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BackgroundAlthough guidelines support aerobic exercise in sub-acute mild traumatic brain injury (mTBI), evidence for adults with persisting post-concussive symptoms (PPCS) after mTBI is lacking. The objective was to evaluate the impact of a sub-symptom threshold aerobic exercise intervention on overall symptom burden and quality of life in adults with PPCS.MethodsThis prospective cohort study was nested within the ACTBI Trial (Aerobic Exercise for treatment of Chronic symptoms following mild Traumatic Brain Injury). A total of 50 adults with a diagnosis of mTBI, PPCS and exercise intolerance completed a 12-week sub-symptom threshold aerobic exercise intervention either immediately after enrollment (i-AEP group; n = 27) or following 6-weeks of stretching (d-AEP group; n = 23). Data from all participants (n = 50) were included in the combined AEP (c-AEP) group. The primary outcome was symptom burden on the Rivermead Post Concussion Symptoms Questionnaire (RPQ). Secondary outcomes included measures of quality of life and specific post-concussive symptoms (depressive and anxiety symptoms, functional impact of headache, fatigue, sleep, dizziness and exercise tolerance). Heart rate, blood pressure and heart rate variability were also assessed to understand autonomic function response to intervention.ResultsParticipants were a mean (SD) of 42.6 (10.9) years old (74% female) and 25.1 (14.1) months post-mTBI. Following 12-weeks of intervention participants had a significant improvement in symptom burden on the RPQ (i-AEP: mean change = −9.415, p

Abstract Background Proprioceptive impairments are common after stroke and are associated with worse motor recovery and poor rehabilitation outcomes. Motor learning may also be an important factor in motor recovery, and some evidence in healthy adults suggests that reduced proprioceptive function is associated with reductions in motor learning. It is unclear how impairments in proprioception and motor learning relate after stroke. Here we used robotics and a traditional clinical assessment to examine the link between impairments in proprioception after stroke and a type of motor learning known as visuomotor adaptation. Methods We recruited participants with first-time unilateral stroke and controls matched for overall age and sex. Proprioceptive impairments in the more affected arm were assessed using robotic arm position- (APM) and movement-matching (AMM) tasks. We also assessed proprioceptive impairments using a clinical scale (Thumb Localization Test; TLT). Visuomotor adaptation was assessed using a task that systematically rotated hand cursor feedback during reaching movements (VMR). We quantified how much participants adapted to the disturbance and how many trials they took to adapt to the same levels as controls. Spearman’s rho was used to examine the relationship between proprioception, assessed using robotics and the TLT, and visuomotor adaptation. Data from healthy adults were used to identify participants with stroke who were impaired in proprioception and visuomotor adaptation. The independence of impairments in proprioception and adaptation were examined using Fisher’s exact tests. Results Impairments in proprioception (58.3%) and adaptation (52.1%) were common in participants with stroke (n = 48; 2.10% acute, 70.8% subacute, 27.1% chronic stroke). Performance on the APM task, AMM task, and TLT scores correlated weakly with measures of visuomotor adaptation. Fisher’s exact tests demonstrated that impairments in proprioception, assessed using robotics and the TLT, were independent from impairments in visuomotor adaptation in our sample. Conclusion Our results suggest impairments in proprioception may be independent from impairments in visuomotor adaptation after stroke. Further studies are needed to understand factors that influence the relationship between motor learning, proprioception and other rehabilitation outcomes throughout stroke recovery.

Abstract Background Studies examining factors associated with patient referral to early supported discharge (ESD)/outpatient rehabilitation (OPR) programs and utilization of ESD/OPR services after discharge from inpatient stroke rehabilitation (IPR) are scarce. Accordingly, we examined utilization of ESD/OPR services following discharge from IPR and patient factors associated with service utilization. Methods Stroke patients discharged from IPR facilities in Alberta between April 2014 and March 2016 were included and followed for one year for ESD/OPR service utilization. Multivariable linear and negative binomial regressions were used to examine association of patients’ factors with ESD/OPR use. Results We included 752 patients (34.4% of 2,187 patients discharged from IPR) who had 40,772 ESD/OPR visits during one year of follow-up in the analysis. Mean and median ESD/OPR visits were 54.2 and 36 visits, respectively. Unadjusted ESD/OPR visits were lower in females and patients aged ≥ 60 years but were similar between urban and rural areas. After adjustment for patient factors, patients in urban areas and discharged home after IPR were associated with 83.5% and 61.9%, respectively, increase in ESD/OPR visits, while having a right-body stroke was associated with 23.5% increase. Older patients used ESD/OPR less than their younger counterparts (1.4% decrease per one year of older age). Available factors explained 12.3% of variation in ESD/OPR use. Conclusion ESD/OPR utilization after IPR in Alberta was low and varied across age and geographic locations. Factors associated with use of ESD/OPR were identified but they could not fully explain variation of ESD/OPR use.

Abstract Background A key motor skill is the ability to rapidly interact with our dynamic environment. Humans can generate goal-directed motor actions in response to sensory stimulus within ~ 60-200ms. This ability can be impaired after stroke, but most clinical tools lack any measures of rapid feedback processing. Reaching tasks have been used as a framework to quantify impairments in generating motor corrections for individuals with stroke. However, reaching may be inadequate as an assessment tool as repeated reaching can be fatiguing for individuals with stroke. Further, reaching requires many trials to be completed including trials with and without disturbances, and thus, exacerbate fatigue. Here, we describe a novel robotic task to quantify rapid feedback processing in healthy controls and compare this performance with individuals with stroke to (more) efficiently identify impairments in rapid feedback processing. Methods We assessed a cohort of healthy controls (n = 135) and individuals with stroke (n = 40; Mean 41 days from stroke) in the Fast Feedback Interception Task (FFIT) using the Kinarm Exoskeleton robot. Participants were instructed to intercept a circular white target moving towards them with their hand represented as a virtual paddle. On some trials, the arm could be physically perturbed, the target or paddle could abruptly change location, or the target could change colour requiring the individual to now avoid the target. Results Most participants with stroke were impaired in reaction time (85%) and end-point accuracy (83%) in at least one of the task conditions, most commonly with target or paddle shifts. Of note, this impairment was also evident in most individuals with stroke when performing the task using their unaffected arm (75%). Comparison with upper limb clinical measures identified moderate correlations with the FFIT. Conclusion The FFIT was able to identify a high proportion of individuals with stroke as impaired in rapid feedback processing using either the affected or unaffected arms. The task allows many different types of feedback responses to be efficiently assessed in a short amount of time.

Abstract Background Ipsilesional motor impairments of the arm are common after stroke. Previous studies have suggested that severity of contralesional arm impairment and/or hemisphere of lesion may predict the severity of ipsilesional arm impairments. Historically, these impairments have been assessed using clinical scales, which are less sensitive than robot-based measures of sensorimotor performance. Therefore, the objective of this study was to characterize progression of ipsilesional arm motor impairments using a robot-based assessment of motor function over the first 6-months post-stroke and quantify their relationship to (1) contralesional arm impairment severity and (2) stroke-lesioned hemisphere. Methods A total of 106 participants with first-time, unilateral stroke completed a unilateral assessment of arm motor impairment (visually guided reaching task) using the Kinarm Exoskeleton. Participants completed the assessment along with a battery of clinical measures with both ipsilesional and contralesional arms at 1-, 6-, 12-, and 26-weeks post-stroke. Results Robotic assessment of arm motor function revealed a higher incidence of ipsilesional arm impairment than clinical measures immediately post-stroke. The incidence of ipsilesional arm impairments decreased from 47 to 14% across the study period. Kolmogorov–Smirnov tests revealed that ipsilesional arm impairment severity, as measured by our task, was not related to which hemisphere was lesioned. The severity of ipsilesional arm impairments was variable but displayed moderate significant relationships to contralesional arm impairment severity with some robot-based parameters. Conclusions Ipsilesional arm impairments were variable. They displayed relationships of varying strength with contralesional impairments and were not well predicted by lesioned hemisphere. With standard clinical care, 86% of ipsilesional impairments recovered by 6-months post-stroke.

Abstract Background Robots can generate rich kinematic datasets that have the potential to provide far more insight into impairments than standard clinical ordinal scales. Determining how to define the presence or absence of impairment in individuals using kinematic data, however, can be challenging. Machine learning techniques offer a potential solution to this problem. In the present manuscript we examine proprioception in stroke survivors using a robotic arm position matching task. Proprioception is impaired in 50–60% of stroke survivors and has been associated with poorer motor recovery and longer lengths of hospital stay. We present a simple cut-off score technique for individual kinematic parameters and an overall task score to determine impairment. We then compare the ability of different machine learning (ML) techniques and the above-mentioned task score to correctly classify individuals with or without stroke based on kinematic data. Methods Participants performed an Arm Position Matching (APM) task in an exoskeleton robot. The task produced 12 kinematic parameters that quantify multiple attributes of position sense. We first quantified impairment in individual parameters and an overall task score by determining if participants with stroke fell outside of the 95% cut-off score of control (normative) values. Then, we applied five machine learning algorithms (i.e., Logistic Regression, Decision Tree, Random Forest, Random Forest with Hyperparameters Tuning, and Support Vector Machine), and a deep learning algorithm (i.e., Deep Neural Network) to classify individual participants as to whether or not they had a stroke based only on kinematic parameters using a tenfold cross-validation approach. Results We recruited 429 participants with neuroimaging-confirmed stroke (

BackgroundHigh blood pressure (BP) is the primary risk factor for recurrent strokes. Despite established clinical guidelines, some stroke survivors exhibit uncontrolled BP over the first 12 months post-stroke. Furthermore, research on BP trajectories in stroke survivors admitted to inpatient rehabilitation hospitals is limited. Exercise is recommended to reduce BP after stroke. However, the effect of high repetition gait training at aerobic intensities (>40% heart rate reserve; HRR) during inpatient rehabilitation on BP is unclear. We aimed to determine the effect of an aerobic gait training intervention on BP trajectory over the first 12 months post-stroke.MethodsThis is a secondary analysis of the Determining Optimal Post-Stroke Exercise (DOSE) trial. Participants with stroke admitted to inpatient rehabilitation hospitals were recruited and randomized to usual care (n = 24), DOSE1 (n = 25; >2,000 steps, 40–60% HRR for >30 min/session, 20 sessions over 4 weeks), or DOSE2 (n = 25; additional DOSE1 session/day) groups. Resting BP [systolic (SBP) and diastolic (DBP)] was measured at baseline (inpatient rehabilitation admission), post-intervention (near inpatient discharge), 6- and 12-month post-stroke. Linear mixed-effects models were used to examine the effects of group and time (weeks post-stroke) on SBP, DBP and hypertension (≥140/90 mmHg; ≥130/80 mmHg, if diabetic), controlling for age, stroke type, and baseline history of hypertension.ResultsNo effect of intervention group on SBP, DBP, or hypertension was observed. BP increased from baseline to 12-month post-stroke for SBP (from [mean ± standard deviation] 121.8 ± 15.0 to 131.8 ± 17.8 mmHg) and for DBP (74.4 ± 9.8 to 78.5 ± 10.1 mmHg). The proportion of hypertensive participants increased from 20.8% (n = 15/72) to 32.8% (n = 19/58). These increases in BP were statistically significant: an effect [estimation (95%CI), value of p] of time was observed on SBP [0.19 (0.12–0.26) mmHg/week, p

Metabolomic biomarkers hold promise in aiding the diagnosis and prognostication of traumatic brain injury. In Canada, over 165,000 individuals annually suffer from a traumatic brain injury (TBI), making it one of the most prevalent neurological conditions. In this pilot investigation, we examined blood-derived biomarkers as proxy measures that can provide an objective approach to TBI diagnosis and monitoring. Using a 1H nuclear magnetic resonance (NMR)-based quantitative metabolic profiling approach, this study determined whether (1) blood-derived metabolites change during recovery in male participants with mild to severe TBI; (2) biological pathway analysis reflects mechanisms that mediate neural damage/repair throughout TBI recovery; and (3) changes in metabolites correlate to initial injury severity. Eight male participants with mild to severe TBI (with intracranial lesions) provided morning blood samples within 1–4 days and again 6 months post-TBI. Following NMR analysis, the samples were subjected to multivariate statistical and machine learning-based analyses. Statistical modelling displayed metabolic changes during recovery through group separation, and eight significant metabolic pathways were affected by TBI. Metabolic changes were correlated to injury severity. L-alanine (R= −0.63, p < 0.01) displayed a negative relationship with the Glasgow Coma Scale. This study provides pilot data to support the feasibility of using blood-derived metabolites to better understand changes in biochemistry following TBI.

The neuropathological sequelae of stroke and subsequent recovery are incompletely understood. Here, we investigated the metabolic dynamics following stroke to advance the understanding of the pathophysiological mechanisms orchestrating stroke recovery. Using a nuclear magnetic resonance (NMR)-driven metabolomic profiling approach for urine samples obtained from a clinical group, the objective of this research was to (1) identify novel biomarkers indicative of severity and recovery following stroke, and (2) uncover the biochemical pathways underlying repair and functional recovery after stroke. Urine samples and clinical stroke assessments were collected during the acute (2–11 days) and chronic phases (6 months) of stroke. Using a 700 MHz 1H NMR spectrometer, metabolomic profiles were acquired followed by a combination of univariate and multivariate statistical analyses, along with biological pathway analysis and clinical correlations. The results revealed changes in phenylalanine, tyrosine, tryptophan, purine, and glycerophospholipid biosynthesis and metabolism during stroke recovery. Pseudouridine was associated with a change in post-stroke motor recovery. Thus, NMR-based metabolomics is able to provide novel insights into post-stroke cellular functions and establish a foundational framework for future investigations to develop targeted therapeutic interventions, advance stroke diagnosis and management, and enhance overall quality of life for individuals with stroke.

Cognitive deficits are common poststroke. Cognitive rehabilitation is typically used to improve cognitive deficits. It is unknown whether higher doses of exercise to promote motor recovery influence cognitive outcomes. Our recent trial, Determining Optimal Post-Stroke Exercise (DOSE), shows more than double the steps and aerobic minutes can be achieved during inpatient rehabilitation versus usual care, and translates to improved long-term walking outcomes. Thus, the secondary analysis aim was to determine the effect of the DOSE protocol on cognitive outcomes over 1-year poststroke. The DOSE protocol progressively increased step number and aerobic minutes during inpatient stroke rehabilitation over 20 sessions. The Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), and Trail Making Test B were completed at baseline, post-intervention, and 6- and 12-months poststroke, administered using standardized guidelines. Using the DOSE data, we used mixed-effect spline regression to model participants’ trajectories of cognitive recovery, controlling for relevant covariates. Participants (Usual Care n = 25, DOSE n = 50) were 56.7(11.7) years old, and 27(10) days post stroke. For the MoCA, there were statistically significant Group × Trajectory(p = 0.019), and Group × ΔTrajectory (p = 0.018) interactions with a substantial clinically meaningful difference, from +5.44 points/month improvement of the DOSE group compared to +1.59 points/month improvement with Usual Care during the 4-week intervention. The DSST and Trails B improved over time but were not different between groups. Taking advantage of this early difference may lend support to continued efforts to increase intensity, during and after discharge from inpatient rehabilitation, to improve cognition.Clinical trial registration: www.clinicaltrials.gov, NCT01915368.

Background: The classical description of poststroke upper limb impairment follows a proximalto-distal impairment gradient. Previous studies are equivocal on whether the hand is more impaired than the arm. Objective: To compare impairment of the arm and hand during subacute stroke. Method: A total of 73 individuals were evaluated for impairment of the upper limb within 30 days (early subacute) and within 90–150 days (late subacute) of stroke. Impairments were quantified using the Chedoke-McMaster Stroke Assessment (CMSA) for the arm and hand, Purdue Pegboard task, and a robotic Visually Guided Reaching task. Results: In the early phase 42% of participants in the early phase and 59% in the late phase received the same CMSA score for the arm and hand, with 88% and 95% of participants in the early and late phases, respectively, receiving a 1-point difference. Strong correlations exist between the CMSA arm and hand scores (early r = 0.79, late r = 0.75), and moderate – strong correlations exist between CMSA arm and hand scores and Purdue Pegboard and Visually Guided Reaching performances (r = 0.66–0.81). No systematic differences were found between the arm and hand. Conclusion: Impairments in the arm and hand during subacute stroke are highly correlated and do not support the presence of a proximal-to-distal gradient. LAY ABSTRACT Motor impairments are a common occurrence after stroke, and are classically believed to present in a gradient from more impairment in the hand to less impairment in the arm. In this study, participants who had recently had a stroke underwent assessment with the Chedoke-McMaster Stroke Assessment, the Purdue Pegboard task, and a Visually Guided Reaching task to quantify impairment and performance of the arm and hand. Levels of impairment in the arm and hand, as measured with the Chedoke-McMaster Stroke Assessment, were found to be highly correlated. The study also showed strong correlations between quantitative measures of performance for both the arm and hand. Overall, our results do not support the presence of a proximal-to-distal gradient of impairment during subacute stroke.

Abstract Background An individual’s rapid motor skills allow them to perform many daily activities and are a hallmark of physical health. Although age and sex are both known to affect motor performance, standardized methods for assessing their impact on upper limb function are limited. Methods Here we perform a cross-sectional study of 643 healthy human participants in two interactive motor tasks developed to quantify sensorimotor abilities, Object-Hit (OH) and Object-Hit-and-Avoid (OHA). The tasks required participants to hit virtual objects with and without the presence of distractor objects. Velocities and positions of hands and objects were recorded by a robotic exoskeleton, allowing a variety of parameters to be calculated for each trial. We verified that these tasks are viable for measuring performance in healthy humans and we examined whether any of our recorded parameters were related to age or sex. Results Our analysis shows that both OH and OHA can assess rapid motor behaviours in healthy human participants. It also shows that while some parameters in these tasks decline with age, those most associated with the motor system do not. Three parameters show significant sex-related effects in OH, but these effects disappear in OHA. Conclusions This study suggests that the underlying effect of aging on rapid motor behaviours is not on the capabilities of the motor system, but on the brain’s capacity for processing inputs into motor actions. Additionally, this study provides a baseline description of healthy human performance in OH and OHA when using these tasks to investigate age-related declines in sensorimotor ability.

Abstract Background Encouraging upper limb use and increasing intensity of practice in rehabilitation are two important goals for optimizing upper limb recovery post stroke. Feedback from novel wearable sensors may influence practice behaviour to promote achieving these goals. A wearable sensor can potentially be used in conjunction with a virtually monitored home program for greater patient convenience, or due to restrictions that preclude in-person visits, such as COVID-19. This trial aims to (1) determine the efficacy of a virtual behaviour change program that relies on feedback from a custom wearable sensor to increase use and function of the upper limb post stroke; and (2) explore the experiences and perceptions of using a program coupled with wearable sensors to increase arm use from the perspective of people with stroke. Methods This mixed-methods study will utilize a prospective controlled trial with random allocation to immediate or 3-week delayed entry to determine the efficacy of a 3-week behaviour change program with a nested qualitative description study. The intervention, the Virtual Arm Boot Camp (V-ABC) features feedback from a wearable device, which is intended to increase upper limb use post stroke, as well as 6 virtual sessions with a therapist. Sixty-four adults within 1-year post stroke onset will be recruited from seven rehabilitation centres. All outcomes will be collected virtually. The primary outcome measure is upper limb use measured by grasp counts over 3 days from the wearable sensor (TENZR) after the 3-week intervention. Secondary outcomes include upper limb function (Arm Capacity and Movement Test) and self-reported function (Hand Function and Strength subscale from the Stroke Impact Scale). Outcome data will be collected at baseline, post-intervention and at 2 months retention. The qualitative component will explore the experiences and acceptability of using a home program with a wearable sensor for increasing arm use from the point of view of individuals with stroke. Semi-structured interviews will be conducted with participants after they have experienced the intervention. Qualitative data will be analysed using content analysis. Discussion This study will provide novel information regarding the efficacy and acceptability of virtually delivered programs to improve upper extremity recovery, and the use of wearable sensors to assist with behaviour change. Trial registration ClinicalTrials.gov NCT04232163 . January 18, 2020.

Magnetic resonance imaging (MRI) can provide a number of measurements relevant to sport-related concussion (SRC) symptoms; however, most studies to date have used a single MRI modality and whole-brain exploratory analyses in attempts to localize concussion injury. This has resulted in highly variable findings across studies due to wide ranging symptomology, severity and nature of injury within studies. A multimodal MRI, symptom-guided region-of-interest (ROI) approach is likely to yield more consistent results. The functions of the cerebellum and basal ganglia transcend many common concussion symptoms, and thus these regions, plus the white matter tracts that connect or project from them, constitute plausible ROIs for MRI analysis. We performed diffusion tensor imaging (DTI), resting-state functional MRI, quantitative susceptibility mapping (QSM), and cerebral blood flow (CBF) imaging using arterial spin labeling (ASL), in youth aged 12-18 years following SRC, with a focus on the cerebellum, basal ganglia and white matter tracts. Compared to controls similar in age, sex and sport (N = 20), recent SRC youth (N = 29; MRI at 8 ± 3 days post injury) exhibited increased susceptibility in the cerebellum (p = 0.032), decreased functional connectivity between the caudate and each of the pallidum (p = 0.035) and thalamus (p = 0.021), and decreased diffusivity in the mid-posterior corpus callosum (p < 0.038); no changes were observed in recovered asymptomatic youth (N = 16; 41 ± 16 days post injury). For recent symptomatic-only SRC youth (N = 24), symptom severity was associated with increased susceptibility in the superior cerebellar peduncles (p = 0.011) and reduced activity in the cerebellum (p = 0.013). Fewer days between injury and MRI were associated with reduced cerebellar-parietal functional connectivity (p < 0.014), reduced activity of the pallidum (p = 0.002), increased CBF in the caudate (p = 0.005), and reduced diffusivity in the central corpus callosum (p < 0.05). Youth SRC is associated with acute cerebellar inflammation accompanied by reduced cerebellar activity and cerebellar-parietal connectivity, as well as structural changes of the middle regions of the corpus callosum accompanied by functional changes of the caudate, all of which resolve with recovery. Early MRI post-injury is important to establish objective MRI-based indicators for concussion diagnosis, recovery assessment and prediction of outcome.

Background. Increasing demand for provision of care to stroke survivors creates challenges for health care planners. A key concern is the optimal alignment of health care resources between provision of acute care, rehabilitation, and among different segments of rehabilitation, including inpatient rehabilitation, early supported discharge (ESD), and outpatient rehabilitation (OPR). We propose a novel application of discrete event simulation (DES) combined with a genetic algorithm (GA) to identify the optimal configuration of rehabilitation that maximizes patient benefits subject to finite health care resources. Design. Our stroke rehabilitation optimal model (sROM) combines DES and GA to identify an optimal solution that minimizes wait time for each segment of rehabilitation by changing care capacity across different segments. sROM is initiated by generating parameters for DES. GA is used to evaluate wait time from DES. If wait time meets specified stopping criteria, the search process stops at a point at which optimal capacity is reached. If not, capacity estimates are updated, and an additional iteration of the DES is run. To parameterize the model, we standardized real-world data from medical records by fitting them into probability distributions. A meta-analysis was conducted to determine the likelihood of stroke survivors flowing across rehabilitation segments. Results. We predict that rehabilitation planners in Alberta, Canada, have the potential to improve services by increasing capacity from 75 to 113 patients per day for ESD and from 101 to 143 patients per day for OPR. Compared with the status quo, optimal capacity would provide ESD to 138 ( s = 29.5) more survivors and OPR to 262 ( s = 45.5) more annually while having an estimated net annual cost savings of $25.45 ( s = 15.02) million. Conclusions. The combination of DES and GA can be used to estimate optimal service capacity. Highlights We created a hybrid model combining a genetic algorithm and discrete event simulation to search for the optimal configuration of health care service capacity that maximizes patient outcomes subject to finite health system resources. We applied a probability distribution fitting process to standardize real-world data to probability distributions. The process consists of choosing the distribution type and estimating the parameters of that distribution that best reflects the data. Standardizing real-word data to a best-fitted distribution can increase model generalizability. In an illustrative study of stroke rehabilitation care, resource allocation to stroke rehabilitation services under an optimal configuration allows provision of care to more stroke survivors who need services while reducing wait time. Resources needed to expand rehabilitation services could be reallocated from the savings due to reduced wait time in acute care units. In general, the predicted optimal configuration of stroke rehabilitation services is associated with a net cost savings to the health care system.

Abstract Background Studies using clinical measures have suggested that proprioceptive dysfunction is related to motor impairment of the upper extremity following adult stroke. We used robotic technology and clinical measures to assess the relationship between position sense and reaching with the hemiparetic upper limb in children with perinatal stroke. Methods Prospective term-born children with magnetic resonance imaging-confirmed perinatal ischemic stroke and upper extremity deficits were recruited from a population-based cohort. Neurotypical controls were recruited from the community. Participants completed two tasks in the Kinarm robot: arm position-matching (three parameters: variability [Varxy], contraction/expansion [Areaxy], systematic spatial shift [Shiftxy]) and visually guided reaching (five parameters: posture speed [PS], reaction time [RT], initial direction error [IDE], speed maxima count [SMC], movement time [MT]). Additional clinical assessments of sensory (thumb localization test) and motor impairment (Assisting Hand Assessment, Chedoke-McMaster Stroke Assessment) were completed and compared to robotic measures. Results Forty-eight children with stroke (26 arterial, 22 venous, mean age: 12.0 ± 4.0 years) and 145 controls (mean age: 12.8 ± 3.9 years) completed both tasks. Position-matching performance in children with stroke did not correlate with performance on the visually guided reaching task. Robotic sensory and motor measures correlated with only some clinical tests. For example, AHA scores correlated with reaction time (R = − 0.61, p

Proprioceptive impairments occur in ~50% of stroke survivors, with 20–40% still impaired six months post-stroke. Early identification of those likely to have persistent impairments is key to personalizing rehabilitation strategies and reducing long-term proprioceptive impairments. In this study, clinical, neuroimaging and robotic measures were used to predict proprioceptive impairments at six months post-stroke on a robotic assessment of proprioception. Clinical assessments, neuroimaging, and a robotic arm position matching (APM) task were performed for 133 stroke participants two weeks post-stroke (12.4 ± 8.4 days). The APM task was also performed six months post-stroke (191.2 ± 18.0 days). Robotics allow more precise measurements of proprioception than clinical assessments. Consequently, an overall APM Task Score was used as ground truth to classify proprioceptive impairments at six months post-stroke. Other APM performance parameters from the two-week assessment were used as predictive features. Clinical assessments included the Thumb Localisation Test (TLT), Behavioural Inattention Test (BIT), Functional Independence Measure (FIM) and demographic information (age, sex and affected arm). Logistic regression classifiers were trained to predict proprioceptive impairments at six months post-stroke using data collected two weeks post-stroke. Models containing robotic features, either alone or in conjunction with clinical and neuroimaging features, had a greater area under the curve (AUC) and lower Akaike Information Criterion (AIC) than models which only contained clinical or neuroimaging features. All models performed similarly with regard to accuracy and F1-score (>70% accuracy). Robotic features were also among the most important when all features were combined into a single model. Predicting long-term proprioceptive impairments, using data collected as early as two weeks post-stroke, is feasible. Identifying those at risk of long-term impairments is an important step towards improving proprioceptive rehabilitation after a stroke.

Abstract Much of our understanding of motor control deficits in children with developmental coordination disorder (DCD) comes from upper limb assessments focusing on the dominant limb. Here, using two robotic behavioural tasks, we investigated motor control in both the dominant and non-dominant limbs of children with DCD. Twenty-six children with diagnosed DCD (20 males; mean age 10.6 years ± 1.3 years) and 155 controls were included in this cross-sectional study. Participants completed a visually guided reaching task with their dominant and non-dominant limbs and a bimanual object hitting task. Motor performance was quantified across nine parameters. We determined the number of children with DCD who fell outside of the typical performance range of the controls on these parameters and compared the DCD and control groups using ANCOVAs, accounting for age. Children with DCD demonstrated impairments in six out of nine parameters; deficits were more commonly noted in the non-dominant limb. Interestingly, when looking at individual performance, several children with DCD performed in the range of controls. These findings indicate that children with DCD display deficits in motor control in both the dominant and non-dominant limb and highlight the importance of including detailed assessments of both limbs when investigating children with DCD. They also demonstrate the variability in motor control performance evidenced by children with DCD.

Abstract Background Robotic rehabilitation after stroke provides the potential to increase and carefully control dosage of therapy. Only a small number of studies, however, have examined robotic therapy in the first few weeks post-stroke. In this study we designed robotic upper extremity therapy tasks for the bilateral Kinarm Exoskeleton Lab and piloted them in individuals with subacute stroke. Pilot testing was focused mainly on the feasibility of implementing these new tasks, although we recorded a number of standardized outcome measures before and after training. Methods Our team developed 9 robotic therapy tasks to incorporate feedback, intensity, challenge, and subject engagement as well as addressing both unimanual and bimanual arm activities. Subacute stroke participants were assigned to a robotic therapy (N = 9) or control group (N = 10) in a matched-group manner. The robotic therapy group completed 1-h of robotic therapy per day for 10 days in addition to standard therapy. The control group participated only in standard of care therapy. Clinical and robotic assessments were completed prior to and following the intervention. Clinical assessments included the Fugl-Meyer Assessment of Upper Extremity (FMA UE), Action Research Arm Test (ARAT) and Functional Independence Measure (FIM). Robotic assessments of upper limb sensorimotor function included a Visually Guided Reaching task and an Arm Position Matching task, among others. Paired sample t-tests were used to compare initial and final robotic therapy scores as well as pre- and post-clinical and robotic assessments. Results Participants with subacute stroke (39.8 days post-stroke) completed the pilot study. Minimal adverse events occurred during the intervention and adding 1 h of robotic therapy was feasible. Clinical and robotic scores did not significantly differ between groups at baseline. Scores on the FMA UE, ARAT, FIM, and Visually Guided Reaching improved significantly in the robotic therapy group following completion of the robotic intervention. However, only FIM and Arm Position Match improved over the same time in the control group. Conclusions The Kinarm therapy tasks have the potential to improve outcomes in subacute stroke. Future studies are necessary to quantify the benefits of this robot-based therapy in a larger cohort. Trial registration: ClinicalTrials.gov, NCT04201613, Registered 17 December 2019—Retrospectively Registered, https://clinicaltrials.gov/ct2/show/NCT04201613 .

Abstract Background Robotic technologies for neurological assessment provide sensitive, objective measures of behavioural impairments associated with injuries or disease such as stroke. Previous robotic tasks to assess proprioception typically involve single limbs or in some cases both limbs. The challenge with these approaches is that they often rely on intact motor function and/or working memory to remember/reproduce limb position, both of which can be impaired following stroke. Here, we examine the feasibility of a single-arm Movement Discrimination Threshold (MDT) task to assess proprioception by quantifying thresholds for sensing passive limb movement without vision. We use a staircase method to adjust movement magnitude based on subject performance throughout the task in order to reduce assessment time. We compare MDT task performance to our previously-designed Arm Position Matching (APM) task. Critically, we determine test-retest reliability of each task in the same population of healthy controls. Method Healthy participants (N = 21, age = 18–22 years) completed both tasks in the End-Point Kinarm robot. In the MDT task the robot moved the dominant arm left or right and participants indicated the direction moved. Movement displacement was systematically adjusted (decreased after correct answers, increased after incorrect) until the Discrimination Threshold was found. In the APM task, the robot moved the dominant arm and participants “mirror-matched” with the non-dominant arm. Results Discrimination Threshold for direction of arm displacement in the MDT task ranged from 0.1–1.3 cm. Displacement Variability ranged from 0.11–0.71 cm. Test-retest reliability of Discrimination Threshold based on ICC confidence intervals was moderate to excellent (range, ICC = 0.78 [0.52–0.90]). Interestingly, ICC values for Discrimination Threshold increased to 0.90 [0.77–0.96] (good to excellent) when the number of trials was reduced to the first 50. Most APM parameters had ICC’s above 0.80, (range, ICC = [0.86–0.88]) with the exception of variability (ICC = 0.30). Importantly, no parameters were significantly correlated across tasks as Spearman rank correlations across parameter-pairings ranged from − 0.27 to 0.30. Conclusions The MDT task is a feasible and reliable task, assessing movement discrimination threshold in ~ 17 min. Lack of correlation between the MDT and a position-matching task (APM) indicates that these tasks assess unique aspects of proprioception that are not strongly related in young, healthy individuals.

Abstract Background Activities of daily living frequently require children to make rapid decisions and execute desired motor actions while inhibiting unwanted actions. Children with hemiparetic cerebral palsy due to perinatal stroke may have deficits in executive functioning in addition to motor impairments. The objective of this study was to use a robotic object hit and avoid task to assess the ability of children with hemiparetic cerebral palsy to make rapid motor decisions. Methods Forty-five children with hemiparetic cerebral palsy due to perinatal stroke and 146 typically developing children (both groups ages 6–19 years) completed a robotic object hit and avoid task using the Kinarm Exoskeleton. Objects of different shapes fell from the top of the screen with increasing speed and frequency. Children were instructed to hit two specific target shapes with either hand, while avoiding six distractor shapes. The number of targets and distractors hit were compared between children with hemiparetic cerebral palsy and typically developing children, accounting for age effects. We also compared performance to a simpler object hit task where there were no distractors. Results We found that children with hemiparetic cerebral palsy hit a greater proportion of total distractors compared to typically developing children, demonstrating impairments in inhibitory control. Performance for all children improved with age. Children with hemiparetic cerebral palsy hit a greater percentage of targets with each arm on the more complex object hit and avoid task compared to the simpler object hit task, which was not found in typically developing children. Conclusions Children with hemiparetic cerebral palsy due to perinatal stroke demonstrated impairments in rapid motor decision making including inhibitory control, which can impede their ability to perform real-world tasks. Therapies that address both motor performance and executive functions are necessary to maximize function in children with hemiparetic cerebral palsy.

Abstract Background While motor deficits are the hallmark of hemiparetic cerebral palsy, children may also experience impairments in visuospatial attention that interfere with participation in complex activities, including sports or driving. In this study, we used a robotic object hitting task to assess bilateral sensorimotor control and visuospatial skills in children with hemiparesis due to perinatal arterial ischemic stroke (AIS) or periventricular venous infarct (PVI). We hypothesized that performance would be impaired bilaterally and be related to motor behavior and clinical assessment of visuospatial attention. Methods Forty-nine children with perinatal stroke and hemiparetic cerebral palsy and 155 typically developing (TD) children participated in the study. Participants performed a bilateral object hitting task using the KINARM Exoskeleton Robot, in which they used virtual paddles at their fingertips to hit balls that fell from the top of the screen with increasing speed and frequency over 2.3 min. We quantified performance across 13 parameters including number of balls hit with each hand, movement speed and area, biases between hands, and spatial biases. We determined normative ranges of performance accounting for age by fitting 95% prediction bands to the TD children. We compared parameters between TD, AIS, and PVI groups using ANCOVAs accounting for age effects. Lastly, we performed regression analysis between robotic and clinical measures. Results The majority of children with perinatal stroke hit fewer balls with their affected arm compared to their typically developing peers. We also found deficits with the ipsilesional (“unaffected”) arm. Children with AIS had greater impairments than PVI. Despite hitting fewer balls, we only identified 18% of children as impaired in hand speed or movement area. Performance on the Behavioral Inattention Test accounted for 21–32% of the variance in number of balls hit with the unaffected hand. Conclusions Children with perinatal stroke-induced hemiparetic cerebral palsy may have complex bilateral deficits reflecting a combination of impairments in motor skill and visuospatial attention. Clinical assessments and interventions should address the interplay between motor and visuospatial skills.

Abstract Background Persistent post-concussive symptoms (PPCS) affect up to 30% of individuals following mild traumatic brain injury. PPCS frequently includes exercise intolerance. Sub-symptom threshold aerobic exercise has been proposed as a treatment option for symptom burden and exercise intolerance in this population. The primary aim of this study is to evaluate whether a progressive, sub-symptom threshold aerobic exercise program can alleviate symptom burden in adults with PPCS. Methods Fifty-six adults (18–65) with PPCS (>3mos-5 yrs) will be randomized into two groups: an immediate start 12-week aerobic exercise protocol (AEP) or delayed start 6-week placebo-like stretching protocol (SP), followed by AEP. Aerobic or stretching activities will be completed 5x/week for 30 mins during the intervention. Online daily activity logs will be submitted. Exercise prescriptions for the AEP will be 70–80% of heart rate at the point of symptom exacerbation achieved on a treadmill test with heart rate monitoring. Exercise prescription will be updated every 3-weeks with a repeat treadmill test. The Rivermead Post-concussion Symptom Questionnaire will be the primary outcome measure at 6 and 12-weeks of intervention. Secondary outcomes include assessments of specific symptoms (headache, quality of life, mood, anxiety, fatigue, dizziness, sleep parameters, daytime sleepiness) in addition to blood biomarkers and magnetic resonance imaging and spectroscopy data for quantification of brain metabolites including γ-aminobutyric acid (GABA), glutathione, glutamate and N-acetyl aspartate (NAA) all measured at 6 and 12-weeks of intervention. Discussion This trial will evaluate the use of aerobic exercise as an intervention for adults with PPCS, thus expanding our knowledge of this treatment option previously studied predominantly for adolescent sport-related concussion. Trial registration ClinicalTrials.gov - NCT03895450 (registered 2019-Feb-11).

AimTo identify challenges of combining robotic upper extremity rehabilitation with tDCS in children with upper extremity bilateral cerebral palsy (CP) by assessing feasibility, tolerability and safety.MethodsThis was an unblinded, open-label, pilot clinical trial. Participants completed 10 × 1 h sessions of robotic rehabilitation combined with motor cortex anodal tDCS. Feasibility, acceptability and practicality, were assessed including the number of participants completing the protocol, factors limiting participation, time required for sessions, and completion of functional assessments and tolerability scales. To assess safety, standardized clinical and robotic measures of sensorimotor function were performed. The trial was registered at clinicaltrials.gov (NCT04233710).ResultsEight children were recruited (mean age 8y ± 1.8y, range 6–11 years) and 5 completed the intervention. There were no serious adverse events. One child developed focal seizures 6 weeks after the trial that were deemed to be unrelated. Barriers to completion included time and scheduling demands and patient factors, specifically cognitive/behavioral impairments and dyskinesia. No decline in clinical function was appreciated.ConclusionsRobotic upper extremity rehabilitation combined with tDCS may be feasible in children with bilateral CP. Careful participant selection, family engagement, and protocol adaptations are recommended to better understand the feasibility and tolerability of future trials.

Proprioceptive deficits are common following stroke, yet the white matter involved in proprioception is poorly understood. Evidence suggests that multiple cortical regions are involved in proprioception, each connected by major white matter tracts, namely: Superior Longitudinal Fasciculus (branches I, II and III), Arcuate Fasciculus and Middle Longitudinal Fasciculus (SLF I, SLF II, SLF III, AF and MdLF respectively). However, direct evidence on the involvement of these tracts in proprioception is lacking. Diffusion imaging was used to investigate the proprioceptive role of the SLF I, SLF II, SLF III, AF and MdLF in 26 participants with stroke, and seven control participants without stroke. Proprioception was assessed using a robotic Arm Position Matching (APM) task, performed in a Kinarm Exoskeleton robotic device. Lesions impacting each tract resulted in worse APM task performance. Lower Fractional Anisotropy (FA) was also associated with poorer APM task performance for the SLF II, III, AF and MdLF. Finally, connectivity data surrounding the cortical regions connected by each tract accurately predicted APM task impairments post-stroke. This study highlights the importance of major cortico–cortical white matter tracts, particularly the SLF III and AF, for accurate proprioception after stroke. It advances our understanding of the white matter tracts responsible for proprioception.

Objective: Millions of sport-related concussions (SRC) occur annually in North America, and current diagnosis of concussion is based largely on clinical evaluations. The objective of this study was to determine whether urinary metabolites are significantly altered post-SRC compared to pre-injury.Setting: Outpatient sports medicine clinic.Participants: Twenty-six male youth sport participants.Methods: Urine was analyzed pre-injury and after SRC by 1H NMR spectroscopy. Data were analyzed using multivariate statistics, pairwise t-test, and metabolic pathway analysis. Variable importance analysis based on random variable combination (VIAVC) was applied to the entire data set and resulted in a panel of 18 features. Partial least square discriminant analysis was performed exploring the separation between pre-injury and post-SRC groups. Pathway topography analysis was completed to identify biological pathway involvement. Spearman correlations provide support for the relationships between symptom burden and length of return to play and quantifiable metabolic changes in the human urinary metabolome.Results: Phenylalanine and 3-indoxysulfate were upregulated, while citrate, propylene glycol, 1-methylhistidine, 3-methylhistidine, anserine, and carnosine were downregulated following SRC. A receiver operator curve (ROC) tool constructed using the 18-feature classifier had an area under the curve (AUC) of 0.887. A pairwise t-test found an additional 19 altered features, 7 of which overlapped with the VIAVC analysis. Pathway topology analysis indicated that aminoacyl-tRNA biosynthesis and beta-alanine metabolism were the two pathways most significantly changed. There was a significant positive correlation between post-SRC 2-hydroxybutyrate and the length of return to play (ρ = 0.482, p = 0.02) as well as the number of symptoms and post-SRC lactose (ρ = 0.422, p = 0.036).Conclusion: We found that 1H NMR metabolomic urinary analysis can identify a set of metabolites that can correctly classify SRC with an accuracy of 81.6%, suggesting potential for a more objective method of characterizing SRC. Correlations to both the number of symptoms and length of return to play indicated that 2-hydroxybutyrate and lactose may have potential applications as biomarkers for sport-related concussion.

Abstract Background Motor impairment after stroke interferes with performance of everyday activities. Upper limb spasticity may further disrupt the movement patterns that enable optimal function; however, the specific features of these altered movement patterns, which differentiate individuals with and without spasticity, have not been fully identified. This study aimed to characterize the kinematic and proprioceptive deficits of individuals with upper limb spasticity after stroke using the Kinarm robotic exoskeleton. Methods Upper limb function was characterized using two tasks: Visually Guided Reaching, in which participants moved the limb from a central target to 1 of 4 or 1 of 8 outer targets when cued (measuring reaching function) and Arm Position Matching, in which participants moved the less-affected arm to mirror match the position of the affected arm (measuring proprioception), which was passively moved to 1 of 4 or 1 of 9 different positions. Comparisons were made between individuals with (n = 35) and without (n = 35) upper limb post-stroke spasticity. Results Statistically significant differences in affected limb performance between groups were observed in reaching-specific measures characterizing movement time and movement speed, as well as an overall metric for the Visually Guided Reaching task. While both groups demonstrated deficits in proprioception compared to normative values, no differences were observed between groups. Modified Ashworth Scale score was significantly correlated with these same measures. Conclusions The findings indicate that individuals with spasticity experience greater deficits in temporal features of movement while reaching, but not in proprioception in comparison to individuals with post-stroke motor impairment without spasticity. Temporal features of movement can be potential targets for rehabilitation in individuals with upper limb spasticity after stroke.

Abstract Background Position sense is commonly impaired after stroke. Traditional rehabilitation methods instruct patients to visualize their limbs to compensate for impaired position sense. Objective Our goal was to evaluate how the use of vision influences impaired position sense. Methods We examined 177 stroke survivors, an average of 12.7 days (+/− 10 days (SD)) post-stroke, and 133 neurologically-intact controls with a robotic assessment of position sense. The robot positioned one limb (affected) and subjects attempted to mirror-match the position using the opposite limb (unaffected). Subjects completed the test without, then with vision of their limbs. We examined three measures of position sense: variability (Var), contraction/expansion (C/E) and systematic shift (Shift). We classified stroke survivors as having full compensation if they performed the robotic task abnormally without vision but corrected performance within the range of normal with vision. Stroke survivors were deemed to have partial compensation if they performed the task outside the range of normal without and with vision, but improved significantly with vision. Those with absent compensation performed the task abnormally in both conditions and did not improve with vision. Results Many stroke survivors demonstrated impaired position sense with vision occluded [Var: 116 (66%), C/E: 91 (51%), Shift: 52 (29%)]. Of those stroke survivors with impaired position sense, some exhibited full compensation with vision [Var: 23 (20%), C/E: 42 (46%), Shift: 32 (62%)], others showed partial compensation [Var: 37 (32%), C/E: 8 (9%), Shift: 3 (6%)] and many displayed absent compensation (Var: 56 (48%), C/E: 41 (45%), Shift: 17 (33%)]. Stroke survivors with an affected left arm, visuospatial neglect and/or visual field defects were less likely to compensate for impaired position sense using vision. Conclusions Our results indicate that vision does not help many stroke survivors compensate for impaired position sense, at least within the current paradigm. This contrasts with historical reports that vision helps compensate for proprioceptive loss following neurologic injuries.

BackgroundKinarm Standard Tests (KSTs) is a suite of upper limb tasks to assess sensory, motor, and cognitive functions, which produces granular performance data that reflect spatial and temporal aspects of behavior (>100 variables per individual). We have previously used principal component analysis (PCA) to reduce the dimensionality of multivariate data using the Kinarm End-Point Lab (EP). Here, we performed PCA using data from the Kinarm Exoskeleton Lab (EXO), and determined agreement of PCA results across EP and EXO platforms in healthy participants. We additionally examined whether further dimensionality reduction was possible by using PCA across behavioral tasks.MethodsHealthy participants were assessed using the Kinarm EXO (N = 469) and EP (N = 170–200). Four behavioral tasks (six assessments in total) were performed that quantified arm sensory and motor function, including position sense [Arm Position Matching (APM)] and three motor tasks [Visually Guided Reaching (VGR), Object Hit (OH), and Object Hit and Avoid (OHA)]. The number of components to include per task was determined from scree plots and parallel analysis, and rotation type (orthogonal vs. oblique) was decided on a per-task basis. To assess agreement, we compared principal components (PCs) across platforms using distance correlation. We additionally considered inter-task interactions in EXO data by performing PCA across all six behavioral assessments.ResultsBy applying PCA on a per task basis to data collected using the EXO, the number of behavioral parameters were substantially reduced by 58–75% while accounting for 76–87% of the variance. These results compared well to the EP analysis, and we found good-to-excellent agreement values (0.75–0.99) between PCs from the EXO and those from the EP. Finally, we were able to reduce the dimensionality of the EXO data across tasks down to 16 components out of a total of 76 behavioral parameters, which represents a reduction of 79% while accounting for 73% of the total variance.ConclusionPCA of Kinarm robotic assessment appears to capture similar relationships between kinematic features in healthy individuals and is agnostic to the robotic platform used for collection. Further work is needed to investigate the use of PCA-based data reduction for the characterization of neurological deficits in clinical populations.

Background. Tic disorders may reflect impaired inhibitory control. This has been evaluated using different behavioural tasks, yielding mixed results. Our objective was to test inhibitory control in children with tics through simultaneous presentation of multiple, mobile stimuli. Methods. Sixty-four children with tics (mean age 12.4 years; 7.5-18.5) were evaluated using a validated robotic bimanual exoskeleton protocol (Kinarm) in an object-hit-and-avoid task, in which target and distractor objects moved across a screen and participants aimed to hit only the targets while avoiding distractors. Performance was compared to 146 typically developing controls (mean age 13 years; 6.1-19.9). The primary outcome was the percentage of distractors struck. Results. ANCOVA (age as covariate) showed participants struck significantly more distractors (participants without comorbid ADHD, 22.71% [SE 1.47]; participants with comorbid ADHD, 23.56% [1.47]; and controls, 15.59% [0.68]). Participants with comorbid ADHD struck significantly fewer targets (119.74 [2.77]) than controls, but no difference was found between participants without comorbid ADHD (122.66 [2.77]) and controls (127.00 [1.28]). Participants and controls did not differ significantly in movement speed and movement area. Just over 20% of participants with tics fell below the age-predicted norm in striking distractors, whereas fewer than 10% fell outside age-predicted norms in other task parameters. Conclusions. In children with tics (without comorbid ADHD), acting upon both targets and distractors suggests reduced ability to suppress responses to potential triggers for action. This may be related to increased sensorimotor noise or abnormal sensory gating.

Abstract Background Robotic technologies to measure human behavior are emerging as a new approach to assess brain function. Recently, we developed a robot-based postural Load Task to assess corrective responses to mechanical disturbances to the arm and found impairments in many participants with stroke compared to a healthy cohort (Bourke et al, J NeuroEngineering Rehabil 12: 7, 2015). However, a striking feature was the large range and skewed distribution of healthy performance. This likely reflects the use of different strategies across the healthy control sample, making it difficult to identify impairments. Here, we developed an intuitive “Unload Task”. We hypothesized this task would reduce healthy performance variability and improve the detection of impairment following stroke. Methods Performance on the Load and Unload Task in the KINARM exoskeleton robot was directly compared for healthy control (n = 107) and stroke (n = 31) participants. The goal was to keep a cursor representing the hand inside a virtual target and return “quickly and accurately” if the robot applied (or removed) an unexpected load to the arm (0.5–1.5 Nm). Several kinematic parameters quantified performance. Impairment was defined as performance outside the 95% of controls (corrected for age, sex and handedness). Task Scores were calculated using standardized parameter scores reflecting overall task performance. Results The distribution of healthy control performance was smaller and less skewed for the Unload Task compared to the Load Task. Fewer task outliers (outside 99.9 percentile for controls) were removed from the Unload Task (3.7%) compared to the Load Task (7.4%) when developing normative models of performance. Critically, more participants with stroke failed the Unload Task based on Task Score with their affected arm (68%) compared to the Load Task (23%). More impairments were found at the parameter level for the Unload (median = 52%) compared to Load Task (median = 29%). Conclusions The Unload Task provides an improved approach to assess fast corrective responses of the arm. We found that corrective responses are impaired in persons living with stroke, often equally in both arms. Impairments in generating rapid motor corrections may place individuals at greater risk of falls when they move and interact in the environment.

Abstract Background Detailed kinematics of motor impairment of the contralesional (“affected”) and ipsilesional (“unaffected”) limbs in children with hemiparetic cerebral palsy are not well understood. We aimed to 1) quantify the kinematics of reaching in both arms of hemiparetic children with perinatal stroke using a robotic exoskeleton, and 2) assess the correlation of kinematic reaching parameters with clinical motor assessments. Methods This prospective, case-control study involved the Alberta Perinatal Stroke Project, a population-based research cohort, and the Foothills Medical Center Stroke Robotics Laboratory in Calgary, Alberta over a four year period. Prospective cases were collected through the Calgary Stroke Program and included term-born children with magnetic resonance imaging confirmed perinatal ischemic stroke and upper extremity deficits. Control participants were recruited from the community. Participants completed a visually guided reaching task in the KINARM robot with each arm separately, with 10 parameters quantifying motor function. Kinematic measures were compared to clinical assessments and stroke type. Results Fifty children with perinatal ischemic stroke (28 arterial, mean age: 12.5 ± 3.9 years; 22 venous, mean age: 11.5 ± 3.8 years) and upper extremity deficits were compared to healthy controls (n = 147, mean age: 12.7 ± 3.9 years). Perinatal stroke groups demonstrated contralesional motor impairments compared to controls when reaching out (arterial = 10/10, venous = 8/10), and back (arterial = 10/10, venous = 6/10) with largest errors in reaction time, initial direction error, movement length and time. Ipsilesional impairments were also found when reaching out (arterial = 7/10, venous = 1/10) and back (arterial = 6/10). The arterial group performed worse than venous on both contralesional and ipsilesional parameters. Contralesional reaching parameters showed modest correlations with clinical measures in the arterial group. Conclusions Robotic assessment of reaching behavior can quantify complex, upper limb dysfunction in children with perinatal ischemic stroke. The ipsilesional, “unaffected” limb is often abnormal and may be a target for therapeutic interventions in stroke-induced hemiparetic cerebral palsy.

Proprioceptive deficits are common after stroke and have been associated with poorer recovery. Relatively little is known about the brain regions beyond primary somatosensory cortex that contribute to the percept of proprioception in humans. We examined a large sample (n = 153) of stroke survivors longitudinally to determine which brain regions were associated with persistent post-stroke proprioceptive deficits. A robotic exoskeleton quantified two components of proprioception, position sense and kinesthesia (movement sense), at 2 weeks and again at 6 months post-stroke. A statistical region of interest (sROI) analysis compared the lesion-behaviour relationships of those subjects with cortical and subcortical stroke (n = 136). The impact of damage to brainstem and cerebellum (n = 17) was examined separately. Results indicate that damage to the supramarginal gyrus, the arcuate fasciculus, and Heschl's gyrus are associated with deficits in position sense and kinesthesia at 6 months post-stroke. These results suggest that regions beyond the primary somatosensory cortex contribute to our sense of limb position and movement. This information extends our understanding of proprioceptive processing and may inform personalized interventions such as non-invasive brain stimulation where specific brain regions can be targeted to potentially improve stroke recovery. Keywords: Proprioception, Lesion analysis, Stroke, Upper extremity, Robotic assessment

Abstract Background Proprioception is the sense of the position and movement of our limbs, and is vital for executing coordinated movements. Proprioceptive disorders are common following stroke, but clinical tests for measuring impairments in proprioception are simple ordinal scales that are unreliable and relatively crude. We developed and validated specific kinematic parameters to quantify proprioception and compared two common metrics, Euclidean and Mahalanobis distances, to combine these parameters into an overall summary score of proprioception. Methods We used the KINARM robotic exoskeleton to assess proprioception of the upper limb in subjects with stroke (N = 285. Mean days post-stroke = 12 ± 15). Two aspects of proprioception (position sense and kinesthetic sense) were tested using two mirror-matching tasks without vision. The tasks produced 12 parameters to quantify position sense and eight to quantify kinesthesia. The Euclidean and Mahalanobis distances of the z-scores for these parameters were computed each for position sense, kinesthetic sense, and overall proprioceptive function (average score of position and kinesthetic sense). Results A high proportion of stroke subjects were impaired on position matching (57%), kinesthetic matching (65%), and overall proprioception (62%). Robotic tasks were significantly correlated with clinical measures of upper extremity proprioception, motor impairment, and overall functional independence. Composite scores derived from the Euclidean distance and Mahalanobis distance showed strong content validity as they were highly correlated (r = 0.97–0.99). Conclusions We have outlined a composite measure of upper extremity proprioception to provide a single continuous outcome measure of proprioceptive function for use in clinical trials of rehabilitation. Multiple aspects of proprioception including sense of position, direction, speed, and amplitude of movement were incorporated into this measure. Despite similarities in the scores obtained with these two distance metrics, the Mahalanobis distance was preferred.

Abstract Background Kinesthesia (sense of limb movement) has been extremely difficult to measure objectively, especially in individuals who have survived a stroke. The development of valid and reliable measurements for proprioception is important to developing a better understanding of proprioceptive impairments after stroke and their impact on the ability to perform daily activities. We recently developed a robotic task to evaluate kinesthetic deficits after stroke and found that the majority (~60%) of stroke survivors exhibit significant deficits in kinesthesia within the first 10 days post-stroke. Here we aim to determine the inter-rater reliability of this robotic kinesthetic matching task. Methods Twenty-five neurologically intact control subjects and 15 individuals with first-time stroke were evaluated on a robotic kinesthetic matching task (KIN). Subjects sat in a robotic exoskeleton with their arms supported against gravity. In the KIN task, the robot moved the subjects’ stroke-affected arm at a preset speed, direction and distance. As soon as subjects felt the robot begin to move their affected arm, they matched the robot movement with the unaffected arm. Subjects were tested in two sessions on the KIN task: initial session and then a second session (within an average of 18.2 ± 13.8 h of the initial session for stroke subjects), which were supervised by different technicians. The task was performed both with and without the use of vision in both sessions. We evaluated intra-class correlations of spatial and temporal parameters derived from the KIN task to determine the reliability of the robotic task. Results We evaluated 8 spatial and temporal parameters that quantify kinesthetic behavior. We found that the parameters exhibited moderate to high intra-class correlations between the initial and retest conditions (Range, r-value = [0.53–0.97]). Conclusions The robotic KIN task exhibited good inter-rater reliability. This validates the KIN task as a reliable, objective method for quantifying kinesthesia after stroke.

Background Understanding how the size of acute lesions and white matter hyperintensities (WMH) impact stroke recovery can improve our ability to predict outcomes and tailor treatments. The aim of this exploratory study was to investigate the role of acute lesion volume and WMH volume on longitudinal recovery of specific sensory, motor, and cognitive impairments after stroke using robotic and clinical measures. Methods and Results Eighty‐two individuals were assessed at 1, 6, 12, and 26 weeks poststroke with robotic tasks and commonly used clinical measures. The volumes of acute lesions and WMH were measured on fluid‐attenuated inversion recovery images. Linear mixed models were used to investigate the role of acute lesions and WMH on parameters derived from the robotic tasks and clinical measures. Regression analysis determined the added value of acute lesion and WMH volumes along with measures of initial performance to predict outcomes at 6 months. Acute lesion volume has widespread effects on sensory, motor, and overall functional recovery poststroke. The impact of WMH was specific to cognitive impairments. Apart from the robotic position sense task, neither lesion volume nor WMH measure had significant ability to predict outcomes at 6 months over using initial impairment as measured by robotic assessments alone. Conclusions While acute lesion volume and WMH may impact different impairments poststroke, their clinical utility in predicting outcomes at 6 months poststroke is limited.