The rapid advancement of artificial intelligence (AI) has sparked renewed discussions on its trustworthiness and the concept of eXplainable AI (XAI). Recent research in neuroscience has emphasized the relevance of XAI in studying cognition. This scoping review aims to identify and analyze various XAI methods used to study the mechanisms and features of cognitive function and dysfunction. In this study, the collected evidence is qualitatively assessed to develop an effective framework for approaching XAI in cognitive neuroscience. Based on the Joanna Briggs Institute and preferred reporting items for systematic reviews and meta-analyses extension for scoping review guidelines, we searched for peer-reviewed articles on MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar. Two reviewers performed data screening, extraction, and thematic analysis in parallel. Twelve eligible experimental studies published in the past decade were included. The results showed that the majority (75%) focused on normal cognitive functions such as perception, social cognition, language, executive function, and memory, while others (25%) examined impaired cognition. The predominant XAI methods employed were intrinsic XAI (58.3%), followed by attribution-based (41.7%) and example-based (8.3%) post hoc methods. Explainability was applied at a local (66.7%) or global (33.3%) scope. The findings, predominantly correlational, were anatomical (83.3%) or nonanatomical (16.7%). In conclusion, while these XAI techniques were lauded for their predictive power, robustness, testability, and plausibility, limitations included oversimplification, confounding factors, and inconsistencies. The reviewed studies showcased the potential of XAI models while acknowledging current challenges in causality and oversimplification, particularly emphasizing the need for reproducibility.
Amyloid-β (Aβ) is a pivotal biomarker in Alzheimer’s disease (AD), attracting considerable attention from numerous researchers. There is uncertainty regarding whether clearing Aβ is beneficial or harmful to cognitive function. This question has been a central topic of research, especially given the lack of success in developing Aβ-targeted drugs for AD. However, with the Food and Drug Administration’s approval of Lecanemab as the first anti-Aβ medication in July 2023, there is a significant shift in perspective on the potential of Aβ as a therapeutic target for AD. In light of this advancement, this review aims to illustrate and consolidate the molecular structural attributes and pathological ramifications of Aβ. Furthermore, it elucidates the determinants influencing its expression levels while delineating the gamut of extant Aβ-targeted pharmacotherapies that have been subjected to clinical or preclinical evaluation. Subsequently, a comprehensive analysis is presented, dissecting the research landscape of Aβ across the domains above, culminating in the presentation of informed perspectives. Concluding reflections contemplate the supplementary advantages conferred by nanoparticle constructs, conceptualized within the framework of multivalent theory, within the milieu of AD diagnosis and therapeutic intervention, supplementing conventional modalities.
Cardiopulmonary bypass (CPB) is often used in cardiothoracic surgery because its nonphysiological state causes pathophysiological changes in the body, causing multiorgan and multitissue damage to varying degrees. Postoperative cognitive dysfunction (POCD) is a common central nervous system complication after cardiac surgery. The etiology and mechanism of POCD are not clear. Neuroinflammation, brain mitochondrial dysfunction, cerebral embolism, ischemia, hypoxia, and other factors are related to the pathogenesis of POCD. There is a close relationship between CPB and POCD, as CPB can cause inflammation, hypoxia and reperfusion injury, and microemboli formation, all of which can trigger POCD. POCD increases medical costs, seriously affects patients' quality of life, and increases mortality. Currently, there is a lack of effective treatment methods for POCD. Commonly used methods include preoperative health management, reducing inflammation response during surgery, preventing microemboli formation, and implementing individualized rehabilitation programs after surgery. Strengthening preventive measures can minimize the occurrence of POCD and its adverse effects.
Cancer cells immediately expand and penetrate adjoining tissues, as opposed to metastasis, that is the spread of cancer cells through the circulatory or lymphatic systems to more distant places via the invasion process. We found that a lack of studies discussed tumor development with the nervous system, by the aspects of cancer-tissue invasion (biological) and chemical modulation of growth that cascades by releasing neural-related factors from the nerve endings via chemical substances known as neurotransmitters. In this review, we aimed to carefully demonstrate and describe the cancer invasion and interaction with the nervous system, as well as reveal the research progress and the emerging neuroscience of cancer. An initial set of 160 references underwent systematic review and summarization. Through a meticulous screening process, these data were refined, ultimately leading to the inclusion of 98 studies that adhered to predetermined criteria. The outcomes show that one formidable challenge in the realm of cancer lies in its intrinsic heterogeneity and remarkable capacity for rapid adaptation. Despite advancements in genomics and precision medicine, there is still a need to identify new molecular targets. Considering cancer within its molecular and cellular environment, including neural components, is crucial for addressing this challenge. In conclusion, this review provides good referential data for direct, indirect, biological, and chemical interaction for nerve tissue–tumor interaction, suggesting the establishment of new therapy techniques and mechanisms by controlling and modifying neuron networks that supply signals to tumors.
This study aims to explore the expression profile of PANoptosis-related genes (PRGs) and immune infiltration in Alzheimer’s disease (AD). Based on the Gene Expression Omnibus database, this study investigated the differentially expressed PRGs and immune cell infiltration in AD and explored related molecular clusters. Gene set variation analysis (GSVA) was used to analyze the expression of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes in different clusters. Weighted gene co-expression network analysis was utilized to find co-expressed gene modules and core genes in the network. By analyzing the intersection genes in random forest, support vector machine, generalized linear model, and extreme gradient boosting (XGB), the XGB model was determined. Eventually, the first five genes (Signal Transducer and Activator of Transcription 3, Tumor Necrosis Factor (TNF) Receptor Super-family Member 1B, Interleukin 4 Receptor, Chloride Intracellular Channel 1, TNF Receptor Superfamily Member 10B) in XGB model were selected as predictive genes. This research explored the relationship between PANoptosis and AD and established an XGB learning model to evaluate and screen key genes. At the same time, immune infiltration analysis showed that there were different immune infiltration expression profiles in AD.
The aim of this study is to investigate the effect of scutellarein on the proliferation of neuroblastoma cells and the underlying mechanism. Six cell lines were used with drug intervention. Cell Counting Kit-8 was used to select the best, namely, SH-SY5Y, and then its IC50 value was determined. To further investigate the mechanism of scutellarin affecting SH-SY5Y proliferation, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of 11 factors. Scutellarin administration with 300 µM significantly reduced the number of SH-SY5Y, especially on the 3rd day of exposure to scutellarin. The IC50 value of scutellarin in SH-SY5Y cells was determined to be 117.8 µM. But the practical results showed that 300 µM was the optimal concentration of scutellarin. qRT-PCR further detected upregulated maternally expressed gene 3 (MEG3), oncogene c-Fos (c-FOS), and c-jun and downregulated M2 isoform of pyruvate kinase (PKM2), non-SMC Condensin I Complex Subunit H (NCAPH), epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-β1, and TGF-α, suggesting that scutellarin with 300 µM volume inhibited the survival of SH-SY5Y by regulating the expression of these 8 factors. Scutellarin could be a novel drug for the treatment of neuroblastoma, and its underlying mechanism may be related to the upregulated levels of MEG3, c-FOS, and c-jun and downregulated the expression of PKM2, NCAPH, EGFR, TGF-β1, and TGF-α.
It was found the expression of progesterone receptor membrane component 2 (PGRMC2) in the histone of epileptic mice was lower than that of normal mice. In this study, we found by the immunofluorescence technique, PGRMC2 was expressed in both astrocytes and neurons of the mouse hippocampus. In addition, the seizure latency and seizure grade of mice in each group were observed after stereotactic injection of the PGRMC2 knockdown virus, PGRMC2 overexpression lentivirus, and related null virus into the hippocampus of mice. It was found that the seizure latency of mice in the PTZ + siPGRMC2 group was prolonged compared with the null virus group. The seizure latency was shortened in the PTZ + PGRMC2 group. The number of grade IV and above seizures in the PTZ + siPGRMC2 group was significantly reduced, while the number of grade IV and above seizures in the PTZ + PGRMC2 group was significantly increased. It was found that the nerve cells in the PTZ + siPGRMC2 group were still intact. In the PTZ + PGRMC2 group, the neural cells were damaged, the intercellular space was widened, and the number of cells was reduced. These findings support that PGRMC2 may be involved in epileptic seizures.
Delayed neurocognitive recovery after surgery is associated with increased morbidity and mortality. However, its mechanism of action remains controversial and complex. A prospective, double-blind, randomized controlled trial was performed at the Affiliated Hospital of Zunyi Medical University. Older patients (aged 65 years and older) who underwent gastrointestinal surgery were randomly divided into sevoflurane-based or propofol-based anesthesia groups. The Mini-Mental State Examination was performed to evaluate cognitive function. Peripheral venous blood was collected to test the levels of choline acetyltransferase and acetylcholin-esterase. A total of 75 patients were enrolled and 30 patients in each group completed the study. On Day 1 postoperation, patients in the sevoflurane group showed worse performance on the Mini-Mental State Examination than patients in the propofol group. Lower blood choline acetyltransferase concentrations and higher acetylcholinesterase concentrations were observed in patients who had sevoflurane anesthesia than in patients who had propofol anesthesia 1 day postoperative. At 3 days postoperation, patients with sevoflurane- or propofol-based general anesthesia did not differ regardless of Mini-Mental State Examination score or choline acetyltransferase and acetylcholinesterase levels. Sevoflurane-based anesthesia has short-term delayed neurocognitive recovery in older surgical patients, which may be related to central cholinergic system degeneration.
Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, but an in vivo understanding of its early pathology remains limited. A recent study used topographic layer imaging to investigate iron and calcium accumulation in the primary motor cortex (M1) of patients with ALS compared with controls. Despite the preserved cortical thickness, ALS patients showed increased iron in layer 6 and calcium accumulation in layer 5a and the superficial layer. Calcium accumulation was particularly prominent in the low-myelin borders, potentially preceding the demyelination. This study reveals a novel in vivo pathology in ALS, suggesting that calcium dysregulation may precede iron accumulation and contribute to early M1 cell degeneration. Further investigation using quantitative susceptibility mapping and complementary techniques, such as diffusion kurtosis imaging, along with ultrahigh-field magnetic resonance imaging, into the role of calcium and early intervention strategies is warranted.
Autoimmune encephalitis (AE) is an autoimmune disease in the central nervous system. Clinical manifestations include cognitive dysfunction, psychiatric-behavioral abnormalities, epilepsy, motor disorders, speech disorders, and memory impairment. Some patients do not have the characteristic clinical manifestations of the disease when they see a doctor, so they are easily diagnosed incorrectly. Autoimmune antibodies originate from genetic and acquired factors. Clinical data have found a correlation between ovarian teratoma and autoimmune encephalitis. This case reports a 34-year-old woman who was diagnosed with teratoma-associated anti-Nmethyl- D- aspartate receptor-mediated autoimmune encephalitis called anti-N-methyl-D-aspartate receptor encephalitis with bilateral hearing loss in 2021. Through this case report, clinicians will pay attention to autoimmune encephalitis and raise awareness of the specific clinical manifestations of autoimmune encephalitis, and focus on early identification. It means that clinicians should be familiar with the representative clinical manifestations of the disease.
Extracranial metastasis of glioma is extremely rare. Herein, we report a case of glioblastoma that originated and showed stepwise malignant transformation from a low-grade glioma (LGG) along with the presence of lung and mediastinal lymph node metastases after repeated craniotomy. A 30-year-old man presented with hemoptysis. Thoracic computed tomography revealed a space-occupying lesion in the right upper lung with mediastinal nodal and metastases in both lungs; lung cancer was suspected. The patient’s medical history showed that he had undergone craniotomy three times in 7 years for a primary LGG disease relapse, and stepwise malignant-transformed high-grade glioma (HGG). However, brain magnetic resonance imaging did not reveal any relapse of intracranial tumors. The diagnosis of extracranial metastatic glioblastoma was confirmed using the morphology and staining results for specific immunohistochemistry markers using the specimen obtained via endobronchial ultrasound transbronchial needle aspiration. Subsequently, the patient received a combination of systemic and local treatments; however, he died of massive hemoptysis after 6 months. The survival time of this glioma patient improved after transformation and metastasis. Detailed descriptions will help us understand the biological behavior of glioma, but more studies are needed to confirm the complex mechanism of extracranial metastasis.