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Current assessment tools for sport-related concussion are limited by a reliance on subjective interpretation and patient symptom reporting. Robotic assessments may provide more objective and precise measures of neurological function than traditional clinical tests.To determine the reliability of assessments of sensory, motor and cognitive function conducted with the KINARM end-point robotic device in young adult elite athletes.Sixty-four randomly selected healthy, young adult elite athletes participated. Twenty-five individuals (25 M, mean age±SD, 20.2±2.1 years) participated in a within-season study, where three assessments were conducted within a single season (assessments labeled by session: S1, S2, S3). An additional 39 individuals (28M; 22.8±6.0 years) participated in a year-to-year study, where annual pre-season assessments were conducted for three consecutive seasons (assessments labeled by year: Y1, Y2, Y3). Forty-four parameters from five robotic tasks (Visually Guided Reaching, Position Matching, Object Hit, Object Hit and Avoid, and Trail Making B) and overall Task Scores describing performance on each task were quantified.Test-retest reliability was determined by intra-class correlation coefficients (ICCs) between the first and second, and second and third assessments. In the within-season study, ICCs were ≥0.50 for 68% of parameters between S1 and S2, 80% of parameters between S2 and S3, and for three of the five Task Scores both between S1 and S2, and S2 and S3. In the year-to-year study, ICCs were ≥0.50 for 64% of parameters between Y1 and Y2, 82% of parameters between Y2 and Y3, and for four of the five Task Scores both between Y1 and Y2, and Y2 and Y3.Overall, the results suggest moderate-to-good test-retest reliability for the majority of parameters measured by the KINARM robot in healthy young adult elite athletes. Future work will consider the potential use of this information for clinical assessment of concussion-related neurological deficits.

Kinesthesia is our sense of limb motion, and allows us to gauge the speed, direction, and amplitude of our movements. Over half of stroke survivors have significant impairments in kinesthesia, which leads to greatly reduced recovery and function in everyday activities. Despite the high reported incidence of kinesthetic deficits after stroke, very little is known about how damage beyond just primary somatosensory areas affects kinesthesia. Stroke provides an ideal model to examine structure-function relationships specific to kinesthetic processing, by comparing lesion location with behavioral impairment. To examine this relationship, we performed voxel-based lesion-symptom mapping and statistical region of interest analyses on a large sample of sub-acute stroke subjects (N=142) and compared kinesthetic performance with stroke lesion location. Subjects with first unilateral, ischemic stroke underwent neuroimaging and a comprehensive robotic kinesthetic assessment (~9 days post-stroke). The robotic exoskeleton measured subjects’ ability to perform a kinesthetic mirror-matching task of the upper limbs without vision. The robot moved the stroke-affected arm and subjects’ mirror-matched the movement with the unaffected arm. We found that lesions both within and outside primary somatosensory cortex were associated with significant kinesthetic impairments. Further, sub-components of kinesthesia were associated with different lesion locations. Impairments in speed perception were primarily associated with lesions to the right post-central and supramarginal gyri whereas impairments in amplitude of movement perception were primarily associated with lesions in the right pre-central gyrus, anterior insula, and superior temporal gyrus. Impairments in perception of movement direction were associated with lesions to bilateral post-central and supramarginal gyri, right superior temporal gyrus and parietal operculum. All measures of impairment shared a common association with damage to the right supramarginal gyrus. These results suggest that processing of kinesthetic information occurs beyond traditional sensorimotor areas. Additionally, this dissociation between kinesthetic sub-components may indicate specialized processing in these brain areas that form a larger distributed network.

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.

Deep brain stimulation (DBS) is an excellent treatment for tremor and is generally thought to be reversible by turning off stimulation. For tremor, DBS is implanted in the ventrointermedius (Vim) nucleus of the thalamus, a region that relays proprioceptive information for movement sensation (kinaesthesia). Gait disturbances have been observed with bilateral Vim DBS, but the long-term effects on proprioceptive processing are unknown. We aimed to determine whether Vim DBS surgical implantation or stimulation leads to proprioceptive deficits in the upper limb. We assessed two groups of tremor subjects on measures of proprioception (kinaesthesia, position sense) and motor function using a robotic exoskeleton. In the first group (Surgery), we tested patients before and after implantation of Vim DBS, but before DBS was turned on to determine if proprioceptive deficits were inherent to tremor or caused by DBS implantation. In the second group (Stim), we tested subjects with chronically implanted Vim DBS ON and OFF stimulation. Compared to controls, there were no proprioceptive deficits before or after DBS implantation in the Surgery group. Surprisingly, those that received chronic long-term stimulation (LT-stim, 3-10 years) displayed significant proprioceptive deficits ON and OFF stimulation not present in subjects with chronic short-term stimulation (ST-stim, 0.5-2 years). LT-stim had significantly larger variability and reduced workspace area during the position sense assessment. During the kinesthetic assessment, LT-stim made significantly larger directional errors and consistently underestimated the speed of the robot, despite generating normal movement speeds during motor assessment. Chronic long-term Vim DBS may potentially disrupt proprioceptive processing, possibly inducing irreversible plasticity in the Vim nucleus and/or its network connections. Our findings in the upper limb may help explain some of the gait disturbances seen by others following Vim DBS

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.

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.

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 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.

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 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

Transcranial direct-current stimulation (tDCS) enhances motor learning in adults. We have demonstrated that anodal tDCS and high-definition (HD) tDCS of the motor cortex can enhance motor skill acquisition in children, but behavioral mechanisms remain unknown. Robotics can objectively quantify complex sensorimotor functions to better understand mechanisms of motor learning. We aimed to characterize changes in sensorimotor function induced by tDCS and HD-tDCS paired motor learning in children within an interventional trial. Healthy, right-handed children (12–18 y) were randomized to anodal tDCS, HD-tDCS, or sham targeting the right primary motor cortex during left-hand Purdue pegboard test (PPT) training over five consecutive days. A KINARM robotic protocol quantifying proprioception, kinesthesia, visually guided reaching, and an object hit task was completed at baseline, posttraining, and six weeks later. Effects of the treatment group and training on changes in sensorimotor parameters were explored. Twenty-four children (median 15.5 years, 52% female) completed all measures. Compared to sham, both tDCS and HD-tDCS demonstrated enhanced motor learning with medium effect sizes. At baseline, multiple KINARM measures correlated with PPT performance. Following training, visually guided reaching in all groups was faster and required less corrective movements in the trained arm (H(2) = 9.250, p=0.010). Aspects of kinesthesia including initial direction error improved across groups with sustained effects at follow-up (H(2) = 9.000, p=0.011). No changes with training or stimulation were observed for position sense. For the object hit task, the HD-tDCS group moved more quickly with the right hand compared to sham at posttraining (χ2(2) = 6.255, p=0.044). Robotics can quantify complex sensorimotor function within neuromodulator motor learning trials in children. Correlations with PPT performance suggest that KINARM metrics can assess motor learning effects. Understanding how tDCS and HD-tDCS enhance motor learning may be improved with robotic outcomes though specific mechanisms remain to be defined. Exploring mechanisms of neuromodulation may advance therapeutic approaches in children with cerebral palsy and other disabilities.