Darcy S. Reisman, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): The goal of the proposed research is to understand the capacity of persons with post-stroke hemiparesis to adapt locomotor interlimb coordination and the influence of this on gait symmetry. Utilizing this knowledge, the applicant's long-term research goal is to develop scientifically-based therapies to advance the physical rehabilitation and recovery of locomotion in persons following a stroke. A five-year research and training plan has been developed to meet these goals. This plan consists of training in the neural mechanisms of locomotion, motor adaptations in persons with neurological damage, gait measurement and analysis and the design and implementation of randomized clinical trials in rehabilitation. This plan will be implemented under the mentorship of the primary mentor, an expert in motor adaptation in persons with neurological damage and the cosponsor, an expert in the analysis of walking in persons with gait dysfunction and in the design and implementation of clinical trials in rehabilitation. Training will consist of structured readings, attendance at course lectures and seminars, structured laboratory experiences and presentation at academic meetings. With complete support from the candidate's department chair, the candidate will have access to two fully equipped laboratories capable of measuring 3-dimensional human movement and force production. The proposed research will test the general hypothesis that persons with post-stroke hemiparesis are able to adapt their locomotor patterns following walking on a split-belt treadmill, where each leg is moved at a different speed. It is hypothesized that the adapted pattern of interlimb coordination following split-belt treadmill locomotion may be used to improve gait symmetry and function in persons post-stroke. Specific aims will test: 1) the capacity of persons with post-stroke hemiparesis to adapt interlimb coordination, 2) the generalization of adapted patterns to overground locomotion and, 3) the feasibility of using split-belt treadmill training to improve gait symmetry in persons post-stroke. Relevance: Of the 700,000 persons affected by stroke each year, 50% will continue to demonstrate long term walking dysfunction, some caused by poor coordination between the legs. This research investigates the potential of a novel type of treadmill walking to influence coordination between the legs in persons who have sustained a stroke. [unreadable] [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Stroke is the leading cause of disability in the US. This disability is a consequence of, and a risk factor for, physical inactivity and stroke survivor, as a group, are extremely inactive. Most studies find that the average chronic stroke survivor is more inactive than even the most sedentary adults. Lack of physical activity has serious consequences in persons with stroke, including an increased risk of a second stroke, developing other diseases (i.e. diabetes) and mortality. The potential consequences of inactivity are even more alarming considering that inactivity gets worse over the first year after stroke. Therefore, left untreated, physical inactivity may be one of the most serious and costly sequela of stroke. Despite the severe consequences of inactivity after stroke, very little attention has been paid to whether activity is influenced by rehabilitation interventions for chronic stroke survivors. Nevertheless, one intervention that appears to hold promise for improving activity in chronic stroke survivors is fast treadmill training. However, even with the improvements observed after this intervention, the physical activity of the participants was still well below recommended levels. It is therefore imperative that interventions are developed to improve real-world physical activity in those with chronic stroke. In other populations, step activity monitorin programs have been shown to be extremely effective for increasing daily walking activity; however, their effectiveness has never been tested in chronic stroke survivors. The primary aim of this proposal is to test whether adding a step activity monitoring program to fast treadmill training can improve walking activity in chronic stroke survivors beyond improvements with fast treadmill training alone. The secondary aims will test whether this intervention also impacts walking speed, endurance and the energy cost of walking, all of which are known to be related to walking activity after stroke and are important measures of function. Using a randomized controlled experimental design, 40 chronic (> 6 months) stroke survivors, will receive either 12 weeks of fast treadmill training alone or 12 weeks of fast treadmill training in combination with a step activity monitoring program. The primary (physical activity) and secondary (walking speed, endurance, energy cost) outcomes will be assessed by blinded evaluators prior to initiating treatment (baseline), immediately after the last treatment (12 weeks post baseline) and 3 months after the last treatment (6 months post baseline). The expected positive effects of this novel intervention combining fast treadmill training and a step activity monitoring program on physical activity will provide strong support for the need to expand rehabilitation interventions t include features that facilitate an increase in the real-world physical activity of chronic stroke survivors. PUBLIC HEALTH RELEVANCE: Stroke is the leading cause of disability in the US and this disability is a consequence of, and a risk factor for, physical inactivity. As a result, stroke survivors, as a group, are extremely inactive and this has serious consequences for them, including an increased risk of a second stroke and developing other diseases. This proposal investigates a novel intervention that combines fast treadmill training with a step activity monitoring program to improve inactivity after stroke.

DESCRIPTION (provided by applicant): Stroke is the leading cause of disability in the United States. The long-term objective of our research is to advance the recovery of functional mobility following stroke to reduce post-stroke disability. After stroke, individuals must learn or relearn movements that have been disrupted due to damage to the brain. Neuroplasticity is the mechanism by which the brain learns behavior and neuroplasticity and learning can occur after stroke. Yet, the literature provides little information about the process of relearning movements or the mechanisms that facilitate or impede this learning after stroke. In particular, very little s known about the process of relearning to walk following stroke, even though recovery of walking is often the primary goal of stroke survivors. A lack of understanding of the factors that contribute to slowed learning, or that can facilitate improved learning, hamper our ability to design optimal rehabilitation interventions. We propose that recent developments in our understanding of the role of brain-derived neurotrophic factor (BDNF) in neuroplasticity and motor learning may be capitalized on to address this gap. BDNF has long been known to be a mediating factor in cortical plasticity and motor learning, making it a logical target for the stud of the brain-behavior relationships that underlie post-stroke motor learning. Neurologically intact humans with a common single-nucleotide polymorphism in the BDNF gene code (Val66Met) that affects activity-dependent BDNF secretion, show deficits in motor learning and persons with stroke and the polymorphism show poorer initial recovery from stroke. Aim 1 of this proposal will determine the impact of the BDNF Val66Met polymorphism on learning a novel walking task after stroke and as such, will identify a potential biomarker that could be used to individualize post-stroke rehabilitation. In contrast, increases in the release of the activity-dependent mature form of BDNF, facilitated by a single bout of high intensity aerobic exercise enhances cognitive and motor learning in neurologically intact humans. Aim 2 of this proposal will determine the effect of a single, short bout of intense exercise on learning a novel walking task after stroke. Because the high intensity exercise bout is hypothesized to improve motor learning through a BDNF mediated mechanism, it is possible that any effect of the exercise will be attenuated in subjects with the polymorphism. We will therefore examine the effect of the BDNF Val66Met polymorphism on the results in this Aim. The knowledge gained from the studies in this proposal will provide exciting new information that can be used in the development of innovative rehabilitation interventions that promote neuroplasticity to improve recovery after stroke.

PROJECT SUMMARY/ABSTRACT The overarching goal of this research is to develop interventions that improve the overall health and quality of life of individuals post-stroke. It is estimated that 75% of all stroke survivors have comorbid cardiovascular conditions and significantly limited cardiovascular capacity. Many studies have shown that cardiovascular fitness after stroke is not commensurate with independent function and is a major contributor to post-stroke disability. The onset of disability makes it difficult for stroke survivors to engage in physical activity, causing them to remain sedentary and extremely inactive and thus a vicious cycle of disability¿inactivity¿poor cardiovascular fitness ensues. Even after intervention, most stroke survivors VO2peak levels remain below the suggested minimum required for independent living. It is therefore necessary to test new interventions that result in greater improvements in cardiovascular fitness and health and walking function after stroke. Among individuals with cardiovascular disease, recent studies have found a high intensity interval training program (HIIT) to be as safe and a more effective stimulus for improving cardiovascular fitness and health compared to traditional aerobic training programs. The efficacy of a HIIT program has not been tested in persons with chronic stroke, but given the success in other populations, it is a promising intervention to investigate in this group. Therefore, the primary aim of this proposal is to test whether a HIIT program results in greater improvements in cardiovascular health and fitness compared to a standard aerobic training program in those with chronic stroke. The secondary aims are to: a) test whether a HIIT program can result in greater improvements in walking function and activity than a standard aerobic training program and b) test whether improvements in cardiovascular fitness and real-world physical activity are linked. Using a randomized controlled experimental design, 53 chronic (> 6 months) stroke survivors, will receive either 12 weeks of a HIIT program or 12 weeks of a standard aerobic treadmill training program. The primary and secondary outcomes of cardiovascular health and fitness and walking activity will be assessed by blinded evaluators prior to initiating treatment (baseline) and immediately after the last treatment (12 weeks post baseline). The expected positive effects of this novel intervention will provide rationale for recommendations for exercise training in chronic stroke and data for larger studies combining aerobic training with interventions designed to improve real-world daily physical activity after stroke.

Project Summary/Abstract The overarching goal of this research is to develop interventions that improve the overall health and quality of life of individuals post-stroke. As a group, stroke survivors are more physically inactive than even the most sedentary older adults. Lack of physical activity has serious consequences in persons with stroke, including an increased risk of recurrent stroke, developing other diseases and mortality. Current rehabilitation interventions do little to improve real-world walking activity after stroke, suggesting that simply improving walking capacity is not sufficient for improving daily physical activity after stroke. Rather, we hypothesize that the combination of a fast walking intervention that improves walking capacity, with a step activity monitoring program that facilitates translation of gains from the clinic to the ?real-world?, would generate greater improvements in real world walking activity than with either intervention alone. Data from our lab provides support for this hypothesis; however, it suggests that the greater efficacy of combining the 2 interventions depends on a participant's initial walking activity. Thus, we do not expect that one intervention will be superior to the others for all participants, but rather that the combined intervention will be superior for those with low levels of baseline walking activity, speed and endurance. The specific objective of this proposal is to test whether and for whom combining fast walking training with a step activity monitoring program (FAST+SAM) is superior in improving real-world walking activity compared to fast walking training alone (FAST) or a step activity monitoring and feedback program alone (SAM) in those with chronic stroke. Using a randomized controlled experimental design, 225 chronic (> 6 months) stroke survivors, will complete 12 weeks of fast walking training (FAST), a step activity monitoring program (SAM) or a fast walking training + step activity monitoring program (FAST+SAM).The primary (steps per day), secondary (self-selected and fastest walking speed, walking endurance, oxygen consumption) and exploratory (vascular events, blood lipids, glucose, blood pressure) outcomes will be assessed by blinded evaluators prior to initiating treatment, after the last treatment and at a 6 and 12 month follow-up. Moderation of specific intervention outcomes by baseline characteristics will be evaluated to determine for whom the interventions are effective. Following completion of this study, we will not only understand the efficacy of the interventions and the individuals for which they are effective, we will have the necessary information to design a study investigating the secondary prevention benefits of improved physical activity post-stroke. This study is, therefore, an important step in the development of secondary prevention guidelines for persons with stroke.

PROJECT SUMMARY / ABSTRACT Despite significant time and money spent on post-stroke rehabilitation, stroke survivors are left with reduced walking capacity and significant disability. Rehabilitation following stroke is required to make gains in walking beyond those achieved through spontaneous recovery during the first several months after stroke and this occurs through relearning movements that have been disrupted due to damage to the brain. Enhancing post- stroke motor learning is therefore critical to improving post-stroke rehabilitation. Most research examining the effects of stroke on locomotor learning has focused on a specific form of implicit locomotor learning (sensorimotor adaptation), which is relatively automatic. Post-stroke rehabilitation, however, is dominated by techniques, such as visual feedback and verbal cues, that are meant to encourage patients? use of explicit learning (requiring attention, awareness). Considering that the effects of stroke on these two categories of learning (explicit and implicit) are likely quite different, since different brain areas are primarily involved in each type of learning, we must understand the effects of stroke on both types of learning. Moreover, factors such as cognitive deficits likely have differing effects, depending on the type of learning. Cognitive function is thought to be critical for more explicit forms of motor learning (specifically strategy-based learning), unlike implicit learning which is thought to place less demand on cognitive resources. Despite the numerous cognitive deficits present after stroke, the influence of cognitive function on motor learning (both implicit and explicit) after stroke has largely been ignored. Finally, differences in explicit and implicit learning may also influence the effects of exercise priming, (the coupling of a short bout of high intensity exercise with a learning task), that has been suggested as a mechanism to enhance motor learning in rehabilitation. In Aims 1 and 2 of this project, using both behavioral and computational data, we will determine the relationship between cognitive deficits (and other factors, such as stroke location) and locomotor learning in both explicit (strategy-based) and implicit (sensorimotor adaptation) locomotor learning tasks in those with chronic (>6 months) stroke. In Aim 3 we examine the effect of a short bout of high intensity exercise immediately following strategy-based locomotor learning on the retention of the newly learned walking pattern, along with its interaction with cognitive deficits, in those with chronic stroke. The results of this proposal have immediate implications for clinical practice because they will inform clinicians when to use certain techniques (e.g.-visual feedback with explicit cues, exercise priming) in patients with stroke with particular cognitive deficits, allowing for the design of personalized rehabilitation interventions.

PROJECT SUMMARY/ABSTRACT Clinical rehabilitations scientists with the formal research training to bring multidisciplinary research approaches to answer important questions related to rehabilitation are scarce. The goal of this pre-doctoral training program is to continue to improve the quality and quantity of individuals who will contribute to the knowledge and evidence that drives best practice in physical rehabilitation. This successful and innovative training program, coordinated through the Department of Physical Therapy, has had 20 years of previous funding. All trainees who have completed the DPT portion of the program have successfully passed the national licensure examination in Physical Therapy on their first attempt and have become licensed to practice physical therapy. All past trainees have become postdoctoral fellows or entered into faculty or research- intensive positions. Those in faculty positions are in some of the most outstanding Physical Therapy programs in the US. Their work has received awards, been published in journals of high quality (highest impact journals in rehabilitation), and been frequently cited. In addition, 6/11 of our trainees who are in faculty positions have been PI or Co-I on NIH funding, with 4 as PIs on active R01 grants. Additionally, our most recent cadre of T32 program graduates have funding from private foundations (e.g., American Heart Association), PCORI, and one is a Fulbright Scholar. These data are a representation of the outstanding scientific impact of our previous trainees. It is also notable that all of the current trainees or those who are in post-doctoral positions have received scholarships and/or external funding, again a testament to the outstanding productivity and quality of work of our trainees. The program fuses two independent training programs: an outstanding entry level Doctorate in Physical Therapy (DPT) and a very successful interdisciplinary PhD program in Biomechanics and Movement Science. The program is analogous to the MD/PhD programs that train medical scientists. By helping to reduce the often sizable debt incurred during the DPT training program, trainees are able to delay the opportunity to earn the salaries that clinicians enjoy and move directly into the PhD program. Students in the program become both physical therapists and rehabilitation research scientists. Trainees are selected from a pool of outstanding students with diverse undergraduate backgrounds who enter the DPT program. Many of these students express an interest in research before admission to the program. This training program attracts the best and brightest individuals with a sincere interest in physical rehabilitation research and tracks them early in their training into research careers. The need is enormous. Both new and established academic physical therapy programs need doctorally trained individuals for teaching and research positions. Graduates of this training program are ideal faculty members who foster excellence in rehabilitation research.