Brain Sci., Volume 14, Issue 5 (May 2024) – 54 articles

Electroencephalography (EEG) is effectively employed to describe cognitive patterns corresponding to different tasks of motor functions for brain–computer interface (BCI) implementation. Explicit information processing is necessary to reduce the computational complexity of practical BCI systems. This paper presents an entropy-based approach to select effective EEG channels for motor imagery (MI) classification in brain–computer interface (BCI) systems. The method identifies channels with higher entropy scores, which is an indication of greater information content. It discards redundant or noisy channels leading to reduced computational complexity and improved classification accuracy. High entropy means a more disordered pattern, whereas low entropy means a less disordered pattern with less information. The entropy of each channel for individual trials is calculated. The weight of each channel is represented by the mean entropy of the channel over all the trials. A set of channels with higher mean entropy are selected as effective channels for MI classification. A limited number of sub-band signals are created by decomposing the selected channels. To extract the spatial features, the common spatial pattern (CSP) is applied to each sub-band space of EEG signals. The CSP-based features are used to classify the right-hand and right-foot MI tasks using a support vector machine (SVM). The effectiveness of the proposed approach is validated using two publicly available EEG datasets, known as BCI competition III–IV(A) and BCI competition IV–I. The experimental results demonstrate that the proposed approach surpasses cutting-edge techniques. Full article

Background: Theory of Mind (ToM) impairment has repeatedly been found in paranoid schizophrenia. The current study aims at investigating whether this is related to a deficit in ToM (undermentalizing) or an increased ToM ability to hyperattribute others’ mental states (overmentalizing). Methods: Mental state attribution was examined in 24 patients diagnosed with schizophrenia (12 acute paranoid (APS) and 12 post-acute paranoid (PPS)) with regard to positive symptoms as well as matched healthy persons using a moving shapes paradigm. We used 3-T-functional magnetic resonance imaging (fMRI) to provide insights into the neural underpinnings of ToM due to attributional processes in different states of paranoid schizophrenia. Results: In the condition that makes demands on theory of mind skills (ToM condition), in patients with diagnosed schizophrenia less appropriate mental state descriptions have been used, and they attributed mental states less often to the moving shapes than healthy persons. On a neural level, patients suffering from schizophrenia exhibited within the ToM network hypoactivity in the medial prefrontal cortex (MPFC) and hyperactivity in the temporo-parietal junction (TPJ) as compared to the healthy sample. Conclusions: Our results indicate both undermentalizing and hypoactivity in the MPFC and increased overattribution related to hyperactivity in the TPJ in paranoid schizophrenia, providing new implications for understanding ToM in paranoid schizophrenia. Full article

This review aims to present age-related changes in the neuroelectric responses of typically developing children (TDC) who are presumed to meet developmental stages appropriately. The review is based on findings from the frequently used neuropsychological tasks of active attention, where attention is deliberately focused versus passive attention where attention is drawn to a stimulus, facilitatory attention, which enhances the processing of a stimulus versus inhibitory attention, which suppresses the processing of a stimulus. The review discusses the early and late stages of attentional selectivity that correspond to early and late information processing. Age-related changes in early attentional selectivity were quantitatively represented in latencies of the event-related potential (ERP) components. Age-related changes in late attentional selectivity are also qualitatively represented by structural and functional reorganization of attentional processing and the brain areas involved. The purely bottom-up or top-down processing is challenged with age-related findings on difficult tasks that ensure a high cognitive load. TDC findings on brain oscillatory activity are enriched by findings from attention deficit hyperactivity disorder (ADHD). The transition from the low to fast oscillations in TDC and ADHD confirmed the maturational lag hypothesis. The deviant topographical localization of the oscillations confirmed the maturational deviance model. The gamma-based match and utilization model integrates all levels of attentional processing. According to these findings and theoretical formulations, brain oscillations can potentially display the human brain’s wholistic–integrative functions. Full article

(1) Background: Transcranial direct current stimulation (tDCS) is a safe intervention, only producing mild and transient adverse effects (AEs). However, there is no detailed analysis of the pattern of adverse effects in an application transferable to the clinic. Therefore, our objective is to describe the AEs produced by tDCS and its temporal evolution. (2) Methods: A total of 33 young volunteers were randomized into a tDCS or sham group. Participants performed a hand dexterity task while receiving the tDCS or sham intervention (20 min and 1 mA), for five consecutive days. AEs were assessed daily after each intervention and classified as somatosensory, pain, or other effects. (3) Results: The number of AEs was generally increased by tDCS intervention. Specifically, tDCS led to more frequent somatosensory discomfort, characterized by sensations like itching and tingling, alongside painful sensations such as burning, compared to the sham intervention. Additionally, certain adverse events, including neck and arm pain, as well as dizziness and blurry vision, were exclusive to the tDCS group. Interestingly, tDCS produced similar AEs across the days; meanwhile, the somatosensory AEs in the sham group showed a trend to decrease. (4) Conclusions: tDCS produces mild and temporary somatosensory and pain AEs during and across sessions. The different evolution of the AEs between the tDCS and sham protocol could unmask the blinding protocol most used in tDCS studies. Potential solutions for improving blinding protocols for future studies are discussed. Full article

Functional connectivity (FC) obtained from resting-state functional magnetic resonance imaging has been integrated with machine learning algorithms to deliver consistent and reliable brain disease classification outcomes. However, in classical learning procedures, custom-built specialized feature selection techniques are typically used to filter out uninformative features from FC patterns to generalize efficiently on the datasets. The ability of convolutional neural networks (CNN) and other deep learning models to extract informative features from data with grid structure (such as images) has led to the surge in popularity of these techniques. However, the designs of many existing CNN models still fail to exploit the relationships between entities of graph-structure data (such as networks). Therefore, graph convolution network (GCN) has been suggested as a means for uncovering the intricate structure of brain network data, which has the potential to substantially improve classification accuracy. Furthermore, overfitting in classifiers can be largely attributed to the limited number of available training samples. Recently, the generative adversarial network (GAN) has been widely used in the medical field for its generative aspect that can generate synthesis images to cope with the problems of data scarcity and patient privacy. In our previous work, GCN and GAN have been designed to investigate FC patterns to perform diagnosis tasks, and their effectiveness has been tested on the ABIDE-I dataset. In this paper, the models will be further applied to FC data derived from more public datasets (ADHD, ABIDE-II, and ADNI) and our in-house dataset (PTSD) to justify their generalization on all types of data. The results of a number of experiments show the powerful characteristic of GAN to mimic FC data to achieve high performance in disease prediction. When employing GAN for data augmentation, the diagnostic accuracy across ADHD-200, ABIDE-II, and ADNI datasets surpasses that of other machine learning models, including results achieved with BrainNetCNN. Specifically, in ADHD, the accuracy increased from 67.74% to 73.96% with GAN, in ABIDE-II from 70.36% to 77.40%, and in ADNI, reaching 52.84% and 88.56% for multiclass and binary classification, respectively. GCN also obtains decent results, with the best accuracy in ADHD datasets at 71.38% for multinomial and 75% for binary classification, respectively, and the second-best accuracy in the ABIDE-II dataset (72.28% and 75.16%, respectively). Both GAN and GCN achieved the highest accuracy for the PTSD dataset, reaching 97.76%. However, there are still some limitations that can be improved. Both methods have many opportunities for the prediction and diagnosis of diseases. Full article

Background: Studies have reported higher in-hospital mortality rates in patients living with dementia (PlwD) with limited evidence across age groups, clinical departments, and admission diagnoses. The aim of this study was to compare the in-hospital mortality rate of PlwD with patients without dementia across groups, clinical departments, and admission diagnoses. Methods: This case-control study included patients aged ≥ 60 years hospitalized in 1 of 14 German hospitals between January 2019 and July 2023. PlwD were matched to patients without dementia. The associations between dementia and in-hospital mortality across groups were assessed using univariable logistic regression analyses. Results: 15,956 patients with and 15,956 without dementia were included (mean age: 83.9 years, 60.7% female). PlwD had a significantly higher in-hospital mortality rate (14.0% vs. 11.7%; OR 1.24, 95% CI: 1.16–1.32) than non-dementia controls. The highest excess mortality rate was observed in the youngest age group (60–70 years: 10.9% vs. 5.7%; OR: 2.05, 95% CI: 1.30–3.24), decreased with age, and became non-significant in the oldest age group (≥90 years: 16.2% vs. 17.3%; OR: 0.93, 95% CI: 0.80–1.08). Significant differences were found for digestive system disorders (OR: 1.59; 95% CI: 1.15–1.89), cardiovascular and cerebrovascular disorders (OR: 1.51; 95% CI: 1.30–1.75), endocrine, nutritional, and metabolic diseases (OR: 1.42; 95% CI: 1.06–1.90), and pneumonia (OR: 1.20; 95% CI: 1.04–1.37), as well as for all clinic departments except for geriatric departments. Conclusion: The excess mortality rate was highest in younger age groups, where the general mortality and complication rate is relatively low in the general population. Appropriate approaches are needed, especially in non-geriatric wards. Full article

The roles of perinatal development, intracellular calcium [Ca²⁺]i, and synaptogenesis disruption are not novel in the autism/ASD literature. The focus on six mechanisms controlling synaptogenesis, each regulated by [Ca²⁺]i, and each aberrant in ASDs is novel. The model presented here predicts that autism epidemic causation involves central roles of both electromagnetic fields (EMFs) and chemicals. EMFs act via voltage-gated calcium channel (VGCC) activation and [Ca²⁺]i elevation. A total of 15 autism-implicated chemical classes each act to produce [Ca²⁺]i elevation, 12 acting via NMDA receptor activation, and three acting via other mechanisms. The chronic nature of ASDs is explained via NO/ONOO(-) vicious cycle elevation and MeCP2 epigenetic dysfunction. Genetic causation often also involves [Ca²⁺]i elevation or other impacts on synaptogenesis. The literature examining each of these steps is systematically examined and found to be consistent with predictions. Approaches that may be sed for ASD prevention or treatment are discussed in connection with this special issue: The current situation and prospects for children with ASDs. Such approaches include EMF, chemical avoidance, and using nutrients and other agents to raise the levels of Nrf2. An enriched environment, vitamin D, magnesium, and omega-3s in fish oil may also be helpful. Full article

In this narrative, comprehensive, and updated review of the literature, we summarize evidence about the effectiveness of interventions aimed at reducing emotion dysregulation and improving emotion regulation in children, adolescents, and adults. After introducing emotion dysregulation and emotion regulation from a theoretical standpoint, we discuss the factors commonly associated with emotion regulation, including neurobiological and neuropsychological mechanisms, and the role of childhood adverse experiences and psycho–social factors in the onset of emotion dysregulation. We then present evidence about pharmacological and non-pharmacological interventions aiming at improving emotion dysregulation and promoting emotion regulation across the lifespan. Although our review was not intended as a traditional systematic review, and the search was only restricted to systematic reviews and meta-analyses, we highlighted important implications and provided recommendations for clinical practice and future research in this field. Full article

Background: tinnitus is a common and often debilitating condition with limited evidence-based treatment options. Deep brain stimulation (DBS) is an approved treatment modality for certain neurological conditions; its experimental use as a treatment modality for severe tinnitus is novel and beginning to show promise. This systematic review focuses on the current evidence for the safety and efficacy of DBS for treatment of refractory tinnitus. Methods: a systematic search in PubMed and EMBASE was performed to identify peer-reviewed studies on DBS of non-cortical structures for the primary indication of tinnitus treatment. Three studies were identified as meeting these criteria, one of which had two related sub-studies. Results: seven patients with available data who underwent DBS for tinnitus were identified. DBS targets included nucleus accumbens (NAc), ventral anterior limb of the internal capsule (vALIC), caudate nucleus, and the medial geniculate body (MGB) of the thalamus. All studies used the Tinnitus Functional Index (TFI) as a primary outcome measure. DBS of the caudate was most commonly reported (n = 5), with a mean TFI improvement of 23.3 points. Only one subject underwent DBS targeting the NAc/vALIC (extrapolated TFI improvement 46.8) and one subject underwent DBS targeting the MGB (TFI improvement 59 points). Conclusions: DBS is a promising treatment option for refractory subjective tinnitus, with early data, from small patient cohorts in multiple studies, suggesting its safety and efficacy. Further studies with a larger patient population are needed to support this safety and efficacy before implementing this treatment to daily practice. Full article

Computerized assessments and digital games have become more prevalent in childhood, necessitating a systematic investigation of the effects of gamified executive function assessments on performance and engagement. This study examined the feasibility of incorporating gamification and a machine learning algorithm that adapts task difficulty to individual children’s performance into a traditional executive function task (i.e., Flanker Task) with children ages 3–5. The results demonstrated that performance on a gamified version of the Flanker Task was associated with performance on the traditional version of the task and standardized academic achievement outcomes. Furthermore, gamification grounded in learning science and developmental psychology theories applied to a traditional executive function measure increased children’s task enjoyment while preserving psychometric properties of the Flanker Task. Overall, this feasibility study indicates that gamification and adaptive machine learning algorithms can be successfully incorporated into executive function assessments with young children to increase enjoyment and reduce data loss with developmentally appropriate and intentional practices. Full article

Fibromyalgia syndrome (FM) is a chronic pain condition that affects a significant portion of the population; yet, this condition is still poorly understood. Prior research has suggested that individuals with FM display a heightened sensitivity to pain and signs of autonomic dysfunction. Recent advances in functional MRI analysis methods to model blood-oxygenation-level-dependent (BOLD) responses across networks of regions, and structural and physiological modeling (SAPM) have shown the potential to provide more detailed information about altered neural activity than was previously possible. Therefore, this study aimed to apply novel analysis methods to investigate altered neural processes underlying pain sensitivity in FM in functional magnetic resonance imaging (fMRI) data from the brainstem and spinal cord. Prior fMRI studies have shown evidence of functional differences in fibromyalgia (FM) within brain regions associated with pain’s motivational aspects, as well as differences in neural activity related to pain regulation, arousal, and autonomic homeostatic regulation within the brainstem and spinal cord regions. We, therefore, hypothesized that nociceptive processing is altered in FM compared to healthy controls (HCs) in the brainstem and spinal cord areas linked to autonomic function and descending pain regulation, including the parabrachial nuclei (PBN) and nucleus tractus solitarius (NTS). We expected that new details of this altered neural signaling would be revealed with SAPM. The results provide new evidence of altered neural signaling in FM related to arousal and autonomic homeostatic regulation. This further advances our understanding of the altered neural processing that occurs in women with FM. Full article

Background: Substance use in adolescents has been separately related to personality traits and parental socialization styles; in this study, our objective was to study these variables in an integrated way. Methods: A cross-sectional observational study was conducted in five institutes in a final sample of 331 students, excluding those with gaming disorder. The sample was stratified into three subgroups: ‘no addiction’, ‘low risk’, and ‘high risk’ of Substance Use Disorders (SUD). Results: 12.9% of the adolescents presented a low risk of SUD, while 18.3% showed a high risk, with both being older (F = 9.16; p < 0.001) than the no addiction group. Adolescents with high risk scored lower in control and structure variables and higher in maternal and paternal indifference factors. Non-addicted subjects presented higher scores in conscientiousness, extraversion, and agreeableness and lower scores in neuroticism. The probability of SUD increased with age (OR = 2.187; p = 0.022), sensation seeking (OR = 1.084; p < 0.001), and neuroticism (OR = 1.049; p = 0.042), while conscientiousness was a protective factor (OR = 0.930; p = 0.008). Conclusions: These results reflect that personality traits are directly related to the development of substance abuse in adolescents. Full article

Phase synchronization serves as an effective method for analyzing the synchronization of electroencephalogram (EEG) signals among brain regions and the dynamic changes of the brain. The purpose of this paper is to study the construction of the functional brain network (FBN) based on phase synchronization, with a special focus on neural processes related to human balance regulation. This paper designed four balance paradigms of different difficulty by blocking vision or proprioception and collected 19-channel EEG signals. Firstly, the EEG sequences are segmented by sliding windows. The phase-locking value (PLV) of core node pairs serves as the phase-screening index to extract the valid data segments, which are recombined into new EEG sequences. Subsequently, the multichannel weighted phase lag index (wPLI) is calculated based on the new EEG sequences to construct the FBN. The experimental results show that due to the randomness of the time points of body balance adjustment, the degree of phase synchronization of the datasets screened by PLV is more obvious, improving the effective information expression of the subsequent EEG data segments. The FBN topological structures of the wPLI show that the connectivity of various brain regions changes structurally as the difficulty of human balance tasks increases. The frontal lobe area is the core brain region for information integration. When vision or proprioception is obstructed, the EEG synchronization level of the corresponding occipital lobe area or central area decreases. The synchronization level of the frontal lobe area increases, which strengthens the synergistic effect among the brain regions and compensates for the imbalanced response caused by the lack of sensory information. These results show the brain regional characteristics of the process of human balance regulation under different balance paradigms, providing new insights into endogenous neural mechanisms of standing balance and methods of constructing brain networks. Full article

Background: The COVID-19 pandemic led to significant lifestyle changes and uncertainties, triggering a secondary wave of mental health issues in society. University students are especially susceptible to mental disorders. International students are considered more vulnerable due to limited emotional and financial support from their families and difficulties accessing community support. Hence, we conducted a longitudinal analysis to compare depressive symptoms among international students before and during the pandemic. Methods: Data from depression screenings conducted at the University of Tsukuba in 2019 and 2020 were utilized. We included all students enrolled in 2019 who underwent health check-ups in both 2019 and 2020. Participants completed the Patient Health Questionnaire-9 (PHQ-9), enabling a comparison of item scores between domestic and international students. Psychopathological network analysis was employed to examine relationships among the items. Results: Prior to the pandemic, international students generally exhibited relatively good mental health compared with domestic students. During the 2020 pandemic, no significant difference was observed, but international students tended to demonstrate better mental health. However, network analysis revealed intergroup variations in the relationships among PHQ-9 items, with concentration problems and suicidal thoughts being more prominent among international students. Conclusion: This study’s findings suggest that young people studying abroad experience mental health crises similar to their domestic counterparts. Nevertheless, the patterns of these crises may differ between the two groups. Full article

Recent research suggests that cognitive deficits in individuals with psychotic disorders could be overestimated because poor cognitive test performance is partly attributable to non-cognitive factors. To further test this, we included non-hospitalized individuals with psychotic disorders (PSY, n = 38), individuals with attenuated psychotic symptoms (n = 40), individuals with obsessive-compulsive disorders (n = 39), and healthy controls (n = 38). Relevant cognitive domains were assessed using the MATRICS Consensus Cognitive Battery. Putative confounding non-cognitive factors—heart rate, self-reported stress, negative affect, performance-related beliefs, and actigraphy-derived sleep—were assessed before cognitive testing. A multivariate analysis of covariance was calculated to examine group differences in cognitive performance while controlling for non-cognitive factors. PSY showed decreased test performance in graphomotor speed, attention, and verbal tasks compared to the other groups, whereas non-verbal/visual-spatial tasks were unimpaired. After accounting for non-cognitive factors, group differences diminished in verbal learning, whereas differences in the other domains remained significant. Against our hypotheses, the present findings indicate that some cognitive deficits in PSY cannot be attributed to momentary confounding factors. Full article

Central Nervous System Germ Cell Tumors (CNS GCTs) represent a subtype of intracranial malignant tumors characterized by highly heterogeneous histology. Current diagnostic methods in clinical practice have notable limitations, and treatment strategies struggle to achieve personalized therapy based on patient risk stratification. Advances in molecular genetics, biology, epigenetics, and understanding of the tumor microenvironment suggest the diagnostic potential of associated molecular alterations, aiding risk subgroup identification at diagnosis. Furthermore, they suggest the existence of novel therapeutic approaches targeting chromosomal alterations, mutated genes and altered signaling pathways, methylation changes, microRNAs, and immune checkpoints. Moving forward, further research is imperative to explore the pathogenesis of CNS GCTs and unravel the intricate interactions among various molecular alterations. Additionally, these findings require validation in clinical cohorts to assess their role in the diagnosis, risk stratification, and treatment of patients. Full article

Handwriting difficulty is a defining feature of Chinese developmental dyslexia (DD) due to the complex structure and dense information contained within compound characters. Despite previous attempts to use deep neural network models to extract handwriting features, the temporal property of writing characters in sequential order during dictation tasks has been neglected. By combining transfer learning of convolutional neural network (CNN) and positional encoding with the temporal-sequential encoding of long short-term memory (LSTM) and attention mechanism, we trained and tested the model with handwriting images of 100,000 Chinese characters from 1064 children in Grades 2–6 (DD = 483; Typically Developing [TD] = 581). Using handwriting features only, the best model reached 83.2% accuracy, 79.2% sensitivity, 86.4% specificity, and 91.2% AUC. With grade information, the best model achieved 85.0% classification accuracy, 83.3% sensitivity, 86.4% specificity, and 89.7% AUC. These findings suggest the potential of utilizing machine learning technology to identify children at risk for dyslexia at an early age. Full article

The ability to inhibit conflicting information is pivotal in the dynamic and high-speed context of fast-ball sports. However, the behavioral and electrophysiological characteristics underlying the cognitive inhibition processes associated with table tennis expertise remain unexplored. This study aims to bridge these research gaps by utilizing the color-word Stroop task and the spatial Stroop task alongside event-related potential (ERP) measurements to investigate domain-general and domain-specific cognitive inhibition among table tennis athletes. The study involved a total of 40 participants, including 20 table tennis athletes (11 males and 9 females; mean age 20.75 years) and 20 nonathletes (9 males and 11 females; mean age 19.80 years). The group differences in the Stroop effect on behavioral outcomes and ERP amplitudes were compared within each task, respectively. In the color-word Stroop tasks, athletes exhibited smaller incongruent-related negative potential amplitudes (N_inc; 300–400 ms; p = 0.036) and a diminished Stroop effect on late sustained potential amplitudes (LSP; 500–650 ms; p = 0.028) than nonathletes, although no significant differences were observed in behavioral outcomes (p > 0.05). Conversely, in the spatial Stroop tasks, athletes not only responded more swiftly but also exhibited reduced Stroop effects on both LSP amplitudes (350–500 ms; p = 0.004) and reaction times (p = 0.002) relative to nonathletes. These findings suggest that table tennis athletes excel in cognitive inhibition in the context of both domain-general and domain-specific tasks, particularly exhibiting enhanced performance in tasks that are closely aligned with the demands of their sport. Our results support the neural efficiency hypothesis and improve our understanding of the interactions between cognitive functions and table tennis expertise. Full article

Information theory explains how systems encode and transmit information. This article examines the neuronal system, which processes information via neurons that react to stimuli and transmit electrical signals. Specifically, we focus on transfer entropy to measure the flow of information between sequences and explore its use in determining effective neuronal connectivity. We analyze the causal relationships between two discrete time series, $\mathit{X}:=\left\{X_t:t\in \mathbb{Z}\right\}$ and $\mathit{Y}:=\left\{Y_t:t\in \mathbb{Z}\right\}$, which take values in binary alphabets. When the bivariate process $(\mathit{X},\mathit{Y})$ is a jointly stationary ergodic variable-length Markov chain with memory no larger than k, we demonstrate that the null hypothesis of the test—no causal influence—requires a zero transfer entropy rate. The plug-in estimator for this function is identified with the test statistic of the log-likelihood ratios. Since under the null hypothesis, this estimator follows an asymptotic chi-squared distribution, it facilitates the calculation of p-values when applied to empirical data. The efficacy of the hypothesis test is illustrated with data simulated from a neuronal network model, characterized by stochastic neurons with variable-length memory. The test results identify biologically relevant information, validating the underlying theory and highlighting the applicability of the method in understanding effective connectivity between neurons. Full article

The brain is complex and metabolically active, and the detection of metabolites plays an important role in brain development and diseases. Currently, there is a lack of research on the metabolic spectrum changes in learning and memory impairment, and hippocampal damage induced by microwave radiation from the metabolic perspective. Aiming to provide sensitive indicators for microwave radiation-induced brain damage and establish a foundation for understanding its injury mechanisms, this study employed non-targeted metabolomics to investigate metabolic fluctuations and key metabolic pathway alterations in rats’ hippocampal tissue after microwave radiation. The memory and spatial exploration abilities of rats decreased after radiation. The postsynaptic densities were thickened in the MW group. The cholesterol sulfate, SM(d16:1/24:1(15Z)), and linoelaidylcarnitine were significantly increased after radiation, whereas etrahydrocorticosterone, L-phenylalanine, and histamine were significantly decreased after radiation. These metabolites were enriched in signaling pathways related to the inflammatory mediator regulation of transient receptor potential (TRP) channels, neuroactive ligand–receptor interaction, steroid hormone biosynthesis, and phenylalanine, tyrosine, and tryptophan biosynthesis. These findings indicate that microwave radiation causes spatial learning and memory dysfunction in rats and structural damage to hippocampal tissue. Full article

The unclear pathogenesis of chronic itch originating from several systemic disorders poses challenges to clinical intervention. Recent studies recapitulate the spinal neurocircuits associated with neuroinflammation and synaptic plasticity responsible for pruriceptive sensations. The resolution of nociception and inflammation by Annexin 1 (ANXA1) has been identified. Given that pain and itch share many neural mechanisms, we employed two mice models of chronic itch to study the underlying targets and therapeutic potential of ANXA1, comprising allergic contact dermatitis-induced itch and cholestatic itch. Herein, we report that spinal expression of ANXA1 is down-regulated in mice with dermatitis-induced itch and cholestatic itch. Repetitive injections of ANXA1-derived peptide Ac2-26 (intrathecal, 10 μg) reduce itch-like scratching behaviors following dermatitis and cholestasis. Single exposure to Ac2-26 (intrathecal, 10 μg) alleviates the established itch phenotypes. Moreover, systemic delivery of Ac2-26 (intravenous, 100 μg) is effective against chronic dermatitis-induced itch and cholestatic itch. Strikingly, Ac2-26 therapy inhibits transferrin receptor 1 over-expression, iron accumulation, cytokine IL-17 release and the production of its receptor IL-17R, as well as astrocyte activation in the dorsal horn of spinal cord in mouse with dermatitis and cholestasis. Pharmacological intervention with iron chelator deferoxamine impairs chronic itch behaviors and spinal iron accumulation after dermatitis and cholestasis. Also, spinal IL-17/IL-17R neutralization attenuates chronic itch. Taken together, this current research indicates that ANXA1 protects against the beginning and maintenance of long-term dermatitis-induced itch and cholestatic itch, which may occur via the spinal suppression of IL-17-mediated neuroinflammation, astrocyte activation and iron overload. Full article

This study aims to investigate the association between HCT (Hematocrit) levels and adverse outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA); 14,832 participants from the China National Stroke Registry-III with AIS or TIA were analyzed. Participants were categorized into quartiles based on baseline HCT levels. The primary outcome was poor functional outcomes (modified Rankin Scale ≥ 3) during three months, with secondary outcomes including all-cause death, stroke recurrence, and combined vascular events. Logistic regression or Cox regression models were used to assess the relationship between HCT and clinical outcomes. Compared to the third quartile, patients in the lowest quartile group showed increased risk of poor functional outcome (adjusted OR: 1.35, 95% CI: 1.15–1.58, p < 0.001), patients in the lowest quartile had a higher risk of all-cause death (adjusted HR: 1.68, 95% CI: 1.06–2.68, p = 0.028), as did those in the highest quartile (adjusted HR: 2.02, 95% CI: 1.26–3.25, p = 0.004). Sensitivity analysis shows that the association of HCT with all-cause death weakened, while the association with poor functional outcome was strengthened after excluding patients with recurrent stroke. Our results indicated that HCT level could be used as a short-term predictor for poor functional outcomes and all-cause death in patients with AIS or TIA. Full article

Individuals with mental health problems are at higher risk of musculoskeletal diseases. However, the association between low muscle mass (LMM) and anxiety symptoms remains uninvestigated. This cross-sectional study enrolled 174,262 adults (73,833 women, 100,429 men), aged 18 to 89, who completed the anxiety scale and body composition analyses. Using bio-electrical impedance analysis, skeletal muscle mass index (SMI) was calculated based on appendicular skeletal muscle mass (ASM) (kg)/height (m²). LMM was defined as SMI < 7.0 kg/m² in men and <5.4 kg/m² in women. Anxiety symptoms were screened using the Clinical Useful Anxiety Outcome Scale (CUXOS) with cut-off scores of 20, 30, and 40. Multivariable logistic regression analyses were performed. LMM prevalence was 20.17% in women, 3.86% in men (p < 0.001). The prevalence of anxiety symptoms in LMM group decreased from mild (CUXOS > 20: women, 32.74%, men, 21.17%) to moderate (CUXOS > 30: 13.34%, 7.32%), to severe anxiety symptoms (CUXOS > 40: 4.00%, 1.73%). In multivariable-adjusted models, LMM was associated with mild (aOR (95% confidence interval)), women, 1.13 (1.08–1.17); men, 1.17 (1.08–1.27)), moderate (1.17 (1.11–1.24); 1.35 (1.19–1.53) and severe anxiety symptoms (1.18 (1.07–1.3), 1.36 (1.06–1.74)), demonstrating an increased risk of ORs with escalating anxiety severity. LMM was independently associated with a higher prevalence of anxiety symptoms. Full article

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that disrupts brain functioning and is characterized by hyperactivity, impulsivity, and inattention. With varying presentations and complex etiological factors contributing to the development of ADHD, along with its persistence into adulthood, ADHD must be studied. Researchers have taken an interest in the relationship between ADHD and suicide, which is a serious public health concern with increasing prevalence rates in the Americas. The current literature reveals conflicting views on the importance of psychiatric comorbidities in the development of suicidal behaviours in ADHD patients. Therefore, this study aimed to determine whether there were significant differences between adult ADHD patients with suicide risk and adult ADHD patients without suicide risk. This study was a naturalistic retrospective chart review pilot study that used a sample of adults with a confirmed diagnosis of ADHD from January 2023 to August 2023. Using convenience sampling and sets of inclusion and exclusion criteria, patient data were sequentially collected from Med Access electronic medical records. The control and experimental groups each consisted of 50 patients (100) ranging from 19 to 58 years old. Our quantitative data were analyzed using non-parametric statistical tests, including the Chi-Square test and the Mann–Whitney U test. The results showed significant associations between ADHD patients with suicide risk and (1) borderline personality disorder; (2) binge eating disorder; (3) seven specific psychosocial risk factors; and (4) a higher number of antidepressant medication trials. No significant associations were found with other psychiatric disorders; however, there are important sex differences in terms of the risk factors. Our pilot study reveals several significant differences between adult ADHD patients with suicide risk and those without suicide risk. However, given our limited sample size and limitations, we hope our study encourages larger-scale studies to further investigate this relationship to improve its generalizability. Full article

Driver fatigue represents a significant peril to global traffic safety, necessitating the advancement of potent fatigue monitoring methodologies to bolster road safety. This research introduces a conditional generative adversarial network with a classification head that integrates convolutional and attention mechanisms (CA-ACGAN) designed for the precise identification of fatigue driving states through the analysis of electroencephalography (EEG) signals. First, this study constructed a 4D feature data model capable of mirroring drivers’ fatigue state, meticulously analyzing the EEG signals’ frequency, spatial, and temporal dimensions. Following this, we present the CA-ACGAN framework, a novel integration of attention schemes, the bottleneck residual block, and the Transformer element. This integration was designed to refine the processing of EEG signals significantly. In utilizing a conditional generative adversarial network equipped with a classification header, the framework aims to distinguish fatigue states effectively. Moreover, it addresses the scarcity of authentic data through the generation of superior-quality synthetic data. Empirical outcomes illustrate that the CA-ACGAN model surpasses various extant methods in the fatigue detection endeavor on the SEED-VIG public dataset. Moreover, juxtaposed with leading-edge GAN models, our model exhibits an efficacy in in producing high-quality data that is clearly superior. This investigation confirms the CA-ACGAN model’s utility in fatigue driving identification and suggests fresh perspectives for deep learning applications in time series data generation and processing. Full article

Psychostimulants alter cellular morphology and activate neuroimmune signaling in a number of brain regions, yet few prior studies have investigated their persistence beyond acute abstinence or following high levels of voluntary drug intake. In this study, we examined the effects of the repeated binge-like self-administration (96 h/week for 3 weeks) of methamphetamine (METH) and 21 days of abstinence in female and male rats on changes in cell density, morphology, and cytokine levels in two addiction-related brain regions—the prefrontal cortex (PFC) and dorsal striatum (DStr). We also examined the effects of similar patterns of intake of the cocaine-like synthetic cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV) or saline as a control. Robust levels of METH and MDPV intake (~500–1000 infusions per 96 h period) were observed in both sexes. We observed no changes in astrocyte or neuron density in either region, but decreases in dendritic spine densities were observed in PFC pyramidal and DStr medium spiny neurons. The microglial cell density was decreased in the PFC of METH self-administering animals, accompanied by evidence of microglial apoptosis. Changes in microglial morphology (e.g., decreased territorial volume and ramification and increased cell soma volume) were also observed, indicative of an inflammatory-like state. Multiplex analyses of PFC and DStr cytokine content revealed elevated levels of various interleukins and chemokines only in METH self-administering animals, with region- and sex-dependent effects. Our findings suggest that voluntary binge-like METH or MDPV intake induces similar cellular perturbations in the brain, but they are divergent neuroimmune responses that persist beyond the initial abstinence phase. Full article

Research indicates that brain-region-specific synapse loss and dysfunction are early hallmarks and stronger neurobiological correlates of cognitive decline in Alzheimer’s disease (AD) than amyloid plaque and neurofibrillary tangle counts or neuronal loss. Even though the precise mechanisms underlying increased synaptic pruning in AD are still unknown, it has been confirmed that dysregulation of the balance between complement activation and inhibition is a crucial driver of its pathology. The complement includes three distinct activation mechanisms, with the activation products C3a and C5a, potent inflammatory effectors, and a membrane attack complex (MAC) leading to cell lysis. Besides pro-inflammatory cytokines, the dysregulated complement proteins released by activated microglia bind to amyloid β at the synaptic regions and cause the microglia to engulf the synapses. Additionally, research indicating that microglia-removed synapses are not always degenerating and that suppression of synaptic engulfment can repair cognitive deficits points to an essential opportunity for intervention that can prevent the loss of intact synapses. In this study, we focus on the latest research on the role and mechanisms of complement-mediated microglial synaptic pruning at different stages of AD to find the right targets that could interfere with complement dysregulation and be relevant for therapeutic intervention at the early stages of the disease. Full article

Background: Up to 34% of patients with schizophrenia are resistant to several treatment trials. Lack of continuous and adequate treatment is associated with relapse, rehospitalization, a lower effect of antipsychotic therapy, and higher risk of side effects. Long-acting injectables antipsychotics (LAI APs) enhance compliance and improve clinical outcomes and quality of life in patients with schizophrenia, and thus it may be advisable to administer two LAI APs at the same time in cases of treatment-resistant schizophrenia. The purpose of this review is to summarize the available literature regarding the combined use of two LAI APs in patients with schizophrenia or other psychotic spectrum disorders. Methods: An extensive literature search for relevant articles regarding any combination of two long-acting injectable antipsychotics has been performed from inception up to 9 February 2024, on PubMed, Scopus and APA PsycInfo, according to the PRISMA statement. Only studies reporting combination of two LAI APs and its clinical outcome in patients with schizophrenia and related disorders were selected. Results: After the selection process, nine case reports, four case series and two observational retrospective studies were included in the final analysis. All patients treated with dual LAI APs reported a good response, and no new or unexpected adverse effects due to the combination of two LAIs were reported. Different drug combinations were used, and the most frequent association resulted in aripiprazole monohydrate + paliperidone palmitate once monthly (32 times). Conclusions: Our review highlights that the treatment regimen with two concurrent LAI APs is already widely used in clinical practice and is recognized as providing a promising, effective, and relatively safe therapeutic strategy for treating the schizophrenia spectrum disorders. Full article