Category: Blog

Moss Rehabilitation Research Institute (MRRI) was pleased to welcome Simon Thibault, PhD, in January of 2022. Since joining the Institute, Dr. Thibault has been working with Institute Scientists Aaron Wong, PhD, and Laurel Buxbaum, PsyD, to further his training and his scientific research. In this interview, Dr. Thibault shares more about his career and his work.

1) Can you tell us more about your academic background and training?

I did my studies in France with my undergraduate and postgraduate degrees in Sports and Human Movement Sciences at the University of Nantes. In Nantes, I became interested in research quite early, and I was at that time mentored by Dr. Thibault Deschamps. Afterwards, I did a 5-month postgraduate internship at the University of Queensland in Australia in Dr. Timothy Carroll’s lab which focuses on exercise science and motor control. My early research projects were related to the interaction between cognition and the motor system, or more general motor control projects. After this internship, I started my PhD at the University of Lyon under the supervision of Dr. Claudio Brozzoli and Dr. Alice Roy. During my PhD, I continued investigating interactions between cognition and the motor system, particularly focusing on the interaction between tool-use and language. I started my postdoc at MRRI about one year ago under the supervision of Dr. Aaron Wong and Dr. Laurel Buxbaum, and my current research projects are examining tool-use impairments in patients with neurological conditions such as stroke.

2) What attracted you to science?

I think I find science attractive because you work at the edge of current knowledge, and you can participate in extending this knowledge. I think that is the thing that excites me the most about science. Also, I like the fact that it requires me to learn and master multiple skills for various tasks, such as creating a new project from scratch, setting up a new experiment, analyzing data, and then sharing these results with the community through conferences or journal papers. More specifically, I have been particularly attracted to neuroscience because the brain is an intriguing part of our body, in which the mechanisms for many functions are still unclear. It is definitely exciting to be part of the research community trying to disentangle how this structure works.

3) Why did you choose to work at MRRI?

MRRI has given me the opportunity to pursue my main research interest in tool-use and complex motor behaviors (and how these motor functions interact with the cognitive system) by studying patients with apraxia. Apraxia occurs after a left-hemisphere cerebrovascular accident, and it impacts the actions of daily life, the use of tools, and complex motor behavior without apparent low-level sensorimotor deficits. For me, this is also a real opportunity to learn about the neuropsychological approach from experts in the field.

4) What are some of the research questions you are currently working to address?

Currently, I am working on determining what makes tools difficult to use for patients with apraxia. Dr. Wong, Dr. Buxbaum, and I think the degree to which the hand motion and tool tip motion differ makes these tools difficult to use for these patients. In parallel, I am planning to lead a project to better understand what makes it difficult for stroke patients (with or without apraxia) to perform an action sequence.

5) What have been some of the key findings of your research thus far?

During my PhD, I demonstrated that that tool-use abilities and syntactic abilities in language involved similar parts of the brain, and they reciprocally influence each other at the behavioral level. This finding has been of interest for a large community of scientists but also therapists because it introduces questions regarding whether patient populations with language or motor impairment may recover function by training the non-impaired ability (either language or motor function).

6) Can you tell us more about the impact or potential impact of your research?

Despite several years of research, apraxia is still a poorly understood deficit, and there are a lot of debates about what is really impaired in these patients and what the underlying mechanisms are. I hope my work will help to better clarify the underlying mechanisms, which could result in the development of new rehabilitation strategies to help these patients to cope with the difficulties they experience in their daily lives.

7) What is something that you have learned or hope to learn during your postdoc at MRRI?

Starting my postdoc at MRRI has been exciting and informative on many levels. First, I needed to familiarize myself with this novel environment and a new country. MRRI has a great environment for training and performing neuropsychological research thanks to the MRRI Research Registry. It has been interesting to learn more about how research is funded and conducted in the United States. Also, I was glad to gain experience working with patients. There are many considerations when conducting research with patient populations, and it is very different from working with neurotypical participants. By coming here, I hope to learn new skills, especially in grant-writing, to become a more independent researcher, as well as to gain new skills in neuroimaging analyses of patients’ data.

8) What is one of your favorite MRRI memories?

I would say the inclusion of the first patient in my study was a stressful but an exciting moment. Given some patients may have some language impairments, it is an additional challenge to make sure they can understand me with my (strong) French accent. However, most of them have been able to understand my instructions so far, and there is always a research assistant around that can help me handle more complex situations. I also have to acknowledge that I was particularly well trained by my advisors before this first patient inclusion to avoid these potentials misunderstandings.

9) What are your long-term career goals?

I would like to get a permanent research position in academia. Most likely, I will return to France for my next position, but I am open to any other interesting opportunities that may arise.

10) What do you like to do in your free time?

I am a big fan of sports, especially basketball, so I am happy to live in the U.S. where basketball is popular. I like to go to the 76ers games, and I also try to keep playing basketball at least once each week. In addition, I spend a lot of time with a group of French expats that are now my friends.

Suicidal thoughts and behaviors are a serious concern after traumatic brain injury (TBI). Research based on the Traumatic Brain Injury Model System National Database – a large database of long-term outcomes after moderate-to-severe TBI including over 1,500 patients recruited from MossRehab – has shown that approximately 3% of individuals report at least one suicide attempt, and over 8% report suicidal thoughts in the first five years after injury. There is an urgent need to identify the risk factors that are associated with these thoughts and behaviors, so clinicians know who needs intervention and how best to intervene.

Amanda Rabinowitz, PhD, is involved in a research project designed to meet this need. Moss Rehabilitation Research Institute (MRRI) is enthusiastic to be one of the sites participating in The Leveraging Nationwide Research Infrastructure to Enrich Brain Health after TBI study, or ENRICH Brain Health for short. This multicenter study, funded by an $8 million Focused Program Award from the Department of Defense to Kristen Dams-O’Connor, PhD, of Mount Sinai, aims to understand and improve long-term cognitive and psychological health after TBI. Moss is participating in one of the five separate projects supported by this award, designed to address a critical gap in understanding risk, resilience, and protective factors associated with cognitive and psychological outcomes among civilians and Veterans with TBI.

This project leverages existing infrastructure of the National Institute of Disability, Independent Living and Rehabilitation Research (NIDILRR)-funded longitudinal civilian and Veteran TBI Model Systems of Care to identify and follow individuals with chronic TBI to investigate factors associated with changes in cognitive function, as well as suicidal thoughts and behaviors over time. Researchers at MRRI will reach out to participants in the TBI Model Systems study who have exhibited changes in their cognitive performance over time to collect new data on potentially-modifiable risk factors and protective factors for cognitive decline. The team will also re-contact Model Systems participants who endorsed high-risk suicidal ideation and/or suicide attempt at a prior study visit to collect data on current suicidality and identify modifiable risk factors and protective factors.

The other projects supported by the award establish a community-based advisory group, broadened recruitment efforts of Veterans with TBI for post-mortem brain donation, histopathological study of post-mortem brain tissue, and brain imaging studies to understand the network-based structural and functional alterations underlying neurobehavioral health deterioration following TBI. Collectively, these projects will contribute to the development of tools for diagnosis and treatment throughout the lives of patients with TBI.

Erica Middleton, PhD, of Moss Rehabilitation Research Institute (MRRI) and Malathi Thothathiri, PhD, of the George Washington University (GWU) have a longstanding history of working together. The two scientists had the good fortune to not only be contemporary postdoctoral fellows under the mentorship of MRRI emeritus Myrna Schwartz, PhD, but they shared an office as well when MRRI was housed at the Einstein facility at Tabor Rd. in Philadelphia. Dr. Middleton reminisced, “I remember getting to know Malathi and all about her family in India during our postdocs. One time, she brought me a fantastic black tea from one of her trips to see her family. She was a great office mate.” Dr. Thothathiri added, “Erica and I had fun talking about all kinds of things from food to philosophy in between work. What was nice was the seamless blending of the personal and professional. I enjoyed meeting Erica’s dog Louie, who in addition to being a great dog was also a great soccer goalie.” Fast forward fourteen years, and Drs. Thothathiri and Middleton are overseeing multiple studies conducted at MRRI, supported by a NIH grant award to GWU and MRRI.

The goal of the research is to test how cognitive control affects sentence comprehension in healthy adults and patients with aphasia. Cognitive control involves regulating your behavior, to meet the specific goals of a given context, including understanding one another in a social interaction. Aphasia is a disorder that affects one’s ability to speak and sometimes understand language, and it is common after a stroke. The research seeks to clarify how cognitive control deficits outside of language comprehension impact the ability of people to interpret sentences. The findings will guide future research on alternative ways to treat language and communication disorders.

In a prior study contrasting two people with aphasia with sentence comprehension impairments, Drs. Thothathiri and Middleton found that each presented with a different reason for their comprehension problems. Multiple measures, including eye tracking and electrophysiological brain recordings, converged to show that one participant had impaired functioning in linguistic cognitive control, whereas the other experienced difficulty because of an overreliance on the meanings of the words at the expense of computing syntax. The identification of distinct underlying problems points to different potential treatment paths for patients who have similar clinical presentations.

Dr. Thothathiri brings to the project her excellent quantitative and methodological skills and expertise in cognitive control, and Dr. Middleton is an internationally recognized expert in designing and conducting studies with people with aphasia from stroke. Drs. Thothathiri and Middleton plan to leverage MRRI’s resources as they prepare a submission for a renewal of the R01 grant award. Dr. Middleton shared, “We’ll be tapping our MRRI colleagues to give feedback on our grant proposal. In this next cycle, we plan to conduct foundational work to begin to translate the findings in the first cycle to address real clinical problems that people with aphasia and their therapists face, including designing different treatment solutions for different individuals. The scientists at MRRI are among the best out there for helping design translational research going from basic scientific findings to clinical application.”

Collaborative projects such as this one allow leading researchers at MRRI and other institutions across the country and around the world to combine their strengths to make meaningful advances in neurorehabilitation.

MossRehab and Moss Rehabilitation Research Institute (MRRI) are devoted to improving the lives of individuals with neurological disabilities through world-class research and outstanding clinical care. MRRI is grateful for the support of donors whose contributions have enabled the Institute to flourish and conduct meaningful scientific research over more than three decades.

Recently, Mr. Thomas Lloyd joined Einstein’s Legacy Circle with a bequest gift that will support research on stroke and Parkinson’s disease. Mr. Lloyd first became acquainted with MossRehab after he experienced a stroke in 2016. He received excellent care at MossRehab as a patient and has been dedicated to the missions of MossRehab and MRRI ever since. In addition to his personal connection with stroke, Mr. Lloyd’s late wife Susan lived with Parkinsonism, and this inspired him to support research on Parkinson’s disease being conducted in MRRI’s Cognitive-Motor Learning Laboratory directed by Aaron Wong, PhD.

“There are many institutions that research what causes Parkinson’s and how to cure it, but I think Moss’ approach to finding out how to make it more bearable through research is just as important, if not more,” remarked Mr. Lloyd. “I look at it, in general, as how do we make people feel better and cope better?”

In his will, Mr. Lloyd has designated a gift that will establish The Thomas Lloyd Stroke Research Fund and the Thomas Lloyd Parkinson’s Research Fund, two endowed funds at MRRI. These donations will support cutting-edge research, equipment, and technologies at the Institute.

“Rehabilitation research improves our understanding of neurological disorders such as stroke and Parkinson’s Disease and helps us identify ways to support better individuals living with these conditions, but these studies take time and require persistent efforts,” said Dr. Wong. “Donations such as Mr. Lloyd’s are therefore critical to sustaining such endeavors over the long term.”

Through his bequest gift, Mr. Lloyd’s generosity will continue to support MRRI’s innovative and impactful work for years to come. Contributions from Mr. Lloyd and other generous donors are instrumental in providing the resources necessary for MRRI to continue advancing the state of science in the field of neurorehabilitation.

To learn more about how you can support the critical research at MRRI, please contact John J. Schlesinger, CFRE, CAP® at 215-456-3258 or john.schlesinger@jefferson.edu.

MRRI is excited to announce that former Director and Institute Scientist Emeritus John Whyte, MD, PhD, has been selected to receive the Distinguished Member Award from the Association of Academic Physiatrists (AAP). The AAP is a professional organization dedicated to improving patient care by advancing physical medicine and rehabilitation (physiatry) through research and education.

The AAP Distinguished Member Award is given to internationally recognized leaders in the field of physiatry who have made significant contributions to the field through their teaching, research, and academic publications and who have demonstrated a history of service to the AAP. Only one candidate per year may be nominated for this award.

Over the course of his career, Dr. Whyte has made substantial clinical and research contributions to the field of neurorehabilitation. He served as principal investigator in establishing the world-class Moss Traumatic Brain Injury Model System and collaborated with subsequent PI’s, Tessa Hart, PhD, and Amanda Rabinowitz, PhD, in its successful development for more than 20 years. Model Systems are highly-competitive federally funded centers of excellence for both treatment and research related to a particular disability. In addition, Dr. Whyte has played a critical role in developing and disseminating the Rehabilitation Treatment Specification System, a standardized system for specifying the components of rehabilitation treatments. Through his research, Dr. Whyte has improved our understanding of attention and executive function impairments in traumatic brain injury, and he has meaningfully advanced clinical practice surrounding the assessment and treatment of disorders of consciousness after brain injury.

Beyond his clinical contributions, Dr. Whyte has dedicated substantial effort to training the next generation of rehabilitation physicians and scientists through leadership of numerous career development initiatives over the years. These initiatives include designing the national Rehabilitation Medicine Scientist Training Program in 2001 (which he continues to co-direct with Michael Boninger, MD) and serving as PI of the T32 Postdoctoral Training Program in Translational Neurorehabilitation Research held jointly with the University of Pennsylvania.

MRRI congratulates Dr. Whyte on this well-deserved recognition for his many career achievements in research and education. He will be presented with the AAP Distinguished Member award on the final day of the AAP’s Annual Meeting, Friday, February 24, 2023.

After six years as Associate Director of Moss Rehabilitation Research Institute, Laurel Buxbaum, PsyD, is transitioning this role to the newly appointed Associate Director Amanda Rabinowitz, PhD. Since taking office in 2018, Dr. Buxbaum has helped lead the institute through multiple landmark events including the start of a new Director, recruitment of multiple new Institute Scientists, the many challenges of the COVID-19 pandemic, and the logistics and opportunities presented by the recent merger of Einstein Healthcare Network and Jefferson Health. While engaged in this leadership role, Dr. Buxbaum has maintained an active and highly productive research program, and she will continue her research at MRRI as an Institute Scientist and Director of the Cognition and Action Laboratory. The scientists and staff of the Institute are deeply grateful to Dr. Buxbaum for her leadership and service over the past several years.

“It has been a great privilege to serve MRRI as Associate Director for the past six years,” Dr. Buxbaum stated. “I’m proud of what we’ve been able to accomplish during times that were both exciting and challenging. With our recruitment of Dylan Edwards, PhD, MRRI Director, as well as several talented Institute Scientists, we are very well-positioned for further growth. I look forward to continuing to play an active role in maintaining the Institute’s profile as a world-class research entity, as well as leading my laboratory’s NIH-funded research program in new directions.”

Dr. Amanda Rabinowitz began work as MRRI’s new Associate Director at the start of this month. In this role, she will assist Director Dylan Edwards, PhD, in guiding the Institute as it continues to grow and further its research programs in the coming years. In addition to her new role, Dr. Rabinowitz is Director of the Brain Injury Neuropsychology Laboratory and Scientific Director of the Moss Traumatic Brain Injury Model System. Dr. Rabinowitz will continue in these roles as well, advancing our understanding of cognitive and emotional outcomes in individuals with chronic brain injury and the impacts of technology-based interventions such as mobile health technology.

“It’s a great honor to have the opportunity to serve MRRI in this leadership role after being a part of the team for the past seven years,” remarked Dr. Rabinowitz. “This is an exciting time for the institute, as we continue to grow and take advantage of new opportunities now that we are under the Jefferson Health umbrella. I’m excited to move forward alongside Dr. Edwards supporting our talented team of Institute Scientists as MRRI continues to advance the science and clinical practice of neurorehabilitation.”

 

The World Health Organization estimates that 250,000 – 500,000 people globally experience a spinal cord injury each year, and these injuries often lead to substantial long-term disability, impacts on quality of life, and high economic costs. Despite substantial investigation in this area of research, scientists have not yet identified a way to trigger damaged neurons in the human adult spinal cord to successfully regenerate or regrow.

In particular, researchers have been investigating various signaling pathways that are active during early development when these axons naturally grow, as well as the physiological changes that occur afterward that prevent neuronal regrowth and regeneration once development is completed. During development of the central and peripheral nervous system, long-distance axon growth is mediated in part by a biochemical pathway within neurons called the RAF–MAP2K (mitogen-activated protein kinase kinase) signaling cascade. This pathway has been identified as a potential target for intervention to facilitate axon regrowth and regeneration after spinal cord injury.

In order to evaluate new potential treatments for spinal cord injury, a critical step is examining the impacts of these interventions in animal models. Further research can then focus on translating these results to develop treatments appropriate for clinical application in humans.

In work led by researchers at Burke Neurological Institute and Weill Cornell Medicine, researchers investigated whether the RAF–MAP2K signaling cascade could be activated using genetic engineering and noninvasive stimulation to promote axon sprouting and functional recovery in the adult nervous system in mice. Their recent findings represent a significant advancement in the translation of a potential non-invasive treatment approach to promote motor recovery after spinal cord injury.

Dylan Edwards, PhD, MRRI Director and Director of the Human Motor Recover Laboratory, is a co-author on the paper recently published in Science Translational Medicine that details their experiments and findings. In particular, Dr. Edwards was instrumental in providing insight for the noninvasive stimulation protocols used in this research. Non-invasive stimulation methods such as repetitive transcranial magnetic stimulation (rTMS) show promise for enhancing recovery after nervous system injury, but there are still many unanswered questions regarding the mechanisms by which these methods confer benefits, the extent of recovery which may be possible, and the optimal parameters of delivery.

Using genetic approaches, the authors demonstrated that activation of BRAF (a protein kinase that plays a key role in the RAF–MAP2K signaling cascade) resulted in upregulation of transcription factors that were shown to be associated with neuronal development and neuronal regeneration in prior studies. Activation of BRAF was also associated with downregulation of transcription factors previously demonstrated to limit the capacity of axons to regenerate. In their subsequent experiments, the authors of this paper showed compelling evidence that BRAF activation allowed axon sprouting, formation of new synapses, and functional recovery in mouse models of spinal cord injury. These results suggest that conditions conducive to regeneration and regrowth can be induced in mature neurons in the corticospinal neurons via the RAF–MAP2K signaling cascade by activating BRAF.

Further, scientists determined that daily high-frequency rTMS sessions activated the RAF–MAP2K signaling pathway and also modulated the expression of the same set of transcription factors associated with regeneration. In addition, high-frequency rTMS resulted in axon sprouting, regeneration, and functional recovery in spinal cord neurons after injury. Moreover, researchers confirmed that a functional RAF–MAP2K signaling pathway was essential to achieving these results.

These findings are important because many genetic approaches used in animal models are not feasible for use in clinical applications in humans. High-frequency rTMS is a non-invasive method that has been demonstrated to be safe to use in numerous clinical research studies, and the results of this study strongly support that it may be an effective approach to facilitate regeneration and recovery after spinal cord injury.

Dr. Edwards and his colleagues have begun clinical trials of a high-frequency rTMS protocol in humans, and they will also continue to investigate related questions in animal models. This line of research has the potential to lead to the development of a non-invasive, low-risk treatment method for spinal cord injury and other nervous system injuries that could improve the lives of millions of people around the world.

This research was made possible by funding from the National Institutes of Health, the New York State Department of Health Spinal Cord Injury Research Board, the Craig H. Neilsen Foundation, the Wings for Life Research Foundation, the Goldsmith Research Foundation, and the Burke Foundation. You can read the published version of the original research article in Science Translational Medicine, and a full-text pre-print of the manuscript is also available on bioRxiv.