This Award will allow the candidate the protected time necessary to focus his efforts on the development of functional MRI (fMRI) research in Primary Generalized Dystonia (PGD) and provide an opportunity to become well-versed in new areas of study relevant to his research field. Under the guidance of his mentors, the candidate will develop independent research skills and abilities in longitudinal clinical investigations and functional magnetic resonance techniques. This mentored training experience will lead to his establishment as an independent, patient-oriented translational investigator in the following years. The overall goal of this study is to use fMRI both at rest and during the performance of specific sensory and motor tasks designed to clarify the pathophysiological basis underlying the development of primary generalized dystonia (PGD), and the changes that occur associated with the symptomatic improvement in PGD as a result of stimulation in the internal segment of the globus pallidus (GPi). PGD is a disorder that begins in children and young adults, and leads to progressive loss of motor control, while sparing intellectual function. The patients are often significantly disabled and unable to care for themselves and often do not respond well to medical therapy. Select centers around the world, including our own, are now using deep brain stimulation (DBS) to treat dystonia. Although it has increasingly been demonstrated as an effective therapy with >50% reduction in dystonic movements, neither the pathophysiological basis underlying the development of PGD nor the mechanism underlying its improvement with DBS is known. These studies will provide insight into both the pathophysiology of dystonia, and the mechanism by which deep brain stimulation produces its benefit. The results of this study will provide a more clear understanding of the activation patterns in subcortical and cortical structures in PGD compared to normal controls and how these activation patterns are changed over time during GPi DBS. The temporal changes in activation patterns will be correlated with the patients'symptoms to clarify their relationship to the patients'symptomatology. These data will not only advance the treatment of dystonia but will also provide important new data regarding the mechanism by which DBS works. This information may be useful for the treatment of other neurologic and psychiatric disorders for which DBS is now being explored.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
NST-2 Subcommittee (NST)
Program Officer
Tagle, Danilo A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Case Western Reserve University
Schools of Medicine
United States
Zip Code
Carr, Sarah J; Borreggine, Kristin; Heilman, Jeremiah et al. (2013) Novel magnetomechanical MR compatible vibrational device for producing kinesthetic illusion during fMRI. Med Phys 40:112303
Vitek, Jerrold L; Lyons, Kelly E; Bakay, Roy et al. (2010) Standard guidelines for publication of deep brain stimulation studies in Parkinson's disease (Guide4DBS-PD). Mov Disord 25:1530-7