Stroke recovery: The exciting trends of the future

Steven A. Kautz, Professor at the Ralph H. Johnson VA Medical Center and the Medical University of South Carolina College of Health Professions gives a glimpse into the future trends for stroke recovery research

There is a crucial need for research into recovery from a stroke that leads to improvements in the long-term quality of life of those who have suffered a stroke. The term “Recovery from Stroke” almost always describes an incomplete process that includes compensatory behaviour and modified neural circuits rather than recovery of the function of pre-morbid neural tissue. This term broadly describes events, such as recovery of damaged neural tissue by neuroprotection, recovery of damaged neural circuitry by reorganisation, recovery of behaviour through rehabilitation, and recovery of quality of life through increased participation in daily living activities.

Most stroke research focuses on acute treatment or prevention within hours or days after stroke, with research to help those with chronic disabilities after stroke having long been underemphasised. Current understanding of how the nervous system repairs and reorganises neural circuitry (i.e., neural plasticity) to promote behaviour, and how neural plasticity can be harnessed to maximise recovery of behaviour through rehabilitation, is inadequate. There is a pressing need to conduct animal and human studies to improve understanding of the mechanisms involved in functional behavioural change and neural plasticity induced by interventional studies, and build a framework to help researchers develop more efficacious, evidence-based interventions.

Such studies will help identify the neural substrates and processes underlying specific behaviours and recovery of these behaviours after stroke, including translational studies in which we model human studies in animals with complementary intervention and measurement paradigms. Multidisciplinary translational research into stroke recovery is of special importance to the people of my state of South Carolina in the U.S. due to their disproportionate rate of stroke and the economic and societal burdens of resulting post-stroke disabilities.

I believe that better understanding of the experience-dependent nature of neural plasticity will allow researchers to investigate and exploit inherent neural recovery processes, develop and translate novel mechanism-based interventional strategies and ultimately, improve the function and quality of life of individuals recovering from a stroke. Currently, outcomes following stroke are suboptimal because of major gaps in foundational understanding of the neural circuitry (substrates and processes) underlying behaviour, as well as their repair and reorganisation (i.e., neural plasticity).

While the translation of methods to augment plasticity inspired by basic science knowledge holds exceptional promise for advancing the field, rehabilitation interventions will necessarily play a central role in advancing recovery from stroke. Even if the highest hopes for cell-based therapies (i.e., neural repair by stem cells), pharmaceuticals or other adjuvant methods of enhancing neural plasticity, such as invasive or non-invasive brain stimulation techniques are realised, rehabilitation will be crucial as the behavioural engine to ‘teach’ the new neural circuitry to perform the necessary functions. Thus, a major focus of current research is to develop and test novel methodologies for performing and augmenting rehabilitation interventions, based on principles consistent with the mechanisms of experience-based plasticity in the nervous system.

I am fortunate to direct a talented team of multidisciplinary researchers at the NIH-funded Center of Biomedical Research Excellence (COBRE) in Stroke Recovery, a collaboration between the Colleges of Health Professions and Medicine at the Medical University of South Carolina in Charleston, South Carolina. The initiative is supported by the NIH’s Institutional Development Award (IDeA) program put in place to promote, augment and strengthen the biomedical research capabilities of institutes in IDeA states. I believe that there are four aspects of our centre that offer insights into the future of stroke recovery research.

Four insights into the future of stroke recovery research

First, multidisciplinary team science is the clear future of stroke recovery research, and these teams should include both clinical and basic scientists. Our centre includes teams with experts in rehabilitation, neuromodulation, statistics, bioinformatics, neuroimaging and neuroscience. In addition, those teams include scientists from the clinical professions that are on the front lines of stroke recovery and rehabilitation – stroke neurologists, physical therapists, occupational therapists, speech-language pathologists, neuropsychologists and psychiatrists, among others.

Second, neuromodulation offers incredible opportunities for application to stroke recovery. Stroke is a disease that affects the nervous system. After the stroke, there are neurons that have died. However, the deficits do not just result from the loss of those neurons, but also from the changes induced in all of the neural circuits and pathways in which those neurons participated. Neuromodulation offers a potential methodology to modify aberrant circuits and improve, or even restore, some of the post-stroke deficits negatively impacting the quality of life. The BRAIN initiative at NIH has led to the development of a number of new tools that allow researchers to better understand how to modify neural circuits. That many of these neuromodulation methods use electricity directly at the aberrant circuit, instead of pharmaceuticals delivered systemically, offers the promise of an approach with greatly reduced potential for side effects.

Third, a better understanding of the experience-dependent nature of neural plasticity and its translation into clinically effective interventions will be crucially facilitated by the development of a theory-based measurement framework that includes quantitative behavioural, neurophysiological and imaging based measures of:

1) Normal neurological function;

2) Underlying structural and functional damage after stroke;

3) Experience-dependent neural plasticity during rehabilitation;

4) Structural and functional changes post-rehabilitation and;

5) The functional recovery of each individual patient.

Fourth, comprehensive multidisciplinary databases enabled by data sharing between studies and between centres offer incredible promise for tackling the difficult problem of determining which treatment or treatments are needed for each stroke survivor. Stroke is heterogeneous and recovery is likely to need to be personalised to the specific deficits and available neural substrates of each individual. Thus, there is a need for a theory-based measurement framework and the data from multidisciplinary domains like imaging, neurophysiology, behaviour, cognition, language, etc. in order to better define the various phenotypes of stroke recovery – what has been called dense phenotyping. The ultimate goal is to connect this dense phenotype data with the electronic health-care records and genomic data.

This is an exciting time in the field of stroke recovery as these emerging trends leave researchers well positioned for breakthroughs that can truly improve the quality of life for stroke survivors. Research centres, such as our COBRE and others throughout the world are assembling innovative multidisciplinary research teams, testing promising technology like neuromodulatory devices, and sharing data to assemble rich multidisciplinary data sets to allow dense phenotyping. I foresee great progress in personalised stroke recovery in the next decade.

 

Steven A Kautz, PhD

The Christie Family Endowed Chair in Stroke Rehabilitation Research
Director, Center of Biomedical Research Excellence (COBRE) in Stroke Recovery
Director, National Center of Neuromodulation for Rehabilitation (NC NM4R)
Chair and Professor, Department of Health Sciences and Research
Professor, Division of Physical Therapy
College of Health Professions
Medical University of South Carolina
Charleston, SC

Research Career Scientist
Ralph H. Johnson VA Medical Center
Charleston, SC
Tel: +1 843 792 3867 (office)
kautz@musc.edu

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