Neural mechanisms of balance deficits, falls, and freezing of gait in Parkinson's disease

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7. PROJECT SUMMARY/ABSTRACT CANDIDATE. I am an electrical engineer with expertise in biomedical computation and previous interdisciplinary training in neuroscience, biomechanics, and biostatistics. I received the Bachelor of Science (Sc.B.) and Master of Science (Sc.M.) degrees in Electrical Engineering from Brown University in 2002 and 2004, completing a thesis on circuit design for brain-computer interfaces that resulted in several engineering publications, and received the Ph.D. degree in Electrical and Computer Engineering from the Georgia Institute of Technology in 2010 under the supervision of Lena Ting, Ph.D. My dissertation research applied musculoskeletal simulation and optimization approaches to answer basic science questions about balance control using legacy data from awake cats. As a postdoctoral fellow, I learned laboratory and analysis techniques for human movement studies using electromyography, and developed a new method and software for the statistical analysis of timeseries data. In 2012, I began investigating balance control in individuals with Parkinson's disease (PD) in a new collaboration with Dr. Ting and Madeleine Hackney, Ph.D., a PD rehabilitation scientist. The objectives of this work are to apply engineering models developed in a basic science context to understand balance control in young healthy individuals to better understand balance dysfunction in PD, and to incorporate biomarkers derived from the models into improved rehabilitative outcome measures. Recently, I received a KL2 fellowship that provides formal training in clinical research methods, epidemiology, and biostatistics, critical topics for using these approaches to answer clinically relevant questions with validity and appropriate statistical rigor. CAREER GOAL. My long-term career goal is to be an independent translational investigator with expertise in balance and gait in individuals with movement disorders with independent laboratory space and strong liaison to clinicians and rehabilitation scientists focusing on parkinsonian balance and gait dysfunction. NEED FOR TRAINING. I need the specialized training proposed in this K25 Mentored Quantitative Research Development Award because the disease-related questions I want to ask as an independent investigator require a detailed command of PD pathophysiology and a thorough understanding of PD clinical management. I will need to augment my current expertise in computational neuroscience and biomechanics with a deep understanding these highly specialized topics in order to design and perform high-impact, clinically relevant, R01-level research in movement disorders. ENVIRONMENT AND KEY ELEMENTS OF TRAINING AND RESEARCH PLAN. The proposed training and research activities will prepare me to answer key questions about the interaction between balance deficits, falls, and freezing of gait in PD, establish a track record of collaborative clinical research, and produce preliminary data that will form the foundation of my independent research portfolio. Under this award, I will receive formal coursework and mentored training in basal ganglia neuroanatomy and pathophysiology under the mentorship of Thomas Wichmann, M.D. and in the clinical diagnosis and management of Parkinson's disease at the Emory University Movement Disorders Clinic under the mentorship of Stewart Factor, D.O. My Key Collaborator/Resource Dr. Ting will provide laboratory space and resources for the proposed experiments. Research activities will recruit a cohort of PD patients, including participants in Dr. Factor's ongoing studies of freezing of gait, which will provide significant opportunities for collaboration and exploratory analyses in addition to the primary research aims. RESEARCH PROJECT. These studies will lead to better predictors of fall risk in PD patients and improved understanding of mechanistic relationships between PD, freezing of gait (FOG), and falls that may lead to new treatments. Gaps in our current understanding of balance deficits, falls, and FOG in Parkinson's disease limit our ability to predict fall risk and to design and assess new therapies. Therefore, we will perform a prospective study of fall risk in PD patients with and without FOG to test the ability of advanced engineering tools developed to quantify balance responses in young healthy individuals and in animal models to predict fall risk when included as a component of a comprehensive battery of established behavioral and neuropsychological assessments for fall risk. Additional analyses will use data from this cohort to quantitatively assess the strength and temporality of associations between objectively quantified FOG severity, postural response abnormality, and fall risk. This work will yield new fundamental knowledge about how the central pathophysiology of PD and FOG influences the motor periphery that will improve our ability to identify patients who are candidates for rehabilitation and that will open new lines of investigation into additional balance impaired patient populations and into collaborative studies incorporating imaging approaches being developed by others on the research team.