Neurorehabilitation and Neural Repair

BackgroundAccumulating results suggest that reticulospinal tract (RST) excitability increases after stroke. While animal studies suggest this hyperexcitability may compensate for corticospinal tract (CST) damage, its role in motor function in people with stroke (PwS) remains debated. This study aimed to: (1) replicate findings of RST hyperexcitability in PwS using the StartReact paradigm, measuring acceleration of motor response to a startling auditory stimulus; (2) examine the relationship between RST hyperexcitability and motor impairments after stroke; and (3) explore whether RST hyperexcitability provides functional benefits in severely impaired PwS. MethodsForty-six PwS completed the StartReact paradigm and motor assessments (Fugl-Meyer, ARAT, grip strength, Modified Ashworth Scale). PwS were categorized into high StartReact effect and typical StartReact effect subgroups based on comparisons with a healthy control group (n=37). Severe impairment was defined as ARAT [≤]10. ResultsPwS exhibited significantly greater StartReact effects than controls. The high StartReact effect subgroup showed worse motor function, weaker grip strength, and higher spasticity. Among severely impaired PwS, high StartReact effect was not associated with improved grip strength. ConclusionsThese findings confirm the existence of RST hyperexcitability after stroke and suggest it is associated with poorer motor outcomes, likely due to reduced cortical input to the brainstem. The absence of functional benefit in severely impaired individuals supports the interpretation that RST hyperexcitability is a maladaptive rather than a compensatory reaction to brain damage. These findings provide insight into the neurophysiological mechanisms underlying motor impairments after stroke and do no imply direct clinical or therapeutic applications.

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.

PurposeThe prognosis of post-stroke ataxia remains controversial. It is unclear whether the proportional recovery rule (PRR) established for hemiparesis applies to ataxia, given that cerebellar plasticity suggests trajectories may not depend solely on initial severity. This study was conducted to quantitatively decompose longitudinal ataxia recovery trajectories into proportional recovery coefficient (r) and time constant ({tau}) using a Bayesian nonlinear mixed-effects model, and elucidate their independent determinants and associations with functional walking independence. MethodsWe analyzed longitudinal SARA scores of 80 subacute patients with stroke to estimate individual initial severity (), r, and {tau}. Recovery patterns were clustered based on these parameters. We analyzed the attainment of independent walking using the Kaplan-Meier method and identified predictors via hierarchical multiple regression analysis. ResultsThree distinct clusters were identified. The moderate group (younger, preserved attention) achieved rapid improvement and early walking independence. In contrast, the severe group showed a significantly prolonged time constant ({tau}) but maintained a high proportional recovery coefficient (r), ultimately achieving walking independence in over 90% of cases. Regression analysis revealed a dissociation: biological age constrained the recovery ceiling (r), while attentional function independently regulated recovery speed ({tau}). ConclusionsRecovery from post-stroke ataxia bifurcates into rapid neurological restoration and a delayed process driven by compensatory learning. Especially in severe cases, long-term learning using attentional resources is crucial. These findings challenge prognosis prediction based solely on initial severity, supporting stratified rehabilitation strategies tailored to individual recovery ceilings and learning speeds.

AIMExecutive functions (EF) are advanced cognitive processes that play an essential role in daily functioning and may be of increased importance in cerebral palsy (CP), given the complexity of primary and associated impairments. This study aims to synthesize existing evidence on the relation between EF and domains of the International Classification of Functioning, Disability and Health (ICF) in individuals with CP, and to quantify the magnitude of these associations through meta-analysis. METHODA systematic literature search was conducted in eight electronic databases up to 14 July 2025, examining associations between EF and ICF domains in CP. EF outcomes were classified into inhibitory control, working memory, cognitive flexibility, higher-order EF, and EF composite scores. Outcome measures were mapped onto ICF domains: Body Functions and Structures, Activity, Participation, and Contextual factors, using the CP Core Sets. Correlation coefficients were transformed to Fishers z and entered into three-level meta-analyses to estimate pooled effect sizes. Single moderator analyses examined CP subtype, EF domain, EF assessment type, and mean age. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. RESULTSFrom 4637 identified records, 38 studies were included, comprising a total sample of 1633 participants with CP. There was substantial heterogeneity in CP subtype, participant age, and EF conceptualization, while the ICF Contextual factors domain was underrepresented. A medium-to-large association was found between EF and functioning across all ICF domains combined (r=0.26, p<0.001). Domain-specific analyses showed a medium association of EF with Body Functions and Structures (r=0.21, p<0.01), a medium-to-large association with Activity (r=0.38, p<0.001) and Participation (r=0.26, p<0.01). CP subtype and mean age significantly moderated the overall EF-functioning association, with mixed CP and younger age associated with stronger effects. INTERPRETATIONEF are meaningfully associated with multiple domains of functioning in individuals with CP. These findings support the relevance of routine EF assessment and suggest that EF are an important cognitive correlate to consider when addressing broader aspects of daily functioning. WHAT THIS PAPER ADDSO_LIExecutive functions (EF) showed medium-to-large associations with all ICF domains in people with cerebral palsy (CP) C_LIO_LIThe strongest and most consistent associations were found between EF and ICF Activity C_LIO_LIOverall associations highlight the relevance of EF as a meaningful intervention target in CP C_LI

Background: High-dose high-intensity upper limb neurorehabilitation can lead to meaningful clinical gains even in chronic stroke, yet substantial variability in recovery remains unexplained. Identifying neurophysiological markers linked to neuroplasticity and recovery could provide mechanistic insights and guide personalised rehabilitation. Objective: To characterise stroke-related alterations in {beta}-activity during movement and neural activity at rest and explore associations between brain activity and changes in upper limb clinical outcomes in chronic stroke survivors undergoing three-week high-dose rehabilitation. Methods: Electroencephalography (EEG) was recorded during the three-week rehabilitation programme in 40 chronic stroke survivors participating in the Queen Square Upper Limb (QSUL) Programme, as well as in 26 healthy controls. Recordings were taken during passive movement of the affected and unaffected index fingers (~70 movements per hand) and at rest (~7 min). Clinical assessments included the Fugl-Meyer Upper Limb Assessment (FM-UE), reflecting impairment-level deficits, and the Chedoke Arm and Hand Activity Inventory (CAHAI-13), capturing real-world upper limb activity, to examine their differential relationships with movement-related {beta}-activity. Results: Stroke survivors showed significant improvements in FM-UE and CAHAI scores following the rehabilitation programme (Mean {Delta}: FM-UE = 7.5, CAHAI = 7.4), exceeding minimum clinically important differences. Compared to controls, stroke survivors exhibited less strong {beta}-event-related desynchronization/synchronization ({beta}-ERD/ERS) during passive movement of the affected and unaffected index finger, with effects lateralised to the lesioned hemisphere. No significant differences at rest were observed between stroke participants and healthy controls. Only improvements in CAHAI, but not FM-UE, were associated with stronger {beta}-ERD (more negative) and stronger {beta}-ERS (more positive) responses during passive movement. Conclusions: Stronger movement-related {beta}-activity is associated with improvements in upper limb activity following high-dose high-intensity neurorehabilitation, suggesting {beta}-activity as a potential marker of neuroplasticity.

Background and PurposeWalking speed is the dominant clinical metric used to classify post-stroke hemiparetic gait severity. However, speed does not describe how mechanical energy is generated and redistributed. We tested whether whole-body center-of-mass (COM) work patterns provide a biomechanically grounded supplement to speed-based severity classification. MethodsLimb-specific COM power and work were computed from ground reaction forces using the individual-limbs method across five walking speeds (0.2-0.7 m/s). We quantified net COM work index of asymmetry (IA_Wnet), positive COM work asymmetry (IA_Wpos), and the Propulsion-Support Ratio (PSR = impFy/impFz). Piecewise and quadratic regressions were used to assess speed-dependent trends. ResultsIA_Wnet remained elevated across speeds and showed no significant high-speed association. IA_Wpos demonstrated a significant quadratic relationship with speed (p=0.023, R{superscript 2}=0.23), decreasing near 0.5 m/s before rising again. Paretic limb PSR remained constrained and exhibited a quadratic association (p=0.012, R{superscript 2}=0.14), while unaffected limb PSR declined significantly at higher speeds (p=0.019, R{superscript 2}=0.38). Below 0.5 m/s, COM power profiles collapsed to a two-phase pattern without paretic limb push-off; at [&ge;]0.5 m/s, a four-phase structure emerged. ConclusionIncreasing walking speed did not normalize interlimb mechanical imbalance. COM work organization revealed a biomechanical transition near 0.5 m/s and distinguished compensation from recovery-based restoration. Supplementing speed with COM work and propulsion-support metrics may refine severity stratification and guide mechanism-targeted rehabilitation.

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.

BackgroundPeople with stroke often walk with temporal asymmetry; which is related to increased fall risk. The purpose of this study was to determine the relationship between temporal gait asymmetry and mechanical stability among people with sub-acute stroke. MethodsThirty-one people with sub-acute stroke (<6 months post-stroke) completed six walking trials in a biomechanics laboratory. Three-dimensional motion capture was recorded. Swing symmetry was calculated as a ratio of swing time on the more affected limb divided by swing time on the less affected limb. Mechanical stability was the minimum margin of stability, relative to the medial and lateral borders of the stance limb, during the single support phase of the gait cycle. Multiple linear regression was used to determine the relationship between swing symmetry and mechanical stability, controlling for step width and walking speed. ResultsThere was a significant negative relationship between swing symmetry and lateral margin of stability on the less affected side (p<0.0001) and medial margin of stability on the more affected side (p=0.023). That is, as swing symmetry increased, the extrapolated centre of mass tended to be closer to the lateral border of the less affected side and farther from the medial border of the more affected side. ConclusionGait asymmetry could, in part, result from a strategy to compensate for poor balance control on the more affected side. Alternatively, reduced lateral margin of stability on the less affected side among asymmetric participants indicates instability in this direction and could increase the risk for falling.

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.

BackgroundChronic stroke-related gait impairment remains a major source of disability. InTandem is an autonomous neurorehabilitation system delivering individualized, progressive rhythmic auditory stimulation for home-based gait rehabilitation. ObjectivesTo evaluate: (1) engagement during a 12-week autonomous, home-based intervention, (2) changes in walking endurance and functional mobility, and (3) outcome differences across pre-defined engagement and baseline speed subgroups. MethodsThis pragmatic, decentralized trial enrolled adults [&ge;]6 months post-stroke with residual gait deficits. Participants were asked to complete 30-minute sessions 3x/week for up to 12 weeks. Engagement was primarily assessed as the proportion achieving moderate-to-high weekly usage (> 4 weeks; benchmark p1 = 0.60). Changes in 6-Minute Walk Test (6MWT) distances and Timed Up and Go (TUG) times were analyzed using linear mixed-effects models. ResultsOf the 204 who initiated the intervention, 81.9% (95% CI [0.76-0.87]) engaged at least 4 weeks, meeting the primary endpoint (p < 0.001). Overall, 58.1% achieved high engagement (> 9 weeks), 23.9% moderate engagement (4-8 weeks), and 18.1% low engagement ([&le;]3 weeks). Significant improvements in 6MWT distance (+ 26.1 {+/-}5.6 m; 95% CI [14.99, 37.22]) and TUG times (-1.45{+/-}0.31 s; 95% CI [-2.06, -0.84]) (p < 0.001) were observed. Engagement influenced effectiveness: each additional week engaged predicted a 5.82 m greater gain in the 6MWT (SE = 2.05; 95% CI [1.77, 9.87], p < 0.005). ConclusionsAutonomous home-based delivery of music-based rhythmic auditory stimulation achieved moderate-to-high engagement and improved walking endurance and functional mobility, supporting InTandem as a scalable approach to chronic stroke gait rehabilitation. Trial registrationTrial registration: Clinicaltrials.gov NCT06051539. Registered on 20 September 2023. https://clinicaltrials.gov/study/NCT06051539

BackgroundHealth-related quality of life is a key secondary endpoint in stroke trials. Differential item functioning (DIF) occurs when individuals with the same underlying HRQOL interpret and respond differently to questionnaire items due to group characteristics, potentially biasing treatment comparisons. This study evaluates DIF in the patient-reported five-level EuroQOL (EQ-5D-5L) among patients with acute ischemic stroke across age, sex, and treatment groups. MethodsData were obtained from the AcT trial, a registry-based randomized comparison of alteplase and tenecteplase. Patients completed the EQ-5D-5L at 90 days post-stroke. DIF was assessed using multigroup graded response models with the Wald-based sweep procedure, which accounts for between-group differences in latent trait distributions. We quantified effect sizes using signed weighted area between curves (sWABC), considering |sWABC| <0.10 as negligible. ResultsAmong 1,264 patients (51.2% tenecteplase; 46.5% female; 30.1% aged [&ge;]80). Omnibus testing revealed significant DIF only for age (X{superscript 2} = 86.9, p < 0.001); neither sex (X{superscript 2} = 31.7, p = 0.063) nor treatment (X{superscript 2} = 22.4, p = 0.379) showed evidence of DIF. At the item level, four items flagged for age-related DIF: self-care, usual activities, pain/discomfort, and anxiety/depression. However, only self-care (sWABC = -0.46) and usual activities (sWABC = - 0.34) showed moderate effects, while pain/discomfort (sWABC = -0.002) and anxiety/depression (sWABC = 0.09) were negligible. Importantly, factor scores from models with and without DIF adjustment correlated (correlation coefficient = 0.98). ConclusionsThe EQ-5D-5L appears to function equivalently across sex and treatment groups in this stroke population. Age-related DIF, though statistically detectable in physical functioning items, had little practical consequence for individual scores, findings that support the instruments use for HRQOL comparisons in stroke trials. RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

BackgroundAdapted dance is a promising rehabilitation intervention for physical and psychosocial impairments in people with chronic stroke. However, in-person attendance is hindered by limited community ambulation, transportation, and schedule conflicts. At-home participation with a live-streamed dance program could address these issues, but psychosocial benefits may be diminished because of reduced social interactions. The primary objective of this study was to assess the feasibility and safety of a live-streamed dance program for chronic stroke. Secondary objectives were to characterize participants who choose live-stream vs in-person options and quantify pre-post changes in balance, gait and social connection. MethodPeople with chronic stroke were given the choice of attending a live-streamed adapted dance program either in-person or at home twice a week for 4 weeks. A priori feasibility criteria were tracked, and participants were characterized with self-report (Center for Epidemiologic Studies Depression Scale; CES-D) and performance-based measures (e.g., Montreal Cognitive Assessment, Chedoke McMaster Assessment) at baseline. Pre-post measures of secondary outcomes included gait speed, Mini Balance Evaluation Systems Test (Mini-BESTest), Activities of Balance Confidence Scale (ABC), and Inclusion of Community in Self scale (ICS). Unpaired median/mean differences in baseline clinical presentation were used to compare in-person and live-stream participants. Paired median/mean differences were used to examine change in secondary outcomes with dance. ResultsInterest and enrollment rates for both groups combined were 87% and 38% respectively. Of the 13 people who enrolled, 8 chose in-person and 5 chose live-stream. In-person and live-stream attendance rates were 83% and 89% respectively, and retention rates were 80% and 75% respectively. At baseline, the in-person group had greater depressive symptoms (CES-D score, median [IQR] difference: 11.5 [-21.5, -5]), and faster mean gait speed (-25.8cm/s [-50.98, 0.006]) than the live-stream group. There were no pre-post changes in secondary outcome measures. ConclusionsA live-streamed dance intervention featuring in-class and at-home participation is safe and feasible for people with chronic stroke. These results will inform a future randomized controlled trial to investigate the effects of a live-stream dance program with a longer duration while considering how factors such as gait function and mood may relate to the choice between in-person and at-home attendance.

Introduction: Adults with spinal cord injury (SCI) often experience reduced or lost sensation and movement, impairing the ability of the brain to locate paralyzed body parts, which, in turn, compromises sensorimotor recovery. This disruption of the internal body map of the brain, or mental body representations (MBR), also contributes to neuropathic pain in about 69% of adults with SCI. Medications for neuropathic pain are often ineffective and can cause adverse reactions. Our previous pilot clinical trial showed that Cognitive Multisensory Rehabilitation (CMR), a physical therapy that restores MBR, produced significant, lasting reductions in neuropathic pain, improved sensorimotor function, and enhanced brain function. Building on these results, we examined whether 8 weeks of CMR or adaptive fitness (1) improved sensorimotor function and reduced pain; (2) greater brain activity and connectivity related to sensorimotor function and MBR in adults with SCI. Methods: Sixteen participants (52+/-8 years old, 13+/-10 years post-SCI) were randomized to 8 weeks of CMR or adaptive fitness (45 min, 3x/week). Ten participants had neuropathic pain of 3/10 or greater. Pain and sensorimotor function were assessed at baseline, post-intervention, and 3-month follow-up using the Numeric Pain Rating Scale (NPRS), ASIA Impairment Scale (AIS), and Neuromuscular Recovery Scale (NRS). Functional MRI included resting-state and 4 tasks: imagining feeling the left leg, imagining moving the left leg, whole-body movement imagery, and a sensation task. Results: After CMR, participants improved on AIS with large effect sizes (touch: d=1.54; pinprick: d=1.83; lower limb motor function: d=1.32), while adaptive fitness had small/moderate effects (touch: d=0.49; pinprick: d=0.53; lower limb motor function: d=0.74). CMR also showed larger effect sizes for NRS (core: d=2.19; upper limb: d=0.69; lower limb: d=0.74) than fitness (core: d=0.73; upper limb: d=0.34; lower limb: d=0.00). Benefits persisted at follow-up. Highest neuropathic pain intensity reduced post-CMR and at 3-month follow-up (d=0.48; d=0.63). Pain increased slightly after fitness (n=6; d=-0.19; d=-0.41). CMR increased brain connectivity and activation during the leg imagery task. Increased activation during whole-body imagery was greater after CMR than fitness. Discussion: These preliminary results support the potential of CMR to improve function and reduce neuropathic pain in adults with SCI, warranting larger confirmatory trials. Clinicaltrial.gov: NCT05167032

Objectives: Among individuals attending stroke rehabilitation, we aimed to determine the proportion who participated in cardiorespiratory exercise, identify patient characteristics predicting participation, and describe exercise characteristics. Design, setting, and participants: This was an observational cohort study involving all patients admitted to four stroke rehabilitation centres in Ontario, Canada, during March or October 2019, or over 12 months starting in 2021. Main measures: Patient characteristics extracted during chart review included age, sex, marital status, employment status, date of stroke, time post-stroke at admission, length of stay for rehabilitation, past medical history that could affect exercise participation, Functional Independence Measure, Functional Ambulation Category, mobility aid use, Chedoke-McMaster Stroke Assessment, Montreal Cognitive Assessment, National Institutes of Health Stroke Scale, and details describing cardiorespiratory exercise completed. Results: 40.1% of stroke patients participated in cardiorespiratory exercise, with 26.4% having it included in their treatment plan. Diagnosed cardiac disease (OR=0.74), poor left ventricular function (OR=0.09), history of mental health conditions (OR=0.69), lower functional ambulation ability (OR=0.74), and wheelchair use at rehabilitation admission (OR=0.46) were associated with lower odds of participating in cardiorespiratory exercise after stroke (p-values<0.05). Use of a walker or rollator at rehabilitation admission (OR=3.22), having a cardiorespiratory exercise goal (OR=2.13), and longer lengths of stay (OR=1.01) were associated with higher odds of participating in cardiorespiratory exercise after stroke (p-values<0.05). Only 1.5% of patients (N=9/601) who participated in cardiorespiratory exercise completed it with recommended intensity and duration. Conclusion: Improving participation in cardiorespiratory exercise during stroke rehabilitation may require addressing cardiovascular, mental health, and mobility-related barriers.

BackgroundRobotic exoskeleton-assisted gait training (RAGT) has emerged as a promising modality for post-stroke rehabilitation. However, the longitudinal trajectory of functional recovery and its association with clinically meaningful milestones such as independent community ambulation remain poorly characterised. Standard analytical approaches that treat longitudinal and survival outcomes separately may yield biased estimates due to informative dropout and the endogenous nature of time-varying functional measures. ObjectiveTo jointly model the longitudinal trajectory of lower-extremity motor function and time to independent community ambulation following RAGT for stroke survivors, while accounting for the mutual dependence between the two processes using a Bayesian joint modelling framework. MethodsA multi-centre retrospective cohort study was conducted across four Canadian rehabilitation hospitals (2019 to 2024). A total of 327 adults with first-ever ischaemic or haemorrhagic stroke who received RAGT using the EksoNR or Indego exoskeleton platforms were included. The primary longitudinal outcome was the Fugl-Meyer Assessment Lower Extremity (FMA-LE) score measured at baseline, weeks 4, 8, 12, 24, and 52. The survival outcome was time to achieving independent community ambulation (Functional Ambulation Category score of 4 or higher sustained for at least two consecutive assessments). A Bayesian shared-parameter joint model was specified, linking a nonlinear mixed-effects longitudinal submodel to a Weibull proportional hazards survival submodel through the current value and slope of the subject-specific FMA-LE trajectory. Estimation was performed using Hamiltonian Monte Carlo sampling with four chains of 5,000 iterations each (2,500 warmup). ResultsThe median age was 62.4 years (IQR 54.1 to 71.8), 58.1% were male, and 63.0% had ischaemic stroke aetiology. The longitudinal submodel revealed a nonlinear recovery pattern best described by a three-knot restricted cubic spline, with rapid improvement during the first 12 weeks (mean gain 8.7 FMA-LE points, 95% CrI 7.2 to 10.3) followed by a plateau phase. The association parameter linking the current FMA-LE value to the hazard of achieving community ambulation was 0.084 (95% CrI 0.061 to 0.109), indicating that each one-point increase in the subject-specific FMA-LE trajectory was associated with an 8.8% increase in the instantaneous hazard (HR = 1.088, 95% CrI 1.063 to 1.115). The trajectory slope parameter was also significant (0.043, 95% CrI 0.012 to 0.078), suggesting that patients with steeper recovery gradients had additional survival advantages beyond their current functional level. At 52 weeks, 54.7% of participants achieved independent community ambulation. Haemorrhagic stroke (HR = 0.68, 95% CrI 0.49 to 0.93), older age (HR per decade = 0.81, 95% CrI 0.70 to 0.94), and higher baseline NIHSS score (HR per point = 0.94, 95% CrI 0.91 to 0.97) were associated with lower hazards of achieving the ambulation milestone. ConclusionsThe Bayesian joint model revealed that both the current functional level and the rate of functional change are independently predictive of achieving community ambulation following RAGT. These findings support individualised rehabilitation planning where treatment intensity may be dynamically adjusted based on the evolving recovery trajectory, and provide further evidence for the clinical value of robotic exoskeleton interventions in stroke rehabilitation.

Walking impairments in Parkinsons disease (PD), including reduced speed, cadence, and stride length, and increased variability, impair mobility and raise fall risk. Conventional treatments may fail to address these deficits, underscoring the need for complementary non-invasive alternatives. This study examined whether combining rhythmic auditory cueing with transcranial direct current stimulation (tDCS) over the supplementary motor area (SMA), a critical region for internally-generated movement, would enhance gait performance in PD. Thirty-three participants with PD and thirty-two healthy controls completed two sessions (anodal vs. sham tDCS) with gait assessed during stimulation, immediately after stimulation, and 15 minutes after stimulation under two auditory conditions: walking in silence and walking to music paced 10% faster than baseline cadence. Spatiotemporal, variability, and stability gait parameters were analyzed using linear mixed-effects models. Rhythmic auditory cueing significantly increased cadence and speed during, immediately after, and especially 15 minutes after stimulation, suggesting sustained effects of rhythmic entrainment. Anodal tDCS produced faster cadence, as well as lower stride time variability and stride width, particularly in individuals with PD. Although both music and anodal tDCS affected gait, no interaction was observed, indicating independent effects. Individuals with PD had greater gait variability overall, and adjusted temporal gait parameters less to music than healthy controls did. Anodal stimulation reduced walking variability in PD, reducing the group differences observed under sham conditions. These findings suggest that rhythmic cueing and SMA stimulation target complementary mechanisms, highlighting the promise of combined tDCS-music interventions for gait rehabilitation in PD.

Background: Moderate- to high-intensity walking training (M-HIT) is an established intervention for improving walking capacity in chronic stroke. Musculoskeletal (MSK) adverse events commonly occur during M-HIT, yet tools to identify individuals at higher risk are limited. Baseline clinical characteristics may provide insight into susceptibility to training-related MSK adverse events during M-HIT. Thus, this study aimed to develop and internally validate a model for predicting MSK adverse events during a 12-week M-HIT program in chronic stroke using baseline clinical characteristics. Methods: Participants (n=100) from HIT-Stroke Trials 1 and 2 were included. Baseline clinical characteristics included measures of orthopedic history, pre-existing pain, motor function, recent exercise history, demographics and health characteristics, stroke chronicity, and psychological health. Logistic regression models evaluated all possible combinations of baseline characteristics with up to three predictors. Leave-one-out cross-validation was used for internal validation to mitigate overfitting. Predictive performance was quantified using the C-statistic, and the candidate model with the highest cross-validated C-statistic was selected as the final model. Results: MSK adverse events occurred in 32.0% of participants. The optimal three-variable model included prior orthopedic condition (Odds ratio [OR] 3.02 [95% CI 1.14-8.64]), Fugl-Meyer lower extremity motor score (OR 1.14 [95% CI 1.02-1.28]), and self-reported participation in regular walking exercise (OR 0.17 [95% CI 0.05-0.49]) at baseline. This model demonstrated moderate discrimination (cross-validated C-statistic = 0.74; apparent C-statistic = 0.78). Conclusions: Participants reporting at least one pre-existing lower extremity or lumbar spine orthopedic condition and those with better lower-extremity motor function exhibited greater odds of experiencing MSK adverse events during M-HIT, while participants reporting participation in regular walking exercise had lower odds. These findings suggest that baseline clinical characteristics may help identify individuals at elevated risk for MSK adverse events during M-HIT who may warrant closer monitoring or risk-reduction strategies. Future studies are needed for external validation. Clinical Trial Registration: https://ClinicalTrials.gov; Unique identifiers: NCT03760016, NCT06268041

Background and purpose: People after mild traumatic brain injury (mTBI) show persistent deficits in reactive balance. Cortical processes engaged during preparation and execution of balance reactions are reflected in distinct cortical activity signatures that can be measured with electroencephalography (EEG). The purpose of this study was to 1) compare preparatory cortical beta activity and evoked cortical N1 responses during balance recovery in people with mTBI and controls, and 2) explore relationships between preparatory and evoked cortical activity. Methods: Participants (age 21-35 years) with symptomatic mTBI (n=5, 27 +/- 13 days post-injury) and controls (n=5) completed the instrumented and modified push & release tests of reactive balance. Cortical activity was recorded using encephalography (EEG). Main outcome measures were 1) preparatory sensorimotor cortical beta-bust power and duration prior to balance perturbation onset (-1s-0s), and 2) cortical N1 response amplitude and latency during the post-perturbation balance recovery (50-250ms). Results: People with mTBI exhibited lower preparatory beta-burst power compared to controls (p=0.044, g=1.18). During balance recovery, cortical N1 responses occurred earlier in people with mTBI compared to controls (p=0.045, g=3.28). Relationships between preparatory and evoked cortical activity were altered after mTBI compared to controls; people after mTBI with greater beta-burst power and longer duration elicited shorter N1 latencies (r's>0.77, p's<0.010). Discussion and conclusion: The results serve as preliminary, hypothesis-generating observations to guide future research directions investigating neural signatures of reactive balance deficits in people after mTBI. The preparatory brain state before reactive balance recovery should be explored as a potential target for post-mTBI balance rehabilitation.

BackgroundDespite recommendations in clinical guidelines, clinical experience indicates that engagement with splints and orthotics varies amongst people after stroke. ObjectivesThe aim of the study was to understand the factors that influence engagement with splints and orthotics in people after stroke. MethodsPeople after stroke who had been wearing a splint or orthotic (also known as devices) for at least 2 months under the care of one Community Neurosciences Team in the UKs National Health Service were included. Semi structured interviews based on the constructs of Banduras Social Cognitive Theory (SCT) were used to gather participants views, and a framework analysis applying the constructs of SCT was completed using NVIVO software. ResultsFour key themes were identified: 1. Self-Regulation; difficulties applying the device and aesthetic acceptability. 2. Self-Efficacy; increased confidence when wearing the device and reduced motivation to wear the device. 3. Outcomes Expectation; reduced falls risk, improved gait, improved balance, maintaining range of movement, and negative effects such as discomfort, pain, itching. 4. Social Support; support needed to apply the device and the burden on family members/carers to apply the device correctly. ConclusionsThe findings of this study highlight key factors that influence engagement with orthotics and splints. These include difficulty applying the device after stroke, device aesthetics, comfort, and the importance of continued support from carers. Manufacturers should consider how people after stroke can independently don and doff devices. Education of carers and family members also appears key to support their engagement.

BackgroundSedentary behavior is highly prevalent following traumatic brain injury (TBI) and compounds existing risks for cardiovascular, neurodegenerative, and affective disorders. The cognitive and behavioral sequelae of TBI, including impaired decision-making, blunted reward processing, and cognitive fatigue, create particular barriers to adopting and maintaining an active lifestyle. Despite this, effective behavior change interventions targeting physical activity in community-dwelling TBI survivors remain scarce. Here, we evaluated the feasibility, compliance, and preliminary efficacy of a 12-week remotely delivered walking intervention combining planning, behavioral reminders, and monetary micro-incentives. MethodsFifty-six adults aged 40-80 years with a mild-to-moderate TBI diagnosed between 3 months and 15 years prior were randomized to either a planning, reminders, and micro-incentives intervention (n=23) or a health advice control condition (n=25). Participants wore a Fitbit Inspire 3 continuously throughout the study. Intervention participants completed weekly phone calls to plan five 30-minute walks for the following week, received daily text message or email reminders on planned walk days, and earned small monetary incentives upon walk completion. Control participants received weekly health education calls. Feasibility was assessed through recruitment, retention, and adverse event rates. Compliance was assessed via phone call completion rates and Fitbit wear time. Efficacy outcomes included weekly walk counts, walking duration, and step counts, modeled using Poisson generalized linear mixed models and linear mixed-effects models over 12 weeks. ResultsForty-eight participants completed the study (retention rate: 84.2%), with high phone call compliance in both groups (intervention: 98.4%; control: 98.1%). Intervention participants completed significantly more walks than controls from week 1 onward (aIRR = 5.33, 95% CI: 2.27-12.5, p < 0.001), with the group difference growing over time (interaction aIRR = 1.09 per week, 95% CI: 1.01-1.17, p = 0.029). Estimated marginal means indicated that intervention participants completed 5.5 times more walks than controls at week 1, increasing to 15.5 times more by week 12. The intervention group also walked significantly longer at week 1 (b = 62.14 min, 95% CI: 1.05-123.23, p = .046), with the advantage growing over time; by week 12, intervention participants walked 5.3 times longer than controls. Similarly, the intervention group accumulated significantly more steps during walks at week 1 (b = 4,779 steps, 95% CI: 45.50-9,513.00, p = .048), accumulating 3.1 times more steps than controls by week 12. ConclusionsA remotely delivered, multicomponent walking intervention targeting planning, behavioral reminders, and micro-incentives was feasible, well-tolerated, and produced meaningful increases in walking activity in community-dwelling adults with TBI. With high retention and compliance, and consistent effects on walk counts, duration, and steps across the intervention period, these findings provide compelling support for a larger, fully powered trial.