A crossover pilot study evaluating the functional outcomes of two different types of robotic movement training in chronic stroke survivors using the arm exoskeleton BONES.

BACKGROUND: To date, the limited degrees of freedom (DOF) of most robotic training devices hinders them from providing functional training following stroke. We developed a 6-DOF exoskeleton ("BONES") that allows movement of the upper limb to assist in rehabilitation. The objectives of this pilot study were to evaluate the impact of training with BONES on function of the affected upper limb, and to assess whether multijoint functional robotic training would translate into greater gains in arm function than single joint robotic training also conducted with BONES. METHODS: Twenty subjects with mild to moderate chronic stroke participated in this crossover study. Each subject experienced multijoint functional training and single joint training three sessions per week, for four weeks, with the order of presentation randomized. The primary outcome measure was the change in Box and Block Test (BBT). The secondary outcome measures were the changes in Fugl-Meyer Arm Motor Scale (FMA), Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and quantitative measures of strength and speed of reaching. These measures were assessed at baseline, after each training period, and at a 3-month follow-up evaluation session. RESULTS: Training with the robotic exoskeleton resulted in significant improvements in the BBT, FMA, WMFT, MAL, shoulder and elbow strength, and reaching speed (p < 0.05); these improvements were sustained at the 3 month follow-up. When comparing the effect of type of training on the gains obtained, no significant difference was noted between multijoint functional and single joint robotic training programs. However, for the BBT, WMFT and MAL, inequality of carryover effects were noted; subsequent analysis on the change in score between the baseline and first period of training again revealed no difference in the gains obtained between the types of training. CONCLUSIONS: Training with the 6 DOF arm exoskeleton improved motor function after chronic stroke, challenging the idea that robotic therapy is only useful for impairment reduction. The pilot results presented here also suggest that multijoint functional robotic training is not decisively superior to single joint robotic training. This challenges the idea that functionally-oriented games during training is a key element for improving behavioral outcomes. TRIAL REGISTRATION: NCT01050231.

Transcription factors in the pathogenesis of pulmonary arterial hypertension-Current knowledge and therapeutic potential.

Pulmonary arterial hypertension (PAH) is a disease characterized by elevated pulmonary vascular resistance and pulmonary artery pressure. Mortality remains high in severe cases despite significant advances in management and pharmacotherapy. Since currently approved PAH therapies are unable to significantly reverse pathological vessel remodeling, novel disease-modifying, targeted therapeutics are needed. Pathogenetically, PAH is characterized by vessel wall cell dysfunction with consecutive remodeling of the pulmonary vasculature and the right heart. Transcription factors (TFs) regulate the process of transcribing DNA into RNA and, in the pulmonary circulation, control the response of pulmonary vascular cells to macro- and microenvironmental stimuli. Often, TFs form complex protein interaction networks with other TFs or co-factors to allow for fine-tuning of gene expression. Therefore, identification of the underlying molecular mechanisms of TF (dys-)function is essential to develop tailored modulation strategies in PAH. This current review provides a compendium-style overview of TFs and TF complexes associated with PAH pathogenesis and highlights their potential as targets for vasculoregenerative or reverse remodeling therapies.

Robot-assisted rehabilitation of hand function.

PURPOSE OF REVIEW: Initial work on robot-assisted neurorehabilitation for the upper extremity aimed primarily at training, reaching movements with the proximal sections of the upper extremity. However, recent years have seen a surge in devices dedicated to hand function. This review describes the state of the art and the promises of this novel therapeutic approach. RECENT FINDINGS: Numerous robotic devices for hand function with various levels of complexity and functionality have been developed over the last 10 years. These devices range from simple mechanisms that support single joint movements to mechanisms with as many as 18 degrees-of-freedom (DOF) that can support multijoint movements at the wrist and fingers. The results from clinical studies carried out with eight out of 30 reported devices indicate that robot-assisted hand rehabilitation reduces motor impairments of the affected hand and the arm, and improves the functional use of the affected hand. SUMMARY: The current evidence in support of the robot-assisted hand rehabilitation is preliminary but very promising, and provides a strong rationale for more systematic investigations in the future.

Minimizing endpoint variability through reinforcement learning during reaching movements involving shoulder, elbow and wrist.

Reaching movements are comprised of the coordinated action across multiple joints. The human skeleton is redundant for this task because different joint configurations can lead to the same endpoint in space. How do people learn to use combinations of joints that maximize success in goal-directed motor tasks? To answer this question, we used a 3-degree-of-freedom manipulandum to measure shoulder, elbow and wrist joint movements during reaching in a plane. We tested whether a shift in the relative contribution of the wrist and elbow joints to a reaching movement could be learned by an implicit reinforcement regime. Unknown to the participants, we decreased the task success for certain joint configurations (wrist flexion or extension, respectively) by adding random variability to the endpoint feedback. In return, the opposite wrist postures were rewarded in the two experimental groups (flexion and extension group). We found that the joint configuration slowly shifted towards movements that provided more control over the endpoint and hence higher task success. While the overall learning was significant, only the group that was guided to extend the wrist joint more during the movement showed substantial learning. Importantly, all changes in movement pattern occurred independent of conscious awareness of the experimental manipulation. These findings suggest that the motor system is generally sensitive to its output variability and can optimize joint-space solutions that minimize task-relevant output variability. We discuss biomechanical biases (e.g. joint's range of movement) that could impose hurdles to the learning process.

SITAR: a system for independent task-oriented assessment and rehabilitation.

INTRODUCTION: Over recent years, task-oriented training has emerged as a dominant approach in neurorehabilitation. This article presents a novel, sensor-based system for independent task-oriented assessment and rehabilitation (SITAR) of the upper limb. METHODS: The SITAR is an ecosystem of interactive devices including a touch and force-sensitive tabletop and a set of intelligent objects enabling functional interaction. In contrast to most existing sensor-based systems, SITAR provides natural training of visuomotor coordination through collocated visual and haptic workspaces alongside multimodal feedback, facilitating learning and its transfer to real tasks. We illustrate the possibilities offered by the SITAR for sensorimotor assessment and therapy through pilot assessment and usability studies. RESULTS: The pilot data from the assessment study demonstrates how the system can be used to assess different aspects of upper limb reaching, pick-and-place and sensory tactile resolution tasks. The pilot usability study indicates that patients are able to train arm-reaching movements independently using the SITAR with minimal involvement of the therapist and that they were motivated to pursue the SITAR-based therapy. CONCLUSION: SITAR is a versatile, non-robotic tool that can be used to implement a range of therapeutic exercises and assessments for different types of patients, which is particularly well-suited for task-oriented training.

3DOM: a 3 degree of freedom manipulandum to investigate redundant motor control.

This paper presents a novel robotic interface to investigate the neuromechanical control of redundant planar arm movements. A unique aspect of this device is the third axis by which the wrist, and hence the pose of the arm can be fully constrained. The topology is based on a 5R, closed loop pantograph, with a decoupled wrist flexion/extension cable actuated mechanism. The design and characterization (in terms of range of motion, impedance, friction and dynamics) are described in this paper. This device is lightweight, safe and has high force capabilities and low impedance. Simple experiments illustrate the advantages of this device for the investigation of redundant motor control in humans.

H-Man: a planar, H-shape cabled differential robotic manipulandum for experiments on human motor control.

In the last decades more robotic manipulanda have been employed to investigate the effect of haptic environments on motor learning and rehabilitation. However, implementing complex haptic renderings can be challenging from technological and control perspectives. We propose a novel robot (H-Man) characterized by a mechanical design based on cabled differential transmission providing advantages over current robotic technology. The H-Man transmission translates to extremely simplified kinematics and homogenous dynamic properties, offering the possibility to generate haptic channels by passively blocking the mechanics, and eliminating stability concerns. We report results of experiments characterizing the performance of the device (haptic bandwidth, Z-width, and perceived impedance). We also present the results of a study investigating the influence of haptic channel compliance on motor learning in healthy individuals, which highlights the effects of channel compliance in enhancing proprioceptive information. The generation of haptic channels to study motor redundancy is not easy for actual robots because of the needs of powerful actuation and complex real-time control implementation. The mechanical design of H-Man affords the possibility to promptly create haptic channels by mechanical stoppers (on one of the motors) without compromising the superior backdriveability and high isotropic manipulability. This paper presents a novel robotic device for motor control studies and robotic rehabilitation. The hardware was designed with specific emphasis on the mechanics that result in a system that is easy to control, homogeneous, and is intrinsically safe for use.

Corticospinal excitability as a predictor of functional gains at the affected upper limb following robotic training in chronic stroke survivors.

BACKGROUND: Robotic training can help improve function of a paretic limb following a stroke, but individuals respond differently to the training. A predictor of functional gains might improve the ability to select those individuals more likely to benefit from robot-based therapy. Studies evaluating predictors of functional improvement after a robotic training are scarce. One study has found that white matter tract integrity predicts functional gains following a robotic training of the hand and wrist. Objective. To determine the predictive ability of behavioral and brain measures in order to improve selection of individuals for robotic training. METHODS: Twenty subjects with chronic stroke participated in an 8-week course of robotic exoskeletal training for the arm. Before training, a clinical evaluation, functional magnetic resonance imaging (fMRI), diffusion tensor imaging, and transcranial magnetic stimulation (TMS) were each measured as predictors. Final functional gain was defined as change in the Box and Block Test (BBT). Measures significant in bivariate analysis were fed into a multivariate linear regression model. RESULTS: Training was associated with an average gain of 6 ± 5 blocks on the BBT (P < .0001). Bivariate analysis revealed that lower baseline motor-evoked potential (MEP) amplitude on TMS, and lower laterality M1 index on fMRI each significantly correlated with greater BBT change. In the multivariate linear regression analysis, baseline MEP magnitude was the only measure that remained significant. CONCLUSION: Subjects with lower baseline MEP magnitude benefited the most from robotic training of the affected arm. These subjects might have reserve remaining for the training to boost corticospinal excitability, translating into functional gains.

Breaking it down is better: haptic decomposition of complex movements aids in robot-assisted motor learning.

Training with haptic guidance has been proposed as a technique for learning complex movements in rehabilitation and sports, but it is unclear how to best deliver guidance-based training. Here, we hypothesized that breaking down a complex movement, similar to a tennis backhand, into simpler parts and then using haptic feedback from a robotic exoskeleton would help the motor system learn the movement. We also examined how the particular form of the decomposition affected learning. Three groups of unimpaired participants trained with the target arm movement broken down in three ways: 1) elbow flexion/extension and the unified shoulder motion independently ("anatomical" decomposition), 2) three component shoulder motions in Euler coordinates and elbow flexion/extension ("Euler" decomposition), or 3) the motion of the tip of the elbow and motion of the hand with respect to the elbow, independently ("visual" decomposition). A control group practiced the same number of movements, but experienced the target motion only, achieving eight times more direct practice with this motion. Despite less experience with the target motion, part training was better, but only when the arm trajectory was decomposed into anatomical components. Varying robotic movement training to include practice of simpler, anatomically-isolated motions may enhance its efficacy.

Supinator Extender (SUE): a pneumatically actuated robot for forearm/wrist rehabilitation after stroke.

The robot described in this paper, SUE (Supinator Extender), adds forearm/wrist rehabilitation functionality to the UCI BONES exoskeleton robot and to the ArmeoSpring rehabilitation device. SUE is a 2-DOF serial chain that can measure and assist forearm supination-pronation and wrist flexion-extension. The large power to weight ratio of pneumatic actuators allows SUE to achieve the forces needed for rehabilitation therapy while remaining lightweight enough to be carried by BONES and ArmeoSpring. Each degree of freedom has a range of 90 degrees, and a nominal torque of 2 ft-lbs. The cylinders are mounted away from the patient's body on the lateral aspect of the arm. This is to prevent the danger of a collision and maximize the workspace of the arm robot. The rotation axis used for supination-pronation is a small bearing just below the subject's wrist. The flexion-extension motion is actuated by a cantilevered pneumatic cylinder, which allows the palm of the hand to remain open. Data are presented that demonstrate the ability of SUE to measure and cancel forearm/wrist passive tone, thereby extending the active range of motion for people with stroke.