NeuroSci最新文献

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.

Behavior is not a mere sequence of responses to stimuli but the dynamic expression of internal processes such as planning, prediction, valuation, and inference. These functions arise from distributed and metabolically costly neural systems and are best understood by considering behavior and neural activity together. This article presents a narrative and conceptual review of the neuroscience of behavior, integrating biological, environmental, and computational perspectives. We synthesize evidence from motor control, neural population dynamics, predictive processing, and spontaneous behavior, showing that behavior cannot be explained without the neural systems that generate it, and that neural activity gains meaning only through detailed behavioral models. Neural dynamics correlate with latent variables, such as intention and prediction error, that structure adaptive action across timescales. Recent advances in behavioral analysis, dimensionality reduction, and computational modeling enable the analysis of neural and behavioral data with comparable complexity, revealing shared computational architectures that link population activity with the organization of action. Our methodology involved a targeted literature search in PubMed and Web of Science (1919-2025), supplemented by seminal earlier works. By combining mechanistic and functional analysis, we outline a unified framework that explains how brains, bodies, and environments together generate flexible, adaptive behavior.

Atypical parkinsonian disorders-progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA)-are rare, rapidly progressive neurodegenerative syndromes characterized by distinct molecular pathologies, heterogeneous clinical phenotypes, and limited therapeutic options. Accurate diagnosis remains a major clinical challenge, especially during early and prodromal phases, due to overlap with Parkinson's disease (PD), phenotypic evolution, and the absence of reliable stand-alone biomarkers. Misclassification delays prognosis, impairs patient care, and hinders clinical trial design. This review synthesizes advances from 2015 to 2025 in clinical, imaging, and biomarker-based diagnosis of PSP, CBD, and MSA. We examine their phenotypic spectra, neuropathological substrates, and epidemiological trends, and critically evaluate the diagnostic performance and translational potential of emerging tools-including quantitative MRI morphometry, second-generation tau and α-synuclein PET ligands, neurophysiological markers such as video-oculography and autonomic testing, and fluid biomarkers such as neurofilament light chain. Persistent diagnostic barriers are identified, from phenotypic mimicry and pathological pleomorphism to the limited specificity of molecular assays and inequitable access to advanced technologies. We propose tiered, multimodal diagnostic algorithms that integrate structured clinical phenotyping with quantitative imaging, molecular diagnostics, systemic risk profiling, and autopsy-linked validation. Such biology-anchored approaches could enable diagnosis years before classical features emerge, improve patient stratification for disease-modifying trials, and lay the foundation for precision medicine in atypical parkinsonian disorders. A paradigm shift from descriptive nosology to mechanistically grounded frameworks is essential to accelerate early intervention and transform the clinical management of these devastating diseases.

Stimulator of interferon genes (STING) is a cytosolic DNA sensor that activates type I interferon (IFN) signaling, which plays a key role in neuroinflammation. Although the role of STING in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), remains debated, its involvement in the development of CNS lesions, particularly within localized pathology, modeled here by targeting the corpus callosum, has yet to be explored. Using a focal EAE model, we compared the induction of lesions in wild-type and STING-deficient (STING^gt/gt) mice. Lesions were analyzed by immunohistochemistry, flow cytometry, and transcriptomics. STING-deficient mice had significantly larger demyelinated lesions, reduced ISG expression, and modified immune cell infiltration. STING signaling limits lesion severity in focal EAE by promoting IFN responses and regulating immune infiltration. These findings position STING as a potential target for MS therapy.

Since its introduction, the construct of executive functions (EFs) has been associated with a set of tests to assess these functions and a brain network centered in the associative frontal brain regions. While the majority of perspectives have endorsed these associations, some studies have started casting doubts on them. In this article, the association between the construct of EFs, the tests used to assess them, and the involvement of frontal regions is examined. A sample of 28 patients with brain injuries was divided into three subgroups according to the region of the injury (anterior, posterior, antero-posterior). Patients were assessed with a battery of tests, including 25 measures of EFs and 6 control measures. A series of regression models revealed no significant differences in performance across the three groups. Findings indicate that the EF tests are not specific enough to differentiate EFs and brain injuries. The alleged reference of EFs to the frontal areas of the brain should attribute a higher role to other associative areas. The present study provides recommendations about how the EFs concept could be improved through methodological refinements and/or its dissemination.

Background: Neural efficiency theory proposes that expert athletes optimize brain resource allocation and functioning. Beta band oscillations are associated with attention, motor preparation, and emotional control, reflecting adaptive patterns of reduced cortical energy expenditure (absolute power) and greater temporal precision (peak frequency). Slow cortical potential (SCP) neurofeedback has emerged as a method to train voluntary cortical regulation, yet its application in sports-particularly in precision-demanding disciplines such as golf-remains underexplored. The aim of this study was to evaluate the effects of SCP neurofeedback on beta band activity in competitive golfers.

Methods: Forty-two golfers were randomly assigned to either an intervention group (n = 21), which completed 16 SCP neurofeedback sessions (2560 trials), or a control group (n = 21). SCP activity was measured during activation and deactivation trials, while EEG beta oscillations were analyzed in terms of peak frequency and absolute power at C3, O2, F8, and T5. These sites were chosen for their relevance to golf: C3 (motor execution), O2 (visual processing), F8 (inhibitory and emotional control), and T5 (visuospatial integration).

Results: The intervention group showed significant increases in positive SCP trials, reflecting improved voluntary cortical inhibition. Peak frequency increased in Beta 1 (C3) and Beta 2 (O2), while absolute power decreased at F8 and T5, which seems to indicate a reduced cortical overload and enhanced visuospatial integration.

Conclusions: SCP neurofeedback modulated beta activity in golfers, enhancing neural efficiency and supporting its potential as an innovative tool to optimize performance in precision sports.

Introduction: Multiple sclerosis (MS) is a chronic neurodegenerative disease that entails high costs, progressive disability, and reduced quality of life (QoL). Telerehabilitation (TR), supported by new technologies, is emerging as an alternative or complement to in-person rehabilitation, potentially lowering socioeconomic impact and improving QoL.

Aim: The objective of this study was to evaluate the effect of TR on the QoL of people with MS compared with in-person rehabilitation or no intervention.

Materials and methods: A systematic review of randomized clinical trials was conducted (March-May 2025) following PRISMA guidelines. Searches were run in the PubMed-Medline, EMBASE, PEDro, Web of Science, and Dialnet databases. Methodological quality was assessed with the CASP scale, risk of bias with the Risk of Bias 2 tool, and evidence level and grade of recommendation with the Oxford Classification. The protocol was registered in PROSPERO (CRD420251110353).

Results: Of the 151 articles initially found, 12 RCTs (598 total patients) met the inclusion criteria. Interventions included (a) four studies employing video-controlled exercise (one involving Pilates to improve fitness, another involving exercise to improve fatigue and general health, and two using exercises focused on the pelvic floor muscles); (b) three studies using a monitoring app to improve manual dexterity, symptom control, and increased physical activity; (c) two studies implementing an augmented reality system to treat cognitive deficits and sexual disorders, respectively; (d) one platform with a virtual reality headset for motor and cognitive training; (e) one study focusing on video-controlled motor imagery, along with the use of a pain management app; (f) a final study addressing cognitive training and pain reduction. Studies used eight different scales to assess QoL, finding similar improvements between groups in eight of the trials and statistically significant improvements in favor of TR in four. The included trials were of good methodological quality, with a moderate-to-low risk of bias and good levels of evidence and grades of recommendation.

Conclusions: TR was more effective in improving the QoL of people with MS than no intervention, was as effective as in-person treatment in patients with EDSS ≤ 6, and appeared to be more effective than in-person intervention in patients with EDSS between 5.5 and 7.5 in terms of QoL. It may also eliminate some common barriers to accessing such treatments.

Different neurodegenerative diseases display varying etiologies and phenotypes, reflecting region-specific neurodegeneration [...].

Background: The Coma Recovery Scale-Revised (CRS-R) is the gold standard for diagnosing chronic disorders of consciousness (DoC); however, its clinical utility is limited by lengthy administration and the need for specialized training. The Simplified Evaluation of Disorders of Consciousness (SECONDs) provides a faster and more user-friendly alternative.

Objective: This study aims to evaluate the validity and reliability of the Argentine adaptation of the SECONDs scale in adults with chronic DoC due to acquired brain injury.

Methods: Twenty-nine patients were evaluated over two consecutive days by three blinded raters. On day one, rater A administered the SECONDs (A1) and rater B administered the CRS-R (B) to assess concurrent validity. On day two, rater A repeated the SECONDs (A2), and rater C performed an additional SECONDs assessment (C), permitting evaluation of intra-rater (A1 vs. A2) and inter-rater (A vs. C) reliability.

Results: The SECONDs demonstrated excellent intra-rater (ICC = 0.98) and inter-rater (ICC = 0.86) reliability. Concurrent validity with the CRS-R was strong (r = 0.73, p < 0.001). Diagnostic agreement was high between A1 and B (κ = 0.75) and between both A1-A2 and A1-C (κ = 0.82). The median administration time was significantly shorter for the SECONDs (10 vs. 15 min; p < 0.001).

Conclusion: The Argentine SECONDs is a valid, reliable, and efficient tool for the clinical assessment of DoC patients in rehabilitation settings.