Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus interna (GPi) has been demonstrated to be effective in the treatment of the cardinal motor symptoms of Parkinson's disease (PD) (tremor, rigidity, and bradykinesia). Both STN and GPi DBS have been documented to be effective in treating parkinsonian motor signs. Due to early limited reports, which suggest more robust improvements in UPDRS motor scores, and the ability to reduce parkinsonian medication with STN, but not GPi, STN has been the preferred target of most centers. There is, however, increasing evidence that STN DBS may be associated with a significant number of mood and cognitive changes. Because of the small size of the STN (158mm3), stimulation within the sensori-motor area can result in spread to limbic and associative areas of STN as well as to surrounding structures and fiber systems that may also affect mood and cognition. Since the Gpi (478mm3) is significantly larger than STN, a lead can be placed in the sensorimotor territory of the GPi with less likelihood of current spread to non-motor portions of the GPi or to adjacent structures and fiber systems that can adversely change mood and cognition. In this proposal we will 1) Characterize and compare the mood and cognitive changes associated with STN and GPi DBS, 2) delineate regions within or around the STN and GPi that are associated with specific mood and cognitive changes during DBS in these regions, and 3) assess the relative effect of right versus left STN or GPi stimulation on mood and cognition. This study will characterize the types and incidence of mood and cognitive changes that occur during stimulation in STN and GPi. It will also compare the relative changes in mood and cognition that occur in each site and examine the role of lead location in mediating them. The research is part of a five-year plan for training and career development for the Principal Investigator. This proposal includes active and experienced mentoring, access to diverse resources, and a scientific environment suited specifically for the development of the PI as an independent physician scientist.
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