Neurorehabilitation and Neural Repair

BackgroundStroke leads to both motor and cognitive impairments that can substantially limit daily activities and independence. Although these impairments are often treated separately in rehabilitation, growing evidence suggests they are interconnected. Understanding how cognitive and motor impairments relate to one another is essential for developing more effective, integrated rehabilitation strategies. ObjectiveThis longitudinal study addressed three key questions: (1) Do motor and cognitive impairments co-occur after stroke? (2) Does cognitive ability influence motor recovery? (3) Are cognitive and motor recovery trajectories associated? MethodsWe followed 148 individuals in the subacute phase of stroke, assessing them at 1 and 3 months post-stroke. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the clock drawing test. Motor impairment was assessed using the Fugl-Meyer Assessment (FMA) and grip strength. Activity was evaluated using the Action Research Arm Test (ARAT), 10-Meter Walk Test (10MW), and Timed Up and Go (TUG). ResultsAt one month post-stroke, cognitive and motor impairment and activity levels were not correlated, although strong within-domain correlations were observed. Baseline cognitive ability did not predict motor impairment recovery. However, improvements in cognitive ability from 1 to 3 months were moderately correlated with gains in motor activity measures (r = 0.22-0.29, p < 0.05). ConclusionsAlthough cognitive and motor impairments may arise independently after stroke, their recovery processes appear partially linked. These findings underscore the importance of addressing both domains in rehabilitation and advancing understanding of shared mechanisms that support recovery across functional systems.

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 [&le;]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.

Introduction: High-intensity locomotor training (HIT) is recommended for improving walking capacity, but treatment responses are variable. Understanding the brain changes underlying responsiveness to training could provide insight into this variability. Emerging evidence suggests upregulation of the contralesional cortico-reticulospinal tract (CRST) may contribute to walking function after stroke. However, it is unclear whether CRST upregulation is supportive or maladaptive, and no studies have examined CRST changes after HIT. This study investigated how CRST and corticospinal tract (CST) strength and laterality reorganize, and their relationship with walking capacity after locomotor HIT. Methods: Ten participants with chronic stroke completed a 4-week no-intervention control phase then 4-weeks of HIT. Diffusion MRI and 6-minute walk distance were obtained at weeks 0, 4, and 8. Analysis tested changes in ipsilesional and contralesional CRST and CST strength and laterality. Associations between changes in tract laterality and walking capacity were examined. Results: During the treatment phase (vs. the control phase), there were significantly greater increases in contralesional CRST strength (1.02 SD [95% CI: 0.25, 1.79]), contralesional CRST laterality (4.44 [2.15, 6.72]), and 6-minute walk distance (33 meters [17, 50]). Walking capacity improvements were associated with changes in CRST laterality (r = 0.77, p = 0.01), but not CST laterality (r = -0.01, p = 0.98). Discussion: Following HIT, increases in contralesional CRST strength and laterality were observed. CRST laterality changes were strongly associated with walking improvements, suggesting a possible supportive role of contralesional CRST in mediating training-related improvements in walking function after stroke.

ImportanceRecovery after upper extremity peripheral nerve injury (PNI) surgery depends on changes in cortical neural patterns that support sensorimotor control. Task-based functional connectivity (FC) can characterize these changes, yet few studies have explored FC during ecologically fine motor valid tasks after PNI. ObjectiveTo investigate task-based FC with the left primary motor cortex (M1) during right hand drawing in individuals following right hand PNI surgery. ParticipantsForty-four right-handed adults, including 12 patients post PNI surgery (n = 8 with nerve repair, n = 4 with nerve transfer) and 32 healthy controls. MethodsAll participants underwent fMRI while performing a RH visuomotor precision drawing task. Seed-based connectivity analysis was performed to characterize the pattern of FC between left M1 and all voxels in the brain. We hypothesized that left M1 FC would differ between patients and controls, between Repair and Transfer groups, and covary with time since surgery. ResultsPatients (vs. controls) showed greater FC between left M1 and right visual and premotor cortices. Nerve transfer (vs. repair) showed greater FC between left M1 and right inferior parietal areas. Time since surgery was not linearly related to FC, though exploratory analyses suggested a negative association between log-time and FC between left M1 and right inferior parietal lobule. ConclusionAfter PNI surgery, visuomotor precision drawing involved distinct and behaviorally relevant neural patterns, which varied by task demand and potentially by surgical group despite clinical heterogeneity. Inferior parietal cortex may be especially engaged in early months after surgery (i.e. log-time). To improve recovery of upper limb function after PNI, clinical recommendations include incorporating early function-specific dexterous training, tailoring rehabilitation across surgical and recovery stages, and using multidimensional assessments of hand function.

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.

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.

Recovery of hand and arm function is critical for improving quality of life in individuals with tetraplegia due to spinal cord injury (SCI). Nerve transfer procedures can restore meaningful hand and arm function in chronic SCI, yet postoperative outcomes vary widely. We conducted a prospective, single-arm, open-label trial to assess the impact of intensive, robot-assisted rehabilitation training on functional recovery and cortical reorganization following nerve transfer. The primary endpoint was assessment of hand and arm function measured by the Box and Blocks Test. We report the results from three participants, AIS A at enrollment, who completed six weeks of intensive robotic training at least 1 year after nerve transfer surgery (NCT04041063). All participants demonstrated minimally important difference improvements in at least one secondary clinical outcome. These improvements were accompanied by cortical reorganization measured by transcranial magnetic stimulation motor mapping, indicating integration of the newly established peripheral motor pathways. No serious adverse events related to surgery or rehabilitation occurred. Although recruitment was limited by the COVID-19 pandemic and precludes definitive conclusions regarding efficacy, these findings suggest that standardized, intensive robotic rehabilitation may enhance functional outcomes after nerve transfer surgery for chronic tetraplegia.

ImportanceMedicare-Medicaid dual eligible beneficiaries experience pronounced disparities in stroke recovery. However, it remains unclear whether inpatient rehabilitation services and outcomes are comparable between dual-eligible beneficiaries enrolled in Medicare fee-for-service (FFS) versus Medicare Advantage (MA) plans. ObjectiveTo compare rehabilitation therapy utilization and associated outcomes among dual-eligible beneficiaries enrolled in FFS versus MA plans with stroke. DesignRetrospective cohort study. SettingInpatient Rehabilitation Facilities (IRF). ParticipantsMedicare beneficiaries admitted to IRF with stroke (n=125,782) between 2017 and 2019. ExposureDual-eligible beneficiaries enrolled in FFS versus MA plans. Main Outcome MeasuresTotal number of minutes of physical and occupational therapy provided within the first 2 weeks of IRF stay, self-care and mobility change scores, and 30-day all-cause hospital readmission. ResultsFor the first 2 weeks of therapy utilization, we did not find significant differences between the four groups. Using the non-dual FFS beneficiaries and low category of change as a reference, we found significantly lower likelihood of achieving high change in self-care scores for the dual FFS (OR=0.73, 95% CI=0.69-0.76), and dual MA (OR=0.93, 95% CI=0.88-0.98). However, non-dual MA patients had a higher likelihood of changes in self-care scores (OR=1.17, 95% CI=1.13-1.22). Similar trends were found for the mobility change scores, compared to non-dual FFS: dual FFS (OR=0.72, 95% CI=0.68-0.75), and dual MA (OR=0.91, 95% CI=0.86-0.96) and non-dual MA (OR=1.16, 95% CI=1.12-1.20). For 30-day readmission risk, dual FFS showed a higher likelihood of readmission (OR=1.19, 95% CI=1.08-1.31), while non-dual MA had a significantly lower likelihood (OR=0.77, 95% CI=0.71-0.83). Conclusions and RelevanceAlthough no differences in rehabilitation therapy utilization for stroke among dual-eligible beneficiaries, they had poorer functional recovery and higher 30-day readmission risk irrespective of FFS vs MA. Whereas non-dual-eligible MA beneficiaries experienced favorable outcomes. These findings underscore the importance of addressing post-IRF discharge needs among disadvantaged populations.

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.

Those living with right hemisphere damage (RHD) often struggle with engaging in aspects of conversation that require understanding what a speaker means. There is growing evidence that conversation relies on deducing the speakers perspective, an ability known as theory of mind (ToM). However, whether conversation deficits after RHD relate to ToM deficits is unknown. Here, we related individual differences in conversational success to ToM in 33 speakers during the early stages of RHD (median 5 days post-stroke) in comparison to 16 age- and education-matched controls. We measured conversational success as the number of differences identified between two images while participants conversed with study coordinators. A non-verbal false belief task measured ToM abilities.1 Baseline cognitive tasks assessed visual inattention, inhibitory control/visual selective attention and working memory. Mixed-effects linear modeling revealed that the ToM ability to explicitly infer others perspectives while managing conflict with ones own was the most significant predictor of conversational success ({beta} = 0.51, p = .02). Results were independent of demographic factors, conversation partner and baseline cognitive abilities. These findings provide the first empirical evidence in unilateral RHD that the ability to reason about a partners knowledge and manage conflict with ones privileged perspective is critical for successful conversation. Results support theoretical models of ToM as a cognitive basis for everyday conversation. The clinical implications underscore the importance of socio-cognitive screening and ToM-based interventions to enhance communication outcomes in stroke rehabilitation.

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.

BackgroundFunctional recovery after chronic stroke remains limited, requiring intensive and engaging rehabilitation approaches. Non-immersive virtual reality (NIVR) provides task-oriented, feedback-driven training that may enhance motor recovery in this population. ObjectiveTo evaluate the clinical effectiveness of a NIVR-based intervention (MindMotion GO) on upper limb motor function in patients with chronic left middle cerebral artery ischaemic stroke (LMCA stroke). MethodsA single-blind randomized controlled trial was conducted in 26 patients with chronic middle cerebral artery stroke. Five participants were lost to follow-up, resulting in a final sample of 21 patients allocated to the non-immersive virtual reality group (NIVR, n = 9) and conventional occupational therapy group (n = 12). Both groups completed an 8-week intervention consisting of two 30-40-minute sessions per week. The primary outcome was upper limb motor function assessed using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE). Secondary outcomes included health-related quality of life (SF-12v2), emotional status (Hospital Anxiety and Depression Scale), and caregiver burden (Zarit Burden Interview). Statistical analyses were performed using the intention-to-treat principle with non-parametric tests. ResultsThe NIVR group showed a clinically meaningful improvement in FMA-UE (median {Delta}21), exceeding the minimal clinically important difference (MCID = 7.35), whereas the control group showed smaller gains ({Delta}2.50) that did not reach clinical relevance. Both groups improved significantly over time; however, between-group differences were not statistically significant (P > 0.05). No significant changes were observed in quality of life, mood, or caregiver burden. ConclusionsNIVR using MindMotion GO is a safe and feasible intervention that can induce clinically meaningful improvements in upper limb motor function in chronic stroke patients. These findings support the incorporation of accessible, task-oriented virtual rehabilitation strategies in long-term stroke care.

BACKGROUNDFreezing of gait (FOG) is a disabling feature of Parkinsons disease (PD). Although physical practice (PP) improves gait, maintaining gains remains challenging. Mental practice (MP), including Dynamic Neuro-Cognitive Imagery (DNI), may enhance gait control, but evidence on remote combined interventions is limited. PURPOSETo investigate whether adding MP grounded in DNI principles to remote physical practice supports greater and more sustained improvements than remote physical practice alone in people with PD and FOG. METHODSA prospective, single-blind, parallel-group randomized controlled trial was conducted. Forty-three participants with idiopathic PD and FOG were randomized to an experimental group (EG, n = 20) or control group (CG, n = 23), stratified by cognitive performance. Both groups received 10 remote sessions over 6 weeks. All performed structured physical practice targeting gait components; the EG additionally performed MP based on DNI, while the CG performed time-matched seated stretching. Assessments were conducted at baseline (BI), post-intervention (AI), and 30-day follow-up (FU). The primary outcome was Rapid Turns Test performance; secondary outcomes included FOG severity, motor aspects of daily living, mobility-related quality of life, and global cognition. RESULTSAll randomized participants were included in intention-to-treat analyses; 38 completed all assessments. Significant group x time interactions were found for Rapid Turns Test duration (p = 0.0019) and FOG time (p = 0.0108). Both groups improved short-term, but only the EG maintained gains at follow-up. Additional interactions favored the EG for mobility-related quality of life (p = 0.001) and global cognition (p = 0.0018). Self-reported FOG improved over time in both groups (p < 0.001) without between-group differences, while motor aspects of daily living showed a time effect only (p = 0.001). CONCLUSIONMP based on DNI principles may enhance retention of gains when combined with remote physical practice, supporting its use as an adjunct in FOG rehabilitation. Trial registrationThis trial is registered at ClinicalTrials.gov with trial registration number NCT06957405 (registered on April 25, 2025). Protocol and statistical analysis planThe full trial protocol and statistical analysis plan are available upon request from the corresponding author. Data sharingThe datasets generated, used and analyzed during the trial are or will be available from the corresponding author upon reasonable request. Funding and conflicts of interestThis article was produced as part of the activities of FAPESP Research, Innovation and Dissemination Center for Neuromathematics (grant #2013/07699-0, Sao Paulo Research Foundation). Co-author PRS received individual support from FAPESP (grant number 2025/14403-7). The authors declare no conflict of interest.

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.

BACKGROUNDDamage to the early visual cortex after an occipital stroke typically results in the loss of conscious vision in the contralateral hemifield. Nonetheless, extensive perceptual training can restore visual motion discrimination in the blind-field. Here, we assessed, in a cohort study, whether improvements transferred to an untrained Gabor detection task and whether awareness within the blind field increased. We then explored the neural underpinnings of these changes. METHODSEighteen participants (6 female; aged 24-74 years; >6 months post-stroke) completed at least six months of visual rehabilitation in their blind field. Rehabilitation consisted of participants practicing a two-alternative, forced-choice, motion discrimination task using random dot stimuli, five days/week, at home, at one or two non-overlapping, locations in their blind-field. Each participant also completed two in-lab visits: one pre- and one post-training. A subset returned to the lab for a follow-up visit three months later to assess persistence of recovery. In addition to the trained task, an untrained, drifting-Gabor detection task was used to measure transfer of learning and changes in visual awareness at the trained locations. To investigate neural mechanisms underlying generalisation of improvements, participants completed MRI scanning at each lab visit. Magnetic resonance spectroscopy (MRS) was used to quantify GABA and glutamate concentrations in the ipsilesional motion sensitive area, hMT+, and a control voxel in the sensorimotor cortex. Functional MRI was conducted to assess BOLD signal changes in hMT+ and across the rest of the brain during passive viewing of high contrast Gabor stimuli in the blind field. RESULTSParticipants showed significant improvements in motion direction discrimination (trained task) between pre- and post-training in-lab visits, which generalised to improvements in Gabor detection and awareness (untrained task). Reduced GABA and glutamate in ipsilesional hMT+ was linked to improved Gabor detection, but not awareness. Increased BOLD signals in hMT+ and dorsolateral prefrontal cortex also correlated with improved Gabor detection, while awareness changes were linked to higher-level areas associated with visual attention in the contralesional prefrontal cortex (area 46) and inferior parietal lobule. CONCLUSIONSLong-term visual rehabilitation using a global motion discrimination task generalised to enhance both detection and awareness of moving Gabors within the blind field of occipital stroke survivors. Improvements were supported by selective changes in brain regions known to be involved in motion perception and attention respectively, suggesting that a broad network supports recovery, which could be targeted to enhance outcomes.