Brain Sciences最新文献

Background/Objectives: Inter-individual variability in injury severity represents a major barrier to reproducibility in neonatal hypoxia-ischemia (HI) models. Objective early postoperative stratification of animals is therefore essential for standardized group allocation and reliable assessment of experimental outcomes. This study aimed to evaluate whether laser speckle contrast imaging (LSCI) can be used as a rapid, noninvasive tool for early post hoc stratification of ischemic brain damage severity in neonatal mice following HI. Methods: Neonatal CD-1 mice (postnatal day 9; n = 60) underwent hypoxia-ischemia using a modified Rice-Vannucci protocol. Cerebral perfusion was assessed by laser speckle contrast imaging at baseline, 3 h, and 7 days after HI. The difference in mean perfusion between ipsilateral and contralateral hemispheres at 3 h (Δ perfusion) was used to stratify animals into severity groups. Brain injury was quantified by 2,3,5-triphenyltetrazolium chloride (TTC) staining at 24 h and 7 days. Survival was monitored for 7 days and analyzed using Kaplan-Meier curves and the log-rank (Mantel-Cox) test. Results: LSCI-derived Δ perfusion at 3 h enabled the formation of distinct injury-severity groups (no visible damage, mild, moderate, and severe) with significant between-group differences (p < 0.0001). TTC-based lesion area increased stepwise across severity groups, and Δ perfusion correlated with lesion size when all animals were analyzed together (r = 0.688, p = 0.0011). No significant correlations were observed within individual severity groups, indicating that the overall association was driven primarily by between-group differences. Survival analysis revealed 75% mortality in the severe injury group (p < 0.0001). Conclusions: LSCI represents a robust and practical approach for early, objective, group-level stratification of neonatal mice by HI injury severity, thereby improving reproducibility and statistical validity in preclinical studies. However, its ability to predict outcomes within individual severity categories is limited, and repeated long-term measurements may pose technical challenges.

Post-traumatic olfactory dysfunction (PTOD) is a common and often persistent sequela of mild traumatic brain injury (mTBI), with limited evidence-based treatment options. We propose that high-frequency rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) may support olfactory recovery via top-down modulation of distributed olfactory, attentional, and reward networks, and we outline key mechanistic and methodological considerations for future studies. We summarize the case of a 70-year-old woman with severe post-traumatic hyposmia persisting for ~5 months, who underwent a 12-week, 10 Hz rTMS course over left DLPFC (36 sessions; 800 pulses/session). Using a structured door diary and repeated ratings across odour categories, she reported stepwise improvement starting around sessions 10-12 (re-emergence of pungent odours) and progressing to broad restoration, including subtle fragrances, by treatment end; no adverse events occurred. While causality cannot be inferred from a single case, this pattern is consistent with a network-level neuromodulatory effect and motivates controlled trials combining standardized olfactory testing with neurophysiology and neuroimaging.

Background: H3K27-altered diffuse midline glioma (DMG) is a highly aggressive central nervous system malignancy with limited therapeutic options and poor prognosis. Precision medicine strategies that integrate molecular profiling with individualized treatment selection represent a critical avenue for improving outcomes. Case presentation: We describe a 31-year-old woman with H3K27-altered DMG who, after standard chemoradiotherapy, was treated with a personalized, mechanism-guided combination regimen based on her tumor's molecular profile. Next-generation sequencing identified pathogenic alterations in ATRX, H3F3A, and NF1, with a high NF1 mutation allelic fraction indicating RAS/MAPK pathway activation. Immunohistochemistry demonstrated elevated phosphorylated mTOR consistent with PI3K/AKT/mTOR pathway upregulation. The individualized regimen comprised trametinib and everolimus for dual pathway inhibition, the tissue-agnostic agent dordaviprone (ONC201), metabolic modulation with 2-deoxy-D-glucose, and electric field-based therapy. At seven months, MRI showed approximately a 60% volumetric reduction in the enhancing tumor component, accompanied by marked T2-weighted signal regression. Clinically, the patient remained neurologically intact with a Karnofsky Performance Score of 100%. Conclusions: This case illustrates the potential clinical value of a genomics-guided, multimodal treatment strategy in H3K27-altered DMG. The systematic integration of comprehensive molecular profiling with mechanistically rational treatment selection may contribute to meaningful radiological and clinical benefit in this otherwise uniformly fatal disease. These observations support further investigation of individualized, pathway-targeted approaches in prospective studies and N-of-1 trial frameworks.

Background/objectives: Sleep stage classification is crucial for assessing sleep quality and diagnosing related disorders. Electroencephalography (EEG) is currently recognized as a primary method for sleep stage classification. High-performance automatic sleep staging methods based on EEG leverage the powerful contextual modeling capabilities of Transformer Encoder architectures. However, the global self-attention mechanism in Transformers incurs significant computational overhead, substantially hindering the training and inference efficiency of automatic sleep staging algorithms.

Methods: To address these issues, we introduce an end-to-end framework for automatic sleep stage classification using single-channel EEG: SleepMFormer. At the algorithmic level, SleepMFormer adopts a task-driven simplification of the Transformer encoder to improve attention efficiency while preserving sequence modeling capability. At the training level, supervised contrastive learning is incorporated as an auxiliary strategy to enhance representation robustness. From an engineering perspective, these design choices enable efficient training and inference under resource-constrained settings.

Results: When integrated with the SleePyCo backbone, the proposed framework achieves competitive performance on three widely used public datasets: Sleep-EDF, PhysioNet, and SHHS. Notably, SleepMFormer reduces training and inference time by up to 33% compared to conventional self-attention-based models. To further validate the generalizability of MaxFormer, we conduct additional experiments using DeepSleepNet and TinySleepNet as alternative feature extractors. Experimental results demonstrate that MaxFormer consistently maintains performance across different model architectures.

Conclusions: Overall, SleepMFormer introduces an efficient and practical framework for automatic sleep staging, demonstrating strong potential for related clinical applications.

Background/objectives: this paper investigates the local vs. global visual processing preference in typically developing (TD) children, youth with Down syndrome (DS), and youth with Williams syndrome (WS). In particular, the global precedence effect (GPE) and the global interference effect (GI) have recently been described as two distinct and at least partially independent effects.

Methods: in this study, 50 participants (TD = 25, DS = 13, WS = 12) completed two experiments requiring the identification of either the global or local level of hierarchical stimuli, which consisted of letters and schematic faces. For each stimulus type, two separate blocks were conducted, one with the task to focus on the local elements and the other with the task to focus on the global shape.

Results: our results indicate that TD children demonstrate a global precedence effect for letters but not for schematic faces, suggesting a developmental modulation of configural processing. In contrast, both DS and WS groups showed a global processing bias for schematic faces and a significant global interference effect in both conditions, likely reflecting deficits in inhibitory control.

Conclusions: these findings challenge the notion that DS and WS individuals can be classified strictly as global or local processors, respectively, emphasizing the influence of stimulus type and cognitive demands. Implications for neurodevelopmental research and clinical interventions are discussed.

Background/Objectives: Neurodegenerative diseases are driven by multiple interconnected pathological mechanisms involving both intrinsic and extrinsic molecular and cellular processes. Efficient bidirectional intracellular transport is essential for neuronal survival and function, enabling the movement of organelles, proteins, and vesicles between the neuronal soma and distal compartments. This process is primarily mediated by kinesin-dependent anterograde transport and dynein-dependent retrograde transport. Disruption of either motor protein compromises endosome-lysosome recycling, leading to cellular dysfunction and neurodegeneration. However, the mechanisms underlying motor protein impairment in Parkinson's disease (PD) remain incompletely understood. Methods: We investigated the involvement of kinesin and dynein in intracellular transport dysfunction using both in vitro and in vivo models of PD. Cultured neuronal cells were exposed to MPP+ (1-methyl-4-phenylpyridinium) to model PD-associated neurotoxicity, and motor protein function, vesicular trafficking, and endosomal recycling were assessed. In parallel, an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse model of PD was used to evaluate dynein-positive fiber density in the spinal cord. The role of calpain-2 was examined by co-treatment with the selective calpain-2 inhibitor zLLYCH2F in both experimental systems. Results: MPP+ exposure disrupted kinesin- and dynein-mediated transport in neuronal cytoplasm, resulting in impaired vesicular trafficking and defective endosome-lysosome recycling. These alterations led to abnormal accumulation of vesicles in both perinuclear regions and at the cell periphery. Pharmacological inhibition of calpain-2 with zLLYCH2F restored motor protein function and normalized vesicle distribution in MPP+-treated cells. Consistent with in vitro findings, MPTP-treated mice exhibited a significant reduction in dynein-positive fiber density within the spinal cord, which was prevented by co-treatment with zLLYCH2F. Conclusions: Our findings demonstrate that calpain-2 activation contributes to kinesin and dynein dysfunction following MPP+/MPTP exposure, leading to impaired intracellular transport and vesicle recycling in PD models. Inhibition of calpain-2 preserves motor protein function, maintains cytoskeletal integrity, and supports normal intracellular trafficking. These results identify calpain-2 as a critical regulator of motor protein stability and suggest that targeting calpain-2 may represent a promising therapeutic strategy for mitigating intracellular transport defects in Parkinson's disease.

Background/Objectives: Dementia, characterised by cognitive decline, significantly impacts language abilities. While the risk of dementia increases with age, it often manifests years before clinical diagnosis. Identifying early warning signs is crucial for timely intervention. Previous research has demonstrated that changes in language, such as reduced vocabulary diversity and simpler sentence structures, may be observed in individuals with dementia. This study investigates the potential of linguistic analysis to detect early signs of cognitive decline by examining the writing of Sir Terry Pratchett, a renowned author diagnosed with Posterior Cortical Atrophy (PCA), typically a form of dementia caused by Alzheimer's disease. Methods: This study analysed 33 Discworld novels by Terry Pratchett, comparing linguistic features before and after a potential turning point identified through analysis of adjective type-token ratios (TTR). Results: A significant decrease in lexical diversity (TTR) was observed for nouns and adjectives in later works. Total wordcount increased, while lexical diversity decreased, suggesting a shift towards simpler language. This shift coincided with a decrease in adjective TTR below a defined threshold, occurring approximately ten years before Pratchett's formal diagnosis. Conclusions: These findings suggest that subtle changes in linguistic patterns, such as decreased lexical diversity, may precede clinical diagnosis of dementia by a considerable margin. This research highlights the potential of linguistic analysis as a valuable tool for early detection of cognitive decline. Further research is needed to validate these findings in larger cohorts and explore the specific linguistic markers associated with different types of dementia.

Background: Common polymorphisms in the MTHFR gene, C677T and A1298C, have been associated with increased risk for psychiatric neurodevelopmental disorders, including autism spectrum disorder (ASD). However, studies provide conflicting evidence for the strength of the association with ASD based on both the allelic variant and population structure of the cohorts studied. Methods: Using systematic literature search and selection criteria, we calculated ASD-associated odds ratios for the two most-reported MTHFR variants. Twenty-two articles reported the association between MTHFR C677T and ASD, including 13913 subjects (4391 cases, 9522 controls). Nine articles, including 3009 subjects (1462 cases, 1547 controls), evaluated the link between MTHFR A1298C and ASD susceptibility. Results: We identified a statistical association between ASD and the MTHFR C677T variant, regardless of race or ethnicity. However, there was no statistical support for an association between ASD and the MTHFR A1298C variant. In both cases, substantial-to-considerable residual heterogeneity remained (I² ~67% and 73%, respectively). Exploring the heterogeneity by meta-regression on race/ethnicity, the African (Egyptian) cohort with MTHFR C677T variants had a higher ASD susceptibility than Asian or European cohorts in most models, though this susceptibility difference was not observed between Africans and Europeans for the homozygous case (TT vs. CC). Similarly, the African (Egyptian) cohort with MTHFR A1298C variants also had a higher ASD susceptibility than Asian or European cohorts in most models, though this susceptibility difference was not observed between Africans and Asians for the homozygous case (CC vs. AA). Conclusions: Our findings support previous analyses that identified a statistical association between ASD and the MTHFR C677T variant but none between ASD and the MTHFR A1298C variant. We also reveal a greater potential for these variants to exacerbate ASD phenotypes in an African (Egyptian) cohort. Future studies should assess the mechanistic contribution of these variants to MTHFR function, especially potential hypomorphic sensitivity in individuals with African (Egyptian) ancestry.

Background/Objectives: Parkinson's disease is the second most common neurodegenerative disorder, affecting patients' daily lives in multiple domains, including functional status, health-related quality of life, and psychological well-being. This study examined the relationship between self-reported global activity level, functional status, Health Related QoL (HRQoL), and psychological state among patients with Parkinson's disease in Greece. Methods: Thirty volunteers (mean age = 69.07, SD = 11.24), members of the Greek Parkinson's Patients and Caregivers Association, completed (a) the Parkinson's Disease Questionnaire to evaluate HRQoL and (b) the Hospital Anxiety and Depression Scale (HADS) to assess psychological state. Participants then performed (a) the Five Times Sit to Stand Test (FTSST) and (b) the Berg Balance Scale (BBS) to evaluate functional status. All questionnaires and the test used in the present study have been validated in Greek. Correlation analysis with Spearman r tests with Bonferroni correction was performed between the above variables. Subsequent linear regression models were used to identify independent predictors of HRQoL and balance using SPSS 29.0.2.0. Results: Participants reported elevated anxiety (M = 9.67, SD = 4.44) and depressive symptoms (M = 8.97, SD = 4.08), alongside relatively high HRQoL scores (M = 40.09, SD = 18.40). Impaired functional performance was observed, with 22 participants failing to complete the FTSST within 16 s and 16 scoring below 40 on the BBS. Functional status was strongly correlated with HRQoL (r = -0.696, p < 0.001) and activity level (r = -0.521, p < 0.008). Depression was also significantly associated with poorer HRQoL (r = 0.618, p < 0.008) and lower activity levels (r = -0.545, p < 0.008). Regression analyses revealed that balance (β = -0.526), disease duration (β = 0.437), anxiety (β = 0.411), and lower limb function (β = -0.351) were significant independent predictors of HRQoL (R² = 0.785; F(9, 20) = 12.69; p < 0.001), while HRQoL (β = -0.738) and lower limb function (β = -0.391) independently predicted balance (R² = 0.699; F(9, 20) = 4.72; p = 0.002), suggesting a bidirectional relationship between physical function and subjective well-being. Conclusions: Activity level, HRQoL, functional status, and psychological state in patients with Parkinson's disease are interrelated factors. Increased levels of anxiety and depression, as well as reduced HRQoL, were observed. The findings point to a potentially reinforcing cycle between poor balance and diminished quality of life, with anxiety and age playing key roles. Overall, the results illustrate that functional, psychological, and HRQoL measures interact in complex ways, emphasizing the multidimensional profile of patients with Parkinson's disease. Further studies with larger samples are required to confirm these findings.

Background: Autism Spectrum Disorder (ASD) is a type of neurodevelopmental disorder, and its exact causes are currently unknown. Neuroimaging research suggests that its clinical features are closely linked to alterations in brain functional network connectivity, yet the specific patterns and mechanisms underlying these abnormalities require further clarification. Methods: We recruited 36 children with ASD and 36 age- and sex-matched typically developing (TD) controls. Resting-state EEG data were used to construct static and dynamic low- and high-order functional networks across four frequency bands (δ, θ, α, β). Graph-theoretical metrics (clustering coefficient, characteristic path length, global efficiency, local efficiency) and state entropy were applied to characterize network topology and dynamic transitions between integration and segregation. Additionally, between-frequency networks were built for six band pairs (δ-θ, δ-α, δ-β, θ-α, θ-β, α-β), and network global measures quantified cross-frequency interactions. Results: Low-order networks in ASD showed increased δ and β connectivity but decreased θ and α connectivity. High-order networks demonstrated increased δ connectivity, reduced α connectivity, and mixed alterations in θ and β. Graph-theoretical analysis revealed pronounced α-band topological disruptions in ASD, reflected by a lower clustering coefficient and efficiency and higher characteristic path length in both low- and high-order networks. Dynamic analysis showed no significant entropy changes in low-order networks, while high-order networks exhibited time- and frequency-specific abnormalities, particularly in δ and α (0.5 s window) and δ (6 s window). Between-frequency analysis showed enhanced β-related coupling in low-order networks but widespread reductions across all band pairs in high-order networks. Conclusions: Young children with ASD exhibit coexisting hypo- and hyper-connectivity, disrupted network topology, and abnormal temporal dynamics. Integrating hierarchical, dynamic, and cross-frequency analyses offers new insights into ASD neurophysiology and potential biomarkers.