Parkinson's Disease (PD) results from the degeneration of dopaminergic neurons in the substantia nigra, yet little is understood about how this loss results in the primary motor symptoms of the disease (rigidity, bradykinesia and tremor). Although a lesion placed in the globus pallidus can relieve rigidity tremor and/or drug-induced dyskinesia, the mechanism underlying this effect is also not understood. Furthermore, the role of the basal ganglia in the control of movement remains to be established. These facts underscore the need for directly studying basal ganglia function in PD patients. The surgical treatment of PD by pallidotomy provides an excellent, and largely unexploited, opportunity for achieving this goal. Our proposed work brings together recent developments in the fields of behavioral science, neurophysiology and clinical neurology to test the hypothesis that specific motor symptoms of PD are the result of specific changes in the spatiotemporal dynamics of the neural activity within the basal ganglia. These properties have received little attention in studies of the human globus pallidus. To establish this relationship, we propose the following specific aims: 1). to determine the severity of the constellation of Parkinsonian motor symptoms in individual patients using a battery of tests that are more quantitative than standard neurological rating scales; 2). to characterize the spatiotemporal dynamics of neural activity in the basal ganglia of individual PD patients who have undergone microelectrode-guided pallidotomy; 3). to determine the neuronal correlates, in the pallidum of the primary motor symptoms of PD by constructing a relational database of the results of the two components of the study. The results of the proposed work should lead to modifications of the current theories of the neural mechanisms underlying the motor symptoms of PD and guide others in their search for the cellular mechanisms which underlie the transformation of the normal striatum and globus pallidus following the loss of striatal dopamine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS039121-01
Application #
2899583
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (01))
Program Officer
Oliver, Eugene J
Project Start
1999-07-01
Project End
2004-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Davis
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Koster, Daniel P; Higginson, Christopher I; MacDougall, Elizabeth E et al. (2015) Subjective Cognitive Complaints in Parkinson Disease Without Dementia: A Preliminary Study. Appl Neuropsychol Adult 22:287-92
Higginson, Christopher I; Wheelock, Vicki L; Levine, Dawn et al. (2011) Predictors of HVOT performance in Parkinson's disease. Appl Neuropsychol 18:210-5
Higginson, Christopher I; Wheelock, Vicki L; Levine, Dawn et al. (2009) The clinical significance of neuropsychological changes following bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease. J Clin Exp Neuropsychol 31:65-72
Higginson, Christopher I; Wheelock, Vicki L; Levine, Dawn et al. (2008) Cognitive deficits in essential tremor consistent with frontosubcortical dysfunction. J Clin Exp Neuropsychol 30:760-5
Shook, Sheryl K; Franz, Elizabeth A; Higginson, Christopher I et al. (2005) Dopamine dependency of cognitive switching and response repetition effects in Parkinson's patients. Neuropsychologia 43:1990-9
Higginson, Christopher I; Wheelock, Vicki L; Carroll, Kimberly E et al. (2005) Recognition memory in Parkinson's disease with and without dementia: evidence inconsistent with the retrieval deficit hypothesis. J Clin Exp Neuropsychol 27:516-28
Hurtado, Jose M; Rubchinsky, Leonid L; Sigvardt, Karen A et al. (2005) Temporal evolution of oscillations and synchrony in GPi/muscle pairs in Parkinson's disease. J Neurophysiol 93:1569-84
Hurtado, Jose M; Rubchinsky, Leonid L; Sigvardt, Karen A (2004) Statistical method for detection of phase-locking episodes in neural oscillations. J Neurophysiol 91:1883-98
Rubchinsky, Leonid L; Kopell, Nancy; Sigvardt, Karen A (2003) Modeling facilitation and inhibition of competing motor programs in basal ganglia subthalamic nucleus-pallidal circuits. Proc Natl Acad Sci U S A 100:14427-32
Hurtado, J M; Lachaux, J P; Beckley, D J et al. (2000) Inter- and intralimb oscillator coupling in parkinsonian tremor. Mov Disord 15:683-91