Author: Peter Schnellenberger

Greater access to high-quality rehabilitation treatments after stroke has the potential to improve movement and reduce disability for millions of people around the world. The National Institutes of Health recently awarded a large-scale five year grant to support a multi-site clinical trial investigating an intensive, home-based telerehabilitation treatment in persons post-stroke. The TR-2 trial was funded jointly by the National Institute of Neurological Disorders and Stroke (NINDS) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

The trial will be co-led by Steven C. Cramer, MD, Professor of Neurology, UCLA School of Medicine, and Medical Director of Research at California Rehabilitation Hospital, and Dylan Edwards, PhD, the Nancy Wachtel Shrier Director of Jefferson Moss Rehabilitation Research Institute and Professor of Rehabilitation Medicine at Thomas Jefferson University in Philadelphia. Both investigators have extensive experience with clinical trials involving rehabilitation robotics, technology and digital gaming and have spent substantial portions of their careers studying recovery of post-stroke motor function. The approach used in the TR-2 trial is built on current theory of motor recovery treatment combined with contemporary technology to improve access to stroke rehabilitation.

After years of study through smaller clinical trials, this new randomized, controlled trial aims to definitively establish the value of high-dose remote rehabilitation, an approach originally developed by Dr. Cramer and colleagues in his laboratory. Dr. Cramer recognized early on that applying a telehealth approach to stroke rehabilitation had tremendous potential for increasing the dose of therapy that patients could receive while overcoming some of the many barriers that limit the amount of therapy delivered through traditional clinic visits, including limited access, difficulty traveling, and low motivation.

“Using telerehabilitation to facilitate the recovery of motor function after stroke made sense. To get this approach into the clinic, we first had the important task of working out the logistics and designing an intervention that was safe, effective, and — importantly — something that people actually wanted to do,” explained Dr. Cramer. Dr. Edwards has been collaborating with Dr. Cramer in this research area for more than a decade, and the positive findings from Dr. Cramer’s preliminary trial published in 2017 were encouraging. They have worked together to continue to refine the intervention, which consists of motor therapy targeting arm function through engaging functional games and exercise videos, as well as stroke education and regular assessments.

Working with a team of exceptional researchers from eleven different sites across the United States, their results from their earlier Phase II trial demonstrated that activity-based training produced substantial gains in arm motor function, regardless of whether the training was provided via home-based telerehabilitation or traditional rehabilitation in a clinical setting (non-inferiority trial). In a recent dual-site study, they also determined that this intensive telerehabilitation approach is feasible, safe, and potentially effective to use for individuals early after a stroke while they are still in an inpatient rehabilitation facility and transition to home with it.

The TR-2 trial builds on collective previous findings of feasibility, safety, and efficacy, but importantly, this is the first phase II progression to a phase III pivotal superiority trial funded by the NIH (StrokeNet). It will do this by directly comparing intensive, home-based rehabilitation therapy to usual clinical care to determine whether the telerehabilitation approach is more effective. This study brings together a multi-disciplinary team of co-investigators with expertise across stroke rehabilitation, neuroimaging, actigraphy, health economics, biostatistics, and clinical trials, as well as experienced research therapists and clinical coordinators at the lead sites.

Beyond examining the effectiveness of adding the intensive, home-based telerehabilitation treatment versus usual care in a larger sample of more than 200 participants across many sites, their newly funded study will evaluate a neuroimaging-based measure of stroke injury that can be used to predict how an individual may benefit from this intensive rehabilitation therapy. This measure will specifically examine the extent of damage to the descending pathways involved in voluntary movement (corticospinal tract), a measure that has been shown to predict arm motor recovery after stroke. They hypothesize that the beneficial effects of their targeted motor therapy depend on having an intact corticospinal tract, and the extent of corticospinal preservation should be related to the degree of benefits this therapy can provide over usual care.

“Determining which patients will respond best to which therapies is a challenge both in everyday clinical practice and in clinical trials because of the large heterogeneity of stroke. Identifying a measure that can successfully predict who will benefit from a particular therapy is critical for optimizing outcomes and utilization for patients who may have a limited amount of time and other resources to dedicate to rehabilitation,” Dr. Edwards remarked.

In addition to causing widespread disability, stroke contributes to significant economic burden, both for individuals and the broader healthcare system. Telerehabilitation may be able to serve as a practical and cost-effective approach for delivering care that can improve function and reduce disability. As part of their new grant, the interdisciplinary research team will also examine the health economic impact of home-based telerehabilitation in patients with recent stroke, directly comparing it to usual care in which rehabilitation therapy is generally provided at very low doses.

Drs. Cramer and Edwards are looking forward to identifying the sites that will participate in the newly initiated TR-2 trial, and they anticipate participant enrollment will begin next year. By dramatically improving access to rehabilitation services and increasing the amount of therapy that individuals with stroke receive, the findings of this study have the potential to change clinical care for stroke rehabilitation worldwide.

Moss Rehabilitation Research Institute (MRRI) is pleased to announce that Dylan Edwards, PhD, is preparing to commence a new research study supported by a Health Research Grant from the Pennsylvania Department of Health. Dr. Edwards is Director of MRRI and Director of MRRI’s Human Motor Recovery Laboratory.

The novel translational research study will apply high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) with the goal of promoting recovery of the nervous system and motor function in people with tetraplegia after a cervical spinal cord injury. The HF-rTMS protocol developed by Dr. Edwards and his colleagues differs from previously investigated rTMS protocols that have been shown to transiently enhance intact pathways in spinal cord injury.

Based on promising results in animal models of spinal cord injury (PI: Jian Zhong, PhD), this new non-invasive approach under investigation has tremendous potential to promote lasting recovery after spinal cord injury. The present project will be the first time the dual-hemispheric HF-rTMS treatment protocol will be assessed in humans with spinal cord injury. Participants will be studied in the inpatient setting in the subacute phase of spinal cord injury, a period during which neural recovery is greatest. Through innovative translational research, MRRI scientists are continuing to advance the field of neurorehabilitation and to develop new treatments to improve the lives of individuals with neurological disabilities.

MRRI recently welcomed Alexander De Angelis to the Institute as a Research Assistant working in the Cognition and Action Laboratory, directed by Laurel Buxbaum, PsyD. Alex graduated from The College of New Jersey (TCNJ) in 2022 with a B.A. in Psychology, specializing in Biopsychology. As an undergraduate student, Alex gained research experience working as an assistant in two different laboratories at TCNJ.

In the Social Psychology Laboratory, led by Dr. Jarret Crawford, Alex studied mental health conditions that could potentially be inherited genetically based on social circumstances experienced by one’s ancestors. The COVID-19 pandemic impacted participant recruitment and other in-person activities within the lab, but Alex had an opportunity to learn more about this research area by reviewing the scientific literature. His literature review focused on previous studies on the potential for mental health conditions, such as depression, to be passed down genetically in a population of people who were descendants of survivors of Stalinist purges in Russia and Ukraine. The findings were mixed, such that in some cases, evidence supported the possibility of genetically inherited depressive symptoms, but there was also evidence suggesting that descendants may have a greater appreciation for life and a better overall quality of life.

While in the Event-Related Potential (ERP) Laboratory, directed by Dr. Andrew Leynes, Alex contributed to a research project investigating the identification of previously encountered information or “recognition memory”. His role included participant recruitment, informed consent, and data collection. Data collection involved recording electroencephalogram (EEG) data from participants and extracting the ERPs, or electrical signals generated in the brain in response to stimuli. Participants were asked to view a series of words and respond whether the words had been presented previously or not. Before a word was shown, participants were primed with brief exposure to a word that matched (match primes), was similar in meaning to (semantic primes), or was similar in structure/spelling to (orthographically similar primes) the target word. They reported that match primes showed the largest effect for accurately recognizing previously viewed words, and participants’ confidence ratings were also the highest. Accuracy and confidence were lower for orthographically similar primes and lowest for semantic primes. The study provided important information on the effects of priming on fluency during an episodic recognition task, and this may impact the design of future studies in the field.

In his final year at TCNJ, Alex conducted an independent research project under the guidance of Dr. Margaret Ruddy. For this project, he performed an in-depth literature review on the efficacy of Psilocybin and ketamine for alleviating treatment-resistant mental health conditions. Through this literature review, Alex learned about theoretical biochemical mechanisms of action of these drugs and how they could potentially benefit patients who had been classified as having treatment-resistant depression and/or anxiety. Additional research is needed to determine the optimal dose, course of treatment, and potential combination of therapies to maximize benefits for patients.

During his time at TCNJ, Alex also served as a teaching assistant for the General Chemistry II and Organic Chemistry II courses, and he worked part time at Princeton Nassau Pediatrics as a medical assistant. After graduating, Alex began working full time as a medical assistant and phlebotomist. In this role, his responsibilities included recording patient vitals, collecting patient blood samples and sending them for testing, and peer training.

At MRRI, Alex will be working with Dr. Buxbaum and Shailesh Kantak, PT, PhD, on research exploring arm nonuse in patients with fronto-parietal stroke, as well as a separate research project further evaluating an experimental treatment for phantom limb pain using virtual reality. In these projects, Alex will assist with participant recruitment and collecting data on motor, language, and cognitive function. Through this research, he hopes to learn more about the neuroanatomy and mechanisms underlying arm nonuse in stroke and phantom limb pain in people with limb loss, and how therapies can be modified to best treat these patients in the future.

Treatment theory, in which active ingredients influence a functional target through a proposed mechanism of action, forms the foundation for the RTSS.

The Rehabilitation Treatment Specification System (RTSS) has been under development for more than 15 years to address one of the most fundamental obstacles to progress in rehabilitation research: the “black box” problem related to our treatments. Whereas drugs are named and categorized in terms of their active ingredients, the vast majority of rehabilitation treatments involve systematic exposure to various kinds of experiences, delivered through interactions with a clinician. The active ingredients of such treatments are not self-evident, so we resort to naming them according to the facility (“3 weeks of inpatient rehabilitation”), discipline (“3 hours/week of physical therapy”), or the problem addressed (“a course of cognitive rehabilitation”). This makes it difficult to replicate research on effective treatments, to know whether two treatments differ in important ways, or to implement successful treatments in the clinic.

Principal investigators of the funded projects that led to the development of the RTSS (Marcel Dijkers, NIDIlRR; John Whyte, PCOR), were recognized with personalized “black boxes” signifying the problem that the RTSS aims to “unpack”.

The RTSS provides a standardized framework for describing all rehabilitation interventions with respect to their known or hypothesized active ingredients, based on an explicit treatment theory. This ensures that the label for the treatment is matched to the active ingredients that it contains, and that dissemination of the treatment will mean dissemination of those ingredients. It also means that clinical trials are much more than empirical comparisons of two treatments. They are tests of an underlying treatment theory, and their results help advance rehabilitation science.

Since the publication of the Manual for Rehabilitation Treatment Specification in 2019 and the organization of the Rehabilitation Treatment Specification Networking Group (RTS-NG) at the American Congress of Rehabilitation (ACRM), the manual has been downloaded by over 1,400 individuals worldwide and been the subject of numerous publications in diverse areas of rehabilitation. Nevertheless, individuals seeking to use the RTSS to guide research design, education, or clinical practice have found some of the implementation tasks to be challenging, despite recognizing the value of the underlying concepts. While the concepts embodied by the RTSS are useful to individual researchers and clinicians once they are understood, other benefits of the RTSS can only be realized with broader implementation so that it becomes a shared communication system. For example, the ability to aggregate research and conduct meaningful meta-analyses requires that the contributing studies report their results in RTSS-compatible ways.

A number of recent activities by members of the RTS-NG have helped explore ways to improve specific practices in rehabilitation, by implementing RTSS-based concepts. Jeanne Zanca, MPT, PhD, at Kessler Rehabilitation Institute, received an engagement contract from the Patient-Centered Outcomes Research Institute (PCORI) to understand barriers and facilitators to researchers’ application of RTSS-related concepts in research reporting, and the barriers and facilitators to clinician’s’ application of published research evidence. These stakeholder discussions provided insight into the targeted education and support materials that would help researchers apply RTSS principles to design and report their research. However, clinicians felt that treatments that were clearly reported along these lines would be feasible to implement by clinicians without requiring their intensive exposure to the RTSS directly.

In April, Moss Rehabilitation Research Institute (MRRI) sponsored and hosted a “RTSS Superusers Summit” to bring together researchers, educators, and clinicians from North America and Europe who have had the most experience in concrete projects involving the RTSS. The invited workshop was attended by 44 individuals from a range of rehabilitation disciplines. The workshop aimed to address two broad goals: to help these “early adopters” address challenges that they faced in their own RTSS-related work; and for RTSS developers to get feedback on the types of centralized infrastructure and support that might be needed to advance further implementation efforts. Questions and challenges faced by participants were surveyed in advance and shaped the contents of the meeting agenda. Cross-cutting questions related to the level of granularity that is optimal for treatment specification and the process needed for arriving at consensus labels for targets and ingredients were central discussion topics. As a result of the workshop, a number of new task forces were formed or reorganized within the RTS-NG, and plans were developed to apply for an ambitious infrastructure grant to support further implementation efforts.

Participants at the SuperUsers Summit engage in discussion.

This last goal was successfully met with the submission of an application for a P50 rehabilitation research infrastructure grant from the National Institutes of Health, led by Jarrad Van Stan, PhD, CCC-SLP, at Harvard as principal investigator. The proposal includes a Resource Core at MRRI, led by John Whyte, MD, PhD, and a Community Engagement and Outreach Core, at the Massachusetts General Hospital Institute for Health Professions, led by Kathleen Lyons, ScD, OTR/L. Should this grant be funded, it would support research on the impact of RTSS consultation on the quality of published research reporting, and on a generalizable method for arriving at standard menus of targets and ingredients in specific treatment domains. Moreover, the grant would provide resources to expand the pool of RTSS experts who can consult to researchers, educators, and clinicians about their implementation efforts. Regardless of the outcome of this specific grant application, the collaborative network of investigators will undoubtedly continue to move forward with implementation efforts.

This fall, at the annual meeting of the ACRM (10/31/24 – 11/3/24, Dallas) the RTS-NG will again offer a full schedule of symposia related to the RTSS. This will include a focus on its use by specific disciplines, its use for specific purposes, such as research design or clinical reasoning, as well as a symposium devoted to summarizing the work of the Superusers Summit, itself. Dr. Whyte will be among the presenters in two ACRM symposia on November 3^rd. The first will discuss how the RTSS can be used to improve the experimental design and reporting for intervention studies, and the second will cover real-life challenges to using the RTSS. Reflecting on recent RTSS-related activities, Dr. Whyte remarked, “Widespread implementation of the RTSS has the potential to transform the field of rehabilitation to improve research and ensure patients receive the best possible care. It has been exciting to see the advances we have made over the years, and scientists at MRRI look forward to continuing to be involved in future developments.”

MRRI is happy to announce that Tejaswini Sudhakar has joined the Institute’s team as a Research Assistant in the Human Motor Recovery Lab led by Dylan Edwards, PhD. Tejaswini’s extensive educational background and real-world expertise are a wonderful fit with the lab’s goal of developing neuromodulation and rehabilitation technology.

Tejaswini graduated from The City College of New York (CUNY) with a bachelor’s degree in biomedical engineering. She immersed herself in research and real-world applications throughout her academic career, showcasing her expertise in biomedical engineering, neurology, and a range of scientific data collection methods. Her research internships and coursework gave her practical knowledge with relevant experimental techniques.

Tejaswini co-founded AutoTENS, a firm that specialized in creating automated transcutaneous electrical nerve stimulation (TENS) devices for the treatment of persistent lower back pain, before joining MRRI. Her capacity to think creatively and effectively within strict regulatory constraints was demonstrated by her leadership, which was crucial in obtaining funds and guaranteeing FDA compliance. Her internships at Pfizer and Cresilon also gave her vital knowledge of process engineering, quality control, biotech manufacturing, and regulatory standards.

Tejaswini has made contributions to research in a variety of fields, including biomedical engineering and nanoscience. Her work at the CUNY Advanced Science Research Center and CCNY was noteworthy since it resulted in publications in respected journals like Soft Matter and Nature Communications. Her passion for expanding scientific knowledge and methods is seen in her meticulous approach to experimental design and data analysis.

As a Research Assistant at MRRI, Tejaswini will play a pivotal role in supporting funded studies involving non-invasive brain stimulation assessments, the development of the Spinal Cord Injury registry database, and intensive gaming/robotics-based training programs. Her responsibilities will encompass participant recruitment, data collection and analysis, literature reviews, and manuscript preparation—all critical components for advancing our understanding of motor recovery in populations with spinal cord injury and stroke.

Tejaswini’s exceptional academic background, entrepreneurial spirit, and passion for research make her a valuable addition to the MRRI team. The Institute looks forward to leveraging her skills and insights to drive forward MRRI’s mission of enhancing motor rehabilitation through cutting-edge technology and scientific inquiry.

MRRI is pleased to announce that Amanda Rabinowitz, PhD, has been selected as this year’s recipient of the Joshua B. Cantor Scholar Award from the American Congress of Rehabilitation Medicine (ACRM). The Cantor Scholar Award was created in memory of the late Joshua B. Cantor, a board-certified rehabilitation psychologist and leader in the field of traumatic brain injury (TBI) research who was deeply involved in ACRM and the organization’s Brain Injury Interdisciplinary Special Interest Group. Dr. Cantor was committed to developing more effective treatments and helping people with TBI lead fuller lives through his research on issues surrounding sleep, fatigue, cognition, and emotion following TBI.

The Cantor Scholar Award recognizes one ACRM Brain Injury Interdisciplinary Special Interest Group member each year who has made substantial contributions to the field of brain injury neurorehabilitation. Each recipient’s research demonstrates the theoretical and methodological soundness, as well as the creativity in research design and/or intervention content that characterized the work of Dr. Cantor. The award will be presented at the ACRM Annual Conference in Dallas, TX, this fall.

Through the research she leads in the Brain Injury Neuropsychology Lab at MRRI, Dr. Rabinowitz has made important contributions to our understanding of chronic brain injury outcomes, spanning the spectrum of TBI severity. She has conducted important research on the psychosocial factors that can improve resilience after TBI, and her work leverages mobile technology and ecological momentary assessment to better assess outcomes and deliver interventions. Dr. Rabinowitz is also the Scientific Director of the Moss Traumatic Brain Injury Model System, and she continues to contribute to collaborative research on long-term brain injury outcomes. Like Dr. Cantor, Dr. Rabinowitz’s work is bringing hope, solace, and potential routes to better outcomes for people with traumatic brain injury.

A year ago, former MRRI Postdoctoral Fellow Solene Kalenine, PhD, received the exciting news that she had been selected as a laureate of the Fulbright-France program. This renowned program aims to foster dynamic and mutually beneficial collaborations between U.S. and French scholars, institutions, and societies by sponsoring mobility programs for students and researchers. Through receipt of this prestigious fellowship, Dr. Kalenine had an opportunity to come back to MRRI for a full year to conduct research with her former post-doctoral mentor Laurel Buxbaum, PsyD, as well as Erica Middleton, PhD, two MRRI scientists who are experts on treatment of action and language deficits after stroke.

Overall, Dr. Kalenine’s research program aims to understand the relationships between knowledge about objects and action. Recently, she developed a line of research that focuses on support images for word learning. In this research, she aims to evaluate whether images that convey motor cues may help people to learn and produce novel or uncommon words. Dr. Kalenine obtained promising results in her previous studies in this area, which were conducted in children and adults with neurotypical cognitive function.

In neurotypical adults, object nouns learned with an image showing the appropriate gesture for the object’s use (for example, a hand holding a hammer) were learned better in a naming task than nouns learned without the gesture cue. Based on this, Dr. Kalenine hypothesized that this type of action-related or motor cue might  also be helpful for people who have language deficits after stroke (aphasia). Re-learning words with images displaying motor cues could facilitate word retrieval and help people who had a stroke name objects more easily.

Twenty participants with post-stroke aphasia are being recruited from the MRRI Research Registry this year, with assistance from Shauna Zodrow, a research assistant. Participants are invited to attend six sessions during which they learn and practice a series of uncommon and difficult-to-retrieve object nouns.

The research team designed specific learning and practice exercises that involve objects, definitions, pictures, and the addition of gesture cues for half of the trained nouns. Dr. Kalenine and her collaborators will then evaluate the impact of training on how easily participants can retrieve these uncommon words in different tasks and situations. In participants who have completed the study to date, preliminary data are very encouraging. Participants all showed better recognition and naming of the object nouns after training, and gesture cues seem to lead to even faster word retrieval.

Drs. Kalenine, Buxbaum, and Middleton are looking forward to completing data collection and examining the full data set later this year. “Leading the Motor Word Learning project at MRRI has been an amazing experience. It has given me the chance to appreciate how a better understanding of basic cognitive processes may support the rehabilitation of cognitive deficits after stroke. Conversely, closely observing patients’ abilities and difficulties aids in thinking about how cognitive functions may be computed and interrelated in the healthy brain,” reflected Dr. Kalenine. She continued, “The translational approach adopted by the researchers at MRRI, beyond their specific area of expertise, has always been inspiring to me. Additionally, people have been very welcoming, and returning to MRRI after many years as a researcher in France felt like going back to my second home.”

Damage to a brain structure called the cerebellum causes a movement disorder called Ataxia. Derived from the Greek word for “lack of order,” Ataxia is marked by poor movement coordination. Ataxic movements have a “drunken” appearance, with lateral veering and oscillations. Many neurologic conditions such as stroke, multiple sclerosis, traumatic brain injury, and a host of genetic conditions can cause damage to the cerebellum, and the individuals affected often have disabling Ataxias that impair their balance, walking, arm movements, and speech. According to the U.S. National Ataxia Foundation, 15,000 – 20,000 people are estimated to have autosomal dominant genetic Spinocerebellar Ataxias in the United States, and tens of thousands more are affected by recessive and sporadic genetic ataxias, as well as other conditions that cause cerebellar damage.

There are no medications to treat Ataxia, leaving rehabilitation therapies like physical, occupational, and speech-language therapies as the only option for symptom management. However, rehabilitation outcomes are mixed in this population, with many individuals not benefiting from current intervention techniques. One reason for this may be that, in addition to its role in movement control, the cerebellum is critical to an important mechanism for learning new movement patterns. Many rehabilitation interventions try to train the brain to move the body in different ways to help compensate for neurologic conditions, and often, these techniques leverage the learning mechanism that depends on the cerebellum.

Research by Amanda Therrien, PhD, Director of the Sensorimotor Learning Laboratory at MRRI, has investigated whether a new training technique using binary reinforcement could help people with Ataxia improve their movement control. Using a combination of virtual reality and motion capture technology, binary reinforcement training aims to leverage a brain mechanism for learning new movements that does not depend as heavily on the cerebellum. Prior work from Dr. Therrien, published in the journals Brain and The Cerebellum, established that individuals with Ataxia can use binary reinforcement training to learn to adjust their arm movements and that it can be leveraged to help improve arm movement control. These findings emphasize that binary reinforcement training warrants further research to determine whether it can be applied to improve rehabilitation therapy for Ataxia more broadly.

One question that came out of Dr. Therrien’s previous work is related to the finding that, while most individuals with Ataxia were able to learn with binary reinforcement, a small percentage of study participants did not benefit from the training. The difference in training outcomes across individuals could not be explained by the severity or type of Ataxia, suggesting that the root cause of this variability in outcomes was more complex. Understanding the causes of variability in outcomes across individuals would advance our understanding of which individuals are most likely to benefit from binary reinforcement training, allowing streamlined screening for clinical trials as well as informing future work investigating whether the training technique can be modified to improve outcomes in individuals who respond poorly to the current protocol.

This past year, Dr. Therrien’s research group published a new study in the journal The Cerebellum that tested whether the historically underappreciated role of the cerebellum in movement perception could explain differences in learning across individuals. Movement perception relies heavily on a sense called proprioception (also called kinesthesia), which is how your brain knows where your body is in space when vision is absent. It is thanks to proprioception that you still know where your feet are, even though you may not be looking at them while reading this article. Proprioception is important for binary reinforcement training because the technique reduces visual information about movement outcomes to reduce dependence on cerebellum-dependent learning. Although cerebellar damage doesn’t impair primary proprioception (people with Ataxia have a normal sense of where their body is in space when they are not moving or if they are passively moved by another person or a device), it can interfere with proprioception when moving voluntarily. The degree to which cerebellar damage can interfere with the perception of voluntary movement varies across individuals and, like the response to binary reinforcement training, is not easily explained by Ataxia type or severity.

In Dr. Therrien’s recent study, a group of individuals with Ataxia performed a short binary reinforcement training task that required them to learn a new reaching movement. They then completed an assessment of their movement perception that tested the difference in proprioception between a condition in which they were passively moved by a robotic device and a condition in which they moved voluntarily. Dr. Therrien’s research group analyzed the relationship between the magnitude of learning achieved in the binary reinforcement task and performance in the movement perception assessment. The study team also included other variables in their analysis, such as the severity of participants’ arm movement impairment, their age, and their movement speed in the binary reinforcement task, to determine whether they also played a role in learning. The results showed a strong relationship in which a greater impairment in the perception of voluntary movement relative to the perception of passive movement was associated with a reduced response to binary reinforcement training. Replicating prior findings, none of the other variables tested exhibited relationships with the training outcome.

Overall, the findings suggest that tests of proprioception of voluntary movement may one day serve as a metric to predict which individuals with Ataxia might benefit from binary reinforcement training. This line of research in MRRI’s Sensorimotor Learning Laboratory is answering important questions that are critical for better understanding motor learning in order to develop more effective and more personalized treatments approaches for people with Ataxia.

Institute Scientists at MRRI, many of whom also hold faculty appointments within the Department of Rehabilitation Medicine at Thomas Jefferson University, are engaged in important clinical trials testing novel treatment approaches to improve outcomes of patients after stroke, spinal cord injury, phantom pain after limb amputation, and other conditions. In celebration of National Clinical Trials Day on May 20th, MRRI is pleased to highlight current clinical trials and acknowledge the important contributions of volunteers who participate in these trials.

Assessing an Animal-Assisted Treatment Program for Adults with Aphasia: The Persons with Aphasia Training Dogs Program

Aphasia is an acquired language impairment characterized by difficulty with word retrieval, and in some cases, difficulty constructing grammatically complete sentences or with auditory comprehension. People living with aphasia report its consequences reach far beyond linguistic, including loss of identity, engagement, and quality of life. This clinical trial, led by MossRehab Aphasia Center Director Sharon M. Antonucci, PhD, CCC-SLP, will determine the feasibility and potential benefits of the Persons with Aphasia Training Dogs (PATD) Program. Founded in the Life Participation Approach to Aphasia, and working from a strength, rather than deficit, perspective, PATD harnesses the pragmatic skill of persons with aphasia, which is critical to working with dogs, and capitalizes on mechanisms of action for animal-assisted treatment, to ameliorate psychosocial consequences of aphasia. The study will determine whether persons with aphasia can implement positive reinforcement techniques to train dogs in basic obedience skills and define participant characteristics associated with positive response to the intervention. This trial is a crucial first step toward the long-term goal to augment the evidence base with well-specified animal-assisted intervention protocols that target the psychosocial consequences of aphasia.

Criterion-learning Based Naming Treatment in Aphasia

Aphasia most commonly occurs following a stroke. The overarching goal of a clinical trial led by Erica Middleton, PhD, is to develop and test early efficacy, efficiency, and the tolerability of a lexical treatment for aphasia in multiple-session regimens that are comprised of retrieval practice, distributed practice, and training dedicated to the elicitation of correct retrievals. The aim of this work is to add to and refine the evidence base for the implementation and optimization of these elements in the treatment of production and comprehension deficits in aphasia, and make important steps towards an ultimate goal of self-administered lexical treatment grounded in retrieval practice principles to supplement traditional speech-language therapy that is appropriate for People with Aphasia from a broad level of severity of lexical processing deficit in naming and/or comprehension. This project cumulatively builds on prior work to develop a theory of learning for lexical processing impairment in aphasia that aims to ultimately explain why and for whom familiar lexical treatments work, and how to maximize the benefits they confer.

Efficacy and Optimization of Speech Entrainment Practice for People with Aphasia

Research has shown that people with chronic aphasia can benefit from treatment, but significant communication challenges often persist after therapy concludes. A clinical trial led by Marja-Liisa Mailend, PhD, aims to test and develop a promising treatment technique, termed speech entrainment, to enhance treatment outcomes for people with aphasia. Speech entrainment refers to speaking in unison with a model speaker by imitating the model in real time. Research has shown that speech entrainment is a ground-breaking technique for prompting connected speech in people with aphasia. The immediate stimulation effect of speech entrainment is well-documented. The present clinical trial will expand on prior findings to determine the direct effect of speech entrainment practice on independent speech production after the entrainment support is removed. The research team will also identify conditions that enhance treatment benefits and examine participant profiles associated with a positive treatment response. Findings from this study will help inform and enhance rehabilitation for individuals with aphasia.

GetUp&Go: A Randomized Controlled Trial of an Intervention to Enhance Physical Activity After TBI

An active lifestyle is known to provide wide-ranging benefits, from lowering the risk of chronic diseases to fostering emotional resilience and mental well-being. For people with moderate to severe traumatic brain injury (TBI), the challenge of meeting recommended activity levels is compounded by mobility limitations, pain, and the loss of social opportunities. The goal of this clinical trial, led by Amanda Rabinowitz, PhD, is to evaluate GetUp&Go, a program to promote increased physical activity in individuals after TBI. GetUp&Go is a remotely delivered program that includes one-on-one sessions with a therapist and a mobile health application (RehaBot). This clinical trial will determine whether the GetUp&Go program increases physical activity and improves mental and physical health in participants, compared to individuals who are put on a waitlist. The study team will also examine whether continued access to RehaBot helps maintain physical activity gains, as well as participant characteristics associated with treatment response. Their findings will inform the development of interventions to facilitate lasting increases in physical activity after TBI.

NIBS Therapy in Subacute Spinal Cord Injury (NIBS-SCI1)

Currently, no approved clinical therapies exist for repair of motor pathways following spinal cord injury (SCI) in humans, leaving permanent disability and devastating personal and socioeconomic cost. Promising findings from pre-clinical studies support that non-invasive brain stimulation (NIBS) may facilitate neural repair following spinal cord injury (SCI). Dylan Edwards, PhD, is leading a clinical trial to begin translating findings from pre-clinical studies to human motor deficits following SCI. This preliminary study will evaluate the effects of a novel non-invasive high-frequency repetitive transcranial magnetic stimulation protocol on arm motor function in people with cervical spinal cord injury. The treatment will involve daily transcranial magnetic stimulation sessions at the inpatient rehabilitation facility. Results from this study will establish the clinical effect size of the intervention, determine the safety and feasibility necessary for a subsequent controlled efficacy trial, and inform preclinical studies for the optimization of dosing.

Transcranial Direct Current Stimulation for Post-stroke Motor Recovery (TRANSPORT 2)

Dr. Edwards is also site principal investigator for a multi-site clinical trial led by Wayne Feng, MD (Duke University). This clinical trial aims to determine if non-invasive brain stimulation at different dosage levels, combined with an efficacy-proven rehabilitation therapy, can improve arm function. The stimulation will be delivered via transcranial direct current stimulation (tDCS), which uses direct currents to stimulate specific parts of the brain affected by stroke. The adjunctive rehabilitation therapy that will be used is called “modified Constraint-Induced Movement Therapy” (mCIMT). During this therapy participants will wear a mitt on the hand of the arm that was not affected by a stroke and will have to use the weaker (more affected) arm. The study will test three different doses of brain stimulation in combination with mCIMT to determine which dose is most effective at improving arm function. Results from this research will help optimize the parameters for non-invasive brain stimulation treatments to enhance motor recovery after stroke.

Virtual Reality Treatment of Phantom Limb Pain

After amputation of an arm or leg, up to 90% of individuals experience a “phantom limb”, a phenomenon characterized by persistent feelings of the missing limb. Many people with a phantom limb experience intense pain in the missing limb that often responds poorly to medications or other interventions. An NIH-funded multi-site clinical trial (NCT05296265) led by Laurel Buxbaum, PsyD, and Branch Coslett, MD (Penn Medicine), is contrasting the efficacy of two virtual reality (VR) treatments for phantom leg pain: an Active VR treatment and a ‘Distractor’ treatment. In the Active VR treatment, participants play a series of novel VR games that provide a realistic rendering of both legs while participants are actively engaged in rewarding VR sports challenges, puzzles, and other immersive activities requiring leg movement. In the Distractor treatment, participants feel passively transported through an immersive VR experience that does not require leg movements. The study is providing important information on how the two types of VR interventions impact pain, psychological health, and quality of life for people with phantom limb pain to inform the optimal clinical treatment of this debilitating condition.

MRRI is pleased to announce the recent receipt of new grants from the Albert Einstein Society to support research studies led by two of the Institute’s postdoctoral fellows.

One of the grant awards will fund a project led by Anna Krason, PhD, with MRRI Institute Scientist Erica Middleton, PhD, as co-investigator. This study will examine the process of conflict adaptation in people with post-stroke aphasia, a language and communication disorder that affects their ability to produce and understand language. While language production deficits have been extensively studied, language comprehension deficits have received limited attention in research and treatment. Moreover, comprehension deficits are multi-determined in that difficulties in comprehension frequently stem from impairments in other modalities, including executive functions. Understanding the underlying mechanisms and factors involved in comprehension deficits is therefore crucial for effective interventions to improve language comprehension.

It has been established that cognitive control, an executive function that enables the detection, revision, and resolution of conflicts between mental representations, plays a pivotal role in language comprehension. Dr. Krason’s study will provide important preliminary knowledge regarding conflict adaptation and whether particular individuals with aphasia could benefit from this potential treatment approach. Specifically, the study will address the question of whether upregulating cognitive control can optimize comprehension in at least some people with aphasia. Drs. Krason and Middleton will also conduct thorough background testing, providing initial observations into linguistic, cognitive control, and neurophysiological traits of individuals who show (or do not show) conflict adaptation. Together, the findings from this study will lay the groundwork for future research to inform patient selection and the development of a new theory-grounded conflict adaptation training for neurorehabilitation of individuals with aphasia after stroke.

As principal investigator of a separate grant award, Simon Thibault, PhD, will work with MRRI Institute Scientist co-investigators Aaron Wong, PhD, and Laurel Buxbaum, PsyD, on a study to clarify the mechanism underlying errors commonly seen in the performance of naturalistic actions (i.e., preparing breakfast and packing a lunchbox) in people with left-hemisphere stroke. Impairments in the ability to perform activities of daily living, such as preparing a meal, have been widely reported after stroke. These impairments are unrelated to underlying motor impairments, such as hemiparesis, as they can be observed when individuals are required to only use their ipsilesional, non-paretic (less-affected) arm.

Although such errors are frequently attributed to an underlying sequencing deficit – i.e., an inability to represent sequential orderings of events – other findings suggest that individuals with left-hemisphere stroke may not be impaired at learning simple finger-tapping sequences. In contrast, individuals with left-hemisphere stroke also frequently exhibit limb apraxia (30-50% of individuals), a disorder characterized by slowed or failed retrieval of single tool-use actions (e.g., stirring with a spoon). To identify the mechanism giving rise to ordering errors in naturalistic actions, the study team will first examine the pattern of impairments across a series of sequencing tasks of increasing complexity. They will then correlate those impairments with performance in naturalistic actions within the same group of individuals with left-hemisphere stroke. This research will address a critical gap in the understanding of impairments in naturalistic actions in individuals following left-hemisphere stroke. It will also bring together two lines of study that have thus far largely been examined separately: naturalistic actions and action sequencing. Ultimately, research in this area will aid in developing rehabilitation techniques that better target the deficits underlying the inability to perform activities of daily living in individuals after stroke, particularly for those who have limb apraxia.