Brain Conflux (ISSN: 3079-6016) is an international, peer-reviewed Open Access Journal, dedicated to publishing high-quality research and emerging trends in life sciences and medicine. This journal strives to bridge basic research with clinical practice, offering a platform for interdisciplinary collaboration and innovation. Brain Conflux aims to accelerate the translation of scientific discoveries into practical healthcare solutions, making significant contributions to public health and policy.
Deep Brain Stimulation for Parkinson’s Disease: A Comprehensive Review of Efficacy, Influencing Factors, and Future Directions
Deep Brain Stimulation (DBS) is a well-established surgical therapy for advanced Parkinson’s disease (PD), effectively alleviating motor symptoms and complications associated with long-term levodopa treatment. This review provides a comprehensive synthesis of current evidence, analyzing the efficacy of the two primary targets, the subthalamic nucleus (STN) and the globus pallidus internus (GPi), on both motor and non-motor symptoms. While STN-DBS allows significant medication reduction and GPi-DBS may better manage dyskinesias and axial symptoms, outcomes are highly dependent on careful patient selection. Key prognostic factors include preoperative levodopa responsiveness, disease duration, motor phenotype, and cognitive status. The review also critically evaluates technological advancements, such as adaptive closed-loop systems and novel targets, which aim to personalize therapy and address treatment-resistant symptoms. Ultimately, DBS represents a transformative intervention whose success hinges on integrated clinical decision-making and continued innovation.
Copyright (c) 2026 Brain Conflux https://creativecommons.org/licenses/by/4.0
Advancing Precision Medicine through Polygenic Risk Scores: From Statistical Innovation to Clinical Implementation
The polygenic risk scores (PRS) have emerged as a transformative approach for quantifying inherited predisposition to complex diseases, leveraging the unprecedented expansion of genome-wide association studies (GWAS) and advances in statistical genetics. By aggregating the marginal effects of millions of common variants, PRS provide a single metric of genetic liability that can achieve predictive performance comparable to traditional clinical risk factors. Current methodologies are undergoing a paradigm shift, moving beyond simple linear additive models to incorporate complex linkage disequilibrium (LD) structures, multi-ancestry frameworks, and functional genomic landscapes. In particular, the integration of regulatory annotations, including expression quantitative trait loci (eQTL), chromatin accessibility, and cell-type-specific enhancers, has enhanced both the biological interpretability and predictive robustness of these scores. This review synthesizes the rapid methodological evolution of PRS, encompassing Bayesian shrinkage frameworks, machine learning algorithms, and functionally informed strategies designed to mitigate the persistent Eurocentric biases in current datasets. We critically evaluate the evidence supporting the integration of PRS into clinical workflows, focusing on cardiovascular diseases, oncology, and neuropsychiatric disorders, where genetic stratification can enhance preventive interventions and diagnostic precision. Despite this progress, we identify significant challenges to widespread adoption, including the reduced portability of scores across diverse populations, the lack of standardized clinical thresholds, and complex ethical considerations related to health equity. Finally, we propose a multidisciplinary roadmap for the future of PRS, emphasizing the necessity of global biobank diversity, dynamic risk modeling that incorporates temporal and environmental factors, and the seamless integration of genomic insights into electronic health records. Collectively, these advancements are essential for transitioning PRS from a powerful research tool into an equitable and actionable component of the precision medicine toolkit.
A Case of Epstein-Barr Virus Encephalitis Misdiagnosed as Glioma
Epstein-Barr virus (EBV) infection can cause central nervous system damage, primarily manifesting as encephalitis, with diverse imaging presentations. We report a case of an EBV-infected patient who presented clinically with cognitive impairment and limb convulsions. Serum and cerebrospinal fluid tests were positive for EBV viral capsid antigen IgM. Cranial MRI revealed multifocal white matter lesions distributed along the lateral ventricles, demonstrating T1 and T2 hyperintensity with associated diffusion restriction in the involved areas, patchy enhancement, and a tumor-mimicking appearance with significant mass effect. Brain biopsy confirmed viral encephalitis. After treatment with antiviral agents and corticosteroids, the patient's symptoms improved. Follow-up cranial MRI one month later showed significant reduction of the lesions. In clinical practice, it is important to be alert to the tumor-like imaging manifestations of EBV encephalitis. Pathological biopsy of brain tissue plays a crucial role in distinguishing this condition from diseases such as glioma.
Copyright (c) 2025 Brain Conflux https://creativecommons.org/licenses/by/4.0
Multiscale Modeling of Transcranial Alternating Current Stimulation:Induced Electric Field and Cellular Responses
Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation technique that generates weak oscillatory electric fields (EFs) in the brain and has shown promise for probing neural oscillations and treating neuropsychiatric disorders. However, its effects on neural activity remain highly variable across studies, and controversies persist regarding whether conventional tACS intensities can genuinely entrain neuronal firing. Experimental approaches alone have limited capacity to resolve these inconsistencies. Computational modeling provides a powerful complementary framework to quantify induced EFs, predict cellular responses, and generate mechanistic hypotheses. In this review, we focus on multiscale models spanning from macroscopic realistic head models to microscopic multi-compartmental neuronal models. Head models elucidate how anatomy, tissue conductivity, stimulation parameters, and electrode montage shape the spatial distribution of tACS-induced fields, while multi-compartmental models reveal how EFs, neuronal morphology, biophysics, and synaptic inputs govern cell-type-specific polarization and spike entrainment. We highlight key insights, unresolved controversies, and emerging trends, including the integration of head and neuronal models, network-level simulations, and the use of artificial intelligence to bridge scales. By critically synthesizing advances in multiscale modeling, we argue that coupling computational frameworks with experimental recordings is essential for explaining the diversity of tACS effects and for translating mechanistic insights into individualized, clinically effective interventions.
Transcranial alternating current stimulation
Cell type- and developmental stage-specific mapping of polygenic risk across schizophrenia, depression, and bipolar disorder
Schizophrenia, depression, and bipolar disorder are highly heritable psychiatric illnesses that share overlapping symptoms but also exhibit disorder-specific features. To dissect the cellular and developmental mechanisms of genetic risk, we integrated large-scale genome-wide association study (GWAS) data with human cortical single-nucleus RNA sequencing (snRNA-seq) data spanning gestation to adulthood (>700,000 nuclei from 106 donors). Gene-based analyses revealed 104 shared genes across disorders and convergent enrichment in synaptic pathways, alongside disorder-specific signals such as metal ion transport in schizophrenia. Using the single-cell disease relevance score (scDRS), we mapped polygenic risk across cortical cell types and developmental windows. Excitatory neurons were consistently implicated across all disorders from postnatal stages through adulthood, while inhibitory neurons showed broader vulnerability in depression and bipolar disorder, extending into the fetal period. Glial cells demonstrated disorder specificity: astrocytes were implicated across disorders during early postnatal synaptogenesis, oligodendrocyte precursor cells (OPCs) showed prolonged associations in depression, and mature oligodendrocytes were uniquely implicated in schizophrenia during childhood. These findings highlighted excitatory-inhibitory imbalance as a shared mechanism, alongside distinct glial and developmental trajectories contributing to disorder-specific pathophysiology. Our findings help to highlight the cortical cell types and developmental windows through which psychiatric genetic risk may act, offering insights into potential critical periods for intervention.
Rapid Progress of Unilateral Cerebral Microbleeds: A Novel Imaging Finding in Cerebral Amyloid Angiopathy-Related Inflammation
Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare but treatable CAA subtype characterized by reversible inflammatory mechanisms, offering unique diagnostic and therapeutic potential. We report a CAA-ri case featuring left-dominant cerebral microbleeds (CMBs) (baseline: 38 left vs. 2 right; 13-month progression to 65 left) with rapid clinical improvement post-corticosteroid therapy. This case expands the phenotypic spectrum of CAA-ri by demonstrating asymmetric CMBs with unilateral progression—a previously underrecognized pattern. This presentation requires heightened awareness in clinical practice to avert misdiagnosis and overlooked diagnoses.
Cerebral Amyloid Angiopathy-Related Inflammation
Middle Meningeal Artery Embolization for Chronic Subdural Hematoma:A 3-Case Series and Literature Review
Objective: To explore the efficacy of middle meningeal artery embolization (MMAE) in the treatment of chronic subdural hematoma (CSDH). Methods: We retrospectively analyzed clinical data of 3 patients (with 4-sided hematomas) diagnosed with CSDH who were admitted to the Department of Neurosurgery, General Hospital of Ningxia Medical University in December 2021. Two patients underwent MMAE (one with bilateral MMA embolization), and one patient received MMAE combined with subdural burr hole drainage. All patients were embolized using Onyx glue. Clinical efficacy was evaluated using the modified Rankin Scale (mRS), with a ≥1-point decrease post-treatment defined as symptom improvement. Hematoma absorption was assessed via imaging. Results: Successful superselective catheterization of the middle meningeal artery (MMA) was achieved in all 3 patients (4-sided hematomas), with complete occlusion of the frontoparietal trunk of the MMA and its main branches. No procedure-related complications occurred. During a 2–4 month follow-up, all patients showed clinical improvement (mRS decreased by 1–2 points). Imaging confirmed complete absorption of all 4-sided hematomas, resolution of clinical symptoms, and no recurrence. Conclusion: MMAE is a safe, effective, and promising treatment for CSDH.
Stage-Specific Multimodal Imaging–Guided Non-Invasive BrainStimulation for Post-Stroke Aphasia: A Structured Narrative Review
Non-invasive brain stimulation (NIBS) modalities—including transcranial magnetic stimulation (TMS), theta-burst stimulation (TBS), and transcranial direct current stimulation (tDCS)—have emerged as promising approaches to promote language recovery in post-stroke aphasia by engaging both functional and structural neuroplasticity. This structured narrative review integrates recent multimodal evidence from functional magnetic resonance imaging (fMRI), DTI, and connectome analyses to delineate the stage-dependent mechanisms underlying NIBS-induced modulation of language networks. Findings across studies suggest a dynamic pattern of reorganization: acute-phase hypoactivation of left-hemisphere language areas and diffuse right-hemisphere disinhibition give way to bilateral upregulation in the subacute phase, followed by gradual restoration of left-dominant connectivity during the chronic stage, which may be limited by persistent contralesional hyperactivity. Low-frequency TMS or continuous TBS targeting right-hemisphere homologues can suppress maladaptive overcompensation, whereas high-frequency TMS or intermittent TBS applied to residual left-hemisphere sites enhances excitability and network centrality. Bilateral or neuronavigation-guided tDCS, particularly when combined with language training, rebalances interhemispheric excitability and supports sustained gains in naming and fluency. DTI-derived increases in arcuate and uncinate fasciculi integrity correlate with clinical improvement, while contralesional temporoparietal cortical thickening reflects concurrent structural remodeling.
Abnormal intrinsic brain functional network dynamicsin amnestic mild cognitive impairment
Background: Amnestic mild cognitive impairment (aMCI), owing to its high prevalence and significant prognostic relevance for dementia, has become a key focus in the early detection and intervention of neurodegenerative diseases. However, the abnormal intrinsic brain functional network dynamics in aMCI patients remain inadequately understood. Methods: A total of 66 participants, comprising 31 aMCI patients and 35 age- and education-matched healthy controls (HCs), underwent resting-state fMRI scans and comprehensive neuropsychological assessments. This study examined intrinsic brain network dynamics in aMCI patients via dynamic functional network connectivity (dFNC) analysis, dynamic graph theoretical analysis, and multilayer network analysis. Results: Compared with HCs, aMCI patients presented a significantly shorter mean dwell time (MDT) in state 2 (P < 0.05). In addition, the modularity coefficient Q was significantly greater in aMCI patients (1.40 ± 1.20) than in HCs (0.90 ± 0.46, P < 0.05). No significant differences were observed between the groups in terms of network efficiency or network switching rates. Conclusion: These findings emphasize significant abnormal intrinsic brain functional network dynamics in aMCI patients, with disrupted network stability and increased modularity indicating maladaptive reorganization of brain networks. These results provide valuable biomarkers for early diagnosis and intervention, contributing to a deeper understanding of the neurobiological underpinnings of cognitive decline in aMCI patients.
Linking Environmental Exposures to Depression: Insights from Epidemiology, Biology, and Methodology
Depression is a leading cause of disability worldwide, with significant personal and societal consequences. Emerging research highlights the critical role of environmental exposures as modifiable risk factors influencing depression risk and progression. Over the past decade, a substantial body of epidemiological evidence has linked diverse environmental factors—including air pollution, limited green space access, chronic noise exposure, adverse features of urbanization, unhealthy lifestyle behaviors, early life adversity, and internal toxicant burdens—to elevated risks of depressive symptoms and clinical depression. These exposures exert their effects through interconnected biological pathways, including chronic systemic inflammation, oxidative stress, hypothalamic-pituitary-adrenal axis dysregulation, blood-brain barrier disruption, and gut microbiota alterations. Recent methodological advances, such as high-resolution environmental exposure assessment, multi-exposure model approaches, longitudinal cohort designs, and enhanced causal inference techniques, have strengthened the evidence base. Nevertheless, challenges remain in accurately characterizing multifactorial exposures and establishing causal relationships across diverse populations. Incorporating a life course perspective and adopting comprehensive exposome frameworks will be essential for future research. Understanding environmental determinants of depression not only advances etiological knowledge but also highlights critical opportunities for prevention. Public health interventions aimed at reducing harmful environmental exposures, enhancing urban green infrastructure, promoting healthy lifestyle behaviors, and mitigating psychosocial stressors offer promising strategies for reducing the burden of depression. Ultimately, integrating environmental health perspectives into mental health research and policy may provide transformative approaches to preventing and alleviating depression at the population level.
Plasma lipidomes, immune cells, and headaches induced by sinusitis: a bidirectional Mendelian randomization studypotential
Background: Chronic rhinosinusitis (CRS) is a complex disease influenced by various factors such as environmental exposure, microbial infection, immune dysfunction, and genetic predisposition. The objective of this research is to examine the causal relationship between plasma lipidomes and CRS, focusing on the potential role of immune cells as mediators. Methods: Utilizing pooled data from genome-wide association studies (GWAS), a two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between genetically predicted plasma lipidomes (7174 cases) and CRS (7529 cases, 444966 controls). Various methods such as inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted mode, and Wald ratio were employed to assess causality. Multiple sensitivity analyses were also conducted to ensure the reliability of the MR results. Furthermore, mediation analysis was used to identify immune cell-mediated pathways linking plasma lipidomes to chronic sinusitis. Results: The study identified 30 plasma lipidomes associated with chronic sinusitis, with only one remaining significant after FDR correction, namely Phosphatidylinositol (18:1_18:2). Additionally, 52 types of immune cells were found to be related to the disease, with only 3 types remaining significant after FDR correction: CD27+/IgD- CD38+ B cells, CD3+/CD28+ CD4+ T cells, and HLA DR+/CD33+ HLA DR+ CD14- cells. Mediation analysis revealed two distinct mediating relationships, indicating potential pathways from plasma lipidomes to chronic sinusitis through two specific immune cells. Sensitivity analysis results indicated no heterogeneity or pleiotropy in the study. Conclusion: The findings of this study reinforce the causal link between plasma lipidomes, immune cells, and chronic sinusitis. Identifying these biomarkers offers fresh insights into the pathogenesis of chronic sinusitis, with implications for improved prevention, diagnosis, and treatment of the condition.
Amide Proton Transfer Imaging in the Central Nervous System: Recent Advances and Clinical Applications
Amide proton transfer (APT) imaging, as a novel magnetic resonance molecular imaging technique based on the chemical exchange saturation transfer (CEST) effect, indirectly reflects molecular-level information such as tissue protein concentration, pH, and microenvironment by detecting the exchange between intracellular free water and amide protons in proteins/peptides. Since it was first proposed by Professor Jinyuan Zhou in 2003, the technique has achieved significant progress in theoretical modeling, sequence optimization, and clinical translation, particularly in its expanding application to central nervous system diseases. In recent years, APT has been widely used for tumor grading, stroke staging, early identification of hypoxic-ischemic encephalopathy (HIE), and pathological tracking of neurodegenerative diseases. This review systematically summarizes the principles and advantages of APT imaging, with a focus on its recent applications in brain tumors, cerebral infarction, and neurodegenerative diseases. It also discusses signal variation characteristics and underlying mechanisms in different disease states, as well as current clinical applications and technical challenges. Keywords: Amide proton transfer (APT); chemical exchange saturation transfer (CEST); magnetic resonance molecular imaging; central nervous system (CNS); brain tumor; cerebral infarction; neurodegenerative disease
chemical exchange saturation transfer (CEST)
Global and Regional Trends in Headache Disorders Among Children and Adolescents Aged 5–19 findings from the global burden of disease study 2021
Background: As highlighted in the Global Burden of Disease (GBD) study, headache disorders represent a major cause of non-fatal disease burden worldwide, given their widespread prevalence and impact on daily functioning. In recent years, the prevalence of headache disorders has risen substantially among children and adolescents, with significant repercussions for their daily functioning and overall well-being. However, despite their growing impact, there remains a critical shortage of comprehensive investigations into the burden and long-term implications of these conditions in younger populations. This study systematically assesses the global and regional burden of headache disorders in individuals aged 5 to 19 years over the period 1990 to 2021, aiming to generate high-resolution epidemiological insights to inform public health strategies and guide data-driven policy decisions. Methods: The 2021 iteration of the GBD study quantified the impact of 371 diseases and injuries through estimates of disability-adjusted life years (DALYs), incidence, and prevalence, integrating data from over 100,000 heterogeneous sources spanning registries, surveys, and health records. Data inputs included vital registration systems, verbal autopsies, national censuses, household surveys, disease-specific registries, healthcare utilization databases, and other relevant sources. DALYs were computed as the sum of years lived with disability (YLDs) and years of life lost (YLLs). YLDs were estimated by multiplying the prevalence of each health sequela—stratified by cause, age, sex, location, and year—by its assigned disability weight. In parallel, YLLs were computed by applying the standard life expectancy, derived from the reference life table, to the number of deaths within each demographic subgroup. Results: From 1990 to 2021, headache disorders consistently imposed a significant global burden on individuals aged 5 to 19. By 2021, the age-standardized incidence rate (ASIR) was 7,874 per 100,000, and the age-standardized prevalence rate (ASPR) reached 19,866 per 100,000, with a DALY rate of 294 per 100,000. Females consistently had higher rates than males across all indicators. Middle-SDI regions contributed the highest total number of cases and DALYs, while high-SDI regions had the highest age-standardized rates. Temporal trend analysis showed the steepest increase in DALY rates in middle- and high-middle-SDI regions, particularly among adolescents aged 15-19. Among headache subtypes, migraine, despite its lower prevalence, contributed more to DALYs due to its higher disability weight. Improved healthcare access and disease recognition in regions with advanced diagnostic infrastructure may lead to more accurate migraine diagnoses, while stigma and limited awareness can delay recognition, further exacerbating its disability burden. Conclusion: Headache disorders remain a significant and persistent health burden among children and adolescents worldwide, with migraine contributing most to disability. Targeted interventions and integration of headache care into primary health systems are urgently needed to address this growing challenge. Keywords: headache disorders, migraine, tension-type headache, incidence, prevalence, Global Burden of Disease (GBD), disability-adjusted life years (DALYs), epidemiology, adolescents, children
headache disorders, migraine, tension-type headache, incidence, prevalence, Global Burden of Disease (GBD), disability-adjusted life years (DALYs), epidemiology, adolescents, children
Casual association between plasma CoQ10 levels and stroke: a mendelian randomization study
Objective: The aim of this study is to investigate the causal relationship between plasma CoQ10 levels and stroke, as well as some cardiovascular diseases, using Mendelian randomization methods. Methods: Causal links were investigated through two-sample Mendelian randomization (MR) analysis. We identified genetic variants that showed significant associations with plasma CoQ10 levels. The inverse variance weighted (IVW) method was employed to estimate the effects. Additionally, sensitivity analysis was used to assess heterogeneity or pleiotropy. Results: Our MR analysis revealed that genetically predicted plasma CoQ10 levels was inversely associated with of any stroke (AS, OR = 0.803, 95% CI: 0.659–0.978, p =0.029), any ischemic stroke (AIS, OR = 0.792, 95% CI 0.651–0.964, p = 0.020) and small vessel stroke (SVS, OR = 0.512, 95% CI 0.294-0.892, p = 0.018). However, no associations were observed between genetically predicted plasma CoQ10 and large artery stroke (LAS), cardioembolic stroke (CES), intracranial hemorrhage (ICH), atrial fibrillation (AF), myocardial infarction (MI) or heart failure (HF). Conclusion: Our MR analysis implies a protective effect between higher plasma CoQ10 levels and AS, AIS or SVS. The results and the underlying pathways or mechanisms between plasma CoQ10 levels and stroke needs further investigation.
plasma CoQ10, ischemic stroke, small vessel stroke, cerebrovascular disease, mendelian randomization
Headache mechanisms: what we still do not know
Primary headaches such as migraine, cluster headache (CH), and tension-type headache (TTH) are highly prevalent neurological disorders with complex and heterogeneous pathophysiology. Traditionally attributed to either vascular or neuronal origins, current evidence supports a neurovascular model involving dynamic interactions between the nervous system and cranial. This Perspective examines the role of two key neuropeptides – calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) – in the generation of primary headaches. CGRP is a validated target in migraine, but its clinical utility is limited by biomarker instability and a significant proportion of non-responders. PACAP is emerging as a complementary target, though its receptor mechanisms remain incompletely understood. While neither CGRP nor PACAP appear to play a major role in TTH, their contribution to migraine and CH highlights the need for precision approaches based on molecular endophenotypes. Understanding these mechanisms may inform the development of more effective, personalized headache treatments.
Migraine, Cluster headache, Tension-type headache, Calcitonin gene-related peptide, Pituitary adenylate cyclase-activating polypeptide
Inauguration of Brain Conflux: A New Era of Interdisciplinary Research Bridging Brain Sciences and Clinical Innovation
As the Editor-in-Chief of Brain Conflux, I am filled with excitement and immense pride as I present this new journal to the global scientific community. Brain Conflux is not just another scientific publication—it is a visionary platform dedicated to advancing the field of neuroscience. With a focus on high-quality research, this peer-reviewed, open-access journal serves as a bridge between fundamental scientific discoveries and their clinical applications, enabling groundbreaking research to translate into meaningful healthcare solutions. In an era where our understanding of the brain is advancing rapidly, the time has come for a unified, interdisciplinary approach to neuroscience. Brain Conflux stands ready to lead this charge, offering an unparalleled platform for collaboration among researchers, clinicians, and policymakers, all working together to solve some of the most urgent challenges in brain health.
Advancements in Understanding Neurogenesis in Alzheimer's Disease: Current Research and Insights
Alzheimer's disease (AD) is increasingly impacting the aging global population, with its prevalence and mortality rates rising steadily. This trend severely affects the quality of life and intensifies the economic strain on both families and society. Despite ongoing research, effective treatments remain elusive. However, enhancing neurogenesis in the hippocampal dentate gyrus (DG) to promote the formation of new neurons and replace those lost in AD patients' hippocampus holds promise as a potential strategy to improve cognitive and memory functions, offering hope for delaying or even treating the disease.
Wilson’s disease presenting with polyneuropathy: a case report
Background: Wilson’s disease (WD) is an inherited autosomal recessive disease affecting copper metabolism in the body. Nearly all neurological symptoms are attributed to the central nervous system, while peripheral neuropathy is rare. Case presentation: A 48-year-old male presented with progressive muscle weakness and atrophy in distal extremities for 7 months. Pure distal motor axonal neuropathy was confirmed by electromyography. Extremely low serum ceruloplasmin level was detected accidentally and gene screening of ATP7B found two known compound heterozygous mutations (c.3859G>A p.(Gly1287Ser), c3155C>T p.(Pro1052Leu)). However, the patient had no typical symptoms or signs of WD. Brain MRI was unremarkable. B ultrasound only revealed mild liver steatosis. He responded well to penicillamine treatment. Electromyography showed nearly normal results 1 year later. Conclusion: WD can present with pure peripheral neuropathy, rendering diagnostic challenging to this disease. Routine serum ceruloplasmin testing seems justifiable for patients with peripheral neuropathy of undetermined cause.
Correlation of nighttime fasting duration with cognitive decline in older adults: a cross-sectional study based on NHANES 2011-2014
Background: Cognitive dysfunction is a significant health challenge in the global elderly population, and its prevalence is associated with multiple factors, including modifiable lifestyle factors. The relationship between nighttime fasting duration, a potential lifestyle factor, and cognitive function has yet to be thoroughly investigated. Objective: To investigate the association between nighttime fasting duration and cognitive function. Methods: This cross-sectional study was based on data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Weighted multiple linear regression was utilized to examine the relationship between nighttime fasting duration and cognitive function, with additional curve fitting and inflection point analysis conducted to further elucidate this association Results: There was a significant negative linear relationship between nighttime fasting duration and cognitive function (Learn: β = -1.2, 95% CI: -1.98, -0.43, P = 0.006; Recall: β = -1.1, 95% CI: -2.11, -0.09, P = 0.036; Animal Fluency: β = -4.49, 95% CI: -7.26, -1.72, P = 0.004; Digit Symbol Substitution Test: β = -12.66, 95% CI: -19.30, -6.01, P = 0.002). Subgroup analyses showed that this negative correlation was prevalent in most subgroups. Curve fitting revealed a linear relationship between nighttime fasting duration and cognitive function scores, but did not identify a significant inflection point. Conclusions: Longer nighttime fasting times may be associated with cognitive decline, either as a continuous or categorical variable.
Neuroimaging Advances in Neuropsychiatric Symptoms Associated with Parkinson’s Disease
Parkinson’s disease (PD) is a prevalent neurodegenerative disorder traditionally defined by its motor symptoms yet increasingly recognized for its wide spectrum of neuropsychiatric symptoms (NPS) including anxiety, depression, apathy, impulse-control behaviors, and hallucinations. Recent neuroimaging advances have provided crucial insights into the neural substrates underlying these comorbidities. Structural imaging studies, using voxel-based morphometry and T1-weighted magnetic resonance imaging, have revealed regional atrophy in the frontal cortex, striatum, limbic areas, and occipital regions. In comparison, functional imaging using positron emission tomography, single-photon emission computed tomography, and resting-state functional MRI have identified abnormal network connectivity in circuits implicated in fear processing, reward regulation, and cognitive control. Overall, these imaging studies suggest shared and distinct pathophysiology of PD-related NPS, emphasizing the need for longitudinal, multimodal investigations to inform targeted therapeutic strategies and to improve clinical outcomes.
De Novo Mutation of POLR3A Associated with 4H Leukodystrophy Syndrome: A Case Report
Background: Pathogenic biallelic variants in POLR3A have been associated with different disorders characterized by progressive neurological deterioration. These include the 4H leukodystrophy syndrome (hypomyelination, hypogonadotropic hypogonadism, and hypodontia) and adolescent-onset progressive spastic ataxia, as well as Wiedemann–Rautenstrauch syndrome (WRS), a recognizable neonatal progeroid syndrome. The phenotypic differences between these disorders are thought to occur mainly due to different functional effects of underlying POLR3A variants. Case presentation: Here, we present the detailed clinical course of a 20-year-old woman who presented with developmental delays, neurological deficits, metabolic abnormalities, and sleep disturbances. She was born to non-consanguineous parents and had an elder sister who usually behaved. Laboratory studies demonstrated low or undetectable LH and FSH levels and abnormally low estradiol levels. MRI showed leukoencephalopathy characterized by white matter lesions and brain atrophy. Homozygous missense mutation c.2984C>T (p.Thr995Ile) was found in POLR3A, which codes for the largest subunit of RNA polymerase Ill. Conclusions: POLR3A-induced leukodystrophy is relatively rare and not well understood, making it challenging to diagnose and easy to overlook. The prognosis for this disease is generally poor, significantly impacting the quality of life of affected individuals. Since Pol III-related leukodystrophies shows various combination of neurologic and non-neurologic features, additional report will help to bring crucial information concerning this molecular diagnosis, the prediction of the disease and practical consequences for genetic counseling.