Effort, success, and side of lesion determine arm choice in individuals with chronic stroke.

In neurotypical individuals, arm choice in reaching movements depends on expected biomechanical effort, expected success, and a handedness bias. Following a stroke, does arm choice change to account for the decreased motor performance, or does it follow a preinjury habitual preference pattern? Participants with mild-to-moderate chronic stroke who were right-handed before stroke performed reaching movements in both spontaneous and forced-choice blocks, under no-time, medium-time, and fast-time constraint conditions designed to modulate reaching success. Mixed-effects logistic regression models of arm choice revealed that expected effort predicted choices. However, expected success only strongly predicted choice in left-hemiparetic individuals. In addition, reaction times decreased in left-hemiparetic individuals between the no-time and the fast-time constraint conditions but showed no changes in right-hemiparetic individuals. Finally, arm choice in the no-time constraint condition correlated with a clinical measure of spontaneous arm use for right-, but not for left-hemiparetic individuals. Our results are consistent with the view that right-hemiparetic individuals show a habitual pattern of arm choice for reaching movements relatively independent of failures. In contrast, left-hemiparetic individuals appear to choose their paretic left arm more optimally: that is, if a movement with the paretic arm is predicted to be not successful in the upcoming movement, the nonparetic right arm is chosen instead.NEW & NOTEWORTHY Although we are seldom aware of it, we constantly make decisions to use one arm or the other in daily activities. Here, we studied whether these decisions change following stroke. Our results show that effort, success, and side of lesion determine arm choice in a reaching task: whereas left-paretic individuals modified their arm choice in response to failures in reaching the target, right-paretic individuals showed a pattern of choice independent of failures.

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.

Corticospinal Tract Microstructure Predicts Distal Arm Motor Improvements in Chronic Stroke.

BACKGROUND AND PURPOSE: The corticospinal tract (CST) is a crucial brain pathway for distal arm and hand motor control. We aimed to determine whether a diffusion tensor imaging (DTI)-derived CST metric predicts distal upper extremity (UE) motor improvements in chronic stroke survivors. METHODS: We analyzed clinical and neuroimaging data from a randomized controlled rehabilitation trial. Participants completed clinical assessments and neuroimaging at baseline and clinical assessments 4 months later, postintervention. Using univariate linear regression analysis, we determined the linear relationship between the DTI-derived CST fractional anisotropy asymmetry (FAasym) and the percentage of baseline change in log-transformed average Wolf Motor Function Test time for distal items (ΔlnWMFT-distal_%). The least absolute shrinkage and selection operator (LASSO) linear regressions with cross-validation and bootstrapping were used to determine the relative weighting of CST FAasym, other brain metrics, clinical outcomes, and demographics on distal motor improvement. Logistic regression analyses were performed to test whether the CST FAasym can predict clinically significant UE motor improvement. RESULTS: lnWMFT-distal significantly improved at the group level. Baseline CST FAasym explained 26% of the variance in ΔlnWMFT-distal_%. A multivariate LASSO model including baseline CST FAasym, age, and UE Fugl-Meyer explained 39% of the variance in ΔlnWMFT-distal_%. Further, CST FAasym explained more variance in ΔlnWMFT-distal_% than the other significant predictors in the LASSO model. DISCUSSION AND CONCLUSIONS: CST microstructure is a significant predictor of improvement in distal UE motor function in the context of an UE rehabilitation trial in chronic stroke survivors with mild-to-moderate motor impairment.Video Abstract available for more insight from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A350).

Dosage Matters.

Background and Purpose- For stroke rehabilitation, task-specific training in animal models and human rehabilitation trials is considered important to modulate neuroplasticity, promote motor learning, and functional recovery. Little is known about what constitutes an effective dosage of therapy. Methods- This is a parallel group, 4 arms, single-blind, phase IIb, randomized controlled trial of 4 dosages of arm therapy delivered in an outpatient setting chronically after stroke. Participants were randomized into groups that varied in duration of scheduled therapy (ie, 0, 15, 30, or 60 hours). Forty-one participants completed the study. Planned primary analyses used linear mixed effects regression to model changes from baseline to postintervention in the Motor Activity Log-Quality of Movement rating and the Wolf Motor Function Test time score over 3 weeks of training as a function of therapy dosage. Results- We observed a dose response for the Motor Activity Log-Quality of Movement: the model that included dose and dose by week interaction significantly better fit the data than the model that included week only (log-likelihood test, P=0.0026). In addition, the greater the dosage of training, the greater the change in Motor Activity Log-Quality of Movement, with the dose by week interaction parameter equal to 0.0045 ( P=0.0016; 95% CI, 0.0018-0.0071). Over the 3 weeks of therapy, there was a gain of 0.92 in Motor Activity Log-Quality of Movement for the 60-hour group compared to the 0-hour group. There was no dose response for the Wolf Motor Function Test. Conclusions- For mild-to-moderately impaired stroke survivors, the dosage of patient-centered, task-specific practice systematically influences the gain in quality of arm use but not functional capacity. We caution that we may have been underpowered for the functional capacity outcome. These findings highlight the importance of recovery outcomes that capture arm use in the natural environment. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01749358.

Impact of motor task conditions on end-point kinematics and trunk movements during goal-directed arm reach.

Task conditions significantly impact human motor control. We investigated how task type, difficulty, and constraints influence the kinematics of goal-directed arm reaching. Non-disabled young adults performed two distinct goal-directed arm reaching tasks: pointing and picking up an object with chopsticks. These tasks were carried out under various conditions, including constrained and unconstrained elbow extension and two different task difficulties. We collected kinematic data using a 3-D motion capture system and analyzed the effects of different task conditions on kinematic variables using linear mixed-effects regression analysis. Our findings revealed statistically significant differences in kinematics between the two tasks. Arm reaching during the picking-up task was slower and exhibited jerkier movements compared to the pointing task. Additionally, when arm reaching was performed with constrained elbow extension, it led to slower and jerkier movements, with an increased involvement of trunk movements compared to the unconstrained condition. These findings show that complex manipulative motor tasks requiring higher hand dexterity necessitate feedback-based control of arm reaching, but simple pointing tasks requiring less hand dexterity do not. In conclusion, our study sheds light on the influence of task conditions on goal-directed arm reaching kinematics and provides valuable insights into the motor control strategies involved in different tasks.

Accuracy and feasibility of a novel fine hand motor skill assessment using computer vision object tracking.

We developed a computer vision-based three-dimension (3D) motion capture system employing two action cameras to examine fine hand motor skill by tracking an object manipulated by a hand. This study aimed to examine the accuracy and feasibility of this approach for detecting changes in a fine hand motor skill. We conducted three distinct experiments to assess the system's accuracy and feasibility. We employed two high-resolution, high-frame-rate action cameras. We evaluated the accuracy of our system in calculating the 3D locations of moving object in various directions. We also examined the system's feasibility in identifying improvement in fine hand motor skill after practice in eleven non-disabled young adults. We utilized color-based object detection and tracking to estimate the object's 3D location, and then we computed the object's kinematics, representing the endpoint goal-directed arm reaching movement. Compared to ground truth measurements, the findings demonstrated that our system can adequately estimate the 3D locations of a moving object. We also showed that the system can be used to measure the endpoint kinematics of goal-directed arm reaching movements to detect changes in fine hand motor skill after practice. Future research is needed to confirm the system's reliability and validity in assessing fine hand motor skills in patient populations.

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.

Antiasthmatic Effects of Herbal Complex MA and Its Fermented Product MA128.

This study was conducted to determine if oral administration of the novel herbal medicine, MA, and its Lactobacillus acidophilus fermented product, MA128, have therapeutic properties for the treatment of asthma. Asthma was induced in BALB/c mice by systemic sensitization to ovalbumin (OVA) followed by intratracheal, intraperitoneal, and aerosol allergen challenges. MA and MA128 were orally administered 6 times a week for 4 weeks. At 1 day after the last ovalbumin exposure, airway hyperresponsiveness was assessed and samples of bronchoalveolar lavage fluid, lung cells, and serum were collected for further analysis. We investigated the effect of MA and MA128 on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production, OVA-specific IgE production, and Th1/Th2 cytokine production in this mouse model of asthma. In BALB/c mice, we found that MA and MA128 treatment suppressed eosinophil infiltration into airways and blood, allergic airway inflammation and AHR by suppressing the production of IL-5, IL-13, IL-17, Eotaxin, and OVA-specific IgE, by upregulating the production of OVA-specific Th1 cytokine (IFN-γ), and by downregulating OVA-specific Th2 cytokine (IL-4) in the culture supernatant of spleen cells. The effectiveness of MA was increased by fermentation with Lactobacillus acidophilus.

Different Patterns of Neural Activity Characterize Motor Skill Performance During Acquisition and Retention.

Motor performance and learning have distinct behavioral and neural signatures and can be uniquely modulated by various informational and motivational factors. Contemporary frameworks describe four different motor learning mechanisms mapped onto specific neural regions which are key for motor skill acquisition: error-based learning (cerebellum), reinforcement learning (basal ganglia), cognitive strategies (prefrontal cortex), and use-dependent learning (motor cortex). However, little is known about the neural circuits engaged during skill acquisition that are modulated specifically by practice-based performance improvement and those that predict recall performance. Based on previous work, we hypothesize that brain activity during practice in primary motor cortex and basal ganglia (1) is associated with trial-by-trial practice performance and (2) is predictive of immediate recall performance. Leveraging the contemporary framework, we use a well-known task paradigm that primarily relies upon cognitive strategy, reinforcement, and use-based learning mechanisms to test our hypotheses. Forty neurotypical young adults were asked to practice a pinch force tracking task. Participants received performance feedback after each trial during practice. We used whole brain analysis of functional magnetic resonance imaging (fMRI) and behavioral performance measures (i.e., time-on-target and self-efficacy) during the practice phase to determine which brain activation patterns are (1) associated with trial-by-trial tracking performance and (2) predictive of immediate no-feedback retention performance. We observed brain activations in the frontal orbital cortex, putamen, amygdala, and insula correlated with tracking performance improvement during practice. In contrast, a different set of performance-related activated regions were observed that were associated with immediate retention performance that included the primary motor cortex, superior frontal gyrus, somatosensory cortex, angular gyrus, and parietal gyrus. Our findings demonstrate that improved practice performance and recall of a sensorimotor skill are correlated with distinct neural activity patterns during acquisition, drawing on different motor learning mechanisms during encoding. While motor performance improvements depend on both cortical and subcortical regions, motor skill recall depends primarily on prefrontal and motor cortices. We discuss possible interpretations for why our hypothesis regarding basal ganglia activity and retention performance was not supported. Understanding the different neural mechanisms engaged in motor performance and learning may inform novel interventions to enhance motor skill learning.

Corticospinal Tract Lesion Load Originating From Both Ventral Premotor and Primary Motor Cortices Are Associated With Post-stroke Motor Severity.

Lesion load of the corticospinal tract (CST-LL), a measure of overlap between a stroke lesion and the CST, is one of the strongest predictors of motor outcomes following stroke. CST-LL is typically calculated by using a probabilistic map of the CST originating from the primary motor cortex (M1). However, higher order motor areas also have projections that contribute to the CST and motor control. In this retrospective study, we examined whether evaluating CST-LL from additional motor origins is more strongly associated with post-stroke motor severity than using CST-LL originating from M1 only. We found that lesion load to both the ventral premotor (PMv) cortex and M1 were more strongly related to stroke motor severity indexed by Fugl-Meyer Assessment cut-off scores than CST-LL of M1 alone, suggesting that higher order motor regions add clinical relevance to motor impairment.

Antiasthmatic effects of hesperidin, a potential Th2 cytokine antagonist, in a mouse model of allergic asthma.

BACKGROUND AND OBJECTIVE: The features of asthma are airway inflammation, reversible airflow obstruction, and an increased sensitivity to bronchoconstricting agents, termed airway hyperresponsiveness (AHR), excess production of Th2 cytokines, and eosinophil accumulation in the lungs. To investigate the antiasthmatic potential of hesperidin as well as the underlying mechanism involved, we studied the inhibitory effect and anti-inflammatory effect of hesperidin (HPN) on the production of Th2 cytokines, eotaxin, IL-17, -OVA-specific IgE in vivo asthma model mice. METHODS: In this paper, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges. We investigated the effect of HPN on airway hyperresponsiveness, pulmonary eosinophilic infiltration, various immune cell phenotypes, Th2 cytokine production and OVA-specific IgE production in a mouse model of asthma. RESULTS: In BALB/c mice, we found that HPN-treated groups had suppressed eosinophil infiltration, allergic airway inflammation, and AHR, and these occurred by suppressing the production of IL-5, IL-17, and OVA-specific IgE. CONCLUSIONS: Our data suggest that the therapeutic mechanism by which HPN effectively treats asthma is based on reductions of Th2 cytokines (IL-5), eotaxin, OVA-specific IgE production, and eosinophil infiltration via inhibition of GATA-3 transcription factor.

The Impact of Motor Task Conditions on Goal-Directed Arm Reaching Kinematics and Trunk Compensation in Chronic Stroke Survivors.

Trunk compensation is the most common movement strategy to substitute for upper extremity (UE) motor deficits in chronic stroke survivors. There is a lack of evidence examining how task conditions impact trunk compensation and goal-directed arm reaching kinematics. This protocol aims to investigate the impact of task conditions, including task difficulty and complexity, on goal-directed arm reaching kinematics. Two non-disabled young adults and two chronic stroke survivors with mild UE motor impairment were recruited for testing the protocol. Each participant performed goal-directed arm reaches with four different task conditions (2 task difficulties [large vs. small targets] X 2 task complexities [pointing vs. picking up]). The task goal was to reach and point at a target or pick up an object located 20 cm in front of the home position as quickly as possible with a stylus or a pair of chopsticks, respectively, in response to an auditory cue. Participants performed ten reaches per task condition. A 3-dimensional motion capture camera system was used to record trunk and arm kinematics. Representative results showed that there was a significant increase in movement duration, movement jerkiness, and trunk compensation as a function of task complexity, but not task difficulty in all participants. Chronic stroke survivors showed significantly slower, jerkier, and more feedback-dependent arm reaches and significantly more compensatory trunk movements than non-disabled adults. Our representative results support that this protocol can be used to investigate the impact of task conditions on motor control strategies in chronic stroke survivors with mild UE motor impairment.

Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide.

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P < 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179; d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = -0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = -0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = -0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes.

Pinellia ternata, Citrus reticulata, and their combinational prescription inhibit eosinophil infiltration and airway hyperresponsiveness by suppressing CCR3+ and Th2 cytokines production in the ovalbumin-induced asthma model.

BACKGROUND AND OBJECTIVE: This study was aimed to analyse the curative effects of Pinellia ternata, Citrus reticulata, and their combination on airway hyperresponsiveness (AHR) to inhaled methacholine, pulmonary eosinophilic infiltration, Th2 cytokine production, and IgE and histamine production in a murine model of asthma. METHODS: For this purpose, BALB/c mice were systemically sensitized to ovalbumin (OVA) followed intratracheally, intraperitoneally, and by aerosol allergen challenges for 12 weeks. We examined the development of pulmonary eosinophilic accumulation, control of Th2 cytokine, immunoglobulin E (IgE), and histamine productions in a murine model of asthma. RESULTS: Our data suggest that the therapeutic mechanism by which Pinellia ternata, Citrus reticulata, and their combinational prescription effectively treats asthma is based on reductions of eosinophil infiltration, eotaxin receptor (CCR3), histamine, OVA-specific IgE productions in serum, and Th2 cytokines (IL-5, IL-13) by marked reductions of IL-5 and IL-13 mRNA expression in lung tissue. CONCLUSIONS: These findings provide evidence that Pinellia ternata, Citrus reticulata, and their combination play a regulatory role in allergic inflammation and offer therapeutic approaches as novel CCR3 antagonists for treatment asthma. However, it is not clear whether pharmacological activities of prescription composed of two herbs are potentiated due to synergistic effect or additive effect.

Luteolin attenuates airway inflammation by inducing the transition of CD4+CD25- to CD4+CD25+ regulatory T cells.

Regulatory T cells play an important role in autoimmunity and have been shown to exert anti-inflammatory effects in allergic asthma. Mouse model of airway inflammation was used to examine the suppressive activity of luteolin-induced CD4+CD25+ regulatory T cells (Tregs) in vivo. In this study, BALB/c mice were sensitized with ovalbumin antigen (OVA) by aerosol challenge. Then, various biological processes were examined, including airway eosinophilia; mucus hypersecretion; elevation of OVA-specific IgE, expression of Th2 cytokines and chemokine levels; expression of eotaxin 2 and CCR3; and airway hyper responsiveness (AHR). Luteolin significantly inhibited OVA-induced increase in immune cell and eosinophil counts as well as IL-4, IL-5, IL-13, and eotaxin levels in bronchoalveolar lavage fluid (BAL Fluid). Luteolin and cyclosporine A (CsA) which was a positive control also substantially reduced OVA-specific IgE levels, eotaxin 2 levels, and CCR3 expression in BAL Fluid. In contrast, luteolin significantly increased IL-10 and IFN-γ protein levels, as well as IL-10 and TGF-ß1 mRNA expression in the lung. In vitro studies showed that the number of luteolin-induced CD4+CD25+ Treg (iTreg) cells was higher, with elevated levels of TGF-ß1 and foxp3 mRNA expression in lungs tissue. Transfer of iTreg cells into OVA-sensitized mice reduced AHR, eosinophil recruitment, eotaxin, IgE, and Th2 cytokine expressions, and increased IFN-γ production in BAL Fluid after allergen challenge. Furthermore, adoptive transfer of iTreg cells prevented disease in a CD25-depleted mouse asthma model. Luteolin via induction of foxp3 and CD4+CD25+ Treg cells may represent a new strategy in the development of therapies for managing asthma.

A comparison of seven different DTI-derived estimates of corticospinal tract structural characteristics in chronic stroke survivors.

BACKGROUND: Different diffusion tensor imaging (DTI) has been used to estimate corticospinal tract (CST) structure in the context of stroke rehabilitation research. However, there is no gold standard for the estimate of CST structure in chronic stroke survivors. This study aims to determine the most accurate DTI-derived CST estimate that is associated with a clinical motor outcome measure. METHODS: We obtained imaging and behavioral data from a phase-I stroke rehabilitation clinical trial. We included thirty-seven chronic stroke survivors with mild-to-moderate motor impairment. Imaging data were processed using BrainSuite16a software. We calculated mean FA for each of 7 different ROIs/VOIs that include manually drawn 2-D ROIs and 3-D VOIs of CST from individual tractography or standard atlas. We compared ipsi- and contralesional CST FA for each method. Partial correlation was conducted between each CST FA asymmetry index and a time-based motor outcome measure, controlling for age and chronicity. RESULTS: Ipsilesional CST FA was significantly lower than contralesional CST FA for each of the 7 methods Only CST FA asymmetry from the 3-D individual CST tractography showed a significant correlation with the primary motor outcome (r = 0.46, p = .005), while CST FA from the other six methods did not. COMPARISON WITH EXISTING METHODS: Compared to the six other methods, CST FA asymmetry from 3-D individual tractography is the most accurate estimate of CST structure in this cohort of stroke survivors. CONCLUSION: We recommend this method for future research seeking to understand brain-behavior mechanisms of motor recovery in chronic stroke survivors.

A large, open source dataset of stroke anatomical brain images and manual lesion segmentations.

Stroke is the leading cause of adult disability worldwide, with up to two-thirds of individuals experiencing long-term disabilities. Large-scale neuroimaging studies have shown promise in identifying robust biomarkers (e.g., measures of brain structure) of long-term stroke recovery following rehabilitation. However, analyzing large rehabilitation-related datasets is problematic due to barriers in accurate stroke lesion segmentation. Manually-traced lesions are currently the gold standard for lesion segmentation on T1-weighted MRIs, but are labor intensive and require anatomical expertise. While algorithms have been developed to automate this process, the results often lack accuracy. Newer algorithms that employ machine-learning techniques are promising, yet these require large training datasets to optimize performance. Here we present ATLAS (Anatomical Tracings of Lesions After Stroke), an open-source dataset of 304 T1-weighted MRIs with manually segmented lesions and metadata. This large, diverse dataset can be used to train and test lesion segmentation algorithms and provides a standardized dataset for comparing the performance of different segmentation methods. We hope ATLAS release 1.1 will be a useful resource to assess and improve the accuracy of current lesion segmentation methods.

Can Neurological Biomarkers of Brain Impairment Be Used to Predict Poststroke Motor Recovery? A Systematic Review.

Background There is growing interest to establish recovery biomarkers, especially neurological biomarkers, in order to develop new therapies and prediction models for the promotion of stroke rehabilitation and recovery. However, there is no consensus among the neurorehabilitation community about which biomarker(s) have the highest predictive value for motor recovery. Objective To review the evidence and determine which neurological biomarker(s) meet the high evidence quality criteria for use in predicting motor recovery. Methods We searched databases for prognostic neuroimaging/neurophysiological studies. Methodological quality of each study was assessed using a previously employed comprehensive 15-item rating system. Furthermore, we used the GRADE approach and ranked the overall evidence quality for each category of neurologic biomarker. Results Seventy-one articles met our inclusion criteria; 5 categories of neurologic biomarkers were identified: diffusion tensor imaging (DTI), transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), conventional structural MRI (sMRI), and a combination of these biomarkers. Most studies were conducted with individuals after ischemic stroke in the acute and/or subacute stage (~70%). Less than one-third of the studies (21/71) were assessed with satisfactory methodological quality (80% or more of total quality score). Conventional structural MRI and the combination biomarker categories ranked "high" in overall evidence quality. Conclusions There were 3 prevalent methodological limitations: (a) lack of cross-validation, (b) lack of minimal clinically important difference (MCID) for motor outcomes, and (c) small sample size. More high-quality studies are needed to establish which neurological biomarkers are the best predictors of motor recovery after stroke. Finally, the quarter-century old methodological quality tool used here should be updated by inclusion of more contemporary methods and statistical approaches.

Low-Level Laser Irradiation Improves Motor Recovery After Contusive Spinal Cord Injury in Rats.

This study investigated the therapeutic effects of low-level laser irradiation (LLLI) on the recovery of motor function and its underlying mechanisms in rats with spinal cord injury (SCI). The spinal cord was contused at the T11 level using a New York University impactor. Thirty-eight rats were randomly divided into four groups: LLLI with 0.08 J, 0.4 J, 0.8 J, and sham. We transcutaneously applied at the lesion site of the spinal contusive rats 5 min after injury and then daily for 21 days. The Basso, Beattie and Bresnahan (BBB) locomotor scale and combined behavioral score (CBS) were used to evaluate motor function. The spinal segments of rostral and caudal from the lesion site, the epicenter, and L4-5 were collected from normal and the all groups at 7 days after SCI. The expression of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) was compared across groups in all regions. In the present study, LLLI with 0.4 J and 0.8 J led to a significant improvement in motor function compared to sham LLLI, which significantly decreased TNF-α expression at the lesion epicenter and reduced iNOS expression in the caudal segment for all LLLI groups and in the L4-5 segments for the 0.4 J and 0.8 J groups when compared to sham LLLI group. Our results demonstrate that transcutaneous LLLI modulate inflammatory mediators to enhance motor function recovery after SCI. Thus, LLLI in acute phase after SCI might have therapeutic potential for neuroprotection and restoration of motor function following SCI.

Torilin ameliorates type II collagen-induced arthritis in mouse model of rheumatoid arthritis.

Advancements in rheumatoid-arthritis-(RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential agents with relative safety and efficacy continues and natural compounds have been considered as alternatives to identify new entities. Since previous in-vivo data and our in-vitro findings showed that torilin has a strong anti-inflammatory property, we further investigated its effect against collagen-induced-arthritis-(CIA) in mice. CIA-induced DBA/1J mice were treated with torilin or methotrexate (MTX) for 5-weeks. Arthritis severity was evaluated by arthritic score and joint histopathology. Draining lymph node (dLN), joint and peripheral-blood mononuclear-cell (PBMC) counts, and activation/localization of T-/B-lymphocytes, dendritic cells (DCs) and neutrophils were examined by FACS analysis. Serum anti-type-II-collagen-(CII) antibody levels and cultured-splenocyte and serum cytokines were also evaluated. Torilin markedly reduced CIA-induced arthritic score, histopathology and leukocyte counts. Besides, torilin suppressed CIA-activated T-cells including CD3+, CD3+/CD69+, CD8+, CD4+ and CD4+/CD25+ in dLNs or joints. It also modified CD19+ or CD20+/CD23+ (B-cells), MHCII+/CD11c+ (DCs) and Gr-1+/CD11b+ (neutrophil) subpopulations. It further depressed total anti-CII-IgG, anti-CII-IgG1 and anti-CII-IgG2a antibody productions. Moreover, while IFN-γ and IL-10 were not affected, torilin suppressed CIA-induced serum TNF-α, IL-1ß and IL-6 levels. Interestingly, torilin also blocked IFN-γ, IL-17 and IL-6 cytokines while it did not affect IL-10 but enhanced IL-4 in splenocytes. These results show that torilin attenuated arthritis severity, modified leukocyte activations in dLNs or joints, and restored serum and splenocyte cytokine imbalances. Torilin may have immunomodulatory and anti-inflammatory properties with the capacity to ameliorate the inflammatory response in CIA-mice.