Dose Response to Upper Extremity Stroke Rehabilitation Varies by Individual: Early Indicators of Treatment Response.

BACKGROUND: Dose response has remained a priority area in motor rehabilitation research for decades, prompting several large randomized trials and meta-analyses. These between-subjects comparisons have revealed equivocal relationships between the duration of motor practice and rehabilitation response. Prior reliance on time-consuming clinical assessments made it infeasible to capture within-subjects dose response, as tracking the dose-response trajectory of an individual requires dozens of repeated administrations. METHODS: This secondary observational cohort analysis of existing data from the gaming arms of the VIGoROUS multisite trial (Video Game Rehabilitation for Outpatient Stroke) describes the rehabilitation dose response of 80 participants with mild-moderate chronic stroke. The 3-dimensional joint position data were captured via the Kinect v2 optical sensor as participants completed a prescribed 15 hours of in-home unsupervised game-based motor practice. Kinematic dose response trajectories were fitted from hundreds to thousands of in-game repetitions for 4 separate upper extremity movements for each participant. RESULTS: Of 75 participants with sufficient data for dose-response analysis, 85% showed improved motor capacity for at least 1 movement. Dose response was bimodal; 42% required <5 hours of motor practice before reaching a plateau in movement kinematics, whereas 55% required >10 and 34% required >30 hours. We could predict with 93% accuracy whether or not an individual would ultimately respond to game-based motor practice within 5 hours of gameplay. CONCLUSIONS: Dose response varies considerably between individuals. About half of chronic stroke patients benefit from higher doses of motor practice than the current standard of care. Individualized dose-response data from motion capture rehabilitation gaming can guide clinical decision-making early on in treatment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02631850.

The Economic Burden of Injuries in Children With ADHD in the U.S. From 2011 to 2020.

OBJECTIVE: Few studies have examined the economic burden of and sociodemographic disparities in injuries on families of children with ADHD on a national scale. The objective of this study was to address these literature gaps. METHODS: Data from 7,102 children with ADHD aged 5 to 17 years in the Medical Expenditure Panel Survey 2011 to 2020 were analyzed for national trends, annualized average, and sociodemographic disparities in injury-related medical expenditures among children with ADHD. RESULTS: The national economic burden of injuries for children with ADHD has nearly doubled over the10-year period. These costs were covered by private insurance (62%), public insurance (29%), and families (9%). Asian race was associated with higher total and family expenditures while having low income and public insurance were associated with lower family expenditures. CONCLUSIONS: Families and society carry significant and increasing economic burdens related to injuries in children with ADHD. Sociodemographic disparities are substantial and of policy relevance.

A Population-Based Study on Injury Risk and Disparities Among Children With ADHD.

OBJECTIVE: Impaired attention and inhibitory control put children with ADHD at potentially high risk of injury-one of the leading causes of disability in the general pediatric population. Existing research has yet to examine this important health risk using nationally representative samples. This population-based study aimed to address this gap. METHODS: National estimates of injury occurrences were generated from 66,236 children in the Medical Expenditures Panel Survey 2010-2019 datasets. Multiple logistic regression models further examined the impact of injury type, age, race/ethnicity, sex, parental education, income, marital and insurance status on injury prevalence. RESULTS: Compared to children without ADHD, those with ADHD have significantly higher injury prevalence (OR = 1.20, 95% CI [1.07, 1.33]) across injury types and most sociodemographic subgroups. CONCLUSIONS: Children with ADHD are more likely to experience injury. Future research should investigate mechanisms of injury disparities to inform future preventive efforts.

Compliance With In-Home Self-Managed Rehabilitation Post-Stroke is Largely Independent of Scheduling Approach.

OBJECTIVE: To investigate how participants self-schedule their engagement with domestic rehabilitation gaming platform, and how their scheduling behavior in turn influence overall compliance. DESIGN: Cohort of individuals randomized to receive in-home rehabilitation gaming during a multi-site randomized controlled trial. SETTING: In-home self-managed rehabilitation. PARTICIPANTS: Eighty community-dwelling participants who were >6 months post-stroke and had mild to moderate upper extremity impairment (N=80). INTERVENTIONS: Participants were prescribed 15 hours of independent in-home self-scheduled game play for upper extremity mobility over 3 weeks. MAIN OUTCOME MEASURES: Total number of hours of active game play was objectively measured by the rehabilitation gaming system. Cluster analysis identified scheduling patterns from the following scheduling characteristics: total number of sessions, average session length, and consistency of play schedule. RESULTS: Four distinct scheduling profiles were revealed, 3 of which were associated with complete or near-complete compliance, while a fourth (inconsistent schedule of short, infrequent sessions) was associated with very poor compliance. Poor compliance could be predicted within the first 7 days of the program with 78% accuracy based on the same play pattern metrics used to identify player profiles. CONCLUSIONS: Our findings support client autonomy in selecting the home practice schedule that works best for them, as compliance can successfully be achieved through a variety of different scheduling patterns. The objective measurements of compliance provided through rehabilitation gaming can assist therapists to identify individuals early on who exhibit scheduling behavior that is predictive of poor compliance.

Self-Supervised Learning for Electroencephalography.

Decades of research have shown machine learning superiority in discovering highly nonlinear patterns embedded in electroencephalography (EEG) records compared with conventional statistical techniques. However, even the most advanced machine learning techniques require relatively large, labeled EEG repositories. EEG data collection and labeling are costly. Moreover, combining available datasets to achieve a large data volume is usually infeasible due to inconsistent experimental paradigms across trials. Self-supervised learning (SSL) solves these challenges because it enables learning from EEG records across trials with variable experimental paradigms, even when the trials explore different phenomena. It aggregates multiple EEG repositories to increase accuracy, reduce bias, and mitigate overfitting in machine learning training. In addition, SSL could be employed in situations where there is limited labeled training data, and manual labeling is costly. This article: 1) provides a brief introduction to SSL; 2) describes some SSL techniques employed in recent studies, including EEG; 3) proposes current and potential SSL techniques for future investigations in EEG studies; 4) discusses the cons and pros of different SSL techniques; and 5) proposes holistic implementation tips and potential future directions for EEG SSL practices.

Tactile Sensation Improves Following Motor Rehabilitation for Chronic Stroke: The VIGoROUS Randomized Controlled Trial.

Background. Up to 85% of people with chronic stroke experience somatosensory impairment, which contributes to poor sensorimotor control and non-use of the affected limb. Neurophysiological mechanisms suggest motor rehabilitation may improve tactile sense post-stroke, however, somatosensory recovery has rarely been reported in controlled trials. Objective. To compare the effect of four upper limb motor rehabilitation programs on the recovery of tactile sensation in adults with chronic stroke. Methods. Adults with chronic stroke and mild or moderate upper extremity hemiparesis (n = 167) were enrolled in a multi-site randomized controlled trial. Participants completed three weeks of gaming therapy, gaming therapy with additional telerehabilition, Constraint-Induced Movement therapy, or traditional rehabilitation. Here, we report the results of a secondary outcome, tactile sensation, measured with monofilaments, before and after treatment, and 6 months later. Results. A mixed-effects general linear model revealed similar positive change in tactile sensitivity regardless of the type of training. On average, participants were able to detect a stimulus that was 32% and 33% less after training and at 6-month follow-up, respectively. One-third of participants experienced recategorization of their level of somatosensory impairment (e.g., regained protective sensation) following training. Poorer tactile sensation at baseline was associated with greater change. Conclusions. About one-third of individuals with mild/moderate chronic hemiparesis experience sustained improvements in tactile sensation following motor rehabilitation, regardless of the extent of tactile input in the rehabilitation program. Potential for sensory improvement is an additional motivator for those post-stroke. Characteristics of those who improve and mechanisms of improvement are important future questions. Clinicaltrials.gov NCT02631850.

Video game rehabilitation for outpatient stroke (VIGoROUS): A multi-site randomized controlled trial of in-home, self-managed, upper-extremity therapy.

BACKGROUND: Integrating behavioral intervention into motor rehabilitation is essential for improving paretic arm use in daily life. Demands on therapist time limit adoption of behavioral programs like Constraint-Induced Movement (CI) therapy, however. Self-managed motor practice could free therapist time for behavioral intervention, but there remains insufficient evidence of efficacy for a self-management approach. METHODS: This completed, parallel, five-site, pragmatic, single-blind trial established the comparative effectiveness of using in-home gaming self-management as a vehicle to redirect valuable therapist time towards behavioral intervention. Community-dwelling adults with post-stroke (>6 months) mild/moderate upper extremity hemiparesis were randomized to receive one of 4 different interventions over a 3-week period: 5 h of behaviorally-focused intervention plus gaming self-management (Self-Gaming), the same with additional behaviorally-focused telerehabilitation (Tele-Gaming), 5 h of Traditional motor-focused rehabilitation, or 35 h of CI therapy. Primary outcomes assessed everyday arm use (Motor Activity Log Quality of Movement, MAL) and motor speed/function (Wolf Motor Function Test, WMFT) immediately before treatment, immediately after treatment, and 6 months later. Intent-to-treat analyses were implemented with linear mixed-effects models on data gathered from March 15, 2016 to November 21, 2019. ClinicalTrials.gov, NCT02631850. RESULTS: Of 193 enrolled participants, 167 began treatment and were analyzed, 150 (90%) completed treatment, and 115 (69%) completed follow-up. Tele-Gaming and Self-Gaming produced clinically meaningful MAL gains that were 1·0 points (95% CI 0·8 to 1·3) and 0·8 points (95% CI 0·5 to 1·0) larger than Traditional care, respectively. Self-Gaming was less effective than CI therapy (-0·4 points, 95% CI -0·6 to -0·2), whereas Tele-Gaming was not (-0·2 points, 95% CI -0·4 to 0·1). Six-month retention of MAL gains across all groups was 57%. All had similar clinically-meaningful WMFT gains; six-month retention of WMFT gains was 92%. INTERPRETATION: Self-managed motor-gaming with behavioral telehealth visits has outcomes similar to in-clinic CI therapy. It addresses most access barriers, requiring just one-fifth as much therapist time that is redirected towards behavioral interventions that enhance the paretic arm's involvement in daily life. FUNDING: PCORI, NIH.

Early Patient-Centered Outcomes Research Experience With the Use of Telehealth to Address Disparities: Scoping Review.

BACKGROUND: Health systems and providers across America are increasingly employing telehealth technologies to better serve medically underserved low-income, minority, and rural populations at the highest risk for health disparities. The Patient-Centered Outcomes Research Institute (PCORI) has invested US $386 million in comparative effectiveness research in telehealth, yet little is known about the key early lessons garnered from this research regarding the best practices in using telehealth to address disparities. OBJECTIVE: This paper describes preliminary lessons from the body of research using study findings and case studies drawn from PCORI seminal patient-centered outcomes research (PCOR) initiatives. The primary purpose was to identify common barriers and facilitators to implementing telehealth technologies in populations at risk for disparities. METHODS: A systematic scoping review of telehealth studies addressing disparities was performed. It was guided by the Arksey and O'Malley Scoping Review Framework and focused on PCORI's active portfolio of telehealth studies and key PCOR identified by study investigators. We drew on this broad literature using illustrative examples from early PCOR experience and published literature to assess barriers and facilitators to implementing telehealth in populations at risk for disparities, using the active implementation framework to extract data. Major themes regarding how telehealth interventions can overcome barriers to telehealth adoption and implementation were identified through this review using an iterative Delphi process to achieve consensus among the PCORI investigators participating in the study. RESULTS: PCORI has funded 89 comparative effectiveness studies in telehealth, of which 41 assessed the use of telehealth to improve outcomes for populations at risk for health disparities. These 41 studies employed various overlapping modalities including mobile devices (29/41, 71%), web-based interventions (30/41, 73%), real-time videoconferencing (15/41, 37%), remote patient monitoring (8/41, 20%), and store-and-forward (ie, asynchronous electronic transmission) interventions (4/41, 10%). The studies targeted one or more of PCORI's priority populations, including racial and ethnic minorities (31/41, 41%), people living in rural areas, and those with low income/low socioeconomic status, low health literacy, or disabilities. Major themes identified across these studies included the importance of patient-centered design, cultural tailoring of telehealth solutions, delivering telehealth through trusted intermediaries, partnering with payers to expand telehealth reimbursement, and ensuring confidential sharing of private information. CONCLUSIONS: Early PCOR evidence suggests that the most effective health system- and provider-level telehealth implementation solutions to address disparities employ patient-centered and culturally tailored telehealth solutions whose development is actively guided by the patients themselves to meet the needs of specific communities and populations. Further, this evidence shows that the best practices in telehealth implementation include delivery of telehealth through trusted intermediaries, close partnership with payers to facilitate reimbursement and sustainability, and safeguards to ensure patient-guided confidential sharing of personal health information.

Effectiveness of Virtual Reality- and Gaming-Based Interventions for Upper Extremity Rehabilitation Poststroke: A Meta-analysis.

OBJECTIVE: To investigate the efficacy of virtual reality (VR)- and gaming-based interventions for improving upper extremity function poststroke, and to examine demographic and treatment-related factors that may moderate treatment response. DATA SOURCES: A comprehensive search was conducted within the PubMed, CINAHL/EBSCO, SCOPUS, Ovid MEDLINE, and EMBASE databases for articles published between 2005 and 2019. STUDY SELECTION: Articles investigating gaming and VR methods of treatment for upper extremity weakness were collected with the following study inclusion criteria: (1) participants aged 18 years or older with upper extremity deficits; (2) randomized controlled trials or prospective study design; (3) Downs-Black rating score of ≥18; and (4) outcome measure was the Wolf Motor Functioning Test, the Fugl-Meyer, or the Action Research Arm Test. DATA EXTRACTION: Thirty-eight articles met inclusion criteria. The primary outcome was proportional improvement on the Wolf Motor Functioning Test, Fugl-Meyer, or Action Research Arm Test. The following individual or treatment factors were extracted: VR or gaming dose, total treatment dose, chronicity (> or <6mo), severity of motor impairment, and presence of a gaming component. DATA ANALYSIS: Random effects meta-analysis models were utilized to quantify (1) the proportional recovery that occurs after VR or gaming; (2) the comparative treatment effect of VR or gaming vs conventional physiotherapy; and (3) whether the benefit of virtual reality differed based on participant characteristics or elements of the treatment. RESULTS: On average, VR or gaming interventions produced an improvement of 28.5% of the maximal possible improvement. Dose and severity of motor impairment did not significantly influence rehabilitation outcomes. Treatment gains were significantly larger overall (10.8%) when the computerized training involved a gaming component vs just visual feedback. VR or gaming interventions showed a significant treatment advantage (10.4%) over active control treatments. CONCLUSIONS: Overall, VR- or gaming-based upper extremity rehabilitation poststroke appears to be more effective than conventional methods. Further in-depth study of variables affecting improvement, such as individual motor presentation, treatment dose, and the relationship between them, are needed.

Predicting Improved Daily Use of the More Affected Arm Poststroke Following Constraint-Induced Movement Therapy.

BACKGROUND: Constraint-induced movement therapy (CI therapy) produces, on average, large and clinically meaningful improvements in the daily use of a more affected upper extremity in individuals with hemiparesis. However, individual responses vary widely. OBJECTIVE: The study objective was to investigate the extent to which individual characteristics before treatment predict improved use of the more affected arm following CI therapy. DESIGN: This study was a retrospective analysis of 47 people who had chronic (> 6 months) mild to moderate upper extremity hemiparesis and were consecutively enrolled in 2 CI therapy randomized controlled trials. METHODS: An enhanced probabilistic neural network model predicted whether individuals showed a low, medium, or high response to CI therapy, as measured with the Motor Activity Log, on the basis of the following baseline assessments: Wolf Motor Function Test, Semmes-Weinstein Monofilament Test of touch threshold, Motor Activity Log, and Montreal Cognitive Assessment. Then, a neural dynamic classification algorithm was applied to improve prognostic accuracy using the most accurate combination obtained in the previous step. RESULTS: Motor ability and tactile sense predicted improvement in arm use for daily activities following intensive upper extremity rehabilitation with an accuracy of nearly 100%. Complex patterns of interaction among these predictors were observed. LIMITATIONS: The fact that this study was a retrospective analysis with a moderate sample size was a limitation. CONCLUSIONS: Advanced machine learning/classification algorithms produce more accurate personalized predictions of rehabilitation outcomes than commonly used general linear models.

A Revised Motor Activity Log Following Rasch Validation (Rasch-Based MAL-18) and Consensus Methods in Chronic Stroke and Multiple Sclerosis.

Objectives. To derive a shorter version of the Motor Activity Log Quality-of-Movement Scale (MAL-28) with enhanced content and construct validity. Design. Validation cohort. Setting. Outpatient rehabilitation within an academic laboratory. Participants. Retrospective consecutive sample of 149 community-dwelling adults with chronic mild/moderate upper-extremity hemiparesis caused by stroke or multiple sclerosis (MS). Intervention. Not applicable. Methods. Participants received the MAL-28 at baseline and following upper-extremity rehabilitation. Rasch Measurement Theory informed threshold ordering of scoring categories, tests of fit, differential item functioning, targeting, response dependency, local dependency, and reliability (person separation index [PSI]). Seasoned examiners rated the content validity of each item. Test-retest reliability of the revised scale was calculated. Results. We established content and construct validity for 18 items. The resultant 18-item MAL fit the model (χ2 = 77.93; df = 72; P = .30) and targeted the population-that is, minimal floor (12.08%) or ceiling effects (0%), with acceptable reliability (PSI = 0.84) and good test-retest reliability [ICC(1, 1) = 0.86]. The hierarchy of item difficulty was independent of sex, age, affected side, diagnosis, or intervention type used, and there was local dependency in 3 pairs of items. Responses from a subsequent testing session were dependent on the responses from prior testing, indicating response dependency, for which a correction was proposed. Once response dependency was neutralized, there was a 15% greater treatment response. Conclusions. Content and construct validity are established for Rasch-based MAL-18 for chronic stages of stroke and MS. A Rasch-based conversion table enables clinical use of the MAL-18.

A Novel Methodology for Extracting and Evaluating Therapeutic Movements in Game-Based Motion Capture Rehabilitation Systems.

Virtual rehabilitation yields outcomes that are at least as good as traditional care for improving upper limb function and the capacity to carry out activities of daily living. Due to the advent of low-cost gaming systems and patient preference for game-based therapies, video game technology will likely be increasingly utilized in physical therapy practice in the coming years. Gaming systems that incorporate low-cost motion capture technology often generate large datasets of therapeutic movements performed over the course of rehabilitation. An infrastructure has yet to be established, however, to enable efficient processing of large quantities of movement data that are collected outside of a controlled laboratory setting. In this paper, a methodology is presented for extracting and evaluating therapeutic movements from game-based rehabilitation that occurs in uncontrolled and unmonitored settings. By overcoming these challenges, meaningful kinematic analysis of rehabilitation trajectory within an individual becomes feasible. Moreover, this methodological approach provides a vehicle for analyzing large datasets generated in uncontrolled clinical settings to enable better predictions of rehabilitation potential and dose-response relationships for personalized medicine.

Improved quality of life following constraint-induced movement therapy is associated with gains in arm use, but not motor improvement.

BACKGROUND: Constraint-induced movement therapy (CI therapy) is one of few treatments for upper extremity (UE) hemiparesis that has been shown to result in motor recovery and improved quality of life in chronic stroke. However, the extent to which treatment-induced improvements in motor function versus daily use of the more affected arm independently contribute to improved quality of life remains largely unexplored. OBJECTIVE: The objective of this study is to identify whether motor function or daily use of a hemiparetic arm has a greater influence on quality of life after CI therapy. METHODS: Two cohorts of participants with chronic stroke received either in-person CI therapy (n = 29) or video-game home-based CI therapy (n = 16). The two cohorts were combined and the motor-related outcomes (Wolf Motor Function Test, Action Research Arm Test, Motor Activity Log [MAL]) and quality of life (Stroke-Specific Quality of Life) were jointly modeled to assess the associations between outcomes. RESULTS: The only outcome associated with improved quality of life was the MAL. Improvements in quality of life were not restricted to motor domains, but generalized to psychosocial domains as well. CONCLUSIONS: Results suggest that improved arm use during everyday activities is integral to maximizing quality of life gains during motor rehabilitation for chronic post-stroke UE hemiparesis. In contrast, gains in motor function were not associated with increases in quality of life. These findings further support the need to implement techniques into clinical practice that promote arm use during daily life if improving quality of life is a main goal of treatment. ClinicalTrials.gov Registration Numbers: NCT01725919 and NCT03005457.

In-Home Delivery of Constraint-Induced Movement Therapy via Virtual Reality Gaming.

PURPOSE: People with chronic hemiparesis are frequently dissatisfied with the recovery of their hand and arm, yet many lack access to effective treatments. Constraint-induced movement therapy (CI therapy) effectively increases arm function and spontaneous use in persons with chronic hemiparesis. The purpose of this study was to determine the feasibility and measure safety and outcomes of an in-home model of delivering CI therapy using a custom, avatar-based virtual reality game. METHODS: Seventeen individuals with chronic hemiparesis participated in this pretest/posttest quasi-experimental design study. The 10-day intervention had three components: 1) high-repetition motor practice using virtual reality gaming; 2) constraint of the stronger arm via a padded restraint mitt; and 3) a transfer package to reinforce arm use. Feasibility of the intervention was evaluated through comparison to traditional CI therapy and through participants' subjective responses. The primary outcome measures were the Wolf Motor Function Test (WMFT) and the Motor Activity Log quality of movement scale (MAL-QOM). RESULTS: On average, participants completed 17.2 ± 8 hours and 19,436 repetitions of motor practice. No adverse events were reported. Of 7 feasibility criteria, 4 were met. WMFT rate and MAL-QOM increased, with effect size (Cohen's d) of 1.5 and 1.1, respectively. CONCLUSIONS: This model of delivering CI therapy using a custom, avatar-based virtual reality game was feasible, well received, and showed preliminary evidence of being a safe intervention to use in the home for persons with chronic hemiparesis.

Gross motor ability predicts response to upper extremity rehabilitation in chronic stroke.

The majority of rehabilitation research focuses on the comparative effectiveness of different interventions in groups of patients, while much less is currently known regarding individual factors that predict response to rehabilitation. In a recent article, the authors presented a prognostic model to identify the sensorimotor characteristics predictive of the extent of motor recovery after Constraint-Induced Movement (CI) therapy amongst individuals with chronic mild-to-moderate motor deficit using the enhanced probabilistic neural network (EPNN). This follow-up paper examines which participant characteristics are robust predictors of rehabilitation response irrespective of the training modality. To accomplish this, EPNN was first applied to predict treatment response amongst individuals who received a virtual-reality gaming intervention (utilizing the same enrollment criteria as the prior study). The combinations of predictors that yield high predictive validity for both therapies, using their respective datasets, were then identified. High predictive classification accuracy was achieved for both the gaming (94.7%) and combined datasets (94.5%). Though CI therapy employed primarily fine-motor training tasks and the gaming intervention emphasized gross-motor practice, larger improvements in gross motor function were observed within both datasets. Poorer gross motor ability at pre-treatment predicted better rehabilitation response in both the gaming and combined datasets. The conclusion of this research is that for individuals with chronic mild-to-moderate upper extremity hemiparesis, residual deficits in gross motor function are highly responsive to motor restorative interventions, irrespective of the modality of training.

Video Game Rehabilitation for Outpatient Stroke (VIGoROUS): protocol for a multi-center comparative effectiveness trial of in-home gamified constraint-induced movement therapy for rehabilitation of chronic upper extremity hemiparesis.

BACKGROUND: Constraint-Induced Movement therapy (CI therapy) is shown to reduce disability, increase use of the more affected arm/hand, and promote brain plasticity for individuals with upper extremity hemiparesis post-stroke. Randomized controlled trials consistently demonstrate that CI therapy is superior to other rehabilitation paradigms, yet it is available to only a small minority of the estimated 1.2 million chronic stroke survivors with upper extremity disability. The current study aims to establish the comparative effectiveness of a novel, patient-centered approach to rehabilitation utilizing newly developed, inexpensive, and commercially available gaming technology to disseminate CI therapy to underserved individuals. Video game delivery of CI therapy will be compared against traditional clinic-based CI therapy and standard upper extremity rehabilitation. Additionally, individual factors that differentially influence response to one treatment versus another will be examined. METHODS: This protocol outlines a multi-site, randomized controlled trial with parallel group design. Two hundred twenty four adults with chronic hemiparesis post-stroke will be recruited at four sites. Participants are randomized to one of four study groups: (1) traditional clinic-based CI therapy, (2) therapist-as-consultant video game CI therapy, (3) therapist-as-consultant video game CI therapy with additional therapist contact via telerehabilitation/video consultation, and (4) standard upper extremity rehabilitation. After 6-month follow-up, individuals assigned to the standard upper extremity rehabilitation condition crossover to stand-alone video game CI therapy preceded by a therapist consultation. All interventions are delivered over a period of three weeks. Primary outcome measures include motor improvement as measured by the Wolf Motor Function Test (WMFT), quality of arm use for daily activities as measured by Motor Activity Log (MAL), and quality of life as measured by the Quality of Life in Neurological Disorders (NeuroQOL). DISCUSSION: This multi-site RCT is designed to determine comparative effectiveness of in-home technology-based delivery of CI therapy versus standard upper extremity rehabilitation and in-clinic CI therapy. The study design also enables evaluation of the effect of therapist contact time on treatment outcomes within a therapist-as-consultant model of gaming and technology-based rehabilitation. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02631850 .

Computer-aided prediction of extent of motor recovery following constraint-induced movement therapy in chronic stroke.

Constraint-induced movement therapy (CI therapy) is a well-researched intervention for treatment of upper limb function. Overall, CI therapy yields clinically meaningful improvements in speed of task completion and greatly increases use of the more affected upper extremity for daily activities. However, individual improvements vary widely. It has been suggested that intrinsic feedback from somatosensation may influence motor recovery from CI therapy. To test this hypothesis, an enhanced probabilistic neural network (EPNN) prognostic computational model was developed to identify which baseline characteristics predict extent of motor recovery, as measured by the Wolf Motor Function Test (WMFT). Individual characteristics examined were: proprioceptive function via the brief kinesthesia test, tactile sensation via the Semmes-Weinstein touch monofilaments, motor performance captured via the 15 timed items of the Wolf Motor Function Test, stroke affected side. A highly accurate predictive classification was achieved (100% accuracy of EPNN based on available data), but facets of motor functioning alone were sufficient to predict outcome. Somatosensation, as quantified here, did not play a large role in determining the effectiveness of CI therapy.

Plasma cytokine levels are related to brain volumes in HIV-infected individuals.

HIV-infected individuals frequently exhibit brain dysfunction despite antiretroviral treatment. The neuropathological mechanisms underlying these abnormalities remain unclear, pointing to the importance of identifying biomarkers sensitive to brain dysfunction. We examined 74 medically stable HIV-infected individuals using T1-weighted MRI. Volumes of the cortical grey matter (GM), white matter (WM), caudate, putamen, globus pallidus, thalamus, hippocampus, amygdala, and ventricles were derived using automated parcellation. A panel of plasma cytokines was measured using multiplexed bead array immunoassay. A model selection algorithm was used to select the combination of clinical and cytokine markers that best predicted each brain volumetric measure in a series of linear regression models. Higher CD4 nadir, shorter HIV infection duration, and antiretroviral treatment were significantly related to higher volumes of the putamen, thalamus, hippocampus, and WM. Older age was related to lower volumes in most brain regions and higher ventricular volume. Higher IFN-γ, MCP-1, and TNF-α were related to higher volumes of the putamen, pallidum, amygdala, GM, and WM. Higher IL-1ß, IL-6, IL-16, IL-18, IP-10, MIP-1ß, and SDF-1α were related to lower volumes of the putamen, pallidum, thalamus, hippocampus, amygdala, GM, and WM; and higher ventricular volume. The current findings provide evidence linking smaller brain volumes to HIV disease history, antiretroviral treatment, and advanced age. Cytokine markers, especially IL-6 and IL-16, showed robust association with brain volumes even after accounting for other clinical variables, demonstrating their utility in examining the mechanisms of HIV-associated brain abnormalities.