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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Mentored Patient-Oriented Research Career Development Award (K23)
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NST-2 Subcommittee (NST)
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Sheehy, Paul A
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University of Florida
Schools of Medicine
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Jones, Jacob D; Marsiske, Michael; Okun, Michael S et al. (2015) Latent growth-curve analysis reveals that worsening Parkinson's disease quality of life is driven by depression. Neuropsychology 29:603-9
Giugni, Juan C; Okun, Michael S (2014) Treatment of advanced Parkinson's disease. Curr Opin Neurol 27:450-60
Okun, Michael S; Wu, Samuel S; Fayad, Sarah et al. (2014) Acute and Chronic Mood and Apathy Outcomes from a randomized study of unilateral STN and GPi DBS. PLoS One 9:e114140
Williams, Nolan R; Foote, Kelly D; Okun, Michael S (2014) STN vs. GPi Deep Brain Stimulation: Translating the Rematch into Clinical Practice. Mov Disord Clin Pract 1:24-35
Dietz, Jenna; Noecker, Angela M; McIntyre, Cameron C et al. (2013) Stimulation region within the globus pallidus does not affect verbal fluency performance. Brain Stimul 6:248-53
Okun, Michael S; Weintraub, Daniel (2013) Should impulse control disorders and dopamine dysregulation syndrome be indications for deep brain stimulation and intestinal levodopa? Mov Disord 28:1915-9
Morishita, Takashi; Okun, Michael S; Burdick, Adam et al. (2013) Cerebral venous infarction: a potentially avoidable complication of deep brain stimulation surgery. Neuromodulation 16:407-13; discussion 413
Zahodne, Laura B; Marsiske, Michael; Okun, Michael S et al. (2012) Components of depression in Parkinson disease. J Geriatr Psychiatry Neurol 25:131-7
Ullman, Michael; Vedam-Mai, Vinata; Resnick, Andrew S et al. (2012) Deep brain stimulation response in pathologically confirmed cases of multiple system atrophy. Parkinsonism Relat Disord 18:86-8
Locke, Maren C; Wu, Samuel S; Foote, Kelly D et al. (2011) Weight changes in subthalamic nucleus vs globus pallidus internus deep brain stimulation: results from the COMPARE Parkinson disease deep brain stimulation cohort. Neurosurgery 68:1233-7; discussion 1237-8

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