Parkinson disease (PD) is a devastating neurodegenerative disease that affects approximately one million Americans. The disease creates problems with movement as well as with cognition and behavior. Effective treatments are available for the movement aspects of the disease. However, we understand much less about the changes in the brain that underlie the thinking and behavior problems and, as such, these symptoms go untreated. This Career Development Award will provide additional training and research opportunities for Dr. Floden to advance her clinical research skills in order to address this disparity. She is a clinical neuropsychologist with experience in cognitive neuroscience research. Her long term goal is to establish a programmatic body of research that characterizes the electrophysiological basis of cognitive and behavioral impairments associated with PD. She will use this knowledge to design methods to modulate these electrophysiological abnormalities in PD and thereby minimize the associated cognitive and behavioral impairments. This award will aid her in achieving these goals through a structured training plan that includes formal course work in neurophysiology, bioelectricity, and computational neuroscience techniques, as well as participation in relevant seminars and laboratory work. She will also receive additional training in grant writing and the design and administration of clinical trials research to facilitate her future translational work. The research project that forms the foundation of the current application is a study of the activity changes in single brain cells and populations of brain cells that occur during response inhibition, a specific cognitive process that is impaired in PD but important for controlling behavior. This activity is measured from electrodes that are placed in an important brain region called the Subthalamic Nucleus (STN) during Deep Brain Stimulation surgery for treatment of motor symptoms in Parkinson disease. This will be the first study to measure single cell firing rates in the human STN during response inhibition. We hypothesize that a) response inhibition-specific cells will be observed in select regions of the STN and b) abnormal cognitive and motor signals will be differentially coded by population activity in distinct frequency bands in those select STN regions. If these hypotheses are correct, this would pave the way to development of spatial- and frequency- tailored stimulation treatments to improve cognitive function. Regardless of the outcome, the findings from this study will represent a significant advance in our knowledge of the electrophysiological mechanisms of cognitive impairment in PD.
The current project addresses a major gap in our knowledge of abnormal neuronal activity related to cognitive deficits in Parkinson disease. Cognitive decline and behavior problems are common in Parkinson disease and significantly contribute to functional impairments, reduced quality of life, and caregiver burden. Unfortunately, effective treatments for the nonmotor symptoms of Parkinson disease are lacking. This project is highly relevant to Public Health given that the findings will provide fundamental knowledge that can be used to develop treatments targeting cognitive and behavioral symptoms of Parkinson disease.
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