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Background: It has long been of interest to characterize the components of the motor abnormality in the arm after stroke. One approach has been to decompose the hemiparesis phenotype into negative signs, such as weakness, and positive signs, such as intrusion of synergies. We sought to identify the contributions of weakness and flexor synergy to motor deficits in sub-acute stroke., Methods: Thirty-three sub-acute post-stroke participants and 16 healthy controls performed two functional arm movements; one within flexor synergy (shoulder and elbow flexion), and the other outside flexor synergy (shoulder flexion and elbow extension). We analyzed upper limb 3D kinematics to assess both overall task performance and intrusion of pathological synergies. Weakness and spasticity were also measured., Results: Both tasks produced similar impairments compared to controls. Analysis of elbow and shoulder multi-joint coordination patterns revealed intrusion of synergies in the out-of-synergy reaching task based on the time spent within a flexion-flexion pattern and the correlation between shoulder and elbow angles. Regression analysis indicated that both weakness and synergy intrusion contributed to motor impairment in the out-of-synergy reaching task. Notably, the Fugl-Meyer Assessment (FMA) was abnormal even when only weakness caused the impairment, cautioning that it is not a pure synergy scale., Conclusions: Weakness and synergy intrusion contribute to motor deficits in the sub-acute post-stroke period. An abnormal FMA score cannot be assumed to be due to synergy intrusion. Careful kinematic analysis of naturalistic movements is required to better characterize the contribution of negative and positive signs to upper limb impairment after stroke., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Knowing how impaired manual dexterity and finger proprioception affect upper limb activity capacity is important for delineating targeted post-stroke interventions for upper limb recovery., Objectives: To investigate whether impaired manual dexterity and finger proprioception explain variance in post-stroke activity capacity, and whether they explain more variance than conventional clinical assessments of upper limb sensorimotor impairments., Methods: Activity capacity and hand sensorimotor impairments were assessed using clinical measures in N = 42 late subacute/chronic hemiparetic stroke patients. Dexterity was evaluated using the Dextrain Manipulandum to quantify accuracy of visuomotor finger force-tracking (N = 36), timing of rhythmic tapping (N = 36), and finger individuation (N = 24), as well as proprioception (N = 27). Stepwise multivariate and hierarchical linear regression models were used to identify impairments best explaining activity capacity., Results: Dexterity and proprioceptive components significantly increased the variance explained in activity capacity: (i) Box and Block Test was best explained by baseline tonic force during force-tracking and tapping frequency (adjusted R 2  = .51); (ii) Motor Activity Log was best explained by success rate in finger individuation (adjusted R 2  = .46); (iii) Action Research Arm Test was best explained by release of finger force and proprioceptive measures (improved reaction time related to use of proprioception; adjusted R 2  = .52); and (iv) Moberg Pick-Up test was best explained by proprioceptive function (adjusted R 2  = .18). Models excluding dexterity and proprioception variables explained up to 19% less variance., Conclusions: Manual dexterity and finger proprioception explain unique variance in activity capacity not captured by conventional impairment measures and should be assessed when considering the underlying causes of post-stroke activity capacity limitations.URL: https://www.clinicaltrials.gov. Unique identifier: NCT03934073., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MT, MAM, and PGL have patented the method for multidimensional measurement of manual dexterity (WO2016184935A3). MT and PGL are founding members of start-up company Dextrain (started in 2021) who owns the commercial rights. MT now works for the start-up full-time. PGL, head of the scientific board, reports no financial gain in advising the company. CR is a member of the scientific board of the company but receives no financial benefits. The other authors report no financial interests or potential conflicts of interest.

Background. Wearable sensors allow for direct measurement of upper limb (UL) performance in daily life. Objective. To map the trajectory of UL performance and its relationships to other factors post-stroke. Methods . Participants (n = 67) with first stroke and UL paresis were assessed at 2, 4, 6, 8, 12, 16, 20, and 24 weeks after stroke. Assessments captured UL impairment (Fugl-Meyer), capacity for activity (Action Research Arm Test), and performance of activity in daily life (accelerometer variables of use ratio and hours of paretic limb activity), along with other potential modifying factors. We modeled individual trajectories of change for each measurement level and the moderating effects on UL performance trajectories. Results. Individual trajectories were best fit with a 3-parameter logistic model, capturing the rapid growth early after stroke within the longer data collection period. Plateaus (90% of asymptote) in impairment (bootstrap mean ± SE: 32 ± 4 days post-stroke) preceded those in capacity (41 ± 4 days). Plateau in performance, as measured by the use ratio (24 ± 5 days), tended to precede plateaus in impairment and capacity. Plateau in performance, as measured by hours of paretic activity (41 ± 6 days), occurred at a similar time to that of capacity and slightly lagged impairment. Modifiers of performance trajectories were capacity, concordance, UL rehabilitation, depressive symptomatology, and cognition. Conclusions. Upper limb performance in daily life approached plateau 3 to 6 weeks post-stroke. Individuals with stroke started to achieve a stable pattern of UL use in daily life early, often before neurological impairments and functional capacity started to stabilize.

Background. Motor recovery after stroke is of great clinical interest. Besides magnetic resonance imaging functional connectivity, electroencephalographic synchrony is also an available biomarker. However, the clinical relevance of electroencephalographic synchrony in hemiparesis has not been fully understood. Objective. We aimed to demonstrate the usefulness of the phase synchrony index (PSI) by showing associations between the PSI and poststroke outcome in patients with hemiparesis. Methods. This observational study included 40 participants with cortical ischemic stroke (aged 69.8 ± 13.8 years) and 22 healthy controls (aged 66.9 ± 6.5 years). Nineteen-channel electroencephalography was recorded at 36.9 ± 11.8 days poststroke. Upper extremity Fugl-Meyer scores were assessed at the time of admission/before discharge (FM-UE1/FM-UE2; 32.6 ± 12.3/121.0 ± 44.7 days poststroke). Then, correlations between the PSIs and FM-UE1 as well as impairment reduction after rehabilitation (FM-UEgain) were analyzed. Results . The interhemispheric PSI (alpha band) between the primary motor areas (M1s) was lower in patients than in controls and was selectively correlated with FM-UE1 ( P = .001). In contrast, the PSI (theta band) centered on the contralesional M1 was higher in patients than in controls and was selectively correlated with FM-UEgain ( P = .003). These correlations remained significant after adjusting for confounding factors (age, time poststroke, National Institute of Health Stroke Scale, and lesion volume). Furthermore, the latter correlation was significant in severely impaired patients (FM-UE1 ≤ 10). Conclusions. This study showed that the PSIs were selectively correlated with motor impairment and recovery. Therefore, the PSIs may be potential biomarkers in persons with a hemispheric infarction.

Background . Stroke is one of the most common causes of physical disability worldwide. The majority of survivors experience impairment of movement, often with lasting deficits affecting hand dexterity. To date, conventional rehabilitation primarily focuses on training compensatory maneuvers emphasizing goal completion rather than targeting reduction of motor impairment. Objective . We aim to determine whether finger dexterity impairment can be reduced in chronic stroke when training on a task focused on moving fingers against abnormal synergies without allowing for compensatory maneuvers. Methods . We recruited 18 chronic stroke patients with significant hand motor impairment. First, participants underwent baseline assessments of hand function, impairment, and finger individuation. Then, participants trained for 5 consecutive days, 3 to 4 h/d, on a multifinger piano-chord-like task that cannot be performed by compensatory actions of other body parts (e.g., arm). Participants had to learn to simultaneously coordinate and synchronize multiple fingers to break unwanted flexor synergies. To test generalization, we assessed performance in trained and nontrained chords and clinical measures in both the paretic and the nonparetic hands. To evaluate retention, we repeated the assessments 1 day, 1 week, and 6 months post-training. Results . Our results showed that finger impairment assessed by the individuation task was reduced after training. The reduction of impairment was accompanied by improvements in clinical hand function, including precision pinch. Notably, the effects were maintained for 6 months following training. Conclusion . Our findings provide preliminary evidence that chronic stroke patient can reduce hand impairment when training against abnormal flexor synergies, a change that was associated with meaningful clinical benefits.

Background and Purpose . Previous studies suggest that individuals poststroke can achieve substantial gains in walking function following high-intensity locomotor training (LT). Recent findings also indicate practice of variable stepping tasks targeting locomotor deficits can mitigate selected impairments underlying reduced walking speeds. The goal of this study was to investigate alterations in locomotor biomechanics following 3 different LT paradigms. Methods . This secondary analysis of a randomized trial recruited individuals 18 to 85 years old and >6 months poststroke. We compared changes in spatiotemporal, joint kinematics, and kinetics following up to 30 sessions of high-intensity (>70% heart rate reserve [HRR]) LT of variable tasks targeting paretic limb and balance impairments (high-variable, HV), high-intensity LT focused only on forward walking (high-forward, HF), or low-intensity LT (<40% HRR) of variable tasks (low-variable, LV). Sagittal spatiotemporal and joint kinematics, and concentric joint powers were compared between groups. Regressions and principal component analyses were conducted to evaluate relative contributions or importance of biomechanical changes to between and within groups. Results . Biomechanical data were available on 50 participants who could walk ≥0.1 m/s on a motorized treadmill. Significant differences in spatiotemporal parameters, kinematic consistency, and kinetics were observed between HV and HF versus LV. Resultant principal component analyses were characterized by paretic powers and kinematic consistency following HV, while HF and LV were characterized by nonparetic powers. Conclusion . High-intensity LT results in greater changes in kinematics and kinetics as compared with lower-intensity interventions. The results may suggest greater paretic-limb contributions with high-intensity variable stepping training that targets specific biomechanical deficits. Clinical Trial Registration . https://clinicaltrials.gov/ Unique Identifier: NCT02507466.

Background . Nonuse (NU) after stroke is characterized by failure to use the contralesional arm despite adequate capacity. It has been suggested that NU is a consequence of the greater effort and/or attention required to use the affected limb, but such accounts have not been directly tested, and we have poor understanding of the predictors of NU. Objective . We aimed to provide preliminary evidence regarding demographic, neuropsychological (ie, apraxia, attention/arousal, neglect), and psychological (ie, self-efficacy) factors that may influence NU in chronic stroke. Methods . Twenty chronic stroke survivors with mild to moderate sensory-motor impairment characterized by the Upper-Extremity Fugl-Meyer (UEFM) were assessed for NU with a modified version of the Actual Amount of Use Test (AAUT), which measures the disparity between amount of use in spontaneous versus forced conditions. Participants were also assessed with measures of limb apraxia, spatial neglect, attention/arousal, and self-efficacy. Using stepwise multiple regression, we determined which variables predicted AAUT NU scores. Results . Scores on the UEFM as well as attention/arousal predicted the degree of NU ( P < .05). Attention/arousal predicted NU above and beyond UEFM ( P < .05). Conclusions . The results are consistent with the importance of attention and engagement necessary to fully incorporate the paretic limb into daily activities. Larger-scale studies that include additional behavioral (eg, sensation, proprioception, spasticity, pain, mental health, motivation) and neuroanatomical measures (eg, lesion volume and white matter connectivity) will be important for future investigations.

Background . Recovery of upper limb function post-stroke can be partly predicted by initial motor function, but the mechanisms underpinning these improvements have yet to be determined. Here, we sought to identify neural correlates of post-stroke recovery using longitudinal magnetoencephalography (MEG) assessments in subacute stroke survivors. Methods . First-ever, subcortical ischemic stroke survivors with unilateral mild to moderate hand paresis were evaluated at 3, 5, and 12 weeks after stroke using a finger-lifting task in the MEG. Cortical activity patterns in the β-band (16-30 Hz) were compared with matched healthy controls. Results. All stroke survivors (n=22; 17 males) had improvements in action research arm test (ARAT) and Fugl-Meyer upper extremity (FM-UE) scores between 3 and 12 weeks. At 3 weeks post-stroke the peak amplitudes of the movement-related ipsilesional β-band event-related desynchronization (β-ERD) and synchronization (β-ERS) in primary motor cortex (M1) were significantly lower than the healthy controls (p<0.001) and were correlated with both the FM-UE and ARAT scores (r=0.51-0.69, p<0.017). The decreased β-ERS peak amplitudes were observed both in paretic and non-paretic hand movement particularly at 3 weeks post-stroke, suggesting a generalized disinhibition status. The peak amplitudes of ipsilesional β-ERS at week 3 post-stroke correlated with the FM-UE score at 12 weeks (r=0.54, p=0.03) but no longer significant when controlling for the FM-UE score at 3 weeks post-stroke. Conclusions. Although early β-band activity does not independently predict outcome at 3 months after stroke, it mirrors functional changes, giving a potential insight into the mechanisms underpinning recovery of motor function in subacute stroke.

Background . Understanding the factors that limit mobility in stroke patients is fundamental for proposing appropriate rehabilitation strategies. A high oxygen cost during walking (Cw) has a strong impact on the community ambulation of hemiparetic patients. The Cw in poststroke cerebellar ataxia is poorly evaluated, unlike hemiparetic gait. Objective . To compare the oxygen cost/self-selected walking speed (S) relationship in stroke individuals with cerebellar ataxia or hemiparetic gait. Methods . Thirty-three subjects were included (14 cerebellar stroke, 19 hemispheric stroke), with stroke confirmed by brain imaging and able to walk without human assistance. We measured Cw using the Metamax3B. The relationship between Cw and self-selected walking speed was modelled by logistic regression and then compared between the cerebellar and hemispheric groups. Results . No significant difference was found between the 2 groups for all characteristics of the population, except motor impairments, spasticity, and ataxia ( P < .01). We identified 2 separate Cw/S relationships with different logistic regression equations for the 2 groups. Faster than 0.4 m s -1 , Cw was 30.6% to 39.9% higher in patients with cerebellar stroke in comparison with hemispheric stroke individuals. The Cw was correlated with ataxia ( r = 0.88; P < .001) in the cerebellar group, whereas there was a correlation with motor impairments ( r = -0.61; P < .01), spasticity ( r = 0.59; P < .01), and ataxia ( r = 0.81; P < .01) in hemispheric stroke individuals. Conclusion . The Cw in poststroke cerebellar ataxia is significantly higher compared with hemiparetic patients at an equivalent walking speed. The impact on community walking needs to be explored in stroke survivors with cerebellar stroke.

Background . Kinematic abundance permits using different movement patterns for task completion. Individuals poststroke may take advantage of abundance by using compensatory trunk displacement to overcome upper limb (UL) movement deficits. However, movement adaptation in tasks requiring specific intersegment coordination may remain limited. Objective . We tested movement adaptation in both arms of individuals with chronic stroke (n = 16) and nondominant arms of controls (n = 12) using 2 no-vision reaching tasks involving trunk movement (40 trials/arm). Methods . In the "stationary hand task" (SHT), subjects maintained the hand motionless over a target while leaning the trunk forward. In the "reaching hand task" (RHT), subjects reached to the target while leaning forward. For both tasks, trunk movement was unexpectedly blocked in 40% of trials to assess the influence of trunk movement on adaptive arm positioning or reaching. UL sensorimotor impairment, activity, and sitting balance were assessed in the stroke group. The primary outcome measure for SHT was gain ( g ), defined as the extent to which trunk displacement contributing to hand motion was offset by appropriate changes in UL movements ( g = 1: complete compensation) and endpoint deviation for RHT. Results . Individuals poststroke had lower gains and greater endpoint deviation using the more-affected compared with less-affected UL and controls. Those with less sensorimotor impairment, greater activity levels, and better sitting balance had higher gains and smaller endpoint deviations. Lower gains were associated with diminished UL adaptability. Conclusions . Tests of condition-specific adaptability of interjoint coordination may be used to measure UL adaptability and changes in adaptability with treatment.

Background. Previous research has detailed the hemisphere dependence and specific kinematic deficits observed for the less-affected arm of patients with unilateral stroke. Objective. We now examine whether functional motor deficits in the less-affected arm, measured by standardized clinical measures of motor function, also depend on the hemisphere that was damaged and on the severity of contralesional impairment. Methods. We recruited 48 left-hemisphere-damaged (LHD) participants, 62 right-hemisphere-damaged participants, and 54 age-matched control participants. Measures of motor function included the following: (1) Jebsen-Taylor Hand Function Test (JHFT), (2) Grooved Pegboard Test (GPT), and (3) grip strength. We measured the extent of contralesional arm impairment with the upper-extremity component of the Fugl-Meyer (UEFM) assessment of motor impairment. Results. Ipsilesional limb functional performance deficits (JHFT) varied with both the damaged hemisphere and severity of contralesional arm impairment, with the most severe deficits expressed in LHD participants with severe contralesional impairment (UEFM). GPT and grip strength varied with severity of contralesional impairment but not with hemisphere. Conclusions. Stroke survivors with the most severe paretic arm impairment, who must rely on their ipsilesional arm for performing daily activities, have the greatest motor deficit in the less-affected arm. We recommend remediation of this arm to improve functional independence in this group of stroke patients.

Background. Severe poststroke arm impairment is associated with greater activation of the nonlesioned hemisphere during movement of the affected arm. The circumstances under which this activation may be adaptive or maladaptive remain unclear. Objective. To identify the functional relevance of key lesioned and nonlesioned hemisphere motor areas to reaching performance in patients with mild versus severe arm impairment. Methods. A total of 20 participants with chronic stroke performed a reaching response time task with their affected arm. During the reaction time period, a transient magnetic stimulus was applied over the primary (M1) or dorsal premotor cortex (PMd) of either hemisphere, and the effect of the perturbation on movement time (MT) was calculated. Results. For perturbation of the nonlesioned hemisphere, there was a significant interaction effect of Site of perturbation (PMd vs M1) by Group (mild vs severe; P < .001). Perturbation of PMd had a greater effect on MT in the severe versus the mild group. This effect was not observed with perturbation of M1. For perturbation of the lesioned hemisphere, there was a main effect of site of perturbation ( P < .05), with perturbation of M1 having a greater effect on MT than PMd. Conclusions. These results demonstrate that, in the context of reaching movements, the role of the nonlesioned hemisphere depends on both impairment severity and the specific site that is targeted. A deeper understanding of these individual-, task-, and site-specific factors is essential for advancing the potential usefulness of neuromodulation to enhance poststroke motor recovery.

Background . Persons with stroke (PwS) are at increased risk of falls, especially toward the paretic side, increasing the probability of a hip fracture. The ability to recover from unexpected loss of balance is a critical factor in fall prevention. Objectives . We aimed to compare reactive balance capacity and step kinematics between PwS and healthy controls. Methods . Thirty subacute PwS and 15 healthy controls were exposed to forward, backward, right, and left unannounced surface translations in 6 increasing intensities while standing. Single step threshold, multiple step threshold, and fall threshold (ie, perturbation intensity leading to a fall into harness system) were recorded as well as reactive step initiation time, step length, and step velocity. Results . Twenty-five PwS fell into harness system during the experiment while healthy controls did not fall. Fourteen out of 31 falls occurred in response to surface translations toward the nonparetic side, that is, falling toward the paretic side. Compared with healthy controls, PwS demonstrated significantly lower fall threshold and multiple step threshold in response to forward, backward, and lateral surface translations. Impairments were more pronounced in response to forward surface translation and toward the nonparetic side (ie, loss of balance toward the paretic side). A trend toward significant shorter step length in response to lateral surface translations was found in PwS compared with healthy controls. Conclusions . Findings highlight the importance of assessing reactive balance capacity in response to perturbations in different directions and intensities in addition to the routine assessment in PwS.

Background/Objective . We investigated interhemispheric interactions in stroke survivors by measuring transcranial magnetic stimulation (TMS)-evoked cortical coherence. We tested the effect of TMS on interhemispheric coherence during rest and active muscle contraction and compared coherence in stroke and older adults. We evaluated the relationships between interhemispheric coherence, paretic motor function, and the ipsilateral cortical silent period (iSP). Methods . Participants with (n = 19) and without (n = 14) chronic stroke either rested or maintained a contraction of the ipsilateral hand muscle during simultaneous recordings of evoked responses to TMS of the ipsilesional/nondominant (i/ndM1) and contralesional/dominant (c/dM1) primary motor cortex with EEG and in the hand muscle with EMG. We calculated pre- and post-TMS interhemispheric beta coherence (15-30 Hz) between motor areas in both conditions and the iSP duration during the active condition. Results . During active i/ndM1 TMS, interhemispheric coherence increased immediately following TMS in controls but not in stroke. Coherence during active cM1 TMS was greater than iM1 TMS in the stroke group. Coherence during active iM1 TMS was less in stroke participants and was negatively associated with measures of paretic arm motor function. Paretic iSP was longer compared with controls and negatively associated with clinical measures of manual dexterity. There was no relationship between coherence and. iSP for either group. No within- or between-group differences in coherence were observed at rest. Conclusions . TMS-evoked cortical coherence during hand muscle activation can index interhemispheric interactions associated with poststroke motor function and potentially offer new insights into neural mechanisms influencing functional recovery.

Background . As stroke survival improves, there is an increasing need for effective, low-cost programs to reduce deconditioning and improve mobility. Objective . To conduct a phase II trial examining whether the community-based Italian Adaptive Physical Activity exercise program for stroke survivors (APA-Stroke) is safe, effective, and feasible in the United States. Methods . In this single-blind, randomized controlled trial, 76 stroke survivors with mild to moderate hemiparesis >6 months were randomized to either APA-Stroke (N = 43) or Sittercise (N = 33). APA-Stroke is a progressive group exercise regimen tailored to hemiparesis that includes walking, strength, and balance training. Sittercise, a seated, nonprogressive aerobic upper body general exercise program, served as the control. Both interventions were 1 hour, 3 times weekly, in 5 community locations, supervised by exercise instructors. Results . A total of 76 participants aged 63.9 ± 1.2 years, mean months poststroke 61.8 ± 9.3, were included. There were no serious adverse events; completion rates were 58% for APA-Stroke, 70% for Sittercise. APA-Stroke participants improved significantly in walking speed. Sample size was inadequate to demonstrate significant between-group differences. Financial and logistical feasibility of the program has been demonstrated. Ongoing APA classes have been offered to >200 participants in county Senior Centers since study completion. Conclusion . APA-Stroke shows great promise as a low-cost, feasible intervention. It significantly increased walking speed. Safety and feasibility in the US context are demonstrated. A pivotal clinical trial is required to determine whether APA-Stroke should be considered standard of care.

Background . Although recent evidence has shown a new role of fluoxetine in motor rehabilitation, results are mixed. We conducted a randomized clinical trial to evaluate whether combining repetitive transcranial magnetic stimulation (rTMS) with fluoxetine increases upper limb motor function in stroke. Methods . Twenty-seven hemiparetic patients within 2 years of ischemic stroke were randomized into 3 groups: Combined (active rTMS + fluoxetine), Fluoxetine (sham rTMS + fluoxetine), or Placebo (sham rTMS + placebo fluoxetine). Participants received 18 sessions of 1-Hz rTMS in the unaffected primary motor cortex and 90 days of fluoxetine (20 mg/d). Motor function was assessed using Jebsen-Taylor Hand Function (JTHF) and Fugl-Meyer Assessment (FMA) scales. Corticospinal excitability was assessed with TMS. Results . After adjusting for time since stroke, there was significantly greater improvement in JTHF in the combined rTMS + fluoxetine group (mean improvement: -214.33 seconds) than in the placebo (-177.98 seconds, P = 0.005) and fluoxetine (-50.16 seconds, P < 0.001) groups. The fluoxetine group had less improvement than placebo on both scales (respectively, JTHF: -50.16 vs -117.98 seconds, P = 0.038; and FMA: 6.72 vs 15.55 points, P = 0.039), suggesting that fluoxetine possibly had detrimental effects. The unaffected hemisphere showed decreased intracortical inhibition in the combined and fluoxetine groups, and increased intracortical facilitation in the fluoxetine group. This facilitation was negatively correlated with motor function improvement (FMA, r 2 = -0.398, P = 0.0395). Conclusion . Combined fluoxetine and rTMS treatment leads to better motor function in stroke than fluoxetine alone and placebo. Moreover, fluoxetine leads to smaller improvements than placebo, and fluoxetine's effects on intracortical facilitation suggest a potential diffuse mechanism that may hinder beneficial plasticity on motor recovery.

Background . Transcranial direct current stimulation (tDCS) has been suggested to improve poststroke recovery. However, its effects on bimanual motor learning after stroke have not previously been explored. Objective . We investigated whether dual-tDCS of the primary motor cortex (M1), with cathodal and anodal tDCS applied over undamaged and damaged hemispheres, respectively, improves learning and retention of a new bimanual cooperative motor skill in stroke patients. Method . Twenty-one chronic hemiparetic patients were recruited for a randomized, double-blinded, cross-over, sham-controlled trial. While receiving real or sham dual-tDCS, they trained on a bimanual cooperative task called CIRCUIT. Changes in performance were quantified via bimanual speed/accuracy trade-off (Bi-SAT) and bimanual coordination factor (Bi-Co) before, during, and 0, 30, and 60 minutes after dual-tDCS, as well as one week later to measure retention. A generalization test then followed, where patients were asked to complete a new CIRCUIT layout. Results . The patients were able to learn and retain the bimanual cooperative skill. However, a general linear mixed model did not detect a significant difference in retention between the real and sham dual-tDCS conditions for either Bi-SAT or Bi-Co. Similarly, no difference in generalization was detected for Bi-SAT or Bi-Co. Conclusion . The chronic hemiparetic stroke patients learned and retained the complex bimanual cooperative task and generalized the newly acquired skills to other tasks, indicating that bimanual CIRCUIT training is promising as a neurorehabilitation approach. However, bimanual motor skill learning was not enhanced by dual-tDCS in these patients.

Introduction: The effects of long-term stretching (>6 months) in hemiparesis are unknown. This prospective, randomized, single-blind controlled trial compared changes in architectural and clinical parameters in plantar flexors of individuals with chronic hemiparesis following a 1-year guided self-stretch program, compared with conventional rehabilitation alone., Methods: Adults with chronic stroke-induced hemiparesis (time since lesion >1 year) were randomized into 1 of 2, 1-year rehabilitation programs: conventional therapy (CONV) supplemented with the Guided Self-rehabilitation Contract (GSC) program, or CONV alone. In the GSC group, specific lower limb muscles, including plantar flexors, were identified for a diary-based treatment utilizing daily, high-load, home self-stretching. Blinded assessments included (1) ultrasonographic measurements of soleus and medial gastrocnemius (MG) fascicle length and thickness, with change in soleus fascicle length as primary outcome; (2) maximum passive muscle extensibility (X V1 , Tardieu Scale); (3) 10-m maximal barefoot ambulation speed., Results: In all, 23 individuals (10 women; mean age [SD], 56 [±12] years; time since lesion, 9 [±8] years) were randomized into either the CONV (n = 11) or GSC (n = 12) group. After 1 year, all significant between-group differences favored the GSC group: soleus fascicle length, +18.1mm [9.3; 29.9]; MG fascicle length, +6.3mm [3.5; 9.1]; soleus thickness, +4.8mm [3.0; 7.7]; X V1 soleus, +4.1° [3.1; 7.2]; X V1 gastrocnemius, +7.0° [2.1; 11.9]; and ambulation speed, +0.07m/s [+0.02; +0.16]., Conclusions: In chronic hemiparesis, daily self-stretch of the soleus and gastrocnemius over 1 year using GSC combined with conventional rehabilitation increased muscle fascicle length, extensibility, and ambulation speed more than conventional rehabilitation alone.

Stroke is the third leading cause of death in the developed world and the primary cause of adult disability. The most common site of stroke is the middle cerebral artery (MCA), an artery that supplies a range of areas involved in both language and motor function. As a consequence, many stroke patients experience a combination of language and motor deficits. Indeed, those suffering from Broca's aphasia have an 80% chance of also suffering hemiplegia. Despite the prevalence of multifaceted disability in patients, the current trend in both clinical trials and clinical practice is toward compartmentalization of dysfunction. In this article, we review evidence that aphasia and hemiplegia do not just coexist, but that they interact. We review a number of clinical reports describing how therapies for one type of deficit can improve recovery in the other and vice versa. We go on to describe how language deficits should be seen as a warning to clinicians that the patient is likely to experience motor impairment and slower motor recovery, aiding clinicians to optimize their choice of therapy. We explore these findings and offer a tentative link between language and arm function through their shared need for sequential action, which we term fluency. We propose that area BA44 (part of Broca's area) acts as a hub for fluency in both movement and language, both in terms of production and comprehension.

Background: The residual hemiparesis after stroke results in a unilateral reduction in propulsive force during gait. Prior work has suggested the presence of a propulsive reserve in the paretic limb., Objective: The purpose of this study was to quantify the paretic propulsive reserve in individuals poststroke and to determine the biomechanical mechanism underlying the generation of additional paretic propulsive limb force., Methods: Ten individuals with chronic hemiparesis poststroke walked on a treadmill against an impeding force (ascending 0% to 10% body weight [BW], in 2.5% BW increments, followed by descending 10% to 0% BW, also in 2.5% BW increments) applied to the body's center of mass. The resulting propulsive forces were measured bilaterally and compared between impeding force levels. We then assessed potential mechanisms (trailing limb angle and plantarflexion moment) underlying the changes in propulsion., Results: Overall, peak paretic propulsive force increased by 92% and the paretic propulsive impulse increased by 225%, resulting in a significant increase in the paretic limb's contribution to propulsion. Participants continued to produce increased paretic propulsion on removal of the impeding force. The trailing limb angle contributed significantly to the increase in paretic propulsion, whereas the plantarflexion moment did not., Conclusions: Participants exhibited a robust propulsive reserve on the paretic limb, suggesting that there is untapped potential that can be exploited through rehabilitation to improve gait recovery. The increase in propulsive symmetry indicates that a greater response was observed by the paretic limb rather than increased compensation by the nonparetic limb.

Background: The relationships between motor impairment of the affected leg, postural control asymmetry, and impaired body sway control after stroke are not well understood., Objective: To examine the relationship between motor impairment of the affected leg and reduced contribution of this leg to body sway control (ie, dynamic control asymmetry [DCA]) and to determine the relationships between impaired body sway control, DCA, and weight-bearing asymmetry (WBA)., Methods: We assessed quiet-standing balance with eyes open in 70 persons with a unilateral supratentorial chronic stroke using 2 force plates. Center-of-pressure (COP) velocity was calculated for both feet together in the anteroposterior (AP) and mediolateral (ML) directions as a measure of body sway control. Bilateral AP COP velocities were used to calculate an index for DCA and weight borne on each side to calculate WBA. Fugl-Meyer assessment of the lower extremity (FMA-LE; range: 0-28) served as a measure of affected-leg motor impairment., Results: All participants with FMA-LE <24 showed pronounced DCA, but this was also true for 21% of those with FMA ⩾24. Higher DCA values were related to more WBA ( r s = 0.496; P < .001), and less ML sway control ( r s = 0.268; P = .025). AP sway control was not significantly related to either DCA or WBA., Conclusions: Even clinically well-recovered stroke survivors with (near) maximal FMA-LE scores may show clear postural asymmetry in terms of the relative contribution of the affected leg to body sway control. WBA seems to be an effective compensatory mechanism to optimize the contribution of the less-affected leg to balance, particularly in the AP direction.

Background: Clinical trials are suggesting efficacy of intensive therapy combined with brain stimulation to improve hand function in hemiparetic children with perinatal stroke. However, individual variability exists and the underlying neuroplasticity mechanisms are unknown. Exploring primary motor cortex (M1) neurophysiology, and how it changes with such interventions, may provide valuable biomarkers for advancing personalized neurorehabilitation., Methods: Forty-five children (age 6-19 years) with hemiparesis participated in PLASTIC CHAMPS, a blinded, sham-controlled, factorial clinical trial. All received 80 hours of goal-directed intensive upper extremity therapy. They were randomized into 4 groups: repetitive transcranial magnetic stimulation (rTMS) of contralesional M1, constraint therapy, both, or neither. Stimulus recruitment curves (SRC), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) for lesioned and contralesional M1 were investigated using TMS. Clinical assessments including the Assisting Hand Assessment (AHA) and Canadian Occupational Performance Measure (COPM) were conducted pre- and postintervention., Results: All children completed the intervention and both function (AHA) and goal performance (COPM) improved with additive effects of rTMS and constraint ( P < .01). After intervention, motor-evoked potential (MEP) amplitudes from the contralesional M1 to the less-affected hand increased (n = 16, P < .02). SRC from the contralesional M1 to the less-affected hand increased (n = 25, P < .01). SICI of the contralesional M1 to the less-affected hand decreased (n = 30, P < .04). No changes were observed for ICF in either hemisphere ( P > .12)., Conclusion: TMS applied before/after intensive neuromodulation therapies can explore M1 neurophysiology and plasticity in children with cerebral palsy. Increased MEP sizes and decreased SICI may reflect mechanisms of interventional plasticity and be potential biomarkers of individualized medicine.

Background: Arm paresis is present in 48% to 77% of acute stroke patients. Complete functional recovery is reported in only 12% to 34%. Although the arm recovery is most pronounced during the first 4 weeks poststroke, few studies examined the effect of upper extremity interventions during this period., Objective: To investigate the effect of electrical somatosensory stimulation (ESS) delivered during early stroke rehabilitation on the recovery of arm functioning., Methods: A total of 102 patients with arm paresis were randomized to a high-dose or a low-dose ESS group within 7 days poststroke according to our sample size estimation. The high-dose group received 1-hour ESS to the paretic arm daily during hospitalization immediately followed by minimum 15-minute task-oriented arm training that was considered a component of the usual rehabilitation. The low-dose group received a placebo ESS followed by identical training. Primary outcome-Box and Block Test (BBT); secondary outcomes-Fugl-Meyer Assessment (FMA), grip strength, pinch strength, perceptual threshold of touch, pain, and modified Rankin Scale (mRS); all recorded at baseline, postintervention and at 6 months poststroke., Results: There were no differences between the high-dose and the low-dose groups for any outcome measures at any time points. Improvements ⩾ minimal clinically important difference were observed for FMA, hand grip strength, and mRS in both groups., Conclusions: Providing the present ESS protocol prior to arm training was equally beneficial as arm training alone. These results are valid for patients with mild-to-moderate stroke and moderate arm impairments. We cannot exclude benefits in patients with other characteristics, in other time intervals poststroke or using a different ESS protocol., Trial Registration: ClinicalTrials.gov (NCT02250365).

Poststroke deficits in upper extremity function occur during activities of daily living due to motor impairments of the paretic arm, including weakness and abnormal synergies, both of which result in altered use of the paretic arm. Over time, chronic disuse and a resultant flexed elbow posture may result in secondary changes in the musculoskeletal system that may limit use of the arm and impact functional mobility. This study utilized extended field-of-view ultrasound to measure fascicle lengths of the biceps (long head) and triceps (distal portion of the lateral head) brachii in order to investigate secondary alterations in muscles of the paretic elbow. Data were collected from both arms in 11 individuals with chronic hemiparetic stroke, with moderate to severe impairment as classified by the Fugl-Meyer assessment score. Across all participants, significantly shorter fascicles were observed in both biceps and triceps brachii ( P < .0005) in the paretic limb under passive conditions. The shortening in paretic fascicle length relative to the nonparetic arm measured under passive conditions remained observable during active muscle contraction for the biceps but not for the triceps brachii. Finally, average fascicle length differences between arms were significantly correlated to impairment level, with more severely impaired participants showing greater shortening of paretic biceps fascicle length relative to changes seen in the triceps across all elbow positions ( r = -0.82, P = .002). Characterization of this secondary adaptation is necessary to facilitate development of interventions designed to reduce or prevent the shortening from occurring in the acute stages of recovery poststroke.

Background: In the chronic phase after stroke, cortical excitability differs between the cerebral hemispheres; the magnitude of this asymmetry depends on degree of motor impairment. It is unclear whether these asymmetries also affect capacity for plasticity in corticospinal tract excitability or whether hemispheric differences in plasticity are related to chronic sensorimotor impairment., Methods: Response to paired associative stimulation (PAS) was assessed bilaterally in 22 individuals with chronic hemiparesis. Corticospinal excitability was measured as the area under the motor-evoked potential (MEP) recruitment curve (AUC) at baseline, 5 minutes, and 30 minutes post-PAS. Percentage change in contralesional AUC was calculated and correlated with paretic motor and somatosensory impairment scores., Results: PAS induced a significant increase in AUC in the contralesional hemisphere ( P = .041); in the ipsilesional hemisphere, there was no significant effect of PAS ( P = .073). Contralesional AUC showed significantly greater change in individuals without an ipsilesional MEP ( P = .029). Percentage change in contralesional AUC between baseline and 5 m post-PAS correlated significantly with FM score ( r = -0.443; P = .039) and monofilament thresholds ( r = 0.444, P = .044)., Discussion: There are differential responses to PAS within each cerebral hemisphere. Contralesional plasticity was increased in individuals with more severe hemiparesis, indicated by both the absence of an ipsilesional MEP and a greater degree of motor and somatosensory impairment. These data support a body of research showing compensatory changes in the contralesional hemisphere after stroke; new therapies for individuals with chronic stroke could exploit contralesional plasticity to help restore function.

Changes in the control of the lower extremities poststroke lead to persistent biomechanical asymmetries during walking. These asymmetries are associated with an increase in energetic cost, leading to the possibility that reducing asymmetry can improve walking economy. However, the influence of asymmetry on economy may depend on the direction and cause of asymmetry. For example, impairments with paretic limb advancement may result in shorter paretic steps, whereas deficits in paretic support or propulsion result in shorter nonparetic steps. Given differences in the underlying impairments responsible for step length asymmetry, the capacity to reduce asymmetry and the associated changes in energetic cost may not be consistent across this population. Here, we identified factors explaining individual differences in the capacity to voluntarily reduce step length asymmetry and modify energetic cost during walking. A total of 24 individuals poststroke walked on a treadmill, with visual feedback of their step lengths to aid explicit modification of asymmetry. We found that individuals who took longer paretic steps had a greater capacity to reduce asymmetry and were better able to transfer the effects of practice to overground walking than individuals who took shorter paretic steps. In addition, changes in metabolic cost depended on the direction of asymmetry, baseline cost of transport, and reductions in specific features of spatiotemporal asymmetry. These results demonstrate that many stroke survivors retain the residual capacity to voluntarily walk more symmetrically on a treadmill and overground. However, whether reductions in asymmetry reduce metabolic cost depends on individual differences in impairments affecting locomotor function.

The loss of independent joint control, clinically referred to as limb synergies, is prevalent in the paretic upper limb of individuals with chronic hemiparetic stroke. To understand the underlying neural mechanisms, we previously reported that an increased overlap of cortical representations of shoulder/elbow could contribute to the abnormal poststroke synergies. However, these previous results were limited to a fixed time window just before the onset of motor tasks. Questions such as (1) how this overlap develops during motor preparation and (2) whether such development is also linked to upper limb synergies, remain unclear. To answer these questions, we investigated cortical overlap during motor preparation of isometric shoulder and elbow torque generation tasks in healthy individuals (n = 8), and individuals with moderate to severe chronic hemiparesis following a subcortical stroke (n = 12). We found a significant group difference in how the cortical overlap developed. In the healthy control and moderately impaired stroke groups, cortical overlap between shoulder and elbow motor tasks decreased during the motor preparation; however, this overlap increased in individuals with severe stroke. Furthermore, the rate of cortical overlap decrease/increase was linked to the upper limb Fugl-Meyer scores and limb synergies. These results demonstrate, for the first time, that the increase in overlap of the cortical activity during motor preparation is associated with the expression of synergies in the paretic upper limb of severely impaired poststroke individuals.

Defective muscle coordination for balance recovery may contribute to stroke survivors' propensity for falling. Thus, we investigated deficits in muscle coordination for postural control and their association to body sway following balance perturbations in people with stroke. Specifically, we compared the automatic postural responses of 8 leg and trunk muscles recorded bilaterally in unimpaired individuals and those with mild to moderate impairments after unilateral supratentorial lesions (>6 months). These responses were elicited by unexpected floor translations in 12 directions. We extracted motor modules (ie, muscle synergies) for each leg using nonnegative matrix factorization. We also determined the magnitude of perturbation-induced body sway using a single-link inverted pendulum model. Whereas the number of motor modules for balance was not affected by stroke, those formed by muscles with long latency responses were replaced by atypically structured paretic motor modules (atypical muscle groupings), which hints at direct cerebral involvement in long-latency feedback responses. Other paretic motor modules had intact structure but were poorly recruited, which is indicative of indirect cerebral control of balance. Importantly, these paretic deficits were strongly associated with postural instability in the preferred activation direction of the impaired motor modules. Finally, these deficiencies were heterogeneously distributed across stroke survivors with lesions in distinct locations, suggesting that different cerebral substrates may contribute to balance control. In conclusion, muscle coordination deficits in the paretic limb of stroke survivors result in direction-specific postural instability, which highlights the importance of targeted interventions to address patient-specific balance impairments.

Background: Individuals with stroke usually show reduced muscle activities of the paretic leg and asymmetrical gait pattern during walking., Objective: To determine whether applying a resistance force to the nonparetic leg would enhance the muscle activities of the paretic leg and improve the symmetry of spatiotemporal gait parameters in individuals with poststroke hemiparesis., Methods: Fifteen individuals with chronic poststroke hemiparesis participated in this study. A controlled resistance force was applied to the nonparetic leg using a customized cable-driven robotic system while subjects walked on a treadmill. Subjects completed 2 test sections with the resistance force applied at different phases of gait (ie, early and late swing phases) and different magnitudes (10%, 20%, and 30% of maximum voluntary contraction [MVC] of nonparetic leg hip flexors). Electromyographic (EMG) activity of the muscles of the paretic leg and spatiotemporal gait parameters were collected., Results: Significant increases in integrated EMG of medial gastrocnemius, medial hamstrings, vastus medialis, and tibialis anterior of the paretic leg were observed when the resistance was applied during the early swing phase of the nonparetic leg, compared with baseline. Additionally, resistance with 30% of MVC induced the greatest level of muscle activity than that with 10% or 20% of MVC. The symmetry index of gait parameters also improved with resistance applied during the early swing phase., Conclusion: Applying a controlled resistance force to the nonparetic leg during early swing phase may induce forced use on the paretic leg and improve the spatiotemporal symmetry of gait in individuals with poststroke hemiparesis.

Background and Objective: Postural muscle responses are often impaired after stroke. We aimed to identify the contribution of deficits in very early postural responses to poorer reactive balance capacity, with a particular focus on reactive stepping as a key strategy for avoiding falls., Methods: A total of 34 chronic stroke survivors and 17 controls were subjected to translational balance perturbations in 4 directions. We identified the highest perturbation intensity that could be recovered without stepping (single stepping threshold [SST]) and with maximally 1 step (multiple stepping threshold [MST]). We determined onset latencies and response amplitudes of 7 leg muscles bilaterally and identified associations with balance capacity., Results: People with stroke had a lower MST than controls in all directions. Side steps resulted in a higher lateral MST than crossover steps but were less common toward the paretic side. Postural responses were delayed and smaller in amplitude on the paretic side only. We observed the strongest associations between gluteus medius (GLUT) onset and amplitude and MST toward the paretic side ( R 2 = 0.33). Electromyographic variables were rather weakly associated with forward and backward MSTs ( R 2 = 0.10-0.22) and with SSTs ( R 2 = 0.08-0.15)., Conclusions: Delayed and reduced paretic postural responses are associated with impaired reactive stepping after stroke. Particularly, fast and vigorous activity of the GLUT is imperative for overcoming large sideways perturbations, presumably because it facilitates the effective use of side steps. Because people with stroke often fall toward the paretic side, this finding indicates an important target for training.

Background: Robots that physically assist movement are increasingly used in rehabilitation therapy after stroke, yet some studies suggest robotic assistance discourages effort and reduces motor learning., Objective: To determine the therapeutic effects of high and low levels of robotic assistance during finger training., Methods: We designed a protocol that varied the amount of robotic assistance while controlling the number, amplitude, and exerted effort of training movements. Participants (n = 30) with a chronic stroke and moderate hemiparesis (average Box and Blocks Test 32 ± 18 and upper extremity Fugl-Meyer score 46 ± 12) actively moved their index and middle fingers to targets to play a musical game similar to GuitarHero 3 h/wk for 3 weeks. The participants were randomized to receive high assistance (causing 82% success at hitting targets) or low assistance (55% success). Participants performed ~8000 movements during 9 training sessions., Results: Both groups improved significantly at the 1-month follow-up on functional and impairment-based motor outcomes, on depression scores, and on self-efficacy of hand function, with no difference between groups in the primary endpoint (change in Box and Blocks). High assistance boosted motivation, as well as secondary motor outcomes (Fugl-Meyer and Lateral Pinch Strength)-particularly for individuals with more severe finger motor deficits. Individuals with impaired finger proprioception at baseline benefited less from the training., Conclusions: Robot-assisted training can promote key psychological outcomes known to modulate motor learning and retention. Furthermore, the therapeutic effectiveness of robotic assistance appears to derive at least in part from proprioceptive stimulation, consistent with a Hebbian plasticity model.

Background: Recovery of arm function after stroke is often incomplete. An improved understanding of brain structure-motor behavior relationships is needed for the development of novel and targeted rehabilitation interventions., Objective: To examine the relationship between skilled reach performance and the integrity of two putative white matter motor pathways, corticospinal tract and corpus callosum, after stroke., Methods: Eleven individuals with chronic stroke (poststroke duration, mean 62.5 ± 42.4 months) and mild motor impairment (upper extremity Fugl-Meyer score, mean 54.2 ± 7.6) reached to six targets presented at three distances and two directions. Fractional anisotropy (FA) obtained from diffusion tensor imaging was used to determine the structural integrity of the corticospinal tract and the corpus callosum., Results: Overall reach performance was decreased in the paretic arm compared with the nonparetic arm. While FA was decreased in the ipsilesional corticospinal tract, FA in the corticospinal tract did not correlate with variability in reach performance between individuals. Instead, FA in the premotor section of the corpus callosum correlated with reach performance; individuals with higher FA in premotor corpus callosum tended to reach faster with both the paretic and nonparetic arms., Conclusions: The structural connections between the two premotor and supplemental cortices that traverse the premotor corpus callosum may play an important role in supporting motor control and could become a target for interventions aimed at improved arm function in this population.

Background: Studies demonstrate that most arm motor recovery occurs within three months after stroke, when measured with standard clinical scales. Improvements on these measures, however, reflect a combination of recovery in motor control, increases in strength, and acquisition of compensatory strategies., Objective: To isolate and characterize the time course of recovery of arm motor control over the first year poststroke., Methods: Longitudinal study of 18 participants with acute ischemic stroke. Motor control was evaluated using a global kinematic measure derived from a 2-dimensional reaching task designed to minimize the need for antigravity strength and prevent compensation. Arm impairment was evaluated with the Fugl-Meyer Assessment of the upper extremity (FMA-UE), activity limitation with the Action Research Arm Test (ARAT), and strength with biceps dynamometry. Assessments were conducted at: 1.5, 5, 14, 27, and 54 weeks poststroke., Results: Motor control in the paretic arm improved up to week 5, with no further improvement beyond this time point. In contrast, improvements in the FMA-UE, ARAT, and biceps dynamometry continued beyond 5 weeks, with a similar magnitude of improvement between weeks 5 and 54 as the one observed between weeks 1.5 and 5., Conclusions: Recovery after stroke plateaued much earlier for arm motor control, isolated with a global kinematic measure, compared to motor function assessed with clinical scales. This dissociation between the time courses of kinematic and clinical measures of recovery may be due to the contribution of strength improvement to the latter. Novel interventions, focused on the first month poststroke, will be required to exploit the narrower window of spontaneous recovery for motor control.

Background: Up to 60% of individuals with moderate to severe chronic hemiparetic stroke experience excessive involuntary wrist/finger flexion that constrains functional hand movements including hand opening. It's not known how stroke-induced brain injury impacts volitional hand opening and grasping forces as a result of the expression of abnormal coupling between shoulder abduction and wrist/finger flexion or the flexion synergy., Objective: The goal of this study is to understand how shoulder abduction loading affects volitional hand opening and grasping forces in individuals with moderate to severe chronic hemiparetic stroke., Methods: Thirty-six individuals (stroke, 26; control, 10) were recruited for this study. Each participant was instructed to perform maximal hand opening and grasping forces while the arm was either fully supported or lifted with a weight equal to 25% or 50% of the participant's maximal shoulder abduction torque. Hand pentagon area, defined as the area formed by the tips of thumb and fingers, was calculated during hand opening. Forces were recorded during grasping., Results: In individuals with moderate stroke, increasing shoulder abduction loading reduced the ability to maximally open the hand. In individuals with severe stroke, who were not able to open the hand, grasping forces were generated and increased with shoulder abduction loading. Stroke individuals also showed a reduced ability to control volitional grasping forces due to the enhanced expression of flexion synergy., Conclusions: Shoulder abduction loading reduced the ability to volitionally open the hand and control grasping forces after stroke. Neural mechanisms and clinical implications of these findings are discussed.

Background: Perinatal stroke causes most hemiparetic cerebral palsy. Ipsilateral connections from nonlesioned hemisphere to affected hand are common. The nonlesioned primary motor cortex (M1) determines function and is a potential therapeutic target but its neurophysiology is poorly understood., Objective: We aimed to characterize the neurophysiological properties of the nonlesioned M1 in children with perinatal stroke and their relationship to clinical function., Methods: Fifty-two participants with hemiparetic cerebral palsy and magnetic resonance imaging-confirmed perinatal stroke and 40 controls aged 8 to 18 years completed the same transcranial magnetic stimulation (TMS) protocol. Single-pulse TMS to nonlesioned M1 determined rest and active motor thresholds (RMT/AMT), motor-evoked potential (MEP) latencies, and stimulus recruitment curves (SRC: 100%-150% RMT). Paired-pulse TMS evaluated short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF). Ipsilateral (IP) participants (ipsilateral MEP ≥0.05 mV in ≥5/20 trials) were compared with contralateral MEP only, nonipsilateral (NI) participants. Assisting Hand and Melbourne assessments quantified clinical function., Results: Twenty-five IP were compared with 13 NI (n = 38, median age 12 years, 66% male). IP had lower motor function. SRC to unaffected hand were comparable between IP and NI while IP had smaller ipsilateral SRC. Ipsilateral MEP latencies were prolonged (23.5 ± 1.8 vs 22.2 ± 1.5 ms contra, P < .001). Contralateral SICI was different between IP (-42%) and NI (-20%). Ipsilateral SICI was reduced (-20%). Contralateral ICF was comparable between groups (+43%) and ipsilaterally (+43%). Measures correlated between contralateral and ipsilateral sides., Conclusion: Neurophysiology of nonlesioned M1 and its relationship to motor function is measureable in children with perinatal stroke. Correlation of excitability and intracortical circuitry measures between contralateral and ipsilateral sides suggests common control mechanisms.

Background: A common assumption is that changes in upper limb (UL) capacity, or what an individual is capable of doing, translates to improved UL performance in daily life, or what an individual actually does. This assumption should be explicitly tested for individuals with UL paresis poststroke., Objective: To examine changes in UL performance after an intensive, individualized, progressive, task-specific UL intervention for individuals at least 6 months poststroke., Methods: Secondary analysis on 78 individuals with UL paresis who participated in a phase II, single-blind, randomized parallel dose-response trial. Participants were enrolled in a task-specific intervention for 8 weeks. Participants were randomized into 1 of 4 treatment groups with each group completing different amounts of UL movement practice. UL performance was assessed with bilateral, wrist-worn accelerometers once a week for 24 hours throughout the duration of the study. The 6 accelerometer variables were tested for change and the influence of potential modifiers using hierarchical linear modeling., Results: No changes in UL performance were found on any of the 6 accelerometer variables used to quantify UL performance. Neither changes in UL capacity nor the overall amount of movement practice influenced changes in UL performance. Stroke chronicity, baseline UL capacity, concordance, and ADL status significantly increased the baseline starting points but did not influence the rate of change (slopes) for participants., Conclusions: Improved motor capacity resulting from an intensive outpatient UL intervention does not appear to translate to increased UL performance outside the clinic.

Background: Trunk function is important for standing balance, mobility, and functional outcome after stroke, but few studies have evaluated the effects of exercises aimed at improving core stability in stroke patients., Objective: To investigate the effectiveness of core stability training on trunk function, standing balance, and mobility in stroke patients., Methods: An assessor-blinded, randomized controlled trial was undertaken in a stroke rehabilitation ward, with 32 participants randomly assigned to an experimental group or a control group (n = 16 each). The experimental group received 400 minutes of core stability training in place of conventional programs within total training time, while the control group received only conventional programs. Primary outcome measures were evaluated using the Trunk Impairment Scale (TIS), which reflects trunk function. Secondary outcome measures were evaluated by pelvic tilt active range of motion in the sagittal plane, the Balance Evaluation Systems Test-brief version (Brief-BESTest), Functional Reach test, Timed Up-and-Go test (TUG), and Functional Ambulation Categories (FAC). A general linear repeated-measures model was used to analyze the results., Results: A treatment effect was found for the experimental group on the dynamic balance subscale and total score of the TIS ( P = .002 and P < .001, respectively), pelvic tilt active range of motion ( P < .001), Brief-BESTest ( P < .001), TUG ( P = .008), and FAC ( P = .022)., Conclusions: Core stability training has beneficial effects on trunk function, standing balance, and mobility in stroke patients. Our findings might provide support for introducing core stability training in stroke rehabilitation.

Background: Mirror therapy provides a visual illusion of a normal moving limb by using the mirror reflection of the unaffected arm instead of viewing the paretic limb and is used in rehabilitation to improve hand function. Little is known about the mechanism underlying its effect in children with hemiparesis., Objective: To investigate the effect of the mirror illusion (MI) on the excitability of the primary motor cortex (M1) in children and adolescents., Methods: Twelve patients with hemiparesis (10-20 years) and 8 typically developing subjects (8-17 years) participated. Corticospinal reorganization was classified as contralateral (projection from contralateral hemisphere to affected hand) or ipsilateral (projection from ipsilateral hemisphere to affected hand). M1 excitability of the hemisphere projecting to the affected (nondominant in typically developing subjects) hand was obtained during 2 different conditions using single-pulse transcranial magnetic stimulation (TMS). Each condition (without/with mirror) consisted of a unimanual and a bimanual task. Motor-evoked potentials (MEPs) were recorded from the abductor pollicis brevis and flexor digitorum superficialis muscles., Results: MEP amplitudes were significantly increased during the mirror condition ( P = .005) in typically developing subjects and in patients with contralateral reorganization. No significant effect of MI was found in subjects with ipsilateral reorganization. MI increased M1 excitability during active movements only. This increase was not correlated to hand function., Conclusion: MI increases the excitability of M1 in hemiparetic patients with contralateral corticospinal organization and in typically developing subjects. This finding provides neurophysiological evidence supporting the application of mirror therapy in selected children and adolescents with hemiparesis.

Background: The Arm Motor Ability Test (AMAT) is used to assess and quantify upper-extremity (UE) functional limitation in stroke and other conditions. However, the AMAT score change indicative of important and clinically meaningful change has not been determined., Objective: To determine the clinically important difference (CID) for the AMAT for individuals with stroke exhibiting mild to moderate hemiparesis., Methods: A total of 146 chronic stroke survivors exhibiting stable, mild to moderate UE hemiparesis were administered the AMAT before and after interventions targeting their affected UEs. Patients and treating therapists rated perceived amount of UE motor recovery for each participant on a global rating of change (GROC) scale evaluating several facets of UE movement (grasp, release, move the affected UE, perform 5 important functional tasks, overall UE function). Estimated CID of the Functional Ability Scale of the AMAT was calculated using the receiver operating characteristics curve with the GROC scale as the anchor. Distribution-based methods were also used to estimate the CID., Results: Mean baseline, postintervention, and change in AMAT values for all participants were 3.0 (0.68), 3.3 (0.73), and 0.33 (0.43) respectively. The CID was estimated as an improvement of 0.32 to 0.42 when anchored by the therapist's perception of improvement and 0.29 to 0.40 when anchored by the patient's perception of improvement. The CID using distribution-based methods ranged from 0.40 to 0.44., Conclusions: A change of 0.44 or greater on the AMAT indicates a clinically meaningful improvement in UE functional movements. Clinicians should use this value to determine goals and interpret change scores.

Background and Objective: Stroke rehabilitation assumes motor learning contributes to motor recovery, yet motor learning in stroke has received little systematic investigation. Here we aimed to illustrate that despite matching levels of performance on a task, a trained patient should not be considered equal to an untrained patient with less impairment., Methods: We examined motor learning in healthy control participants and groups of stroke survivors with mild-to-moderate or moderate-to-severe motor impairment. Participants performed a series of isometric contractions of the elbow flexors to navigate an on-screen cursor to different targets, and trained to perform this task over a 4-day period. The speed-accuracy trade-off function (SAF) was assessed for each group, controlling for differences in self-selected movement speeds between individuals., Results: The initial SAF for each group was proportional to their impairment. All groups were able to improve their performance through skill acquisition. Interestingly, training led the moderate-to-severe group to match the untrained (baseline) performance of the mild-to-moderate group, while the trained mild-to-moderate group matched the untrained (baseline) performance of the controls. Critically, this did not make the two groups equivalent; they differed in their capacity to improve beyond this matched performance level. Specifically, the trained groups had reached a plateau, while the untrained groups had not., Conclusions: Despite matching levels of performance on a task, a trained patient is not equal to an untrained patient with less impairment. This has important implications for decisions both on the focus of rehabilitation efforts for chronic stroke, as well as for returning to work and other activities.

Background: Upper limb (UL) poststroke hemiparesis commonly leads to chronic disability. Despite moderate-to-good clinical recovery, many patients with UL hemiparesis still do not fully use their arm in daily tasks. Decreased arm use may be related to deficits in performance of more complex movement than what is usually assessed clinically., Objective: To identify differences between poststroke and nondisabled control subjects in making complex corrective movements to avoid an obstacle in the reaching path., Methods: Subjects rapidly reached for a juice bottle on a refrigerator shelf with their hemiparetic or dominant (controls) arm viewed in a large-screen projected 3D virtual environment. In random trials, a sliding door partially obstructed the reaching path. A successful trial was one in which subjects touched the bottle without their arm or hand hitting the door., Results: Fewer participants with stroke (12%) were successful at a 65% success rate in avoiding the door compared to controls (42%). Subjects with stroke also initiated corrections later (further) in the reaching path (100.7 ± 77.6 mm) compared to controls (51.6 ± 31.0 mm) resulting in a reduced margin of error. While both groups used similar endpoint movement strategies for obstructed reaching, subjects with stroke used less elbow and more trunk movement. Participants who reported being more confident using their hemiparetic arm had higher success rates., Conclusion: Arm movement deficits can be identified when complex tasks are evaluated. Deficits in higher-order motor function such as obstacle avoidance behavior may decrease actual arm use in individuals with mild-to-moderate hemiparesis and should be evaluated in routine clinical practice.

Background: Robot technology for poststroke rehabilitation is developing rapidly. A number of new randomized controlled trials (RCTs) have investigated the effects of robot-assisted therapy for the paretic upper limb (RT-UL)., Objective: To systematically review the effects of poststroke RT-UL on measures of motor control of the paretic arm, muscle strength and tone, upper limb capacity, and basic activities of daily living (ADL) in comparison with nonrobotic treatment., Methods: Relevant RCTs were identified in electronic searches. Meta-analyses were performed for measures of motor control (eg, Fugl-Meyer Assessment of the arm; FMA arm), muscle strength and tone, upper limb capacity, and basic ADL. Subgroup analyses were applied for the number of joints involved, robot type, timing poststroke, and treatment contrast., Results: Forty-four RCTs (N = 1362) were included. No serious adverse events were reported. Meta-analyses of 38 trials (N = 1206) showed significant but small improvements in motor control (~2 points FMA arm) and muscle strength of the paretic arm and a negative effect on muscle tone. No effects were found for upper limb capacity and basic ADL. Shoulder/elbow robotics showed small but significant effects on motor control and muscle strength, while elbow/wrist robotics had small but significant effects on motor control., Conclusions: RT-UL allows patients to increase the number of repetitions and hence intensity of practice poststroke, and appears to be a safe therapy. Effects on motor control are small and specific to the joints targeted by RT-UL, whereas no generalization is found to improvements in upper limb capacity. The impact of RT-UL started in the first weeks poststroke remains unclear. These limited findings could mainly be related to poor understanding of robot-induced motor learning as well as inadequate designing of RT-UL trials, by not applying an appropriate selection of stroke patients with a potential to recovery at baseline as well as the lack of fixed timing of baseline assessments and using an insufficient treatment contrast early poststroke.

Stroke survivors often have a slow, asymmetric walking pattern. They also walk with a higher metabolic cost than healthy, age-matched controls. It is often assumed that spatial-temporal asymmetries contribute to the increased metabolic cost of walking poststroke. However, elucidating this relationship is made challenging because of the interdependence between spatial-temporal asymmetries, walking speed, and metabolic cost. Here, we address these potential confounds by measuring speed-dependent changes in metabolic cost and implementing a recently developed approach to dissociate spatial versus temporal contributions to asymmetry in a sample of stroke survivors. We used expired gas analysis to compute the metabolic cost of transport (CoT) for each participant at 4 different walking speeds: self-selected speed, 80% and 120% of their self-selected speed, and their fastest comfortable speed. We also computed CoT for a sample of age- and gender-matched control participants who walked at the same speeds as their matched stroke survivor. Kinematic data were used to compute the magnitude of a number of variables characterizing spatial-temporal asymmetries. Across all speeds, stroke survivors had a higher CoT than controls. We also found that our sample of stroke survivors did not choose a self-selected speed that minimized CoT, contrary to typical observations in healthy controls. Multiple regression analyses revealed negative associations between speed and CoT and a positive association between asymmetries in foot placement relative to the trunk and CoT. These findings suggest that interventions designed to increase self-selected walking speed and reduce foot-placement asymmetries may be ideal for improving walking economy poststroke., Competing Interests: Declaration of Conflicting Interests The author(s) have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objective: Advances in technology are providing new forms of human-computer interaction. The current study examined one form of human-computer interaction, augmented reality (AR), whereby subjects train in the real-world workspace with virtual objects projected by the computer. Motor performances were compared with those obtained while subjects used a traditional human-computer interaction, that is, a personal computer (PC) with a mouse., Methods: Patients used goal-directed arm movements to play AR and PC versions of the Fruit Ninja video game. The 2 versions required the same arm movements to control the game but had different cognitive demands. With AR, the game was projected onto the desktop, where subjects viewed the game plus their arm movements simultaneously, in the same visual coordinate space. In the PC version, subjects used the same arm movements but viewed the game by looking up at a computer monitor., Results: Among 18 patients with chronic hemiparesis after stroke, the AR game was associated with 21% higher game scores (P = .0001), 19% faster reaching times (P = .0001), and 15% less movement variability (P = .0068), as compared to the PC game. Correlations between game score and arm motor status were stronger with the AR version., Conclusions: Motor performances during the AR game were superior to those during the PC game. This result is due in part to the greater cognitive demands imposed by the PC game, a feature problematic for some patients but clinically useful for others. Mode of human-computer interface influences rehabilitation therapy demands and can be individualized for patients., (© The Author(s) 2015.)

Background: Step length asymmetry (SLA) is a common hallmark of gait poststroke. Though conventionally viewed as a spatial deficit, SLA can result from differences in where the feet are placed relative to the body (step position strategy), the timing between foot strikes (step time strategy), or the velocity of the body relative to the feet (step velocity strategy)., Objective: The goal of this study was to characterize the relative contributions of each of these strategies to SLA., Methods: We developed an analytical model that parses SLA into independent step position, step time, and step velocity contributions. This model was validated by reproducing SLA values for 25 healthy participants when their natural symmetric gait was perturbed on a split-belt treadmill moving at either a 2:1 or 3:1 belt-speed ratio. We then applied the validated model to quantify step position, step time, and step velocity contributions to SLA in 15 stroke survivors while walking at their self-selected speed., Results: SLA was predicted precisely by summing the derived contributions, regardless of the belt-speed ratio. Although the contributions to SLA varied considerably across our sample of stroke survivors, the step position contribution tended to oppose the other 2-possibly as an attempt to minimize overall SLA., Conclusions: Our results suggest that changes in where the feet are placed or changes in interlimb timing could be used as compensatory strategies to reduce overall SLA in stroke survivors. These results may allow clinicians and researchers to identify patient-specific gait abnormalities and personalize their therapeutic approaches accordingly., (© The Author(s) 2015.)

Background: Elucidation of the relative importance of commonly targeted biomechanical variables to poststroke long-distance walking function would facilitate optimal intervention design., Objectives: To determine the relative contribution of variables from 3 biomechanical constructs to poststroke long-distance walking function and identify the biomechanical changes underlying posttraining improvements in long-distance walking function., Methods: Forty-four individuals >6 months after stroke participated in this study. A subset of these subjects (n = 31) underwent 12 weeks of high-intensity locomotor training. Cross-sectional (pretraining) and longitudinal (posttraining change) regression quantified the relationships between poststroke long-distance walking function, as measured via the 6-Minute Walk Test (6MWT), and walking biomechanics. Biomechanical variables were organized into stance phase (paretic propulsion and trailing limb angle), swing phase (paretic ankle dorsiflexion and knee flexion), and symmetry (step length and swing time) constructs., Results: Pretraining, all variables correlated with 6MWT distance (rs = .39 to .75, Ps < .05); however, only propulsion (Prop) and trailing limb angle (TLA) independently predicted 6MWT distance, R(2) = .655, F(6, 36) = 11.38, P < .001. Interestingly, only ΔProp predicted Δ6MWT; however, pretraining Prop, pretraining TLA, and ΔTLA moderated this relationship (moderation model R(2)s = .383, .468, .289, respectively)., Conclusions: The paretic limb's ability to generate propulsion during walking is a critical determinant of long-distance walking function after stroke. This finding supports the development of poststroke interventions that target deficits in propulsion and trailing limb angle., (© The Author(s) 2014.)

Background: Recent work has shown that resting-state functional connectivity (rsFC) between homotopic, motor-related brain regions is associated with upper-extremity control early after stroke., Objectives: This study examined various patterns of rsFC in chronic stroke, a time at which extensive neural reorganization has occurred. Associations between homotopic somatomotor connectivity and clinical measures, representing separate domains of upper-extremity function, were determined., Methods: A total of 19 persons ≥6 months poststroke participated. Four connectivity patterns within a somatomotor network were quantified using functional magnetic resonance imaging. Upper-extremity gross muscle activation, control, and real-world use were evaluated with the Motricity Index, Action Research Arm Test, and accelerometry, respectively., Results: Connectivity between homotopic regions was stronger than that in the contralesional and ipsilesional hemispheres. No differences in connectivity strength were noted between homotopic pairs, indicating that a specific brain structure was not driving somatomotor network connectivity. Homotopic connectivity was significantly associated with both upper-extremity control (r = 0.53; P= .02) and real-world use (r = 0.54; P= .02); however, there was no association with gross muscle activation (r = 0.23; P=.34). The combination of clinical measures accounted for 40% of the variance in rsFC (= .05)., Conclusions: The results reported here expand on previous findings, indicating that homotopic rsFC persists in chronic stroke and discriminates between varying levels of upper-extremity control and real-world use. Further work is needed to evaluate its adequacy as a biomarker of motor recovery following stroke., (© The Author(s) 2014.)

Background Thus far, most of the brain-computer interfaces (BCIs) developed for motor rehabilitation used electroencephalographic signals to drive prostheses that support upper limb movement. Only few BCIs used hemodynamic signals or were designed to control lower extremity prostheses. Recent technological developments indicate that functional near-infrared spectroscopy (fNIRS)-BCI can be exploited in rehabilitation of lower limb movement due to its great usability and reduced sensitivity to head motion artifacts. Objective The aim of this proof of concept study was to assess whether hemodynamic signals underlying lower limb motor preparation in stroke patients can be reliably measured and classified. Methods fNIRS data were acquired during preparation of left and right hip movement in 7 chronic stroke patients. Results Single-trial analysis indicated that specific hemodynamic changes associated with left and right hip movement preparation can be measured with fNIRS. Linear discriminant analysis classification of totHB signal changes in the premotor cortex and/or posterior parietal cortex indicated above chance accuracy in discriminating paretic from nonparetic movement preparation trials in most of the tested patients. Conclusion The results provide first evidence that fNIRS can detect brain activity associated with single-trial lower limb motor preparation in stroke patients. These findings encourage further investigation of fNIRS suitability for BCI applications in rehabilitation of patients with lower limb motor impairment after stroke., (© The Author(s) 2014.)

Background: γ-Aminobutyric acid (GABA) plasticity plays an important role in stroke motor recovery in a mouse model. However, little is known about changes over time in neuronal excitability mediated by GABA receptors in human stroke patients., Objectives: To establish the mechanism of neuroplasticity during the recovery phase following ischemic stroke by assessing the changes in cerebral GABA activity using [(18)F]flumazenil ([(18)F]FMZ) positron emission tomography (PET)., Methods: A total of 10 patients with unilateral ischemic stroke were studied at 1 month (T0) and 3 months (T1) postonset using [(18)F]FMZ PET. Changes in regional GABAergic activity were assessed longitudinally, and values were also compared with those in 15 age-matched controls. Upper-extremity motor function was evaluated using the Fugl-Meyer score (FMS)., Results: During the follow-up period, statistical parametric mapping analysis demonstrated a decrease in GABAA receptor availability throughout the cerebral cortex and cerebellum, especially the contralateral hemisphere. GABAA availability in the bilateral primary motor cortex, contralateral supplemental motor cortex, and globus pallidus at T0 was positively correlated with the FMS score at T1 CONCLUSIONS: This is the first prospective, controlled longitudinal study showing that the change in GABA receptor availability over time is significantly related to motor recovery after stroke in humans. This work supports the rationale for a novel strategy to promote motor recovery after stroke., (© The Author(s) 2014.)

Background Previous research has shown that during simulated activities of daily living, right-handed stroke patients use their contralesional arm more after left- than right-hemisphere stroke. These findings were attributed to a hand preference effect. However, these decisions about when to use the contralesional arm may be modulated by where in the work space the task is performed, a factor that could be used in physical rehabilitation to influence recovery by decreasing learned nonuse. Objective To examine how target location and side of stroke influences arm selection choices for simple reaching movements. Methods A total of 14 right-handed stroke patients (7 with left-hemisphere and 7 with right-hemisphere damage [RHD]), with similar degrees of hemiparesis (Fugl-Meyer motor score), and 16 right-handed controls participated in this experiment. In a pseudorandom fashion, 32 targets were presented throughout the reachable horizontal plane work space, and the participants were asked to select 1 hand to reach the target on each trial. Results The group with left-hemisphere damage chose their contralesional arm significantly more often than the group with RHD. Patients with RHD also chose their left (contralesional) arm significantly less often than the control group. However, these patterns of choice were most pronounced in the center of the workspace. Conclusion Both the side of hemisphere damage and work space location played a significant role in the choice of whether to use the contralesional arm for reaching. These findings have implications for structuring rehabilitation for unilateral stroke patients., (© The Author(s) 2014.)