Search Results (5,300)

Spinal muscular atrophy (SMA) therapies that restore SMN expression improve survival and motor function but often fail to fully stabilize distal motor units or sustain endurance. We propose a hypothesis-driven adjunctive approach, intended to complement SMN-restoring therapies, in which localized nanotube-enabled interfaces acting at or near the distal motor unit and neuromuscular junction enhance neuromuscular transmission reliability in surviving, remodeled motor units. The model predicts a temporal cascade: improved junctional reliability and reduced activity-dependent failure, followed by consistent motor unit output across repeated activation, and ultimately, enhanced endurance and functional reserve. Phenotype-specific responsiveness identifies patients most likely to benefit, specifically those with preserved-but-limited residual motor unit substrate accompanied by measurable neuromuscular junction instability. Drawing on shared mechanisms from ALS, spinal cord injury, and other neuromuscular disorders, we discuss mechanistic, translational, safety, regulatory, and ethical considerations. This framework links objective physiological constructs to functional outcomes, offering a mechanistically grounded path for adjunctive therapy development in SMA and related conditions. Full article

Background: Low back pain (LBP) is a leading cause of disability, particularly in young adults. Decreased trunk endurance and altered movement patterns have been associated with lumbar symptoms and functional limitations; however, their concurrent relationships in active populations with minimal disability remain insufficiently characterized. This study was designed as an exploratory cross-sectional analytical study. Methods: The sample comprised 71 physically active university students (mean age, ~23 years; 79% men). Trunk endurance was assessed using the McGill isometric tests, and selected movement-pattern measures were obtained from four Functional Movement Screen (FMS) tasks focused on lumbopelvic control. The total FMS score was calculated, asymmetries were recorded in the Inline Lunge and Rotary Stability tasks, and lumbar-related disability was measured using the Oswestry Disability Index (ODI). Associations were analyzed using correlations and adjusted linear regression, and asymmetry-based comparisons were evaluated using non-parametric tests. Results: The average ODI was very low (approximately 4%), suggesting a floor effect. Greater trunk endurance was associated with lower ODI values, whereas the association between total FMS and ODI was weak and did not reach statistical significance in the adjusted model. Inline Lunge asymmetry was associated with higher ODI values, but this finding should be interpreted cautiously because of the very small subgroup size. Conclusions: In this physically active young adult sample, trunk endurance and selected movement-pattern measures provided complementary descriptive information on lumbar-related function; however, the observed associations were modest and should be interpreted cautiously. Full article

Background: The integration of active breaks during the school day has been widely demonstrated to be effective in counteracting sedentary behaviors. The present study assessed the efficacy of a structured active breaks (ABs) intervention implemented during recess on multiple domains of Physical Literacy (PL) in primary-school children. Methods: A single-blind randomized controlled trial was conducted with 139 children (aged 9–10 years). Classes were randomized into an Experimental Group (EG, n = 66) and a Control Group (CG, n = 73). The EG participated in an 8-week intervention (six sessions/week, ~10 min) consisting of coordinative and interdisciplinary motor tasks during recess. Pre- and post-intervention assessments included physical fitness (SLJ, 4 × 10 m SR, 6MWT, MBT), gross motor skills (TGMD-2), selective attention (Bell Test), physical activity levels (PAQ-C), physical self-perception (PSP), and enjoyment (PACES). Results: A mixed-design MANOVA revealed a significant multivariate Time × Group interaction (p < 0.001). Univariate analyses showed significant improvements in the EG compared to the CG for explosive strength (p < 0.001), agility (p < 0.001), Gross Motor Quotient (p = 0.003), and selective attention (p < 0.001). Furthermore, the EG demonstrated significant increases in physical activity levels, self-perception, and enjoyment (p < 0.05). No significant gender interaction was found, indicating equal effectiveness for boys and girls. Conclusions: Transforming recess into a structured opportunity for movement through ABs effectively enhances physical, cognitive, and affective domains. This intervention represents a sustainable strategy for Health-Promoting Schools to foster PL and psychophysical well-being without reducing curricular instruction time. Full article

This paper proposes a generalized high-order linear active disturbance rejection control (GHO-LADRC) method to suppress non-stationary disturbances in VICTS antenna direct-drive motors during high-dynamic scanning. First, a fourth-order generalized extended state observer is constructed, in which the derivative of the total disturbance is explicitly modeled as an extended state. This configuration enables real-time observation of the disturbance rate of change and suppresses the phase lag inherent in traditional ADRC during rapid disturbance variations through disturbance feedforward compensation. Secondly, drawing on singular perturbation theory and the motor’s dual-time-scale characteristics, this work precisely decouples and explicitly extracts the nonlinear friction and electromagnetic damping terms during the modeling stage. By integrating the extracted electromagnetic damping terms and the disturbance variation rate, an improved model-assisted control law is formulated, enabling active compensation for intense dynamic interference. Theoretical analysis and experimental results demonstrate that the proposed method significantly enhances disturbance rejection capability and satellite communication accuracy. As the first application of GHO-LADRC in the field of direct-drive VICTS antenna control, this work validates its effectiveness in improving system robustness within complex dynamic environments. Full article

Background/Objectives: Freezing of gait (FOG) and sleep disturbances are common in people with Parkinson’s disease (PwPD). A bidirectional association between them has been suggested, but quantitative evaluations are scarce. This study aimed to compare sleep disturbances in mild-to-moderate PwPD with (PD+FOG) and without FOG (PD−FOG), and to assess the association between FOG severity and sleep parameters. Methods: Data from 54 PwPD with disease stage <4 and no severe cognitive decline were included (27 PD+FOG and 27 propensity score-matched for age, sex, and disease duration PD−FOG). Demographics and clinical variables were collected. Clinical assessment included the new freezing of gait questionnaire (NFOG-Q), Parkinson’s Disease Sleep Scale (PDSS-2), Epworth Sleepiness Scale (ESS) and Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Mann–Whitney U, Fisher’s exact and Spearman’s tests were used for group comparisons and correlations, respectively. Results: Significant differences were observed between PD+FOG and PD−FOG groups in MDS-UPDRS part II (p = 0.011) and part IV (p = 0.011), with higher scores in PD+FOG participants. No significant differences were found in PDSS-2 or ESS between the two groups. A significant moderate positive correlation was found between NFOG-Q score and PDSS-2 (ρ = 0.416; p = 0.044) in PD+FOG participants. Conclusions: FOG severity was positively associated with sleep disturbances within the PD+FOG group. However, no significant difference in sleep quality or excessive daytime sleepiness was found between PD+FOG and PD−FOG after propensity score matching. PD+FOG participants experienced more severe motor complications and greater impairment in daily activities compared to PD−FOG. Full article

Background: The absence of disease-modifying treatments for Parkinson’s disease (PD)—a neurodegenerative condition with escalating global incidence—represents a critical unmet medical need. Traditionally utilized for both dietary consumption and medicinal preparations, the fruit derived from Rosa roxburghii Tratt demonstrates a remarkably rich profile of biologically active compounds, with flavonoids, triterpenoids, and organic acids representing the predominant classes. Experimental evidence indicates that these compounds elicit robust antioxidative, anti-inflammatory, and neuroprotective effects, making them promising candidates for neurodegenerative disease modulation. This study aimed to systematically evaluate the neuroprotective effects of Rosa roxburghii Tratt juice concentrate powder (RRJCP) across the preventive, interventional, and therapeutic stages of PD and to elucidate its underlying molecular mechanisms. Methods: Rosa roxburghii Tratt juice was subjected to rotary evaporation concentration and vacuum freeze-drying to obtain the juice concentrate powder. C57BL/6 mice were randomly assigned to three main groups (prevention, intervention, and treatment), each containing subgroups including a normal control, an MPTP model group, low-, medium-, and high-dose RRCJP groups (50, 100, and 200 mg/kg), and a positive control Madopar group, totaling 18 subgroups. A chronic MPTP-induced PD mouse model was established. Motor function was assessed via the open field test, pole test, and wire hang test. Substantia nigra neuronal morphology was examined by hematoxylin and eosin staining. The area of tyrosine hydroxylase (TH)-positive regions was measured by immunohistochemistry. The levels of oxidative stress indicators in serum were measured using biochemical kits. Network pharmacology was employed to predict core targets, and the expression of PI3K/AKT pathway and apoptosis-related proteins was determined by Western blotting. Results: Compared with the MPTP model group, RRCJP (200 mg/kg) significantly increased the total distance traveled in the open field, shortened the pole climbing time, and improved the wire hang score. It attenuated the morphological disorganization and nuclear pyknosis of substantia nigra neurons, increased the TH-positive area and TH protein expression, reduced serum MDA content, and elevated the activities of SOD and GSH-Px. Network pharmacology analysis indicated that the PI3K/AKT signaling pathway was among the core targets. Western blotting results further showed that the juice concentrate powder upregulated the expression of p-PI3K, p-AKT, and Bcl-2, while downregulating Bax and Cleaved Caspase-3 levels, which was consistent with the network pharmacology prediction. Conclusions: RRCJP exerts neuroprotective effects across the preventive, interventional, and therapeutic stages in PD model mice, the mechanisms of which may be associated with activation of the PI3K/AKT signaling pathway, attenuation of oxidative stress, and inhibition of neuronal apoptosis. Full article

Gambling disorder (GD) is a behavioral addiction associated with significant psychosocial consequences and high psychiatric comorbidity, including anxiety, depression, and impulsivity; however, the role of physical activity (PA) as a potential modulator of these alterations remains unclear. The aim of this study was to examine the relationship between PA levels and symptoms of anxiety, depression, and impulsivity in patients with GD. An observational study was conducted with 62 adults diagnosed according to DSM-5 criteria, recruited from AJUPAREVA (Valladolid, Spain). PA was assessed using the International Physical Activity Questionnaire (IPAQ), Personality trails where evaluated with CEPER III, impulsivity with the Barratt Impulsiveness Scale (BIS-11) and the Plutchik Impulsivity Scale, and anxiety and depression with the Hamilton Anxiety (HAM-A) and Depression (HAM-D) scales. Participants were predominantly male (91.5%) and reported moderate-to-high PA levels. No significant differences were found in total impulsivity across PA levels; however, motor impulsivity was higher in highly active individuals, while non-planning impulsivity was greater in those with low PA. Anxiety and depression were highly prevalent (~65%) with no significant associations with PA. In conclusion, PA was not significantly associated with psychiatric outcomes in this clinical sample, highlighting the need for larger, longitudinal studies to clarify its potential role within multidisciplinary interventions for GD. Full article

Spinal cord injury (SCI) is an acute, devastating neurologic condition that results in permanent progressive motor deficits, sensory disturbances, and autonomic dysfunctions, which limit function, participation, and quality of life. Although substantial progress has been made during the last several decades for both early trauma care and rehabilitation protocols following SCI, long-term neurological recovery remains unpredictable and often incomplete. This manuscript summarizes mechanistic and clinical evidence regarding robotic-assisted rehabilitation (RAR) and spinal neuromodulation (SN), which have been published since 2010 until the present time in a structured narrative review of the literature on these two emerging areas for neurorehabilitation after SCI. RAR provides high-intensity, task-specific training that consistently results in improvements in functional outcomes such as balance, coordination, and independence; however, its impact is limited when it comes to walking speed or voluntary motor control. SN (particularly epidural stimulation) can activate the residual neural pathways to standing up and stepping even after a complete injury but effects are typically stimulus dependent, with heterogeneous clinical results that often lack strong long-term evidence due in part to variability in patient selection, stimulation parameters and rehabilitation protocols. However, there is emerging mechanistic data supporting combining modulation of excitability through SN approaches along with structured sensorimotor training as an approach for enhancing recovery. Collectively, these findings support a shift toward more physiology-driven neurorehabilitation strategies and the need for future research to improve clinical translation and outcome predictability by patient stratification using standardized intervention protocols that include longitudinal evaluation. Full article

Neurodegenerative disorders, including Parkinson’s disease (PD), are largely treated with symptomatic therapies, underscoring the need for strategies that target underlying disease mechanisms. Glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R), a class B G protein-coupled receptor best known for metabolic regulation, have attracted interest due to the increasing evidence of central nervous system (CNS) actions. This review synthesises mechanistic, preclinical, and clinical evidence examining GLP-1R signalling in PD and related neurodegenerative contexts. We integrate findings from cellular and animal models with early-phase clinical studies of GLP-1 receptor agonists (GLP-1RAs). Across experimental systems, GLP-1R activation engages conserved intracellular pathways—cAMP/PKA, PI3K/Akt, and ERK—that regulate mitochondrial function, oxidative stress, autophagy-lysosomal dynamics, and inflammatory signalling. In PD-relevant models, these pathways intersect with key pathogenic features, including α-synuclein accumulation, dopaminergic neuron vulnerability, and glial reactivity. Clinical studies to date demonstrate acceptable safety and tolerability, alongside biomarker evidence of central pathway engagement and variable effects on motor and non-motor outcomes. However, uncertainties remain regarding CNS target engagement, peripheral versus CNS mechanisms, and disease-stage dependence. Overall, the current evidence positions GLP-1R signalling as a biologically plausible therapeutic pathway in PD that warrants further mechanistic clarification and rigorous evaluation in ongoing and future clinical trials. Full article

Spinal cord stimulation (SCS) has expanded beyond pain treatment, becoming a neuromodulatory method capable of recruiting spinal and supraspinal circuits involved in motor recovery. This review summarises mechanistic knowledge, supports engineering developments, and describes the changing clinical translation of SCS in rehabilitation. Mounting scientific data shows that SCS’s effects go beyond dorsal column modulation and may involve segmental networks that promote activity-dependent plasticity and sensorimotor pathway restoration, probably due to a combination of Hebbian and non-Hebbian mechanisms (synaptic potentiation, interneuronal reorganisation, and altered afferent–efferent coupling). More recent advances, such as bursts and the high-frequency paradigm, closed-loop control, and data-driven parameter optimisation methods, improve the precision, stability, and calibration of stimulation for each individual. By combining SCS with non-invasive forms of neuromodulation (TMS, tDCS, and peripheral nerve stimulation), one can potentially further intensify corticospinal plasticity and maintain improvements in functions. Spinal cord stimulation remains an established treatment for chronic neuropathic pain, including failed back surgery syndrome and complex regional pain syndrome. In recent years, however, increasing attention has been directed toward its potential role in motor recovery after spinal cord injury and stroke. Progress in this area is limited by patient heterogeneity, variability in outcome measures, the complexity of multimodal rehabilitation protocols, and regulatory and logistical constraints—particularly when adaptive or closed-loop systems are used. Current evidence suggests that motor-restorative applications of SCS should be interpreted cautiously and integrated within carefully designed rehabilitation programmes, with attention to patient selection and realistic expectations regarding the durability of the benefit. Full article

Background and Clinical Significance: Guillain–Barré syndrome (GBS) can rarely progress to fulminant paralysis with loss of brainstem reflexes, mimicking coma or brain death despite preserved cortical function. Case Presentation: A 38-year-old man developed rapidly progressive weakness following a diarrheal illness, culminating in quadriplegia, areflexia, respiratory failure, and complete loss of brainstem reflexes within 72 h. Neuroimaging was unrevealing. EEG demonstrated preserved cerebral activity with an alpha coma pattern. Despite initial intravenous immunoglobulin therapy, neurological deterioration continued, prompting escalation to plasma exchange. Gradual recovery of brainstem reflexes and motor function ensued, followed by substantial functional improvement over nine months. This case highlights the diagnostic and prognostic challenges of fulminant GBS at the interface of peripheral and brainstem dysfunction. Neurophysiologic assessment and disciplined exclusion of central etiologies are essential. Timely immunotherapy and supportive care can lead to meaningful recovery even in extreme presentations. Conclusions: Fulminant GBS should be recognized as a potentially reversible cause of apparent coma, underscoring the importance of early diagnosis and aggressive treatment. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and widespread alterations in brain networks. Circulating biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect neuroaxonal damage and astroglial activation, respectively, but their relationship with large-scale brain connectivity remains poorly understood. Seventy-three PD patients and thirty-four healthy controls underwent diffusion magnetic resonance imaging. Whole-brain tractography was used to reconstruct structural connectivity networks, and graph-theoretical measures were derived. Serum NfL and GFAP levels were quantified, and their associations with network metrics and clinical variables were assessed. PD patients showed significant alterations in global and nodal network organization compared to controls. Higher NfL and GFAP levels were associated with reduced global clustering coefficient and efficiency, as well as increased path length and modularity. At the regional level, higher biomarker levels were associated with reduced network measures in the right thalamus and right cerebellar cortex. No significant associations were observed in healthy controls. These findings demonstrate that circulating biomarkers of neurodegeneration are linked to both global and regional disruptions of structural brain connectivity in PD, supporting the integration of blood-based biomarkers and connectomics to better characterize disease-related network alterations. Full article

As a common brain-computer interface (BCI) paradigm, electroencephalogram (EEG)-based motor imagery provides a critical pathway for both assistive technology to (restoring communication and control) and active rehabilitation (promoting neural plasticity and functional recovery). Domain adaptation has been shown to effectively enhance the decoding performance of motor intentions for target subjects by leveraging labeled data from source subjects. However, EEG data from source subjects often contains extensive personal privacy, and the direct access to source EEG data easily leads to privacy leakage issues. An important research topic is to achieve domain adaptation without directly accessing the source subjects’ raw data. To address this challenge, a privacy-preserving source-free domain adaptation framework, termed Transformer-based SFDA with Class-balanced Multicentric Dynamic Pseudo-labeling (T-CMDP), is proposed for cross-subject motor-imagery EEG classification. This framework consists of three coupled stages. In the source model training stage, a Transformer-based encoder combined with Riemannian manifold-aware feature extraction is employed to learn transferable and discriminative EEG feature representations. In the source-free target adaptation stage, only the pretrained source model is transferred to the target domain and adapted through knowledge distillation and information maximization, without accessing raw source EEG data. In the self-supervised learning stage, class-balanced multicentric prototypes and high-confidence pseudo-label updates are introduced to progressively refine the target-domain decision boundaries. Extensive experiments on three motor-imagery EEG datasets demonstrate that the proposed T-CMDP framework consistently outperforms eleven representative baselines from traditional machine learning, deep learning, and source-free transfer approaches, achieving average accuracies of 56.85%, 76.34%, and 74.49%, respectively. These results indicate that T-CMDP effectively alleviates inter-subject EEG distribution discrepancies and ensures the privacy preserving of source subjects, thereby facilitating more reliable and practical deployment of EEG-based BCI systems. Full article

Children with Autism Spectrum Disorder (ASD) frequently present impairments in executive functions and motor skills, which can negatively affect academic performance, adaptive behavior, and daily functioning. Exergames have emerged as a potentially engaging cognitive–motor intervention. The objective of this systematic review was to analyze the effects of exergame-based interventions on executive function components (particularly inhibitory control and cognitive flexibility) and motor skills in children with ASD. A systematic review was conducted in accordance with PRISMA guidelines, with the protocol registered in PROSPERO. Electronic searches were performed in PubMed, Scopus, Web of Science, and ERIC. Intervention studies published within the last five years and assessing exergame-based interventions in children with ASD were included. Methodological quality was evaluated using the PEDro scale. Six studies met the inclusion criteria. Exergame-based interventions were associated with improvements in executive functions, particularly inhibitory control (reported in two studies using Stroop- and Flanker-type tasks) and cognitive flexibility (assessed in two studies using the Wisconsin Card Sorting Test), although results varied depending on intervention duration and design. Acute interventions (single-session) primarily influenced inhibitory control, whereas longer-term programs showed broader cognitive and motor adaptations. Improvements in motor outcomes, including gross motor development, coordination, and fundamental motor skills, were reported in four studies. Methodological quality ranged from 4 to 6 points on the PEDro scale, indicating fair to good quality. Considerable heterogeneity was observed in intervention protocols, duration, and outcome measures. Exergame-based interventions may represent a potentially promising approach for targeting executive functions and motor skills in children with ASD; however, the current evidence is limited and heterogeneous. Not all included studies assessed both cognitive and motor outcomes, and findings should therefore be interpreted with caution. Further high-quality randomized controlled trials are needed to confirm these effects and establish optimal intervention parameters. Full article

Background: Isolated Generalized Dystonia (IGD) severely reduces quality of life. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is effective for refractory IGD, but the factors influencing efficacy remain unclear. Methods: Twelve IGD patients treated with bilateral STN-DBS (2016–2021) were retrospectively analyzed. Clinical outcomes (BFMDRS, HAMA, HAMD, MOCA, MMSE) were evaluated at baseline and the last follow-up (12–60 months). The electrode position and volume of tissue activated (VTA) in STN subregions were analyzed using Lead-DBS V3.0. Results: STN-DBS significantly improved BFMDRS-M and BFMDRS-D scores (p < 0.001) without cognitive or mood deterioration. BFMDRS-M improvement correlated positively with the VTA of the whole STN and motor subregion (p < 0.05) but not with associative/limbic subregions. The preoperative HAMD score was negatively associated with motor improvement (p = 0.002). Conclusions: STN-DBS safely improves motor function in IGD. Efficacy depends on the VTA within the STN sensorimotor subregion. The preoperative HAMD score may predict the long-term outcome, helping guide patient selection and surgical planning. Full article