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.

Stroke often results in compensatory movement strategies that combine use of trunk movements with nonuse of the affected upper extremity, which is considered detrimental to recovery. In this study, we investigate whether compensation and nonuse can be more than a suboptimal counterpart to recovery. We explore the influence of neuromechanics on nonuse and compensation in 22 stroke survivors and 22 controls. We asked seated participants to reach a target under two nonuse conditions (spontaneous or with minimized trunk compensation) and under three arm weight conditions (control, lightened and weighted). We replicated the findings that stroke induces more trunk compensation, more anterior deltoid activation and greater effort. We found that, in stroke patients, reduced arm weight decreased nonuse, while in controls, increased arm weight induced trunk compensation similar to what is observed after stroke. Furthermore, reaching with nonuse after stroke required less effort and preserved a force reserve at the shoulder. Our results show that both poststroke and healthy individuals engage in similar nonuse and compensation in the face of their neuromechanical limitations, as predicted by an optimal control policy aiming to succeed at the task while keeping a force reserve at each joint. We derive two theoretical predictions for future clinical research. First, patients whose nonuse yields few functional gains should benefit most from interventions to reduce compensation. Second, improving shoulder strength after stroke should reduce relative muscle activation, thereby decreasing trunk compensation and upper extremity nonuse. Clinical Trial: NCT04747587

BackgroundAfter stroke, patients can experience a rapid and generalised improvement in the control of movements, including movements that have not been trained (spontaneous recovery). This generalised improvement in motor control (or behavioural repair) is more effective in supporting functional recovery than task-specific training or behavioural compensation but has to date only been observed in the first few months after stroke. MethodsWe studied 81 chronic stroke patients at two time points, 3-weeks apart. 52 patients underwent a 3-week high-dose high-intensity upper limb neurorehabilitation programme (QSUL), and 29 chronic stroke patients receiving no treatment acted as control subjects (SC). At each time point, we assessed arm motor control kinematically using a 2D-planar reaching, a task which cannot be improved through compensation nor functional task training in 3D during neurorehabilitation. In addition, we measured strength, active range of joint motion and the upper extremity Fugl-Meyer score (FMA-UL). ResultsThe FMA-UL increased by 6 points (IQR 3-8) in the QSUL-group and 0 points (IQR -1-1) in the SC-group. There were significant improvements in smoothness, movement time and accuracy of 2D-planar reaching in the QSUL-group compared to SC-group (all group x timepoint interactions P<0.03), which were independent of changes in strength or active range of joint motion. ConclusionsChronic stroke patients retain the capacity for generalised improvement in motor control in response to high-dose high-intensity neurorehabilitation. Normal or closer to normal motor control should remain a therapeutic target for improving arm paresis at all stages after stroke.

In non-disabled individuals, arm choice in pointing movements depends on expected biomechanical effort, expected success, and a handedness bias. Following a stroke, is arm choice re-optimized to account for the decreased motor performance, or does it follow a pre-injury habitual pattern? Because premorbidly right-handed individuals with left hemiparesis generally use their affected arm less than those with right hemiparesis, we hypothesized that arm choice follows a more habitual pattern in right-than in left-hemiparetic individuals. Participants with mild to moderate chronic stroke who were right-handed before stroke performed pointing movements in both free- and forced-choice blocks, both under a no-time constraint condition and under a fast-time constraint condition designed to promote habitual choice. Mixed-effects models of arm choice revealed that expected effort and side of stroke predicted choices overall. However, expected success predicted choice in left-, but not of right-hemiparetic individuals. Furthermore, while left-hemiparetic individuals tended to avoid unsuccessful movements in the fast condition by selecting their non-paretic arm, right-hemiparetic individuals persevered in choosing their more affected arm. In addition, reaction times decreased in left-hemiparetic individuals between the no-time and the fast condition but showed no changes in right-hemiparetic individuals. Finally, arm choice in the no-time condition correlated with a clinical measure of spontaneous arm use for right-, but not for left-hemiparetic individuals. Our results thus show that, in premorbidly right-handed individuals with mild to moderate chronic stroke, arm choice is habitual in right-hemiparetic individuals, but shows a greater degree of optimality by taking account expected success in left-hemiparetic individuals. New & Noteworthy Although we are seldom aware of it, we constantly make decisions to use one arm or the other in our daily activities. Here, we study whether these decisions change following a chronic mild to moderate stroke that affects motor control. Our results show that chronic stroke survivors with a right hemiparesis make arm choice using a habitual strategy, while those with left hemiparesis re-optimize their choices to account for their impaired motor performance.

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

Many individuals with limb apraxia after left-hemisphere stroke exhibit a lack of awareness of their tool-related action errors, i.e., unawareness of apraxia (UA; also called anosognosia of apraxia). Little is known about the prevalence of UA, the relationship between UA and apraxia severity, or its underlying mechanisms. Here, we assessed both the causes and consequences of UA. Based on a mechanistic model, we hypothesized that UA may arise because of deficits in representations signaling how tool-related movements should look and feel--a component of action knowledge--and that degradation of this knowledge impedes the detection of mismatches between planned and actual tool-related actions. We further predicted that a consequence of UA is a reduction in error-correction attempts. Fifty-six individuals with chronic LCVA gestured to show how to use tools. Immediately after the gesture production task, participants were asked if they made any errors. All participants also completed an action knowledge task to measure the integrity of tool-related movement goals. Individuals were denoted as exhibiting UA if they performed below a normative cutoff for apraxia yet reported making no errors. Our sample included 21 individuals with apraxia; of these, nearly half (48%) exhibited UA. These two groups made a comparable number of gesture errors and were of equivalent stroke severity, yet individuals with UA had significantly more impaired action knowledge. Additionally, individuals with UA were less likely to attempt to correct their errors compared to individuals who were aware of their apraxia. These data support the hypothesis that action knowledge (how tool actions look and feel) serves a key role in error detection and awareness of apraxia and may contribute to the difficulties with everyday tasks experienced by many people with apraxia.

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.

Stroke is a leading cause of long-term disability, but advances for rehabilitation have lagged those for acute treatment. Large biological studies (e.g., "omics"-based approaches) may offer mechanistic insights for recovery, but to enable those studies, researchers need to collect detailed recovery phenotypes at scale, e.g., in thousands of people with minimal burden for participants and researchers. This study investigates the concurrent validity between remotely collected wearable sensor data and clinical assessments of motor recovery post-stroke. We specifically focus on the "use ratio", which is the activity level of the paretic arm relative to the non-paretic arm, measured via bilateral wrist-worn accelerometers. Utilizing a large, harmonized multi-site dataset of adults with stoke, we analyzed cross-sectional (N=198) and longitudinal (N=98) changes in use ratio, the Action Research Arm Test (ARAT) and the Fugl-Meyer Assessment upper extremity subscale (FM-UE). Our findings indicate strong concurrent validity of the use ratio and the ARAT, and the use ratio and the FM-UE both cross-sectionally (i.e., differences between people) and longitudinally (i.e., changes within a person). Notably, while the use ratio strongly correlated with FM-UE and ARAT initially, the strength of these correlations reduced over time. This decreasing correlation might be explained by the increasing influence that personal and environmental factors play as recovery progresses. Additionally, these correlations were also stronger for the use ratio than for hours of activity for the paretic/nonparetic arm alone, suggesting that it is specifically asymmetry of activity that correlates with clinical measures. Thus, the use ratio is an efficient and clinically valid measure of motor recovery post-stroke that can be deployed at scale to collect biologically meaningful phenotypes.

Measuring neuromotor control after stroke is crucial for identifying the mechanisms underlying asymmetrical walking and guiding rehabilitation. The lower extremity portion of the Fugl-Meyer (FM-LE) and the number of muscle synergies are commonly used measures, but have important limitations. The dynamic motor control index has emerged as a complementary metric, yet its relationship to established clinical measures (i.e., FM-LE), muscle synergy number, and gait biomechanics remains unclear. This study evaluated the ability of the dynamic motor control index to quantify post-stroke neuromotor impairment relative to FM-LE and muscle synergy number and examined its relationship with propulsion asymmetry. Electromyography data from 22 individuals post-stroke and 31 neurotypical controls were analyzed using non-negative matrix factorization. The dynamic motor control index and not the muscle synergy number differentiated paretic, non-paretic, and neurotypical limbs ({chi}2(2) = 27.57, p < .001). It also differed significantly between less and more impaired individuals classified by FM-LE (p = .05) and demonstrated good discriminative performance between these groups (AUC: 0.777, p = .017). The index also moderated the relationship between FM-LE and propulsion asymmetry ({Delta}R2 = 0.223, p = .007). These findings support the dynamic motor control index as a clinically relevant msarker of post-stroke neuromotor impairment and recovery.

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.

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.

In 1951, the neurologist Thomas Twitchell published a seminal paper in Brain describing the time-course of recovery from hemiplegia after stroke in 25 participants from hospitalization to when they reached what he deemed steady state. His main emphasis was on the evolution of voluntary movements at the shoulder, elbow and hand, first within an obligatory flexor synergy, and then independently out-of-synergy. We thought that 75 years later, an update using modern motion capture technology should be attempted as it would allow for finer granularity in the characterization of the time courses of both functional recovery and of the flexor synergy, and then relate them to each other, to weakness and to well-established clinical scales. To this end, we used marker-less 3D kinematics to assess task performance and intrusion of synergies in thirty-three stroke participants longitudinally, from the early sub-acute stage (1 - 8 weeks post-stroke) to the chronic stage (24 - 64 weeks post-stroke). Participants performed an out-of-flexor synergy (shoulder flexion and elbow extension) reaching task. We assessed the time course of recovery of obligatory intrusion of pathological synergies based on measures derived from the angular velocity profiles of the shoulder and the elbow joints. Task-related kinematic measures were obtained and compared to sixteen healthy controls. Grip strength, Motor impairment (FMA), and function (ARAT) scores were also collected. Task kinematics were different from controls in the early, late sub-acute, and chronic stages, but showed gradual recovery over time. Weakness in the hand remained impaired at all time points. Flexor-synergy intrusion was maximal in the early sub-acute stage and then began to subside. Regression analysis with functional kinematic and clinical (FMA, ARAT) measures indicated that flexor-synergy intrusion was a significant predictor in the early and late sub-acute stages, but not in the chronic stage, while weakness remained a significant predictor at all stages of recovery. To better address the relationship between synergies, weakness, and function, we analyzed the more severe cases (ARAT<21) separately. In the sub-acute stage, most of them (11/13) suffered from intrusion of synergies, whereas in the chronic phase, only a minority (2/8) did. Weakness seemed to be the main contributor to poor outcome in the chronic phase. We conclude that weakness and synergy intrusion evolve separately from the subacute to the chronic phase, perhaps more so when neurorehabilitation is given at a dose higher than standard of care.

This Phase IIa biomarker-guided stroke rehabilitation trial aimed to determine if a 3-week programme of high-dose, high-intensity (HDHI) virtual exploratory movement (VEM) therapy using MindPod Dolphin could improve upper limb recovery and outcomes early after stroke. Sixty-four participants were randomised into VEM (n=31) or conventional therapy (CoT) groups (n=33) and began intervention within two weeks of stroke. Participants were given 90 minutes of therapist time per weekday for three weeks to undertake intensive upper limb therapy over and above their usual customary care. Outcomes were obtained immediately post-intervention, three and six months post-stroke. The primary endpoint was change in Action Research Arm Test (ARAT) score between baseline and three months post-stroke. Secondary outcomes were Fugl-Meyer assessment (FM-UE), hand dexterity, reaching kinematics and transcranial magnetic stimulation-derived measures across post-intervention time points up to six months. Data from all participants were analysed for intention to treat, while fifty-four met the weekly target of active therapy minutes, permitting inclusion in a per protocol analysis. The average weekly time on task increased over the intervention period, with progressively greater distances of arm movements (VEM) or task repetitions (CoT) made each week. Still, during the final week of intervention, participants analysed per protocol spent an average of only 50 (VEM) - 66% (CoT) of the extra time available on task. For the intention-to-treat analysis, there was no effect of group for the primary endpoint. For the per protocol analysis, there was no effect of group or group by time interaction for any secondary outcome measure. An expected effect of time was observed indicative of recovery from impairment (mean {Delta}FM at 6 months = 23 points), increased activity capacity (mean {Delta}ARAT at 6 months = 31 points) and improved secondary neuroscientific measures. Per protocol participants from both groups were compared to an historical cohort matched for baseline age, stroke severity and impairment who only received usual customary care. Despite three-fold difference in active upper limb therapy minutes there were no differences in the three-month ARAT or {Delta}FM. Indeed, the recovery in FM-UE at 3 months was proportional to baseline impairment, suggesting that the gains could be largely attributable to spontaneous biological recovery. While patient-related factors limited the dose of therapy achievable in this trial, clinician and service-related factors would also need to be overcome in routine clinical practice, to deliver equivalent doses at this early phase. It may be necessary to forego HDHI therapy until the late sub-acute phase.

BackgroundConventional evaluations of digital health interventions typically assess mean treatment effects, potentially masking heterogeneous impacts across the functional recovery distribution. Patients at the lower and upper tails of recovery trajectories may respond differently to AI-enhanced telerehabilitation, yet standard regression approaches cannot capture these distributional nuances. ObjectiveThis study applied Recentered Influence Function (RIF) quantile regression with Oaxaca-Blinder decomposition to examine how AI-enhanced telerehabilitation differentially affects functional recovery outcomes across the entire distribution, and to decompose observed disparities into explained (composition) and unexplained (structure) components. MethodsWe analyzed data from 486 post-stroke patients across three rehabilitation centres in Singapore (January 2023-December 2025). Patients received either AI-enhanced telerehabilitation (n=241) incorporating natural language processing-based progress monitoring and adaptive exercise prescription, or standard care (n=245). RIF-quantile regressions were estimated at the 10th, 25th, 50th, 75th, and 90th quantiles of the Functional Independence Measure (FIM) score distribution. Oaxaca-Blinder decomposition at each quantile partitioned group differences into composition effects (attributable to differences in observable characteristics) and structure effects (attributable to differential returns to those characteristics). ResultsThe AI-enhanced telerehabilitation group demonstrated significantly greater FIM improvements across all quantiles, with the largest effects at the 10th quantile ({beta} = 12.74, 95% CI: 8.92-16.56, p < 0.001) and 25th quantile ({beta} = 9.83, 95% CI: 6.71-12.95, p < 0.001), diminishing at the 90th quantile ({beta} = 3.21, 95% CI: 0.88-5.54, p = 0.007). RIF decomposition revealed that at the 10th quantile, 68.3% of the treatment-control gap was attributable to structure effects, indicating that AI-enhanced telerehabilitation fundamentally altered recovery mechanisms for lower-performing patients rather than merely leveraging differences in patient characteristics. ConclusionsAI-enhanced telerehabilitation produces its most pronounced benefits among patients at the lower end of the functional recovery distribution, suggesting a potential mechanism for reducing outcome inequality in stroke rehabilitation. RIF-quantile regression decomposition offers a methodologically rigorous framework for understanding distributional treatment effects that are invisible to conventional mean-focused analyses.

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.

BackgroundRobot-assisted training is increasingly being adopted to deliver high-intensity, repetitive, and task-specific treatments with real-time feedback to augment recovery. However, the causal role of robotic assistance in sensorimotor recovery, an underlying core mechanistic feature, remains unclear. ObjectiveThis study systematically reviewed randomized controlled trials (RCTs) on upper-limb rehabilitation that isolated the effect of robotic assistance by comparing similar interventions differing only in presence, level, or mode of robotic assistance. MethodThree electronic bibliographic databases-PubMed, Scopus and Google Scholar were searched. Twelve RCTs were included in the qualitative synthesis, and data from eight studies (all involving stroke survivors) were meta-analysed with the Fugl-Meyer Assessment score (measure of impairment) as the primary outcome. The main analysis was done to assess the overall effect of robotic assistance, regardless of disease stage, assistance level and targeted limb area, whereas subgroup analyses were conducted to evaluate the impact of robot-assisted therapy on chronic stroke survivors and to compare therapies focused on the shoulder-elbow versus the hand (wrist/fingers). ResultsThe main analyses yielded a significant positive effect size (0.462) favouring robotic assistance in impairment recovery, however with a significant heterogeneity between the studies. Subgroup analyses suggested potential benefits in chronic phase (moderate significant effect size 0.588), and similar therapy gain for shoulder-elbow and hand-specific training. ConclusionLimited available RCTs with small sample sizes and moderate heterogeneity prevented any firm conclusion to be drawn, and highlighted the need for systematic, controlled studies with large sample sizes to better understand the direct role (mechanistic feature) of robotic assistance in sensorimotor recovery.

BackgroundAbnormal muscle co-activation contributes to arm impairment after stroke. This single-blind, randomized, sham-controlled trial evaluated the feasibility and efficacy of home-based, personalized myoelectric interface for neurorehabilitation (MINT) conditioning to reduce abnormal co-activation and enhance arm function and determine the optimal number of abnormally co-activating muscles to target during training. MethodsModerately to severely impaired chronic stroke survivors were randomized to one of three MINT groups (who played customized games requiring independent activation of 2 or 3 abnormally co-activating muscles) or a sham control group (played using one muscle). All groups trained 90 minutes/day, 5 days/week at home and 1 day/week in lab, for 6 weeks, and changed trained muscle sets every 2-3 weeks. The primary outcome was the Wolf Motor Function Test (WMFT) at 6 weeks. ResultsFifty-nine participants completed the training. Participants performed 315 {+/-} 85 (mean {+/-} SD) repetitions daily. At week 6, participants in all MINT groups combined improved by 4 s on WMFT (p=0.0008), exceeding the minimal clinically important difference (1.5 s). Participants who trained 3 muscles simultaneously improved by 6.8 s (p=0.001), while the 2-muscle and sham groups did not change significantly. In per-protocol analysis, the 3-muscle group, but not 2-muscle groups, improved significantly more than sham (p=0.046), though not in intention-to-treat analysis. All MINT groups continued improving at 4 weeks post-training. Importantly, severely impaired participants in combined MINT groups improved more than those in sham (p=0.02). Importantly, combined MINT groups also improved their reaching range of motion significantly more than sham. Co-activation decreased by 76% in MINT groups during training. Notably, reduction in co-activation during reaching correlated significantly with improved arm function and range of motion. Other secondary outcomes did not show clinically important improvement. Stroke involving the posterior limb of the internal capsule negatively predicted response to MINT. ConclusionsHome-based MINT conditioning, especially the 3-muscle variant, is feasible, reduces co-activation, and improves arm movement and function. Clinical Trial RegistrationClinicalTrials.gov (NCT03401762)

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.