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George F. Wittenberg, MD, PhD

Academic Title:

Adjunct Associate Professor

Primary Appointment:

Neurology

Secondary Appointment(s):

Physical Therapy

Additional Title:

Director, VA Rehabilitation Research & Development Center (MERCE/NEST)

Location:

VAMC/GRECC, AHB 2nd floor

Phone (Primary):

410-706-4456

Phone (Secondary):

(410) 328.5803

Fax:

410-706-0186

Education and Training

1980-1983 A.B. cum laude in Engineering and Applied Sciences (“Bioelectricity” Specialization) Harvard College, Cambridge, MA
1984-1986 Medical student, School of Medicine, University of California, San Diego
1986-1991 Dept. of Biology, University of California, San Diego, Graduate student in laboratory of William B. Kristan, Jr., PhD., Dissertation: “Intersegmental coordination of shortening behavior in the leech.” Ph. D. granted 3/1991
1991-1993 School of Medicine, University of California, San Diego, Medical student
1993-1994 Intern Physician, Dept. of Medical Education, Mercy Hospital, San Diego
1994-1998 Resident Physician and Neurorehabilitation Fellow, Dept. of Neurology, Washington University, St. Louis, MO
1998-2000 Senior Staff Fellow, Human Cortical Physiology Section, Medical Neurology Branch, NINDS, NIH, Bethesda, MD
2012-2013 Senior Fellow, KU Leuven, Dept. of Kinesiology, Leuven, Belgium

Biosketch

 

NAME: Wittenberg, George F.

eRA COMMONS USER NAME (credential, e.g., agency login): gwittenb

POSITION TITLE: Staff Physician, VAMHCS; Associate Professor (with tenure) of Neurology, UMB SOM

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

INSTITUTION AND LOCATION DEGREE (if applicable) Completion Date MM/YYYY FIELD OF STUDY
Harvard College, Cambridge, Massachusetts A.B. 06/83 Engineering & Appl. Sci.
University of California, San Diego, California Ph.D. 06/91 Biology
University of California, San Diego, California M.D. 06/93 Medicine
Mercy Hospital, San Diego, California Internship 06/94 Transitional
Washington University, St. Louis, Missouri Residency / Fellowship 07/94-06/98 Neurology / Neurorehabilitation
National Institute for Neurological Disorders and Stroke Fellowship 07/98-05/00 Human Cortical Physiology / Mvmt. D/O

 

A. Personal Statement

 

As a mentor on this award application, I will lend my expertise in non-invasive brain physiology and my administrative support as Director of the VA Maryland Exercise and Robotics Center of Excellence. I have the expertise, leadership and motivation necessary to successfully enhance such multifaceted, human-centered research as is proposed. I have a broad background in neuroscience, with specific training and expertise in key research areas. (As a physician-scientist from an MSTP program, I have extensive research and medical training, with the delay that entailed in being able to pursue research during every phase of my academic career.) As a postdoctoral fellow at NIH, I carried out longitudinal studies of brain physiology in the context of intensive therapy during the chronic period after stroke, developing expertise in transcranial magnetic stimulation (TMS). At Wake Forest University, I expanded my research to include functional MRI and expanded my area of study into motor deficits in cerebral palsy. When I arrived at University of Maryland in 2006, my goal was to use the robotic rehabilitation and TMS resources to perform mechanistic studies of the effect of repetitive task practice on the motor cortex and that has been a successful research line that has resulted in several interesting results. This has also been an excellent training opportunity for post-doctoral fellows and others to integrate studies of activity-dependent plasticity in a clinically relevant context. I also have newly acquired expertise after a sabbatical in the Kinesiology Dept. of KU Leuven, and will endeavor in the proposed work to connect the motor function results to brain mechanisms of movement and help Dr. Woytowicz created useful explanatory models of bimanual function.

 

  1. Jones-Lush L, Judkins T, Wittenberg G. Arm movement maps evoked by cortical magnetic stimulation in a robotic environment. Neuroscience. 2010;165(3):774-81.
  2. Kantak S, Jones-Lush L, Narayanan P, Judkins T, Wittenberg G. Rapid plasticity of motor corticospinal system with robotic reach training. Neuroscience. 2013;247:55-64.
  3. Massie CL, Kantak SS, Narayanan P, Wittenberg GF. Timing of motor cortical stimulation during planar robotic training differentially impacts neuroplasticity in older adults. Clin Neurophysiol. 2015;126(5):1024-32.

 

B. Positions and Honors

Positions and Employment

8/1983-6/1984        Research Assistant, Dept. Pathology, Harvard Medical School, Boston, MA

1/1993-2/1993        Visiting Postdoctoral Fellow, Dept. Biology, UCSD, San Diego, CA

3/1993-6/1993        Visiting Scientist, Scripps Research Institute, San Diego, CA

6/1993-6/1993        Transitional Internship, Mercy HealthCare, San Diego, CA

7/1994-3/1997        Neurology Residency, Washington University, St. Louis, MO

7/1997-6/1998        Attending Staff and Neurorehabilitation Fellow, Barnes Jewish Hospital, St. Louis, MO

6/1998-5/2000        Sr. Staff Fellow, National Institute of Neurological Disorders and Stroke, Bethesda, MD

6/2000-6/2006        Assistant Professor, Department of Neurology, Wake Forest Univ., Winston-Salem, NC

8/2006-6/2008        Assistant Professor, Dept. of Neurology, Univ. of Maryland Sch. of Med., Baltimore, MD

8/2006-                   Staff Physician, Geriatrics Research and Clinical Education Center, VAMC Baltimore

11/2006-                 Associate/Affiliate status: University of Maryland Graduate School

11/2006-                 Associate/Affiliate status: Department of Physical Therapy and Rehabilitation Science,

11/2006-                 Associate/Affiliate status: Program in Neuroscience

7/2008-                   Associate Professor, Dept. of Neurology, Univ. of Maryland Sch. of Med., Baltimore, MD

7/2008-                  Deputy Director, VA Maryland Exercise and Robotics Center of Excellence

6/2009-                   Member, Clinical Advising Subcommittee of the MD/PhD Program, Univ. MD, SOM.

9/12-10/13              Senior Fellow, Dept. of Kinesiology, KU Leuven, Belgium

 

Other Experience and Professional Memberships

7/1999-5/2000        Fellows Committee Representative (and Committee Co-chair) - NINDS

2003-6/2006           MRI Research Imaging Committee, Wake Forest University School of Medicine

2004-2006              Society for Neuroscience – Secretary/Treasurer of Western North Carolina Chapter

1995-present          American Academy of Neurology

2000-present          American Society of Neurorehabilitation – multiple offices, now President

2001-present          American Heart Association Stroke Council

 

Honors and Awards

1993-1994 Mercy Hospital “Outstanding Transitional Intern on the Pediatric Service” and “Certificate of Excellence”

1996                American Academy of Neurology – Annual Meeting Scholarship

1997                World Congress of Neurorehabilitation – Presidential Award

C. Contribution to Science

  1. My early publications were related to sensorimotor integration and segmental specialization of sensory input in an invertebrate animal model, the medicinal leech. The work in the laboratory of William Kristan led to a publication of work done during a lab rotation, as I developed a pulse train method for searching for connectivity that worked where single pulse stimulation would have failed. I also contributed to the application of neural network simulation methods to the understanding of connectivity, as even a so-called “simple” nervous system has far too much complexity in connectivity to explain behavior purely on the basis of circuit diagrams. A key results from my dissertation work was that segmental connections are either reiterated or have a center surround pattern. This work led to a publication in Natureand extension of the method to my dissertation work.
    1. Lockery SR, Wittenberg G, Kristan WB Jr., Cottrell GW: Function of identified interneurons in the leech elucidated using neural networks trained by back-propagation. Nature 1989; 340: 468-471.
    2. Wittenberg G, Loer CM, Adamo SA, & Kristan WB Jr. Segmental specialization of neuronal connectivity in the leech. Journal of Comparative Physiology A 1990; 167: 453-459.
    3. Wittenberg G, Kristan WB Jr. Analysis and modeling of the multisegmental coordination of shortening behavior in the medicinal leech: II. Role of identified interneurons. J. Neurophysiol. 1992; 68: 1693-1707.
    4. Wittenberg G, Kristan WB Jr. Analysis and modeling of the multisegmental coordination of shortening behavior in the medicinal leech: I. Motor output pattern. J. Neurophysiol. 1992; 68: 1693-1707.

 

  1. After completing the MSTP program, I changed fields to recovery of sensorimotor integration after stroke, as the most interesting human applications of the principles discovered in the prior work seemed to be in the field of recovery after CNS injury. This has resulting in involvement in clinical trials, mechanistic studies related to clinical trials, and more purely mechanistic studies related to the functional neuroimaging of realistic sensorimotor tasks. The highlights of the contributions of this work include demonstrations of the effectiveness of intensive arm training, with or without a robotic device to assist that training, in upper extremity motor impairments in chronic stroke, and the relationship of task difficulty to functional neuroimaging measures.
    1. Wittenberg GF, Bastian AJ, Dromerick AW, Thach WT, Powers WJ. Mirror movements complicate cerebral activation changes during recovery from subcortical infarction. Neurorehabilitation and Neural Repair 2000;14:213-221.
    2. Lo AC, Guarino PD, Richards LG, Haselkorn JK, Wittenberg GF, Federman DG, Ringer RJ, Wagner TH, Krebs HI, Volpe BT, Bever CT Jr, Bravata DM, Duncan PW, Corn BH, Maffucci AD, Nadeau SE, Conroy SS, Powell JM, Huang GD, Peduzzi P. Robot-assisted therapy for long-term upper-limb impairment after stroke. N Engl J Med. 2010 Apr 16 [Epub ahead of print]
    3. Wittenberg GF, Lovelace CT, Foster DJ, Maldjian JA. Functional neuroimaging of dressing-related skills. Brain Imaging Behav. 2012 Oct 16. [Epub ahead of print] PubMed PMID: 23070748

 

  1. The remapping of motor cortex after early or late injury to the brain has been an important field of inquiry. The most novel finding in this area was my recognition that motor cortex maps in some children with cerebral palsy were shifted laterally. (There had been only one previous citation in this area and those researchers mapped only the lower extremity and not the upper.) I also studied the expansion of arm motor maps with constraint-induced therapy at multiple times in my career, demonstrating that it is a reproducible effect, but one that is not correlated with recovery. While not all of this work has been closely thematically related, the themes is that TMS can be used to measure changes in motor representation. The most innovative of these finding is that rehabilitation robots can be used to measure proximal arm movements with high precision and the motor cortical maps accessible by TMS are subject to practice-related plasticity and that this plasticity can be influence by TMS synchronized with the task. This is a practical application of spike-timing dependent plasticity and has broad implications for designing sensorimotor rehabilitation paradigms. 

  

  1. Sawaki L, Butler A, Leng X, Wassenaar P, Mohammad Y, Blanton S, Sathian K, Nichols-Larson D, Wolf S, Good D, Wittenberg GF. Constraint-induced Movement Therapy results in increased motor map area in subjects 3-9 months after stroke. Neurorehabilitation and Neural Repair 2008; 22 (5):505-513.
  2. Kesar TM, Sawaki L, Burdette JH, Cabrera N, Kolaski K, Smith BP, O’Shea TM, Koman LA, Wittenberg GF. Functional Relevance of Abnormalities in Motor Cortex Representational Geometry in Cerebral Palsy. Dev. Med. & Child Neurol. 2012 Jul;123(7):1383-90. Epub 2011 Dec 6. PubMed PMID: 22153667; PubMed Central PMCID: PMC3309071.

Complete List of Published Work in MyBibliography:   http://www.ncbi.nlm.nih.gov/sites/myncbi/george.wittenberg.1/bibliography/45600173/public/?sort=date&direction=ascending.

 

D. Research Support

NIH R01 HD061462

Wittenberg (PI)

07/01/11–6/30/17

Driving Cortical Plasticity for Rehabilitation of Reaching after Stroke

The goal of this project is to define the effect of timing and location of non-invasive cortical stimulation that best enhances practice-related plasticity in normal participants and those with hemiparetic stroke.

Role: Principal Investigator

 

VA Merit Review

Wittenberg (PI)

   01/01/14-12/31/17

Brain Neurophysiological Biomarkers of Functional Recovery in Stroke

This study examines the changes primarily in EEG signals that occur with planning and initial execution of reaching movements in stroke patients, with the goal of improving the timing of robotic assistance to maximize practice-related improvements in movement ability.

Role: Principal Investigator

 

VA Merit Review

Wittenberg (PI)

07/01/15-06/30/19

Neurophysiological and Kinematic Predictors of Response in Chronic Stroke

Chronic stroke affected participants will be enrolled into a single arm clinical trial of robotic rehabilitation with transition to talk practice. The response to intervention will be used to create a predictive model of function and disability following the intervention

Role: Principal Investigator

 

Pending Research Support

NIH R01 MH

Wittenberg (PI)

10/01/16–9/30/21

Cortical Transfer Function for Induction of Plasticity

The goal of this project is to define the effect of relative dose of stimulation and effort to move that effect induction of practice-related plasticity. A major part of the proposed work is finding EEG biomarkers of effective combinations for such plasticity and to test the use of EEG triggering to stimulate at the most effective times.

Role: Principal Investigator

 

Select Completed Research Support

VA Merit Review

Bever (PI)

07/01/10–06/30/14

Evaluation of Robot Assisted Neuro-rehabilitation

This study compares the effect, on chronic stroke patients, of purely robotic-assisted rehabilitation training with mixed sessions of robotic and transition to task training.

Role: Investigator

 

 

 

Research/Clinical Keywords

Rehabilitation, Recovery, Motor Control, transcranial magnetic stimulation, functional MRI, stroke, movement disorders, robotics, EEG

Highlighted Publications

  1. Jones-Lush L, Judkins T, Wittenberg G. Arm movement maps evoked by cortical magnetic stimulation in a robotic environment. Neuroscience. 2010;165(3):774-81.
  2. Kantak S, Jones-Lush L, Narayanan P, Judkins T, Wittenberg G. Rapid plasticity of motor corticospinal system with robotic reach training. Neuroscience. 2013;247:55-64.
  3. Massie CL, Kantak SS, Narayanan P, Wittenberg GF. Timing of motor cortical stimulation during planar robotic training differentially impacts neuroplasticity in older adults. Clin Neurophysiol. 2015;126(5):1024-32.

Additional Publication Citations

1. Virgin HW IV, Wittenberg GF, Unanue ER. Immune complex effects on murine macrophages I. Immune complexes suppress interferon-γ induction of Ia expression. J. Immunol. 1985; 135: 3735-3743.

2. Virgin HW IV, Kurt-Jones EA, Wittenberg GF, Unanue ER. Immune complex effects on murine macrophages II. Immune complex effects on activated macrophages cytotoxicity, membrane IL 1 and antigen presentation. J. Immunol. 1985; 135: 3745-3749.

3. Virgin HW IV, Wittenberg GF, Bancroft GJ, Unanue ER. Suppression of immune response to Listeria monocytogenes: mechanisms of immune complex suppression. Infection and Immunity 1985; 50: 343-351.

4. Levich JD, Signorella AP, Wittenberg G, Weigle WO. Macrophage handling of a tolerogen and the role of IL 1 in tolerance induction in a helper T cell clone in vitro. J. Immunol. 1987; 138: 3675-3679.

5. Lockery SR, Wittenberg G, Kristan WB Jr., Cottrell GW: Function of identified interneurons in the leech elucidated using neural networks trained by back-propagation. Nature 1989; 340: 468-471.

6. Wittenberg G, Loer CM, Adamo SA, & Kristan WB Jr. Segmental specialization of neuronal connectivity in the leech. Journal of Comparative Physiology A 1990; 167: 453-459.

7. Wittenberg G, Kristan WB Jr. Analysis and modeling of the multisegmental coordination of shortening behavior in the medicinal leech: II. Role of identified interneurons. J. Neurophysiol. 1992; 68: 1693-1707.

8. Wittenberg G, Kristan WB Jr. Analysis and modeling of the multisegmental coordination of shortening behavior in the medicinal leech: I. Motor output pattern. J. Neurophysiol. 1992; 68: 1693-1707.

9. Randall RD, Lee SY, Meyer JH, Wittenberg GF, Gruol DL: Acute alcohol blocks neurosteroid modulation of synaptic transmission and long-term potentiation in the rat hippocampal slice. Brain Res. 1995; 701: 238-48.

10. Meyer JH, Lee S, Wittenberg GF, Randall RD, Gruol DL. Neurosteroid regulation of inhibitory synaptic transmission in the rat hippocampus in vitro. Neuroscience 1999; 90:1177-83.

11. Wittenberg GF, Bastian AJ, Dromerick AW, Thach WT, Powers WJ. Mirror movements complicate cerebral activation changes during recovery from subcortical infarction. Neurorehabilitation and Neural Repair 2000;14:213-221.

12. Ziemann U, Wittenberg GF, Cohen LG. Stimulation-Induced Within- Representation and Across-Representation Plasticity in Human Motor Cortex. Journal of Neuroscience 2002; 22: 5563-5571.

13. Muellbacher W, Richards C, Ziemann U, Wittenberg G, Weltz D, Boroojerdi B, Cohen L, Hallett M. Improving hand function in chronic stroke. Archives of Neurology 2002; 59:1278-1282.

14. Wittenberg GF, Chen R, Ishii K, Bushara KO, Eckloff S, Croarkin E, Taub E, Gerber LH, Hallett M, Cohen LG. Constraint-Induced therapy in stroke: magnetic-stimulation motor maps and cerebral activation. Neurorehabilitation and Neural Repair 2003; 17:111-119.

15. Wittenberg GF*, Werhahn KJ*, Wassermann EM, Herscovitch P, Cohen LG. Functional connectivity between somatosensory and visual cortex in early blind humans. Eur J Neurosci. 2004 Oct; 20(7):1923-1927. (*Official co-first authors)

16. Hancox JG, Wittenberg GF, Yosipovitch G. A patient with nasal ulceration after brain surgery. Arch Dermatol. 2005 June; 141(6):796-798.

17. Gerloff C, Bushara K, Sailer A, Wassermann EM, Chen R, Matsuoka T, Waldvogel D, Wittenberg GF, Ishii K, Cohen LG, Hallett M. Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke. Brain 2006;129: 791-808.

18. Wittenberg GF, Bastings EP, Fowlkes A, Morgan TM, Good DC, Pons TP. Dynamic course of intracortical TMS paired-pulse responses during recovery of motor function after stroke. Neurorehabilitation and Neural Repair 2007 21:568-573.

19. Zhang L, Butler AJ, Sun CK, Sahgal V, Wittenberg GF, Yue GH. Fractal dimension assessment of brain white matter structural complexity post stroke in relation to upper-extremity motor function. Brain Research  2008;1228:229-240

20. Sawaki L, Butler A, Leng X, Wassenaar P, Mohammad Y, Blanton S, Sathian K, Nichols-Larson D, Wolf S, Good D, Wittenberg GF. Constraint-induced Movement Therapy results in increased motor map area in subjects 3-9 months after stroke. Neurorehabilitation and Neural Repair 2008; 22 (5):505-513.

21. Procacci NM, Stanford TR, Wittenberg GF. The relationship between visual orienting and interlimb synchrony in a patient with a superior parietal infarction: A case study. Neurocase 2009; 26:1-16.

22. Starr CJ, Sawaki L, Wittenberg GF, Burdette JH, Oshiro Y, Quevedo AS, Coghill RC. Roles of the insular cortex in the modulation of pain: insights from brain lesions. J Neurosci. 2009; 29:2684-2694.

23. Wittenberg GF, Schaechter JD. The neural basis of constraint-induced movement therapy. Curr Opin Neurol. 2009 Sep 5 [Epub ahead of print]

24. Wittenberg GF. Motor mapping in cerebral palsy. Dev Med Child Neurol.2009 Oct;51 Suppl 4:134-9.

25. Wittenberg GF. Neural plasticity and treatment across the lifespan for motor deficits in cerebral palsy. Dev Med Child Neurol. 2009 Oct;51 Suppl4:130-3.

26. Lo AC, Guarino P, Krebs HI, Volpe BT, Bever CT, Duncan PW, Ringer RJ, Wagner TH, Richards LG, Bravata DM, Haselkorn JK, Wittenberg GF, Federman DG, Corn BH, Maffucci AD, Peduzzi P. Multicenter Randomized Trial of Robot-Assisted Rehabilitation for Chronic Stroke: Methods and Entry Characteristics for VA ROBOTICS. Neurorehabil Neural Repair. 2009 Oct;23 (8): 775-783.

27. Wittenberg GF. Experience, cortical remapping, and recovery in brain disease. Neurobiol Dis. 2010 Feb; 37 (2): 252-258.

28. Jones-Lush LM, Judkins TN, Wittenberg GF. Arm movement maps evoked by cortical magnetic stimulation in a robotic environment. Neuroscience 2010 Feb 3;165 (3):774-781

29. Lo AC, Guarino PD, Richards LG, Haselkorn JK, Wittenberg GF, Federman DG, Ringer RJ, Wagner TH, Krebs HI, Volpe BT, Bever CT Jr, Bravata DM, Duncan PW, Corn BH, Maffucci AD, Nadeau SE, Conroy SS, Powell JM, Huang GD, Peduzzi P. Robot-assisted therapy for long-term upper-limb impairment after stroke. N Engl J Med. 2010 May 13;362(19):1772-83. doi: 10.1056/NEJMoa0911341.

30. Starr CJ, Sawaki L, Wittenberg GF, Burdette JH, Oshiro Y, Quevedo AS, McHaffie JG, Coghill RC. The contribution of the putamen to sensory aspects of pain:insights from structural connectivity and brain lesions. Brain. 2011 Jul;134(Pt 7):1987-2004. Epub 2011 May 26. PubMed PMID: 21616963; PubMed Central PMCID: PMC3122370.

31. Wittenberg GF. Elastic properties and yield stress of fetal membranes.Conf Proc IEEE Eng Med Biol Soc. 2011;2011:2123-6. PubMed PMID:22254757

32. Conroy SS, Whitall J, Dipietro L, Jones-Lush LM, Zhan M, Finley MA, Wittenberg GF, Krebs HI, Bever CT. Effect of gravity on robot-assisted motor training after chronic stroke: a randomized trial. Arch Phys Med Rehabil. 2011 Nov;92(11):1754-61. Epub 2011 Aug 17. PubMed PMID:21849168.

33. Wagner TH, Lo AC, Peduzzi P, Bravata DM, Huang GD, Krebs HI, Ringer

RJ,Federman DG, Richards LG, Haselkorn JK, Wittenberg GF, Volpe BT, Bever CT, Duncan PW, Siroka A, Guarino PD. An economic analysis of robot-assisted therapy for long-term upper-limb impairment after stroke. Stroke. 2011 Sep;42(9):2630-2. Epub 2011 Jul 14. PubMed PMID:21757677.

34. Kesar TM, Sawaki L, Burdette JH, Cabrera N, Kolaski K, Smith BP, O’Shea TM, Koman LA, Wittenberg GF. Functional Relevance of Abnormalities in Motor Cortex Representational Geometry in Cerebral Palsy. Dev. Med. & Child Neurol. 2012 Jul;123(7):1383-90. Epub 2011Dec 6. PubMed PMID: 22153667; PubMed Central PMCID: PMC3309071.

35. Krakauer JW, Carmichael ST, Corbett D, Wittenberg GF. Getting neurorehabilitation right: what can be learned from animal models? Neurorehabil Neural Repair. 2012 Oct;26(8):923-31. Epub 2012 Mar 30. PubMed PMID: 22466792.

36. Wittenberg GF, Lovelace CT, Foster DJ, Maldjian JA. Functional neuroimaging of dressing-related skills. Brain Imaging Behav. 2012 Oct16. PubMed PMID: 23070748

37. Kantak SS, Wittenberg GF, Liao WW, Magder LS, Rogers MW, Waller SM. Posture-related modulations in motor cortical excitability of the proximal and distal arm muscles. Neurosci Lett. 2012 Nov 1. pii: S0304-3940(12)01416-4. S0304-3940(12)01416-4.10.1016/j.neulet.2012.10.048. [Epub ahead of print] PMID: 23123777

38. Kantak SS, Jones-Lush LM, Narayanan P, Judkins TN, Wittenberg GF. Rapid Plasticity of Motor Cortex with Robotic Reach Training. Neuroscience. 2013 Sep 5;247:55-64. doi: 10.1016/j.neuroscience.2013.05.001. PMID: 23669007

39. Dutta TM, Josiah AF, Cronin CA, Wittenberg GF, Cole JW. Altered taste and stroke: a case report and literature review. Top Stroke Rehabil. 201320(1):78-86. PMID: 23340074.

40. Massie C, Narayanan P, Kantak SS, Jones-Lush LM, Judkins TN, Wittenberg GF. Effects of Motor Cortical Stimulation during Planar Reaching. J Rehab Robotics 2013 1:42-53, DOI: http://dx.doi.org/10.12970/2308-8354.2013.01.01.5.

41. Ommaya AK, Adams KM, Allman RM, Collins EG, Cooper RA, Dixon CE, Fishman PS, Henry JA, Kardon R, Kerns RD, Kupersmith J, Lo A, Macko RF, McArdle R, McGlinchey RE, McNeil MR, O'Toole TP, Peckham PH, Tuszynski, MH, Waxman SG, Wittenberg GF. Research opportunities in rehabilitation research. Journal of Rehabilitation Research and Development Sept. 2013 (now online). J Rehabil Res Dev. 2013 50(6):vii- xxxii. doi: 10.1682/JRRD.2012.09.0167. PMID: 24203548

42. Matthews CC, Fishman PS, Wittenberg GF. Tetanus Toxin Reduces Local and Descending Regulation of the H-Reflex. Muscle and Nerve2013, DOI: 10.1002/mus.23938

43. Beets I, Gooijers J, Boisgontier M, Pauwels L, Coxon J, Wittenberg GF, Swinnen SP. Reduced neural differentiation between feedback conditions after training bimanual coordination with and without augmented visual feedback, Cerebral Cortex 2014, Feb DOI:10.1093/cercor/bhu00

44. Boisgontier MP, Wittenberg G, Fujiyama H, Levin O and Swinnen SP. Complexity of central processing in simple and choice multi-limb reaction time tasks. PLoS One. 2014 Feb 28;9(2):e90457. doi: 10.1371/journal.pone.0090457. PMID: 24587371.

45. Wittenberg GF and Dimyan MA. How do the physiology and transcallosal effects of the unaffected hemisphere change during inpatient rehabilitation after stroke? (editorial) Clin. Neurophysiol., 2014 Feb 28. pii: S1388-2457(14)00117-5. doi: 10.1016/j.clinph.2014.02.016.

46. Massie C, Kantak SS, Narayanan P, Wittenberg GF. Timing of motor cortical stimulation during planar robotic training differentially impacts neuroplasticity in older adults. Clin Neurophysiol. 2014 Sep 16. pii: S1388-2457(14)00482-9. doi: 10.1016/j.clinph.2014.06.053. [Epub ahead of print] PMID: 25283712

47. Sawaki L, Butler AJ, Leng X, Wassenaar PA, Mohammad YM, Blanton S, Sathian K, Nichols-Larson DS, Wolf SL, Good DC, Wittenberg GF. Differential patterns of cortical reorganization following constraint-induced movement therapy during early and late period after stroke: a preliminary study. NeuroRehabilitation, 2015, [Epub ahead of print].

48. Rietschel JC. McDonald CG, Goodman RN, Miller MW, Jones-Lush LM, Wittenberg GF, Hatfield, BD. Psychophysiological support of increasing attentional reserve during the development of a motor skill. Biological Psychology 2014 Dec;103:349-56. doi: 10.1016/j.biopsycho.2014.10.008. Epub 2014 Oct 23. PMID: 25457640

49. Massie C, Yue, D, Conroy S, Krebs HI, Wittenberg GF, Bever C, Whitall J. A clinically relevant method of analyzing continuous change in robotic upper- extremity chronic stroke rehabilitation. Neurorehabil Neural Repair. 2015 Dec 14. pii: 1545968315620301. [Epub ahead of print] PubMed PMID: 26671216.

Research Interests

All projects based in the Laboratory for Research on Arm Function and Therapy (RAFT) are related to upper extremity function and particularly reaching behavior. They run the gamut from the basic science of movement representation in the motor cortex to clinical technology for improvement of arm function after stroke.

Specific Projects

NIH R01: Driving Cortical Plasticity for Reach Rehabilitation after Stroke (Wittenberg, P.I.)

Stroke is one of the most common causes of disability of the arm and there is tremendous room for improvement in rehabilitation techniques. We are testing a method that combines transcranial magnetic stimulation with robotic therapy. We are determining the parameters of stimulation timing and location that enhance useful brain changes in normal volunteers and chronic stroke patients. The resulting method can be applied in clinical trials to enhance the effects of practice for people with stroke.

  • Brain stimulation, when precisely timed with movement, can intensify the brain’s representation of the movement that was practiced, and this can be useful for stroke patients who have trouble with particular movements.

VA Merit: Evaluation of Robot Assisted Neuro-rehabilitation

In the current phase of this continuing project on robotic arm rehabilitation after stroke, we are determining the value of using special training to connect robotic practice to real life tasks. We also determine the brain changes that occur over the course of intensive therapy, using transcranial magnetic stimulation and MRI. The clinical impact will be twofold: 1. Developing the best method to improve independence of chronic stroke patients, and 2. Learning who can best benefit from intensive rehabilitation late after stroke.

  • Making a transition from repetitive basic movement practice to real-world tasks can help chronic stroke patients become more functionally independent.
  • The brain changes that occur after an hour or several hours of intensive practice can be detected with brain stimulation and MRI.

Pilot: Multimodal physiology of Reaching

Our preliminary data indicate that it is feasible to collect quality EEG in survivors of stroke as they volitionally perform motor tasks. Moreover, we detected brain-derived biomarkers that reliably encoded for aspects of reach, i.e., the intended direction to move and timing of movement onset. Using these biomarkers as input to a Bayesian classifier robustly predicted the timing of the intent to move on a trial-by-trial basis. Thus, the classification will only improve when many more brain-derived biomarkers are available to this classification system with regard to timing and direction. Our objective is to

  • characterize the neurophysiological signals that best predict the onset and direction of volitional reaching movements in survivors of stroke, and
  • determine how these identified signals change as stroke survivors recover from subacute to chronic stages.

Identifying the brain-derived biomarkers encoding for specific components of reach in stroke survivors will reveal the neurophysiology underlying natural recovery and guide future rehabilitation strategies.

 

Lab Techniques and Equipment:

  1. TMS – Transcranial Magnetic Stimulation is a technique for the non-invasive activation of neurons that uses pulsed magnetic fields. It has a long history of use to activate upper motor neurons, including studies of impaired motor function after stroke and in cerebral palsy. The RAFT lab has a number of stimulators, including a rapid stimulator capable of modulating brain activity for several minutes.
  2. Kinematics – The analysis of human movement depends on first the capture of body position in space and time and then in the analysis of that data. The position of the arm end-effector (i.e. the hand) can be measured with the same robot used for rehabilitation, or a more comprehensive analysis of movement can be performed using recording of markers distributed over the body. We use both approaches and have a growing set of technology that includes the Kinereach system from Penn State University.
  3. Functional imaging – Brain activity can measured in a few ways, including changes in blood oxygenation that affect the MRI signal (the so-called “BOLD” effect) and absorbance of light (Near-infrared spectroscopy) as well as through assessing changes in the electrical signals generated by the brain (Electroencephalography.)

 

Clinical Specialty Details

Dr. Wittenberg’s clinical activities at UMB have included inpatient acute stroke care at UMMC and stroke/traumatic brain injury rehabilitation at UM Rehab (Kernan) Hospital. He participates in an outpatient service at the Neurology Ambulatory Practice for patients with motor disorders that result most commonly from stroke, brain injury, and multiple sclerosis.  One of the most common features of these disorders is the presence of spasticity, overactivity in affected muscles that interferes with many activities of daily living. The service is therefore called “Neurorehabilitation and Spasticity.”