Manipulated overlapping reactivation of multiple memories promotes explicit gist abstraction.

Sleep is considered to promote gist abstraction on the basis of spontaneous memory reactivation. As speculated in the theory of 'information overlap to abstract (iOtA)', 'overlap' between reactivated memories, beyond reactivation, is crucial to gist abstraction. Yet so far, empirical research has not tested this theory by manipulating the factor of 'overlap'. In the current study, 'overlap' itself was manipulated by targeted memory reactivation (TMR), through simultaneously reactivating multiple memories that either contain or do not contain spatially overlapped gist information, to investigate the effect of overlapping reactivation on gist abstraction. This study had a factorial design of 2 factors with 2 levels respectively (spatial overlap/no spatial overlap, TMR/no-TMR). Accordingly, 82 healthy college students (aged 19 ∼ 25, 57 females) were randomized into four groups. After learning 16 pictures, paired with 4 auditory cues (4 pictures - 1 cue) according to the grouping, participants were given a 90-minute nap opportunity. Then TMR cueing was conducted during N2 and slow wave sleep of the nap. Performance in memory task was used to measure gist abstraction. The results showed a significant main effect of TMR on both implicit and explicit gist abstraction, and a marginally significant interaction effect on explicit gist abstraction. Further analyses showed that explicit gist abstraction in the spatial overlap & TMR group was significantly better than in the control group. Moreover, explicit gist abstraction was positively correlated with spindle density. The current study thus indicates that TMR facilitates gist abstraction, and explicit gist abstraction may benefit more from overlapping reactivation.

A systematic review and meta-analysis of long term physical and mental sequelae of COVID-19 pandemic: call for research priority and action.

The long-term physical and mental sequelae of COVID-19 are a growing public health concern, yet there is considerable uncertainty about their prevalence, persistence and predictors. We conducted a comprehensive, up-to-date meta-analysis of survivors' health consequences and sequelae for COVID-19. PubMed, Embase and the Cochrane Library were searched through Sep 30th, 2021. Observational studies that reported the prevalence of sequelae of COVID-19 were included. Two reviewers independently undertook the data extraction and quality assessment. Of the 36,625 records identified, a total of 151 studies were included involving 1,285,407 participants from thirty-two countries. At least one sequelae symptom occurred in 50.1% (95% CI 45.4-54.8) of COVID-19 survivors for up to 12 months after infection. The most common investigation findings included abnormalities on lung CT (56.9%, 95% CI 46.2-67.3) and abnormal pulmonary function tests (45.6%, 95% CI 36.3-55.0), followed by generalized symptoms, such as fatigue (28.7%, 95% CI 21.0-37.0), psychiatric symptoms (19.7%, 95% CI 16.1-23.6) mainly depression (18.3%, 95% CI 13.3-23.8) and PTSD (17.9%, 95% CI 11.6-25.3), and neurological symptoms (18.7%, 95% CI 16.2-21.4), such as cognitive deficits (19.7%, 95% CI 8.8-33.4) and memory impairment (17.5%, 95% CI 8.1-29.6). Subgroup analysis showed that participants with a higher risk of long-term sequelae were older, mostly male, living in a high-income country, with more severe status at acute infection. Individuals with severe infection suffered more from PTSD, sleep disturbance, cognitive deficits, concentration impairment, and gustatory dysfunction. Survivors with mild infection had high burden of anxiety and memory impairment after recovery. Our findings suggest that after recovery from acute COVID-19, half of survivors still have a high burden of either physical or mental sequelae up to at least 12 months. It is important to provide urgent and appropriate prevention and intervention management to preclude persistent or emerging long-term sequelae and to promote the physical and psychiatric wellbeing of COVID-19 survivors.

First-night effect in insomnia disorder: a systematic review and meta-analysis of polysomnographic findings.

Polysomnographic studies have been performed to investigate the first-night effect in insomnia disorder. However, these studies have revealed discrepant findings. This meta-analysis aimed to summarise and quantify the characteristics of the first-night effect in insomnia disorder. We performed a systematic search of the PubMed, Medline, EMBASE, Web of Science and PsycINFO databases to identify studies published through October 2019. A total of 11,862 articles were identified, and seven studies with eight independent populations were included in the meta-analysis. A total of 639 patients with insomnia disorder and 171 healthy controls underwent more than 2 consecutive nights of in-laboratory polysomnography. Pooled results demonstrated that both variables of sleep continuity and sleep architecture, other than slow-wave sleep were significantly altered in the first-night effect in insomnia disorder. Furthermore, the results indicated that patients with insomnia disorder had a disruption of sleep continuity in the first-night effect, including increased sleep onset latency and reduced total sleep time, compared to healthy controls. Overall, the findings show that patients with insomnia disorder experience the first-night effect, rather than reverse first-night effect, and the profiles of the first-night effect in patients with insomnia are different from healthy controls. These indicate that an adaptation night is necessary when sleep continuity and sleep architecture is to be studied in patients with insomnia disorder. More well-designed studies with large samples are needed to confirm the results.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

The insensitivity of sleep to an unfamiliar sleeping environment in patients with insomnia disorder.

BACKGROUND: Sleeping in an unfamiliar environment, such as a sleep laboratory, is thought to disturb sleep in healthy individuals and could express a hyperarousal state called the first night effect. Insomnia disorder (ID) is a highly prevalent health problem characterized by increased arousal during the night and daytime. Whether or not a similar phenomenon occurs in patients with ID is unclear. This study aimed to investigate the effect of an unfamiliar environment on the sleep of patients with ID. METHODS: In an unfamiliar sleep laboratory, polysomnographic recording testing was performed for two consecutive nights in patients with ID and age- and sex-matched healthy control subjects (HC). We collected sleep diaries and questionnaires regarding sleep, medical conditions, psychological status, and health history. Sleep continuity and architecture in both groups were compared and analyzed for two consecutive nights. RESULTS: Participants with ID (n = 39)  and HC (n = 35) demonstrated differentially poor sleep on laboratory adaptation after exposure to the sleep laboratory. Patients with ID had longer rapid eye movement (REM) latency on the first night than on the second sleep night. HC showed increased duration and percentage of N1, decreased duration and percentage of N3, and decreased REM percentage during initial nights compared to subsequent nights. The other sleep variables showed no differences between the first and second sleep nights in patients with ID and HC. CONCLUSIONS: An unfamiliar sleep environment does not aggravate the disruption of sleep continuity and sleep architecture but only affects the REM latency in patients with ID compared with HC.

Challenges and Suggestions of Ethical Review on Clinical Research Involving Brain-Computer Interfaces.

Brain-computer interface (BCI) technology is rapidly advancing in medical research and application. As an emerging biomedical engineering technology, it has garnered significant attention in the clinical research of brain disease diagnosis and treatment, neurological rehabilitation, and mental health. However, BCI also raises several challenges and ethical concerns in clinical research. In this article, the authors investigate and discuss three aspects of BCI in medicine and healthcare: the state of ethical governance, multidimensional ethical challenges pertaining to BCI in clinical research, and suggestive concerns for ethical review. Despite the great potentials of frontier BCI research and development in the field of medical care, the ethical challenges induced by itself, clinical research and complexity of brain function has put forward new special fields for ethics on BCI. To ensure "responsible innovation" BCI research in healthcare and medicine, the creation of an ethical global governance framework and system, along with special guidelines for cutting-edge BCI research in medicine are suggested.

State-dependent and region-specific alterations of cerebellar connectivity across stable human wakefulness and NREM sleep states.

Sleep regulation and functioning may rely on systematic coordination throughout the whole brain, including the cerebellum. However, whether and how interactions between the cerebellum and other brain regions vary across sleep stages remain poorly understood. Here, using simultaneous EEG-fMRI recordings captured from 73 participants during wakefulness and non-rapid eye movement (NREM) sleep, we constructed cerebellar connectivity among intrinsic functional networks with intra-cerebellar, neocortical and subcortical regions. We uncovered that cerebellar connectivity exhibited sleep-dependent alterations: slight differences between wakefulness and N1/N2 sleep and greater changes in N3 sleep than other states. Region-specific cerebellar connectivity changes between N2 sleep and N3 sleep were also revealed: general breakdown of intra-cerebellar connectivity, enhancement of limbic-cerebellar connectivity and alterations of cerebellar connectivity with spatially specific neocortices. Further correlation analysis showed that functional connectivity between the cerebellar Control II network and regions (including the insula, hippocampus, and amygdala) correlated with delta power during N3 and beta power during N2 sleep. These findings systematically reveal altered cerebellar connectivity among intrinsic networks from wakefulness to deep sleep and highlight the potential role of the cerebellum in sleep regulation and functioning.

Depression, anxiety, and burnout among psychiatrists during the COVID-19 pandemic: a cross-sectional study in Beijing, China.

BACKGROUND: With the rise of reported mental disorders and behavioral issues after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, psychiatrists and mental health care are urgently needed more than ever before. The psychiatric career carries a high emotional burden and stressful demands, which bring issues on psychiatrists' mental health and well-being into question. To investigate the prevalence and risk factors of depression, anxiety, and work burnout among psychiatrists in Beijing during the COVID-19 pandemic. METHODS: This cross-sectional survey was conducted from January 6 to January 30, 2022, two years after COVID-19 was declared a global pandemic. Recruitment was performed using a convenience sample approach by sending online questionnaires to psychiatrists in Beijing. The symptoms of depression, anxiety, and burnout were evaluated using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Maslach Burnout Inventory-General Survey (MBI-GS). The perceived stress and social support were measured by the Chinese Perceived Stress Scale (CPSS) and Social Support Rating Scale (SSRS), respectively. RESULTS: The data of 564 psychiatrists (median [interquartile range] age, 37 [30-43] years old) of all 1532 in Beijing were included in the statistical analysis. The prevalence of symptoms of depression, anxiety and burnout were 33.2% (95% CI, 29.3-37.1%, PHQ-9 ≥ 5), 25.4% (95% CI, 21.8-29.0%, GAD-7 ≥ 5) and 40.6% (95% CI, 36.5-44.7%, MBI-GS ≥ 3 in each of the three subdimensions), respectively. The psychiatrist with a higher score on perceived stress was more likely to suffer from depressive symptoms (adjusted odds ratios [ORs]: 4.431 [95%CI, 2.907-6.752]); the anxiety symptoms (adjusted ORs: 8.280 [95%CI, 5.255-13.049]), and the burnout conditions (adjusted ORs: 9.102 [95%CI, 5.795-14.298]). Receiving high social support was an independent protective factor against symptoms of depression (adjusted ORs: 0.176 [95%CI, [0.080-0.386]), anxiety (adjusted ORs: 0.265 [95%CI, 0.111-0.630]) and burnout (adjusted ORs: 0.319 [95%CI, 0.148-0.686]). CONCLUSIONS: Our data suggest a considerable proportion of psychiatrists also suffer from depression, anxiety, and burnout. Perceived stress and social support influence depression, anxiety, and burnout. For public health, we must work together to reduce the pressure and increase social support to mitigate mental health risks in psychiatrists.

The disruption of white matter integrity of systemic striatal circuits in alcohol-dependent males with physiological cue reactivity.

Alcohol dependence (AD) is a chronic and relapsing disorder. Conditioned cues associated with the rewarding properties of drugs could trigger motivational/physiological reactions and render subjects vulnerable to relapse. Striatal circuit dysfunction has been implicated in alcohol addiction behaviours. However, little is known about the striatal tracts structural connectivity changes underlying cue induced reactivity in AD. In our present study, we recruited 51 patients with AD; 31 individuals had physiological response. We used seed-based classification by probabilistic tractography with nine target masks to explore the white matter integrity of striatal circuits in physiological responders (N = 31), non-responders (N = 20), and healthy controls (N = 27). Compared with healthy controls, physiological responders showed lower fractional anisotropy (FA) and/or higher mean diffusivity in the striatum-dorsolateral prefrontal cortex (dlPFC), striatum-ventral lateral prefrontal cortex, striatum-supplementary motor area (SMA), and striatum-insular. Considering age and smoking are potential nuisances to diffusion parameters, an analysis of covariance also was conducted and similar results were found. We also found the cue-induced physiological response was negatively associated with the FA of the striatum-SMA (r = -0.287; p = 0.045) and left striatum-dlPFC (r = -0.253; p = 0.079) in AD. In our study, we found abnormal integrity of striatal circuit structural connectivity in AD with physiological cue reactivity, especially trajectory from prefrontal cortex and insular. We also found the FA of striatal tracks was negatively associated with the degree of cue reactivity. Our findings provide further evidence for reduced white matter integrity of striatal circuits for cue reactivity in male individuals with AD.

[Identifying Depressive Disorder With Sleep Electroencephalogram Data: A Study Based on Deep Learning].

Objective: To explore the effectiveness of using deep learning network combined Vision Transformer (ViT) and Transformer to identify patients with depressive disorder on the basis of their sleep electroencephalogram (EEG) signals. Methods: The sleep EEG signals of 28 patients with depressive disorder and 37 normal controls were preprocessed. Then, the signals were converted into image format and the feature information on frequency domain and spatial domain was retained. After that, the images were transmitted to the ViT-Transformer coding network for deep learning of the EEG signal characteristics of the rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep in patients with depressive disorder and those in normal controls, respectively, and to identify patients with depressive disorder. Results: Based on the ViT-Transformer network, after examining different EEG frequencies, we found that the combination of delta, theta, and beta waves produced better results in identifying depressive disorder. Among the different EEG frequencies, EEG signal features of delta-theta-beta combination waves in REM sleep achieved 92.8% accuracy and 93.8% precision for identifying depression, with the recall rate of patients with depression being 84.7%, and the F0.5 value being 0.917±0.074. When using the delta-theta-beta combination EEG signal features in NREM sleep to identify depressive disorder, the accuracy was 91.7%, the precision was 90.8%, the recall rate was 85.2%, and the F0.5 value was 0.914±0.062. In addition, through visualization of the sleep EEG of different sleep stages for the whole night, it was found that classification errors usually occurred during transition to a different sleep stage. Conclusion: Using the deep learning ViT-Transformer network, we found that the EEG signal features in REM sleep based on delta-theta-beta combination waves showed better effect in identifying depressive disorder.

Identification of novel risk loci with shared effects on alcoholism, heroin, and methamphetamine dependence.

Different substance dependences have common effects on reward pathway and molecular adaptations, however little is known regarding their shared genetic factors. We aimed to identify the risk genetic variants that are shared for substance dependence (SD). First, promising genome-wide significant loci were identified from 3296 patients (521 alcoholic/1026 heroin/1749 methamphetamine) vs 2859 healthy controls and independently replicated using 1954 patients vs 1904 controls. Second, the functional effects of promising variants on gene expression, addiction characteristics, brain structure (gray and white matter), and addiction behaviors in addiction animal models (chronic administration and self-administration) were assessed. In addition, we assessed the genetic correlation among the three SDs using LD score regression. We identified and replicated three novel loci that were associated with the common risk of heroin, methamphetamine addiction, and alcoholism: ANKS1B rs2133896 (Pmeta = 3.60 × 10-9), AGBL4 rs147247472 (Pmeta = 3.40 × 10-12), and CTNNA2 rs10196867 (Pmeta = 4.73 × 10-9). Rs2133896 in ANKS1B was associated with ANKS1B gene expression and had effects on gray matter of the left calcarine and white matter of the right superior longitudinal fasciculus in heroin dependence. Overexpression of anks1b gene in the ventral tegmental area decreased addiction vulnerability for heroin and methamphetamine in self-administration rat models. Our findings could shed light on the root cause for substance dependence and will be helpful for the development of cost-effective prevention strategies for general addiction disorders.

Somatic symptoms mediate the association between subclinical anxiety and depressive symptoms and its neuroimaging mechanisms.

BACKGROUND: Subclinical anxiety, depressive and somatic symptoms appear closely related. However, it remains unclear whether somatic symptoms mediate the association between subclinical anxiety and depressive symptoms and what the underlying neuroimaging mechanisms are for the mediating effect. METHODS: Data of healthy participants (n = 466) and participants in remission of major depressive disorder (n = 53) were obtained from the Human Connectome Project. The Achenbach Adult Self-Report was adopted to assess anxiety, depressive and somatic symptoms. All participants completed four runs of resting-state functional magnetic resonance imaging. Mediation analyses were utilized to explore the interactions among these symptoms and their neuroimaging mechanisms. RESULTS: Somatic symptoms partially mediated the association between subclinical anxiety and depressive symptoms in healthy participants (anxiety→somatic→depression: effect: 0.2785, Boot 95% CI: 0.0958-0.3729; depression→somatic→anxiety: effect: 0.0753, Boot 95% CI: 0.0232-0.1314) and participants in remission of MDD (anxiety→somatic→depression: effect: 0.2948, Boot 95% CI: 0.0357-0.7382; depression→somatic→anxiety: effect: 0.0984, Boot 95% CI: 0.0007-0.2438). Resting-state functional connectivity (FC) between the right medial superior frontal gyrus and the left thalamus and somatic symptoms as chain mediators partially mediated the effect of subclinical depressive symptoms on subclinical anxiety symptoms in healthy participants (effect: 0.0020, Boot 95% CI: 0.0003-0.0043). The mean strength of common FCs of subclinical depressive and somatic symptoms, somatic symptoms, and the mean strength of common FCs of subclinical anxiety and somatic symptoms as chain mediators partially mediated the effect of subclinical depressive symptoms on subclinical anxiety symptoms in remission of MDD (effect: 0.0437, Boot 95% CI: 0.0024-0.1190). These common FCs mainly involved the insula, precentral gyri, postcentral gyri and cingulate gyri. Furthermore, FC between the triangular part of the left inferior frontal gyrus and the left postcentral gyrus was positively associated with subclinical anxiety, depressive and somatic symptoms in remission of MDD (FDR-corrected p < 0.01). CONCLUSIONS: Somatic symptoms partially mediate the interaction between subclinical anxiety and depressive symptoms. FCs involving the right medial superior frontal gyrus, left thalamus, triangular part of left inferior frontal gyrus, bilateral insula, precentral gyri, postcentral gyri and cingulate gyri maybe underlie the mediating effect of somatic symptoms.

Workforce situation of the Chinese mental health care system: results from a cross-sectional study.

BACKGROUND: High-quality mental health services can improve outcomes for people with mental health problems and abate the burden of mental disorders. We sought to identify the challenges the country's mental health system currently faces and the human resource situation related to psychological services and to provide recommendations on how the mental health workforce situation could be addressed in China. METHODS: This study used a cross-sectional survey design. A web-based questionnaire approach and a convenience sampling method were adopted. It was carried out from September 2020 to January 2021 in China, and we finally included 3824 participants in the analysis. Descriptive statistical analysis of the characteristics of the study sample was performed. The risk factors for competence in psychological counseling/psychotherapy were assessed using multiple linear regression analysis. RESULTS: Workforce related to psychotherapy is scarce in China, especially in Western China and community mental health sectors. Psychiatrists (39.1%) and nurses (38.9%) were the main service providers of psychotherapy in psychiatric hospitals, and clinical psychologists (6.9%) and counsellors (5.0%) were seriously scarce in mental health care sectors. A total of 74.2% of respondents had no systematic psychological training, and 68.4 and 69.2% of them had no self-experience and professional supervision, respectively. Compared with clinical psychologists and counselors, psychiatrists and nurses had less training. Systematic psychological training (ß = - 0.88), self-experience (ß = - 0.59) and professional supervision (ß = - 1.26) significantly influenced psychotherapy capacity (P<0.001). CONCLUSIONS: Sustained effort will be required to provide a high-quality, equitably distributed psychotherapy workforce in China, despite challenges for community mental health sectors and western China being likely to continue for some time. Because mental illness is implicated in so many burgeoning social ills, addressing this shortfall could have wide-ranging benefits.

Functional connectivity of the human hypothalamus during wakefulness and nonrapid eye movement sleep.

Animal experiments indicate that the hypothalamus plays an essential role in regulating the sleep-wake cycle. A recent neuroimaging study conducted under resting wakefulness conditions suggested the presence of a wake-promoting region and a sleep-promoting region in the human posterior hypothalamus and anterior hypothalamus, respectively, and interpreted their anticorrelated organization in resting-state functional networks as evidence for their opposing roles in sleep-wake regulation. However, whether and how the functional networks of the two hypothalamic regions reorganize according to their wake- or sleep-promoting roles during sleep are unclear. Here, we constructed functional networks of the posterior and anterior hypothalamus during wakefulness and nonrapid eye movement (NREM) sleep using simultaneous electroencephalography and functional magnetic resonance imaging data collected from 62 healthy participants. The functional networks of the posterior and anterior hypothalamus exhibited inversely correlated organizations during both wakefulness and NREM sleep. The connectivity strength of the posterior hypothalamic functional network was stronger during wakefulness than during stable sleep. From wakefulness to sleep, the anterior cingulate gyrus, paracingulate gyrus, insular cortex, and fontal operculum cortex showed decreased positive connectivity, while the precentral gyrus and postcentral gyrus showed decreased negative connectivity with the posterior hypothalamus. Additionally, the insular cortex and frontal operculum cortex showed negative connectivity during wakefulness and positive connectivity during sleep with the anterior hypothalamus, exhibiting an increasing trend. These findings provide insights into the correspondence between the functional network organizations and hypothalamic sleep-wake regulation in humans.

Altered thalamic connectivity in insomnia disorder during wakefulness and sleep.

Insomnia disorder is the most common sleep disorder and has drawn increasing attention. Many studies have shown that hyperarousal plays a key role in the pathophysiology of insomnia disorder. However, the specific brain mechanisms underlying insomnia disorder remain unclear. To elucidate the neuropathophysiology of insomnia disorder, we investigated the brain functional networks of patients with insomnia disorder and healthy controls across the sleep-wake cycle. EEG-fMRI data from 33 patients with insomnia disorder and 31 well-matched healthy controls during wakefulness and nonrapid eye movement sleep, including N1, N2 and N3 stages, were analyzed. A medial and anterior thalamic region was selected as the seed considering its role in sleep-wake regulation. The functional connectivity between the thalamic seed and voxels across the brain was calculated. ANOVA with factors "group" and "stage" was performed on thalamus-based functional connectivity. Correlations between the misperception index and altered functional connectivity were explored. A group-by-stage interaction was observed at widespread cortical regions. Regarding the main effect of group, patients with insomnia disorder demonstrated decreased thalamic connectivity with the left amygdala, parahippocampal gyrus, putamen, pallidum and hippocampus across wakefulness and all three nonrapid eye movement sleep stages. The thalamic connectivity in the subcortical cluster and the right temporal cluster in N1 was significantly correlated with the misperception index. This study demonstrated the brain functional basis in insomnia disorder and illustrated its relationship with sleep misperception, shedding new light on the brain mechanisms of insomnia disorder and indicating potential therapeutic targets for its treatment.

Augmentation of fear extinction by theta-burst transcranial magnetic stimulation of the prefrontal cortex in humans.

Background: Fear extinction alone does not erase the original fear memory. Interventions that enhance extinction can be beneficial for the treatment of fear-related disorders. Repetitive transcranial magnetic stimulation has been shown to improve memory performance. The present study examined the effects of intermittent theta-burst stimulation (iTBS) on fear extinction and the return of fear memory in humans. Methods: Ninety-one young healthy volunteers underwent 3 experiments using a randomized controlled experimental design. Participants first acquired fear conditioning, after which they received 30 Hz iTBS before and after extinction training. The iTBS was applied to 1 of 2 targets: the left dorsolateral prefrontal cortex (dlPFC) and the vertex (control). Fear responses were measured 24 hours later and 1 month later. Results: During the spontaneous recovery and reinstatement tests, iTBS of the left dlPFC before and after extinction significantly reduced fear response, whereas iTBS of the vertex had no effect on fear memory performance. This combined approach had a relatively long-lasting effect (i.e., at least 1 month). Limitations: We did not explore the effect of iTBS of the dlPFC on the expression of fear without extinction training. The neural mechanisms of iTBS with fear extinction to inhibit the fear response are unclear. Our results are preliminary and should be interpreted with caution. Conclusion: `The present results showed that 30 Hz iTBS of the left dlPFC enhanced retention of fear extinction. Our study introduces a new intervention for fear memory and suggests that the left dlPFC may be a treatment target for fear-related disorders.

Association between functional and structural connectivity of the corticostriatal network in people with schizophrenia and unaffected first-degree relatives.

Background: Dysfunction of the corticostriatal network has been implicated in the pathophysiology of schizophrenia, but findings are inconsistent within and across imaging modalities. We used multimodal neuroimaging to analyze functional and structural connectivity in the corticostriatal network in people with schizophrenia and unaffected first-degree relatives. Methods: We collected resting-state functional magnetic resonance imaging and diffusion tensor imaging scans from people with schizophrenia (n = 47), relatives (n = 30) and controls (n = 49). We compared seed-based functional and structural connectivity across groups within striatal subdivisions defined a priori. Results: Compared with controls, people with schizophrenia had altered connectivity between the subdivisions and brain regions in the frontal and temporal cortices and thalamus; relatives showed different connectivity between the subdivisions and the right anterior cingulate cortex (ACC) and the left precuneus. Post-hoc t tests revealed that people with schizophrenia had decreased functional connectivity in the ventral loop (ventral striatum-right ACC) and dorsal loop (executive striatum-right ACC and sensorimotor striatum-right ACC), accompanied by decreased structural connectivity; relatives had reduced functional connectivity in the ventral loop and the dorsal loop (right executive striatum-right ACC) and no significant difference in structural connectivity compared with the other groups. Functional connectivity among people with schizophrenia in the bilateral ventral striatum-right ACC was correlated with positive symptom severity. Limitations: The number of relatives included was moderate. Striatal subdivisions were defined based on a relatively low threshold, and structural connectivity was measured based on fractional anisotropy alone. Conclusion: Our findings provide insight into the role of hypoconnectivity of the ventral corticostriatal system in people with schizophrenia.

Immunohistochemical Analysis of mTOR Pathway-Related Proteins in Kaposiform Hemangioendothelioma.

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors have been shown to have excellent effects in the management of kaposiform hemangioendothelioma (KHE); however, the mechanism of action is unclear. This study identified the expressions of mTOR pathway-related proteins in different vascular tumors to provide insight into the pathogenesis of KHE. METHODS: We retrospectively reviewed the pathologic specimens of 30 patients (KHE, 15; tufted angioma [TA], 5; infantile hemangioma [IH], 5; and lymphatic malformation [LM], 5). The immunohistochemical expression of mTOR-related proteins tuberous sclerosis complex 2 (TSC2), phosphatase and tensin homologue (PTEN), phosphorylated eukaryotic translation initiation factor 4E binding protein 1 (p-4EBP1), phosphorylated mTOR (p-mTOR), and phosphorylated ribosomal protein S6 kinase B1 (p-P70S6K) were analyzed using Image-Pro Plus software. KHE had the following pattern of expression in the spindle vascular endothelial cells: TSC2 (-); PTEN (-); p-4EBP1 (+); p-mTOR (+); and p-P70S6K (+). RESULTS: All 3 patients treated with sirolimus had good responses. The TA results were similar to KHE with no significant differences (p-4EBP1: p = 0.0687; p-mTOR: p = 0.0832). The expressions of TSC2, PTEN, p-4EBP1, p-mTOR, and p-P70S6K were negative or weakly positive in IH with a statistically significant difference compared to KHE (p-4EBP1: p < 0.001; p-mTOR: p < 0.001; p-P70S6K: p < 0.001). LM had no significant differences when compared to KHE. CONCLUSIONS: The absence of TSC2 and PTEN caused abnormal activation of the mTOR signaling pathway and may be involved in the pathogenesis of KHE. The expression of mTOR-related proteins in TA and LM was similar to KHE, unlike IH. The KHE pattern of expression [PTEN (-), TSC2 (-), p-mTOR (+), p-P70S6K (+), and p-4EBP1 (+)] suggested that sirolimus may be a good therapeutic choice.

Knowledge and attitudes about transcranial magnetic stimulation among psychiatrists in China.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive form of brain stimulation. It has been used in many mental health institutions to treat mental disorders worldwide. However, comprehensive knowledge about rTMS is not yet widespread among psychiatrists. The present study assessed psychiatrists' knowledge and attitudes about rTMS in China and investigated related factors. METHODS: A quantitative observational cross-sectional study was conducted using an online survey. The sample consisted of 522 psychiatrists. Multinomial logistic regression and multiple linear regression analyses were used to explore factors that contributed to psychiatrists' knowledge about rTMS. We also ascertained psychiatrists' attitudes about rTMS and provide recommendations for the more widespread use of rTMS. RESULTS: The majority of respondents (86.4%) reported having access to rTMS at their institution. A total of 379 psychiatrists (72.6%) knew that rTMS was approved by the United States Food and Drug Administration for treatment-resistant depression. Univariate logistic regression indicated that psychiatrists who were older, had a senior professional title, worked more years, had an onsite clinical rTMS program in their hospital, and received formal training in theory and application (all p <  0.05) were more likely to know that rTMS was approved by the Food and Drug Administration for the treatment of depression. The percentages of respondents who knew most or all indications, the mechanism of action, parameter settings, adverse reactions were 51.9, 40.2, 27.4, and 41.4%. Linear regression showed that formal training in rTMS theory and practice were associated with higher knowledge scores (all p <  0.05). Most of the subjects had negative attitudes about using rTMS to treat mental disorders. When asked about their attitudes about continuing rTMS education, nearly all of the respondents indicated that they were willing to pursue continuing training in rTMS in the future. CONCLUSIONS: Many psychiatrists had an insufficient level of knowledge about rTMS and negative attitudes about rTMS. Psychiatrists who had formal rTMS training experience had higher levels of rTMS knowledge. rTMS training and relevant policy making should be strengthened.

Skip Re-Entry Trajectory Detection and Guidance for Maneuvering Vehicles.

The re-entry trajectory of maneuvering vehicles with medium to high hypersonic lift-to-drag ratios is generally planned using quasi-equilibrium flight conditions known from Space Shuttles. They may exhibit an oscillation re-entry phenomenon termed skip re-entry when related components or sensors fail. However, conventional re-entry guidance only considers quasi-equilibrium flights and ignores the possibility of the occurrence of an unexpected skip trajectory; this may lead to the failure of the re-entry mission due to a lack of a corresponding guidance strategy. However, the detection of a skip trajectory is the necessary reference for the decision-making of calling a related guidance algorithm that helps improve the safety of vehicle re-entry. Herein, a skip re-entry detection and trajectory control solution is proposed to play an emergency role in the cases of skip re-entry. Firstly, the oscillation frequency characteristics of the linearized re-entry motion equation of a vehicle are analyzed, and an approximate analytical relationship is constructed for skip altitude estimation. Then, the residual deviation between the altitude feedback data and the estimated skip altitude is calculated and compared with the threshold to determine the occurrence of skip re-entry. In addition, a method for controlling the skip re-entry trajectory with the range extension is developed by controlling the bank angle with a fixed angle of attack profile, satisfying the path constraint requirements. The results indicate that the method effectively performs skip re-entry detection and that it can help extend the range of the vehicles in abnormal re-entry scenarios, keeping the flight within the path constraints and guiding it to the expected location.