Search Results (1,879)

Background: Electroencephalographic (EEG) functional connectivity analysis requires multiple signal-processing, source-modelling, and statistical steps that can limit its adoption in clinician-led randomised controlled trials (RCTs). NeuroStat was developed as a prototype research tool to integrate this workflow; formal usability validation with clinician end-users has not yet been conducted. Methods: NeuroStat is an open-source Python/PyQt6 desktop application that integrates automated artefact removal (a Generalised Eigenvalue Decomposition for Artefact Identification [GEDAI] pathway and a traditional Artefact Subspace Reconstruction (ASR)/Independent Component Analysis (ICA)/ICLabel pathway), boundary element model (BEM) source localisation using the Desikan–Killiany atlas (68 cortical regions), Phase Lag Index (PLI) connectivity estimation across five canonical frequency bands, and RCT-oriented statistical analysis. Evaluation separated sensor-space and source-space claims: a sensor-level simulation (repeated across five independent random seeds) tested preprocessing robustness, a repeated source-space simulation tested recovery of a known cortical parcel-pair contrast after forward projection and inverse reconstruction, a PhysioNet benchmark tested posterior Desikan–Killiany alpha PLI in 20 healthy adults, and an illustrative application to 20 sessions from a published chiropractic RCT demonstrated real-world workflow applicability. Results: In the sensor-level simulation benchmark, the Traditional pathway achieved a mean absolute error of $0.168\pm 0.017$ PLI units and root mean squared error of $0.219\pm 0.045$ (mean ± SD across five independent random seeds) across all artefact conditions. In the source-space simulation, reconstructed alpha PLI for the known bilateral lateral-occipital parcel pair exceeded anterior control edges across 60 repeated condition runs (mean known-control difference = 0.105 PLI units, 95% CI 0.096–0.114; $t\left(59\right)=22.61$, $p<0.001$). In the PhysioNet source-space benchmark, posterior Desikan–Killiany alpha PLI was higher during eyes-closed than eyes-open rest (Cohen’s $d=0.85$, $p=0.001$; 16/20 subjects showing the expected direction) after ICLabel-enabled preprocessing. In the pilot RCT application, all 20 sessions completed processing without manual intervention, with default-mode network alpha PLI showing a pre-to-post change of +0.071 in the intervention group versus +0.015 in the active control group. Conclusions: NeuroStat integrates preprocessing, source-space construction, connectivity estimation, and statistical reporting within a parameter-logged desktop workflow for EEG functional connectivity studies. Current evidence supports initial technical feasibility, sensor-level preprocessing robustness for one pathway in controlled simulations, source-space recovery of a known parcel-level contrast, source-space sensitivity to an expected posterior alpha resting-state contrast, and error-free processing across 20 real RCT sessions in a pilot workflow demonstration. Formal usability testing, test–retest reliability analysis, participant-specific source-model validation, and clinical-population validation remain necessary before clinician-facing or trial-deployment claims can be made. Full article

Improvement in the in vitro maturation (IVM) of oocyte quality is a gateway to enhancing the efficiency of in vitro embryo production. The anti-Müllerian hormone (AMH) is a crucial hormone secreted by granulosa cells that effectively suppresses primordial follicle recruitment and regulates follicular growth and development. This study was designed to investigate the role of AMH on the IVM of sheep oocytes. In this current study, oocytes in vitro were cultured in media supplemented with AMH. We comprehensively analyzed the impact of AMH on various developmental parameters of sheep oocytes, such as cellular activity, cortical granules (CGs) migration, cytoskeleton and mitochondrial function of oocytes. Furthermore, Smart-seq2 single-cell RNA sequencing (scRNA-seq) was employed to elucidate the oocytes’ development. The results showed that treatment with 100 ng/mL improved the maturation rate of the oocytes, the normal distribution rate of cortical granules and mitochondrial function, while reducing the rate of spindle abnormalities in oocytes. A total of 741 differentially expressed genes (DEGs) were observed between the FSH_12 h and AMH_12 h groups, and 746 DEGs were observed between the FSH_24 h and A+F groups. KEGG pathway analysis revealed that the FSH_12 h and AMH_12 h groups significant enrichment in DEGs were associated with p53, MAPK, PI3K-Akt and TGF-beta signaling pathways, and the FSH_12 h and AMH_24 h groups significant enrichment in DEGs were associated with cAMP, AMPK, Hedgehog and estrogen signaling pathways. These findings suggest that AMH may regulates oocytes IVM via several candidate signaling pathways. Our results provide preliminary clues for exploring the regulatory mechanism of sheep oocyte maturation and optimizing relevant culture systems. Full article

Unloading-induced bone loss is a major medical challenge during long-duration human spaceflight, largely driven by suppressed osteoblast-mediated bone formation, and practical countermeasures are needed. Electromagnetic stimulation has shown benefits for bone repair, and its non-invasiveness supports potential space use; however, its single-modality efficacy remains limited. Here, we investigated a combined electromagnetic field (CEMF) integrating a static magnetic field (SMF, 0.4–0.6 T) and a pulsed electromagnetic field (PEMF, 0.38 ± 0.19 mT) to attenuate unloading-related bone loss and examine field-induced mechanical stimulation. Finite-element simulations mapped magnetic flux density, field gradient, induced current density, and Lorentz force density in bone tissue. CEMF was evaluated in vivo in hindlimb unloading (HLU) mice and in vitro in MC3T3-E1 osteoblasts. CEMF improved bone mineral density, trabecular and cortical microarchitecture, and mechanical properties in HLU mice, with increased osteoblast number and mineral apposition rate. In vitro, CEMF promoted osteogenic differentiation and upregulated COL1A1 and RUNX2. Transcriptome analysis suggested activation of ECM–integrin mechanical signaling and the PI3K–AKT pathway. These findings indicate that CEMF-induced multiphysics stimulation enhances osteogenic responses and may serve as a complementary, non-invasive countermeasure for spaceflight-associated bone loss. Full article

Background: Immune mechanisms are increasingly implicated in the heterogeneity of schizophrenia spectrum disorders. Cytomegalovirus (CMV), a latent immunomodulatory herpesvirus, is linked to cognitive and immunological alterations, but its electrophysiological correlates remain largely unexplored. This study investigates the relationships among CMV serostatus, EEG features, inflammatory markers, and clinical–cognitive variables. Methods: In this prospective cross-sectional study, 123 patients with schizophrenia spectrum disorders underwent integrated clinical, cognitive, laboratory, and qualitative visual EEG assessments. CMV exposure was determined via IgG serology. Results: Global electroencephalographic EEG organization did not differ by CMV serostatus. However, a descriptive increase in resting-state sharp-wave discharges was observed in CMV-seronegative patients, independent of baseline cortical rhythms. Immunologically, CMV-seropositive individuals exhibited significantly higher total leukocyte counts, consistent with latent viral immune remodeling rather than overt systemic inflammation. Clinically, CMV-seropositive patients demonstrated descriptively higher scores on the disorganization dimension derived from the PANSS (Positive and Negative Syndrome Scale) five-factor consensus model. While these variations did not retain statistical significance after multiple testing correction, separate dimensional analyses revealed that patients exhibiting sharp waves demonstrated better overall cognitive functioning and superior performance within a memory-related item grouping. Notably, the presence of sharp-wave activity was independent of both peripheral inflammatory profiles and treatment-resistant status, underscoring a distinct electrophysiological phenotype. Conclusions: CMV exposure represents a modulating biological background associated with corrected leukocyte elevations and subtle electrophysiological variability, rather than a direct determinant of global clinical severity. The nominal EEG variations and their independent link to better-preserved memory performance highlight non-linear neuroimmune interactions. Given the cross-sectional design, these exploratory patterns warrant a non-causal interpretation but outline a foundation for future longitudinal investigations. Full article

Chronic kidney disease (CKD) is common in older cats, but cortical transcript-level relationships among hypoxia response, iron handling, and lipid oxygenation are poorly defined. This analysis-plan-guided, hypothesis-generating secondary analysis used public feline renal RNA-seq data (GSE303653). The internal plan fixed the gene panel, composite construction, primary inferential test, and quality-control thresholds before the review of the present expression results, but was not publicly registered. After technical quality control, 21 renal cortex samples from control, CKD 1/2, and CKD 3/4 cats were analyzed. A 23-gene panel and whole-transcriptome differential expression were evaluated using likelihood ratio testing as the primary panel-level screen, with pairwise DESeq2 contrasts, Spearman summaries, enrichment, medulla, composite, and marker-set analyses as secondary or exploratory context. VEGFA, FTL, and NCOA4 decreased with ordinal disease group, whereas ALOX5 and HIF1A increased; eight panel genes were stage-associated by likelihood ratio testing. The equal-weight composite was nonmonotonic. Advanced CKD enrichment was dominated by immune and inflammatory terms, while GPX4 and ferroptosis-pathway enrichment were not stage-significant. The findings support heterogeneous transcript-level remodeling, including ALOX5-associated inflammatory/lipid-oxygenation signal and HIF1A–VEGFA divergence, rather than evidence of ferroptotic cell death, pathway activation, or cell-specific mechanism. Full article

Accumulation of aggregated amyloid beta (Aβ) species is a defining pathological hallmark of Alzheimer’s disease and is associated with extensive neuronal structural abnormalities. Mild cognitive impairment (MCI), a transitional stage between normal aging and the onset of dementia, is thought to represent an early phase of this pathological continuum. Studies at the cellular level suggest that the conditions impair the maintenance of established neuronal processes/networks and restrict their capacity for elongation or re-elongation. They may also attenuate the activation and process extension of quiescent neural progenitor or stem-like cells. These early cellular changes precede overt neurodegeneration in neural tissue and are likely to contribute to cognitive decline. They highlight the importance of in vitro models for identifying molecular targets involved in recovery from disease. In this study, we investigated the effects of aggregated Aβ (25–35) on neuronal process elongation and associated intracellular events in the N1E-115 cell line, a widely used model of neuronal differentiation. Addition of aggregated Aβ to cultured N1E-115 cells attenuated process elongation in a concentration-dependent manner. This morphological impairment was accompanied by decreased expression of neuronal differentiation markers. In contrast, at the half-maximal inhibitory concentration for process elongation, long-term cultured cells did not exhibit apparent process retraction or degenerative morphology. This mild but progressive impairment, without extensive cell death, is consistent with the cellular features of early-stage conditions rather than advanced Alzheimer’s pathologies. Similar results were observed in primary cortical neurons. Aβ also decreased the level of GTP-bound Ras and phosphorylation of the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). Furthermore, treatment with hesperetin, a bioactive flavonoid compound, recovered the Aβ-induced inhibition of neuronal process elongation. Hesperetin also restored Ras and MAPK/ERK states, suggesting that its effects are associated, at least in part, with modulation of signaling through Ras and MAPK/ERK. Our findings suggest that hesperetin may serve as a useful molecular probe for modulating early cellular responses associated with Alzheimer’s disease-related pathology. This in vitro model might serve as a useful platform for investigating the molecular target candidates involved in recovery from nervous system disorders. Full article

Background/Objectives: A current debate addresses where syntactic Merge primarily resides: the left-hemisphere posterior inferior frontal gyrus (IFG) or the temporo-parietal cortex. For proponents of the former, the temporo-parietal cortex supports more effortful processing; for the latter, the IFG supports integration and conflict resolution. We examine aperiodic activity in processing wh-filler-gap dependencies in French for evidence from network dynamics addressing engagement in syntax across L1 and L2. Methods: We extracted aperiodic activity 1/f components (considering offsets as a reflection of neuronal spiking and exponents as a reflection of excitatory–inhibitory balance) out of power spectrum density at 0.5–40 Hz across occipital and bilateral frontal and temporo-parietal regions of interest (ROIs) in reading. Results: Greater exponents arose in temporo-parietal than frontal ROIs in L1 and L2, with strong spiking and regulation suggested by greater offsets and exponents in the occipital ROI in L2—unlike L1—and with potential modulation by L1–L2 representation overlaps. These patterns suggest distributed cell assemblies for L1 and L2 processing. Increased regulation in temporo-parietal ROIs across L1 and L2 cell assemblies might suggest a structural function across temporo-parietal cortices in syntactic processing. Conclusions: Aperiodic activity reflecting connectivity in L1 and L2 processing supports distinct L1 and L2 cell assemblies, with L2 patterns suggesting potential overlap between L1 and L2 circuit modules. Greater exponents in bilateral temporo-parietal ROIs across L1 and L2 indicate increased regulation, supporting the engagement of lateralized temporo-parietal cortices in computations. These effects are discussed by considering advances in syntactic theory and the biology of language readiness. Full article

Background: Tinnitus is a prevalent auditory disorder associated with maladaptive cortical plasticity and aberrant neural synchronization across auditory and non-auditory brain networks. Acoustic desynchronization-based sound therapies, such as coordinated reset neuromodulation, aim to counteract pathological oscillatory patterns but commonly require prolonged daily listening sessions and specialized delivery formats, which may limit their accessibility and practicality in routine clinical settings. To address this limitation, a modified desynchronization protocol embedding therapeutic tones within music was developed to improve tolerability and engagement. This study aimed to evaluate the clinical effects of modified Music-Integrated Desynchronization Sound Therapy (mMIDST) on tinnitus severity in patients with chronic tinnitus. Methods: In this prospective, randomized, controlled, single-blind pilot trial conducted at the Otolaryngology Department of Hospital Clínico Universidad de Chile (Santiago, Chile) between July 2024 and July 2025, adults aged 18–75 years with chronic non-pulsatile tinnitus were assigned to receive either mMIDST or an active control intervention consisting of low-frequency stimulation (LFS) embedded within identical music tracks. Participants listened to personalized sound files for one hour daily, five days per week. Tinnitus severity was assessed using the Tinnitus Handicap Inventory (THI), with audiometric evaluations performed at baseline and after one, two, and three months. Between-group differences were analyzed using the Mann–Whitney U test. Results: Twenty-five participants completed the study (15 mMIDST, 10 LFS). Baseline audiometric thresholds and THI scores were comparable between groups. The mMIDST group showed significantly greater reductions in THI scores than the LFS group at two and three months of treatment (p < 0.05). Conclusions: mMIDST was associated with time-dependent improvements in tinnitus-related distress compared with an active control condition. Embedding desynchronization-based tonal stimulation within music may represent a promising and well-tolerated non-invasive approach for chronic tinnitus management. Full article

Metabolic dysfunction and proteinopathy are hallmarks of neurodegenerative disease, yet their mechanistic interplay remains poorly understood. Here, we show that loss of the neuronal NAD⁺-synthesizing enzyme Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) disrupts amyloid precursor protein (APP) processing in cortical neurons, leading to accumulation of APP C-terminal fragments (APP-CTFs). NMNAT2 deficiency lowers the NAD⁺/NADH redox ratio coincident with APP-CTF buildup. Temporal profiling reveals a biphasic increase in APP-CTFs, with an initial gradual rise followed by rapid accumulation, paralleling the expansion of differentially expressed proteins. Pathway analysis indicates early activation of JNK/MAPK signaling, followed by late-stage suppression of mitochondrial pathways and induction of endoplasmic reticulum stress and unfolded protein response programs. Seahorse analyses reveal early glycolytic impairment followed by deficits in mitochondrial respiration. Knockdown of the NAD⁺ hydrolase sterile alpha and TIR motif-containing protein 1 (SARM1) restores mitochondrial function and normalizes APP-CTF levels in NMNAT2 knockout neurons, whereas NAD⁺ supplementation provides only modest rescue. Together, these data demonstrate that neuronal NAD⁺ depletion drives progressive, SARM1-dependent disruption of glucose metabolism and proteostasis, impairing APP processing. The NMNAT2–SARM1 axis thus links metabolic stress to proteinopathy and highlights SARM1 as a central mediator of neurodegenerative dysfunction. Full article

Based on their domain organisation, four proteins from the protist Dictyostelium discoideum have been assigned to the IQGAP family of scaffold proteins. Although these proteins are shorter than animal IQGAPs, their involvement in the regulation of the actin cytoskeleton in cell motility, macroendocytosis, cytokinesis, and adhesion appears to be broadly conserved between these evolutionarily distant organisms. In this article, we show that the putative three-dimensional structure of Dictyostelium IQGAP-related proteins, as predicted by AlphaFold 3, closely corresponds to the C-terminal half of human IQGAP1, thus supporting their common origin. IqgD is the largest IQGAP-related protein in Dictyostelium, with an overall domain organisation similar to human IQGAPs. IqgD is localised in the cell cortex, interacts with F-actin and Rac1 GTPases, and primarily supports cell adhesion to the underlying surface and cell growth on bacterial lawns. DGAP1 and GAPA are truncated proteins that have retained a 700-residue-long C-terminal region of homology compared to their animal relatives. They play important, yet opposite, roles in regulating contractile cortical assemblies comprising F-actin, myosin II, and the actin-bundling proteins cortexillins, which are especially important for cytokinesis and epithelial morphogenesis. Finally, IqgC, although structurally resembling other IQGAPs, turns out to be more closely related to GAP1 proteins from fungi. This multifaceted protein carries RasGAP activity, interacts with several other small GTPases, and positively regulates macroendocytosis and cell–substratum adhesion. Full article

Symmetrical resistance training induces corticospinal and cortical network plasticity; however, the neural consequences of asymmetrical resistance training (offset loading or OL) remain unclear. In this preliminary study, fourteen healthy adults completed eighteen supervised upper-extremity training sessions over a 6-week intervention period. Participants were allocated to either an offset loading (OL) intervention group (n = 8) or a conventional symmetrical resistance training active control group (AC; n = 6). Electroencephalography (EEG) recordings were acquired during motor task performance at baseline, 3 weeks, and 6 weeks. Directed functional connectivity among predefined cortical regions was quantified, and longitudinal changes were assessed using Friedman tests with false-discovery-rate correction for multiple comparisons. Significant changes in the OL group were observed involving two cortical pathways after correction for multiple testing. Connectivity from the right parietal cortex to the right sensorimotor cortex increased over time (Friedman χ² = 8.00, q = 0.037), with post hoc analyses showing a significant increase between the midpoint and post-training assessments (q = 0.047; effect size r = 0.894). No significant longitudinal changes in cortical connectivity were identified in the AC group. Six weeks of OL training was associated with selective strengthening of directed connectivity within prefrontal-to-sensorimotor and parietal-to-sensorimotor cortical pathways. In contrast, conventional symmetrical resistance training was not associated with detectable changes in connectivity. These findings suggest that asymmetrical loading may induce task-specific reorganization of cortical networks involved in sensorimotor processing and motor control. Full article

Spinal cord injury (SCI) is frequently accompanied by abnormal muscle tone and spasticity, which impair voluntary motor control, mobility, and quality of life. Although classically defined as velocity-dependent hyperreflexia, tone abnormalities after SCI encompass a broader spectrum, including sustained muscle activation, co-contraction, clonus, and non–velocity-dependent resistance to movement. These manifestations arise from distributed changes across spinal and supraspinal motor systems. At the segmental level, SCI induces maladaptive plasticity involving motoneurons, interneurons, sensory afferents, and muscle, including dysregulated persistent inward currents, altered inhibitory neurotransmission, afferent hyperexcitability, synaptic reorganization, and structural muscle remodeling. In parallel, supraspinal adaptations—including cortical motor map reorganization, reduced intracortical inhibition, corticospinal–reticulospinal imbalance, loss of monoaminergic modulation, and altered brainstem and cerebellar regulation—further amplify spinal circuit gain and impair inhibitory control of tone. Current pharmacologic treatments largely suppress symptoms without addressing these underlying circuit changes, while invasive neuromodulatory strategies are limited by surgical risk or state-dependent effects. This review synthesizes emerging insights into the multilevel mechanisms regulating abnormal tone after SCI and examines neuromodulatory approaches targeting spinal and supraspinal networks. Particular attention is given to transcutaneous spinal cord stimulation (TcSCS), a non-invasive method capable of modulating segmental reflex circuits and descending control pathways. Advances in transcriptomic and epigenetic profiling may further enable mechanism-based therapies and biomarker-guided strategies for treating spasticity. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder traditionally defined by dopaminergic neuronal loss and Lewy body pathology; however, increasing evidence indicates that metabolic dysfunction contributes to both motor and non-motor manifestations of disease. While metabolomics studies in PD have largely focused on peripheral biofluids or subcortical brain regions, metabolic remodeling within cortical regions critical for cognition remains poorly characterized. Here, we applied LC-MS/MS-based untargeted metabolomics to post-mortem frontal cortex tissue from PD and neurologically normal control donors, with statistical models adjusted for age, sex, and post-mortem interval. A total of 893 metabolites were quantified, of which 234 exhibited significant differential abundance following false discovery rate correction. Pathway enrichment and network-based integration revealed coordinated metabolic remodeling characterized by predicted inhibition of β-alanine metabolism and pantothenate-dependent coenzyme A biosynthesis alongside activation of amino acid, vitamin B-dependent, cofactor-related, redox-associated, oxidative stress, and inflammatory pathways. Recurrent alterations in pantothenic acid, β-alanine-related intermediates, arginine- and histidine-derived metabolites, lumichrome, and vitamin B₆-associated species may reflect cortical metabolic perturbations associated with mitochondrial bioenergetic vulnerability and oxidative stress. Together, these findings indicate selective metabolic vulnerability in the PD frontal cortex rather than diffuse metabolic collapse. Full article

Background: Action observation (AO) and motor imagery (MI) are widely used cognitive training strategies. Recent evidence suggests that their combination may enhance motor simulation through synergistic neural mechanisms. However, the effects of this approach on complex whole-body movements in elite athletes remain unclear. Methods: Twenty-seven elite ski jumpers performed AO, MI, and concurrent AO + MI tasks, while cortical hemodynamic responses were recorded using functional near-infrared spectroscopy (fNIRS). Channel-level changes in oxygenated hemoglobin (ΔHbO) were analyzed using one-sample and paired-sample t-tests, with false discovery rate (FDR) correction applied for multiple comparisons. Additionally, mixed-design ANOVAs were conducted to examine the potential modulation of athlete level (master-level vs. first-class). Results: Significant activation was observed only in the AO + MIcondition after FDR correction, primarily in channels corresponding to the precentral gyrus, postcentral gyrus, and middle frontal gyrus. No channels in the AO and MI conditions survived FDR correction. Between-condition comparisons revealed significant differences in several channels located in frontoparietal regions, including the inferior parietal lobule, supramarginal gyrus, and middle frontal gyrus, with AO + MIgenerally showing stronger responses. No significant effects related to athlete level were found. Conclusions: These findings indicate that concurrent AO + MI is more effective than AO or MI alone in eliciting cortical activation in elite ski jumpers. This may reflect enhanced engagement of frontoparietal networks involved in action representation and visuomotor integration. These results may be compatible with a neural efficiency interpretation in highly trained athletes, although further studies with behavioral outcomes and broader skill-level comparisons are needed. AO + MI may represent a promising strategy for off-snow cognitive training in high-risk sports. Full article

The entorhinal cortex (EC) is a central structure of the medial temporal lobe, functioning as the main cortical gateway to the hippocampus (HPC) and playing a crucial role in memory, spatial navigation, and temporal representation. This review outlines the distinct yet complementary contributions of its two main subdivisions, the medial (MEC) and lateral (LEC) entorhinal cortices. Despite being historically viewed as functionally segregated, they operate instead in close coordination to support the encoding and retrieval of multidimensional experiences. While the MEC is prominently involved in mapping spatial relationships and movement through specialized cell populations, and the LEC in processing object-related and contextual information, growing evidence shows substantial integration between these domains, challenging strict dichotomies. The MEC encodes elapsed time through persistent firing and time cell sequences, while the LEC signals temporal context via rate remapping; their convergent projections to the hippocampus enable the formation of temporally structured episodic memories. The review assesses recent findings on memory, navigation, and time processing, and highlights how the EC supports each through its layered architecture, local microcircuitry, and widespread interactions with HPC, cortical, and subcortical networks. Moreover, alterations in EC activity patterns emerge as the earliest signs of pathologies such as Alzheimer’s disease and temporal lobe epilepsy. Altogether, this review offers an up-to-date view of the EC not as a set of parallel modules, but as a highly interactive and dynamic system essential for structuring experience across space, time, and context. Full article