The basal ganglia (BG) are a group of subcortical nuclei receiving extensive projections from cortex and sending extensive projections to thalamus and which are, among other things, involved in neural control of movement. Interest in BG physiology is also motivated by BG-related disorders, especially Parkinson's disease (PD) - a major neurodegenerative disorder characterized by chronic dopamine (DA) deficiency resulting in a set of primarily movement-related symptoms. Although BG plays a significant role in motor control and in motor deficits of PD, the physiological mechanisms responsible for this control and for PD motor deficits remain poorly understood. Recent studies indicate that patterns of oscillatory synchronous activity in BG, although very variable, are strongly relevant to BG physiology and BG disorders, such as PD. The dynamics of these oscillations and their mechanisms are the subjects of this study. Patterns of synchronous oscillatory behavior in spiking units and local field potentials (LFP) will be recorded from BG of human patients and analyzed using a method of synchronous episodes detection. Models, which are adequately constrained by the results of analysis of the variable patterns of synchronous activity recorded from the patients, will be developed. This model will be used as a tool to investigate the mechanisms responsible for the origin of intermittent synchronous behavior and thus identify possible mechanisms in vivo. Bifurcations underlying the occurrence of physiologically realistic dynamics in numerical experiments with the full model and in an analytical approach to a reduced system will be studies. As a result, the mechanisms of the intermittent synchronous activity in BG both in the """"""""biological language"""""""" (features of synapses, cells, and connectivity, which give birth to intermittent synchrony) and in """"""""mathematical language"""""""" (bifurcations in the system, exhibiting realistic rhythmicity) will be understood. Based on the understanding of the mechanisms, potential methods for modulation and suppression of this rhythmicity (which is believed to be pathological) will be suggested.

Public Health Relevance

The project will enhance understanding of physiology of human brain in Parkinson's disease, a major neurodegenerative disorder. The results of the project may assist in development of new therapies for this disease and related disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS067200-02
Application #
7883303
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (50))
Program Officer
Liu, Yuan
Project Start
2009-07-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$240,176
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Zauber, S Elizabeth; Ahn, Sungwoo; Worth, Robert M et al. (2014) Oscillatory neural activity of anteromedial globus pallidus internus in Tourette syndrome. Clin Neurophysiol 125:1923-4
Dovzhenok, Andrey; Park, Choongseok; Worth, Robert M et al. (2013) Failure of delayed feedback deep brain stimulation for intermittent pathological synchronization in Parkinson's disease. PLoS One 8:e58264
Guo, Yixin; Park, Choongseok; Worth, Robert M et al. (2013) Basal ganglia modulation of thalamocortical relay in Parkinson's disease and dystonia. Front Comput Neurosci 7:124
Ahn, Sungwoo; Rubchinsky, Leonid L (2013) Short desynchronization episodes prevail in synchronous dynamics of human brain rhythms. Chaos 23:013138
Dovzhenok, Andrey; Rubchinsky, Leonid L (2012) On the origin of tremor in Parkinson's disease. PLoS One 7:e41598
Rubchinsky, Leonid L; Park, Choongseok; Worth, Robert M (2012) Intermittent neural synchronization in Parkinson's disease. Nonlinear Dyn 68:329-346
Park, Choongseok; Rubchinsky, Leonid L (2012) Potential mechanisms for imperfect synchronization in parkinsonian basal ganglia. PLoS One 7:e51530
Park, Choongseok; Worth, Robert M; Rubchinsky, Leonid L (2011) Neural dynamics in Parkinsonian brain: the boundary between synchronized and nonsynchronized dynamics. Phys Rev E Stat Nonlin Soft Matter Phys 83:042901
Ahn, Sungwoo; Park, Choongseok; Rubchinsky, Leonid L (2011) Detecting the temporal structure of intermittent phase locking. Phys Rev E Stat Nonlin Soft Matter Phys 84:016201
Park, Choongseok; Rubchinsky, Leonid L (2011) Intermittent synchronization in a network of bursting neurons. Chaos 21:033125

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