sample studies are needed to verify and expand the present findings.

Purpose. The aim of this study was to evaluate the effects of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) on stroke patients with motor dysfunction and to investigate the underlying neural mechanism.Methods. Fifteen stroke patients were assigned to the rTMS treatment (RT) group and conventional treatment (CT) group. Patients in the RT received 10 Hz rTMS stimulation on the ipsilesional primary motor cortex for 10 days plus conventional treatment of CT, which consisted of acupuncture and antiplatelet aggregation medication. Difference in fractional anisotropy (FA) between pretreatment and posttreatment and between two groups was determined. Correlations between FA values and neurological assessments were also calculated.Results. Both groups significantly improved the neurological function after treatment. rTMS-treated patients showed better improvement in Fugl-Meyer Assessment (FMA) score and increased FA value in motor-related white matter and gray matter cortices compared with CT-treated patients and pretreatment status. Besides, the increased FA value in the ipsilesional posterior limb of the internal capsule in RT group was significantly correlated with the improved FMA score.Significance. HF-rTMS could be a supplement therapy to CT in improving motor recovery in patients with stroke. And this benefit effect may be achieved through modulating the ipsilesional corticospinal tracts and motor-related gray matter cortices.

Background Ischemic stroke (IS) is considered to be a heterogeneous, multifactorial disease with a strong genetic background. This study aims to determine whether variants in the antisense noncoding RNA in the INK4 locus (ANRIL) gene are associated with IS in Han Chinese, as well as whether there is evidence of a gene-environment interactions. Materials and Methods A case-controlled association study was conducted in which only patients with atherothrombotic stroke (ATS) were enrolled. Multifactor dimensionality reduction model was employed to screen the best interaction combinations among gene and environmental risk factors; Results A total of 405 subjects (200 cases and 205 controls) and 16 single nucleotide polymorphisms (SNPs) in ANRIL gene were included in this study. The 4 SNPs (rs1537378, rs2184061, rs7044859, and rs7865618) were found to be significantly related to ATS in Chinese Han nationality. In overall people or subjects aged 45 years or older, the GG genotype and G allele of rs1537378, the AA genotype and A allele of rs2184061 and rs7865618, and the AA genotype of rs7044859 increased the risk of ATS. In males, the GG genotype and G allele of rs1537378, the AA genotype and A allele of rs7865618, and the A allele of rs2184061 conferred a susceptibility to ATS. Additionally, the AAAGAGCAAAAAATAG haplotype exhibited an elevated risk of ATS, and a significant interaction was found in ATS susceptibility between ANRIL gene and dyslipidemia; Conclusions The ANRIL gene was related to ATS susceptibility in a Han Chinese. Future studies should be performed with larger samples and among different ethnic populations.

Background: Increasing evidence supports an analgesic effect of repetitive transcranial magnetic stimulation (rTMS) for neuropathic pain (NP). However, the optimal parameters of rTMS (stimulation frequency and treatment sessions) for achieving long-term analgesic effects remain unknown. This study analyzed the current findings in the literature. Objective: The aim of this study was to assess the optimal parameters of rTMS for NP, including the rTMS sessions needed for inducing acute as well as long-term analgesic effects. Study Design: A meta-analysis of the analgesic effect of high frequency rTMS (HF- rTMS) for neuropathic patients. Setting: This meta-analysis examined all studies involving the analgesic efficacy of HF-rTMS for NP. Methods: PubMed, Embase, and the Cochrane library were searched for clinical studies of rTMS treatment on NP published before December 31, 2014. Crude standardized mean differences (SMD) with 95% confidence interval (CI) were calculated for pain intensity after different treatment sessions (from 1 to 10) and follow-up of one or 2 months after rTMS treatment using random effect models. Results: Twenty-five studies (including 32 trials and 589 patients) were selected for the metaanalysis according to the inclusion and exclusion criteria. All 3 HF-rTMS treatments (5, 10, and 20 Hz) produced pain reduction, while there were no differences between them, with the maximal pain reduction found after one and 5 sessions of rTMS treatment. Further, this significant analgesic effect remained forone month after 5 sessions of rTMS treatment. Limitations: There are limitations of this meta-analysis. For example, the long-term analgesic effects of different HF-rTMS and low frequency (LF) rTMS sessions, including the single session of rTMS on different NP of varying origins have yet not been evaluated; the full degree of pain relief is still unclear for many rTMS studies. Conclusions: HF-rTMS stimulation on primary motor cortex is effective in relieving pain in NP patients. Although 5 sessions of rTMS treatment produced a maximal analgesic effect and may be maintained for at least one month, further large-scale and well-controlled trials are needed to determine if this enhanced effect is specific to certain types of NP such as post-stroke related central NP. Key words: High frequency, repetitive transcranial magnetic stimulation, neuropathic pain, single stimulation, multiple stimulation, meta-analysis

Recent studies have indicated that repetitive transcranial magnetic stimulation (rTMS) could improve cognitive function in people with Alzheimer's disease (AD). Yet the results are inconclusive.This meta-analysis aimed to evaluate recent rTMS studies conducted in mild to moderate AD patients.PubMed, Embase, MEDLINE databases and Science Direct were searched for studies of rTMS treatment on AD patients with cognitive impairment published before February 2015. The relevant primary outcomes of cognition were extracted from those included studies. A crude standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by using random effect models.Seven studies with a total of 94 mild to moderate AD patients were included in this meta-analysis. A significant overall rTMS treatment effect on cognition was found for all AD patients (p = 0.0008, SMD = 1.00, 95% CI = 0.41-1.58). Stratification analysis showed that this effect is stimulation frequency- and hemisphere-dependent. High frequency stimulation (1.0 Hz) (p 0.05) but not low frequency stimulation (≤1.0 Hz) (p 0.05) was significantly effective in improving the cognition of AD patients. Further, rTMS stimulation on right dorsolateral prefrontal cortex (DLPFC) and bilateral DLPFC (p 0.05), but not on the left DLPFC (p 0.05) was significantly effective in improving cognitive function of AD patients. A significant effect was observed in the rTMS subgroup (p 0.05), rather than in the rTMS+drug subgroup (p 0.05).This meta-analysis supports that high frequency rTMS stimulation on right- or bilateral-DLPFC has significant therapeutic effect on cognitive function in patients with mild to moderate AD. Due to small number of studies included, more well-controlled rTMS studies should be evaluated in AD patients in the future.

Objective: The aim of this study was to evaluate the short- and long-term effects as well as other parameters of repetitive transcranial magnetic stimulation (rTMS) on upper limb motor functional recovery after stroke. Data sources: The databases of PubMed, Medline, Science Direct, Cochrane, and Embase were searched for randomized controlled studies reporting effects of rTMS on upper limb motor recovery published before October 30, 2016. Review methods: The short- and long-term mean effect sizes as well as the effect size of rTMS frequency of pulse, post-stroke onset, and theta burst stimulation patterns were summarized by calculating the standardized mean difference (SMD) and the 95% confidence interval using fixed/random effect models as appropriate. Results: Thirty-four studies with 904 participants were included in this systematic review. Pooled estimates show that rTMS significantly improved short-term (SMD, 0.43; P < 0.001) and long-term (SMD, 0.49; P < 0.001) manual dexterity. More pronounced effects were found for rTMS administered in the acute phase of stroke (SMD, 0.69), subcortical stroke (SMD, 0.66), 5-session rTMS treatment (SMD, 0.67) and intermittent theta burst stimulation (SMD, 0.60). Only three studies reported mild adverse events such as headache and increased anxiety . Conclusions: Five-session rTMS treatment could best improve stroke-induced upper limb dyskinesia acutely and in a long-lasting manner. Intermittent theta burst stimulation is more beneficial than continuous theta burst stimulation. rTMS applied in the acute phase of stroke is more effective than rTMS applied in the chronic phase. Subcortical lesion benefit more from rTMS than other lesion site.

Coronary artery fistula (CAF) is an uncommon vascular malformation. As the majority of patients remain asymptomatic, approximately half of the cases may be clinical undetectable. We report here a rare case of a 10-year-old female with CAF from the left main coronary artery to the superior vena cava detected on echocardiography and CT angiography.

Objectives: A meta-analysis and systematic review was conducted to investigate the potential effects of repetitive transcranial magnetic stimulation on dysphagia in patients with stroke, including different parameters of frequency and stimulation site. Methods: PubMed, Embase, MEDLINE databases and the Cochrane Library, were searched for randomized controlled studies of repetitive transcranial magnetic stimulation treatment of dysphagia published before March 2016. Results: Six clinical randomized controlled studies of a total of 163 stroke patients were included in this meta-analysis. A significant effect size of 1.24 was found for dysphagic outcome (mean effect size, 1.24; 95% confidence interval (CI), 0.67–1.81). A subgroup analysis based on frequency showed that the clinical scores were significantly improved in dysphagic patients with low frequency repetitive transcranial magnetic stimulation treatment ( P 0.05). The analysis of the follow-up data shows that patients in the repetitive transcranial magnetic stimulation groups still maintained the therapeutic benefit of repetitive transcranial magnetic stimulation four weeks after the last session of repetitive transcranial magnetic stimulation therapy ( P Conclusion: This meta-analysis indicates that repetitive transcranial magnetic stimulation has a positive effect on dysphagia after stroke. Compared with low-frequency repetitive transcranial magnetic stimulation, high-frequency repetitive transcranial magnetic stimulation may be more beneficial to the patients. This meta-analysis also supports that repetitive transcranial magnetic stimulation on an unaffected – or bilateral – hemisphere has a significant therapeutic effect on dysphagia.

Introduction Therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on motor recovery of Parkinson's disease (PD) have been reported; however, the protocols of these studies varied greatly. The aim of this meta‐analysis was to evaluate the optimal rTMS parameters for motor recovery of PD. Methods Electronic databases were searched for studies investigating the therapeutic effects of rTMS on motor function in patients with PD. The section III of the Unified Parkinson's Disease Rating Scale (UPDRS) was extracted as the primary outcome, and the standardized mean difference (SMD) with 95% confidence interval (CI) was calculated. Results Twenty‐three studies with a total of 646 participants were included. The pooled estimates of rTMS revealed significant short‐term (SMD, 0.37; p

Meditation involves attentional regulation and may lead to increased activity in brain regions associated with attention such as dorsal lateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Using functional magnetic resonance imaging, we examined whether DLPFC and ACC were activated during meditation. Subjects who meditate were recruited and scanned on a 3.0 Tesla scanner. Subjects meditated for four sessions of 12 min and performed four sessions of a 6 min control task. Individual and group t-maps were generated of overall meditation response versus control response and late meditation response versus early meditation response for each subject and time courses were plotted. For the overall group (n= 13), and using an overall brain analysis, there were no statistically significant regional activations of interest using conservative thresholds. A region of interest analysis of the entire group time courses of DLPFC and ACC were statistically more active throughout meditation in comparison to the control task. Moreover, dividing the cohort into short (n= 8) and long-term (n= 5) practitioners (>10 years) revealed that the time courses of long-term practitioners had significantly more consistent and sustained activation in the DLPFC and the ACC during meditation versus control in comparison to short-term practitioners. The regional brain activations in the more practised subjects may correlate with better sustained attention and attentional error monitoring. In summary, brain regions associated with attention vary over the time of a meditation session and may differ between long- and short-term meditation practitioners.

The relationship between reaction time and both state and trait personality variables was investigated in 37 participants after 30 h of sleep deprivation. Regression analyses suggested that endorsement of greater Novelty Seeking, anger/hostility, and depression/dejection, and less confusion, was associated with greater reaction time declines on one Multi-Attribute Task Battery index after sleep deprivation. Further, greater Novelty Seeking and depression/dejection, and less vigor/activity, was associated with greater reaction time declines after sleep deprivation on another Multi-Attribute Task Battery index. Additional correlational analyses indicated that better reaction times were associated with greater Novelty Seeking and lower anger/hostility prior to sleep deprivation, and less confusion/bewilderment following sleep deprivation. Findings suggest that both state and trait personality variables are associated with reaction time performance following sleep deprivation.

Dopamine D1 receptors play an important role in memory and cognition in non-human primates. Dopamine D1 agonists have been shown to reverse performance deficits in both aged non-human primates and in primates with lesions to dopamine systems. This study explored whether a single dose of the first full D1 agonist dihydrexidine (DAR-0100) would cause changes in brain activity (perfusion) in dopamine-rich brain regions. We used a new gadolinium-contrast magnetic resonance perfusion scanning technique to measure brain activity. A within-subject cross-over double-blind randomized design was used in 20 adults with SCID-diagnosed schizophrenia. Each morning at 0800 h, they were scanned on a 3.0 T MRI scanner for perfusion. They then received either 20 mg of dihydrexidine, or placebo, subcutaneously over 15 min. Over the next 45 min, they had intermittent MRI scans. Two days later, they had a repeat of the Day 1 schedule, but received the opposite treatment from that given on the first day. Within-day, as well as between-day, comparisons were made to test for perfusion effects of dihydrexidine. Analysis revealed that dihydrexidine induced a significant increase in both prefrontal and non-prefrontal perfusion compared to placebo. The greatest increases occurred approximately 20 min after dihydrexidine infusion, consistent with the short pharmacokinetic half-life of dihydrexidine. These data are consistent with the hypothesis formulated from studies of non-human primates that dihydrexidine and other D1 agonists may be able to modulate prefrontal dopaminergic function.

Vagus nerve stimulation (VNS) therapy has shown antidepressant effects in open acute and long-term studies of treatment-resistant major depression. Mechanisms of action are not fully understood, although clinical data suggest slower onset therapeutic benefit than conventional psychotropic interventions. We set out to map brain systems activated by VNS and to identify serial brain functional correlates of antidepressant treatment and symptomatic response. Nine adults, satisfying DSM-IV criteria for unipolar or bipolar disorder, severe depressed type, were implanted with adjunctive VNS therapy (MRI-compatible technique) and enrolled in a 3-month, double-blind, placebo-controlled, serial-interleaved VNS/functional MRI (fMRI) study and open 20-month follow-up. A multiple regression mixed model with blood oxygenation level dependent (BOLD) signal as the dependent variable revealed that over time, VNS therapy was associated with ventro-medial prefrontal cortex deactivation. Controlling for other variables, acute VNS produced greater right insula activation among the participants with a greater degree of depression. These results suggest that similar to other antidepressant treatments, BOLD deactivation in the ventro-medial prefrontal cortex correlates with the antidepressant response to VNS therapy. The increased acute VNS insula effects among actively depressed participants may also account for the lower dosing observed in VNS clinical trials of depression compared with epilepsy. Future interleaved VNS/fMRI studies to confirm these findings and further clarify the regional neurobiological effects of VNS.

Increasing evidence supports an analgesic effect of repetitive transcranial magnetic stimulation (rTMS) for neuropathic pain (NP). However, the optimal parameters of rTMS (stimulation frequency and treatment sessions) for achieving long-term analgesic effects remain unknown. This study analyzed the current findings in the literature.The aim of this study was to assess the optimal parameters of rTMS for NP, including the rTMS sessions needed for inducing acute as well as long-term analgesic effects.A meta-analysis of the analgesic effect of high frequency rTMS (HF- rTMS) for neuropathic patients.This meta-analysis examined all studies involving the analgesic efficacy of HF-rTMS for NP.PubMed, Embase, and the Cochrane library were searched for clinical studies of rTMS treatment on NP published before December 31, 2014. Crude standardized mean differences (SMD) with 95% confidence interval (CI) were calculated for pain intensity after different treatment sessions (from 1 to 10) and follow-up of one or 2 months after rTMS treatment using random effect models.Twenty-five studies (including 32 trials and 589 patients) were selected for the meta-analysis according to the inclusion and exclusion criteria. All 3 HF-rTMS treatments (5, 10, and 20 Hz) produced pain reduction, while there were no differences between them, with the maximal pain reduction found after one and 5 sessions of rTMS treatment. Further, this significant analgesic effect remained forone month after 5 sessions of rTMS treatment.There are limitations of this meta-analysis. For example, the long-term analgesic effects of different HF-rTMS and low frequency (LF) rTMS sessions, including the single session of rTMS on different NP of varying origins have yet not been evaluated; the full degree of pain relief is still unclear for many rTMS studies.HF-rTMS stimulation on primary motor cortex is effective in relieving pain in NP patients. Although 5 sessions of rTMS treatment produced a maximal analgesic effect and may be maintained for at least one month, further large-scale and well-controlled trials are needed to determine if this enhanced effect is specific to certain types of NP such as post-stroke related central NP.

Background Sleep deprivation (SD) and repetitive transcranial magnetic stimulation (rTMS) have been commonly used to treat depression. Recent studies suggest that co-therapy with rTMS and SD may produce better therapeutic effects than either therapy alone. Therefore, this study was to review the current findings to determine if rTMS can augment the therapeutic effects of SD on depression. Methods Embase, JSTOR, Medline, PubMed, ScienceDirect, and the Cochrane Central Register of Controlled Trials were searched for clinical studies published between January 1985 and March 2015 using the search term “rTMS/repetitive transcranial magnetic stimulation AND sleep deprivation AND depress*”. Only randomized and sham-controlled trials (RCTs) involving the combined use of rTMS and SD in depression patients were included in this systematic review. The scores of the Hamilton Rating Scale for Depression were extracted as primary outcome measures. Results Three RCTs with 72 patients that met the inclusion criteria were included for the systematic review. One of the trials reported skewed data and was described alone. The other two studies, which involved 30 patients in the experimental group (SD + active rTMS) and 22 patients in the control group (SD + sham rTMS), reported normally distributed data. The primary outcome measures showed different results among the three publications: two of which showed great difference between the experimental and the control subjects, and the other one showed non-significant antidepressant effect of rTMS on SD. In addition, two of the included studies reported secondary outcome measures with Clinical Global Impression Rating Scale and a self-reported well-being scale which presented good improvement for the depressive patients in the experiment group when compared with the control. The follow-up assessments in two studies indicated maintained results with the immediate measurements. Conclusions From this study, an overview of the publications concerning the combined use of rTMS and SD is presented, which provides a direction for future research of therapies for depression. More studies are needed to confirm whether there is an augmentative antidepressant effect of rTMS on SD. Electronic supplementary material The online version of this article (doi:10.1186/s12888-015-0674-8) contains supplementary material, which is available to authorized users.

s / Brain Stimulation 8 (2015) 412e427 421 conventional HD-tDCS had 0.31 V/m of maximum cortical EF, while implanting the channel induced 1.6 V/m and 2.58 V/m peaks for shafts with diameter of 2 mm and 4 mm, respectively and it had more focal effects. T-shaped channels had increased peaks compared to shaft only. Finally, it was found that transcranial channels may yield the improved performance in intensity and focality compared to the conventional HD-tDCS; moreover, T-shaped channel had better performance than shaft only and was better for stabilizing the shaft relative to the skull.

s / Brain Stimulation 8 (2015) 412e427 416 Understanding the actions of other people is a crucial skill to function in a social environment. When observing actions, one can understand implied goals and mental-states. The mirror neuron system (MNS) plays an important role in action understanding by internal simulation of the observed movements. This simulation process may be sufficient to decipher thoughts and intentions incorporated in an action. However, a more abstract mentalizing network may be necessary to efficiently process these inner states. In a recent fMRI study, we demonstrated that nodes of the theory-of-mind network (ToM) are activated when participants observe hesitations conveyed in hand movements. However, activation of a brain region does not the imply its necessity to perform the given task. Therefore, we designed a repetitive TMS study using the same experimental paradigm. On three experimental days, participants received 15 minutes of 1-Hz inhibitory rTMS stimulation, either on a MNS node (PF in the inferior parietal lobe), a ToM node (temporo-parietal junction (TPJ)), or a control region (vertex). After the stimulation, the participants performed three tasks: judging the size of a chosen object based on hand aperture, judging the level of hesitation and a control task. The first hypothesis was that a virtual lesion of PF would impair the performance in the hand aperture and hesitation task because they require the analysis of movement nuances. The second hypothesis was that a virtual lesion of the TPJ would influence the performance on the hesitation task only, because it requires inference about a mental state (confidence of choice). As predicted, we observed increased response latencies on the hand aperture task following the PF stimulation and increased response latencies on the hesitation task following both PF and TPJ stimulation. These results suggest that the TPJ is necessary to efficiently decipher mental states encoded in hand actions.

Functional magnetic resonance imaging (fMRI) studies suggest that stroke-induced motor deficits are associated with an interhemispheric imbalance of motor activation. This meta-analysis aims to determine the changes of interhemispheric activation balance (IHAB) in motor-related cortices along with post-stroke motor recovery.We searched PubMed for fMRI studies that investigated IHAB in stroke patients with motor recovery. Laterality indexes (LIs, (ipsilesional activation-contralesional activation)/(ipsilesional activation+contralesional activation)) before and after motor improvement were extracted as the outcome measures of IHAB. Data were synthesized by calculating standardized mean difference (SMD, Hedges' adjusted g) with 95% confidence intervals (CI).After the rejection of 459 studies, 22 trials fulfilled the inclusion criteria and were included in the systematic review and meta-analysis. The LIs of sensorimotor cortex (SMC, 22 trials, 195 subjects), premotor cortex (PMC, 12 trials, 93 subjects), supplementary motor area (SMA, 12 trials, 92 subjects), and cerebellum (CB, 4 trials, 31 subjects) were assessed. Studies sampling from stroke patients with motor improvement showed positive changes of LI in SMC (SMD, 0.71; 95% CI, 0.41-1.01; P0.00001) and PMC (SMD, 0.68; 95% CI, 0.36-1.00; P0.0001), but not in SMA (SMD, 0.07; 95% CI, -0.62 to 0.75; P=0.85) and CB (SMD, -0.17; 95% CI, -1.52 to 1.19, P=0.81). Studies involving stroke patients with poor motor recovery showed non-significant changes in all of the four motor-related cortices (P0.05).This meta-analysis suggests that along with good motor recovery of stroke patients, the IHAB is up-regulated in SMC and PMC, but not significantly changed in SMA and CB. Because of the limited data, further studies are needed to verify the findings.

S1 Checklist. PRISMA 2009 Checklist. (PDF 201 kb)

Background The ability to accurately detect deception is presently very limited. Detecting deception might be more accurately achieved by measuring the brain correlates of lying in an individual. In addition, a method to investigate the neurocircuitry of deception might provide a unique opportunity to test the neurocircuitry of persons in whom deception is a prominent component (i.e., conduct disorder, antisocial personality disorder, etc.). Methods In this study, we used functional magnetic resonance imaging (fMRI) to show that specific regions were reproducibly activated when subjects deceived. Subjects participated in a mock crime stealing either a ring or a watch. While undergoing an fMRI, the subjects denied taking either object, thus telling the truth with some responses, and lying with others. A Model-Building Group (MBG, n = 30) was used to develop the analysis methods, and the methods were subsequently applied to an independent Model-Testing Group (MTG, n = 31). Results We were able to correctly differentiate truthful from deceptive responses, correctly identifying the object stolen, for 93% of the subjects in the MBG and 90% of the subjects in the MTG. Conclusions This is the first study to use fMRI to detect deception at the individual level. Further work is required to determine how well this technology will work in different settings and populations.

Recent evidence suggests that underlying patterns of cortical activation may partially account for individual differences in susceptibility to the effects of sleep deprivation. Here, functional magnetic resonance imaging (fMRI) was used to examine the activation of military pilots whose sleep-deprivation vulnerability previously was quantified. A Sternberg Working Memory Task (SWMT; S. Sternberg, 1966) was completed alternately with a control task during a 13-min blood oxygen level-dependent fMRI scan. Examination of the activated voxels in response to SWMT indicated that, as a group, the pilots were more similar to fatigue-resistant nonpilots than to fatigue-vulnerable nonpilots. Within the pilots, cortical activation was significantly related to fatigue vulnerability on simulator-flight performance. These preliminary data suggest that baseline fMRI scan activation during a working memory task may correlate with fatigue susceptibility.

STUDY OBJECTIVE: To examine whether differences in patterns of brain activation under baseline conditions relate to the differences in sleep-deprivation vulnerability. DESIGN: Using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging, we scanned 33 healthy young men while they performed the Sternberg working memory task following a normal night of sleep and again following 30 hours of sleep deprivation. From this initial group, based on their Sternberg working memory task performance, we found 10 subjects resilient to sleep deprivation (sleep deprivation-resilient group) and then selected 10 age- and education-matched subjects vulnerable to sleep deprivation (sleep deprivation-vulnerable group). SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Data from 10 young men (mean age 27.8 +/- 1.7 years) in the sleep deprivation-resilient group and 10 young men (mean age 28.2 +/- 1.9 years) in the sleep deprivation-vulnerable group were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We compared functional magnetic resonance imaging BOLD signal at rested baseline and sleep deprivation states in the 2 groups. As hypothesized, following sleep deprivation, both groups showed significant decreases in global brain activation compared to their rested group baseline. At rested baseline and in the sleep-deprivation state, the sleep deprivation-resilient group had significantly more brain activation than did the sleep deprivation-vulnerable group. There were also differences in functional circuits within and between groups in response to sleep deprivation. CONCLUSIONS: These preliminary data suggest that patterns of brain activation during the Sternberg working memory task at the rested baseline and the sleep-deprivation state, differ across individuals as a function of their sleep-deprivation vulnerability. Language: en

In 1992, Dr Jake Zabara discovered in a canine model that repeated stimulation of the vagus nerve in the neck could stop seizures. Since that time, repeated stimulation of the vagus nerve has been FDA approved as an anticonvulsant. Zabara's work is built on a 50-year-old theme in the literature where scientists had sought to exploit the fact that the vagus nerve is composed of 80% afferent fibers. Thus vagus stimulation might potentially provide a ‘window’ into the brain. This manuscript reviews the basic science and brain imaging work done to date with VNS, attempting to understand how VNS affects the brain. This research is crucial to perfecting VNS as an anticonvulsant, and for determining other neuropsychiatric conditions that might be helped by VNS.

Applying a precisely timed pulse of transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC) can produce temporary visuo-spatial neglect-like effects. Although the TMS is applied over PPC, it is not clear what other brain regions are involved. We applied TMS within a functional magnetic resonance imaging (fMRI) scanner to investigate brain activity during TMS induction of neglect-like bias in three healthy volunteers, while they performed a line bisection judgment task (i.e., the landmark task). Single-pulse TMS at 115% of motor threshold was applied 150 ms after the visual stimulus onset. Participants completed two different TMS/fMRI sessions while performing this task: one session while single-pulse TMS was intermittently and time-locked applied to the right PPC and a control session with TMS positioned over the vertex. Perceptual rightward bias was observed when TMS was delivered over the right PPC. During neglect-like behavior, the fMRI maps showed decreased neural activity within parieto-frontal areas, which are often lesioned or dysfunctional in patients with left neglect. Vertex TMS induced behavioral effects compatible with leftward response bias and increased BOLD signal in the left caudate (a site which has been linked to response bias). These results are discussed in relation to recent findings on neural networks subserving attention in space.