The basal ganglia comprise several nuclei in the forebrain, diencephalon, and midbrain that are thought to play a significant role in the control of posture and movement. It is well known that human patients with certain degenerative diseases of the basal ganglia (e.g., Parkinson's, Wilson's, and Huntington's diseases) suffer from rigidly held abnormal body postures, slowing of movement, involuntary movements, or a combination of these abnormalities. However, it is not known exactly what features the basal ganglia contribute to normal movement, nor is it known how their dysfunction causes the associated movement abnormalities. There are several current models of basal ganglia function, but many of these lack specificity and no one mode is widely accepted. The proposed experiments will test the hypothesis that the basal ganglia act during voluntary movement to inhibit motor programs that would otherwise compete with the one which has been selected. The basal ganglia will be mapped carefully by injecting small amounts of the GABA agonist muscimol in awake, behaving monkeys to temporarily inactivate discrete areas of these nuclei. The hypothesis predicts that inactivation of the basal ganglia output will 'release' motor programs which would normally be suppressed during an intended movement. This will be assessed in four ways. First, monkeys will perform step-tracking wrist movements before and after inactivation. Movement velocity and amplitude, EMG of agonist, antagonist, and other muscles, and the presence or absence of adventitious movements will be measured before and after inactivation with muscimol. Second, torque pulse and torque step perturbations will be applied during maintained wrist position and prompt wrist movement. The perturbations will allow the measurement of resistance to stretch (tone) and the latency and magnitude of the monosynaptic and transcortical stretch reflexes. Third, unit activity will be recorded in downstream structures (e.g., motor cortex, supplementary motor cortex) during maintained posture and movement of the wrist before and after basal ganglia inactivation. Fourth, multijoint reaching will be evaluated with a two-dimensional video-based digital movement analysis system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS001808-03
Application #
2431074
Study Section
NST-2 Subcommittee (NST)
Program Officer
Oliver, Eugene J
Project Start
1995-08-01
Project End
2000-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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