Neurorehabilitation and Neural Repair

Background. Although coordination between the upper limbs (ULs) is essential for daily life activities and may benefit from early post-stroke plasticity, how patients early after stroke achieve bimanual motor skill learning (bim-MSkL) remains poorly understood. We investigated whether acute and subacute stroke patients retained bim-MSkL capacity, whether bimanual control policy and motor sequence were dissociable components, whether bim-MSkL was more impaired in the distal than proximal UL segment, and whether clinical factors predicted bim-MSkL. Methods. Ninety-seven (sub)acute stroke patients and 60 age-matched healthy individuals (HI) trained over three days on proximal and distal bimanual tasks in this randomized trial. Baseline motor and neuropsychological impairments were assessed. On day 3, participants were randomized into two subgroups on the proximal task to dissociate control policy from motor sequence. Learning trajectories, perturbation-related performance disruption, and predictors of improvement were analyzed. Results. Accuracy and coordination improved in patients on both the distal and proximal tasks over three days, although less than in HI, while proximal speed improvement remained limited. Control policy swap induced larger performance disruption than motor sequence change, whereas the relearning slopes did not differ in patients. Unlike HI, patients showed no proximal-to-distal gradient in bim-MSkL despite greater distal than proximal baseline impairment. Baseline tasks performances, subacute motor and attentional impairments were the strongest predictors of bim-MSkL impairment early after stroke. Conclusions. Most patients with mild-to-moderate impairment exhibited substantial residual proximal and distal bimanual motor learning capacity early after stroke. Impairment profiles support individualized bimanual rehabilitation strategies integrating both motor and cognitive demands.

Feedforward control is impaired after stroke, but whether practice improves it in the chronic stage remains unclear. In fast single-joint movements, feedforward control scales initial acceleration to movement amplitude. Feedback-error-learning theory predicts that fast practice should promote recalibration. We tested whether speed-emphasized reach training improved this scaling in the more-affected arm. Thirty-six individuals with mild-to-moderate chronic stroke completed 2,080 reaches over four sessions emphasizing Speed (n = 17) or Accuracy (n = 19). At baseline, 3 days, and 1 month after training, participants performed single-joint elbow movements of three amplitudes without online visual feedback. The slope relating initial peak acceleration to target amplitude quantified feedforward scaling. At baseline, scaling was reduced on the more-affected side for extension and flexion. Speed training increased flexion scaling at 3 days, with 14 of 17 participants improving. The group-by-session interaction showed a greater increase after Speed than Accuracy training. Scaling declined by 1 month; no training-related changes occurred for extension. Peak acceleration occurred within 100 ms. Time to peak velocity, an index of pulse width, showed no group-specific training effect. Thus, speed-emphasized training produced a short-term improvement in early flexion acceleration scaling that transferred to an untrained single-joint task and was consistent with improved feedforward control. Transfer primarily reflected acceleration pulse-height rather than pulse-width modulation.

Background: Paretic-arm nonuse and trunk compensation after stroke are often interpreted as impairment or learned behavior but may also reflect task-dependent optimization. We previously showed that gravitational shoulder effort and force reserve shape these behaviors. Here, we tested whether endpoint precision is an additional constraint. Methods: Twenty-two individuals with stroke and 22 matched controls performed a seated Proximal Arm Nonuse reaching task toward small (2 cm) and large (12 cm) targets. Stroke participants were tested at normal arm weight and with the paretic arm mechanically lightened; controls were tested at normal arm weight and while holding a dumbbell corresponding to 85% of maximal voluntary shoulder force. Results: In stroke participants, trunk compensation was 15% lower for the large target than for the small target, independently of arm weight condition (F(1,13)=8.166, p=.013, pes=.39). Target size did not significantly affect trunk compensation in controls or anterior deltoid activation in either group. In stroke participants, movement time was 24% longer for the small target than for the large target (F(1,13)=8.533, p=.012, pes=.40). In controls, the small target increased movement time only when the arm was weighted (F(1,18)=14.9, p=.001, pes=.45), not at normal arm weight (F(1,18)=0.158, p=.695, pes=.01). Conclusions: Endpoint precision altered reaching after stroke partly independently of gravitational shoulder effort. Trunk compensation after stroke was therefore modulated by task demands rather than fixed by impairment, a pattern consistent with, although not a direct demonstration of, an optimal-control account. Rehabilitation should evaluate compensation by its functional role and the cost of suppressing it, not only by its deviation from typical kinematics, and should treat target size as an adjustable parameter of the task. Clinical Trial: NCT04747587. https://clinicaltrials.gov/study/NCT04747587

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.

ABSTRACT Background Stroke often leads to upper-extremity motor impairments, including abnormal neuromuscular coordination (i.e., motor modules), which reduce independent joint control and impair activities of daily living. Conventional rehabilitation mainly targets the resultant motor deficits (e.g., impaired movement) rather than the underlying neuromuscular dysfunction, potentially limiting transferability of gains beyond trained tasks. Therefore, we propose a customized, motor module-guided exercise facilitated by human-machine interaction to improve neuromuscular coordination and reduce motor impairment. Methods Five chronic stroke survivors with severe-to-mild upper extremity impairment participated in a six-week motor module-guided intervention in which they learned to selectively activate muscle groups identified in healthy individuals. In addition, three stroke survivors completed a force-guided intervention as an active control group. Standardized clinical assessments, including the Upper Extremity Fugl-Meyer Assessment and Action Research Arm Test, were performed before and after training and repeated one and three months later to assess retention. Neuromuscular coordination was quantified using non-negative matrix factorization of surface electromyography, and inter-joint coordination was evaluated during dynamic tasks using a motion capture system before and after training. Results Four of the five participants in the motor module-guided intervention improved neuromuscular coordination. These participants also showed clinically meaningful improvements in motor impairment, which were generally maintained at one and three months after training. In contrast, although the force-guided group showed improvements in task-specific performance and force control, no significant changes in neuromuscular coordination or motor impairment were observed. Notably, improvements in motor impairment correlated with enhanced stroke-induced motor module composition. Finally, findings suggest potential transferability of enhanced neuromuscular control from the trained isometric condition to untrained dynamic behaviors. Conclusion This pilot study showed that motor module-guided rehabilitation could induce improvement of stroke-affected neuromuscular coordination, even in severely impaired chronic stroke survivors, reducing motor impairment and improving motor control beyond the trained task. These findings support neuromuscular coordination-guided rehabilitation as a promising framework for post-stroke recovery.

ObjectiveRecovery from post-stroke aphasia is traditionally thought to plateau within a year after stroke. As such, no studies have characterized long-term recovery using comprehensive behavioral assessment and longitudinal functional MRI. We sought to characterize behavioral and neuroplastic changes over nearly six years in a patient with chronic post-stroke aphasia. MethodsA patient with chronic left hemisphere stroke underwent behavioral assessment and task-based fMRI at 9, 22, 33 and 71 months after stroke. Testing assessed auditory comprehension, semantic and phonological processing, naming, reading, spelling, motor speech, and executive function. Task-related activation during an adaptive semantic matching paradigm was quantified within language and semantic regions of interest. ResultsBehavior improved across multiple language domains. WAB-R Aphasia Quotient increased from 49.2 to 69.2, along with the large gains in word finding, connected speech, reading and spelling, whereas auditory comprehension remained relatively stable. fMRI demonstrated progressively increasing activation within left-hemisphere language regions, reaching normative range by the final assessment, along with increasing activation in semantic/executive regions. DiscussionRecovery of language production abilities can continue for years after stroke, supported by neuroplastic changes in the brain. Neurologists should inform stroke survivors that aphasia recovery can continue indefinitely after stroke.

Stroke-induced hemiparesis often results in slow walking and an asymmetrical gait; however, these impairments vary widely across patients. Indeed, some individuals walk fast despite severe gait asymmetry, whereas others walk slowly despite mild asymmetry. We posit that speed and symmetry reflect distinct dimensions of walking and may serve as complementary biomarkers of stroke recovery. In this cross-sectional study, 57 individuals with chronic hemiparesis were classified as "slow" or "fast" and as having "severe" or "mild" asymmetry, using pre-defined thresholds (i.e., speed = 0.8 m/s; symmetry = 31.5%). Kruskal-Wallis and regression analyses were used to evaluate differences in gait biomechanics (i.e., limb and joint propulsive power and the metabolic cost of walking) and ambulatory function (i.e., speed, distance, and functional balance) associated with these impairment classifications. When examined independently, slower speeds and greater asymmetry were similarly associated with a higher metabolic cost of walking ({Delta} range: 77% to 83% higher, p < 0.05) and reduced balance and walking function ({Delta} range: 26% to 82% lower, p < 0.05). However, the two classification approaches revealed different underlying biomechanical mechanisms: whereas slower walking corresponded to reduced paretic propulsive power ({Delta} : 71% lower, p < 0.05), greater asymmetry indicated a distal-to-proximal shift in power generation ({Delta} : 200% shift from the ankle to the hip, p < 0.05). Furthermore, multiple regression analyses revealed that each classifier was an independent predictor of metabolic cost (R2=0.70, p < 0.001) and ambulatory function (R2 range: 0.34 to 0.55, p < 0.001). These findings demonstrate the complementary diagnostic value of measuring both walking speed and propulsion asymmetry, supporting the development of multi-dimensional phenotypes to enable precision neurorehabilitation.

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: Gait propulsion (anterior ground reaction force) is commonly impaired after stroke. Force plates and wearable sensors can quantify propulsion but are not routinely available in clinical settings. Walking speed alone does not adequately capture the heterogeneity of propulsion deficits. Objective: To determine whether standardized clinical measures can estimate post-stroke propulsion metrics and classify propulsion impairment. Methods: Forty individuals post-stroke participated: 33 for model development and cross-validation (11 with repeated observations for longitudinal validation) and 7 for independent-cohort validation. Clinical measures included the 6-Minute Walk Test (6MWT), comfortable walking speed (CWS), Functional Gait Assessment (FGA), Fugl-Meyer Assessment of the Lower Extremity (FMA-LE), Short Physical Performance Battery (SPPB), Timed Up and Go test (TUG), and stroke chronicity. Regression models were developed to estimate three propulsion metrics: paretic propulsion peak and impulse, and interlimb propulsion symmetry. Model performance was evaluated using R2 and RMSE. Propulsion impairment was classified from symmetry estimates using a prespecified cutoff of 31.5%, with classification accuracy reported. Results: Models using the 6MWT, SPPB, TUG, and chronicity estimated paretic propulsion peak (R2 = 0.77, RMSE = 3.00 %body weight) and impulse (R2 = 0.81, RMSE = 0.65 %body weight {middle dot} %stance phase). FMA-LE, SPPB, TUG, and chronicity estimated propulsion symmetry (R2 = 0.75, RMSE = 8.56%) and classified propulsion impairment with 84.8% accuracy. Classification accuracy was 91.7% in longitudinal validation and 85.7% in independent-cohort validation. Conclusions: A multidomain clinical assessment framework may support practical and accurate estimation and classification of post-stroke propulsion impairment in clinical settings where specialized instrumentation is unavailable.

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: Motor imagery neurofeedback (MI-NF) engages sensorimotor brain networks and has shown potential for motor recovery after stroke. While laboratory-based studies have demonstrated neural and behavioral effects, evidence on real-world MI-NF training and its impact on brain activity and connectivity in stroke survivors remains limited. The Motor Imagery Neurofeedback Training in Stroke (MINTS) study investigates the effects of intensive, home-based MI-NF training using mobile EEG in chronic stroke survivors. Specifically, the study examines whether MI-NF training induces changes in neural activity and functional connectivity and whether these changes are accompanied by improvements in upper-limb motor function. Additionally, the study explores the temporal evolution of neural and behavioral changes across repeated baseline and training measurements. Methods: MINTS is a prospective, single-group, multimodal intervention study using an across-subjects multiple-baseline design. Twenty-one individuals with chronic stroke (at least 6 months post-stroke) and persistent upper-limb motor impairments undergo a pre-assessment phase, a variable-length baseline period, an intervention phase with 14 MI-NF training sessions, a post-assessment phase, and an exploratory three-month follow-up. MI-NF training is performed every second day at participants' homes using mobile EEG. Repeated baseline and training measurements include grip strength, resting-state EEG, motor imagery tasks with and without neurofeedback, and daily-life movement monitoring. Pre- and post-assessments comprise comprehensive motor and cognitive testing, stationary EEG, and functional MRI. Primary outcomes are resting-state EEG coherence as an index of functional connectivity and MI-related EEG activity derived from mobile EEG within the multiple-baseline design. Secondary outcomes include MI-related EEG activity derived from stationary EEG, fMRI-based measures of brain activity and connectivity, clinical motor outcomes, and quantitative movement characteristics derived from movement sensors and video recordings. Tertiary outcomes and exploratory directions address broader motor and cognitive performance, associations between neural and behavioral changes, lesion-related effects, and persistence of training-related changes. Discussion: By combining intensive home-based MI-NF training with repeated multimodal assessments, MINTS is designed to characterize neural and behavioral dynamics of motor recovery after stroke and to evaluate the potential clinical relevance of MI-NF training in everyday life settings. Trial Registration: The study protocol was registered in the German Clinical Trials Register (DRKS00036147) on 25 March 2025.

Background: Task challenge is recognized as a core principle of neurorehabilitation and is frequently mentioned within stroke rehabilitation guidelines. However, guidance for operationalizing challenge in clinical practice remains limited. Examining how therapists and people with stroke currently use challenge in practice may help address this gap. Objective: To examine how challenge is operationalized in routine stroke rehabilitation practice. Methods: This study used focused video analysis to examine eight video-recorded stroke rehabilitation sessions across physiotherapy, occupational therapy, and speech-language therapy contexts. Video data were supplemented by observational memos. Analysis was conducted iteratively through four stages: immersion, detailed transcription, in-depth episode analysis, and comparative analysis. These stages enabled examination of material, embodied, social, and contextual aspects of challenge-related interactions as they unfolded during rehabilitation. Results: Twenty individuals, comprising four patient-therapist dyads and four triads participated. Challenge was operationalized through three intersecting practices: (i) Structuring challenge-related work through temporal phases determined when challenge was introduced, experienced, and consolidated across the session and within tasks; (ii) Establishing the macro-architecture of challenge guided what and how it was operationalized by constructing a challenge plan, shaping an optimal bandwidth by tailoring challenge to the persons abilities and/or experiences, and facilitating its transfer beyond the session; (iii) Modulating challenge through micro-calibrations involved moment-to-moment adjustments (e.g., adapting physical assistance, communication style, environmental setup) to modulate active practice, navigate differing perspectives, and cultivate an atmosphere conducive to engaging with challenge. These overarching practices were dynamically enacted through a range of explicit and implicit practices. Conclusion: Challenge in stroke rehabilitation is not merely a task parameter; it is operationalized through an interplay of explicit and implicit practices that structure and enable its responsive implementation. Considering challenge through these practices may help therapists and people with stroke co-construct meaningful experiences of challenge, both within and beyond formal stroke rehabilitation sessions.

Background: Our long-term goal is to determine the optimal volume of reactive balance training (RBT) in people with sub-acute stroke. This study aims to inform the design of a larger trial to address this long-term goal. Trial design: Assessor-blinded three-arm pilot randomized controlled trial. Methods: Participants (n=36) with sub-acute stroke were randomly allocated to one of three groups: 1, 3, or 6 RBT sessions. All sessions were delivered over 2-3 weeks. Feasibility outcomes included recruitment and retention rates, intervention fidelity and adherence, and completeness of outcome assessments. Participants reported falls and physical activity for 6 months post-training; falls data were used to estimate sample size for a future trial. Functional balance, balance confidence, and balance reactions were assessed at: 1) study enrolment; 2) post-training; and 3) 6 months post-training to estimate effect sizes for a future trial. Results: Thirty-five participants initiated training and 34 contributed post-training assessment data. Intervention adherence was high: participants completed 1.0, 2.9, and 5.7 RBT sessions on average in the 1-, 3- and 6-session, respectively. Functional and questionnaire outcomes were [&ge;]80% complete at most time points, although follow-up questionnaires at 2 and 4 months met only 74% completeness. Falls monitoring data were available for 30 participants, with 15 falls reported. Estimated sample sizes for a definitive trial using falls as the primary outcome (n=408-782) were not feasible for a single site; alternative primary outcomes (stability following balance perturbations) produced more feasible sample size estimates (n=30-72). Minor adverse events were reported by 1, 2, and 6 participants in the 1-, 3- and 6-session groups, respectively. Conclusions: The modified intervention and assessment procedures were feasible; however, a definitive single-site trial using falls as the primary outcome is not feasible. Stability-based outcomes may support a more feasible future trial. Trial registration: clinicaltrials.gov, NCT04219696

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.

Importance: Upper extremity impairment is a leading cause of post-stroke disability, yet clinically approved neuromodulation therapies are currently limited by the risks and costs of surgical implantation. There is an unmet need for non-invasive brain stimulation. Objective: To evaluate the feasibility, safety, and preliminary clinical efficacy of a novel form of non-invasive brain stimulation, kilohertz transcranial magnetic perturbation (kTMP), for upper limb motor recovery after stroke. Design: A single-center, open-label trial was conducted between September 2025 and April 2026 and comprised a 4-week standard-of-care baseline period, 4 weeks of active treatment with kTMP combined with motor training, and a 4-week follow-up. Setting: Academic research center. Participants: Seven individuals with chronic stroke and upper extremity motor deficits. Intervention: Four weeks of kTMP (3 sessions/week), a brain stimulation approach using magnetic induction to generate subthreshold electric fields, paired with motor tasks. Main Outcomes: Change in Fugl-Meyer Assessment for Upper Extremity (FMA-UE) scores across study periods (standard-of-care baseline, active treatment, follow up). Secondary outcomes included measures of movement smoothness (Spectral Arc Length, SPARC) and fragmentation (mean velocity peak count), and intervention tolerability ratings. Results: Across 7 participants (mean [SD] age, 57.4 [8.7] years; 4 males; mean [SD] time poststroke, 3.5 [2.1] years). No device-related adverse events occurred, and the intervention was well-tolerated (participants rated sensation intensity at an average of less than 0.5 on a 0-10 scale). FMA-UE scores remained stable during the baseline period (mean change, +0.14 points; 95% CI, -1.21 to 1.50; adjusted P = .98), increased significantly following the kTMP-intervention (mean change, +7.00 points; 95% CI, 5.31 to 8.69; adjusted P = .047), and were sustained at the 4-week follow-up (mean change, -1.33 points; 95% CI, -2.42 to -.25 points; adjusted P = .13). Movement smoothness improved significantly within 1 week of kTMP onset (mean change, 1.48 points; 95% CI, .49 to 2.47; adjusted P = .03); movement fragmentation showed a similar but nonsignificant trend. Conclusions and Relevance: This pilot trial provides preliminary evidence that kTMP combined with motor tasks is safe, feasible, and may support upper extremity recovery. These pilot data warrant large, randomized controlled trials to evaluate efficacy in support of poststroke motor recovery. Trial Registration: ClinicalTrials.gov Identifier: NCT06317194

Rehabilitation is the cornerstone of clinical care following spinal cord injury (SCI) and is frequently incorporated into preclinical studies to evaluate emerging therapies. However, the variables that influence the effectiveness of rehabilitation interventions in rodent models remain poorly characterized, limiting the translational value of preclinical research. Here, we performed a meta-analysis of 150 preclinical studies comprising more than 3000 rodents and 292 effect sizes to identify such factors associated with successful rehabilitation after SCI. Rehabilitation improved functional outcomes across multiple behavioral domains, with larger effects observed in thoracic than cervical injury models. Meta-regression identified environmental enrichment as the most effective strategy, particularly when combined with task-specific training. Longer rehabilitation duration was associated with improved recovery, whereas greater daily exposure to forced rehabilitation was associated with smaller gains. In contrast, prolonged access to voluntary rehabilitation did not show this relationship. Rehabilitation improved outcomes when initiated at all time points after injury, with greater benefits when initiated during the late subacute and intermediate phases. Rehabilitation approaches associated with higher stress burden produced reduced benefits, suggesting that stress may limit rehabilitation-induced recovery. Collectively, these findings identify rehabilitation type, duration, and delivery context as important determinants of recovery after SCI and support a broad therapeutic window for intervention. Our results favor low-stress, voluntary rehabilitation strategies that promote sustained engagement and provide principles for designing effective and biologically appropriate rehabilitation strategies, potentially improving translational success for emerging SCI therapies. One Sentence SummarySustained voluntary rehabilitation promotes functional recovery across stages of experimental spinal cord injury, whereas prolonged forced training may reduce its benefits.

Post-stroke gait impairment is associated with altered muscle coordination. Understanding how functional muscle coordination contributes to joint control is essential for clarifying the mechanisms of gait impairment after stroke. Functional muscle network approaches quantify how muscle interactions contribute to joint kinematics. We investigated how gait-related functional muscle networks are reorganized after stroke and how this reorganization relates to motor impairment and gait dysfunction. Thirty-five participants with subacute stroke and 25 healthy controls underwent gait analysis using surface electromyography and lower-limb kinematics. We quantified functionally similar (redundant information), complementary (synergistic information), and independent (unique information) muscle interactions underlying joint kinematics. Participants with stroke exhibited greater redundant information and lower independent information than healthy controls. Stroke-specific functional muscle network modules emerged through merging modules observed in healthy controls. Stroke-specific module activation was also associated with motor impairment and gait performance. Overall, these findings identify a shift toward more redundant muscle coordination and stroke-specific reorganization of functional network modules, providing new insights into post-stroke gait dysfunction.

Background: Virtual and Augmented Reality (VR/AR) are increasingly used in medicine and may offer novel interventions for Functional Neurological Disorder (FND) by targeting mechanisms of impaired motor control. However, evidence for the effect of different modalities on movement in FND is limited. Moreover, it is hypothesized that visual feedback of one s affected arm could reinforce FND symptoms through maladaptive self-monitoring. The present study aims to compare motor performance under visual feedback of a virtual avatar versus the real arm. Methods: Fifteen FND patients and eighteen healthy controls completed a dual motor reaching task (touching a virtual fruit such as orange or apple appearing in front of them) with a virtual headset across three modalities: Augmented Reality (AR), where participants saw their real arm; Virtual Reality (VR), with a virtual arm; and Virtual Reality Improved (VRI), with artificially enhanced straightness and larger collision zone with the target. Their movement speed, straightness and number of velocity peaks were calculated for each fruit catch. Additionally, the number of collisions between the eyes and the body was calculated with eye tracking technology. Results: FND participants were slower and produced less smooth movements in AR compared to VR (b = 1.09, z = 8.83, P < .001) and VRI (b = 0.85, z = 6.91, P < .001), while the opposite effect was found in healthy controls. Eye tracking showed that FND patients looked more at their affected hand than unaffected hand (b = -1.46, SE = 0.34, z = -4.23, p < .001; OR = 0.23). Conclusions: Virtual feedback of their limbs avatar appears to support better motor performance, while visual feedback of their real limb appears to exacerbate motor impairments in FND patients, likely reinforcing maladaptive self-monitoring. These findings highlight the therapeutic potential of VR interventions and provide the basis for future studies examining longer protocols, clinical outcome and potential implementation in standard motor rehabilitation.

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: Balance control is essential for independence in activities of daily living, and its impairment is a leading contributor to falls in stroke survivors. Stroke-induced brain reorganization alters cortical activation patterns; however, localized changes do not reveal the underlying network dynamics critical for the exchange of task-related information. How stroke affects balance-related cortical network dynamics remains unclear. Methods: We studied cortical functional connectivity during a challenging balance task in fifteen chronic stroke survivors and fifteen age- and gender-matched healthy adults. Whole-head electroencephalography (EEG) was recorded while participants performed a balance sway-referenced task. Balance-related cortical sources were localized to the supplementary motor area/premotor area (SMA-PM), posterior cingulate cortex (PCC), and bilateral lateral prefrontal cortex (LPFC). Directed task-related functional connectivity was estimated across multiple frequency bands. Results: Stroke participants demonstrated elevated gamma-band SMA-PM to PCC connectivity, ipsilesional LPFC to SMA-PM connectivity, and SMA-PM to contralesional LPFC connectivity compared to healthy participants. Stroke participants also showed poorer performance on both the clinical Berg Balance Scale (BBS) and the laboratory-based balance task. Stronger SMA-PM to contralesional LPFC connectivity, but not SMA-PM to PCC connectivity, was associated with better BBS scores in stroke survivors. Conclusions: These findings suggest less reliable SMA-PM to PCC sensorimotor pathways and a compensatory recruitment of SMA-PM to contralesional LPFC pathway for the control of balance post-stroke. Cortical network reorganization after stroke leads to directional connectivity changes adaptive to functional needs, with implications for designing targeted interventions to reduce fall risk in stroke survivors.