COBRE Newsletter Vol 2 Issue 3 January 2016

Recovers Volume 2

Issue 3

Winter 2016

Newsletter of the COBRE in Stroke Recovery

Newsletter of the COBRE in Stroke Recovery Medical University of South Carolina

Medical University of South Carolina

Inside Recovers The Medical University of South Carolina was awarded a major grant from the National Institutes of Health (NIH) to support the development of a Center for Biomedical Research Excellence (COBRE). This award (P20GM109040) is part of the Institutional Development Award (IDeA) program administered by the National Institute of General Medical Sciences (NIGMS).

Visit: http://www.nigms.nih.gov/Research/CRC B/IDeA/Pages/default.aspx to learn more about the IDeA program.

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From the Director NeuroModulation for Rehabilitation Workshops 2nd Annual Meeting Poster Presentation Publication Highlight New Team Members Visiting Scholar Professional Milestones Grants Upcoming Events Contact Us

y From T

the Director

Happy 2016 to all. It has been an eventful second year for the COBRE in Stroke Recovery. As we near the beginning of our third year in April, it is an appropriate time to reflect on some great accomplishments that have accumulated as we have worked diligently to build a strong translational research program. Preeminent among our accomplishments in this great year has been amazing success with extramural funding. When the COBRE was awarded in June 2014, MUSC investigators had just over $2 million in annual funding for stroke recovery-related research. We are not even finished with this year and our annual funding is already above $8 million. Perhaps no successes reflect the value of the COBRE infrastructure better than our being awarded two centers in highvisibility national networks this year. Robert Adams leads the WISSDOM team (Wide Spectrum Investigation of Stroke Outcome Disparities on Multiple Levels) that was awarded one of four centers in the American Heart Association’s Strategically Focused Research Network on Disparities in Heart Disease and Stroke. I lead the NC NM4R team (National Center of NeuroModulation for Rehabilitation) that was awarded one of six centers in the Medical Rehabilitation Research Infrastructure Network, funded by the Eunice Kennedy Shriver National Institute of Child Health & Human Development. Both centers strategically advance the Stroke Recovery Research program for which the COBRE provides the foundation. WISSDOM brings several great new elements to MUSC stroke recovery research: a community-based research project, a focus on health disparities, and new collaborators in the College of Nursing. NC NM4R establishes MUSC as a national leader in the development and application of neuromodulation for rehabilitation and recovery, essentially making the COBRE infrastructure available on a national scale. The COBRE will benefit in many ways.

Increased use of and support for our cores will move us closer to financial independence. Many talented researchers at all levels are coming to campus to interact with us in many ways—from trainees first learning the technology to world leaders in the field giving seminars, consulting and collaborating. Furthermore, the BSTIM Core now has a dedicated funding stream to perform its own research projects whose synergies will help advance COBRE research projects.

Another big accomplishment was our second annual meeting, where we received a glowing review from our stellar External Advisory Board who were “impressed by the extraordinary productivity and palpable cohesion demonstrated by this talented group of investigators. We want to congratulate the team on an incredible job, and we encourage them to keep up this level of engagement and productivity.” They gave us a number of excellent suggestions that we will seek to implement in the new grant year. Chief among these are: 1. Support for developing an Animal Behavioral Core.

2. Training in clinical trials definitions and registrations as NINDS starts enforcing special rules for clinical trials applications.

3. Engaging local rehabilitation hospitals to improve recruitment.

4. Coordinating with the NC NM4R to maximize impact.

5. Better tracking of clear goal-directed metrics.

6. Starting now to identify the next generation of junior investigators.

7. Working with the wider research community to standardize the data collected in RESTORE so that other centers can benefit from a welldefined set of measures.

8. Leveraging the successes of the COBRE to gain additional support from the administration for Phase II and III applications.

It has been a great second year and I look forward to even greater successes in our third year.

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Steve Kautz, PhD Director, COBRE in Stroke Recovery

Aim 3: Develop a research community in NM4R by being an active catalyst to coalesce an interactive community that shares ideas, collaborates extensively, and contributes to setting future goals for the field.

National Center of NeuroModulation for Rehabilitation (NC NM4R) The National Center of Neuromodulation for Rehabilitation (NC NM4R) is an infrastructure resource center funded by National Institutes of Health (National Institute of Child Health and Human Development/National Center for Medical Rehabilitation Research). Housed within MUSC’s College of Health Professions and College of Medicine, the Center’s leadership is directly involved in the COBRE mission and strategic planning. Steve Kautz is the Program Director, Mark George is the Scientific Director, and Colleen Hanlon and DeAnna Adkins serve on the Executive Committee. In addition, a number of other COBRE investigators and staff contribute to the NC NM4R. The mission of NC NM4R embraces many opportunities for people interested in neuromodulation. With the goal of exerting a sustained, powerful influence on the research field of neuromodulation for rehabilitation, the center focuses on translational activities and programming to achieve the following aims: Aim 1: Train researchers in NM4R through workshops, advanced hands-on training, consultations with MUSC laboratories, and mentorship in research skills and grantsmanship.

Aim 2: Provide scientific programming in NM4R through webinars, national/international conference sessions, and specialized NM4R conferences.

Aim 4: Advance the field of NM4R by: (a) sponsoring a focused technical development program that will define material for promulgation in the workshops and other forums and continue to develop and advance NM4R methods, particularly those needed in critical translational studies, and (b) offering peer-reviewed pilot projects utilizing human and/or animal models.

The overall focus for NC NM4R is development of its research community. Specifically, this community will be created from a group of clinical and basic researchers who are currently working in the field of neuromodulation for rehabilitation and who are interested in gaining immediate knowledge and training in cutting edge and next generation NM4R applications. These applications will allow researchers to study neuroplastic changes associated with brain stimulation and operant conditioning and help understand mechanisms of neuroplasticity. As a result, members will be better equipped to develop new rehabilitation interventions. Members in this community will receive access to the extensive research data base to enhance their research and practice. Please join by going to the website: http://musc.edu/ncnm4r/

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NM4R Workshops - March 2016 March 7-11, 2016 Introductory (Level 1) Workshop The purpose of this Level 1 workshop is to introduce a range of concepts of NM4R (brain stimulation and operant conditioning) and teach skills in basic TMS and operant conditioning neurophysiology.

Individuals desiring certification will be tested by Dr. Mark George on TMS use. Successful individuals will receive a certificate for learning and demonstrating the basic skills.

Advanced (Level 2) Workshops The Level 2 workshops are appropriate for those with existing expertise in neuromodulation.

March 14-16, 2016 Operant Conditioning of EMG Evoked Potential Workshop This workshop provides hands-on opportunities to learn and practice the fundamentals of human operant conditioning protocols.

March 16-18, 2016 Repetitive Transcranial Magnetic Stimulation for Rehabilitation This workshop addresses significant innovations achieved in restoring motor function through noninvasive human brain stimulation for patients who have experienced a stroke or traumatic brain injury.

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Conference Registration March 7-11, 2016 in Charleston, SC Level 1 NM4R Workshop Limited to 25 participants, apply by 5 pm (EST) February 9, 2016 March 14-18, 2016 in Charleston, SC Level 2 NM4R Workshop Limited to 10 participants per track, apply by 5 pm (EST) February 9, 2016 There is no charge to participants for the workshops.

Please visit the website and complete the application form: http://musc.edu/ncnm4r For further information: jonesant@musc.edu

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COBRE Annual Meeting On January 20-21, the Second Annual Meeting of the COBRE in Stroke Recovery provided the opportunity for the Center’s External Advisory Board to review the progress of the five Junior Investigator projects and the four scientific cores. Steve Cramer, MD, Felipe Fregni, MD, Argye Hillis, MD, Randy Nudo, PhD, and Steve Wolf, PhD, serve as the Center’s external advisors, offering valuable review and insight to guide the Center’s progress and development through its third year as a Center of Biomedical Research Excellence (COBRE).

Board Chairman Steven L. Wolf, PhD, PT, FAPTA, FAHA Professor, Departments of Rehabilitation Medicine and Medicine Professor, Department of Cell Biology Emory University School of Medicine Center of Rehabilitation Medicine Senior Research Scientist, Atlanta VA Center for Visual and Neurocognitive Rehabilitation

Board Member Steve Cramer, MD Professor and Vice Chair of Research, Neurology Professor, Anatomy & Neurobiology Clinical Director, Sue & Bill Gross Stem Cell Research Center University of California, Irvine, School of Medicine

Board Member Felipe Fregni, MD, PhD, MPH, MEd Associate Professor of Physical Medicine & Rehabilitation Associate Professor of Neurology Harvard Medical School Director, Spaulding Neuromodulation Center, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital

Board Member Argye Beth Hillis, MD, MA Professor of Neurology Executive Vice Chair, Department of Neurology Director, Cerebrovascular Division Johns Hopkins University School of Medicine

Board Member Randolph J. Nudo, PhD Director, Landon Center on Aging Professor and Vice Chairman of Research Department of Rehabilitation Medicine Marion Merrell Dow Distinguished Professor in Aging University of Kansas Medical Center

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2nd Annual Stroke Recovery Poster Presentation

For the second year, a highlight of the COBRE Annual Meeting was a poster presentation held Wednesday, January 20th, in the College of Health Profession’s Atrium. Twenty-three presenters participated in the event, representing 27 projects, and highlighting the full scope of MUSC’s talent and resources impacting stroke recovery research.

Updates for the COBRE’s seven currently funded pilot projects were included among the posters for the External Advisory Board’s review. Additionally, post-doctoral fellows and graduate students participated, demonstrating the training and mentoring promoted through the COBRE in Stroke Recovery.

Ryan Downey presents: “Sensory Stimulation to Enhance Hand Function Post Stroke.”

Kendrea Garand presents: “Novel Training Approach for Treatment of Swallowing Impairment in Patients with Refractory Dysphagia after Stroke.”

The COBRE has fostered tremendous growth at MUSC in the area of stroke recovery research, and the poster presentation highlighted the potential for this research to positively impact quality of life for stroke survivors.

Thank you to all who participated!

Scott Hutchison discusses: “Survivor to Thriver: a PCORI Tier I Project.”

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Tyra Dingle & JacKetta Cobbs present: “WISSDOM CENTER: Project 3Community-based Intervention under Nurse Guidance after Stroke (CINGS).”

Xingbao Li presents: “Paired Associative Stimulation Modulates Motor Excitability and Plasticity in Chronic Stroke Patients.”

Shraddha Srivastava presents: “Comparing Muscle Activity Patterns Post-stroke with Normative Profile at Self-selected Walking Speeds.”

Catherine VanDerwerker presents: “The Effects of Aerobic Exercise on Poststroke Depression, Functional Mobility, and Metabolic Capacity in Individuals with Chronic Stroke.”

Elizabeth Wonsetler presents: “Excitatory and Inhibitory rTMS as Mechanistic Contributors to Walking Recovery.”

Rachel Weber presents: “Stimulating B2adrengric Receptors to Enhance Motor Recovery Following Experimental Stroke.”

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Christian Finetto presents: “Effects of Postural Cues on Fine Motor Skills during a Seated Tracing Task.”

Janina Wilmskoetter presents: “Hospital Readmissions for Stroke Patients with PEG Feeding Tubes: An Analysis of HCUP SID Florida 2012.”

Daniel Lench presents: “The Effects of Theta-burst Stimulation on Corticospinal Excitability: A Preliminary Analysis among Healthy Participants.”

Ezequiel Gleichgerrcht presents: “Connectome-based Symptom Mapping Identifies Structural Neural Systems that Support Clinical Language Performance.”

Emily Grattan presents: “Examining the Effects of a Repetitive Task Practice Program among Individuals with Unilateral Spatial Neglect.”

Christina Thompson & Stephanie Pudlik present: “Operant Downconditioning of the Soleus H-reflex in Spastic Hemiparesis after Stroke.”

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Publication Highlight medius (GM) activity was influenced by the simultaneous state of the stance limb, and (2) mediolateral foot placement location was influenced by swing phase GM activity and the mechanical state of the swing limb at the start of the step. We found that both age-matched controls and people with stroke classified as having a low fall risk (Dynamic Gait Index [DGI] score >19) essentially used the stabilization strategy previously described in young controls. In contrast, this strategy was disrupted for people with stroke classified as higher fall risk (DGI </=19), particularly for steps taken with the paretic limb. These results suggest that a reduced ability to appropriately control foot placement may contribute to poststroke instability.

Foot placement control and gait instability among people with stroke.

Dean JC, Kautz SA Abstract Gait instability is a common problem following stroke, as evidenced by increases in fall risk and fear of falling.

However, the mechanism underlying gait instability is currently unclear. We recently found that young, healthy humans use a consistent gait stabilization strategy of actively controlling their mediolateral foot placement based on the concurrent mechanical state of the stance limb. In the present work, we tested whether people with stroke (n = 16) and age-matched controls (n = 19) used this neuromechanical strategy. Specifically, we used multiple linear regressions to test whether (1) swing phase gluteus

KEYWORDS: balance; biomechanics; foot placement; frontal plane; kinematics; motor control; muscle activity; stability; stroke; walking

February is Heart Month

To learn more visit: http://www.cdc.gov/features/heartmonth/ Recovers 9

New Team Members

Administrative Assistant Mara Steedley

Recruitment Coordinator Holly Boggan We welcome our newest member in the Clinical & Translational Tools and Resources (CTTR) Core, Holly Boggan! Coordinating outpatient recruitment efforts for the COBRE’s Registry for Stroke Recovery, RESTORE, Ms. Boggan serves as the primary point of contact for the Center’s non-acute recruitment efforts. In her role, Ms. Boggan informs stroke survivors of the opportunities available to them in stroke recovery research, provides education on the COBRE and RESTORE, and oversees the consent process for RESTORE enrollments.

We expect that these outpatient recruitment efforts will provide a large pool of participants within RESTORE for investigators to query for study participation. This population of stroke subjects will meet the recruitment and retention needs for current investigator projects, as well as prepare the Center for its projected growth in stroke recovery research.

In addition, Holly is developing community outreach activities designed to enhance the Center’s mission and vision. These activities include working with collaborating facilities, building relationships with local physicians and clinicians, and attending local support group meetings.

As the newest member in the Administrative Core, Mara Steedley provides administrative support for Dr. Kautz and the administrative team for activities related to the management of the COBRE. She handles scheduling, coordination and follow-up for all meetings. Additionally, Ms. Steedley serves as the first contact in organizing lab tours and visiting scholars, including facilitation of all COBRE-related travel arrangements and reimbursements.

Welcome to the team, Mara Steedley!

Visit http://www.dana.org/BAW/ to learn how to join the global campaign to increase public awareness of the progress and benefits of brain research.

Welcome to the team, Holly Boggan!

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Visiting Professor Yue Wang The COBRE in Stroke Recovery hosted a visiting scholar, Yue Wang, PhD, Assistant Professor, Clemson University, on Friday, January 29th. The visit included a presentation on Dr. Wang’s research accomplishments and interests, a roundtable discussion with COBRE leaders and investigators, and lab tours.

Dr. Wang’s research interests lie in the intersections of controls, robotics and human factors. More specifically, she is interested in incorporating the analysis of human’s trust in robots and human decision-making behaviors

in the autonomous control of robots. Her research in cooperative control and decisionmaking in human-agent collaborative teams was recognized by a prestigious NSF CAREER award in 2015. NASA has funded her research in haptic feedback control of unmanned aerial vehicles in 2014. She was awarded an Air Force Summer Faculty Fellowship for her research on trust in aerospace autonomous systems in 2015. She also is the Principal Investigator (PI) on Clemson’s manufacturing initiative in human-robot collaborative manufacturing, and was the PI on a University Research Grant on swarm robotics in 2013.

Actively seeking collaborations with neuroscientists, human factors engineers and psychologists, Dr. Wang has strong interests in discovering how the human brain works and how autonomous control can help humans and robots work better together.

The Poetry of the Brain

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Professional Milestones  Dr. Mark Bowden was named Developing Scholar of the Year by MUSC’s College of Health Professions

 Dr. Steve Kautz was named Scholar of the Year by MUSC’s College of Health Professions.  Dr. Michelle Woodbury was named a Health Care Hero in the category of Health Care Researcher by the Charleston Regional Business Journal during their 11th annual Health Care Heroes Event.

COBRE Funded Grants Investigator

Title

Awgulewitsch, Alexander

Exploring Potential Roles of Hox Genes in Stroke Recovery

Bowden, Mark

Excitatory and Inhibitory rTMS as Mechanistic Contributors to Walking Recovery

Dean, Jesse

Application of Ultrasound Technology to Enhance the Quantitative Measurement of Post-stroke Behavior and Function

Feng, Wayne

Optimizing Transcranial Direct Current Stimulation Current and Electrode Montage for Stroke Patients

Gregory, Chris

Treating Depression and Enhancing Locomotor Recovery Post-stroke

Hanlon, Colleen

Investigating the Neurobiologic Basis for Loss of Cortical Laterality in Chronic Stroke Patients

Li, Xingbao

Paired Associative Stimulation Modulates Motor Excitability and Plasticity in Chronic Stroke Patients

Roberts, Donna

fMRI BOLD Signal as a Biomarker for Optimal Dosing of rTMS of Rehabilitation in Chronic Stroke Patients

Seo, Na Jin

Sensory Stimulation to Enhance Hand Function Post-stroke

Shih, Andy

Microvascular Function and Neuroplasticity after Stroke

Thompson, Aiko

Operant Down-conditioning of the Soleus H-Reflex Hemiparesis after Stroke

Tomlinson, Stephen

Complement-dependent Inflammation and Experience-dependent Neural Plasticity after Stroke

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COBRE Affiliated – New Grant Applications Faculty/PI Name

Title

Funding

Dean, Jesse

The Role of Proprioception in the Adaptation toward Economical Gait

Dean, Jesse

Improving Post-stroke Function through Restoration of a Control Strategy for Gait Stabilization

Dean, Jesse Gregory, Chris Kautz, Steve Woodbury, Michelle

National Science Foundation

Veterans Administration A Novel Mechanics-based Intervention to Improve Veterans Post-stroke Gait Stability Administration Optimizing Exercise Prescription in Young Stroke Veterans Survivors to Improve Walking Administration The Effects of Impaired Post-stroke Coordination Veterans and Motor Pathway Integrity on Mobility Performance Administration Does Dynamic Trunk Motor Control Improve with an Veterans Arm Recovery Stroke Rehabilitation Program Administration

COBRE Affiliated – New Awards Faculty/ PI Name

Title

Funding Agency

Project Dates

Funding

Shih, Andy

Pericytes as Inducers of Blood-brain Barrier Injury during Stroke

NIH

2/1/16-1/31/18

$275,000

COBRE Affiliated – Active Grants Faculty/ PI Name

Title

Funding Agency

Project Dates

Funding

Adams, Robert

Strategically Focused Disparities in Cardiovascular Disease Research Network

AHA

6/1/15-5/31/19

$3.7 million

Bonilha, Leo

Brain Connectivity Supporting Language Recovery in Aphasia

NIH/NIDCD

6/10/14-5/31/19

$350,388

Bowden, Mark

Augmentation of Locomotor Adaptation Post-stroke

VA/RRD

7/1/13-6/30/18

$907,000

Dean, Jesse

Post-stroke Contributors to Increased Energetic Cost and Decreased Gait Stability

VA/RRD

10/2012-9/2016

$639,100

Feng, Wayne

ASPIRE: Adult Spasticity International Registry on BOTOX Treatment

Allergan, Inc.

9/2014-10/2017

$77,031

Feng, Wayne

Prediction and Imaging Biomarker for Post-stroke Motor Recovery

AHA

1/2014-12/2017

$77,000

Feng, Wayne/ Woodbury, Michelle

The Halo-MUSC Motor Stroke Rehabilitation Clinical Trial

Halo Neurosciences

2/1/15-1/30/16

$286,770

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Faculty/ Title PI Name Finetto, Christian Biomechanical Assessment of the Relationship between Postural Control and Fine Motor Skills in People with Stroke George/Bonilha

Gregory, Chris Gregory, Chris

Jensen, Jens

Kautz, Steve

Funding Agency MUSC InterProfessional

Project Dates 1/1/15-12/31/15

Funding

Trans-cranial Direct Current Stimulation to Treat Aphasia: Phase II Trial Rural Veterans Telerehabilitation Initiative: RVTRI Stroke Skeletal Muscle Plasticity as an Indicator of Functional Performance Post-stroke

NIH/NIDCD

4/17/12-4/1/17

$904,029

Veterans Administration VA/RRD

10/1/14-9/30/15

$275,050

Prediction of Motor Outcome after Acute Stroke using Diffusional Kurtosis Imaging Research Career Scientist

NIH/NINDS

2/1/20141/31/16

$250,000

Veterans Administration

10/2014 â&#x20AC;&#x201C; 9/2019

$530,000 $250,500

$20,000

10/1/13-9/30/17 $1,100,000

Kautz, Steve

Relationship between Impaired Post- Veterans stroke Coordination and Dynamic Administration Balance and Mobility

10/1/15-9/30/18

Kautz, Steve

National Center of Neuromodulation for Rehabilitation (NC NM4R)

NIH/NICHD

10/1/15-6/30/20 $1,225,000

Seo, Na Jin

Altering Activation Patterns in the Distal Upper Extremity after Stroke (Subaward; Yr 1)

Rehabilitation Institute of Chicago/NIH

2/9/15-5/31/15

$49,939

Seo, Na Jin

Delays in Muscle Relaxation: A Novel Approach to Neuromechanism-based Stroke Rehabilitation (Transfer) Development of a Low-Cost Computerized Clinical Assessment Tool for Movement Quality (Subaward) In Vivo Optogenetic Control of Vascular Contractile Cells Diffusional Kurtosis Imaging of the Corticospinal Tract and Motor Outcome Prediction in Acute S Novel Therapies to Improve Functional Recovery after Stroke Patient-targeted Upper Extremity Rehabilitation after Stroke Telerehabilitation in the Home Versus Therapy In Clinic for Patients with Stroke

AHA

5/1/15-6/30/16

$138,022

NIH

6/1/15-5/31/16

$25,414

AHA

7/1/14-6/30/16

$70,000

SCTR

7/27/15-7/26/16

$25,000

VAMC

4/1/14-3/31/18

$243,700

VA/RRD

4/1/13-3/31/17

$1,100,000

NIH

9/8/15-2/7/17

$33,539

Seo, Na Jin

Shih, Andy Spampinato, Maria Tomlinson, Stephen Woodbury, Michelle Woodbury, Michelle

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Upcoming Events Monday, February 22 Visiting Professor Trisha Kesar, PT, PhD Emory University School of Medicine Tuesday, February 23 Visiting Professor Michael Borich, DPT, PhD Emory University School of Medicine March 7-18 NeuroModulation for Rehabilitation Workshops Thursday, March 10 Executive Committee Meeting Thursday, April 14 Executive Committee Meeting Monday, April 25 Visiting Professors Lara Boyd, PT, PhD The University of British Columbia Monday, May 9 Visiting Professor Winston Byblow, PhD The University of Auckland Thursday, May 12 Executive Committee Meeting

www.SCresearch.org or (843)792-1589 Learn more about current stroke recovery research studies

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COBRE in STROKE RECOVERY 77 President Street Charleston SC, 29425 (843)792-1589 stroke-recovery@musc.edu http://academicdepartments.musc.edu/srrc/

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