Wearable Sensors to Monitor, Enable Feedback, and Measure Outcomes of Activity and Practice.

PURPOSE OF REVIEW: Measurements obtained during real-world activity by wearable motion sensors may contribute more naturalistic accounts of clinically meaningful changes in impairment, activity, and participation during neurologic rehabilitation, but obstacles persist. Here we review the basics of wearable sensors, the use of existing systems for neurological and rehabilitation applications and their limitations, and strategies for future use. RECENT FINDINGS: Commercial activity-recognition software and wearable motion sensors for community monitoring primarily calculate steps and sedentary time. Accuracy declines as walking speed slows below 0.8 m/s, less so if worn on the foot or ankle. Upper-extremity sensing is mostly limited to simple inertial activity counts. Research software and activity-recognition algorithms are beginning to provide ground truth about gait cycle variables and reveal purposeful arm actions. Increasingly, clinicians can incorporate inertial and other motion signals to monitor exercise, activities of daily living, and the practice of specific skills, as well as provide tailored feedback to encourage self-management of rehabilitation. Efforts are growing to create a compatible collection of clinically relevant sensor applications that capture the type, quantity, and quality of everyday activity and practice in known contexts. Such data would offer more ecologically sound measurement tools, while enabling clinicians to monitor and support remote physical therapies and behavioral modification when combined with telemedicine outreach.

Behavioral self-management strategies for practice and exercise should be included in neurologic rehabilitation trials and care.

PURPOSE OF REVIEW: Rehabilitation trials and postacute care to lessen impairments and disability after stroke, spinal cord injury, and traumatic brain injury almost never include training to promote long-term self-management of skills practice, strengthening and fitness. Without behavioral training to develop self-efficacy, clinical trials, and home-based therapy may fail to show robust results. RECENT FINDINGS: Behavioral theories about self-management and self-efficacy for physical activity have been successfully incorporated into interventions for chronic diseases, but rarely for neurologic rehabilitation. The elements of behavioral training include education about the effects of practice and exercise that are relevant to the person, goal setting, identification of possible barriers, problem solving, feedback about performance, tailored instruction, decision making, and ongoing personal or social support. Mobile health and telerehabilitation technologies offer new ways to remotely enable such training by monitoring activity from wearable wireless sensors and instrumented exercise devices to allow real-world feedback, goal setting, and instruction. SUMMARY: Motivation, sense of responsibility, and confidence to practice and exercise in the home can be trained to increase adherence to skills practice and exercise both during and after formal rehabilitation. To optimize motor learning and improve long-term outcomes, self-management training should be an explicit component of rehabilitation care and clinical trials.

Predictors and biomarkers of treatment gains in a clinical stroke trial targeting the lower extremity.

BACKGROUND AND PURPOSE: Behavioral measures are often used to distinguish subgroups of patients with stroke (eg, to predict treatment gains, stratify clinical trial enrollees, or select rehabilitation therapy). In studies of the upper extremity, measures of brain function using functional magnetic resonance imaging (fMRI) have also been found useful, but this approach has not been examined for the lower extremity. The current study hypothesized that an fMRI-based measure of cortical function would significantly improve prediction of treatment-induced lower extremity behavioral gains. Biomarkers of treatment gains were also explored. METHODS: Patients with hemiparesis 1 to 12 months after stroke were enrolled in a double-blind, placebo-controlled, randomized clinical trial of ropinirole+physical therapy versus placebo+physical therapy, results of which have previously been reported (NCT00221390).(15) Primary end point was change in gait velocity. Enrollees underwent baseline multimodal assessment that included 19 measures spanning 5 assessment categories (medical history, impairment, disability, brain injury, and brain function), and also underwent reassessment 3 weeks after end of therapy. RESULTS: In bivariate analysis, 8 baseline measures belonging to 4 categories (medical history, impairment, disability, and brain function) significantly predicted change in gait velocity. Prediction was strongest, however, using a multivariate model containing 2 measures (leg Fugl-Meyer score and fMRI activation volume within ipsilesional foot sensorimotor cortex). Increased activation volume within bilateral foot primary sensorimotor cortex correlated positively with treatment-induced leg motor gains. CONCLUSIONS: A multimodal model incorporating behavioral and fMRI measures best predicted treatment-induced changes in gait velocity in a clinical trial setting. Results also suggest potential use of fMRI measures as biomarkers of treatment gains.

Body-weight-supported treadmill rehabilitation after stroke.

BACKGROUND: Locomotor training, including the use of body-weight support in treadmill stepping, is a physical therapy intervention used to improve recovery of the ability to walk after stroke. The effectiveness and appropriate timing of this intervention have not been established. METHODS: We stratified 408 participants who had had a stroke 2 months earlier according to the extent of walking impairment--moderate (able to walk 0.4 to <0.8 m per second) or severe (able to walk <0.4 m per second)--and randomly assigned them to one of three training groups. One group received training on a treadmill with the use of body-weight support 2 months after the stroke had occurred (early locomotor training), the second group received this training 6 months after the stroke had occurred (late locomotor training), and the third group participated in an exercise program at home managed by a physical therapist 2 months after the stroke (home-exercise program). Each intervention included 36 sessions of 90 minutes each for 12 to 16 weeks. The primary outcome was the proportion of participants in each group who had an improvement in functional walking ability 1 year after the stroke. RESULTS: At 1 year, 52.0% of all participants had increased functional walking ability. No significant differences in improvement were found between early locomotor training and home exercise (adjusted odds ratio for the primary outcome, 0.83; 95% confidence interval [CI], 0.50 to 1.39) or between late locomotor training and home exercise (adjusted odds ratio, 1.19; 95% CI, 0.72 to 1.99). All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life. Neither the delay in initiating the late locomotor training nor the severity of the initial impairment affected the outcome at 1 year. Ten related serious adverse events were reported (occurring in 2.2% of participants undergoing early locomotor training, 3.5% of those undergoing late locomotor training, and 1.6% of those engaging in home exercise). As compared with the home-exercise group, each of the groups receiving locomotor training had a higher frequency of dizziness or faintness during treatment (P=0.008). Among patients with severe walking impairment, multiple falls were more common in the group receiving early locomotor training than in the other two groups (P=0.02). CONCLUSIONS: Locomotor training, including the use of body-weight support in stepping on a treadmill, was not shown to be superior to progressive exercise at home managed by a physical therapist. (Funded by the National Institute of Neurological Disorders and Stroke and the National Center for Medical Rehabilitation Research; LEAPS ClinicalTrials.gov number, NCT00243919.).

Wearable motion sensors to continuously measure real-world physical activities.

PURPOSE OF REVIEW: Rehabilitation for sensorimotor impairments aims to improve daily activities, walking, exercise, and motor skills. Monitoring of practice and measuring outcomes, however, is usually restricted to laboratory-based procedures and self-reports. Mobile health devices may reverse these confounders of daily care and research trials. RECENT FINDINGS: Wearable, wireless motion sensor data, analyzed by activity pattern-recognition algorithms, can describe the type, quantity, and quality of mobility-related activities in the community. Data transmission from the sensors to a cell phone and the Internet enable continuous monitoring. Remote access to laboratory quality data about walking speed, duration and distance, gait asymmetry and smoothness of movements, as well as cycling, exercise, and skills practice, opens new opportunities to engage patients in progressive, personalized therapies with feedback about the performance. Clinical trial designs will be able to include remote verification of the integrity of complex physical interventions and compliance with practice, as well as capture repeated, ecologically sound, ratio scale outcome measures. SUMMARY: Given the progressively falling cost of miniaturized wearable gyroscopes, accelerometers, and other physiologic sensors, as well as inexpensive data transmission, sensing systems may become as ubiquitous as cell phones for healthcare. Neurorehabilitation can develop these mobile health platforms for daily care and clinical trials to improve exercise and fitness, skills learning, and physical functioning.

New evidence for therapies in stroke rehabilitation.

Neurologic rehabilitation aims to reduce impairments and disabilities so that persons with serious stroke can return to participation in usual self-care and daily activities as independently as feasible. New strategies to enhance recovery draw from a growing understanding of how types of training, progressive task-related practice of skills, exercise for strengthening and fitness, neurostimulation, and drug and biological manipulations can induce adaptations at multiple levels of the nervous system. Recent clinical trials provide evidence for a range of new interventions to manage walking, reach and grasp, aphasia, visual field loss, and hemi-inattention.

Harnessing neuroplasticity for clinical applications.

Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.

Reliability and validity of bilateral ankle accelerometer algorithms for activity recognition and walking speed after stroke.

BACKGROUND AND PURPOSE: Outcome measures of mobility for large stroke trials are limited to timed walks for short distances in a laboratory, step counters and ordinal scales of disability and quality of life. Continuous monitoring and outcome measurements of the type and quantity of activity in the community would provide direct data about daily performance, including compliance with exercise and skills practice during routine care and clinical trials. METHODS: Twelve adults with impaired ambulation from hemiparetic stroke and 6 healthy controls wore triaxial accelerometers on their ankles. Walking speed for repeated outdoor walks was determined by machine-learning algorithms and compared to a stopwatch calculation of speed for distances not known to the algorithm. The reliability of recognizing walking, exercise, and cycling by the algorithms was compared to activity logs. RESULTS: A high correlation was found between stopwatch-measured outdoor walking speed and algorithm-calculated speed (Pearson coefficient, 0.98; P=0.001) and for repeated measures of algorithm-derived walking speed (P=0.01). Bouts of walking >5 steps, variations in walking speed, cycling, stair climbing, and leg exercises were correctly identified during a day in the community. Compared to healthy subjects, those with stroke were, as expected, more sedentary and slower, and their gait revealed high paretic-to-unaffected leg swing ratios. CONCLUSIONS: Test-retest reliability and concurrent and construct validity are high for activity pattern-recognition Bayesian algorithms developed from inertial sensors. This ratio scale data can provide real-world monitoring and outcome measurements of lower extremity activities and walking speed for stroke and rehabilitation studies.

The insidious impact of under-diagnosed proximal weakness induced by statins.

Introduction: This Perspective reassesses the consensus opinion that statin-associated muscle symptoms (SAMS) occur in <1% of users and associated myopathic proximal muscle weakness is even more rare.Areas covered: Of the over 180,000 participants in clinical trials and large registries of statin users, only a few studies have included a standard manual muscle test (MMT), dynamometry or a focused questionnaire to assess for proximal weakness and related disability in daily and recreational activities. Formal strength testing suggests, however, that weakness can be demonstrated in at least 10% of users.Expert opinion: Reporting inaccuracies about SAMS, confirmation bias among experts and physicians, absence of a standard questionnaire regarding the potential consequences of weakness on physical capacity, and the failure to routinely perform an objective assessment of strength may have led to under-diagnosis of statin-induced myopathy. A brief MMT before cholesterol-lowering agents are started and at follow-up visits, a 12-week withdrawal of the statin in the presence of new paresis without an alternative cause, and the exam finding that strength recovers off the statin are necessary to assess the incidence of drug-induced proximal weakness and inform alternative therapeutic strategies.

Randomized, placebo-controlled, double-blind study of ropinirole in chronic stroke.

BACKGROUND AND PURPOSE: Evidence suggests the potential to improve motor status in patients with stroke by modifying brain catecholaminergic tone. The current study hypothesized that increased dopaminergic tone via the dopamine agonist ropinirole, when combined with physiotherapy (PT), would significantly and safely increase gait velocity. METHODS: Patients with moderate motor deficits due to stroke 1 to 12 months prior were randomized (double blinded) to 9 weeks of immediate-release ropinirole or placebo, each with PT, and followed up for 3 additional weeks. Drug dose (0.25 to 4 mg once daily) was titrated weekly, as tolerated. The primary end point was gait velocity during the 12 weeks of study participation. RESULTS: Patients in the ropinirole+PT group averaged 2.4 mg/d by end of week 9, although the target dose was at least 3 mg/d. Ropinirole+PT was generally safe and well tolerated, including no drug-related serious adverse events. Across all 33 enrollees, significant gains were found over time for gait velocity and for most secondary end points. However, gains did not differ by treatment assignment. PT and occupational therapy were commonly prescribed outside of the trial, although the extent of these was not correlated with study outcomes. CONCLUSIONS: At doses achieved in this trial, increased dopaminergic tone via ropinirole+PT was generally well tolerated but did not show any improvement over and above the effects of PT alone.

Motor rehabilitation after stroke, traumatic brain, and spinal cord injury: common denominators within recent clinical trials.

PURPOSE OF REVIEW: Experimental studies and clinical trials that aim to improve motor function for use of the upper extremity and walking are traditionally separated by the category of neurological disease. This boundary may deter investigators from finding common denominators in the conceptual basis and deployment of rehabilitation interventions, especially across nonprogressive diseases in adults, such as stroke, brain trauma, and spinal cord injury. RECENT FINDINGS: The results of recent randomized clinical trials for walking by treadmill training and robotic devices and for the upper extremity by constraint-induced therapy, robotics, and brain stimulation suggest that more efficient strategies are needed to devise and prove the value of new therapies. SUMMARY: Investigators should consider working across disease platforms to develop and test the most optimal methods for training patients, the most practical trial designs, the best dose-response characteristics of interventions, the most meaningful outcome measures, and the likelihood of transfer of trained performance to real-world settings. Clinicians in the community may be more likely to adopt evidence-based practices drawn from positive trial results if these treatment strategies focus on key motor impairments and related disabilities, rather than on diseases.

Collaborative models for translational neuroscience and rehabilitation research.

Little formal research has been conducted on strategies to structure basic, preclinical, and clinical research to increase the likelihood of discovering efficacious interventions for patients with neurological diseases. How academic research is organized and funded by government agencies and foundations seems likely to affect the quality and rate of production of valued therapeutic agents. Few models for translational biomedical research, however, have been defined and no strategies have been compared. Given the narrow width of expertise and laboratory capacity of individual investigators, the complexity of identifying and manipulating mechanisms of disease components over time, and the demand for solutions from society, our continued reliance on funding therapeutic discovery through standalone investigators and projects seems counterproductive. Models are described for funding collaborations of basic and clinical scientists to work in iterative, adaptable, cross-disciplinary interactions around key progress-limiting questions. Problem-oriented collaborations require leadership, incentives, trust, ongoing assessment, and an efficient infrastructure that overcomes barriers. These models are as testable as the hypotheses that drive scientific research.

Progressive Staging of Pilot Studies to Improve Phase III Trials for Motor Interventions.

Based on the suboptimal research pathways that finally led to multicenter randomized clinical trials (MRCTs) of treadmill training with partial body weight support and of robotic assistive devices, strategically planned successive stages are proposed for pilot studies of novel rehabilitation interventions. Stage 1, consideration-of-concept studies, drawn from animal experiments, theories, and observations, delineate the experimental intervention in a small convenience sample of participants, so the results must be interpreted with caution. Stage 2, development-of-concept pilots, should optimize the components of the intervention, settle on most appropriate outcome measures, and examine dose-response effects. A well-designed study that reveals no efficacy should be published to counterweight the confirmation bias of positive trials. Stage 3, demonstration-of-concept pilots, can build out from what has been learned to test at least 15 participants in each arm, using random assignment and blinded outcome measures. A control group should receive an active practice intervention aimed at the same primary outcome. A third arm could receive a substantially larger dose of the experimental therapy or a combinational intervention. If only 1 site performed this trial, a different investigative group should aim to reproduce positive outcomes based on the optimal dose of motor training. Stage 3 studies ought to suggest an effect size of 0.4 or higher, so that approximately 50 participants in each arm will be the number required to test for efficacy in a stage 4, proof-of-concept MRCT. By developing a consensus around acceptable and necessary practices for each stage, similar to CONSORT recommendations for the publication of phase III clinical trials, better quality pilot studies may move quickly into better designed and more successful MRCTs of experimental interventions.

Provocative Walking Test of Strength for Diagnosis, Management, and Outcome Assessment of Symptomatic Lumbar Spinal Stenosis.

Background. Clinical care and randomized trials of rehabilitation or surgery for symptomatic lumbar spinal stenosis with neurogenic claudication (LSS) are complicated by the lack of standard criteria for diagnosis and outcome measurement. Objective. To evaluate whether manual muscle testing (MMT) can detect transient lower-extremity weakness provoked by walking in patients with likely LSS. Methods. A total of 19 patients with symptoms and MRI findings suggestive of LSS were tested for a decline in lower-extremity strength, using the British Medical Council scale of MMT, by comparing strength at rest to a change in strength within 60 s of completing a 400-foot walk. They were retested after reclining supine for another 2 minutes. This examination was repeated following decompressive lumbar surgery. Results. All patients developed bilateral weakness in the distribution of their LSS, but always including the hip extensors and knee flexors, when tested immediately after the provocative walking test. Most patients were not aware of weakness or change in gait during the walking task. They recovered to baseline strength after resting supine. The patients did not improve with physical therapy. When examined within 8 weeks after decompressive laminectomy, no one developed weakness during the 400-foot walk, and daily lower-extremity pain had resolved. Conclusions. A careful repetitive motor examination can detect transient paraparesis in patients with definite LSS. This finding supports the diagnosis and the functional severity of LSS while providing an objective outcome measurement for physical therapy and surgical interventions that goes beyond symptoms of pain.

DeepBehavior: A Deep Learning Toolbox for Automated Analysis of Animal and Human Behavior Imaging Data.

Detailed behavioral analysis is key to understanding the brain-behavior relationship. Here, we present deep learning-based methods for analysis of behavior imaging data in mice and humans. Specifically, we use three different convolutional neural network architectures and five different behavior tasks in mice and humans and provide detailed instructions for rapid implementation of these methods for the neuroscience community. We provide examples of three dimensional (3D) kinematic analysis in the food pellet reaching task in mice, three-chamber test in mice, social interaction test in freely moving mice with simultaneous miniscope calcium imaging, and 3D kinematic analysis of two upper extremity movements in humans (reaching and alternating pronation/supination). We demonstrate that the transfer learning approach accelerates the training of the network when using images from these types of behavior video recordings. We also provide code for post-processing of the data after initial analysis with deep learning. Our methods expand the repertoire of available tools using deep learning for behavior analysis by providing detailed instructions on implementation, applications in several behavior tests, and post-processing methods and annotated code for detailed behavior analysis. Moreover, our methods in human motor behavior can be used in the clinic to assess motor function during recovery after an injury such as stroke.

Reliable assessment of lower limb motor representations with fMRI: use of a novel MR compatible device for real-time monitoring of ankle, knee and hip torques.

This study describes the use of a novel magnetic resonance imaging (MRI) compatible system capable of measuring isometric ankle, knee and hip joint torques in real-time during functional MRI (fMRI) testing in healthy volunteers. The motor representations of three isometric torques--ankle dorsiflexion, ankle plantarflexion and knee extension--were studied at two time points. The reliability of motor performance and fMRI-derived measures of brain activity across sessions was examined. Reproducible motor performance was observed for each of the tasks; torques of the requested amplitude, assisted by visual feedback, were generated at the relevant joint with good accuracy, both within and across the two sessions. Significant blood oxygen level dependent (BOLD) signal increases were observed in the left primary sensorimotor cortex (SM1) in the paracentral lobule and in secondary motor areas for all tasks. Within these areas there was substantial overlap of the motor representations though differential activation was observed in SM1, with greater activation of inferior paracentral lobule during knee extension than for either ankle task. Also, BOLD signal decreases were observed bilaterally within SM1 in the hand knob region for all tasks. No major session-related effects were identified at the group level. High intraclass correlation coefficients were observed for t-values of voxels in cortical motor areas for each contraction type for individuals, suggesting that fMRI-derived activity across time points was reliable. These findings support the use of this apparatus in serial studies of lower limb function.