Neurorehabilitation and Neural Repair

Background. Abnormal muscle co-activation, also called abnormal synergies by clinicians, is an important contributor to arm impairment after stroke. While abnormal co-activation is well-described in chronic stroke, it remains unclear how early abnormal patterns appear and whether their spatial and temporal characteristics resemble those seen in the chronic phase. We sought to determine how soon after stroke abnormal muscle co-activation appears. Methods. In this cross-sectional study, thirty-nine participants with hemiparesis in the early subacute period (<21 days) and sixty-eight participants in the chronic period (>6 months) after stroke performed targeted reaching movements while surface electromyography (EMG) was recorded from nine upper-limb muscles. Muscle synergies (patterns of coordinated muscle activation) were identified using non-negative matrix factorization. Synergy composition (spatial structure) and activation profile (temporal structure) were compared across the contralesional arms of subacute and chronic participants and the ipsilesional arm, which served as the reference for normal coordination. Results. Three primary synergies accounted for most EMG variance during reaching in each arm group. A deltoid-dominant synergy characterized by abnormal co-activation of anterior and posterior deltoids, was present in both subacute and chronic stages in the contralesional arm but was absent in the ipsilesional arm. In addition, the elbow flexor synergy co-activated with the deltoid synergy in both contralesional groups but not in the ipsilesional arm. Abnormal co-activation between elbow flexor and elbow extensor synergies was also seen in contralesional, but not ipsilesional, arms. These abnormalities were already present 15 days after stroke and did not differ between subacute and chronic groups. Conclusions. Abnormal muscle co-activation appears within the first few weeks after stroke and persists in chronically impaired survivors. Its full development this early suggests these patterns arise rapidly rather than emerging gradually during recovery, and that interventions targeting abnormal co-activation may be most useful when applied early. Clinical Trial Registration? NCT03401762.

Background Upper limb dysfunction is among the most disabling consequences of stroke, yet transcranial direct current stimulation (tDCS), an extensively investigated adjunct to motor rehabilitation, has not demonstrated consistent benefit in large randomized trials. Unaccounted interindividual variability is a likely contributor, and sex is one plausible source given anatomical and neurophysiological differences affecting tDCS responsiveness. This exploratory post-hoc analysis of the multicenter, randomized, sham-controlled NETS trial examined sex as a moderator of tDCS response. Extending the primary analysis, confined to the primary outcome at end of intervention, all assessment time points were modelled across the 90-day follow-up and outcomes spanning the three domains of the International Classification of Functioning, Disability and Health (ICF). Methods NETS randomized 119 patients with subacute ischemic stroke to anodal tDCS (1 mA) over the ipsilesional primary motor cortex or sham stimulation alongside standardized rehabilitation. Longitudinal mixed-effects models with autoregressive correlation structures examined treatment-by-sex interactions for the Upper-Extremity-Fugl-Meyer Assessment (UEFMA; body function), Box-and-Block Test (BBT; activity), and Stroke Impact Scale participation domain (SIS; participation). Sensitivity analyses included continuous-time models and three-way sex-by-treatment-by-time interactions. Analyses were performed on intention-to-treat (ITT) and per-protocol (PP) populations. Results Treatment-by-sex interactions were found for the UEFMA and BBT, but not for SIS participation. Female participants receiving active stimulation improved more than those receiving sham, with clinically relevant estimated marginal mean differences of 6.0 points (UEFMA) and 8.4 points (BBT). No relevant treatment effect was observed in males for either measure. Results were consistent across ITT and PP populations. Conclusions This exploratory analysis provides preliminary evidence that sex may moderate tDCS response in post-stroke upper limb rehabilitation, with effects extending across ICF impairment and activity domains. Together with converging signals from independent trials, these findings suggest that sex-stratified designs may be necessary to detect tDCS efficacy in stroke rehabilitation.

Background: Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional primary motor cortex is widely used for post-stroke upper-limb rehabilitation, but treatment response varies substantially. This systematic review and meta-analysis aimed to quantify the efficacy of contralesional LF-rTMS and to examine whether baseline motor impairment severity and corticospinal tract (CST) integrity modify treatment effects. Methods: We searched seven databases from inception to July 2026 for randomized controlled trials of contralesional LF-rTMS ([&le;]1 Hz) versus sham after stroke, with comparable rehabilitation in both arms. The primary outcome was the change in Fugl-Meyer Assessment for the upper extremity (FMA-UE) scores. Random-effects meta-analysis used restricted maximum likelihood estimation with Knapp-Hartung adjustment. Effect modification was examined through meta-regression and biomarker-stratified analyses, and neurophysiological outcomes were also synthesized. Results: Thirty trials (33 comparisons, 1,668 participants) were included. LF-rTMS produced greater FMA-UE improvement than sham (mean difference 4.11 points, 95% CI 2.83-5.39; Hedges g 0.64, 95% CI 0.45-0.84), with substantial heterogeneity. Baseline severity did not significantly modify the effect in continuous meta-regression. However, exploratory within-trial biomarker-stratified analyses suggested larger effects in participants with preserved CST integrity or positive motor-evoked potential (MEP) status. LF-rTMS also shortened MEP latency and central motor conduction time, but these measures could not be validated as surrogate endpoints. Conclusions: Contralesional LF-rTMS provides a statistically significant but modest improvement in post-stroke upper-limb motor recovery. Baseline clinical severity alone may not identify responders, whereas CST integrity is an exploratory, hypothesis-generating candidate biomarker. It requires confirmation in adequately powered biomarker-stratified trials before it can inform clinical decisions. Trial Registration The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD420261441561).

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

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

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

Impaired motor control post-stroke results in reduced walking speeds and increased gait variability. This variability reduces reliability and makes identifying longitudinal changes via gait analysis difficult since changes may occur within the margin of measurement error. We quantified intra-class correlation coefficients (ICC) and minimal detectable change (MDC) in post-stroke individuals and neurotypical individuals walking at matched speeds, to isolate the impact of gait speed and post-stroke impairments on gait-analysis reliability. We collected gait data over two days from N=15 post-stroke individuals walking on a treadmill at their self-selected speed, and from N=13 age- and sex-matched neurotypical controls walking at both their self-selected speed and a speed matched to a post-stroke participant. We calculated ICC and MDC values for spatiotemporal variables, bilateral joint ranges of motion (ROM), and bilateral peak propulsive and peak vertical ground reaction forces (GRF). Spatiotemporal ICCs showed excellent reliability across groups (range [0.813-0.988]), yet MDC values were greater post-stroke than in speed-matched controls. ICCs for joint ROM ranged from poor to excellent reliability across groups ([0.362-0.960]). Post-stroke joint ROM MDCs were 27%-53% of the gait ROM compared to 11%-42% in neurotypical controls. ROM MDCs were greater in the non-paretic compared to the paretic extremity. ICC for peak GRFs showed good to excellent reliability across groups (range [0.778-0.980]), with post-stroke peak GRF MDCs greater than in speed-matched controls. Our results suggest that stroke related neuromotor impairments influence reliability beyond the effects of walking speed alone, and we provide quantitative MDC benchmarks for interpreting gait changes post stroke following clinical interventions.

Objective: To investigate the clinical validity of finger-worn accelerometers for providing a comprehensive assessment of upper-limb motor performance in stroke survivors in real-world environments, compared to wrist-worn accelerometers, and to examine how the clinimetric properties of wearable-based motor performance measures vary with the duration of patient data collection. Design: Cross-sectional observational design. Setting: Research laboratory and free-living environments. Participants: Twenty-seven stroke survivors aged 18-80 years with ischemic or hemorrhagic stroke at least six months prior to enrollment and mild-to-moderate upper-limb impairment without severe range-of-motion restrictions were enrolled. Three participants were ineligible and four withdrew, resulting in a final cohort of 20 participants (N = 20). Interventions: Not applicable. Main Outcome Measures: Wearable-based motor performance measures derived from fine-hand movements, gross-arm movements, and the combination of fine-hand and gross-arm movements captured by finger-worn and wrist-worn accelerometers in naturalistic settings for 6.4 {+/-} 1.8 days. Results: Wearable-based motor performance measures from fine-hand movements demonstrated the strongest convergent validity, known-group validity, and test-retest reliability, followed by those from combined and gross-arm movements. Convergent validity and test-retest reliability of wearable-based motor performance measures improved with longer monitoring durations, with four days being sufficient to obtain accurate and reliable upper-limb measures. Conclusions: Wearable-based motor performance measures from finger-worn accelerometers provide a more comprehensive assessment of upper-limb motor performance than those from wrist-worn accelerometers, supporting their use for real-world monitoring in stroke survivors. Furthermore, the improvements in clinimetric properties of wearable-based motor performance measures with longer monitoring durations highlight the importance of multi-day monitoring to mitigate day-to-day variability and ensure robust assessment.

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

Purpose: To explore how 12-weeks of robotic walking impacts physical function and sequelae of inactivity for individuals with pediatric-onset neuromotor impairments. Methods: A single-arm mixed-methods interventional study examined robotic walking for 12-weeks in home and community settings, with 12-week follow-up. Outcomes included family goals (Goal Attainment Scale (GAS)) and perspectives (Interviews), postural control (Early Clinical Assessment of Balance), physical activity (Actigraphy, Habitual Activity Estimation Scale, Patient Reported Outcome Measurement Information System (PROMIS) Physical Activity) and sequelae of inactivity (PROMIS Sleep Disturbances, Bowel Function Diary). GAS was collected pre-training, post-training, and 12-week follow-up. All other quantitative outcomes were collected every 4-weeks. Quantitative data are described with median (25th-75thpercentile) and analyzed using a Skillings-Mack test with post-hoc Wilcoxon Signed-Rank. Qualitative interviews were conducted before and after training and analyzed thematically. Results: 15 participants aged 4-23 completed this study. Participants had cerebral palsy (10/15) or rare genetic conditions (5/15), and most used a wheelchair in community settings. Postural control improved (test-statistic = 23.0, p<0.001) after 8 weeks (change=5.0(0.0-21.4), p=0.016) and was maintained through 12-week follow-up (change=13.7(3.1-23.7), p=0.008). Over half of the participants achieved goals (t-score > 50) after training. Exploratory analyses suggest improvements in sleep disturbance immediately after training (p=0.025) and 4-weeks after (p=0.047). All measures of physical activity did not improve. Parents reported improvements in walking, activities of daily living, and sequelae of inactivity (i.e., bowel function, appetite, and sleep). Conclusions: Improvements were seen across a range of measures and notably postural control improvements were maintained at the follow-up. Parents perceived improvements in physical function and activities of daily living. Future research is warranted to further understand the impacts of robotic walking for children and small adults with mobility impairments.

Background Mirror therapy (MT)-specifically paradigms using mirror visual feedback (MVF)-is widely used in neurorehabilitation; however, mechanistic implementations vary substantially in movement content, rhythmicity and attentional demands. This protocol describes an acute mechanistic, within-participant fNIRS screening study designed to compare three prespecified upper-limb mirror-therapy task paradigms and to quantify associated subjective experience after each condition in healthy adults during a single visit. Methods and analysis This is a single-centre, within-participant, randomised crossover study conducted at Wuhan Wuchang Hospital (Wuhan, China). Healthy adults aged 18-35 years will complete three task conditions once each in a counterbalanced order using a 3*3 Latin-square scheme: UMT1 (task-oriented rhythmic functional movement), UMT2 (open-ended free movement with auditory control), and UMT3 (non-functional rhythmic movement). fNIRS will be acquired using the NirSmart-6000A system during a standardised block design. The primary outcome is ROI-level HbO activation quantified as GLM-derived {beta} estimates within the prespecified primary ROIs (bilateral SM1/M1 and bilateral PMC). Secondary outcomes include ROI-level windowed {Delta}HbO (5-20 s post-onset relative to the immediately preceding rest; descriptive only), ROI-level {Delta}HbR, and post-condition subjective ratings (illusion, immersion, confusion and fatigue; 1-7 Likert). Condition effects will be analysed using linear mixed-effects models with fixed effects for condition and period and prespecified multiplicity-adjusted pairwise contrasts. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Wuchang Hospital Affiliated to Wuhan University of Science and Technology (Approval No.: 2025-112-01; approved on 2025-08-21). The study is expected to be minimal risk. Findings will be disseminated through publication of this protocol manuscript and subsequent results manuscripts and conference presentations. Trial registration number Chinese Clinical Trial Registry (ChiCTR2600116634). This study is conducted as a prespecified mechanistic sub-study under the overarching registered project.

Introduction Post stroke dysphagia is common, associated with poor functional outcome and lacks treatment strategies beyond behaviour therapies delivered by speech & language therapists. Here, we present the statistical analysis plan for the ongoing pharyngeal electrical stimulation for acute stroke dysphagia trial (PhEAST). PES is a candidate treatment for dysphagia present in non-ventilated stroke patients. Methods PhEAST is an investigator-initiated international prospective randomised open-label blinded-endpoint phase-4 superiority trial involving 650 participants with tube-dependent post-stroke dysphagia. Consenting patients are randomised to PES versus no PES given on top of standard care with PES given daily for 6 days. The primary outcome is the dysphagia severity rating scale (DSRS), a measure of swallowing impairment, made at days 14 and 90 and analysed using repeated measures regression. Conclusion We present the statistical analysis plan for the main analyses based on data up to day 90 along with planned secondary analyses including presentation of baseline data, health economics, cognition and extended follow-up to 12 months.

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

Conventional transfemoral amputation disrupts native neuromuscular pathways, limiting prosthetic joint control, sensory feedback, and the perception of the prosthesis as part of the body. To ameliorate these pathologies, we restored the agonist-antagonist relationship of residual muscles in two individuals with above-knee amputation through an interventional surgical revision. Participants trained with a bionic knee prosthesis before and after the surgical revision while generating neuromuscular, cortical, functional, and affective data. Both individuals demonstrated improvements after the revision that could not readily be attributed to training effects, including: 1) increased proprioceptive afferents and stronger activation in cortical regions associated with sensorimotor integration of their missing joints, 2) improved control of the bionic knee during functional tasks including sit-to-stand and stair ascent, and 3) generally greater prosthesis embodiment, proprioception, and phantom limb definition as assessed through questionnaires and interviews. In contrast, training outcomes were more participant-specific and more variably correlated with amount of exposure, especially before the revision. These pilot findings suggest that revisional augmentation of residual neuromuscular tissues to restore agonist-antagonist dynamics may promote sensorimotor coherence and enhance both functional and perceptual integration with a bionic prosthesis, and remaining participant-specific heterogeneities may be attributable to inter-individual difference in residual limbs neuromuscular system, amputation history, and personal beliefs about prosthesis usage.

Background: Aerobic exercise is recommended during stroke rehabilitation to improve cardiorespiratory fitness and support recovery; however, participation rates remain low. While institutional and system-level barriers have been widely examined, less is known about how individual patient factors influence engagement in aerobic exercise during rehabilitation. Objectives: We aimed to determine whether depressive symptoms, apathy, self-efficacy and outcome expectations for exercise, perceived barriers, or past exercise history were associated with aerobic exercise participation in stroke rehabilitation. Methods: In this prospective cohort sub-study, adults admitted to in- or out-patient stroke rehabilitation at three urban hospitals completed validated questionnaires assessing depressive symptoms, apathy, exercise self-efficacy, outcome expectations for exercise, perceived barriers to being active, and premorbid exercise history. Participants were separated into two groups for analysis: those who completed aerobic exercise during rehabilitation and those who did not. Equivalence testing and between-group comparisons were performed. Results: Sixty-two participants were enrolled; 16 participated in aerobic exercise and 46 did not. Groups were not equivalent on any individual-level factors. Compared to non-participants, those who performed aerobic exercise had significantly higher depressive symptom scores (p=0.0025) and lower self-efficacy for exercise (p=0.0087). Non-participants demonstrated significantly higher apathy (p=0.0007). No significant differences were found for outcome expectations, perceived barriers, or exercise history. Conclusion: Depressive symptoms and lower self-efficacy did not impede aerobic exercise participation during rehabilitation. Increased apathy, however, was associated with non-participation. Findings highlight the need for individually tailored aerobic exercise prescriptions that consider motivational and affective factors to optimize engagement during stroke rehabilitation.

Background: Storage symptoms after stroke-isolated urgency, urgency with frequency, and isolated frequency are common but traditionally attributed to a single overactive bladder mechanism via suprapontine disinhibition. However, clinical heterogeneity in symptom presentation suggests distinct underlying mechanisms. We aimed to characterize the neural substrates of three storage symptom subtypes after stroke using comprehensive lesion-symptom mapping. Methods: We prospectively evaluated 1,498 consecutive subacute stroke patients admitted for inpatient rehabilitation (1,105 men, 73.8%; median age 61 years). Storage symptoms were classified into three subtypes: isolated urgency (n=109), urgency with frequency (n=32), and isolated frequency (n=19). Multivariable logistic regression models with Bonferroni correction identified independent predictors across demographic, clinical, white matter hyperintensity (WMH), brain atrophy, and lesion location variables. Results: The three subtypes demonstrated largely distinct sets of independent predictors. The left genu of the corpus callosum (aOR=20.06, 95% CI 7.78-51.74, P<0.001) and the inferior frontal gyrus (aOR=3.48, 95% CI 1.81-6.67, P<0.001) were independently associated with isolated urgency and survived Bonferroni correction, together with a right IFG-insula synergistic effect (OR=21.46, 95% CI 10.49-43.88, P<0.001). Urgency with frequency was associated with a broad fronto-cingulate network-the IFG (aOR=11.45, 95% CI 3.10-42.33, P<0.001, surviving Bonferroni correction) and the ACC (aOR=11.53, 95% CI 2.40-55.49, P=0.002) with diffuse right-hemisphere dominance, older age and brain atrophy. Isolated frequency was associated with anterior corona radiata involvement (aOR=5.46, 95% CI 1.92-15.54, P=0.002) and male sex (aOR=10.62, 95% CI 1.36-82.98, P=0.024), though none reached the strict Bonferroni threshold. Conclusions: These findings identify three mechanistically distinct post-stroke storage symptom subtypes with separable neural substrates, lateralization profiles, and clinical determinants. The triple dissociation across subtypes supports a discrete pathway model over the traditional unitary OAB framework, providing a neuroanatomically grounded basis for subtype-stratified treatment Keywords: storage symptoms; subacute stroke; hemispheric lateralization; structural synergy; lesion-syndrome mapping

Hand dexterity impairment is a major contributor to long-term disability after acquired brain injury, yet the white matter substrates supporting residual dexterity remain incompletely understood. We investigated diffusion MRI markers of hand dexterity in individuals with chronic stroke (n = 9) and traumatic brain injury (TBI; n = 8) using complementary tract-specific and whole- brain approaches. Partial least squares regression (PLSR) was used to evaluate the cross-validated predictive relevance of bilateral corticospinal tract (CST) diffusion and tractometry features, while quantitative anisotropy (QA)-based correlational tractography was used to identify distributed white matter pathways associated with dexterity performance measured using Box and Block Test (BBT) and MusicGlove Dexterity Test(MGDT). In stroke, CST features predicted BBT performance (Q2 = 0.69, r = 0.85, permutation p = .010) and, more modestly, MGDT performance (Q2= 0.22, r = 0.72, permutation p = .008). In contrast, CST-based models showed no predictive relevance for dexterity outcomes in TBI. Whole-brain connectometry revealed that better dexterity after stroke was associated with greater QA across distributed pathways extending beyond the CST, including commissural, association, and projection fibers. Box and Block Test performance was prominently associated with callosal and cingulum-related pathways, whereas MusicGlove performance showed greater representation of CST and projection pathways. In TBI, significant connectometry findings for the BBT similarly implicated distributed commissural and association pathways, whereas no significant pathways were identified for the MusicGlove test. Together, these findings suggest that the structural correlates of hand dexterity extend beyond the CST and vary across dexterity measures and injury populations. Although preliminary given the small cohorts, the complementary tractometry and connectometry findings support a network-level characterization of residual hand function after acquired brain injury and motivate validation in larger cohorts.

Background: Prolonging ambulation is an important treatment goal in children with Duchenne muscular dystrophy (DMD). Clinical management targets 'actionable' (i.e., modifiable) impairments, such as progressive muscle weakness and contractures, that underlie gait pathology. Gait classification may improve clinical decision-making, but the utility of gait classification in clinical practice depends on understanding how underlying, actionable impairments contribute to distinct gait patterns, which remains insufficiently understood. The research questions were: (1) Can DMD gait patterns be accurately classified from actionable impairments? and (2) Can the model's predictions be explained, and do these explanations provide clinical utility and increase trust in the model? Methods: A retrospective dataset of 274 lower-limb observations from 137 assessments in 30 boys with DMD was analyzed, including 3D gait analysis, instrumented strength assessment, and clinical examination (manual muscle testing, goniometry and clinical stiffness scale). Observations were classified into the mildly affected, tiptoeing, or flexion gait pattern. Ten predictors representing actionable impairments were included: nine predictors related to muscle weakness and contractures, and body mass index (BMI). A balanced random forest classifier was evaluated with leave-one-group-out cross-validation. Model interpretability was explored using SHapley Additive exPlanations to generate global and local explanations. An interview with a clinical expert assessed the utility of the explanations as the primary outcome, with trust in and expectations of both the model and the explanations as secondary outcomes. Results: The model achieved an accuracy of 74.5%. Global explanations identified hip and knee weakness, gastrocnemius-soleus contractures, and BMI as the most important predictors across gait patterns. Local explanations illustrated how patient-specific impairments informed individual predictions. The user study demonstrated the clinical utility of the explanations, as they were perceived as interpretable, provided useful insights, and these insights were actionable. The explanations largely aligned with the expectations and increased self-reported trust in the model. Conclusions: Gait patterns in DMD can be predicted from clinically actionable impairments, and explainable artificial intelligence can translate model outputs into meaningful clinical insights. This approach is promising for supporting both general and personalized rehabilitation and orthopedic strategies aimed at prolonging ambulation in DMD. Further validation in larger, multi-center cohorts is needed.

Motor sequence performance improves during and between brief practice bouts (micro-online and offline gains). We compared both metrics across two groups: one exposed to an implicit motor sequence, and one not. Micro-online gains drove sequence-specific learning and positively correlated with overall skill. However, micro-offline gains were comparable between groups and did not track sequence-specific learning. We conclude that implicit motor sequence learning is driven by micro-online rather than micro-offline gains.

Impaired gait performance and stability is a key symptom often defining disease outcome in people with Multiple Sclerosis. Step-by-step foot placement control in response to variations in the center-of-mass kinematic state is a crucial gait stability mechanism, especially in the mediolateral direction. Even though it is known that people with Multiple Sclerosis are at an increased risk of falling, step-by-step foot placement control remains to be characterized in this population. Here, we explored characteristic foot placement control in ten people with early stage Multiple Sclerosis, compared to 21 controls walking at a similar average gait speed, during 1-minute steady-state treadmill walking. Kinematic data were analyzed using a linear feedback model that correlated foot placement with the center-of-mass kinematic state during the preceding swing phase. People with Multiple Sclerosis demonstrated step-by-step foot placement control in both the mediolateral and anteroposterior directions. No differences were found in foot placement precision between groups. However, foot placement responses to variations in center-of-mass velocity proved stronger in people with Multiple Sclerosis. Moreover, the contribution of mediolateral center-of-mass velocity feedback to the control mechanism was higher in people with Multiple Sclerosis as compared to neurologically healthy controls. Our results suggest that foot placement control is still retained in early clinically evident stages of Multiple Sclerosis, but is realized through differently weighted sensory feedback control.