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George F Wittenberg
 

George F Wittenberg M.D., Ph.D.

Academic Title: Associate Professor
Primary Appointment: Neurology
Secondary Appointments: Physical Therapy and Rehabilitation Science
Additional Title(s): VA GRECC Staff Physician
GWittenberg@SOM.UMaryland.edu
Location: VAMC/GRECC, 2-227; BRB, 12-047
Phone: 410-706-4456
Phone: 410-637-3216
Fax: 410-605-7913
Cell: 410-389-8502 (pager)
Lab: 410-637- 3221

Personal History:

Dr. Wittenberg was born in Brooklyn, New York. He received training in Engineering, Medicine, Neurology and Neurobiology at Harvard, UC San Diego, Washington U., St. Louis, and the National Institutes of Health. His clinical and research interests are in neurorehabilitation, stroke, cerebral palsy and movement disorders. He uses transcranial magnetic stimulation, functional imaging, kinematics and rehabilitation robotics to study recovery of motor function.

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.

Clinical Speciality:

Dr. Wittenberg’s clinical activities at UMB include inpatient acute stroke care at UMMC and stroke/traumatic brain injury rehabilitation at Kernan Hospital. He participates in an outpatient service at Kernan Hospital 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.”

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.)

Laboratory Personnel:

  1. Crystal Massie, PhD, OTR is a post-doctoral research fellow working in the RAFT laboratory under Dr. Wittenberg. Her research interests are to better understand the mechanisms underlying neuroplasticity associated with stroke interventions. A more thorough understanding of these mechanisms will maximize the potential to develop novel treatments and technologies. One of her research areas has focused on combining non-invasive brain stimulation with motor training to enhance neuroplasticity in survivors of stroke.
  2. Jeremy Rietschel, PhD is a post-doctoral research fellow working in the RAFT laboratory under Dr. Wittenberg. He graduated from the University of Maryland, College Park from the Neuroscience and Cognitive Science Program. His research interests include understanding how neural processes change as a function of learning and neurorehabilitation with particular focus on attention and cognitive workload. Recently, he has developed a novel, EEG derived measure of cognitive workload. His current projects include trying to reduce the cognitive workload associated with rehabilitation as well as dynamically changing rehabilitation intensity to match a patient’s current mental load.
  3. Priya Narayanan, PhD, is a Mechanical Engineer working in the RAFT laboratory under the supervision of Dr. Wittenberg. She is currently working on Robotic control for NeuroRehabilitation for stroke patients and is using her skills in instrumentation and controls as well dynamic modeling in biomedical application and contributing towards study of human motor system. She is also involved in the development of an Electroencephalography (EEG) based non-invasive Brain Computer Interface (BCI) system for robotic rehabilitation of stroke patients with hemparesis
  4. Jaime Lush is the lab manager. He has degrees in physics and mathematics from Univerisity of South Dakota and was a Fulbright scholar at the Max-Planck-Institut für Physik, München-Freimann, Germany October 1998 – July 1999) He provides technical support for all aspects of research in the lab.
  5. Michael Dimyan, MD is as Assistant Professor of Neurology. Please see his Faculty Profile for details.

Laboratory Alumni:

  1. Lauren Jones-Lush has an extensive background in signal processing in a variety of fields, including neuroscience. She was a graduate student in the Program at Neuroscience at the University of Maryland, performing her thesis work with Dr. Asaf Keller providing novel insight on sensory processing in the whisker system. She began a post-doctoral fellowship in the laboratory of Brandeis Professor Dr. Donald B. Katz at the Volen Center for Complex Systems and proposed a dynamic systems approach to gustatory. Her second post-doctoral fellowship was in RAFT lab, where she worked on TMS-evoked movement in the planar robot and on a clinical trial of upper extremity robotics. She was Assistant Dean of the Grauate Program at the University of Maryland and is now Director of the Office of Academic Affairs in the Maryland Higher Education Commission.
  2. Shailesh Kantak began his professional career as a physiotherapist. After completing the Master of Science (Physical Therapy) degree with neurophysiotherapy elective from Mumbai University, India, he worked extensively in physical rehabilitation of patients with stroke, Parkinson’s disease and cerebral palsy. In 2004, he joined the Biokinesiology PhD program at the Division of Biokinesiology and Physical Therapy at the University of Southern California (USC). His PhD work began in Dr. Carolee Winstein’s Motor Behaviour and Neurorehabilitation Laboratory where he conducted traditional behavioral research on motor learning in children. His PhD dissertation research used low frequency repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex and dorsolateral prefrontal cortex to interfere with memory consolidation following practice under different schedules in healthy adults. After completion of his PhD, he joined the Neuroplasticity Lab (NPL) as a post-doctoral fellow under the direction of Dr. James Stinear. This laboratory is part of the Sensory Motor Performance Program at the Rehabilitation Institute of Chicago. He was in the RAFT from 2011-2013, and also worked with Sandy McCombe Waller to understand how cortical plasticity can be harnessed within robotic and other rehabilitation environments. He is now on the faculty of Moss Rehabilitation Research Institute in Pennsylvania.

Publications:

  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. 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.
  3. 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.
  4. 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.
  5. 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)
  6. 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.
  7. 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.
  8. 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
  9. 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.
  10. 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.
  11. 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.
  12. Wittenberg GF, Schaechter JD. The neural basis of constraint-induced movement therapy. Curr Opin Neurol. 2009 Sep 5 [Epub ahead of print]
  13. Wittenberg GF. Motor mapping in cerebral palsy. Dev Med Child Neurol. 2009 Oct;51 Suppl 4:134-9.
  14. Wittenberg GF. Neural plasticity and treatment across the lifespan for motor deficits in cerebral palsy. Dev Med Child Neurol. 2009 Oct;51 Suppl 4:130-3.
  15. 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.
  16. Wittenberg GF. Experience, cortical remapping, and recovery in brain disease. Neurobiol Dis. 2010 Feb; 37 (2): 252-258.
  17. 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
  18. Lo AC, Guarino PD, Richards LG, Haselkorn JK, Wittenberg GF, Federman.  Robot-assisted therapy for long-term upper-limb impairment after stroke.  N Engl J Med. 2010 Apr 16 [Epub ahead of print]
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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
  25. 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
  26. Kantak SS, Jones-Lush LM, Narayanan P, Judkins TN, Wittenberg GF. Rapid Plasticity of Motor Cortex with Robotic Reach Training. Neuroscience 2013 (accepted with revisions).
  27. Massie C, Narayanan P, Kantak SS, Jones-Lush LM, Judkins TN, Wittenberg GF. Effects of Motor Cortical Stimulation during Planar Reaching. J Rehab Robotics (submitted).
  28. 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 2013 (in press).