Safety and Feasibility of a First-Person View, Full-Body Interaction Game for Telerehabilitation Post-Stroke

This study explored the feasibility and safety of pairing the Microsoft Kinect® sensor with the Oculus Rift® Head Mounted Display (HMD) as a telerehabilitation technology platform for persons post-stroke. To test initial safety, fourteen participants without disabilities (age 30 ± 8.8 years) engaged in a game-based task using the Microsoft Kinect® with a first-person view using the Oculus Rift®. These tasks were repeated for five participants post-stroke (age 56 ± 3.0 years). No significant adverse events occurred in either study population. When using the Oculus Rift® HMD, three participants without disabilities reported dizziness and nausea. All of the participants post-stroke required hands-on assistance for balance and fall prevention. The intensive nature of physical support necessary for this type of interaction limits the application as a telerehabilitation intervention.  Given the increasing availability of HMDs for commercial use, it is crucial that the safety of immersive games and technologies for telerehabilitation is fully explored

Reliability of computerized eye-tracking reaction time tests in non-athletes, athletes, and individuals with traumatic brain injury

Background: Eye tracking technologies and methodologies have advanced significantly in recent years. Specifically, the use of eye tracking to quantitatively measure oculomotor and psychophysiological constructs is gaining momentum. Reaction time has been measured in a number of different ways from a simple response to a stimulus to more challenging choice or discrimination responses to stimuli. Traditionally, reaction time is measured from the beginning of a stimulus event to a response event and includes both visual and motor response times. Eye tracking technology can provide a more discrete measurement of reaction time to include visual components such as visual latencies and visual speed, and can identify if the person was looking at the target area when a stimulus is presented. The aim of this paper was to examine the reliability of the simple reaction time, choice reaction time, and discriminate reaction time tests measured using eye tracking technology. Additionally, we sought to establish performance norms and examine gender differences in reaction time in the general population. A final objective was to conduct a preliminary comparison of reaction time measures across different populations including non-athletes, athletes, and individuals that had sustained a traumatic brain injury. Methods: A sample of 125 participants were recruited to undertake test-retest reliability, analysed using Cronbach’s alpha and intraclass correlation coefficients. A different data set of 1893 individuals, including athletes (n = 635), non-athletes (n = 627) and people with traumatic brain injury (n = 631) were compared using MANOVA to explore group differences in reaction time. Results: Results demonstrated that overall, the tests had good test-retest reliability. No significant differences were found for gender. Significant differences were found between groups with athletes performing best overall. Reaction times of people with traumatic brain injury were overall much more variable, showing very large standard deviations, than those of the non-athletes and athletes. Conclusions: Future research should consider the accuracy of eye movements and various demographic variables within groups

Virtual reality for stroke rehabilitation (Review)

Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. This review is made available in accordance with Cochrane Database of Systematic Review's repositories policyBackground Virtual reality and interactive video gaming have emerged as recent treatment approaches in stroke rehabilitation with commercial gaming consoles in particular, being rapidly adopted in clinical settings. This is an update of a Cochrane Review published first in 2011 and then again in 2015. Objectives Primary objective: to determine the efficacy of virtual reality compared with an alternative intervention or no intervention on upper limb function and activity. Secondary objectives: to determine the efficacy of virtual reality compared with an alternative intervention or no intervention on: gait and balance, global motor function, cognitive function, activity limitation, participation restriction, quality of life, and adverse events. Search methods We searched the Cochrane Stroke Group Trials Register (April 2017), CENTRAL, MEDLINE, Embase, and seven additional databases. We also searched trials registries and reference lists. Selection criteria Randomised and quasi‐randomised trials of virtual reality ("an advanced form of human‐computer interface that allows the user to 'interact' with and become 'immersed' in a computer‐generated environment in a naturalistic fashion") in adults after stroke. The primary outcome of interest was upper limb function and activity. Secondary outcomes included gait and balance and global motor function. Data collection and analysis Two review authors independently selected trials based on pre‐defined inclusion criteria, extracted data, and assessed risk of bias. A third review author moderated disagreements when required. The review authors contacted investigators to obtain missing information. Main results We included 72 trials that involved 2470 participants. This review includes 35 new studies in addition to the studies included in the previous version of this review. Study sample sizes were generally small and interventions varied in terms of both the goals of treatment and the virtual reality devices used. The risk of bias present in many studies was unclear due to poor reporting. Thus, while there are a large number of randomised controlled trials, the evidence remains mostly low quality when rated using the GRADE system. Control groups usually received no intervention or therapy based on a standard‐care approach. Primary outcome: results were not statistically significant for upper limb function (standardised mean difference (SMD) 0.07, 95% confidence intervals (CI) ‐0.05 to 0.20, 22 studies, 1038 participants, low‐quality evidence) when comparing virtual reality to conventional therapy. However, when virtual reality was used in addition to usual care (providing a higher dose of therapy for those in the intervention group) there was a statistically significant difference between groups (SMD 0.49, 0.21 to 0.77, 10 studies, 210 participants, low‐quality evidence). Secondary outcomes: when compared to conventional therapy approaches there were no statistically significant effects for gait speed or balance. Results were statistically significant for the activities of daily living (ADL) outcome (SMD 0.25, 95% CI 0.06 to 0.43, 10 studies, 466 participants, moderate‐quality evidence); however, we were unable to pool results for cognitive function, participation restriction, or quality of life. Twenty‐three studies reported that they monitored for adverse events; across these studies there were few adverse events and those reported were relatively mild. Authors' conclusions We found evidence that the use of virtual reality and interactive video gaming was not more beneficial than conventional therapy approaches in improving upper limb function. Virtual reality may be beneficial in improving upper limb function and activities of daily living function when used as an adjunct to usual care (to increase overall therapy time). There was insufficient evidence to reach conclusions about the effect of virtual reality and interactive video gaming on gait speed, balance, participation, or quality of life. This review found that time since onset of stroke, severity of impairment, and the type of device (commercial or customised) were not strong influencers of outcome. There was a trend suggesting that higher dose (more than 15 hours of total intervention) was preferable as were customised virtual reality programs; however, these findings were not statistically significant

Agile development of a virtual reality cognitive assessment

In recent years user-centered design, participatory design and agile development have seen much popularity in the field of software development. More specifically, applying these methods to user groups with cognitive and motor disabilities has been the topic of numerous publications. However, neuropsychological assessment and training require special consideration to include therapists and brain-injured patients into the development cycle. Application goals, development tools and communication between all stakeholders are interdependent and outlined in a framework that promotes elements of agile development. The framework is introduced by example of a virtual reality cognitive assessment for patients with traumatic brain injuries. The assessment has seen a total of 20 iterations over the course of nine months including changes in task content, task difficulty, user interaction and data collection. The framework and development of the cognitive assessment are discussed.Peer Reviewe

Vgf is a novel biomarker associated with muscle weakness in amyotrophic lateral sclerosis (ALS), with a potential role in disease pathogenesis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Previous proteomic evidence revealed that the content of certain peptide fragments including Vgf-derived peptide aa 398-411 (Vgf398-411) of the precursor Vgf protein in the cerebral spinal fluid (CSF) correctly identified patients with ALS from normal and disease controls. Using quantitative ELISA immunoassay we found that the CSF levels of Vgf decreases with muscle weakness in patients with ALS. In SOD1 G93A transgenic mice, loss of full-length Vgf content in CSF, serum and in SMI-32 immunopositive spinal cord motor neurons is noted in asymptomatic animals (approximately 75 days old) and continues to show a progressive decline as animals weaken. In vitro studies show that viral-mediated exogenous Vgf expression in primary mixed spinal cord neuron cultures attenuates excitotoxic injury. Thus, while Vgf may be a reliable biomarker of progression of muscle weakness in patients with ALS, restoration of Vgf expression in spinal cord motor neurons may therapeutically rescue spinal cord motorneurons against excitotoxic injury

Exploration of pathomechanisms triggered by a single-nucleotide polymorphism in titin\u27s I-band: the cardiomyopathy-linked mutation T2580I

Missense single-nucleotide polymorphisms (mSNPs) in titin are emerging as a main causative factor of heart failure. However, distinguishing between benign and disease-causing mSNPs is a substantial challenge. Here, we research the question of whether a single mSNP in a generic domain of titin can affect heart function as a whole and, if so, how. For this, we studied the mSNP T2850I, seemingly linked to arrhythmogenic right ventricular cardiomyopathy (ARVC). We used structural biology, computational simulations and transgenic muscle in vivo methods to track the effect of the mutation from the molecular to the organismal level. The data show that the T2850I exchange is compatible with the domain three-dimensional fold, but that it strongly destabilizes it. Further, it induces a change in the conformational dynamics of the titin chain that alters its reactivity, causing the formation of aberrant interactions in the sarcomere. Echocardiography of knock-in mice indicated a mild diastolic dysfunction arising from increased myocardial stiffness. In conclusion, our data provide evidence that single mSNPs in titin\u27s I-band can alter overall muscle behaviour. Our suggested mechanisms of disease are the development of non-native sarcomeric interactions and titin instability leading to a reduced I-band compliance. However, understanding the T2850I-induced ARVC pathology mechanistically remains a complex problem and will require a deeper understanding of the sarcomeric context of the titin region affected

Reconstructing CNV genotypes using segregation analysis: combining pedigree information with CNV assay

<p>Abstract</p> <p>Background</p> <p>Repeated blocks of genome sequence have been shown to be associated with genetic diversity and disease risk in humans, and with phenotypic diversity in model organisms and domestic animals. Reliable tests are desirable to determine whether individuals are carriers of copy number variants associated with disease risk in humans and livestock, or associated with economically important traits in livestock. In some cases, copy number variants affect the phenotype through a dosage effect but in other cases, allele combinations have non-additive effects. In the latter cases, it has been difficult to develop tests because assays typically return an estimate of the sum of the copy number counts on the maternally and paternally inherited chromosome segments, and this sum does not uniquely determine the allele configuration. In this study, we show that there is an old solution to this new problem: segregation analysis, which has been used for many years to infer alleles in pedigreed populations.</p> <p>Methods</p> <p>Segregation analysis was used to estimate copy number alleles from assay data on simulated half-sib sheep populations. Copy number variation at the Agouti locus, known to be responsible for the recessive self-colour black phenotype, was used as a model for the simulation and an appropriate penetrance function was derived. The precision with which carriers and non-carriers of the undesirable single copy allele could be identified, was used to evaluate the method for various family sizes, assay strategies and assay accuracies.</p> <p>Results</p> <p>Using relationship data and segregation analysis, the probabilities of carrying the copy number alleles responsible for black or white fleece were estimated with much greater precision than by analyzing assay results for animals individually. The proportion of lambs correctly identified as non-carriers of the undesirable allele increased from 7% when the lambs were analysed alone to 80% when the lambs were analysed in half-sib families.</p> <p>Conclusions</p> <p>When a quantitative assay is used to estimate copy number alleles, segregation analysis of related individuals can greatly improve the precision of the estimates. Existing software for segregation analysis would require little if any change to accommodate the penetrance function for copy number assay data.</p