NSF DARE-Transforming modeling in neurorehabilitation: Four threads for catalyzing progress.

We present an overview of the Conference on Transformative Opportunities for Modeling in Neurorehabilitation held in March 2023. It was supported by the Disability and Rehabilitation Engineering (DARE) program from the National Science Foundation's Engineering Biology and Health Cluster. The conference brought together experts and trainees from around the world to discuss critical questions, challenges, and opportunities at the intersection of computational modeling and neurorehabilitation to understand, optimize, and improve clinical translation of neurorehabilitation. We organized the conference around four key, relevant, and promising Focus Areas for modeling: Adaptation & Plasticity, Personalization, Human-Device Interactions, and Modeling 'In-the-Wild'. We identified four common threads across the Focus Areas that, if addressed, can catalyze progress in the short, medium, and long terms. These were: (i) the need to capture and curate appropriate and useful data necessary to develop, validate, and deploy useful computational models (ii) the need to create multi-scale models that span the personalization spectrum from individuals to populations, and from cellular to behavioral levels (iii) the need for algorithms that extract as much information from available data, while requiring as little data as possible from each client (iv) the insistence on leveraging readily available sensors and data systems to push model-driven treatments from the lab, and into the clinic, home, workplace, and community. The conference archive can be found at (dare2023.usc.edu). These topics are also extended by three perspective papers prepared by trainees and junior faculty, clinician researchers, and federal funding agency representatives who attended the conference.

Initial development of skill with a reversed bicycle and a case series of experienced riders.

Riding a bicycle is considered a durable skill that cannot be forgotten. Here, novice participants practiced riding a reversed bicycle, in which a reversing gear inverted the handlebar's rotation. Although learning to ride the reversed bicycle was possible, it was slow, highly variable, implicit, and followed an S-shape pattern. In the initial learning phase, failed attempts to ride the normal bicycle indicated strong interference between the two bicycle skills. While additional practice decreased this interference effect, a subset of learners could not ride either bicycle after eight sessions of practice. Experienced riders who performed extensive practice could switch bicycles without failed attempts and exhibited similar performance (i.e., similar handlebar oscillations) on both bicycles. However, their performance on the normal bicycle was worse than that of the novice bicycle riders at baseline. In conclusion, "unlearning" of the normal bicycle skill precedes the initial learning of the reversed bicycle skill, and a signature of such unlearning is still present following extensive practice.

Theoretical limits on the speed of learning inverse models explain the rate of adaptation in arm reaching tasks.

An essential aspect of human motor learning is the formation of inverse models, which map desired actions to motor commands. Inverse models can be learned by adjusting parameters in neural circuits to minimize errors in the performance of motor tasks through gradient descent. However, the theory of gradient descent establishes limits on the learning speed. Specifically, the eigenvalues of the Hessian of the error surface around a minimum determine the maximum speed of learning in a task. Here, we use this theoretical framework to analyze the speed of learning in different inverse model learning architectures in a set of isometric arm-reaching tasks. We show theoretically that, in these tasks, the error surface and, thus the speed of learning, are determined by the shapes of the force manipulability ellipsoid of the arm and the distribution of targets in the task. In particular, rounder manipulability ellipsoids generate a rounder error surface, allowing for faster learning of the inverse model. Rounder target distributions have a similar effect. We tested these predictions experimentally in a quasi-isometric reaching task with a visuomotor transformation. The experimental results were consistent with our theoretical predictions. Furthermore, our analysis accounts for the speed of learning in previous experiments with incompatible and compatible virtual surgery tasks, and with visuomotor rotation tasks with different numbers of targets. By identifying aspects of a task that influence the speed of learning, our results provide theoretical principles for the design of motor tasks that allow for faster learning.

Multi-Site Identification and Generalization of Clusters of Walking Behaviors in Individuals With Chronic Stroke and Neurotypical Controls.

BACKGROUND: Walking patterns in stroke survivors are highly heterogeneous, which poses a challenge in systematizing treatment prescriptions for walking rehabilitation interventions. OBJECTIVES: We used bilateral spatiotemporal and force data during walking to create a multi-site research sample to: (1) identify clusters of walking behaviors in people post-stroke and neurotypical controls and (2) determine the generalizability of these walking clusters across different research sites. We hypothesized that participants post-stroke will have different walking impairments resulting in different clusters of walking behaviors, which are also different from control participants. METHODS: We gathered data from 81 post-stroke participants across 4 research sites and collected data from 31 control participants. Using sparse K-means clustering, we identified walking clusters based on 17 spatiotemporal and force variables. We analyzed the biomechanical features within each cluster to characterize cluster-specific walking behaviors. We also assessed the generalizability of the clusters using a leave-one-out approach. RESULTS: We identified 4 stroke clusters: a fast and asymmetric cluster, a moderate speed and asymmetric cluster, a slow cluster with frontal plane force asymmetries, and a slow and symmetric cluster. We also identified a moderate speed and symmetric gait cluster composed of controls and participants post-stroke. The moderate speed and asymmetric stroke cluster did not generalize across sites. CONCLUSIONS: Although post-stroke walking patterns are heterogenous, these patterns can be systematically classified into distinct clusters based on spatiotemporal and force data. Future interventions could target the key features that characterize each cluster to increase the efficacy of interventions to improve mobility in people post-stroke.

Moderate-intensity cardiovascular exercise performed before motor practice attenuates offline implicit motor learning in stroke survivors but not age-matched neurotypical adults.

The acute impact of cardiovascular exercise on implicit motor learning of stroke survivors is still unknown. We investigated the effects of cardiovascular exercise on implicit motor learning of mild-moderately impaired chronic stroke survivors and neurotypical adults. We addressed whether exercise priming effects are time-dependent (e.g., exercise before or after practice) in the encoding (acquisition) and recall (retention) phases. Forty-five stroke survivors and 45 age-matched neurotypical adults were randomized into three sub-groups: BEFORE (exercise, then motor practice), AFTER (motor practice, then exercise), and No-EX (motor practice alone). All sub-groups practiced a serial reaction time task (five repeated and two pseudorandom sequences per day) on three consecutive days, followed 7 days later by a retention test (one repeated sequence). Exercise was performed on a stationary bike, (one 20-min bout per day) at 50% to 70% heart rate reserve. Implicit motor learning was measured as a difference score (repeated-pseudorandom sequence response time) during practice (acquisition) and recall (delayed retention). Separate analyses were performed on the stroke and neurotypical groups using linear mixed-effects models (participant ID was a random effect). There was no exercise-induced benefit on implicit motor learning for any sub-group. However, exercise performed before practice impaired encoding in neurotypical adults and attenuated retention performance of stroke survivors. There is no benefit to implicit motor learning of moderately intense cardiovascular exercise for stroke survivors or age-matched neurotypical adults, regardless of timing. Practice under a high arousal state and exercise-induced fatigue may have attenuated offline learning in stroke survivors.

Reinforcement learning establishes a minimal metacognitive process to monitor and control motor learning performance.

Humans and animals develop learning-to-learn strategies throughout their lives to accelerate learning. One theory suggests that this is achieved by a metacognitive process of controlling and monitoring learning. Although such learning-to-learn is also observed in motor learning, the metacognitive aspect of learning regulation has not been considered in classical theories of motor learning. Here, we formulated a minimal mechanism of this process as reinforcement learning of motor learning properties, which regulates a policy for memory update in response to sensory prediction error while monitoring its performance. This theory was confirmed in human motor learning experiments, in which the subjective sense of learning-outcome association determined the direction of up- and down-regulation of both learning speed and memory retention. Thus, it provides a simple, unifying account for variations in learning speeds, where the reinforcement learning mechanism monitors and controls the motor learning process.

Long-term forecasting of a motor outcome following rehabilitation in chronic stroke via a hierarchical bayesian dynamic model.

BACKGROUND: Given the heterogeneity of stroke, it is important to determine the best course of motor therapy for each patient, i.e., to personalize rehabilitation based on predictions of long-term outcomes. Here, we propose a hierarchical Bayesian dynamic (i.e., state-space) model (HBDM) to forecast long-term changes in a motor outcome due to rehabilitation in the chronic phase post-stroke. METHODS: The model incorporates the effects of clinician-supervised training, self-training, and forgetting. In addition, to improve forecasting early in rehabilitation, when data are sparse or unavailable, we use the Bayesian hierarchical modeling technique to incorporate prior information from similar patients. We use HBDM to re-analyze the Motor Activity Log (MAL) data of participants with chronic stroke included in two clinical trials: (1) the DOSE trial, in which participants were assigned to a 0, 15, 30, or 60-h dose condition (data of 40 participants analyzed), and (2) the EXCITE trial, in which participants were assigned a 60-h dose, in either an immediate or a delayed condition (95 participants analyzed). RESULTS: For both datasets, HBDM accounts well for individual dynamics in the MAL during and outside of training: mean RMSE = 0.28 for all 40 DOSE participants (participant-level RMSE 0.26 ± 0.19-95% CI) and mean RMSE = 0.325 for all 95 EXCITE participants (participant-level RMSE 0.32 ± 0.31), which are small compared to the 0-5 range of the MAL. Bayesian leave-one-out cross-validation shows that the model has better predictive accuracy than static regression models and simpler dynamic models that do not account for the effect of supervised training, self-training, or forgetting. We then showcase model's ability to forecast the MAL of "new" participants up to 8 months ahead. The mean RMSE at 6 months post-training was 1.36 using only the baseline MAL and then decreased to 0.91, 0.79, and 0.69 (respectively) with the MAL following the 1st, 2nd, and 3rd bouts of training. In addition, hierarchical modeling improves prediction for a patient early in training. Finally, we verify that this model, despite its simplicity, can reproduce previous findings of the DOSE trial on the efficiency, efficacy, and retention of motor therapy. CONCLUSIONS: In future work, such forecasting models can be used to simulate different stages of recovery, dosages, and training schedules to optimize rehabilitation for each person. Trial registration This study contains a re-analysis of data from the DOSE clinical trial ID NCT01749358 and the EXCITE clinical trial ID NCT00057018.

Gait speed and individual characteristics are related to specific gait metrics in neurotypical adults.

Gait biofeedback is a well-studied strategy to reduce gait impairments such as propulsion deficits or asymmetric step lengths. With biofeedback, participants alter their walking to reach the desired magnitude of a specific parameter (the biofeedback target) with each step. Biofeedback of anterior ground reaction force and step length is commonly used in post-stroke gait training as these variables are associated with self-selected gait speed, fall risk, and the energy cost of walking. However, biofeedback targets are often set as a function of an individual's baseline walking pattern, which may not reflect the ideal magnitude of that gait parameter. Here we developed prediction models based on speed, leg length, mass, sex, and age to predict anterior ground reaction force and step length of neurotypical adults as a possible method for personalized biofeedback. Prediction of these values on an independent dataset demonstrated strong agreement with actual values, indicating that neurotypical anterior ground reaction forces can be estimated from an individual's leg length, mass, and gait speed, and step lengths can be estimated from individual's leg length, mass, age, sex, and gait speed. Unlike approaches that rely on an individual's baseline gait, this approach provides a standardized method to personalize gait biofeedback targets based on the walking patterns exhibited by neurotypical individuals with similar characteristics walking at similar speeds without the risk of over- or underestimating the ideal values that could limit feedback-mediated reductions in gait impairments.

Multi-site identification and generalization of clusters of walking behaviors in individuals with chronic stroke and neurotypical controls.

Background: Walking patterns in stroke survivors are highly heterogeneous, which poses a challenge in systematizing treatment prescriptions for walking rehabilitation interventions. Objective: We used bilateral spatiotemporal and force data during walking to create a multi-site research sample to: 1) identify clusters of walking behaviors in people post-stroke and neurotypical controls, and 2) determine the generalizability of these walking clusters across different research sites. We hypothesized that participants post-stroke will have different walking impairments resulting in different clusters of walking behaviors, which are also different from control participants. Methods: We gathered data from 81 post-stroke participants across four research sites and collected data from 31 control participants. Using sparse K-means clustering, we identified walking clusters based on 17 spatiotemporal and force variables. We analyzed the biomechanical features within each cluster to characterize cluster-specific walking behaviors. We also assessed the generalizability of the clusters using a leave-one-out approach. Results: We identified four stroke clusters: a fast and asymmetric cluster, a moderate speed and asymmetric cluster, a slow cluster with frontal plane force asymmetries, and a slow and symmetric cluster. We also identified a moderate speed and symmetric gait cluster composed of controls and participants post-stroke. The moderate speed and asymmetric stroke cluster did not generalize across sites. Conclusions: Although post-stroke walking patterns are heterogenous, these patterns can be systematically classified into distinct clusters based on spatiotemporal and force data. Future interventions could target the key features that characterize each cluster to increase the efficacy of interventions to improve mobility in people post-stroke.

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (ß = 0.21; 95% CI 0.04-0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (ß = -0.28; 95% CI -0.41 to -0.15, p < 0.001) and across multiple domains of function (ß = -0.14; 95% CI -0.22 to -0.06, p < 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%-58%, p = 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01-1.08, p = 0.004). DISCUSSION: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.

Speed-dependent biomechanical changes vary across individual gait metrics post-stroke relative to neurotypical adults.

BACKGROUND: Gait training at fast speeds is recommended to reduce walking activity limitations post-stroke. Fast walking may also reduce gait kinematic impairments post-stroke. However, it is unknown if differences in gait kinematics between people post-stroke and neurotypical adults decrease when walking at faster speeds. OBJECTIVE: To determine the effect of faster walking speeds on gait kinematics post-stroke relative to neurotypical adults walking at similar speeds. METHODS: We performed a secondary analysis with data from 28 people post-stroke and 50 neurotypical adults treadmill walking at multiple speeds. We evaluated the effects of speed and group on individual spatiotemporal and kinematic metrics and performed k-means clustering with all metrics at self-selected and fast speeds. RESULTS: People post-stroke decreased step length asymmetry and trailing limb angle impairment, reducing between-group differences at fast speeds. Speed-dependent changes in peak swing knee flexion, hip hiking, and temporal asymmetries exaggerated between-group differences. Our clustering analyses revealed two clusters. One represented neurotypical gait behavior, composed of neurotypical and post-stroke participants. The other characterized stroke gait behavior-comprised entirely of participants post-stroke with smaller lower extremity Fugl-Meyer scores than the post-stroke participants in the neurotypical gait behavior cluster. Cluster composition was largely consistent at both speeds, and the distance between clusters increased at fast speeds. CONCLUSIONS: The biomechanical effect of fast walking post-stroke varied across individual gait metrics. For participants within the stroke gait behavior cluster, walking faster led to an overall gait pattern more different than neurotypical adults compared to the self-selected speed. This suggests that to potentiate the biomechanical benefits of walking at faster speeds and improve the overall gait pattern post-stroke, gait metrics with smaller speed-dependent changes may need to be specifically targeted within the context of fast walking.

Adaptive control is reversed between hands after left hemisphere stroke and lost following right hemisphere stroke.

Human motor adaptability is of utmost utility after neurologic injury such as unilateral stroke. For successful adaptive control of movements, the nervous system must learn to correctly identify the source of a movement error and predictively compensate for this error. The current understanding is that in bimanual tasks, this process is flexible such that errors are assigned to, and compensated for, by the limb that is more likely to produce those errors. Here, we tested the flexibility of the error assignment process in right-handed chronic stroke survivors using a bimanual reaching task in which the hands jointly controlled a single cursor. We predicted that the nondominant left hand in neurotypical adults and the paretic hand in chronic stroke survivors will be more responsible for cursor errors and will compensate more within a trial and learn more from trial to trial. We found that in neurotypical adults, the nondominant left hand does compensate more than the right hand within a trial but learns less trial-to-trial. After a left hemisphere stroke, the paretic right hand compensates more than the nonparetic left hand within-trial but learns less trial-to-trial. After a right hemisphere stroke, the paretic left hand neither corrects more within-trial nor learns more trial-to-trial. Thus, adaptive control of visually guided bimanual reaching movements is reversed between hands after the left hemisphere stroke and lost following the right hemisphere stroke. These results indicate that responsibility assignment is not fully flexible but depends on a central mechanism that is lateralized to the right hemisphere.

Corpus Callosal Microstructure Predicts Bimanual Motor Performance in Chronic Stroke Survivors: a Preliminary Cross-Sectional Study.

BACKGROUND: Microstructural changes in the corpus callosum (CC) are associated with more severe motor impairment in the paretic hand, poor recovery, and general disability. The purpose of this study was to determine if CC microstructure predicts bimanual motor performance in chronic stroke survivors. METHODS: We examined the relationship between the fractional anisotropy (FA) across the CC, in both the sensorimotor and non-sensorimotor regions, and movement times for two self-initiated and self-paced bimanual tasks in 41 chronic stroke survivors. Using publicly available control datasets (n = 52), matched closely for imaging acquisition parameters, we also explored the effect of stroke and age on callosal microstructure. RESULTS: In mild-to-moderate chronic stroke survivors with relatively localized lesions to the motor areas, lower callosal FA values, suggestive of a more disorganized microstructure, were associated with slower bimanual performance. Associations were strongest for the primary motor fibers (b = -2.19 ± 1.03, p = .035), followed closely by premotor/supplementary motor (b = -2.07 ± 1.07, p = .041) and prefrontal (b = -1.92 ± 0.97, p = .05) fibers of the callosum. Secondary analysis revealed that compared to neurologically age-similar adults, chronic stroke survivors exhibited significantly lower mean FA in all regions of the CC, except the splenium. CONCLUSION: Remote widespread changes in the callosal genu and body are associated with slower performance on cooperative bimanual tasks that require precise and interdependent coordination of the hands. Measures of callosal microstructure may prove to be a useful predictor of real-world bimanual performance in chronic stroke survivors.

Essential Role of Social Context and Self-Efficacy in Daily Paretic Arm/Hand Use After Stroke: An Ecological Momentary Assessment Study With Accelerometry.

OBJECTIVE: To determine the momentary effect of social-cognitive factors, in addition to motor capability, on post-stroke paretic arm/hand use in the natural environment. DESIGN: A 5-day observational study in which participants were sent 6 Ecological Momentary Assessment (EMA) prompts/day. SETTING: Participants' daily environment. PARTICIPANTS: Community-dwelling, chronic stroke survivors with right-dominant, mild-moderate upper extremity paresis (N=30). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Time duration of bimanual and unimanual paretic arm/hand use indexed by accelerometry; social-cognitive factors (social context, self-efficacy, mood) captured by EMA; motor capability of the paretic limb measured by Fugl-Meyer Upper Extremity Motor Assessment (FM). RESULTS: After accounting for participants' motor capability, we found that momentary social context (alone or not) and self-efficacy significantly predicted post-stroke paretic arm/hand use behavior in the natural environment. When participants were not alone, paretic arm/hand movement increased both with and without the less-paretic limb (bimanual and unimanual movements, P=.018 and P<.001, respectively). Importantly, participants were more likely to use their paretic arm/hand (unimanually) if they had greater self-efficacy for limb use (P=.042). EMA repeated-measures provide a real-time approach that captures the natural dynamic ebb and flow of social-cognitive factors and their effect on daily arm/hand use. We also observed that people with greater motor impairments (FM<50.6) increase unimanual paretic arm/hand movements when they are not alone, regardless of motor capability. CONCLUSIONS: In addition to motor capability, stroke survivors' momentary social context and self-efficacy play a role in paretic arm/hand use behavior. Our findings suggest the development of personalized rehabilitative interventions which target these factors to promote daily paretic arm/hand use. This study highlights the benefits of EMA to provide real-time information to unravel the complexities of the biopsychosocial (ie, motor capability and social-cognitive factors) interface in post-stroke upper extremity recovery.

Increased cognitive load in immersive virtual reality during visuomotor adaptation is associated with decreased long-term retention and context transfer.

BACKGROUND: Complex motor tasks in immersive virtual reality using a head-mounted display (HMD-VR) have been shown to increase cognitive load and decrease motor performance compared to conventional computer screens (CS). Separately, visuomotor adaptation in HMD-VR has been shown to recruit more explicit, cognitive strategies, resulting in decreased implicit mechanisms thought to contribute to motor memory formation. However, it is unclear whether visuomotor adaptation in HMD-VR increases cognitive load and whether cognitive load is related to explicit mechanisms and long-term motor memory formation. METHODS: We randomized 36 healthy participants into three equal groups. All groups completed an established visuomotor adaptation task measuring explicit and implicit mechanisms, combined with a dual-task probe measuring cognitive load. Then, all groups returned after 24-h to measure retention of the overall adaptation. One group completed both training and retention tasks in CS (measuring long-term retention in a CS environment), one group completed both training and retention tasks in HMD-VR (measuring long-term retention in an HMD-VR environment), and one group completed the training task in HMD-VR and the retention task in CS (measuring context transfer from an HMD-VR environment). A Generalized Linear Mixed-Effect Model (GLMM) was used to compare cognitive load between CS and HMD-VR during visuomotor adaptation, t-tests were used to compare overall adaptation and explicit and implicit mechanisms between CS and HMD-VR training environments, and ANOVAs were used to compare group differences in long-term retention and context transfer. RESULTS: Cognitive load was found to be greater in HMD-VR than in CS. This increased cognitive load was related to decreased use of explicit, cognitive mechanisms early in adaptation. Moreover, increased cognitive load was also related to decreased long-term motor memory formation. Finally, training in HMD-VR resulted in decreased long-term retention and context transfer. CONCLUSIONS: Our findings show that cognitive load increases in HMD-VR and relates to explicit learning and long-term motor memory formation during motor learning. Future studies should examine what factors cause increased cognitive load in HMD-VR motor learning and whether this impacts HMD-VR training and long-term retention in clinical populations.

Rey-Osterrieth complex figure recall scores and motor skill learning in older adults: A non-linear mixed effect model-based analysis.

Age-related declines in motor learning are well documented. Visuospatial memory has been proposed as a key factor explaining age-related declines in sensorimotor adaptation, but most studies have not used standardized visuospatial memory tests nor controlled for age-related visuospatial memory declines. The present study explores the relationship between visuospatial memory and motor learning in older adults while also controlling for age and utilizing a standardized visuospatial memory test. Forty-nine nondemented older adults repetitively practiced a functional upper-extremity motor task and were re-assessed one week later. Training data were modeled with mixed-effect exponential decay functions, with parameters representing amount of performance change, rate of improvement, and final performance. Age and visuospatial memory were included as possible covariates for the parameter measuring rate of improvement (τ). After controlling for age, higher visuospatial memory scores were associated with faster rates of skill acquisition and better short-term retention one week later. These associations with visuospatial memory were dependent, however, on the level of initial skill. These findings suggest that the extent of re-learning motor skills in geriatric physical rehabilitation may depend on intact visuospatial memory.

Design of an Isometric End-Point Force Control Task for Electromyography Normalization and Muscle Synergy Extraction From the Upper Limb Without Maximum Voluntary Contraction.

Muscle synergy analysis via surface electromyography (EMG) is useful to study muscle coordination in motor learning, clinical diagnosis, and neurorehabilitation. However, current methods to extract muscle synergies in the upper limb suffer from two major issues. First, the necessary normalization of EMG signals is performed via maximum voluntary contraction (MVC), which requires maximal isometric force production in each muscle. However, some individuals with motor impairments have difficulties producing maximal effort in the MVC task. In addition, the MVC is known to be highly unreliable, with widely different forces produced in repeated measures. Second, synergy extraction in the upper limb is typically performed with a multidirection reaching task. However, some participants with motor impairments cannot perform this task because it requires precise motor control. In this study, we proposed a new isometric rotating task that does not require precise motor control or large forces. In this task, participants maintain a cursor controlled by the arm end-point force on a target that rotates at a constant angular velocity at a designated force level. To relax constraints on motor control precision, the target is widened and blurred. To obtain a reference EMG value for normalization without requiring maximal effort, we estimated a linear relationship between joint torques and muscle activations. We assessed the reliability of joint torque normalization and synergy extraction in the rotating task in young neurotypical individuals. Compared with normalization with MVC, joint torque normalization allowed reliable EMG normalization at low force levels. In addition, the extraction of synergies was as reliable and more stable than with the multidirection reaching task. The proposed rotating task can, therefore, be used in future motor learning, clinical diagnosis, and neurorehabilitation studies.

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis.

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; ß=0.16) but not contralesional (P=0.96; ß=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; ß=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; ß=-0.26) and contralesional (P=0.006; ß=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; ß=-0.21) and extent of sensorimotor damage (P=0.003; ß=-0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.

Virtuous and Vicious Cycles of Arm Use and Function Post-stroke.

Large doses of movement practice have been shown to restore upper extremities' motor function in a significant subset of individuals post-stroke. However, such large doses are both difficult to implement in the clinic and highly inefficient. In addition, an important reduction in upper extremity function and use is commonly seen following rehabilitation-induced gains, resulting in "rehabilitation in vain". For those with mild to moderate sensorimotor impairment, the limited spontaneous use of the more affected limb during activities of daily living has been previously proposed to cause a decline of motor function, initiating a vicious cycle of recovery, in which non-use and poor performance reinforce each other. Here, we review computational, experimental, and clinical studies that support the view that if arm use is raised above an effective threshold, one enters a virtuous cycle in which arm use and function can reinforce each other via self-practice in the wild. If not, one enters a vicious cycle of declining arm use and function. In turn, and in line with best practice therapy recommendations, this virtuous/vicious cycle model advocates for a paradigm shift in neurorehabilitation whereby rehabilitation be embedded in activities of daily living such that self-practice with the aid of wearable technology that reminds and motivates can enhance paretic limb use of those who possess adequate residual sensorimotor capacity. Altogether, this model points to a user-centered approach to recovery post-stroke that is tailored to the participant's level of arm use and designed to motivate and engage in self-practice through progressive success in accomplishing meaningful activities in the wild.

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain-behavior relationships after stroke.

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.