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Effects of Exergame Balance Training with Variable Cognitive Motor Challenges on Serum BDNF, p-tau181, and Cognitive Functions in Adults with Mild Cognitive Impairment: A Randomized Trial.

INTRODUCTION: Cognitive-motor exergame balance training may increase attentional demands and neuronal processing, potentially affecting serum levels of brain-derived neurotrophic factor (BDNF), A&#x3b2;1-42, and p-tau181, as well as train cognitive abilities in adults with mild cognitive impairment (MCI). This study aimed to compare the effects of exergame balance training of mild, moderate, high-difficulty, and Wii Fit&#x2122; groups on blood serum levels of BDNF, A&#x3b2;1-42, p-tau181, and cognition function in adults with MCI. METHODS: In this four-arm, parallel group randomized clinical trial, 97 adults with MCI were randomly assigned to exergame balance training groups of mild, moderate, high-difficulty, and Wii Fit exergame as a control group. All participants received 40 min/session, 3 times/week for 8 weeks. Assessment of serum levels of p-tau181, A&#x3b2;1-42, BDNF, and cognitive functions was conducted at baseline, after weeks 4 and 8. A mixed-model analysis of covariance was used, with post-baseline measurements (weeks 4 and 8) specified as the within-subject factor and the corresponding baseline value entered as a covariate to adjust for initial between-group variability. RESULTS: A significant group &#xd7; time interaction was found for BDNF, F(3,92) = 6.413, P = 0.017, &#x3b7;p2 = 0.181; p-tau181, F(3,92) = 4.640, P = 0.040, &#x3b7;p2 = 0.138; attention, F(3,92) = 4.171, P = 0.045, &#x3b7;p2 = 0.057; abstraction, F(3,92) = 4.263, P = 0.043, &#x3b7;p2 = 0.058; and visuospatial skills, F(3,92) = 6.931, P < 0.001, &#x3b7;p2 = 0.234. CONCLUSION: Cognitive-motor challenge-based exergame balance training was associated with an increase in serum BDNF, a reduction in p-tau181. In contrast, the A&#x3b2;1-42 levels remained stable. These changes were accompanied by improvement in selective cognitive functions (attention, abstraction, and visuospatial skills) in individuals with MCI. Greater effects were observed in moderate and high-difficulty groups, suggesting the importance of intervention intensity in promoting cognitive and neurobiological outcomes in MCI.

Humans

Game changer? Cognitive-motor effects of VR exergaming compared to video-based training.

BACKGROUND/OBJECTIVE: Virtual reality (VR) exergaming enhances several cognitive domains through multisensory engagement. Acute cognitive benefits of VR are established, but evidence for direct comparisons with non-immersive controls is limited. This study aimed to determine whether VR exercise provides additional cognitive and cognitive-motor benefits beyond a matched non-immersive active stick-fight video (SFV) intervention, and whether effects persist after training. METHODS: In this randomized quasi-experimental study, N&#x2009;=&#x2009;55 healthy adults (VR: n&#x2009;=&#x2009;30; SFV: n&#x2009;=&#x2009;25; 25.5&#x2009;&#xb1;&#x2009;7.1&#x2009;years; 41.8% female) completed an 8-week program (2&#x2009;&#xd7;&#x2009;30&#x2009;min/week), of VR or SFV matched in movement patterns, frequency, intensity and duration. Measurements included reaction time (RT), Stroop Test (versions 1-3), Letter Cancellation Test (LCT), Trail Making Test (TMT), Trail Walking Test (TWT) and Fitts task (difficulty level 1-4). Data were analyzed using mixed-design ANOVAs. RESULTS: Improvements were observed in Stroop reading (F(1,53) = 14.84, p < .001, &#x3b7;2 = 0.219), Stroop inhibition (F(1,53) = 10.99, p = .002, &#x3b7;2 = 0.172), and LCT (F(1,53) = 4.57, p = .037, &#x3b7;2 = 0.079). A time&#x2009;&#xd7;&#x2009;group interaction was found for TMT (F(1,53) = 6.55, p = .031, &#x3b7;2 = 0.110), indicating greater changes following VR training. Both groups improved cognitive-motor performance (TWT: F(1,25) = 55.32, p < .001, &#x3b7;2 = 0.689; Fitts3: F(1,53) = 44.97, p < .001, &#x3b7;2 = 0.459), with greater gains for VR in Fitts3 (p = .006). CONCLUSION(S): Eight weeks of VR and SFV enhanced cognitive and cognitive-motor performance. VR provided domain-specific advantages in executive function, but these effects were not uniformly persistent. SFV sustained more improvements in real-world-relevant cognitive-motor tasks.

Humans

Response-optimised training improves learning of a complex motor task and closely related motor tasks.

Regular physical exercise is essential for promoting healthy aging and longevity. In older adults with varying physical and cognitive decline, optimising exercise interventions is crucial to maximise benefits. A promising approach to achieve this goal is by adjusting task demands to individual abilities in turn preventing over- or underloading their abilities. In the field of motor learning, it is currently unclear whether such an optimised training improves not only performance on the trained task but also transfers to untrained motor and cognitive tasks. We conducted a randomized, single-blinded, 6-week dynamic balance training (DBT) with healthy older adults (n&#xa0;=&#xa0;30). Training was tailored to individual balance ability. Participants were assigned to either suboptimal (high or low difficulty) or optimal (moderate difficulty) training groups. Transfer effects were assessed via cognitive tasks (memory and executive) and motor tasks (untrained DBT variations and other balance tasks) measured pre-, mid- and post-intervention. Multivariate longitudinal statistical analysis showed higher performance gains in the optimal training group in three out of six sessions compared to the suboptimal groups, especially under testing conditions with high task demands. The optimal group also showed greater improvements in near motor transfer tasks mid- and post-intervention, while no significant differences were observed in the cognitive tasks. Within-group DBT learning positively correlated with transfer gains, highlighting the role of training response in achieving transfer. In conclusion, optimised task difficulty in balance training enhances both task-specific performance and related motor skills, supporting the use of personalised interventions to maintain function and independence in older adults.

Humans

Not just when, but how: An exploratory dual-control approach to video feedback in motor learning.

The present study provides exploratory evidence for a novel dual-control paradigm. It examines whether combining temporal over video feedback timing with learner-controlled interactive playback functions (pause, slow-motion, rewind) would enhance motor skill acquisition beyond temporal autonomy alone. Sixty-four novice adults were randomly assigned to one of four conditions: Full Control (self-controlled timing + interactive replay), Partial Control (self-controlled timing + non-interactive replay), Yoked Full Control (externally controlled timing + interactive replay), or Yoked Partial Control (externally controlled timing + non-interactive replay). Motor accuracy (Radial Error), movement consistency (Bivariate Variable Error), technical execution, and self-efficacy were assessed at pre-test, 24-h retention, and 72-h retention following two acquisition sessions on a dart-throwing task (120 trials total). The Full Control group demonstrated the greatest and most durable learning gains across all outcomes. The Group &#xd7; Time interaction was significant across all dependent variables (&#x3b7;2&#x209a; ranging from 0.140 to 0.234), with Full Control demonstrating superior retention at both 24 and 72&#xa0;h relative to other groups (though differences relative to Partial Control were more pronounced at 72-h retention). Critically, the Yoked Full Control group showed comparatively weaker outcomes despite access to the same interactive playback functions. These findings suggest that interactive video tools may be most useful when learners can regulate both when feedback is accessed and how it is inspected. Theoretical and practical implications for the design of learner-centered video feedback systems are discussed.

Humans

Using the OPTIMAL Theory to Optimize Aerodynamics in Respiratory Training for Healthy Adults and Individuals With Parkinson's Disease.

BACKGROUND: The OPTIMAL (Optimizing Performance Through Intrinsic Motivation and Attention for Learning) theory is a motor learning framework proposing that optimizing intrinsic motivation enhances motor performance and learning. The theory identifies three key components-Enhanced Expectancies (EE), Autonomy Support (AS) and External Focus of Attention (EF)-which facilitate more efficient, goal-directed movement. These components have been shown to improve motor outcomes in limb-based tasks; however, their application to respiratory training, particularly in clinical contexts such as voice and swallowing therapy in patients with Parkinson's disease (pwPD), has not yet been systematically explored. AIMS: This study aimed to investigate whether implementing OPTIMAL theory strategies during a respiratory muscle strength training (RMST) task improves immediate respiratory motor performance in healthy adults and pwPD. Additionally, we aimed to examine the effects of these strategies on motivation and cognitive engagement. METHODS: This quasi-randomized, single-session trial included 47 participants: Healthy CONTROL (n = 17), Healthy OPTIMAL (n = 16) and PD OPTIMAL (n = 14). Healthy participants were quasi-randomly assigned to either intervention or control conditions, whereas pwPD completed the intervention only. All participants completed a single respiratory session that included baseline, practice and retention phases. Outcome measures included peak expiratory flow, cough peak expiratory flow, cognitive engagement (EEG-based Cognitive Engagement Index) and self-administered motivation questionnaire. OUTCOMES AND RESULTS: Exhalation force improved from baseline to retention in the Healthy OPTIMAL group (baseline: M = 296 L/min; retention: M = 338 L/min; p < 0.001) and the PD OPTIMAL group (baseline: M = 315 L/min; retention: M = 370 L/min; p < 0.0001), but not in the Healthy CONTROL group (p > 0.05). No significant changes in cough strength were observed in any group. No correlations were found between cognitive engagement and exhalation force or motivation scores. However, motivation increased more in the Healthy OPTIMAL group (Questionnaire 1: M = 57.2; Questionnaire 2: M = 60.7) and the PD OPTIMAL group (Questionnaire 1: M = 60.1; Questionnaire 2: M = 62.8) than in the Healthy CONTROL group (Questionnaire 1: M = 61.1; Questionnaire 2: M = 62.5). CONCLUSIONS AND IMPLICATIONS: Implementing the OPTIMAL theory enhances immediate respiratory motor performance in both healthy participants and pwPD. OPTIMAL theory has clinical value in voice and swallowing therapy, although further research is needed to establish long-term efficacy and clinical impact. WHAT THIS PAPER ADDS: What is already known on the subject Motivation is a critical factor in rehabilitation. The OPTIMAL theory has been shown to improve both motivation and motor performance in limb-based tasks. Its impact on respiratory training, however, has not been previously examined. What this paper adds to the existing knowledge This study shows that applying OPTIMAL strategies during a respiratory muscle strength training task significantly improved peak expiratory flow in both healthy adults and people with Parkinson's disease. What are the potential or clinical implications of this work? Integrating the OPTIMAL theory principles into respiratory therapy may enhance motor outcomes, supporting voice, swallowing and cough rehabilitation.

Humans

Nondominant Hand Training in Laparoscopy for Surgical Interns: Feasibility and Impact.

OBJECTIVE: Laparoscopy requires bimanual proficiency, yet early trainees demonstrate underdeveloped nondominant hand (NDH) performance. Although deliberate practice of NDH skill contributes to overall performance, NDH training is rarely incorporated into residency simulation curricula and has not been formally evaluated in surgical trainees. We assessed feasibility and impact of integrating structured NDH training with established laparoscopic curriculum for surgery interns. DESIGN: Prospective, single-institution randomized pilot study. Interns were assigned the standard 4-week curriculum of laparoscopic dominant hand and bimanual tasks (Control) or completed assigned NDH tasks in addition to the standard curriculum (Intervention). Feasibility was determined by assigned task completion, daily standard and NDH-specific self-reported practice time, and improvement in bimanual task performance. Performance was video recorded weekly and assessed by blinded evaluators using MISTELS and GOALS scoring. Cognitive workload during laparoscopic tasks was measured via NASA-TLX. Exploratory analyses were conducted within a Bayesian framework. SETTING: A single academic institution with a surgical simulation training program. PARTICIPANTS: General surgery interns on their 4-week simulation rotation. RESULTS: Eleven general surgery interns (6 intervention, 5 controls; all right-hand dominant) completed the study with 100% task completion and practice log compliance. Both groups improved in bimanual performance and perceived cognitive load. Reduction in cognitive workload during bimanual task performance was greater in the NDH group. Time spent on NDH practice over 4 weeks was associated with improved bimanual performance, independent of time spent on standard curriculum tasks. CONCLUSIONS: Structured NDH training is feasible to implement within an existing curriculum and reduces perceived cognitive workload during bimanual laparoscopic tasks. NDH practice demonstrates a beneficial dose-response relationship with performance, supporting its integration into early laparoscopic training.

Laparoscopy

A systematic review and meta-analysis of visuospatial attentional deficits in Parkinson's patients.

Parkinson's disease (PD) is a neurodegenerative condition primarily characterized by motor deficits, yet cognitive impairments are increasingly recognized. While deficits in executive functioning are well documented even in the absence of cognitive decline, evidence of attentional deficits in PD remains inconsistent, and the role of motor symptom lateralization is unclear. In this systematic review and meta-analysis, we examined visual attention in right-handed, cognitively unimpaired idiopathic PD patients, focusing on the canonical attentional domains (sustained, selective, divided) and processes (alerting, endogenous and exogenous orienting, reorienting), as well as visuospatial bias. Four databases were searched for studies comparing PD patients with healthy controls. Meta-analytic estimates were derived using Hedges' g within random-effects models, and studies that could not be quantitatively integrated were summarized narratively. In addition, studies directly comparing patients with left- and right-predominant motor symptoms (LPD vs. RPD) were reviewed qualitatively. Across 51 studies, PD patients exhibited deficits in sustained, selective, and divided attention. Among attentional processes, only exogenous orienting was impaired, whereas alerting, endogenous orienting, and reorienting were preserved. Findings from the few studies examining visuospatial bias indicated small, context-dependent shifts in spatial attention rather than a consistent directional bias. These findings indicate that PD patients show visual-attentional impairments, particularly under high-demand conditions, while basic alertness and voluntary orienting appear preserved. Exogenous orienting deficits and subtle rightward spatial tendencies in LPD suggest disruption of right-hemisphere attentional networks. These results have implications for early cognitive assessment, rehabilitation strategies, and understanding the neural bases of attentional dysfunction in PD.

Humans

Exercise with motor cortex high-definition transcranial direct current stimulation enhances cardiovascular efficiency and lower-limb function in multiple sclerosis: A crossover, double-blind, and proof-of-principle study.

Combining exercise with high-definition transcranial direct current stimulation (HD-tDCS) could offer a strategy to help people with Multiple Sclerosis improve outcomes. In this crossover study, participants with MS (Expanded Disability Status Scale &#x2265;3.0, n&#x202f;=&#x202f;12) and controls (n&#x202f;=&#x202f;10) completed baseline testing, followed by three randomized experimental conditions: 1) exercise+active HD-tDCS; 2) exercise+sham HD-tDCS; and 3) HD-tDCS alone. Exercise performance metrics [heart rate, work rate, heart rate-to-work rate (HR/WR) ratio, and perceived exertion] were compared across the exercise conditions. Secondary outcomes included the Symbol Digit Modalities Test (SDMT), Timed 25-Foot Walk (T25F), Nine-Hole Peg Test (9HPT), and acute symptom ratings (fatigue and pain), assessed pre-, immediately post-, and 1h-Post. Cardiovascular efficiency (HR/WR ratio) significantly improved during exercise+HD-tDCS compared to exercise alone, particularly in older MS participants (p&#x202f;=&#x202f;0.010). SDMT declined immediately post HD-tDCS alone, 1h-post-exercise alone, and at both time points during exercise+active HD-tDCS (p&#x202f;<&#x202f;0.05). Both groups increased walking speed only post-exercise+active HD-tDCS, while no condition affected upper-limb function (p&#x202f;<&#x202f;0.05). These results are in line with the tDCS literature in the general population, suggesting that tDCS improves exercise performance and selectively improves engaged motor function. The trade-off between physical and cognitive outcomes underscores the importance of personalized neuromodulation strategies in neurorehabilitation to maximize therapeutic benefits while minimizing adverse effects, and warrants further large-scale, long-term investigations of this approach in MS.

Humans

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (&#x394;CAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p&#x202f;=&#x202f;0.049), particularly for those with higher non-planning impulsivity (p&#x202f;=&#x202f;0.012). In participants randomized to CPT improvement in PTSD symptom severity (&#x394;CAPS) was negatively related to baseline total impulsivity (p&#x202f;=&#x202f;0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (&#x3b2;&#xa0;=&#xa0;-0.45; 95%CI[-0.70, -0.19]; FDR-p&#xa0;=&#xa0;0.003) and verbal memory (&#x3b2;&#xa0;=&#xa0;-0.45; 95%CI[-0.72, -0.18]; FDR-p&#xa0;=&#xa0;0.003). Significant time &#xd7; group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans

Clinical efficacy and brain mechanism characteristics of guide chi and regulate spirit tuina therapy in the treatment of post-stroke walking dysfunction: A randomized controlled trial based on fNIRS.

BACKGROUND: This study aims to preliminarily evaluate the role of Guide Chi and Regulate Spirit(GCRS) Tuina in enhancing walking function in post-stroke patients with walking dysfunction; secondly, by using functional near-infrared spectroscopy (fNIRS), it investigates the effect of GCRS Tuina on the restoration of brain function in this patient population. METHODS: Participants in the control group received 4-week rehabilitation treatment, while those in the Combined Tuina Group (CTG) additionally received GCRS Tuina therapy for another 4 weeks on this basis. Functional Ambulation Category (FAC), Fugl - Meyer Assessment Scale for Lower Extremity Motor Function (FMA - LE), and Modified Barthel Index (MBI) were evaluated at the baseline and after 4 treatment weeks. A gait and motion analysis system was used to measure step length, stride, walking speed, and step frequency. FNIRS was used to measure the resting-state functional connectivity(FC) strength, as well as the &#x3b2; - value and HbO2 concentration mean during the walking task. RESULTS: A total of 60 participants completed the randomized, and 53 completed the trial and entered the statistical analysis. Compared with the Single Rehabilitation Group(SRG), the CTG group had higher FAC, FMA-LE, and MBI scores after 4 weeks. After the treatment course, the standardized step length, stride, walking speed, and step frequency of the CTG were higher than SRG. At the Region of Interest(ROI) level, the CTG exhibited 13 inter-ROI FC strengths that were higher than SRG, and the differences could survive the FDR correction (PFDR<0.05). Under the walking task, the CTG group had higher &#x3b2; values in 18 channels and higher Oxyhemoglobin(HbO2) concentrations in 19 channels than the SRG (PFDR <0.05). CONCLUSION: GCRS Tuina therapy can significantly improve patients' walking function, enhance lower limb motor ability and daily living ability. It can improve walking efficiency. Tuina can significantly increase the FC and enhance the activation levels and HbO2 concentrations. The stimulation of Tuina may help reconstruct the brain's motor control network, restore impaired motor function, promote the occurrence of neural plasticity, strengthen the neural circuits in the cognitive-motor-sensory cortex to improve walking function. TRIAL REGISTRATION: This study has been registered with the International Traditional Medicine Clinical Trial Registry (ITMCTR2024000654).

Humans

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (&#x3c7;), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA&#xa0;=&#xa0;5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated &#x3c7; in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific &#x3c7; alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

Humans

RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.

In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging predisposes neurons to dysfunction remain incompletely understood. While genomic instability, proteostasis decline, mitochondrial dysfunction, and chronic inflammation have dominated prevailing models, recent evidence highlights RNA dysregulation as a central component of age-associated decline. In this review, we summarize recent findings suggesting that aging progressively erodes RNA regulatory fidelity through alterations in RNA-binding protein abundance, localization, biophysical behavior, and RNA interactions. We argue that age-dependent RNA dysregulation represents an important mechanism that converges with genetic risk to drive neuronal vulnerability and neurodegeneration.

RNA dysregulation

Multi-centre randomised controlled feasibility trial with embedded process evaluation of a samba percussion intervention for people living with Parkinson's disease: a protocol for the Sparky Samba trial.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder, its principal symptom being deterioration of motor function. Current treatment options are limited to symptom management but there is evidence that physical activity can provide motor benefits. More recently there is evidence to suggest that rhythmic auditory stimulation may improve gait and balance in PD. Sparky Samba is a community initiative in South Wales, UK, founded by a person living with PD. Sessions incorporate the following samba rhythms from a trained facilitator and are held weekly in a community setting. METHODS: The Sparky Samba trial is a multi-site, non-blinded, randomised controlled feasibility trial of Sparky Samba compared with activity as usual. A total of 60 people with PD will be randomised 1:1 to take part in a local Sparky Samba group for 12 weeks or continue their normal activities for the same length of time. The primary outcome is feasibility defined by recruitment, retention, data completeness and intervention adherence. Secondary outcomes relating to motor function, cognition, well-being and self-efficacy will also be assessed at baseline and at 12 weeks. Additionally, we will conduct a process evaluation to understand contextual mechanisms surrounding Sparky Samba. This will be achieved through qualitative interviews and structured participant questionnaires following individual trial completion and through structured questionnaires with intervention delivery staff, supplemented with qualitative interviews. ANALYSIS: Feasibility outcomes will be assessed according to pre-defined criteria. For secondary outcomes, means and standard deviations (or medians and IQRs) will be calculated by arm, alongside 95% CIs for change from baseline to 12-week follow-up. Qualitative data will be subject to thematic analysis using NVivo software. ETHICS AND DISSEMINATION: This study received a favourable ethical opinion from the North of Scotland Research Ethics Committee in April 2025 (REC reference 25/NS/0037). Study results will be disseminated through the peer-review literature, the ISRCTN registry and directly to participants, which will be facilitated by the study's public and patient involvement steering group. TRIAL REGISTRATION NUMBER: ISRCTN11861663.

Humans

Use of wearable technologies for physical activity promotion in older adults: A systematic review.

This systematic review, conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251055299), examined the use of wearable technologies for promoting physical activity (PA) in adults aged 60 years and older. Searches across five databases (PubMed, Scopus, Web of Science, CINAHL, Cochrane) identified 2438 records, of which only six randomized controlled trials published between 2021 and 2025 met inclusion criteria, with sample sizes ranging from 36 to 551 participants and mean ages between 65 and 79 years. Given the small number of included studies, findings should be interpreted as preliminary. The studies ranged from the standalone use of commercial trackers (Fitbit, Polar, ActiGraph) to multicomponent interventions combining wearables with physiotherapist feedback, telephone counseling, web-based platforms, or interactive cognitive-motor training. Wearables used alone, as in the REACT trial, produced small or non-significant PA effects. In contrast, interventions integrating devices with personalized feedback, professional support, or digital platforms, such as PROMOTE and TASMANIA, were associated with more consistent improvements in PA, physical function, and cognitive outcomes. Multicomponent programs, such as PEER and ICMT, reported broader benefits, including cognition, balance, and reductions in sedentary behavior, though these findings derive from individual trials and require replication. Risk of bias, assessed with the Cochrane Risk of Bias tool version 2 (RoB 2.0), was rated as "some concerns" for five studies and low for only one, mainly due to gaps in randomization reporting, missing data, and lack of preregistration. Tentatively, and based on a very limited evidence base, wearables may have greater impact when embedded within broader behavioral systems, incorporating feedback, coaching, or interactive components, rather than when used in isolation as passive monitoring tools. Adherence and psychosocial outcomes appeared related to comfort and perceived usefulness among older adults, though larger and more robust trials are needed to confirm these patterns.

Humans

Effects of anodal transcranial direct current stimulation over the right primary motor cortex on a sequential motor finger tapping task in developmental stuttering.

INTRODUCTION: This study investigates the impact of anodal transcranial direct current stimulation (tDCS) on non-speech sequential motor practice in adults who stutter (AWS), compared to non-stuttering controls (ANS). Recent research has explored the effects of tDCS on speech fluency in stuttering. However, its effect on non-speech motor tasks has not yet been studied. METHODS: 20 AWS and 30 ANS right-handed participants were randomly assigned to anodal or sham tDCS conditions, performing a sequential finger tapping task. We targeted over the right primary motor cortex, stimulating at 2&#x202f;mA for 20&#x202f;min. Sequence duration and reaction time were analyzed. RESULTS: AWS analysis revealed that the anodal condition had significantly slower reaction times in the second half of the task compared to sham. For sequence durations, AWS in the anodal condition had slower overall sequence durations than the sham condition. However, there were no block-by-block differences in sequence duration. When comparing AWS and ANS, no significant differences were observed for sequence duration. However, there were significant differences in reaction time between AWS and ANS, specifically in earlier blocks. Additionally, there was no significant Group &#xd7;&#x202f;Condition interaction. DISCUSSION: The findings suggest that anodal stimulation impeded finger sequencing in AWS, showing overall slower sequence durations and a diminishing effect on reaction times in the second half of the experiment, suggesting anodal tDCS may interact uniquely with the neural mechanisms in stuttering. Future studies should explore the effects of anodal tDCS on non-speech motor tasks to gain a broader understanding of its impact on motor control and motor learning.

Humans

Revisiting somatosensory evoked potentials in motor neuron diseases: neurophysiological insights from a large cohort.

OBJECTIVE: To systematically investigate Somatosensory Evoked Potential (SEP) abnormalities in a large cohort of patients with Motor Neuron Disease (MND), and to explore their relationship with Motor Evoked Potentials (MEPs) and clinical phenotypes. METHODS: We retrospectively analyzed 267 patients with confirmed MND who underwent standardized SEPs and transcranial magnetic stimulation. Patients were divided into pure/predominant Upper Motor Neuron (UMN) and pure/predominant Lower Motor Neuron/Amyotrophic Lateral Sclerosis (LMN/ALS) groups. SEP abnormalities were assessed using internal normative data, including prolonged latencies, reduced amplitudes, and increased N20-P25 amplitudes. MEPs were classified semi-quantitatively as normal or abnormal by independent raters. RESULTS: At least one SEP abnormality was detected in 75&#xa0;% of patients, with no significant differences between the UMN and LMN/ALS groups. Increased N20-P25 amplitudes were observed in both phenotypes, suggesting widespread sensory cortical hyperexcitability across the MND spectrum. In contrast, abnormal MEPs were significantly more frequent in UMN patients (p&#xa0;<&#xa0;0.001). No significant association was found between SEP abnormalities and MEP findings. Upper- and lower-limb SEP latencies were strongly correlated (all p&#xa0;<&#xa0;0.001), whereas increased SEP amplitudes did not correlate with latency abnormalities. CONCLUSIONS: SEP abnormalities are highly prevalent in MND and appear largely independent from corticospinal dysfunction. Increased SEP amplitudes likely reflect primary cortical sensory hyperexcitability rather than impaired sensory conduction. SIGNIFICANCE: These findings support the concept of MND as a multisystem network disorder that involves sensory cortical circuits and highlight the role of SEPs in the diagnostic workup.

Humans

Age-related differences in motor unit behaviours and maximal strength: A systematic review and meta-analysis.

Ageing is associated with a decline in strength; however, the neural mechanisms underpinning these changes remain poorly understood. Motor unit discharge rate (MUDR) and recruitment threshold (MURT) regulate the magnitude of motoneuron output through rate coding and orderly recruitment, while discharge rate variability (MUDRV) reflects the steadiness of motoneuron output. Yet, age-related differences in these properties remain inconsistent across the literature. Therefore, this systematic review and meta-analysis quantified age-related differences in motor unit behaviours and their contribution to maximal isometric strength. Electronic databases (Medline, Embase, Scopus, PsycINFO, Ovid Emcare, CENTRAL, and Web of Science) were searched up to May 2025, yielding 1493 records; of these, 48 studies met the inclusion criteria. Standardised mean differences (SMDs) were calculated using random-effects models to compare older and younger adults, and methodological quality was assessed using the AXIS tool. Older adults exhibited markedly lower maximal strength than younger adults (SMD = -1.01; 95% CI -1.22, -0.79). MUDR was lower in older adults across all contraction intensities, with greater reductions at high forces (> 60% maximal voluntary contraction (MVC): SMD =&#x202f;-0.65; 95% CI -0.96, -0.34) compared to low forces (< 30% MVC: SMD = -0.34; 95% CI -0.50, -0.18). Discharge rate variability was greater (SMD = 0.44; 95% CI 0.15, 0.72), whereas recruitment thresholds relative to MVC were lower (SMD = -0.42; 95% CI -0.80, -0.03) in older adults. Collectively, these findings suggest that age-related alterations in motor unit discharge behaviour may contribute, at least in part, to reduced maximal strength in older adults.

Aging