Journal of NeuroEngineering and Rehabilitation

Prosthesis non-use and abandonment remain common among people with lower-limb amputation, yet current outcome measures capture only limited aspects of how prostheses are used in everyday life. Clinical assessments are typically conducted in controlled settings and rely on self-report or aggregate activity counts, which do not adequately represent functional performance, physiological effort, or lived experience during real-world prosthesis use. Wearable and ambient sensing offer a means of addressing this gap, but existing approaches tend to measure single dimensions in isolation and are rarely validated against laboratory reference standards before free-living deployment. This protocol describes an integrated multimodal framework for assessing real-world lower-limb prosthesis use across three complementary domains: classification of activities of daily living, estimation of energy expenditure, and assessment of emotional state. Approximately 40 adults with unilateral transfemoral or transtibial amputation complete a two-phase protocol. In the laboratory phase, wearable inertial, physiological, and ambient sensing are validated against established reference standards, including video annotation and indirect calorimetry. In the free-living phase, validated models are applied during a single seven-day home monitoring period, unifying all three domains within one deployment. A defined data harmonisation and quality-control procedure aligns heterogeneous sensor streams and preserves traceability between laboratory calibration and free-living measurement, enabling reproducible interpretation of functional behaviour, metabolic cost, and momentary emotional experience in relation to established clinical outcome domains. By integrating multimodal sensing at the level of study design rather than post-hoc analysis, the framework provides a validated, reproducible methodology for characterising prosthesis use beyond the capacity of conventional instruments, offering a transferable approach for real-world monitoring in rehabilitation research

Objective: To investigate the clinical validity of finger-worn accelerometers for providing a comprehensive assessment of upper-limb motor performance in stroke survivors in real-world environments, compared to wrist-worn accelerometers, and to examine how the clinimetric properties of wearable-based motor performance measures vary with the duration of patient data collection. Design: Cross-sectional observational design. Setting: Research laboratory and free-living environments. Participants: Twenty-seven stroke survivors aged 18-80 years with ischemic or hemorrhagic stroke at least six months prior to enrollment and mild-to-moderate upper-limb impairment without severe range-of-motion restrictions were enrolled. Three participants were ineligible and four withdrew, resulting in a final cohort of 20 participants (N = 20). Interventions: Not applicable. Main Outcome Measures: Wearable-based motor performance measures derived from fine-hand movements, gross-arm movements, and the combination of fine-hand and gross-arm movements captured by finger-worn and wrist-worn accelerometers in naturalistic settings for 6.4 {+/-} 1.8 days. Results: Wearable-based motor performance measures from fine-hand movements demonstrated the strongest convergent validity, known-group validity, and test-retest reliability, followed by those from combined and gross-arm movements. Convergent validity and test-retest reliability of wearable-based motor performance measures improved with longer monitoring durations, with four days being sufficient to obtain accurate and reliable upper-limb measures. Conclusions: Wearable-based motor performance measures from finger-worn accelerometers provide a more comprehensive assessment of upper-limb motor performance than those from wrist-worn accelerometers, supporting their use for real-world monitoring in stroke survivors. Furthermore, the improvements in clinimetric properties of wearable-based motor performance measures with longer monitoring durations highlight the importance of multi-day monitoring to mitigate day-to-day variability and ensure robust assessment.

Purpose: To explore how 12-weeks of robotic walking impacts physical function and sequelae of inactivity for individuals with pediatric-onset neuromotor impairments. Methods: A single-arm mixed-methods interventional study examined robotic walking for 12-weeks in home and community settings, with 12-week follow-up. Outcomes included family goals (Goal Attainment Scale (GAS)) and perspectives (Interviews), postural control (Early Clinical Assessment of Balance), physical activity (Actigraphy, Habitual Activity Estimation Scale, Patient Reported Outcome Measurement Information System (PROMIS) Physical Activity) and sequelae of inactivity (PROMIS Sleep Disturbances, Bowel Function Diary). GAS was collected pre-training, post-training, and 12-week follow-up. All other quantitative outcomes were collected every 4-weeks. Quantitative data are described with median (25th-75thpercentile) and analyzed using a Skillings-Mack test with post-hoc Wilcoxon Signed-Rank. Qualitative interviews were conducted before and after training and analyzed thematically. Results: 15 participants aged 4-23 completed this study. Participants had cerebral palsy (10/15) or rare genetic conditions (5/15), and most used a wheelchair in community settings. Postural control improved (test-statistic = 23.0, p<0.001) after 8 weeks (change=5.0(0.0-21.4), p=0.016) and was maintained through 12-week follow-up (change=13.7(3.1-23.7), p=0.008). Over half of the participants achieved goals (t-score > 50) after training. Exploratory analyses suggest improvements in sleep disturbance immediately after training (p=0.025) and 4-weeks after (p=0.047). All measures of physical activity did not improve. Parents reported improvements in walking, activities of daily living, and sequelae of inactivity (i.e., bowel function, appetite, and sleep). Conclusions: Improvements were seen across a range of measures and notably postural control improvements were maintained at the follow-up. Parents perceived improvements in physical function and activities of daily living. Future research is warranted to further understand the impacts of robotic walking for children and small adults with mobility impairments.

Physical human-device interaction is central to many emerging technologies in neurorehabilitation and assistive robotics, but simulation-based research in this area remains fragmented across musculoskeletal models, assistive-device representations, task definitions, and controller-development workflows. This fragmentation limits the accessibility, reproducibility, and extensibility of studies on prostheses, exoskeletons, wearable rehabilitation devices, and related human-device systems. Here we introduce MyoAssist 1.0, an open-source framework for neuromechanical simulation of physical human-device interaction built within the MyoSuite ecosystem. MyoAssist organizes each simulation environment as a composed human-device-task system that combines compatible musculoskeletal, assistive-device, and task-scenario components through a shared composition pipeline. The current release includes 15 assistive-device models spanning gait assistance, upper-body support, manipulation, and seated mobility and supports compatible musculoskeletal models ranging from reduced lower-limb models to a 416-muscle full-body model. These human-device systems can be simulated within the broad task scenarios provided by MyoSuite, while MyoAssist adds locomotion-specific task scenarios with configurable terrain and target-velocity conditions for gait-assistive studies. MyoAssist also provides two complementary controller-development frameworks: a reinforcement-learning framework for training adaptive policies and a controller-optimization framework for tuning structured, interpretable human and device controllers. Both frameworks operate on the same simulation environments and provide standardized evaluation outputs for inspecting, comparing, reusing, and extending learned and structured control strategies. By integrating modular human models, assistive-device models, task scenarios, and training workflows under a shared open-source interface, MyoAssist aims to lower the barrier to reproducible simulation-based research and to support collaborative development of assistive technologies for neurorehabilitation and physical human-device interaction.

Importance: There are very few interventions designed for individuals with the most severe mobility impairments. Robotic walking may be an effective way to facilitate exercise in this population. Objective: To examine how robot-assisted walkers physical parameters and user characteristics moderate the exercise intensity achieved by individuals with neuromotor disorders causing mobility impairments. Design: A prospective study. Intervention: A single-session intervention involving an overground robot-assisted walker that can be used in an endurance mode requiring no voluntary movement or a strength mode during which voluntary movement could impact the gait pattern. Participants: Individuals with pediatric-onset mobility impairments Main Outcome Measures: Participants were characterized based on their age, sex, diagnosis, and Gilette Functional Assessment Questionnaire (FAQ) levels. Heart rate during the final minute of four 5-minute walking conditions: strength mode at fast speed, strength mode at slow speed, endurance mode at fast speed and endurance mode at slow speed was expressed as a percentage of each participant heart rate reserve (%HRR). Linear mixed-effects models were used to evaluate the impact of speed, device mode and user characteristics on the level of exercise achieved. Results: 29 individuals (aged 2-26 years) with mobility impairments (FAQ levels 1-6) completed this study. Fast speeds were associated with a higher %HRR (beta= 2.11, SE = 1.03, p = 0.044). Participants in FAQ class 1 exhibited significantly higher %HRR compared with those in FAQ classes 2 and 3 (beta=18.6, SE=7.31, p=0.017; beta= 16.9, SE = 8.13, p = 0.047, respectively). No other device or participant characteristics were associated with exercise intensity. Conclusions: To facilitate higher exercise levels, users of robot-assisted walkers can increase their speed. Individuals who cannot take steps due to their neuromotor impairments experience the highest levels of exercise. Relevance: The findings in this study highlight the promise of robot-assisted walkers to improve health, particularly in those who often face the greatest barriers to exercise.

Background: Prolonging ambulation is an important treatment goal in children with Duchenne muscular dystrophy (DMD). Clinical management targets 'actionable' (i.e., modifiable) impairments, such as progressive muscle weakness and contractures, that underlie gait pathology. Gait classification may improve clinical decision-making, but the utility of gait classification in clinical practice depends on understanding how underlying, actionable impairments contribute to distinct gait patterns, which remains insufficiently understood. The research questions were: (1) Can DMD gait patterns be accurately classified from actionable impairments? and (2) Can the model's predictions be explained, and do these explanations provide clinical utility and increase trust in the model? Methods: A retrospective dataset of 274 lower-limb observations from 137 assessments in 30 boys with DMD was analyzed, including 3D gait analysis, instrumented strength assessment, and clinical examination (manual muscle testing, goniometry and clinical stiffness scale). Observations were classified into the mildly affected, tiptoeing, or flexion gait pattern. Ten predictors representing actionable impairments were included: nine predictors related to muscle weakness and contractures, and body mass index (BMI). A balanced random forest classifier was evaluated with leave-one-group-out cross-validation. Model interpretability was explored using SHapley Additive exPlanations to generate global and local explanations. An interview with a clinical expert assessed the utility of the explanations as the primary outcome, with trust in and expectations of both the model and the explanations as secondary outcomes. Results: The model achieved an accuracy of 74.5%. Global explanations identified hip and knee weakness, gastrocnemius-soleus contractures, and BMI as the most important predictors across gait patterns. Local explanations illustrated how patient-specific impairments informed individual predictions. The user study demonstrated the clinical utility of the explanations, as they were perceived as interpretable, provided useful insights, and these insights were actionable. The explanations largely aligned with the expectations and increased self-reported trust in the model. Conclusions: Gait patterns in DMD can be predicted from clinically actionable impairments, and explainable artificial intelligence can translate model outputs into meaningful clinical insights. This approach is promising for supporting both general and personalized rehabilitation and orthopedic strategies aimed at prolonging ambulation in DMD. Further validation in larger, multi-center cohorts is needed.

Purpose: Lower-limb prosthesis use involves interacting physical, psychosocial, and device-related outcomes that may not be fully captured by conventional clinical assessment. This study aimed to develop and evaluate a stakeholder-informed framework of outcome domains relevant to meaningful everyday prosthesis use. Materials and Methods: A mixed-methods participatory design comprised a structured synthesis of selected clinically relevant content from five established patient-reported outcome measures; semi-structured interviews and importance and actionability ratings with 18 contributors (12 prosthesis users, four clinicians, and two industrial partners); and integration of the synthesis, qualitative, and rating findings. Interview records were analysed using reflexive thematic analysis, and ratings were analysed descriptively. Results: The resulting framework comprised four interrelated domains: Mobility, Physical Function, Psychosocial Wellbeing, and Prosthesis Experience. Mobility showed the clearest convergence across stakeholder perspectives. Prosthesis users showed the largest importance actionability gap for Prosthesis Experience (4.5 vs 3.0), whereas clinicians showed the largest gap for Psychosocial Wellbeing (5.0 vs 3.0). Interviews highlighted day-to-day variability in prosthesis use and the influence of confidence, fatigue, comfort, environmental conditions, social context, and device usability. Conclusions: Meaningful outcome assessment in prosthetic rehabilitation should extend beyond mobility alone to consider physical function, psychosocial wellbeing, and prosthesis experience within everyday contexts. The proposed framework provides a stakeholder-informed foundation for multidimensional outcome assessment in prosthetic rehabilitation.

Impaired motor control post-stroke results in reduced walking speeds and increased gait variability. This variability reduces reliability and makes identifying longitudinal changes via gait analysis difficult since changes may occur within the margin of measurement error. We quantified intra-class correlation coefficients (ICC) and minimal detectable change (MDC) in post-stroke individuals and neurotypical individuals walking at matched speeds, to isolate the impact of gait speed and post-stroke impairments on gait-analysis reliability. We collected gait data over two days from N=15 post-stroke individuals walking on a treadmill at their self-selected speed, and from N=13 age- and sex-matched neurotypical controls walking at both their self-selected speed and a speed matched to a post-stroke participant. We calculated ICC and MDC values for spatiotemporal variables, bilateral joint ranges of motion (ROM), and bilateral peak propulsive and peak vertical ground reaction forces (GRF). Spatiotemporal ICCs showed excellent reliability across groups (range [0.813-0.988]), yet MDC values were greater post-stroke than in speed-matched controls. ICCs for joint ROM ranged from poor to excellent reliability across groups ([0.362-0.960]). Post-stroke joint ROM MDCs were 27%-53% of the gait ROM compared to 11%-42% in neurotypical controls. ROM MDCs were greater in the non-paretic compared to the paretic extremity. ICC for peak GRFs showed good to excellent reliability across groups (range [0.778-0.980]), with post-stroke peak GRF MDCs greater than in speed-matched controls. Our results suggest that stroke related neuromotor impairments influence reliability beyond the effects of walking speed alone, and we provide quantitative MDC benchmarks for interpreting gait changes post stroke following clinical interventions.

People with lower limb amputation lack somatosensory feedback from their prosthesis, and this loss contributes to functional deficits, including balance and gait impairments. Recent advances in neuroprostheses have demonstrated that electrical stimulation of sensory nerves in the residual limb and spinal cord can restore lost sensations in the lower limb. To maximize the efficacy of these somatosensory neuroprostheses, the restored sensations should be intuitive, seamlessly integrating into the sensorimotor network. However, it is challenging to quantify the intuitiveness of these evoked sensations. Recent studies have proposed using crossmodal congruency effect (CCE) tasks for this purpose in people with upper-limb amputation. The current study tests the feasibility of the CCE task for assessing the intuitiveness of sensory feedback in the lower limb. We hypothesized that CCE score would reliably differentiate between a more natural (pneumatic) sensation and a less natural (electric) sensation at two locations: the knee and the foot. Across fifteen able-bodied individuals, we observed that the CCE task differentiates sensory modalities at the knee, but not at the foot. Identification of external factors affecting the CCE is needed before it can be implemented to measure intuitiveness of sensory feedback in lower-limb amputees.

Background. Abnormal muscle co-activation, also called abnormal synergies by clinicians, is an important contributor to arm impairment after stroke. While abnormal co-activation is well-described in chronic stroke, it remains unclear how early abnormal patterns appear and whether their spatial and temporal characteristics resemble those seen in the chronic phase. We sought to determine how soon after stroke abnormal muscle co-activation appears. Methods. In this cross-sectional study, thirty-nine participants with hemiparesis in the early subacute period (<21 days) and sixty-eight participants in the chronic period (>6 months) after stroke performed targeted reaching movements while surface electromyography (EMG) was recorded from nine upper-limb muscles. Muscle synergies (patterns of coordinated muscle activation) were identified using non-negative matrix factorization. Synergy composition (spatial structure) and activation profile (temporal structure) were compared across the contralesional arms of subacute and chronic participants and the ipsilesional arm, which served as the reference for normal coordination. Results. Three primary synergies accounted for most EMG variance during reaching in each arm group. A deltoid-dominant synergy characterized by abnormal co-activation of anterior and posterior deltoids, was present in both subacute and chronic stages in the contralesional arm but was absent in the ipsilesional arm. In addition, the elbow flexor synergy co-activated with the deltoid synergy in both contralesional groups but not in the ipsilesional arm. Abnormal co-activation between elbow flexor and elbow extensor synergies was also seen in contralesional, but not ipsilesional, arms. These abnormalities were already present 15 days after stroke and did not differ between subacute and chronic groups. Conclusions. Abnormal muscle co-activation appears within the first few weeks after stroke and persists in chronically impaired survivors. Its full development this early suggests these patterns arise rapidly rather than emerging gradually during recovery, and that interventions targeting abnormal co-activation may be most useful when applied early. Clinical Trial Registration? NCT03401762.

Proprioception can be assessed in several ways, including movement detection, joint position matching, and matching across sensory frames of reference. These task types make different demands, yet they are rarely compared within the same participants on the same device, and psychometric data for wrist-focused batteries are limited. This work had two aims: to compare performance across different levels of proprioceptive judgment, and to establish the within-day test-retest reliability of each. We evaluated three robotic wrist tasks spanning judgments within a single reference frame and across reference frames: joint detection threshold (JDT), same-frame joint-to-joint matching (J-to-J), and cross-frame joint-to-visual matching (J-to-V). Methods. Twenty neurotypical adults completed two identical sessions on the same day, separated by at least two hours, using a single-degree-of-freedom wrist robot. Outcomes were the kinematic detection threshold (degrees) for JDT and the mean absolute matching error (degrees) for J-to-J and J-to-V. Relative reliability was quantified with ICC (2,1) and 95% confidence intervals. Absolute reliability was quantified with the standard error of measurement (SEM) and the smallest detectable change at 95% confidence (SDC 95). Learning effects and differences across task levels were evaluated with paired t-tests or Wilcoxon signed-rank tests. Results. ICC (2,1) was 0.959 [95% CI: 0.900 to 0.980] for JDT, 0.837 [0.640 to 0.930] for J-to-J, and 0.769 [0.500 to 0.900] for J-to-V. The %SEM ranged from 11.9% (J-to-J) to 15.6% (J-to-V). SDC95 was 0.85, 1.71, and 3.54 degrees for JDT, J-to-J, and J-to-V, respectively. A small but significant practice effect was observed for JDT, but this was below the SDC95, and no learning effect was observed for J-to-J or J-to-V. We also observed that the absolute error increased monotonically across task levels, with all pairwise comparisons (JDT < J-to-J < J-to-V; all p < 0.01). Conclusions. All three tasks demonstrated good-to-excellent within-day relative reliability. Error scaled with the computational demand of each task, with the largest errors observed for the cross-frame task, which required a transformation between the visual and joint reference frames. The reported SDC95 values provide task-specific thresholds for distinguishing measurement noise from true change in future intervention studies. Inter-day reliability and validation in clinical populations are the next steps.

Background: Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional primary motor cortex is widely used for post-stroke upper-limb rehabilitation, but treatment response varies substantially. This systematic review and meta-analysis aimed to quantify the efficacy of contralesional LF-rTMS and to examine whether baseline motor impairment severity and corticospinal tract (CST) integrity modify treatment effects. Methods: We searched seven databases from inception to July 2026 for randomized controlled trials of contralesional LF-rTMS ([&le;]1 Hz) versus sham after stroke, with comparable rehabilitation in both arms. The primary outcome was the change in Fugl-Meyer Assessment for the upper extremity (FMA-UE) scores. Random-effects meta-analysis used restricted maximum likelihood estimation with Knapp-Hartung adjustment. Effect modification was examined through meta-regression and biomarker-stratified analyses, and neurophysiological outcomes were also synthesized. Results: Thirty trials (33 comparisons, 1,668 participants) were included. LF-rTMS produced greater FMA-UE improvement than sham (mean difference 4.11 points, 95% CI 2.83-5.39; Hedges g 0.64, 95% CI 0.45-0.84), with substantial heterogeneity. Baseline severity did not significantly modify the effect in continuous meta-regression. However, exploratory within-trial biomarker-stratified analyses suggested larger effects in participants with preserved CST integrity or positive motor-evoked potential (MEP) status. LF-rTMS also shortened MEP latency and central motor conduction time, but these measures could not be validated as surrogate endpoints. Conclusions: Contralesional LF-rTMS provides a statistically significant but modest improvement in post-stroke upper-limb motor recovery. Baseline clinical severity alone may not identify responders, whereas CST integrity is an exploratory, hypothesis-generating candidate biomarker. It requires confirmation in adequately powered biomarker-stratified trials before it can inform clinical decisions. Trial Registration The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD420261441561).

Conventional transfemoral amputation disrupts native neuromuscular pathways, limiting prosthetic joint control, sensory feedback, and the perception of the prosthesis as part of the body. To ameliorate these pathologies, we restored the agonist-antagonist relationship of residual muscles in two individuals with above-knee amputation through an interventional surgical revision. Participants trained with a bionic knee prosthesis before and after the surgical revision while generating neuromuscular, cortical, functional, and affective data. Both individuals demonstrated improvements after the revision that could not readily be attributed to training effects, including: 1) increased proprioceptive afferents and stronger activation in cortical regions associated with sensorimotor integration of their missing joints, 2) improved control of the bionic knee during functional tasks including sit-to-stand and stair ascent, and 3) generally greater prosthesis embodiment, proprioception, and phantom limb definition as assessed through questionnaires and interviews. In contrast, training outcomes were more participant-specific and more variably correlated with amount of exposure, especially before the revision. These pilot findings suggest that revisional augmentation of residual neuromuscular tissues to restore agonist-antagonist dynamics may promote sensorimotor coherence and enhance both functional and perceptual integration with a bionic prosthesis, and remaining participant-specific heterogeneities may be attributable to inter-individual difference in residual limbs neuromuscular system, amputation history, and personal beliefs about prosthesis usage.

Breast cancer survivors frequently experience upper-limb impairments, making continuous monitoring essential for effective rehabilitation. We propose REINA (Recognize-Then-Infer Wearable-to-App AI Framework), a two-stage deep-learning approach for remote monitoring of motor function during breast cancer rehabilitation using wearable-device data. Inertial measurement unit (IMU) signals from wearable devices are first used to recognize physical activities via supervised learning, followed by an activity-specific recurrent neural network (RNN) to infer corresponding electromyography (EMG) signals. REINA establishes reliable inference of neuromuscular activity from wearable IMU data, enabling real-time, cost-effective assessment of motor function recovery in real-world settings.

Pathological tremor is a neurological condition that impairs fine motor tasks, affecting 1% of the general population and 4% of the elderly. Tremors arise when muscles micro-oscillations synchronize and phase lock, typically within a 4-12 Hz frequency range. Administering beta-blockers can reduce tremor severity, but doses are hard to personalize, with heavy doses of propranolol correlating with low blood pressure, dizziness, and nausea. In this project, we aimed to model tremor and create a closed-loop control framework to suppress tremor amplitude while minimizing pharmacological dependence. Because side effects constrain the use of pharmacological suppression alone, we investigated noninvasive neuromodulation. We used vibrotactile stimulation (VTS) to disrupt pathological tremor synchronization and reduce oscillatory amplitude. We hypothesized that tremor suppression involving VTS followed a nonmonotonic relationship, tested by determining whether maximum relief requires an adaptable framework. The procedure consisted of constructing a propranolol-reduction simulation by implementing a Hill curve, where we calculated and utilized tremor reduction, heart rate (HR) drop, and blood pressure (BP) drop. We then built a device to capture tremor-related data and create vibration using two linear resonant actuator (LRA) coin motors. We connected it to a microcontroller, where we determined optimal vibration frequencies through a feedback loop. Across 50 trials, VTS alone reduced tremor amplitude by an average of 37.3%, reducing the propranolol dose needed to reach 50% total tremor reduction by 71.9%, lowering the modeled blood pressure drop from 38.1 to 18.9 mmHg. This device demonstrates proof-of-concept for a nonmonotonic tremor-vibration relationship to reduce dependency on propranolol in the treatment of pathological tremor. These propranolol dose-reduction estimates are derived from computational simulation and have not been clinically validated; they are not intended as a recommendation to alter prescribed medication.

Introduction Post stroke dysphagia is common, associated with poor functional outcome and lacks treatment strategies beyond behaviour therapies delivered by speech & language therapists. Here, we present the statistical analysis plan for the ongoing pharyngeal electrical stimulation for acute stroke dysphagia trial (PhEAST). PES is a candidate treatment for dysphagia present in non-ventilated stroke patients. Methods PhEAST is an investigator-initiated international prospective randomised open-label blinded-endpoint phase-4 superiority trial involving 650 participants with tube-dependent post-stroke dysphagia. Consenting patients are randomised to PES versus no PES given on top of standard care with PES given daily for 6 days. The primary outcome is the dysphagia severity rating scale (DSRS), a measure of swallowing impairment, made at days 14 and 90 and analysed using repeated measures regression. Conclusion We present the statistical analysis plan for the main analyses based on data up to day 90 along with planned secondary analyses including presentation of baseline data, health economics, cognition and extended follow-up to 12 months.

Background Upper limb dysfunction is among the most disabling consequences of stroke, yet transcranial direct current stimulation (tDCS), an extensively investigated adjunct to motor rehabilitation, has not demonstrated consistent benefit in large randomized trials. Unaccounted interindividual variability is a likely contributor, and sex is one plausible source given anatomical and neurophysiological differences affecting tDCS responsiveness. This exploratory post-hoc analysis of the multicenter, randomized, sham-controlled NETS trial examined sex as a moderator of tDCS response. Extending the primary analysis, confined to the primary outcome at end of intervention, all assessment time points were modelled across the 90-day follow-up and outcomes spanning the three domains of the International Classification of Functioning, Disability and Health (ICF). Methods NETS randomized 119 patients with subacute ischemic stroke to anodal tDCS (1 mA) over the ipsilesional primary motor cortex or sham stimulation alongside standardized rehabilitation. Longitudinal mixed-effects models with autoregressive correlation structures examined treatment-by-sex interactions for the Upper-Extremity-Fugl-Meyer Assessment (UEFMA; body function), Box-and-Block Test (BBT; activity), and Stroke Impact Scale participation domain (SIS; participation). Sensitivity analyses included continuous-time models and three-way sex-by-treatment-by-time interactions. Analyses were performed on intention-to-treat (ITT) and per-protocol (PP) populations. Results Treatment-by-sex interactions were found for the UEFMA and BBT, but not for SIS participation. Female participants receiving active stimulation improved more than those receiving sham, with clinically relevant estimated marginal mean differences of 6.0 points (UEFMA) and 8.4 points (BBT). No relevant treatment effect was observed in males for either measure. Results were consistent across ITT and PP populations. Conclusions This exploratory analysis provides preliminary evidence that sex may moderate tDCS response in post-stroke upper limb rehabilitation, with effects extending across ICF impairment and activity domains. Together with converging signals from independent trials, these findings suggest that sex-stratified designs may be necessary to detect tDCS efficacy in stroke rehabilitation.

Background Mirror therapy (MT)-specifically paradigms using mirror visual feedback (MVF)-is widely used in neurorehabilitation; however, mechanistic implementations vary substantially in movement content, rhythmicity and attentional demands. This protocol describes an acute mechanistic, within-participant fNIRS screening study designed to compare three prespecified upper-limb mirror-therapy task paradigms and to quantify associated subjective experience after each condition in healthy adults during a single visit. Methods and analysis This is a single-centre, within-participant, randomised crossover study conducted at Wuhan Wuchang Hospital (Wuhan, China). Healthy adults aged 18-35 years will complete three task conditions once each in a counterbalanced order using a 3*3 Latin-square scheme: UMT1 (task-oriented rhythmic functional movement), UMT2 (open-ended free movement with auditory control), and UMT3 (non-functional rhythmic movement). fNIRS will be acquired using the NirSmart-6000A system during a standardised block design. The primary outcome is ROI-level HbO activation quantified as GLM-derived {beta} estimates within the prespecified primary ROIs (bilateral SM1/M1 and bilateral PMC). Secondary outcomes include ROI-level windowed {Delta}HbO (5-20 s post-onset relative to the immediately preceding rest; descriptive only), ROI-level {Delta}HbR, and post-condition subjective ratings (illusion, immersion, confusion and fatigue; 1-7 Likert). Condition effects will be analysed using linear mixed-effects models with fixed effects for condition and period and prespecified multiplicity-adjusted pairwise contrasts. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Wuchang Hospital Affiliated to Wuhan University of Science and Technology (Approval No.: 2025-112-01; approved on 2025-08-21). The study is expected to be minimal risk. Findings will be disseminated through publication of this protocol manuscript and subsequent results manuscripts and conference presentations. Trial registration number Chinese Clinical Trial Registry (ChiCTR2600116634). This study is conducted as a prespecified mechanistic sub-study under the overarching registered project.

Impaired gait performance and stability is a key symptom often defining disease outcome in people with Multiple Sclerosis. Step-by-step foot placement control in response to variations in the center-of-mass kinematic state is a crucial gait stability mechanism, especially in the mediolateral direction. Even though it is known that people with Multiple Sclerosis are at an increased risk of falling, step-by-step foot placement control remains to be characterized in this population. Here, we explored characteristic foot placement control in ten people with early stage Multiple Sclerosis, compared to 21 controls walking at a similar average gait speed, during 1-minute steady-state treadmill walking. Kinematic data were analyzed using a linear feedback model that correlated foot placement with the center-of-mass kinematic state during the preceding swing phase. People with Multiple Sclerosis demonstrated step-by-step foot placement control in both the mediolateral and anteroposterior directions. No differences were found in foot placement precision between groups. However, foot placement responses to variations in center-of-mass velocity proved stronger in people with Multiple Sclerosis. Moreover, the contribution of mediolateral center-of-mass velocity feedback to the control mechanism was higher in people with Multiple Sclerosis as compared to neurologically healthy controls. Our results suggest that foot placement control is still retained in early clinically evident stages of Multiple Sclerosis, but is realized through differently weighted sensory feedback control.

Static force plates (FP) are the gold standard for measuring ground reaction forces (GRF) and computing joint moments through inverse dynamics in gait analysis. However, they are restricted to controlled environments, and the number of steps analyzed is limited by the plates embedded in the floor. To address these limitations, portable solutions such as sensorized insoles, socks, or shoes have emerged. Yet, creating wearable systems capable of measuring three-dimensional GRF in real-world conditions remains challenging. Current sensorized shoes often incorporate thick sensors (up to 2 cm), reducing usability and limiting their application in pathological populations or dynamic tasks like running. This study evaluates the usability of ShokacShoes, a novel sensorized shoe integrating three thin, three-dimensional force sensors, and explores its potential as a Wearable Force Plate (WFP). Eight healthy participants performed slow, natural, and fast walking using two insole configurations. Force and temporal metrics were derived from WFP and FP data. Results indicate that WFP enables accurate step segmentation and detects significant effects of speed and insole type on temporal and force metrics, confirming its reliability under different walking conditions. Comparisons with FP revealed differences in force metrics and signal morphology, though temporal parameters remained consistent. These results are likely due to sensor quantity and positioning. Thereby, ShokacShoes represent a valid solution capable of measuring three-dimensional forces within commercial footwear. Future work will focus on validating the applicability of a new version of ShokacShoes against gold-standard FP in a comprehensive validation study involving diverse real-world scenarios and pathological conditions.