Carolee J. Winstein - US grants

Stroke is the leading cause of disability among adults in the United States. Each year in the U.S., approximately 550,000 people suffer strokes and nearly 400,000 survive with some level of disability. The cumulative total of living, stroke-affected Americans is nearly 3 million. Thirty billion dollars annually is the estimated burden from stroke-related disability. Despite the enormity of these statistics, there have been few scientific studies of the effectiveness of post-stroke rehabilitation interventions. As a result, the recently published Clinical practice guidelines for post-stroke rehabilitation have been forced to rely primarily on expert opinion and not on well controlled scientific studies. This project is a first step toward remedying this; it will provide pilot data for a large scale randomized clinical trial of rehabilitation interventions during the subacute phase. The goal of this small grants proposal is to obtain preliminary data to: 1) Assess the feasibility of conducting a large scale, randomized, clinical trial (RCT) evaluating the effectiveness of three physical rehabilitative interventions ("usual care", "strengthening" and "functional use") on restoration of arm use after unilateral stroke, 2) Fine tune the experimental design and intervention procedures for a large scale RCT to evaluate the effectiveness of these three interventions and 3) Obtain preliminary data on short-term and long-term effectiveness. Specifically, the proposal is designed to: 1) Assess recruitment, retention, and compliance; develop the operational components including a manual of procedures and standardized data collection forms; and build a database system and a communications system, 2) Examine eligibility/ineligibility criteria; assess the benefits/detriments of a two vs. three arm RCT design; and assess intervention time, outcome measures, and sensitivity of assessment instruments and 3) Determine requisite sample size power calculations; obtain preliminary data pertaining to the prognostic implications of initial impairments (neurological and neuromuscular) with regard to each of the interventions; and obtain preliminary data regarding whether the recovery and response is influenced by lesion characteristics.

This is the first year funding of a three-year continuing award. The goal of the "Virtual Trainer" is to create a computer-based animation that can interactively teach how to move. The hardware requirements for the Virtual Trainer in its final stage would be an inexpensive state-of-the-art personal computer equipped with a camera system. The Virtual Trainer will be able to demonstrate movements to its user, monitor the execution of these movements by the user, and suggest corrections in case of inadequate performance. The Virtual Trainer will be useful in a large number of applications, including rehabilitation of movement-impaired patients (e.g., stroke-patients), sport and exercise education, dance instruction, and interactive entertainment industry. Additionally, the technology developed for the Virtual Trainer has the potential to pioneer new algorithms for robot control using "teaching from demonstration", to contribute to the development of automated monitoring systems for human environments, to the generation of humanoid computer simulations, and also to gaining new insights into biological motor control and the functioning of the nervous system. The research team of this project will primarily focus on issues of movement recognition and movement generation with the Virtual Trainer for rehabilitating stroke-impaired patients with upper and lower limb disabilities.

DESCRIPTION (provided by applicant): Of all impairments that result from brain stroke, perhaps the most serious and most needing of rehabilitation effectiveness studies is hemiparesis of the upper extremity. Overall, this proposal will use 3-D behavioral kinematics and MRI neuroimaging techniques to examine the motor control and cerebral activity changes associated with constraint-induced (CI) movement therapy for patients with sub-acute stroke who are between 3 and 6 months post stroke. This is a companion study to the previously funded multi-center randomized clinical trial (H D37606-01), Extremity Constraint-Induced Therapy Evaluation (EXCITE). This project complements EXCITE by probing the neurobiological and behavioral mechanisms underlying this clinical intervention in stroke rehabilitation. The specific aims are to: 1) determine the relationship between lesion size and location, residual hand capability, and responsiveness to CI therapy; 2) determine the effects of CI therapy on the motor control of reaching and grasping actions; 3) determine the effects of Cl therapy on the cortical sensorimotor neural network associated with the planning and execution of goal-directed wrist and grasping actions; and 4) determine the persistence and or stability of these changes in motor control, brain activity, and functional outcomes one year later as a consequence of Cl therapy. Expected changes in sensorimotor area activation (learning-dependent neural plasticity) and motor behavior associated with two weeks of intensive practice of the impaired upper extremity in combination with restraint of the less affected upper extremity in stroke patients (n = 14) who meet the EXCITE inclusion criteria will be determined by comparison with that of a delayed-intervention stroke group (n = 14) who will receive "usual and customary" care. This comparison will allow the direct effects of "forced use" to be exposed at both the neurobiological (brain activity) and behavioral (motor performance and function) levels while controlling for spontaneous recovery processes and those achieved through standard post-stroke physical rehabilitation methods.

[unreadable] DESCRIPTION (provided by applicant): This six-day institute will provide a catalyst for advancement of physical therapy for people with movement dysfunction through the translation of movement science into effective clinical interventions. New discoveries in the areas of motor control, learning, and development are usually discussed in the laboratory and shared among the basic science community. Less frequently, these discussions are converted into clinical practice. Conferences that bridge the basic science findings to clinical practice are increasingly important for advances in rehabilitation. This is the third in a series, over nearly four decades to be held July 5-21, 2005, at the University of Utah, SLC, Utah. The mission of this Symposium on Translating Evidence into Practice (STEP) is to explore existing and developing theories, models and knowledge regarding movement science; to integrate these theories, models and evidence into physical therapy education and practice; to identify, discuss and analyze areas where clinical practice is evolving; and to identify and discuss the implications of scientific advances for physical therapy practice. The intended international group of participants includes physical therapy educators, clinicians and researchers whose intent is to integrate scientific evidence into clinical practice. A select group of graduate students and junior faculty will be invited and encouraged to participate. The institute format will be morning general plenary sessions followed by afternoon concurrent focused breakout sessions by leading basic and clinical scientists from the fields of health services, neuroscience, neurology, developmental neurobiology, psychology, rehabilitation medicine, motor behavior, and physical therapy. An evening Gordon-like conference panel and evening poster sessions will facilitate dialogue and collaboration. At the conclusion of the institute, key participants will be asked to summarize each day's research agenda through specific topic reports. The last afternoon will focus on strategies to develop academic-clinical partnerships to facilitate the development of more effective clinical interventions. [unreadable] [unreadable]

Robotics has the potential of positively impacting quality of life, especially for people with special needs. If we are to meet the demand for personalized one-on-one care for the growing populations of elderly individuals and those with special cognitive and social needs throughout life, great strides must be made in human-robot interaction (HRI) in order to bring robotics into everyday application domains. This interdisciplinary project identifies a specific set of HRI research questions in socially assistive robotics, the study of robotic systems capable of providing help through social rather than physical interaction. The research foci of the study are: embodiment, personality, empathy, and adaptivity toward the development of an assistive HRI model for customized time-extended assistive interaction. The research will be grounded in the stroke rehabilitation domain, where personalized and dedicated care is needed to provide supervision, motivation, and training during the critical post-stroke period and beyond, and where assistive HRI can play a key role. Specifically, a novel assistive HRI model will be developed based on personality matching between the user and the robot, in order to optimize the user's task performance on rehabilitation exercises. The model will be evaluated on multiple testbeds with a large pool of human subjects from the stroke patient population. An online learning algorithm will enable the robot to adapt to the user both over the course of short-term interactions during a single therapy sessions (e.g., in response to mood and fatigue), and time-extended interactions over multiple therapy sessions (e.g., in response to the evolving recovery process over months of rehabilitation). The work is the first to study the role of personality and empathy in assistive HRI with human subjects, as well as to engage in longitudinal assistive HRI research to assess time-extended human-machine interaction in the assistive context. An important contribution of the research is the unified and tightly integrated end-to-end approach, which combines key HRI issues of embodiment, personality, empathy and adaptivity in hypothesis-testing experiments. Project outcomes will also include a large and unique corpus of multi-modal data, which will be collected and analyzed, and made available to researchers across the relevant disciplines. The scientific impact will go well beyond novel insights toward a better understanding of the fundamentals of assistive HRI, and the role and potential for assistive human-machine interaction for stroke patient populations and rehabilitation in general.

Broader Impacts: Currently there are about 750,000 new strokes per year in the United States, and some expect the number to double in the next twenty years with the growing elderly population. Project outcomes will provide pilot data necessary for translating the methodologies developed toward clinical applications.

21+ years old; Acute; Address; Adult; After Care; After-Treatment; Aftercare; Apoplexy; Arm; Awareness of self; Bilateral; Caring; Cerebral Stroke; Cerebrovascular Accident, Acute; Cerebrovascular Apoplexy; Cerebrovascular Stroke; Cerebrovascular accident; Chronic Phase; Class; Classification; Clinical; Clinical Trials; Clinical Trials, Unspecified; Community Trial; Complex; Daily; Development; Dose; ENPT; Effectiveness; Elements; End Point; EndPointCode; Endpoints; Environment; Evaluation; Evidence based treatment; Exercise; Exercise, Physical; Extremities; Family; Future; Gait; Goals; Hand; Hand functions; Health Insurance for Aged and Disabled, Title 18; Health Insurance for Aged, Title 18; Health Insurance for Disabled Title 18; Home; Home environment; Hour; Household; Human, Adult; Hybrids; Impairment; Inpatients; Intervention; Intervention Strategies; Kinesiology; Laboratories; Learning; Leg; Leisure Activities; Level of Evidence; Limb structure; Limbs; Lower Extremity; Lower Limb; Masks; Measures; Medicare; Membrum inferius; Membrum superius; Modality; Monitor; Motor; Movement; Movement science; Muscle Paresis; Muscular Paresis; Non-Trunk; Numbers; Occupational Therapy; Out-patients; Outcome; Outcome Measure; Outpatients; Paresis; Participant; Patient Self-Report; Patients; Performance; Personal awareness; Phase; Physical Health Services / Rehabilitation; Programs (PT); Programs [Publication Type]; Protocol; Protocols documentation; QOL; Quality of life; Randomized; Randomized Controlled Trials; Recommendation; Recovery; Recovery of Function; Rehabilitation; Rehabilitation therapy; Rehabilitation, Medical; Residual; Residual state; Resolution; Reversal Learning; Review, Systematic; Review, Systematic (PT); Review, Systematic [Publication Type]; SUBGP; Score; Secondary to; Self Care; Self Perception; Self image; Self view; Self-Report; Services; Site; Solutions; Stroke; Strokes, Acute; Subgroup; Systematics; Testing; Time; Title 18; Training; Translations; Travel; Upper Extremity; Upper Limb; Upper arm; Using hands; Vascular Accident, Brain; Walking; Week; Wolves; abstracting; acute stroke; adult human (21+); base; body movement; brain attack; cerebral vascular accident; clinical investigation; constraint induced therapy; cost; design; designing; disability; experience; functional outcomes; functional recovery; health insurance for disabled; improved; instrument; interventional strategy; locomotor learning; motor control; motor impairment; motor learning; muscle strength; personal care; post stroke; poststroke; programs; randomisation; randomization; randomized controlled study; randomly assigned; rehabilitative; remediation; self awareness; self knowledge; skill acquisition; skills; stroke; stroke recovery; stroke rehab; stroke rehabilitation; tool; trend

DESCRIPTION (provided by applicant): Residual disability after stroke is substantial, with about 65% of patients at 6 months unable to incorporate the paretic hand effectively into daily activities. In turn, this degree of functional deficit contributes to a reduced quality of life after stroke. The primary objective of I-CARE (Interdisciplinary Comprehensive Arm Rehabilitation Evaluation) is to improve outpatient therapy for arm paresis after stroke. We will conduct a Phase III, single- blind, multi-center, randomized control trial to investigate the effectiveness of ASAP (Accelerated Skill Acquisition Program), a focused, intense, evidence-based, upper extremity rehabilitation program. ASAP combines aspects of constraint-induced therapy, skill-based/impairment-mitigating task-specific training with embedded motivational enhancements and includes 30 hours of one-on-one therapy initiated during the early post-acute outpatient interval (1-3 months) after stroke. This RCT has one primary aim: Compare ASAP to a dose equivalent usual and customary occupational therapy (high dose) group. There are two secondary aims: a) Compare ASAP to a true (monitoring only) usual and customary therapy group (low dose) and b) Compare the high dose usual and customary occupational therapy group to the low dose usual and customary occupational therapy group. We will randomize 360 adults, within one to three months of stroke onset, with mild to moderate upper extremity impairment. Our primary outcome is a performance-based arm function test, Wolf Motor Function Test (WMFT) at one year after participation. Secondary outcomes include patients' self-perception of paretic hand function, a domain of the Stroke Impact Scale (SIS) and the full SIS. Specific subgroup analyses will explore important moderating factors including duration from onset, stroke type, and motor impairment. Given the trend toward diminished total reimbursable time for stroke rehabilitation, our ultimate goal is to provide evidence toward an optimal allocation of therapy services within the approved number of treatment sessions that will reduce disability, lessen the societal burden, and provide a standardized evidence-based treatment useful for the rehabilitation clinician and future clinical trialist.

DESCRIPTION (provided by applicant): Because each patient post stroke has unique impairments and function, it is important to depart from a one size fits all approach to rehabilitation. Although there is now evidence that motor therapy can improve function and use of the more affected limb for patients with moderate to mild impairments, change in use in the months following therapy is variable: for some patients there is an increase in use, but for others a decrease in use. Our long-term goal is to determine prospectively the dose of therapy that leads to further improvements of use after therapy for individual patients while keeping cost at reasonable levels - we call this dose critical dose. Our objective here is to investigate long-term predictions of use as a function of the dose of therapy and of the patient's neurological and behavioral characteristics. Our general hypothesis is that, for a subset of patients, there is a threshold level for arm and hand function to be achieved after therapy, such that if therapy brings function above this threshold, spontaneous use and function will reinforce each other in a virtuous circle. We formulated our hypothesis based on computational models that demonstrate such a threshold and account for existing data. We will address our general hypothesis and accomplish our objective with two aims. Aim 1. Determine the effect of a distributed dose of therapy on immediate and long-term gains in upper extremity use. Aim 2: Develop a means to compute the critical dose for individual patients. With the first aim, we will test our general hypothesis and generate relevant clinical data of function and use. The data will then be used in the second aim to develop a predictive model, based on the Extended Kalman Filter, of long-term arm and hand use as a function of the dose of therapy as well as behavioral and neurological data. Our proposed work is significant because such a predictive model of stroke recovery, once subjected under future funding to clinical trials, can be used to influence policy regarding the necessary dosage of effective treatments at a reasonable cost for the growing number of persons who have survived stroke. This work will also make an important neuro- scientific contribution as we will model, and test behaviorally, the causal and adaptive linkages between the decisions to use the affected arm and recovery of motor function.

Summary (Abstract) The 2016 American Society of Neurorehabilitation (ASNR) conference is planned for November in San Diego, CA, in conjunction with the Society for Neuroscience meeting (SfN). The mission of the ASNR is to promote the medical and social wellbeing of persons with disabling neurological disorders, to advance training and research in the basic and clinical sciences that can lead to functional recovery of neurologically impaired persons, and to disseminate the knowledge of this research among professionals and the general public. Our annual meeting provides interactions among neurorehabilitation clinicians, basic scientists, industry representatives, foundations and funders in a dynamic environment of presentations and lively discussions. The ASNR has the advantage of attracting a broad audience of research-oriented clinician-scientists representing a diverse group of professionals (e.g., MD, PT, OT), many with dual academic and professional degrees (e.g., MD, PhD), as well as neuroscientists deeply interested in translational work. Based on the two previous years, we expect between 200 and 300 attendees, both professionals and trainees from the disciplines described above. The successful 2015 two-day conference program format will serve as the model format for the proposed 2016 conference program. The first day's program will use a single-track format, while the second day's program will feature concurrent sessions inter-leaved with the Translational and Computational Motor Control SfN Satellite in the morning with concurrent sessions in the afternoon. There will be an opening Presidential Oration, followed by five selected scientific symposia, two distinguished award lectures, two unopposed poster sessions, a platform oral abstract session, and a final interactive session focused on controversies/hot topics in neurorehabilitation. This R13 application requests $25,000 to support travel costs for diversity fellowships and non-ASNR member speakers, audio-visual expenses, poster awards, a mentoring activity (e.g., breakfast), child care services (if warranted) and meeting management services.

R13 Conference Grant for 2017 ASNR Annual Meeting Winstein, C Summary (Abstract) The 2017 American Society of Neurorehabilitation (ASNR) conference is planned for November in Washington DC, as a pre-meeting unofficial satellite of the Society for Neuroscience annual meeting (SfN). The mission of the ASNR is to promote the medical and social wellbeing of persons with disabling neurological disorders, to advance training and research in the basic and clinical sciences that can lead to functional recovery of neurologically impaired persons, and to disseminate the knowledge of this research among professionals and the general public. Our annual meeting provides interactions among neurorehabilitation clinicians, basic scientists, industry representatives, foundations and funders in a dynamic environment of presentations and lively discussions. The ASNR has the advantage of attracting a broad audience of research-oriented clinician-scientists representing a diverse group of professionals (e.g., MD, PT, OT), many with dual academic and professional degrees (e.g., MD, PhD), as well as neuroscientists deeply interested in translational work. Based on the three previous years, we expect between 200 and 300 attendees, both professionals and trainees from the disciplines described above. The successful 2016 two-day conference program format will serve as the model format for the proposed 2017 conference program. This single-track format featured four Symposia (2/day), an hour long Oral abstract session of selected abstracts presented by early career or student investigators, two Poster and Exhibit sessions (1/day), 1.5 hr awards ceremony including two special lectures and the now high-profile closing session, Controversies in Neurorehabilitation. This R13 application requests $10,000 to support travel awards for up to four diversity fellowships, publication costs for the conference brochure, name tags etc., support to defray registration fees and travel for special attendees, a portion of the audio-visual expenses, and two poster awards 1

Project Summary: In the previous cycle of this grant, we characterized hemisphere-specific motor control deficits in the non- paretic arm of unilaterally lesioned stroke survivors. Our preliminary data indicate these deficits are substantial and functionally limiting in patients with severe paresis. We have specifically designed an intervention to remediate the hemisphere-specific deficits in the non-paretic arm, using a virtual-reality platform, and then follow this training with manipulation training of a variety of real objects, designed to facilitate generalization and transfer to functional behaviors encountered in the natural environment. We propose a 2-site, two-group randomized intervention with a treatment group, which will receive unilateral training of the non-paretic arm, through our Virtual Reality and Manipulation Training (VRMT) protocol. This intervention protocol is grounded in the premise that targeted remediation of fundamental control deficits exhibited by the non-paretic arm will generalize and transfer beyond practiced tasks to performance of activities of daily living (ADL). This approach contrasts with the more pragmatic approach of task-specific training of essential ADL?s, which is limited in scope, more cumbersome, and ignores known fundamental motor control deficits. Our control group will receive conventional intervention, guided by recently released practice guidelines for upper limb intervention in adult stroke. The impact of the proposed research is that we address persistent functional performance deficits in chronic stroke patients with severe paresis, who?s non- paretic arm impairments are generally ignored in most current rehabilitation protocols. Our first aim addresses the overall effectiveness of this intervention, relative to our control group: To determine whether non-paretic arm VRMT in chronic stroke survivors with severe paresis will produce durable improvements in non-paretic arm motor performance that will generalize to improve functional activities and functional independence to a greater extent than conventional therapy focused on the paretic arm. Our second aim focuses on the mechanistic basis of potential training-related improvements in motor performance: To determine whether intervention-induced improvements in non-paretic arm performance are associated with improvements in hemisphere-specific reaching kinematics. Finally, our third aim monitors for potential negative effects of our experimental intervention on paretic arm impairment. We have already integrated the PI?s laboratories (Sainburg-PSU, Winstein-USC) for our pilot research project that has provided excellent support for aims 1 and 3. !