Brain Sciences最新文献

The landscape of pharmacological treatment for Alzheimer's disease (AD) has undergone significant transformations with the advent of disease-modifying therapies (DMTs) targeting β-Amyloid (Aβ) accumulation, one of the hallmark pathologies of AD. The approval and market introduction of monoclonal antibodies mark the dawn of a new era in AD therapeutics as well. Furthermore, considerable progress has also been made in the development of new drugs targeting non-Aβ and non-Tau protein pathways. These advancements are key in tackling the root causes of AD, offering hope for treatments that both relieve symptoms and slow disease progression, improving patient outcomes and quality of life. This review aims to provide a comprehensive update on the advances in drug development and application for AD, including those currently in clinical trials and those already approved for the market to treat patients.

Purpose: To assess spatial contrast sensitivity (CS) in suspected primary open-angle glaucoma (POAG) patients.

Methods: CS was measured using sinusoidal gratings of 4 cycles/degree. First, foveal and peripheral CS were assessed in 34 suspected POAG patients and compared with 71 and 28 age-matched healthy individuals for foveal and peripheral conditions, respectively. Second, foveal CS was assessed in 34 early POAG patients age-matched with suspected POAG patients. Analyses were performed considering two age ranges: Under and Over 50 y.o. Correlations were evaluated between CS and clinical parameters. Diagnostic accuracy was also analyzed.

Results: Peripheral CS was lower in older suspected POAG patients (23.4 ± 16.1) than the control group (39.1 ± 28.2) (p = 0.040). Foveal CS was reduced in suspected POAG participants (Under 50: 146.8 ± 63.3; p = 0.004. Over 50: 110.5 ± 65.0; p = 0.044) and in early POAG patients (Under 50: 141.2 ± 72.6; p = 0.002. Over 50: 80.2 ± 54.5 p < 0.001), both compared to the control group (Under 50: 213.5 ± 66.2. Over 50: 138.6 ± 71.7). CS was lower in early POAG than in POAG suspected in older patients (p = 0.042). Foveal CS was correlated with age (Early: p = 0.001. Suspect: p = 0.002) and with the cup-disc ratio only in early POAG patients (p < 0.001). Foveal CS had fair (AUC = 0.74) diagnostic accuracy for early POAG patients.

Conclusions: CS in suspected POAG patients is lower than in healthy individuals. Our findings evidence the spatial vision loss before the onset of POAG.

Background: In the oddball paradigm, the dorsolateral prefrontal cortex (DLPFC) is often associated with active cognitive responses, such as maintaining information in working memory or adapting response strategies. While some evidence points to the DLPFC's role in passive auditory deviance perception, a detailed understanding of the spatiotemporal neurodynamics involved remains unclear.

Methods: In this study, event-related optical signals (EROS) and event-related potentials (ERPs) were simultaneously recorded for the first time over the prefrontal cortex using a 64-channel electroencephalography (EEG) system, during passive auditory deviance perception in 12 right-handed young adults (7 women and 5 men). In this oddball paradigm, deviant stimuli (a 1500 Hz pure tone) elicited a negative shift in the N1 ERP component, related to mismatch negativity (MMN), and a significant positive deflection associated with the P300, compared to standard stimuli (a 1000 Hz tone).

Results: We hypothesize that the DLPFC not only participates in active tasks but also plays a critical role in processing deviant stimuli in passive conditions, shifting from pre-attentive to attentive processing. We detected enhanced neural activity in the left middle frontal gyrus (MFG), at the same timing of the MMN component, followed by later activation at the timing of the P3a ERP component in the right MFG.

Conclusions: Understanding these dynamics will provide deeper insights into the DLPFC's role in evaluating the novelty or unexpectedness of the deviant stimulus, updating its cognitive value, and adjusting future predictions accordingly. However, the small number of subjects could limit the generalizability of the observations, in particular with respect to the effect of handedness, and additional studies with larger and more diverse samples are necessary to validate our conclusions.

The delivery of nutrients to the brain is provided by a 600 km network of capillaries and microvessels. Indeed, the brain is highly energy demanding and, among a total amount of 100 billion neurons, each neuron is located just 10-20 μm from a capillary. This vascular network also forms part of the blood-brain barrier (BBB), which maintains the brain's stable environment by regulating chemical balance, immune cell transport, and blocking toxins. Typically, brain microvascular endothelial cells (BMECs) have low turnover, indicating a stable cerebrovascular structure. However, this structure can adapt significantly due to development, aging, injury, or disease. Temporary neural activity changes are managed by the expansion or contraction of arterioles and capillaries. Hypoxia leads to significant remodeling of the cerebrovascular architecture and pathological changes have been documented in aging and in vascular and neurodegenerative conditions. These changes often involve BMEC proliferation and the remodeling of capillary segments, often linked with local neuronal changes and cognitive function. Cerebrovascular plasticity, especially in arterioles, capillaries, and venules, varies over different time scales in development, health, aging, and diseases. Rapid changes in cerebral blood flow (CBF) occur within seconds due to increased neural activity. Prolonged changes in vascular structure, influenced by consistent environmental factors, take weeks. Development and aging bring changes over months to years, with aging-associated plasticity often improved by exercise. Injuries cause rapid damage but can be repaired over weeks to months, while neurodegenerative diseases cause slow, varied changes over months to years. In addition, if animal models may provide useful and dynamic in vivo information about vascular plasticity, humans are more complex to investigate and the hypothesis of glymphatic system together with Magnetic Resonance Imaging (MRI) techniques could provide useful clues in the future.

Background: Intravenous thrombolysis is one of the most effective therapies for the treatment of acute ischemic stroke (AIS), with urokinase offering a cost-effective alternative to newer agents like alteplase and tenecteplase, especially in resource-limited settings.

Methods: This review provides a comprehensive overview of the application of intravenous thrombolysis with urokinase for AIS in the clinical practice of stroke management, including the efficacy, safety, and cost-effectiveness of urokinase compared to other thrombolytic agents.

Results: Urokinase, a first-generation thrombolytic drug, is a non-specific plasminogen activator that offers a cost-effective alternative. It has been used in clinical practice for over two decades to improve neurological outcomes in patients with AIS if administered within 6 h of ictus. Numerous studies have indicated that urokinase remains a viable option for patients who cannot access alteplase or tenecteplase because of economic constraints, time window limitations, availability, or other reasons.

Conclusions: In low- and middle-income countries, urokinase is a cost-effective alternative thrombolytic drug. High-level evidence-based medical research is therefore urgently needed to confirm that urokinase is not inferior to new-generation thrombolytic drugs, and to assess whether it may even be superior in some patient populations.

The dorsal raphe nucleus (DRN) has gained attention owing to its involvement in various physiological functions, such as sleep-awake, feeding, and emotion, with its analgesic role being particularly significant. It is described as the "pain inhibitory nucleus" in the brain. The DRN has diverse projections from hypothalamus, midbrain, and pons. In turn, the DRN is a major source of projections to diverse cortex, limbic forebrain thalamus, and the midbrain and contains highly heterogeneous neuronal subtypes. The activation of DRN neurons in mice prevents the establishment of neuropathic, chronic pain symptoms. Chemogenetic or optogenetic inhibition neurons in the DRN are sufficient to establish pain phenotypes, including long-lasting tactile allodynia, that scale with the extent of stimulation, thereby promoting nociplastic pain. Recent progress has been made in identifying the neural circuits and cellular mechanisms in the DRN that are responsible for sensory modulation. However, there is still a lack of comprehensive review addressing the specific neuron types in the DRN involved in pain modulation. This review summarizes the function of specific cell types within DRN in the pain regulation, and aims to improve understanding of the mechanisms underlying pain regulation in the DRN, ultimately offering insights for further exploration.

Background: Mental health issues are increasingly prominent worldwide, posing significant threats to patients and deeply affecting their families and social relationships. Traditional diagnostic methods are subjective and delayed, indicating the need for an objective and effective early diagnosis method. Methods: To this end, this paper proposes a lightweight detection method for multi-mental disorders with fewer data sources, aiming to improve diagnostic procedures and enable early patient detection. First, the proposed method takes Electroencephalography (EEG) signals as sources, acquires brain rhythms through Discrete Wavelet Decomposition (DWT), and extracts their approximate entropy, fuzzy entropy, permutation entropy, and sample entropy to establish the entropy-based matrix. Then, six kinds of conventional machine learning classifiers, including Support Vector Machine (SVM), k-Nearest Neighbors (kNN), Naive Bayes (NB), Generalized Additive Model (GAM), Linear Discriminant Analysis (LDA), and Decision Tree (DT), are adopted for the entropy-based matrix to achieve the detection task. Their performances are assessed by accuracy, sensitivity, specificity, and F1-score. Concerning these experiments, three public datasets of schizophrenia, epilepsy, and depression are utilized for method validation. Results: The analysis of the results from these datasets identifies the representative single-channel signals (schizophrenia: O1, epilepsy: F3, depression: O2), satisfying classification accuracies (88.10%, 75.47%, and 89.92%, respectively) with minimal input. Conclusions: Such performances are impressive when considering fewer data sources as a concern, which also improves the interpretability of the entropy features in EEG, providing a reliable detection approach for multi-mental disorders and advancing insights into their underlying mechanisms and pathological states.

Objectives. There is a significant correlation between EEG microstate and the neurophysiological basis of mental illness, brain state, and cognitive function. Given that the unclear relationship between network dynamics and different microstates, this paper utilized microstate, brain network, and control theories to understand the microstate characteristics of short-term memory task, aiming to mechanistically explain the most influential microstates and brain regions driving the abnormal changes in brain state transitions in patients with schizophrenia. Methods. We identified each microstate and analyzed the microstate abnormalities in schizophrenia patients during short-term memory tasks. Subsequently, the network dynamics underlying the primary microstates were studied to reveal the relationships between network dynamics and microstates. Finally, using control theory, we confirmed that the abnormal changes in brain state transitions in schizophrenia patients are driven by specific microstates and brain regions. Results. The frontal-occipital lobes activity of microstate D decreased significantly, but the left frontal lobe of microstate B increased significantly in schizophrenia, when the brain was moving toward the easy-to-reach states. However, the frontal-occipital lobes activity of microstate D decreased significantly in schizophrenia, when the brain was moving toward the hard-to-reach states. Microstate D showed that the right-frontal activity had a higher priority than the left-frontal, but microstate B showed that the left-frontal priority decreased significantly in schizophrenia, when changes occur in the synchronization state of the brain. Conclusions. In conclusion, microstate D may be a biomarker candidate of brain abnormal activity during the states transitions in schizophrenia, and microstate B may represent a compensatory mechanism that maintains brain function and exchanges information with other brain regions. Microstate and brain network provide complementary perspectives on the neurodynamics, offering potential insights into brain function in health and disease.

Background: In recent years, there has been growing interest in the evaluation of autism spectrum disorder (ASD) and autistic traits in prison populations and offenders. Due to misleading headlines and highly publicized criminal cases, the belief that autistic individuals are more prone to commit crimes has spread among the general population, also leading to increasing research on this matter. Aims: In this context, this narrative review aimed to analyze the available scientific literature on the bi-directional link between ASD and criminal behaviors and to assess the key characteristics of eventual ASD offenders, including sociodemographic data, comorbidities, crime-related features, and interactions with the criminal justice system. Results: Our review highlighted that the available studies lack methodological rigor and present controversial results. Overall, the current state of research does not support any definitive correlation between ASD or autistic traits and the predisposition to engage in criminal conduct. Further studies are needed to confirm or reject this hypothesis.

Background: Cognitive deficits following ischemic stroke significantly impair quality of life, highlighting the need for effective interventions. This study evaluates the efficacy and safety of extended N-Pep-12 dietary supplementation in enhancing cognitive recovery post-stroke. Methods: In this randomized, open-label, controlled study, 106 patients with supratentorial ischemic stroke were enrolled to receive either 90mg N-Pep-12 or no supplementation daily for 360 days and were followed-up for 360 days. Cognitive function and emotional well-being were assessed using established neuropsychological scales at baseline, 90 days, and 360 days post-stroke. Safety was monitored through adverse events and mortality rates. Results: Significant improvements were observed in the N-Pep-12 group compared to controls, particularly in the Montreal Cognitive Assessment scores at both 90 and 360 days, and in the Digit Symbol Coding scores at 360 days, suggesting enhanced cognitive recovery with extended N-Pep-12 supplementation. A linear regression for a composite outcome analysis at day 360 further confirmed the efficacy of N-Pep-12 in contributing to cognitive improvement. Safety profiles were favorable, with no significant adverse effects attributed to N-Pep-12. Conclusions: Extended dietary supplementation with N-Pep-12 appears to offer a safe and effective approach to support cognitive recovery in ischemic stroke survivors. These findings underscore the potential of the supplement as an add-on intervention for managing post-stroke cognitive impairments.