NeuroSci最新文献

The rising prevalence of neuroimmune disorders such as multiple sclerosis and fibromyalgia has renewed interest in the hygiene hypothesis, which posits that reduced early-life microbial exposure deprives the immune system of formative "noise" that calibrates thresholds of tolerance. We extended this framework by introducing stochastic resonance (SR), a system phenomenon in which optimally tuned noise enhances weak-signal detection in nonlinear networks, as a potential surrogate for missing microbial variability. As electrical noise and subthreshold stimulation have been shown to modulate cortical excitability and enhance perception, microbial noise may be necessary for sustaining immune plasticity. Conversely, a lack of stimulation, whether microbial or electrical, can lead to maladaptive states characterized by dysregulated signaling and heightened vulnerability to chronic inflammation. Evidence from immunology highlights noise-aware processes, such as T-cell receptor proofreading, NF-κB pulsatility, and cytokine quorum sensing, all of which exploit stochastic fluctuations. Computational tumor-immune models similarly suggest that tuned noise can optimize immune surveillance. Clinical data from neuroscience demonstrate that subsensory electrical noise improves motor excitability and sensory perception, whereas vagus nerve stimulation modulates inflammatory pathways, underscoring translational feasibility. We propose that SR reframes noise from a biological error to a therapeutic resource capable of recalibrating dysregulated neuroimmune thresholds. This conceptual synthesis positions microbial and electrical noise as parallel modulators of tolerance and outlines testable predictions with translational potential for neuroimmune disorders.

Background: Autism Spectrum Disorder (ASD) is a complex and heterogeneous neurodevelopmental condition. Diagnosing ASD in adults, especially in milder forms, remains challenging due to camouflaging strategies, adaptive behaviors, and frequent psychiatric comorbidities. Despite increased awareness, there is a critical need to improve recognition and tailored interventions for adults with ASD. This study aims to examine the prevalence of psychiatric comorbidities among individuals diagnosed with ASD.

Methods: This retrospective cross-sectional study examined 64 adults diagnosed with ASD (n = 29 females, 45.3%; age: range, 18-57 years; mean ± SD, 30.9 ± 8.92), who accessed two university hospital outpatient units in Rome between September 2023 and January 2025. All participants were assessed using the Autism Diagnostic Observation Schedule, Second Edition-Module 4 (ADOS-2). Psychiatric comorbidities were evaluated using clinical assessments and the Mini-International Neuropsychiatric Interview (M.I.N.I.) Plus.

Results: All patients received an ASD diagnosis without intellectual disability. Forty-four (68.8%) presented with at least one psychiatric comorbidity, most commonly depressive (25.0%) and anxiety disorders (9.4%). Over half of the participants (57.4%) reported at least mild depressive symptoms, and 42.6% exhibited moderate to severe depressive levels.

Conclusions: High rates of psychiatric comorbidities, particularly mood and anxiety disorders, were observed, underscoring the importance of comprehensive, multidisciplinary assessment and individualized interventions. Further research using larger samples and rigorous methodologies is warranted to better characterize the ASD phenotype in adults and guide targeted therapeutic strategies.

A comprehensive study of the contribution of dysfunction AKT/mTOR signaling to the pathogenesis of schizophrenia is needed. The aim of the study is to determine the expression of the protein kinase AKT/mTOR signaling pathway in peripheral mononuclear cells (PMCs) of patients with schizophrenia. Determination of AKT1, mTOR, p70S6K, GSK3-α, and GSK3-β in mononuclears was performed on multiplex analyzers. Statistical data processing was carried out using SPSS. The critical significance level for the differences was 0.05. The study included 58 patients with schizophrenia (F20) and 60 healthy individuals. We found an increase in the expression of AKT1 and p706SK in PM׳s of patients (p = 0.006, p = 0.001). Analysis of kinase expression was carried out depending on clinical characteristics (type of course, leading symptoms and duration of the schizophrenia). Increased expression of GSK3-α and GSK3-β was detected in patients with a duration of disease more than 5 years (p = 0.019, p = 0.018). The AKT/mTOR signaling cascade may play a significant role in the pathogenesis of schizophrenia. We can assume that signaling pathways are involved in neurobiological processes and can be targets for new methods of pharmacotherapy, prognosis and diagnosis of mental disorders.

Duropathies encompass a spectrum of disorders linked to spinal dural tears and cerebrospinal fluid (CSF) leaks, resulting in significant neurological manifestations. This review synthesizes the current literature on duropathies, focusing on their anatomical and pathophysiological aspects, including conditions such as superficial siderosis, spontaneous intracranial hypotension, and spinal cord herniation. The methodologies employed include comprehensive evaluations through neuroimaging techniques such as MRI and CT myelography, alongside clinical assessments of symptoms like ataxia, hearing loss, and cognitive impairment. Key findings highlight the prevalence of dural defects in patients with superficial siderosis and the association of persistent CSF leaks with various neurological impairments. The review emphasizes the need for a standardized diagnostic and therapeutic approach to enhance patient management and improve outcomes. By addressing the interrelated nature of these conditions, the study underscores the importance of early intervention to mitigate long-term neurological consequences. Overall, the findings advocate for further research to elucidate the mechanisms underlying duropathies and the development of effective treatment strategies, ultimately aiming to improve the quality of life for affected individuals.

Frontotemporal dementia (FTD) represents a cluster of adult-onset neurodegenerative diseases resulting from a combination of genetic and epigenetic factors. Currently, treatment is symptomatic and there are no licensed disease-modifying therapies available. The aim of this review was to provide an overview of ongoing or recently completed clinical studies targeting disease modification in FTD. A structured search of interventional trials of pharmacological compounds was conducted on three clinical trial registries (National Library of Medicine Clinical Trials, European Union Clinical Trials, and the Australian New Zealand Clinical Trials registries) up to September 2025. Twelve interventional trials were found. Half targeted autosomal-dominant progranulin (GRN) mutations (n = 6) and half examined therapies targeting neuroinflammatory-induced sporadic FTD (n = 6). The interim results of the early-phase (1/2) randomized controlled trials (RCTs), comprising three ongoing gene replacement studies (PROCLAIM, ASPIRE-FTD, upliFT-D) and one immune-modulating monoclonal antibody (INFRONT, now in phase 3)-all targeting the FTD-GRN mutation-show safety, tolerability, and effectiveness in restoring progranulin levels. Two recently completed phase 2 RCTs for sporadic FTD targeting neuroinflammation, the PEA-FTD and C9orf72 ALS/FTD trials, show disease-modifying potential. While interim results from six trials suggest clear mechanistic efficacy, prospective high-quality later-phase RCTs are required to ascertain long-term clinical efficacy. Since familial FTD encompasses less than half of the people with this disease, it is important to continue exploring the underlying pathophysiology, neuroimmunology, and treatment of epigenetic-induced sporadic FTD.

Intraoperative ultrasound (IOUS) has developed from a rudimentary adjunct into a versatile modality that now plays a crucial role in neurosurgery. Offering real-time, radiation-free and repeatable imaging at the surgical site, it provides distinct advantages over intraoperative magnetic resonance (MRI) and computed tomography (CT) in terms of accessibility, workflow integration and cost. The clinical spectrum of IOUS is broad: in cranial surgery it enhances the extent of resection of gliomas and metastases, supports dissection in meningiomas and enables localization of MRI-negative pituitary adenomas; in spinal surgery, it guides resection of intradural and intramedullary tumors, assists in myelotomy planning and confirms decompression in degenerative conditions such as cervical myelopathy and ossification of the posterior longitudinal ligament. IOUS also offers unique insights into cerebrospinal fluid disorders, including arachnoid webs, cysts, syringomyelia and Chiari malformation, where it visualizes cord compression and CSF flow restoration. In trauma and oncological emergencies, it provides immediate confirmation of decompression, directly influencing surgical decisions. Recent innovations, including contrast-enhanced ultrasound, elastography, three-dimensional navigated systems and experimental integration with artificial intelligence and robotics, are extending its functional scope. Despite heterogeneity of evidence and operator dependence, IOUS is steadily transitioning from an adjunctive tool to a cornerstone of multimodal intraoperative imaging, bridging precision, accessibility and innovation in contemporary neurosurgical practice.

Categorical liaison-defined as the obligatory pronunciation of a latent word in the form of a final consonant when followed by a vowel as the initial word or a word beginning with a silent "h" (e.g., des‿ours [dezuʁs])-is a robust phonological phenomenon in French and an informative window into morphophonological development. This exploratory behavioral study investigates the dissociation between perception and production of categorical liaisons among 24 French-speaking children aged 6-10 years diagnosed with expressive Developmental Language Disorder (DLD). A battery of nine ad hoc tasks assessed perception and production across words, pseudowords, noun phrases, and sentences. Results showed that children with DLD performed comparably to typically developing peers in perceiving unrealized categorical liaisons but exhibited significantly more omissions in production, regardless of context or age. Production deficits correlated with reduced working memory and inhibitory control. These preliminary findings provide descriptive data that can inform the development of standardized assessment tools and generate hypotheses about the cognitive mechanisms underlying categorical liaison difficulties in DLD.

Background: Patients with multiple sclerosis (PwMS) frequently experience dysphagia, which affects their quality of life. The swallowing disturbance questionnaire (SDQ) has demonstrated potential in screening dysphagia in different disorders. The objective of this study was to evaluate the validity and reliability of the Persian version of SDQ in PwMS.

Methods: In this cross-sectional study, 198 PwMS were enrolled. The translation of SDQ into Persian was performed using the forward-backward method. Participants completed both the SDQ and the Dysphagia in Multiple Sclerosis (DYMUS) questionnaires. Convergent validity was assessed using the Spearman correlation, construct validity was evaluated by principal component analysis (PCA), and reliability was assessed by Cronbach's alpha. Screening ability was evaluated with receiver operating characteristic (ROC) curve analysis, using DYMUS as the reference measure.

Results: The Persian SDQ showed high internal consistency (Cronbach's alpha = 0.913) after removing one item. PCA revealed a single dominant factor accounting for 49.4% of the variance. The 14-item SDQ correlated strongly with both DYMUS (Spearman's rho = 0.62, p < 0.001) and Expanded Disability Status Scale (EDSS) (Spearman's rho = 0.388, p < 0.001). The area under the curve of 0.957 revealed high screening power with a sensitivity of 91.7% and a specificity of 88.9%.

Conclusions: The Persian SDQ is a valid and reliable tool for early detection and quick monitoring of dysphagia in PwMS.

Microcephaly with early-onset, intractable seizures, and developmental delay (MCSZ) is a rare inherited neurological disorder caused by biallelic loss-of-function variants in the polynucleotide kinase/phosphatase (PNKP) gene, which encodes an enzyme critical for DNA repair. Here, we describe the clinical history of two novel patients presenting with microcephaly, epilepsy, growth deficiency, language impairment, and severe intellectual disability. Brain MRI in both cases revealed complex cerebral malformations, including lissencephaly, ventriculomegaly, dysmorphic hippocampi, and cerebellar atrophy. Next-generation sequencing (NGS) analyses identified compound heterozygous PNKP variants in both patients. In case #1, we detected the missense variant p.Gln50Glu (c.148C>G) in exon 2 (rs756746191) and a novel nonsense variant, p.Gln248Ter (c.742C>T), leading to a premature stop codon in exon 7. In case #2, we identified the frameshift variant p.Thr424GlyfsTer49, caused by a 17-nucleotide duplication (c.1253_1269dupGGGTCGCCATCGACAAC) in exon 14 (rs587784365), along with a 15-nucleotide deletion (c.1386+49_1387-33delCCTCCTCCCCTGACCCC) in intron 15 (rs752902474). Over long-term follow-up (20 and 36 years for case #1 and case #2, respectively), seizures persisted in the first patient, while full control was achieved in the second case with combined therapy of valproate and clobazam. Along with a review of the literature, these two novel cases confirm the broad phenotypic spectrum of PNKP-associated disorders and underscore the importance of including PNKP in the genetic screening of patients presenting with developmental and epileptic encephalopathy (DEE) and microcephaly.

Background: Cognitive impairment after stroke often reduces independence and quality of life. Cognitive rehabilitation is therefore essential, and recent research on computer-based interventions has shown promising results. This proof-of-concept study investigated the effects of additional self-administered cognitive training using an electronic device, compared with traditional paper-and-pencil methods, on attentional functions in individuals with subacute stroke.

Methods: Participants were randomly assigned to an experimental group or a control group. For two consecutive weeks, both groups received forty-five-minute, face-to-face cognitive therapy sessions each morning, delivered via an electronic device. In addition, the experimental group engaged in sixty minutes of self-administered cognitive training using the same device, while the control group completed conventional exercises with paper-and-pencil tools. Neuropsychological assessments were conducted before and after the intervention.

Results: Twenty-three participants were included (experimental group: eleven; control group: twelve). No significant differences in safety or attentional performance were observed between groups. Within-group analyses showed improvements in the experimental group in attentional shifting, inhibitory control, visuospatial planning, and problem-solving, while the control group improved in visuospatial planning and problem-solving.

Conclusions: These preliminary findings suggest that self-administered electronic cognitive training may be a feasible approach to support attentional recovery in individuals with subacute stroke.