Ming Wu, Ph.D. - US grants

DESCRIPTION (provided by applicant): The goal of this proposed research is to improve the efficacy of body weight supported treadmill training (BWSTT) in people post-stroke using a novel robotic therapy that applies forces to the paralyzed leg during the swing phase of gait. Impaired mobility is an important factor in determining the degree of physical disability after stroke. While up to 80% of individuals with stroke may ultimately recover the ability to walk short distance, most of them do not achieve the locomotor capacity necessary for community ambulation. As a result, there is a desire to develop new techniques to enhance the therapeutic effect in this population. While statistically significant improvements in walking recovery with BWSTT have been shown, it remains unclear whether therapeutic effects of such training are maximized. In addition, a major limitation of BWSTT is the requirement of greater involvement of physical therapist. Robotic assisted BWSTT demonstrates effectiveness in reducing therapist labor in locomotor training but shows relatively limited functional gains for some patients. Our goal is therefore to enhance the efficacy of BWSTT by applying assistance as needed or resistance as tolerated to the paralyzed leg during treadmill training. Evidence from animal studies indicates that gait retraining is more effective with assistance as needed than with a fixed trajectory paradigm. Similarly, results from human arm study indicated that causing adaptation by using error-augmentation training might be an effective way to promote functional motor recovery for patients with stroke. We postulate that providing assistance as needed or resistance as tolerated load based on the motor performance of the patient will improve the training outcomes of BWSTT through enhanced patient effort that effectively engages adaptive sensorimotor processes. Accordingly, our specific aims are: Aim1. Demonstrate motor adaptation to applied loads in individuals post stroke. Specifically, we aim to assess the motor adaptation to a resistance/assistance load in individuals post stroke. The muscle activities and kinematics of the lower extremities will be recorded to quantify the motor adaptive effects of resistance/assistance loads. We expect that leg muscle activity and limb kinematics will adapt to the applied loads and show aftereffects when removed;Aim 2. Improve gait training paradigms using resistance as tolerated strategy. We aim to assess locomotor recovery using resistance as tolerated/assistance as needed strategy to control the load applied to the paralyzed leg during BWSTT. Gait kinematics and clinical measurements of impairment and walking function will be obtained at pre, post training, and at the follow up. Significant improvements are expected in the BWSTT combined with resistance, compared to the assistance training group. The results from this study will lead to innovative clinical therapies aimed at improving locomotor recovery in patients post stroke. We anticipate that this technique will be useful for improving gait in individuals post stroke through robotic-assisted BWSTT. PUBLIC HEALTH RELEVANCE: The purpose of the proposed research is to improve the efficacy of body weight supported treadmill training (BWSTT) in people post-stroke using a novel robotic therapy that applies controlled forces to the paralyzed leg during walking. The results from this study will lead to innovative clinical therapies aimed at improving locomotor recovery in patients post stroke. We anticipate that this technique will be useful for improving gait in individuals post stroke through robotic-assisted BWSTT.

DESCRIPTION (provided by applicant): The goal of this proposed study is to improve the efficacy of body weight supported treadmill training (BWSTT) in children with cerebral palsy (CP) using a novel robotic therapy that applies controlled forces to the leg during the swing phase of gait. CP is the most prevalent physical disability originating in childhood with an incidence of 2-3 per 1,000 live births. Reduced waking speed and endurance are two of the main functional problems. As a consequence, there is a desire to develop new techniques to improve walking function in children with CP. While BWSTT has been used to improve locomotor function in children with CP, it remains unclear whether therapeutic effects of such training are maximized and further evidence is needed to support BWSTT in pediatric practice. In addition, a major limitation of BWSTT is that it requires greater involvement of the physical therapist. Current robot assisted BWSTT demonstrates effectiveness in reducing therapist labor in locomotor training but shows limited functional gains in some patients. Our goal is therefore to improve the efficacy of BWSTT by applying controlled resistance load to the leg during treadmill training. Evidence from animal studies indicates that gait retraining is more effective with assistance as needed than with a fixed trajectory paradigm. Similarly, results from adults post stroke arm study suggested that causing adaptation by using error-augmentation training might be an effective way to promote functional motor recovery. We postulate that providing tolerated resistance load based on the motor performance of the children with CP will improve the training outcomes of BWSTT through enhanced patient effort that effectively engages adaptive sensorimotor processes. Accordingly, our specific aims are: Aim1. Demonstrate motor adaptation to applied loads in children with CP. Specifically, we aim to assess the motor adaptation to controlled resistance load in children with CP. The muscle activities and kinematics of the lower extremities will be recorded to quantify the motor adaptive effects of resistance loads. We expect that leg muscle activity and limb kinematics will adapt to applied loads and show aftereffects when removed. In addition, we will exam the carryover of the motor adaption associated with the resistance training from the treadmill to overground walking. Aim 2. Improve gait in children with CP using a resistance as tolerated strategy. We will assess the locomotor function improvement in children with CP following resistance load training. Specifically, gait speed, endurance, and clinical measurements of motor function will be obtained at pre, post training, and at the follow up. Significant improvements are expected in the BWSTT combined with resistance, compared to the assistance training group. The results from this study will lead to an innovative clinical therapy aimed at improving locomotor function in children with CP. We anticipate that this technique will be useful for improving gait in children with CP through robot-assisted BWSTT. PUBLIC HEALTH RELEVANCE: The purpose of the proposed research is to improve the efficacy of body weight supported treadmill training (BWSTT) in children with cerebral palsy (CP) using a novel robotic therapy that applies controlled force to the leg during treadmill walking. The results from this study will lead to innovative clinical therapies aimed at improving locomotor function in children with CP. We anticipate that this technique will be extremely useful for improving walking function in children with CP through robot-assisted BWSTT.

? DESCRIPTION (provided by applicant): The objective of the proposed study is to test whether the efficacy of locomotor training will be improved through the application of constraint induced forced use of the affected leg during locomotor training. We will also identify the neural mechanisms underlying the improvements in locomotor function after training in individuals post-stroke. Locomotor training using a treadmill is a promising technique that provides a safe and convenient environment for improving walking capability in individuals post-stroke. While the improvements in walking function after treadmill training are statistically significant, the functional gains are relatively small for many patients. One of primary reasons of the less effectiveness of treadmill training may be due to the compensatory motor strategies employed by patients during locomotor training, i.e., patients with hemiparesis often rely more on the unaffected leg for performing bipedal walking during treadmill training. Repetitive practice in thi manner may actually lead to reinforcing the compensatory motor strategies, which results in limited improvement in motor control of the affected leg, resulting in limited functional gains aftr training, which suggests a need of developing new training paradigms in order to maximize functional gains. Constraint induced movement therapy (CIMT) has been utilized to improve motor function of the affected arm in individuals post-stroke through forced use of their affected arm and by restricting movements of the unaffected arm. Previous studies have shown promising improvements in motor skills and in the use of the affected arm and hand in daily activities after CIMT. However, such interventions have not been effectively applied to lower limb training in individuals post-stroke due to the strong coupling between the two legs during bipedal gait and the risk of falling. Thus, we propose to develop a novel strategy to test CIMT for lower limb training in individuals post-stroke. Specifically, we will apply a controlled force to te pelvis and/or unaffected leg, which will serve to overcome the compensatory motor strategies employed by patients, and induce forced use of the affected leg during locomotor training. Our central hypothesis is that the efficacy of locomotor training will be improved by applying a controlled assistance force to the pelvis and/or resistance force to the unaffected leg to reduce the compensatory movements of the unaffected leg, and induce forced use of the affected leg of individuals post-stroke during training. Results from this study will lead to an innovative clinica therapy paradigm aimed at improving locomotor function in individuals post-stroke. We expect that this study will demonstrate the feasibility of a novel robotic training strategy, i.e., applyig a controlled force to the pelvis and/or the unaffected leg to induce forced use of the affected leg during locomotor training. The successful completion of the proposed study will have a high potential to make a significant impact on the field of locomotor rehabilitation in individuals post stroke through the application of a novel treatment paradigm. This paradigm may also be applied to other patient populations, such as patients with hemiparetic cerebral palsy.

? DESCRIPTION (provided by applicant): A major goal of patients with spinal cord injury (SCI) is to regain walking ability, as limitations in mobility can affect most activities of daily living In addition, patients with SCI may experience a higher incidence of falls due to impaired balance and gait. Further, the consequence of falls in patients with SCI is much greater than that for healthy older adults. Dynamic balance control plays a crucial role during locomotion in human SCI. Thus, improved dynamic balance may facilitate locomotion in this population. Current balance training paradigms can be effective in improving balance during standing, but are less effective in improving dynamic balance during locomotion in humans with SCI. Thus, there is a need to develop new paradigms for improving dynamic balance and locomotor function in patients with SCI. The goal of this proposed research is to explore motor adaptation to a mediolateral force applied at the pelvis during walking in humans with SCI and test whether pelvis perturbation training paired with transcutaneous spinal direct current stimulation (tsDCS) will be effective in improving dynamic balance and locomotor function in humans with SCI. We postulate that providing a perturbation force to the pelvis during treadmill training will increase the activation of muscles used for maintaining lateral balance while walking. Further, repeated activation of particular sensorimotor pathways (through repeated exposure to a pelvic perturbation force) may reinforce circuits and synapses used for lateral balance control through a use-dependent neural-plasticity mechanism. However, the excitability of spinal cord neural circuitries may be depressed due to the reduced descending drive signals from the upper level control center after SCI, which may reduce the efficacy of neural plastic changes achieved following rehabilitation. The excitability of neural pathways is crucial for neural reorganization achieved following rehabilitation. Recently studies indicate that tsDCS may modulate the excitability of neural circuitries of the spinal cord in patients with SCI. Thus, we postulate that controlled pelvis perturbation training paired with tsDCS will be more effective than that paired with a sham in improving dynamic balance and locomotor function in humans with SCI. Results obtained from this study will lead to an innovative clinical therapy aimed at improving balance and walking function in humans with SCI. Improvements in balance and walking function may allow for increased participation in community-based ambulation and activities, and significantly improve quality of life in humans with SCI. The improvements of scientific knowledge obtained from this study may be extended to other SCI patients with lower walking function, or other patient populations, such as individuals post-stroke.

Abstract Many children with cerebral palsy (CP) show impairments in trunk postural control, which significantly impact their walking capacity and daily activities. For instance, children with severe CP, who have difficulties sitting independently, show poor directional specificity, with antagonists activating before agonists, which is distinct from typically developed children. Compared to typically developed peers, children with CP have a large range of motion for pelvis tilt, thorax, head, and kyphosis and lordosis during gait, even for some high functioning children with CP. While the significance of trunk motor control dysfunction in children with CP has been recognized, effective interventions for this core deficit are still lacking. Children with CP often receive or participate in a wide range of passive and active interventions aimed to improve postural control, but results have shown that current intervention approaches are not often effective in improving postural control in children with CP. For instance, hippotherapy, an intervention strategy that applies rhythmical force perturbations to the pelvis during sitting astride using horseback movement, has been used for improving balance and gait in children with CP for decades. However, while some studies showed improvements in balance and motor function in children with CP after hippotherapy, other studies indicated a mixed result regarding the effect of hippotherapy on Gross Motor Function Measure scores in children with CP. Thus, there is a critical need to improve the efficacy of current interventions for improving trunk postural control and gait in children with CP, which requires a thorough examination of the underlying neuromuscular mechanisms of the interventions. Our long-term goal is to develop rational-based intervention strategies to improve trunk postural control and gait in children with CP. The overall objective of this study is to examine the neuromuscular mechanisms of the trunk muscles to a force perturbation applied to the pelvis during sitting astride, and determine whether repeated exposure to pelvic perturbations during sitting astride using a robotic system will be effective in improving trunk postural control and gait in children with CP. Our central hypothesis is that repetitive activation of specific sensorimotor pathways through applying targeted force perturbations will improve postural control in children with CP, which may be due to the reinforcement in circuits and synapses used for trunk postural control through a use-dependent neuroplasticity mechanism. The rationale for the proposed study is that an understanding of the neuromuscular mechanisms of trunk muscle control in children with CP and determination of the therapeutic effect of targeted force perturbation are likely to provide a strong scientific foundation whereby new force perturbation based intervention strategies can be developed to improve postural control and gait in children with CP. The results from this study may be used to develop innovative clinical therapies aimed at improving trunk postural control and walking function in children with CP.