The applicant is a clinical neuropsychologist with graduate training in neuropsychology and postdoctoral training in neuropharmacology and positron emission tomography (PET). The goal of this career development award is to integrate and advance these two areas of interest to answer questions about the neuropharmacological and neurophysiological basis of cognitive dysfunction in movement disorders such as Parkinson's disease (PD). This award will provide the applicant with training in the technical and theoretical issues related to using cognitive and pharmacological activation techniques in functional magnetic resonance imaging (fMRI). Long-term objectives are to address questions about the neural basis of cognitive dysfunction in movement disorders related to dopaminergic and/or basal ganglia dysfunction, such as PD, Tourette's syndrome and Huntington's disease. In addition, questions about the effects of dopaminergic treatments for these and other disorders (e.g. dystonia) on cognitive and neurophysiological functioning are also of interest. Cognitive dysfunction in these diseases, either due to the disease process itself or its treatments, can be limiting and disabling. Understanding the neurophysiologic basis for these symptoms may aid in assessing the effectiveness of current treatments or in developing better treatments. During the award period, the applicant will develop expertise in the use of fMRI, cognitive and neuropharmacological techniques to study these disorders, and will continue to hone her clinical skills in the neuropsychological assessment of movement disorders. The applicant will apply these new techniques to investigate the role of dopamine in working memory.
The specific aims of the proposed studies are to test the hypothesis that 1) PD affects prefrontal cortex involvement in working memory and 2) dopaminergic modulation of working memory primarily occurs due to changes in lateral prefrontal cortical activity. To test these hypotheses, the applicant will first perform a behavioral study examining the effects of a steady-state infusion of levodopa, a dopamine precursor, on verbal and spatial working memory in PD patients and controls. The results of this study will then guide the choices of working memory tasks for an fMRl study. Subjects will be asked to perform working memory tasks before and during a steady-state infusion of levodopa. Modulation of the lateral prefrontal cortex is predicted during levodopa infusion. The degree of modulation is predicted to depend on baseline dopaminergic status (PD vs control) and the degree of memory load (low vs high).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS041248-05
Application #
6898198
Study Section
NST-2 Subcommittee (NST)
Program Officer
Oliver, Eugene J
Project Start
2001-07-15
Project End
2007-05-31
Budget Start
2005-06-01
Budget End
2007-05-31
Support Year
5
Fiscal Year
2005
Total Cost
$126,986
Indirect Cost
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Hill, K K; Campbell, M C; McNeely, M E et al. (2013) Cerebral blood flow responses to dorsal and ventral STN DBS correlate with gait and balance responses in Parkinson's disease. Exp Neurol 241:105-12
Foster, Erin R; Hershey, Tamara (2011) Everyday Executive Function Is Associated With Activity Participation in Parkinson Disease Without Dementia. OTJR (Thorofare N J) 31:16-22
Foster, Erin R; McDaniel, Mark A; Repovs, Grega et al. (2009) Prospective memory in Parkinson disease across laboratory and self-reported everyday performance. Neuropsychology 23:347-58
Hershey, T; Wu, J; Weaver, P M et al. (2008) Unilateral vs. bilateral STN DBS effects on working memory and motor function in Parkinson disease. Exp Neurol 210:402-8
Videen, Tom O; Campbell, Meghan C; Tabbal, Samer D et al. (2008) Validation of a fiducial-based atlas localization method for deep brain stimulation contacts in the area of the subthalamic nucleus. J Neurosci Methods 168:275-81
Campbell, M C; Karimi, M; Weaver, P M et al. (2008) Neural correlates of STN DBS-induced cognitive variability in Parkinson disease. Neuropsychologia 46:3162-9
Tabbal, Samer D; Revilla, Fredy J; Mink, Jonathan W et al. (2007) Safety and efficacy of subthalamic nucleus deep brain stimulation performed with limited intraoperative mapping for treatment of Parkinson's disease. Neurosurgery 61:119-27;discussion 127-9
Gordon, Mollie; Markham, Joanne; Hartlein, Johanna M et al. (2007) Intravenous levodopa administration in humans based on a two-compartment kinetic model. J Neurosci Methods 159:300-7
Tabbal, S D; Mink, J W; Antenor, J A V et al. (2006) 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced acute transient dystonia in monkeys associated with low striatal dopamine. Neuroscience 141:1281-7
Perlmutter, Joel S; Mink, Jonathan W (2004) Dysfunction of dopaminergic pathways in dystonia. Adv Neurol 94:163-70

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