Neurorehabilitation and Neural Repair

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.

Sensorimotor adaptation is a motor learning process that contributes to movement flexibility and is thought to arise from the interaction of fast and slow adaptive processes. Evidence suggests that declarative memory contributes to adaptation through its influence on the fast process. Although adaptation deficits are common following stroke, the mechanisms underlying these deficits remain unclear. This study investigated differences in locomotor adaptation rate and forgetting between individuals with chronic stroke and age-matched controls and examined how these measures were associated with immediate declarative memory performance. Individuals with chronic stroke (n = 23) and age- and education-matched controls (n = 21) completed four 4-minute bouts of split-belt treadmill adaptation separated by rest breaks. Adaptation rate, adaptation magnitude, and forgetting were quantified from exponential fits to normalized step-length asymmetry data. Immediate declarative memory was quantified using the Repeatable Battery for the Assessment of Neuropsychological Status, and associations between adaptation measures and immediate declarative memory were evaluated using robust linear regression. Participants with stroke adapted less (p = 0.001) and more slowly (p = 0.039) than controls during early adaptation and forgot less of the adapted behavior during the first rest break (p = 0.024). Notably, poorer immediate declarative memory performance was associated with reduced forgetting during the initial rest break, irrespective of group assignment (p = 0.035). This relationship supports the hypothesis that declarative memory contributes to adaptation through a cognitively mediated fast process. These findings suggest that cognitive impairment contributes to altered adaptation following stroke and highlight the importance of considering cognitive factors when investigating motor learning mechanisms and rehabilitation outcomes in neurological populations.

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: 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).

Background: Post-stroke motor impairment is the leading contributor to long-term disability. Despite evidence that high dose, high intensity (HDHI) and virtual reality (VR) interventions are effective in reducing post-stroke motor impairment, access to such interventions is limited, especially in community-based models. The purpose of this study was to explore the effect of one community-based HDHI VR intervention, Next-Generation NeuroAnimation Therapy (NG-NAT), on motor impairment for community-dwelling stroke survivors. Methods: The study employed a retrospective pre-test post-test design of de-identified data sets of one cohort of stroke survivors who participated in an HDHI NG-NAT intervention at a community-based center from March to December 2025. The intervention consisted of three hours of daily therapy, five days a week, for three weeks. Two hours were allocated for NG-NAT gameplay, while one hour focused on non-VR activity. The NG-NAT was provided in a small studio with a large screen monitor and 12 motion caption cameras mapping client movements to play the game. The upper extremity Fugl Meyer Assessment was used to measure motor impairment at pre- and post-testing. Linear regressions were run to determine the relational strength between pre- and post-UEFMA scores. Wilcoxon Signed Rank Tests were run to calculate median differences in pre- and post-UEFMA scores and account for non-parametric data distributions at baseline and the small sample size. Effect size was explored using the Rank Biserial Correlation. Frequency of minimally clinically important differences (MCID), minimal detectable changes (MDC), recovery stage transition were calculated. Content analysis and co-review of documentation contextualized statistical findings. Results: Nineteen participants completed three weeks of intensive NG-NAT. All experienced positive UEFMA score improvements from pre- to post-testing with a median difference of 8 points. Fifteen achieved MDC and MCID; one experienced a ceiling effect. Eight participants transitioned into better recovery stages. There was a highly significant, positive relationship with narrow confidence intervals and pre-score predicted post-score (e.g., those with mild/moderate impairment improved better than those with severe impairment). Conclusion: This study provides evidence supporting the efficacy of NG-NAT as a community-based intervention to reduce motor impairment for individuals with stroke. Given its ability to deliver intense and engaging therapy, NG-NAT offers a promising adjunctive strategy to expand access for stroke survivors to improve clinically relevant health outcomes. These findings underscore the need for pragmatic trials evaluating effectiveness, implementation, and cost-effectiveness.

Background Clinical assessments of Amyotrophic Lateral Sclerosis (ALS) are typically collected infrequently in clinic visits and may not fully capture domain-specific functional decline in daily life. Digital Health Technologies (DHTs) can support remote monitoring, but passive free-living measures often require prolonged wear time and may be influenced by non-motor factors. This study evaluated whether short, standardized, at-home lower limb exercises recorded with ankle-worn accelerometers provide objective and interpretable measures of lower limb disease progression in ALS. Methods We analyzed data from 349 participants with ALS enrolled in the decentralized ALS Research Collaborative Study. Participants completed repeated self-entry ALS Functional Rating Scale-Revised (ALSFRS-RSE) assessments and wore bilateral ankle accelerometers during monitoring periods between September 2014 and January 2023. During each period, participants performed brief seated knee flexion-extension exercises at home. A previously developed signal processing pipeline was used to derive four exercise metrics: count, duration, intensity, and similarity. We examined baseline correlations with ALSFRS-RSE total and subdomain scores, longitudinal change using linear mixed-effects models, associations with gross motor item scores, differences by anatomical site of disease onset, and comparisons with free-living gait metrics. Results At baseline, exercise-derived metrics, particularly intensity and similarity, showed the strongest associations with the gross motor subdomain. Longitudinally, duration increased while intensity and similarity decreased, consistent with progressive slowing, reduced movement vigor, and reduced movement consistency (all p < 0.001); count did not change significantly. Worsening responses to gross motor items related to turning in bed, walking, and stair climbing were consistently associated with fewer, slower, less vigorous, and less consistent lower limb repetitions. Baseline intensity and similarity were lower in participants with lower limb disease onset on the corresponding side. Exercise-derived intensity showed model fit comparable to the strongest free-living gait metrics, while requiring substantially less observation time. Conclusions Short at-home lower limb exercises recorded using ankle-worn accelerometers provide scalable, objective, and interpretable measures of amyotrophic lateral sclerosis-related functional decline. Movement quality metrics, particularly intensity and similarity, may complement passive free-living monitoring and support remote digital clinical outcome assessment in ALS research. Trial registration NCT06885918.

Background: People with chronic stroke retain the capacity to learn new motor skills, yet how preserved motor learning is expressed during practice remains incompletely understood. Sequence learning provides a useful model for examining these within-session learning dynamics and their neural basis after stroke. Objective: To characterize a temporally resolved behavioral phenotype of motor sequence learning in chronic stroke and establish its neural context using task-based functional MRI (fMRI). Methods: Twenty-four individuals with chronic stroke and 14 neurologically healthy controls performed a bimanual force-tracking sequence-learning task during functional MRI. Performance convergence was defined as the sequence-specific reduction in the accuracy difference between the paretic and less-affected hands across practice. Neural activity was evaluated using whole-brain, region-of-interest, and functional-connectivity analyses following preprocessing tailored to structurally heterogeneous stroke lesions. Results: Stroke participants demonstrated significant performance convergence despite persistent motor impairment, indicating preserved expression of sequence learning during practice that was not detected by conventional behavioral measures. Lesion-aware fMRI identified robust task-related activation and preserved stage-dependent modulation within cerebellar, premotor, and striatal learning networks, together with reduced bilateral putaminal activity after stroke. However, preregistered analyses found no reproducible associations between individual differences in performance convergence and learning-related activation or functional connectivity. Conclusions: Performance convergence provides a sensitive, temporally resolved behavioral phenotype of preserved motor sequence learning in chronic stroke that complements conventional endpoint measures. Together, performance convergence and task-based functional MRI provide a framework for investigating individual differences in motor learning capacity and their implications for rehabilitation responsiveness.

Background: Mobility recovery after stroke is highly variable, yet is typically described using average patterns that obscure meaningful differences between individuals. Identifying distinct recovery trajectories may improve prognostication and guide rehabilitation strategies. Methods: We conducted a retrospective cohort study of adults admitted for stroke to a large health system between 2016 and 2024. Mobility was assessed using Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility, which was collected during routine clinical care. Growth mixture modeling was used to identify subgroups with distinct mobility recovery trajectories during the first 180 days after stroke. Subgroups were then characterized with baseline personal and clinical characteristics. Results: Seven hundred and fifty individuals contributed 3,389 mobility observations (median 4 per person). A five-class solution was selected based on model fit and classification quality. Distinct trajectories were identified: low stable (n=127), low rapidly improving (n=29), mid declining (n=169), mid improving (n=365), and high stable (n=60). Subgroups differed in both baseline mobility and patterns of change over time, with some demonstrating improvement, others remaining stable, and one declining. Individuals in improving subgroups were generally younger, more likely to be independent before stroke, received physical therapy on a greater proportion of hospital days, and were more frequently discharged to inpatient rehabilitation. In contrast, those in low or declining trajectories had lower baseline function, longer hospital stays, and were more likely to be discharged to skilled nursing facilities. Conclusions: The distinct mobility recovery trajectories identified in this work reflect the heterogeneity present in routine clinical practice. Subgroups differed in both recovery patterns and characteristics. Early identification of trajectory membership may improve prognostication and inform more targeted rehabilitation strategies.

Traditional views assume that pragmatic deficits after stroke, which compromise the interpretation of communicative intentions and non-literal meanings, follow damage to the right hemisphere (RHD), with left-hemisphere damage (LHD) primarily linked to aphasia and structural language impairment. To examine hemispheric contributions to post-stroke pragmatic profiles, we assessed 99 stroke patients (40 LHD, including 14 with aphasia of minimal-to-moderate severity; 59 RHD) and 60 healthy controls with the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS). While stroke patients overall performed worse than controls, LHD and RHD profiles were largely comparable across three converging analyses: (1) permutation tests revealed no hemispheric differences except on the two tasks requiring expressive components (Interview and Figurative Language 2), which in turn lowered the composites (APACS Production and Total); (2) equivalence testing established equivalence for most measures, with only these same tasks and composites remaining inconclusive; and (3) unsupervised clustering did not group patients by lesion side. Theory of Mind was robustly associated with pragmatic performance in both groups, whereas structural language abilities related specifically to LHD performance and general cognition only to RHD. Excluding aphasic LHD patients strengthened the evidence for comparable profiles, indicating that aphasic LHD patients largely drove the residual differences. In conclusion, primary pragmatic impairment, especially in the receptive domain, emerged comparably after LHD and RHD, with the only residual LHD disadvantage limited to tasks demanding open verbal output. These findings challenge the assumption of right-hemispheric specialization for pragmatics, stressing the need for pragmatic assessment in all post-stroke patients.

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.

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.

BACKGROUND Recruitment in stroke neurorehabilitation trials is often difficult, particularly in studies requiring MRI and repeated laboratory visits. The recruitment efficiency was analyzed to identify the major barriers to enrollment in a stroke neurorehabilitation trial. METHODS In this observational screening study, 1201 patients were screened at a neurological rehabilitation center in Germany between October 2023 and February 2026. Recruitment barriers were analyzed using a stepwise recruitment flow approach. RESULTS Of 678 patients with ischemic stroke, 13 were ultimately enrolled (1.9%; 1.1% of all 1201 screened rehabilitation patients). The most common exclusion reasons were strict clinical eligibility criteria (52.2%), travel distance to the study center (23.9%), and predefined age restrictions (17.9%). Recruitment losses occurred across multiple stages of the screening process. CONCLUSION Recruitment in stroke neurorehabilitation trials is strongly limited by restrictive study criteria and logistical barriers. More pragmatic and inclusive study designs may improve recruitment efficiency and better reflect real-world stroke populations.

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.

Background/Objectives: Traumatic Brain Injuries (TBIs) affect more than 50 million individuals worldwide each year. Approximately 90% of individuals survive and experience persistent motor, cognitive, and emotional deficits, substantially contributing to a reduced quality of life and a global economic burden. TBI mechanisms are a foundational determinant of long-term recovery. The objective of this study was to examine long-term trends in functional locomotion ability over extended follow-up durations (>10 years) across distinct TBI mechanisms. The researchers hypothesized that TBIs caused by falls or violent mechanisms would be associated with poorer functional locomotor abilities and, subsequently, lower item scores than those sustained through automotive or recreational activities. Methods: Data were obtained from the Traumatic Brain Injury Model Systems (TBIMS) database at Craig Hospital in Englewood, Colorado, the largest longitudinal TBI data repository in the world. Functional locomotion was assessed using the Functional Independence Measure (FIM) Locomotion item as the primary outcome measure. To enhance measurement precision and ensure interval-level scaling, raw FIM scores were converted into logit-based estimates of latent functional ability using Rasch modeling. Longitudinal changes of these Rasch-transformed scores were analyzed using linear mixed-effects regression, accounting for individual-level variability and unbalanced follow-up data. Results: The findings demonstrated a clinically meaningful decline in functional ability among individuals with TBIs from violent mechanisms, particularly assault-related injuries and gunshot wounds, which were associated with chronic medical complications and limited functional independence. Conversely, TBIs from bicycling, unclassified vehicular incidents, and winter sports showed significant positive estimates, possibly reflecting higher premorbid physical fitness. Motor vehicle, motorcycle, pedestrian, and fall-related TBIs demonstrated steep early gains, followed by a period of recovery stabilization and plateau. In contrast, violence-related mechanisms were characterized by consistently low median scores, with minimal long-term improvement. Falls, gymnastics, track & field, and water sports did not exhibit meaningful changes in the context of the primary hypothesis. Conclusions: TBI mechanisms play a vital role in shaping long-term functional locomotion outcomes, with violence-related TBIs associated with poorer long-term functional independence. The results have clinically important implications, supporting earlier identification of high-risk populations and the development of targeted rehabilitation strategies during periods of heightened neuroplasticity. Rasch analysis integrated with linear mixed-effects modeling yields a robust analytic framework that uncovers subtle but meaningful differences in recovery trajectories across TBI mechanisms.

Introduction: Several gait rehabilitation approaches after stroke rely on explicit feedback to promote task-specific voluntary corrections of walking patterns. While these approaches show effectiveness at a group level, individual responses to voluntary corrections can differ, limiting the benefits and translation of task-specific gait interventions. Our goal is to identify biomechanical, neuromuscular, and cognitive characteristics associated with the ability to perform voluntary corrections of walking using explicit visual feedback in people with chronic stroke. Methods: Twenty-eight individuals with chronic stroke completed a single-session treadmill walking protocol, consisting of baseline walking, a voluntary correction condition guided by real-time visual feedback, and a short retention trial without feedback. Reducing step length asymmetry was used as the target to guide voluntary corrections. Clinical assessments included measures of motor impairment, balance, gait function, cognition, and walking capacity. Muscle coactivation was characterized using dimensionality reduction. Associations of clinical assessments with baseline step length asymmetry and residual error in step length asymmetry during voluntary correction were examined using univariate analyses and multivariate regression with LASSO-based variable selection. Results: Eighteen participants successfully reduced step length asymmetry using visual feedback, while ten participants did not reduce asymmetry. Greater residual asymmetry during voluntary correction was independently associated with greater baseline asymmetry, greater lower extremity motor impairment, reduced balance, and increased paretic muscle coactivation (adjusted R2 = 0.46). Neither the direction of asymmetry nor cognitive outcome measures were associated with the ability to correct asymmetry during walking. Immediate retention after feedback removal was limited, with only 4 participants maintaining improvements. Discussion: The ability to perform voluntary corrections of the walking pattern using voluntary corrections after stroke is constrained by motor impairment, balance function, and muscle coactivation. These findings suggest that explicit, feedback-based gait interventions to guide voluntary corrections may benefit individuals with mild to moderate impairments, while individuals with more severe impairments require alternative strategies to guide corrections of the walking pattern.

Background/Objectives: Traumatic Brain Injuries (TBIs) often cause profound functional impairments, yet the influence of TBI mechanisms on stair-climbing functional independence over extended timelines remains poorly understood. This study assesses whether Rasch-transformed FIM Stairs scores varied by TBI mechanism over follow-ups spanning 10 years or more. Methods: Data from the TBI Model Systems database were analyzed. The original 30,768 data entries were reduced to 6,226, corresponding to individuals with at least 10 years of data. Functional Independence Measure Stairs data were transformed to logit units via Rasch analysis before being evaluated with a linear mixed-effects regression, incorporating TBI mechanisms, age, follow-up time, and their interactions, with random effects accounting for the participant ID and pre-injury residence location. Results: TBI mechanisms meaningfully shape very long-term stair-climbing. Gunshot wounds and pedestrian-related accidents are associated with poorer performances, whereas motorcycles, bicycles, unclassified vehicular accidents, winter sports, other sports, and fall-related TBIs demonstrated relatively better function. Age, follow-up time, and their interaction also reached significance. Conclusions: Stair-climbing recovery trajectories over extended time significantly vary by TBI mechanism, with individuals with TBIs from gunshots and pedestrian-related accidents showing the most unfavorable recoveries. These findings support the development of mechanism-specific prognostic guidance and individualized rehabilitation strategies, thereby encouraging tailored approaches to improve outcomes.

Introduction/Aims To evaluate the usefulness of the Goal Attainment Scale (GAS) light for assessing response to risdiplam in patients with SMA aged [&ge;]15 years. Methods In this population-based, longitudinal, ambispective study, patients were evaluated before and at 12 and 24 months after risdiplam initiation using motor scales (SMA Functional Composite Score Revised [SMA-FCR]), pinch strength (MyoPinch), functional scales (EK2, ALSFRS-R), patient and clinician global impression of change (PGIC and CGIC), and GAS light. Longitudinal changes were assessed using linear mixed-effects models. The minimal detectable change (MDC) and minimal clinically important change (MCIC) of GAS light were calculated. Results Forty-four patients (median age 32 years; 56.8% female) were included: 31.8% non-sitters, 56.8% sitters, and 11.4% walkers. GAS light priorities differed across functional subgroups, with patients prioritising moderately affected domains. After 24 months of risdiplam treatment, motor outcomes showed non-significant improvements in walkers, whereas functional scales improved significantly only in non-sitters. In contrast, GAS light detected significant, increasing improvements across all functional subgroups. The MCIC and MDC for GAS light were 6.5 and 10.65 points, respectively. According to the CGIC, 58% of patients improved slightly, 29% remained stable, and 13% worsened slightly at 24 months. Using the MCIC threshold, 64.5% achieved clinically meaningful goal improvement. Discussion GAS light is a feasible, sensitive, patient-centred tool that may complement standardised outcome measures when evaluating treatment response in adults with SMA. These findings further support risdiplam as a valuable therapeutic option in this population.

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.

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.

ObjectiveStroke-related corticospinal tract (CST) disruption causes lasting hand impairments, but many stroke survivors retain some residual CST connections. In neurotypical adults, motor cortex (M1) TMS interventions can strengthen CST transmission when coupled to EEG brain states reflecting heightened M1 excitability. Because stroke alters the relationship between these brain states and cortical excitability, we aimed to identify poststroke brain states that accurately capture ipsilesional M1 excitability. We hypothesized that heightened ipsilesional M1 excitability would be represented by a common, group-level EEG pattern and a participant- specific, personalized pattern. MethodsWe acquired single-pulse TMS-EEG-EMG datasets in 15 chronic stroke survivors with residual CST connections. We then identified group-level and individual-specific EEG power patterns that distinguished between high and low ipsilesional M1 excitability states. ResultsAt the group level, bilateral sensorimotor mu power was significantly suppressed during high versus low excitability states, but this suppression did not correlate with hand impairment severity or trait-level ipsilesional M1 excitability. At the individual level, spatiotemporally varied EEG activity patterns distinguished between excitability states, but these patterns were only present in 60% of individuals. Conclusion and SignificanceThis study is the first to systematically characterize poststroke EEG brain states reflecting ipsilesional M1 excitability. Findings suggest that individual-specific EEG patterns may inconsistently index ipsilesional M1 excitability and instead identify bilateral sensorimotor mu power suppression as a group-level excitability marker that is present across the full spectrum of poststroke hand impairment. HighlightsO_LIWe analyzed TMS-EEG-EMG to identify group and individual level ipsilesional motor cortical excitability states in chronic stroke C_LIO_LIBilateral sensorimotor mu suppression marked heightened ipsilesional motor cortical excitability across hand impairment severity C_LIO_LI60% participants had individual level scalp patterns linked to motor cortical excitability states, challenging their reliability C_LI