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Background Previous sleep electroencephalography studies have detected abnormalities in sleep architecture and sleep spindle deficits in schizophrenia (SCZ), but the consistency of these results was not robust, which might be due to the small sample size and the influence of clinical factors such as the various medication therapies and symptom heterogeneity. This study aimed to regard auditory verbal hallucinations (AVHs) as a pointcut to downscale the heterogeneity of SCZ and explore whether some sleep architecture and spindle parameters were more severely impaired in SCZ patients with AVHs compared with those without AVHs. Methods A total of 90 SCZ patients with AVHs, 92 SCZ patients without AVHs, and 91 healthy control subjects were recruited, and parameters of sleep architecture and spindle activities were compared between groups. The correlation between significant sleep parameters and clinical indicators was analyzed. Results Deficits of sleep spindle activities at prefrontal electrodes and intrahemispheric spindle coherence were observed in both AVH and non-AVH groups, several of which were more serious in the AVH group. In addition, deficits of spindle activities at central and occipital electrodes and interhemispheric spindle coherence mainly manifested accompanying AVH symptoms, most of which were retained in the medication-naive first-episode patients, and were associated with Auditory Hallucination Rating Scale scores. Conclusions Our results suggest that the underlying mechanism of spindle deficits might be different between SCZ patients with and without AVHs. In the future, the sleep feature of SCZ patients with different symptoms and the influence of clinical factors, such as medication therapy, should be further illustrated.

Despite low-frequency repetitive transcranial magnetic stimulation (rTMS) is effective in treating schizophrenia patients with auditory verbal hallucinations (AVH), the underlying neural mechanisms of the effect still need to be clarified. Using the cerebellar dentate nucleus (DN) subdomain (dorsal and versal DN) as seeds, the present study investigated resting state functional connectivity (FC) alternations of the seeds with the whole brain and their associations with clinical responses in schizophrenia patients with AVH receiving 1 Hz rTMS treatment. The results showed that the rTMS treatment improved the psychiatric symptoms (e.g., AVH and positive symptoms) and certain neurocognitive functions (e.g., visual learning and verbal learning) in the patients. In addition, the patients at baseline showed increased FC between the DN subdomains and temporal lobes (e.g., right superior temporal gyrus and right middle temporal gyrus) and decreased FC between the DN subdomains and the left superior frontal gyrus, right postcentral gyrus, left supramarginal gyrus and regional cerebellum (e.g., lobule 4-5) compared to controls. Furthermore, these abnormal DN subdomain connectivity patterns did not persist and decreased FC of DN subdomains with cerebellum lobule 4-5 were reversed in patients after rTMS treatment. Linear regression analysis showed that the FC difference values of DN subdomains with the temporal lobes, supramarginal gyrus and cerebellum 4-5 between the patients at baseline and posttreatment were associated with clinical improvements (e.g., AVH and verbal learning) after rTMS treatment. The results suggested that rTMS treatment may modulate the neural circuits of the DN subdomains and hint to underlying neural mechanisms for low-frequency rTMS treating schizophrenia with AVH.

Rock bolt anchorage performance is crucial for tunnel support safety. We investigate the mechanical behaviour of reinforced rock and the bolts that reinforce it from the micro-scale to the macro-scale. Bolt pull-out tests were performed on soft rock using the distinct element method, in which a new contact model that considers bond size, is employed to constrain the main rock mechanical behaviour. The minimum sample width and height values for which the boundary effect can be neglected are first proposed through numerous tests on the influence of sample size on peak load and bond breakage. The influence of sample width is substantially greater than that of sample height. We then select an appropriate sample size to study the influence of bolt embedment length and confining pressure on the mechanical behaviours of the rock and bolt. The results show that increased rock bolt embedment length and confining pressure can increase the peak load; however, the bolt length effect is limited when exceeding the critical anchorage length. In cases without confining pressure, bond breakage occurs in the rock around the grout-rock interface and the breakage zone is rectangular, whereas in cases under confining pressure, the breakage zone presents an inverted cone shape. We use our results to discuss the influence of bond strength at the bolt–grout interface on the peak load and failure mode. The failure mode changes gradually from complex failure to single failure along the bolt–grout interface with decreasing interfacial bond strength.

Background Recent progress in neuroscience research has provided evidence that schizophrenia is a disease that involves dysconnectivity of brain networks. Widespread gray matter loss was commonly observed but how these gray matter abnormalities are characterized at the large-scale network-level in schizophrenia, especially patients with first-episode (FE-SCZ) remains unclear. Methods In this study, gray matter structural network aberrations were investigated by applying structural covariance network analysis to 193 first episode schizophrenia patients and 178 age and gender-matched healthy controls (HCs). The mean gray matter volume in seed regions relating to eight specific networks (visual, auditory, sensorimotor, speech, semantic, default-mode, executive control, and salience) were extracted, and voxel-wise analyses of covariance were conducted to compare the association between whole-brain gray matter volume and each seed region for FE-SCZ and HCs. Results The auditory network was less extended in FE-SCZ compared with HCs, with a significant decrease in the structural association between the Hesch's gyrus and the middle frontal gyrus and the superior frontal gyrus. Hyperconnectivity was observed in executive control network with a significant increase in the structural association between the dorsal lateral prefrontal cortex and the superior frontal gyrus and supplementary motor area. Conclusion Our research shows that seed based structural covariance analysis can well characterize multiple large-scale networks, the observed changes might underly the hallucinations and cognitive impairments observed in FE-SCZ. Given that these patients were experiencing their first episode of schizophrenia, our findings suggest that such structural network deficits are present at an early stage in this disorder.

Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has shown potential in the treatment of AVH. However, the underlying neural mechanismof rTMS in the treatment of AVH remains largely unknown. In this study, we used a static and dynamic functional network connectivity approach to investigate the connectivity changes among the brain functional networks in schizophrenia patients with AVH receiving 1 Hz rTMS treatment. The static functional network connectivity (sFNC) analysis revealed that patients at baseline had significantly decreased connectivity between the default mode network (DMN) and language network (LAN), and within the executive control network (ECN) as well as within the auditory network (AUD) compared to controls. However, the abnormal network connectivity patterns were normalized or restored after rTMS treatment in patients, instead of increased connectivity between the ECN and LAN, as well as within the AUD. Moreover, the dynamic functional network connectivity (dFNC) analysis showed that the patients at baseline spent more time in this state that was characterized by strongly negative connectivity between the ENC and AUD, as well as within the AUD relative to controls. While after rTMS treatment, the patients showed a higher occurrence rate in this state that was characterized by strongly positive connectivity among the LAN, DMN, and ENC, as well as within the ECN. In addition, the altered static and dynamic connectivity properties were associated with reduced severity of clinical symptoms. Both sFNC and dFNC analyses provided complementary information and suggested that low-frequency rTMS treatment could induce intrinsic functional network alternations and contribute to improvements in clinical symptoms in patients with AVH.

Recently, the insular cortex (IC) was identified as part of the neuronal circuit responsible for the reward expectations in cue-triggered behaviours. Moreover, there are evidences that connections between the IC and the ventral striatum, particularly with the nucleus accumbens (NAc), may mediate the retrieval and performance of actions based on incentive memory. However, the precise role of the IC-NAc connections in cue-related drug-seeking behaviour remains unclear. We used the morphine-induced conditioned place preference (CPP) paradigm to assess the formation and relapse of cue-related drug-seeking. cFos immunostaining was used to determine the activation of the brain regions. Chemogenetic and optogenetic methods were used to manipulate the activity of IC-to-NAc projection neurons. The result showed that neurons in IC and NAc core but not NAc shell were activated following cue-induced morphine-seeking behaviour. Negligible effect of inhibition of IC-to-NAc core projection (IC→NAc core) on morphine CPP expression, whereas chemogenetic inactivation of this projection potently blocked the reinstatement of expressed morphine CPP. Furthermore, optogenetic inhibition of glutamatergic IC→NAc core inputs significant suppressed the CPP reinstatement without significant effect on CPP expression. We demonstrated here, for the first time, that IC→NAc core glutamatergic projection is required for the reinstatement of cue-associated drug seeking behaviour in mice. The present study provide insights into modulations of relapse of cue-associated drug-seeking behaviour following repeated overexposure to opioids in humans.

Despite evidence of structural brain abnormalities in schizophrenia, the current study aimed to explore the effects of antipsychotic treatment on gray matter (GM) volume using structural magnetic resonance imaging (MRI) and investigate the relationship between brain structure and treatment response. The GM volumes of 33 patients with first-episode schizophrenia were calculated with voxel-based morphometry (VBM), with 33 matched healthy controls. Longitudinal volume changes within subjects after 4-month antipsychotic treatment were also evaluated. Correlation between volumetric changes and clinical symptoms derived from the Positive and Negative Syndrome Scale (PANSS) were further investigated. Compared with healthy controls, decreased GM volumes in the frontal gyrus were observed in schizophrenia patients. After 4-month treatment, patients showed significantly decreased GM volume primarily in the bilateral frontal, temporal and left parietal brain regions. In addition, the GM volume changes of the left postcentral gyrus was positively correlated with negative symptoms improvement, and the correlation analysis revealed the total PANSS scores changes were associated with GM volume changes in the right inferior frontal gyrus and the right superior temporal gyrus. Besides, non-responders had reduced GM volume in the bilateral middle frontal gyrus and the right superior frontal gyrus compared with responders and healthy controls. Our results suggest that the abnormality in the right frontal gyrus exists in the early stage of schizophrenia. Moreover, the relationship between antipsychotics and structural changes was identified. The GM volume might have the potential to reflect the symptom improvement in schizophrenia patients. And MRI may assist in predicting the antipsychotic treatment response in first-episode schizophrenia patients.

Electroacupuncture (EA) is a clinically useful physiological therapy that has been recently adopted to treat several brain disorders. However, the potential role of early EA intervention in the prevention of posttraumatic stress disorder (PTSD) as well as its potential cellular and molecular mechanism has never been investigated previously. In the present study, we used an enhanced single prolonged stress (ESPS) model to access the effects of early EA intervention on the prevention of anxiety-like and fear learning behaviors, as well as the influence of the expression of post-synaptic density protein 95 (PSD95), synaptophysin (Syn), brain derived neurotrophic factor (BDNF), diacylglycerol lipase alpha (DAGLα) and cannabinoid type 1 receptor (CB1R) in the hippocampus with or without DAGLα or CB1R knockdown by a short hairpin RNA (shRNA) in the hippocampus. Moreover, the effects of electrical stimulation with different parameters on the expression of DAGLα and CB1R in the hippocampal astrocytes were also observed. The results showed that Early EA intervention improved hippocampal synaptic plasticity and ameliorated PTSD-like behaviors and also increased expression of BDNF, DAGLα and CB1R. However, either DAGLα or CB1R knockdown by a short hairpin RNA (shRNA) eliminated the neuroprotective effects of early EA intervention. Furthermore, electrical stimulation with 2/15 Hz 1 mA elevated the expression of DAGLα and CB1R. Altogether, our findings provide new insights regarding the possibility of using early EA intervention in the prevention of PTSD, and the protective effects of EA is involving the activation of DAGLα and CB1R.

Objective We aimed to evaluate the functional network properties in first-episode schizophrenia (SZ) patients at baseline and after 4-months treatment with second-generation antipsychotic drugs. Methods Resting-state functional magnetic resonance imaging and graph theory approaches were utilized to evaluate the functional integration and segregation of brain networks in 36 first-episode patients (20 male/16 female) with SZ and 36 age and sex matched healthy controls (20 male/16 female). Results Compared with healthy controls, SZ at baseline showed lower clustering coefficient (Cp) and local network efficiency (Eloc), and this abnormal pattern was modulated with treatment of antipsychotic drugs at follow-up. Longitudinally, the increase of Cp was associated with the improvement of negative symptom. We found that the strength of functional connectivity between brain regions were significantly increased in three connections after treatment, mainly involving the frontal, parietal and occipital lobes. Conclusion The current study suggested that antipsychotic drugs could modulate the faulty local clustering of the functional connectome in SZ. Furthermore, Cp, the parameter that reflects local clustering of topological organization, demonstrated the potential to be a connectome-based biomarker of treatment response to second-generation antipsychotics in patients with SZ.

The “hunger” hormone ghrelin regulates food-intake and preference for high-calorie (HC) food through modulation of the mesocortico-limbic dopaminergic pathway. Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery to treat morbid obesity. We tested the hypothesis that LSG-induced reductions in appetite and total ghrelin levels in blood are associated with reduced prefrontal brain reactivity to food cues. A functional magnetic resonance imaging (fMRI) cue-reactivity task with HC and low-calorie (LC) food pictures was used to investigate brain reactivity in 22 obese participants tested before and one month after bariatric surgery (BS). Nineteen obese controls (Ctr) without surgery were also tested at baseline and one-month later. LSG significantly decreased (1) fasting plasma concentrations of total ghrelin, leptin and insulin, (2) craving for HC food, and (3) brain activation in the right dorsolateral prefrontal cortex (DLPFC) in response to HC vs. LC food cues (P(FWE) < 0.05). LSG-induced reduction in DLPFC activation to food cues were positively correlated with reduction in ghrelin levels and reduction in craving ratings for food. Psychophysiological interaction (PPI) connectivity analyses showed that the right DLPFC had stronger connectivity with the ventral anterior cingulate cortex (vACC) after LSG; and changes in BMI were negatively correlated with changes in connectivity between the right DLPFC and vACC in the LSG group only. These findings suggest that LSG-induced weight-loss may be related to reductions in ghrelin, possibly leading to decreased food craving and hypothetically reducing DLPFC response to the HC food cues.

Rock bolts are widely employed as an effective and efficient reinforcement method in tunnel engineering. Owing to the difficulty in considering the rock breakage due to tunneling, and lack of the ability to reveal the microscopic mechanism of the interaction of bolt and rock mass properly by the conventional numerical methods, the reinforcement mechanism of bolts is not very clear. A new efficient hybrid DEM-Analytical model is proposed in this study for analysis of the deeply buried tunnels, where the DEM and analytical solutions are respectively employed to model the nearby and far fields of tunnel opening. The accuracy and applicability of the model are tested by comparing the hybrid model with analytical and full DEM model. The largest deviations of stresses and displacements for elastic problem are within 7–8% from the analytical solution, and the bond breakage regions obtained by hybrid model and full DEM model are about the same on average when the rock breakage is considered. The computational time of hybrid model is only about one-third of that of the full DEM model in this case. In addition, the variation of bolt axial forces obtained by the hybrid model is in good qualitative agreement with field measurements. The reinforcement mechanism of fully grouted passive rock bolting and the effect of supporting parameters are analyzed by the proposed hybrid model. Some useful numerical results are presented. It is found that rock bolts prevent the breakage of particle bonds immediately around them, and two transmission patterns of bond forces are observed in the nearby areas of rock bolts. Increasing the number of bolts contributes to significantly reduce the rock breakage region and bond breakage number. A threefold reduction of the number of broken bonds occurs passing from 4 to 12 rock bolts. The reinforcement of rock bolts is not obvious when the length is less than 0.5 r 0 , however, the increase of bolt length is not efficient in preventing rock breakage when the length exceeds 1.0 r 0 - 1.2 r 0 . Therefore, a reasonable efficient bolt length is suggested under the specific conditions of this study.

The size of intergranular bonds significantly affects the macroscopic mechanical properties of geomaterials. A size-dependent bond contact model is desired in the distinct element method (DEM) for geomaterials formed by aggregates of bonded particles. This paper proposes an analytical solution of highly-precise stress fields of a biconcave bond between two identical disc-shaped particles under different loading paths based on Dvorkin’s solution. The Unified Strength theory is then introduced to obtain the initial failure domain in the bond. The proposed solution is consistent with results predicted by finite element simulations and experimental observations. The functions of bond stiffness with respect to all influencing parameters, i.e. bond width/thickness, particle radius and elastic parameters of bond material, are provided by the solution and empirically formulated by fitting a large number of analytical results. Additionally, the failure criterion or envelope under different combined loads is formulated for typical brittle bonds. The resulting failure criterion, approximated as an ellipsoid, depends on the size and material properties of the bonds. The proposed solution and equation can be implemented into a bond contact model used in DEM simulations of a geomaterial, where variation of bond sizes is significant and size-dependent contact model is important.

The goal of the study was to investigate cerebral blood flow (CBF) and its connectivity (an across-subject covariance measure) patterns of schizophrenia (SZ) patients with auditory verbal hallucinations (AVHs). A total of demographically matched 25 SZ patients with AVHs, 25 without AVHs, and 25 healthy controls (HCs) underwent resting state perfusion imaging using a pulsed arterial spin labeling sequence. CBF and its connectivity were analyzed and then CBF topological properties were calculated. AVHs patients exhibited decreased CBF in the bilateral superior and middle frontal gyri and postcentral gyri, and right supplementary motor area compared with SZ patients without AVHs. SZ patients without AVHs showed reduced CBF in the left middle frontal gyrus relative to HCs. Moreover, AVHs groups showed distinct connectivity pattern, an intermediate level between HCs and patients without AVHs in the global efficiency. Our study demonstrates aberrant CBF in the brain regions associated with inner speech monitoring and language processing in SZ patients with AVHs. The complex network measures showed by CBF-derived functional connectivity indicate dysconnectivity between different functional units within the network of AVHs in SZ. Our findings might shed light on the neural underpinnings behind AVHs in this devastating disease at the level of CBF and its connectivity.

Effective charge-carrier separation and molecular oxygen activation are crucial factors for photocatalytic environmental purification. Herein, an efficient Fe-doped Bi7O9I3 microflowers photocatalyst was synthesized. It was discovered that Fe doping could not only tune the concentration of oxygen vacancies of Bi7O9I3 to optimize the dissociation of excitons, but also promote the separation of charge-carriers and the activation of oxygen molecules. Meanwhile, the inducing of surface oxygen vacancies and Fe3+/Fe2+ by Fe optimal doping can act as the activation center for catalytic reactions, which also significantly enhances the photocatalytic activity. Benefiting from the optimized properties, the photocatalytic activity of Fe-doped Bi7O9I3 photocatalyst has been significantly improved by more than 4 times. Finally, we proposed that a highly efficient catalytic oxidation reaction mechanism can be achieved via modulating Fe doping to induce oxygen vacancies to promote charge separation and molecular oxygen activation. This work provides a novel approach for designing efficient photocatalysts.

Heterogeneous findings across studies of structural abnormality in schizophrenia (SZ) have impeded the development a unified theory of white matter pathology. As a cardinal symptom of SZ, auditory verbal hallucination (AVH) has been suspected to be associated with improper communication among several brain regions, which might indicated white matter pathology. Participants comprised 25 first-episode (FE) patients with AVH, 25 patients without AVH and 25 healthy subjects. Diffusion tensor imaging (DTI) measures were calculated using the TBSS of FSL. Voxel-based ANOVA tests were performed among the three groups and threshold-free cluster enhancement (TFCE) method correction was used for multiple comparisons. Voxel-based one-way ANOVA showed significant group effects for fractional anisotropy (FA) and radial diffusivity (RD) values. Post-hoc t-tests indicated that schizophrenia patients had lower FA and higher RD values in the internal capsule and anterior corona radiata than control subjects. Post-hoc analyses exhibited more widespread fiber disruptions in AVH patients than non-AVH patients. These results hinted on the important role of projection fiber disruption in schizophrenia patients. In addition, the current study also suggested that direct comparison between studies using patients with different symptom profiles should be interpreted with caution.

Functional constipation (FC) is a common functional gastrointestinal disorder (FGID) with a higher prevalence in clinical practice. The primary brain regions involved in emotional arousal regulation, somatic, sensory and motor control processing have been identified with neuroimaging in FGID. It remains unclear how these factors interact to influence the baseline brain activity of patients with FC. In the current study, we combined resting-state fMRI (RS-fMRI) with Granger causality analysis (GCA) to investigate the causal interactions of the brain areas in 14 patients with FC and in 26 healthy controls (HC). Our data showed significant differences in baseline brain activities in a number of major brain regions implicated in emotional process modulation (i.e. dorsal anterior cingulate cortex-dACC, anterior insula-aINS, orbitofrontal cortex-OFC, hippocampus-HIPP), somatic and sensory processing, and motor control (i.e., supplementary motor area-SMA, precentral gyrus-PreCen) (P

The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) has been extensively studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of depression and may be a targeted mechanism for treatment. However, the influence of rTMS on lipid composition and the differences between these effects compared to antidepressants like fluoxetine (Flx) have never been investigated. Using a chronic unpredictable stress (CUS) model in rats, we assessed the antidepressive effects of rTMS and Flx treatments and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. Both rTMS and Flx treatments ameliorated depressive-like behaviors induced by CUS. Moreover, changes in lipid composition, especially glycerophospholipids, sphingolipids, and glycerolipids induced by CUS in the hippocampus were more robust than those observed in the PFC. CUS led to decreased levels of 20 carbon-containing fatty acyls and polyunsaturated fatty acyls in the PFC, and decreased levels of acyl carnitines (AcCa) in both the hippocampus and PFC. Notably, rTMS treatment had higher impact than Flx on composition of glycerophospholipids and sphingolipids in the hippocampus that were altered by CUS, while Flx attenuated CUS-induced changes in the PFC to a greater extent than rTMS. However, neither was able to restore fatty acyls and AcCa to baseline levels. Altogether, modulation of the brain lipidome may be involved in the antidepressant action of rTMS and Flx, and the degree to which these treatments induce changes in lipid composition within the hippocampus and PFC might explain their differential antidepressant effects.

Aim The aim of this study was to determine the efficacy and safety of cranial electrotherapy stimulation (CES) as an add-on treatment for TD. Methods A randomized, double-blind, sham-controlled trial was conducted at an outpatient, single-center academic setting. A total of 62 patients aged 6–17 years with TD and lack of clinical response to 4 weeks’ pharmacotherapy were enrolled. Patients were divided randomly into 2 groups and given 4 weeks’ treatment, including 30 min sessions of active CES (500 μA–2 mA) or sham CES (lower than 100 μA) per day for 40 d on weekdays. Change in Yale Global Tic Severity Scale (YGTSS), Clinical Global Impression-severity of illness-severity (CGI-S) and Hamilton Anxiety Scale-14 items (HAMA-14) were performed at baseline, week 2, week 4. Adverse events (AEs) were also evaluated. Results 53 patients (34 males and 9 females) completed the trial, including 29 in the active CES group and 24 in the sham CES group. Both groups showed clinical improvement in tic severities compared to baseline respectively at week 4. Participants receiving active CES showed a reduction of 31.66 % in YGTSS score, compared with 23.96 % in participants in sham CES group, resulting in no significant difference between the two groups (t = 1.54, p = 0.13). Conclusion Four-week’s treatment of CES for children and adolescents with TD is effective and safe, but the improvement for tic severity may be related to placebo effect.

Background: Evidence from neuroimaging has implicated abnormal cerebral cortical patterns in schizophrenia. Application of machine learning techniques is required for identifying a structural signature at the individual level reflecting neurobiological substrates of schizophrenia. Methods: 52 Patients and 66 healthy controls were recruited within the same period. Multivariate computation was used to examine the abnormalities of cortical features in schizophrenia. Features were selected by least absolute shrinkage and the selection operator (LASSO) method. The diagnostic capacity of multi-dimensional cortical neuroanatomical pattern-based classification was evaluated based on diagnostic tests. Findings: The features of mean curvature (left insula and left inferior frontal gyrus), cortical thickness (left fusiform gyrus), and metric distortion (left cuneus and right superior temporal gyrus) revealed both group differences and diagnostic capacity. Area under the receiver operating characteristic curve was 0.88, and the sensitivity, specificity, and accuracy were 94%, 82%, and 88% respectively. There was a positive association between the index score derived from multi-dimensional patterns and symptom severity (r = 0.40, P< 0.01) for patients. Our findings demonstrated a view of cortical differences with the capacity to discriminate patients with schizophrenia. Structural neuroimaging-based signatures hold potential promise of paving the road for clinical utility in schizophrenia. Interpretation: Our findings demonstrate a view of cortical differences with capacity to discriminate patients with schizophrenia. Structural neuroimaging-based signatures hold potential promise of paving the road for clinical utility in schizophrenia. Funding Statement:This study was supported by the National Basic Research Program of China under Grant Nos. 2014CB543203 and 2015CB856403, the National Natural Science Foundation of China under Grant Nos. 81471811, 81471738 and 61401346, the Fundamental Research Funds for the Central Universities (Dr Qin) and grants 81571651 from the National Natural Science Foundation of China and 2017ZDXM-SF-048 from the Key Research and Development Program of Shaanxi Province (Dr Yin). Declaration of Interest: No disclosure was reported. Ethics Approval Statement: This study was approved by the local Research Ethics Committee (Xijing Hospital, Fourth Military Medical University). All participants gave written informed consent after a complete description of this study

Rosmarinic acid (RA) is an important component of Chinese herbal medicine treatments and has been demonstrated to exert therapeutic effects in mood disorders. The present study was designed to assess the effects of RA on post-traumatic stress disorder (PTSD)-like symptoms, hippocampal cell proliferation and phosphorylation extracellular regulated protein kinases (pERK1/2) expression. We found that administration of RA (10mg/kg) alleviated PTSD-like symptoms in rats exposed to an enhanced single prolonged stress (ESPS) paradigm and restored hippocampal proliferation and pERK1/2 expression. Interestingly, the effects of RA were inhibited by the blockage of the ERK signaling. These data support the use of RA for treating PTSD and indicate that the ERK1/2 signaling cascade may play a critical role in the therapeutic efficacy of RA in treating such conditions.

Repetitive transcranial magnetic stimulation (rTMS) to treat depression has been thoroughly investigated in recent years. However, the underlying mechanisms are not fully understood. In this study, a chronic unpredictable mild stress (CUMS) paradigm was applied to male Sprague Dawley rats. Then rTMS was performed for 7 consecutive days, and the anti-depressive effects were evaluated by the sucrose preference test (SPT), the forced swimming test (FST), and the open-field test (OFT). Hippocampal cannabinoid type I receptor (CB1) expression was measured, and the expression levels of brain-derived neurotrophic factor (BDNF), Bcl-2, and Bax and the number of bromodeoxyuridine (BrdU)-positive cells were also investigated. These parameters were also observed after the selective CB1 receptor antagonist AM251 was used as a blocking agent. The results showed that CUMS induced a significant decrease in sucrose preference, a significant increase in immobility time in the FST, and a significantly decreased horizontal distance in the OFT. In addition, reduced hippocampal CB1 receptor, BDNF, and Bcl-2/Bax protein expression levels in CUMS rats, as well as decreased cell proliferation were also observed in the dentate gyrus. Meanwhile, rTMS treatment up-regulated cell proliferation; elevated CB1 receptor, BDNF, and Bcl-2/Bax expression levels in the hippocampus; and ameliorated depressive-like behaviors. All of these beneficial effects were abolished by AM251. These results indicate that rTMS increases BDNF production and hippocampal cell proliferation to protect against CUMS-induced changes through its effect on CB1 receptors.

Ziprasidone, a widely used atypical antipsychotic drug, has been demonstrated to have therapeutic effects in patients with post-traumatic stress disorder (PTSD), but its underlying mechanisms remain poorly understood. One possible explanation is that the neuroprotective and neurogenetic actions of ziprasidone can attenuate the neuronal apoptosis which occurs in the hippocampus. To test this hypothesis, the present study was designed to assess the effects of ziprasidone treatment on anxiety-like behaviors, hippocampal neurogenesis, and in vivo/in vitro expression of pERK1/2 and Bcl-2 in male Sprague-Dawley rats. The methodology involved 3 different experiments, and the investigations also included the assessment of U0126 interference in ziprasidone treatment. It was found that the in vivo, administration of ziprasidone not only reversed the anxiety-like behaviors in rats that exposed to an enhanced single prolonged stress paradigm, but also restored the proliferation and the protein expression of pERK1/2 and Bcl-2 in the hippocampus of these rats. Also, mild concentrations of ziprasidone promoted the in vitro proliferation of hippocampal-derived neural stem cells (NSCs) and increased the levels of pERK1/2 and Bcl-2 in NSCs. Interestingly, the observed effects of ziprasidone were inhibited by U0126. These data support the use of ziprasidone for the treatment of PTSD and indicate that the changes in the ERK1/2 signaling cascade may play a critical role in the pathophysiology of PTSD and its treatment modalities. Further investigations are needed to elucidate the detailed signal cascades involved in the pathophysiology of stress-related disorders, and confirm the efficacy of ziprasidone in anti-PTSD treatment.

A variety of structural abnormalities have been described in post traumatic stress disorder (PTSD), but only a few studies have focused on cortical thickness alterations in recent onset PTSD. In this study, we adopted surface-based morphometry (SBM), which enables an exploration of global structural changes throughout the brain, in order to compare cortical thickness alterations in recent onset PTSD patients, trauma-exposed subjects but without PTSD, and normal controls. Moreover, we used region of interest (ROI) partial correlation analysis to evaluate the correlation among PTSD symptom severity and significant changes of cortical thickness. The widespread cortical thickness reduction relative to the normal controls were found in bilateral inferior and superior parietal lobes, frontal lobes, hippocampus, cingulate cortex, and right lateral occipital lobes in trauma survivors, whereas cortical thickness was only increased in left calcarine cortex in PTSD group. The average cortical thickness of hippocampus and cingulate cortex decreased by 10.75% and 9.09% in PTSD, 3.48% and 2.86% in non PTSD. We further demonstrated that the cortical thicknesses of bilateral ACC and PCC, superior frontal lobes, and hippocampus are negatively correlated with CAPS scores in all trauma survivors. Our study results suggest that stress widens cortical thinning regions and causes more serious effect in recent onset PTSD than non PTSD. It also shows that the cortical thinning in recent onset PTSD predicts the symptom severity., Highlights • PTSD caused by rare, severe disaster (69 miners trapped in 1.4 km underground for 75 h). • The surface-based morphometry is based on such serious, sustained and acute trauma. • The comparisons are among healthy, survivors with, and without recent onset PTSD. • Hippocampus and cingulate thickness in PTSD decreased 3 times than non PTSD. • The altered regions in PTSD group are negatively correlated with CAPS scores.

Antidepressant treatments enhance synaptic connectivity in stress-sensitive brain regions such as the medial prefrontal cortex (mPFC). The mPFC plays a key role in controlling cognition and emotion. While several signaling pathways are involved in this enhancement process, the exact mechanisms are not fully established. In the present study, we evaluated the role of the glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway in the antidepressant effect of citalopram in rats exposed to forced swim stress. The acute stress group received the classic, two-day variant of the forced swimming test (FST), whereas the chronic stress group received swim stress for 14 consecutive days. We found that rats exposed to acute swim stress showed depressive-like behaviors and expressed normal GSK3β and β-catenin levels in the mPFC. Chronic swim stress, also induced a significant behavior changes but was associated with decreased levels of phosphorylated GSK3β and β-catenin in the rat's mPFC. Chronic citalopram treatment alleviated these behavioral changes in chronically stressed rats and normalized the downregulation of GSK3β/β-catenin signaling. Our results suggest that GSK3β/β-catenin signaling plays an important role in chronic but not acute stress-related depression and contributes, at least in part, to the antidepressant effects of citalopram in distinct brain regions associated with mood regulation.

Objective Previous studies have demonstrated the effectiveness of electroconvulsive therapy (ECT) in pharmacotherapy-resistant neuropsychiatric conditions. This study aimed to evaluate the efficacy and safety of ECT in adolescents with first-episode psychosis. Method This case–control study was conducted in inpatients aged 13–20 years with first-episode psychosis. Every three similar age and same gender patients consecutively recruited were randomly allocated to control and ECT group at a ratio of 1:2, while they had antipsychotic treatment. ECT treatment was performed for 3 sessions per week with a maximum of 14 sessions. The endpoint was discharge from hospital. Clinical outcomes were measured using hospital stay days, the Positive and Negative Syndrome Scale (PANSS) and response rate. Polysomnography (PSG) was conducted at baseline and at week 2. Safety and tolerability were also evaluated. Results Between March 2004 and November 2009, 112 eligible patients were allocated to control (n = 38) and ECT (n = 74) group. Additional ECT treatment significantly reduced hospital stay compared to controls (23.2 ± 8.2 days versus 27.3 ± 9.3 days, mean ± SD, P = 0.018). Survival analysis revealed that the ECT-treated group had a significantly higher cumulative response rate than controls (74.3% versus 50%, relative risk (RR) = 1.961, P = 0.001). Additional ECT also produced significantly greater improvement in sleep efficiency, rapid eye movement (REM) latency and density than control condition. The PSG improvement significantly correlated with reduction in scores on overall PANSS, positive symptoms, and general psychopathology. No patients discontinued ECT treatment regimen during hospital stay. The incidence of most adverse events was not different in the two groups, but ECT-treated group had more complaints of transient headache and dizziness than controls. Conclusions ECT is an effective and safe intervention used in adolescents with first-episode psychosis. Its antipsychotic effects are associated with improved PSG variables. ECT can be considered as an early psychosis intervention.

Sertraline is one of the most commonly used antidepressants in clinic. Although it is well accepted that sertraline exerts its action through inhibition of the reuptake of serotonin at presynaptic site in the brain, its effect on the neural stem cells (NSCs) has not been well elucidated. In this study, we utilized NSCs separated from the hippocampus of fetal rat to investigate the effect of sertraline on the proliferation and differentiation of NSCs. The study demonstrated that sertraline had no effect on NSCs proliferation but it significantly promoted NSCs to differentiate into serotoninergic neurons other than glia cells. Furthermore, we found that sertraline protected NSCs against the lipopolysaccharide-induced cellular damage. These data indicate that sertraline can promote neurogenesis and protect the viability of neural stem cells.

High-sustained positive acceleration (+Gz) exposures might lead to impairment in cognitive function. Our previous studies have shown that electroacupuncture (EA) pretreatment can attenuate transient focal cerebral ischemic injury in the rats. In this study we aimed to investigate whether EA pretreatment could ameliorate the impairment of learning and memory induced by a sustained +Gz exposure. Using the centrifuge model, rats of experimental groups were exposed to +10 Gz for 5 min. Morris water maze was used for assessing the cognitive ability, and the apoptotic hippocampal CA1 pyramidal neuronal cells were evaluated by caspase-3 activity and TUNEL staining. Our results showed that +Gz exposure significantly caused pyramidal neuronal damage, increased neuronal apoptosis and caspase-3 activity in hippocampal CA1 region, as well as resulted in an impairment of spatial learning and memory, as compared to the sham group animals. Furthermore, the EA pretreatment significantly attenuated the neuronal apoptosis, preserved neuronal morphology and inhibited the caspase-3 activity in hippocampal CA1 region resulted from +Gz exposure. The EA pretreatment also ameliorated the learning and memory function in rats exposed to +Gz. These findings indicate that EA pretreatment provides a novel method to prevent the cognitive damage caused by +Gz, which could significantly protect neuronal damage and impairment of learning and memory.

Free and Easy Wanderer Plus (FEWP) is a well-known traditional Chinese medicine that has been shown to be effective in treating various mood disorders. The purpose of the present study was to determine whether FEWP could ameliorate stress-associated behavior in rats. Following the exposure to enhanced single prolonged stress (ESPS) paradigm, consisting of 2-hr constraint, 20-min forced swimming, ether-induced loss of consciousness, and an electric foot shock, animals were administered orally with FEWP (2.5, 5, or 10 mg/kg daily) or vehicle for 2 weeks. Animals were then tested in the open field, elevated plus-maze, and Morris water maze. ESPS exposure resulted in pronounced anxiety-like behavior, without impairing locomotor activity, as indicated by significant decreases of time spent and number of entries into open arms in the elevated plus-maze test, and unaltered distance traveled in the open field test compared to unexposed animals. ESPS-exposed animals also displayed marked cognitive impairments, with significant increases of distance traveled and the escape latency to the underwater platform, and a striking decrease of time spent in the target quadrant with and without the removal of the platform in the water maze test. However, repeated treatment with FEWP, particularly at higher doses, reversed the aforementioned behavioral values in the elevated plus-maze and water maze tests to the levels similar to unexposed animals. These results indicate that FEWP possesses anxiolytic and cognition-improving effects and may be an effective herbal preparation for the treatment of stress-associated conditions, such as posttraumatic stress disorder (PTSD).

This paper is a summary of our recent researches on the applications of a weighted average method determining times of solar cycle extrema in the prediction of solar activity. Some correlation coefficients among the parameters in solar cycle according to this definition are higher than those according to the conventional definition. The descending time is found to be correlated ( r = −0.77) with the ascending time 3 cycles earlier. The amplitude of solar cycle is found to be correlated ( r = −0.77) with the max–max solar cycle length 2 cycles earlier. The ascending time is found to be correlated ( r = −0.72) with the amplitude. A newly defined parameter called effective duration is found to be well correlated ( r = 0.86) with the amplitude 5 cycles later. These correlations suggest that earlier cycles should influence later ones. The next (24th) solar cycle is estimated to start in March 2007 ± 7 months, reach its maximum in January 2011 ± 14 months, with a size of 150 ± 22, larger than those from some correlations according to the conventional definition.

Nowadays operational models for solar activity forecasting are still based on the statistical relationship between solar activity and solar magnetic field evolution. In order to set up this relationship, many parameters have been proposed to be the measures. Conventional measures are based on the sunspot group classification which provides limited information from sunspots. For this reason, new measures based on solar magnetic field observations are proposed and a solar flare forecasting model supported with an artificial neural network is introduced. This model is equivalent to a person with a long period of solar flare forecasting experience.

Solar activity prediction services started in 1960’s in National Astronomical Observatories, Chinese Academy of Sciences (NAOC). As one of the members of the International Space Environment Service (ISES), Regional Warning Center of China (RWC-China) was set up in 1990’s. Solar Activity Prediction Center (SAPC), as one of the four sub-centers of RWC-China, is located in NAOC. Solar activity prediction studies and services in NAOC cover short-term, medium-term, and long-term forecast of solar activities. Nowadays, certain prediction models, such as solar X-ray flare model, solar proton event model, solar 10 cm radio flux model, have been established for the practical prediction services. Recently, more and more physical analyses are introduced in the studies of solar activity prediction, such as the magnetic properties of solar active regions and magnetic structure of solar atmosphere. Besides traditional statistics algorithms, Machine Learning and Artificial Intelligence techniques, such as Support Vector Machine (SVM) method, are employed in the establishment of forecast models. A Web-based integrated platform for solar activity data sharing and forecast distribution is under construction.

Studying the statistical correlation between the solar flare productivity and photospheric magnetic fields is very important and necessary. It is helpful to set up a practical flare forecast model based on magnetic properties and improve the physical understanding of solar flare eruptions. In the previous study ([ Cui, Y.M., Li, R., Zhang, L.Y., He, Y.L., Wang, H.N. Correlation between solar flare productivity and photospheric magnetic field properties 1. Maximum horizontal gradient, length of neutral line, number of singular points. Sol. Phys. 237, 45–59, 2006 ]; from now on we refer to this paper as ‘Paper I’), three measures of the maximum horizontal gradient, the length of the neutral line, and the number of singular points are computed from 23990 SOHO/MDI longitudinal magnetograms. The statistical relationship between the solar flare productivity and these three measures is well fitted with sigmoid functions. In the current work, the three measures of the length of strong-shear neutral line, total unsigned current, and total unsigned current helicity are computed from 1353 vector magnetograms observed at Huairou Solar Observing Station. The relationship between the solar flare productivity and the current three measures can also be well fitted with sigmoid functions. These results are expected to be beneficial to future operational flare forecasting models.

The support vector machine (SVM) combined with K-nearest neighbors (KNN), called the SVM-KNN method, is new classing algorithm that take the advantages of the SVM and KNN. This method is applied to the forecasting models for solar flares and proton events. For the solar flare forecasting model, the sunspot area, the sunspot magnetic class, and the McIntosh class of sunspot group and 10 cm solar radio flux are chosen as inputs; for the solar proton event forecasting model, the inputs include the longitude of active regions, the flux of soft X-ray, and those for the solar flare forecasting model. Detailed tests are implemented for both of the proposed forecasting models, in which the SVM-KNN and the SVM methods are compared. The testing results demonstrate that the SVM-KNN method provide a higher forecasting accuracy in contrast to the SVM. It also gives an increased rate of ‘Low’ prediction at the same time. The ‘Low’ prediction means occurrence of solar flares or proton events with predictions of non-occurrence. This method show promise for forecasting models of solar flare and proton events.

The photospheric vector magnetic fields, Hα and soft X-ray images of AR 7321 were simultaneously observed with the Solar Flare Telescope at Mitaka and the Soft X-ray Telescope of Yohkoh on 26 October 1992, when there were no drastic activities in this region. Taking the observed photospheric vector magnetic fields as the boundary condition, the 3D magnetic fields above the photosphere were computed with a new extrapolation method. Through a comparison among 3D magnetic fields, Hα features, and soft X-ray features, the following results have been obtained: (a) Magnetic separatrices or quasi-separatrix layers play an important role in chromospheric and coronal heating, but they do not seem to be dominant in the enhanced coronal heating. (b) The enhanced coronal heating might be due, not only to the magnetic shear, but also to the emerging magnetic flux.