The applicant's long-term research objectives are to understand the interdependent relationship between the neural control of multi-joint movements and the mechanical design of the human motor system, and to understand how injury to either of these systems compromises normal motor function. The focus of this particular study is on the stretch reflex contributions to the regulation of human arm mechanics, and how this spinally mediated regulation is altered following stroke. Approximately 400,000 Americans suffer their first stroke each year, and this number is expected to exceed 1,000,000 by the year 2050. Cerebral vascular injuries such as stroke can result in a variety of movement related disorders including muscular weakness, abnormal motor synergies and spasticity. Many of these motor disorders are thought to arise from changes in the behavior of spinal circuits contributing to motor behavior; however, few studies have examined the effect of these changes on the coordination of whole limb function. This study seeks to fill this void by using estimates of limb impedance and the stretch reflex contributions to this impedance to quantify changes in the regulation of multi-joint arm mechanics following stroke.
The specific aims are (1) to examine the reflex contributions to whole limb stiffness regulation in able-bodied individuals maintaining arm posture, (2) to quantify the changes in whole limb stiffness regulation and the spinal contributions to this regulation following stroke, and (3) to examine the possible mechanisms by which tizanidine, a promising drug for restoring motor function following stroke, alters multi-joint reflex behavior. For all aims, limb mechanics will be quantified using estimates of arm limb impedance, which describes the dynamic relationship between externally imposed displacements of limb posture and the forces generated in response. Impedance will be quantified in all degrees of freedom (DOFs) relevant to normal motor function using a 6 DOF robotic manipulator to perturb arm posture and a 6DOF load cell to measure the corresponding forces in all DOF relevant to normal function. Measurements will be made in able-bodied individuals and in individuals who have suffered a stroke. A small, complementary animal study will be performed to investigate possible mechanisms underlying the actions of tizanidine. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25HD044720-02
Application #
6791358
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Nitkin, Ralph M
Project Start
2003-09-01
Project End
2008-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2004
Total Cost
$124,200
Indirect Cost
Name
Northwestern University at Chicago
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Krutky, Matthew A; Ravichandran, Vengateswaran J; Trumbower, Randy D et al. (2010) Interactions between limb and environmental mechanics influence stretch reflex sensitivity in the human arm. J Neurophysiol 103:429-40
Trumbower, Randy D; Ravichandran, Vengateswaran J; Krutky, Matthew A et al. (2010) Contributions of altered stretch reflex coordination to arm impairments following stroke. J Neurophysiol 104:3612-24
Cui, Lei; Maas, Huub; Perreault, Eric J et al. (2009) In situ estimation of tendon material properties: differences between muscles of the feline hindlimb. J Biomech 42:679-85
Finley, James M; Dhaher, Yasin Y; Perreault, Eric J (2009) Regulation of feed-forward and feedback strategies at the human ankle during balance control. Conf Proc IEEE Eng Med Biol Soc 2009:7265-8
Trumbower, Randy D; Krutky, Matthew A; Yang, Bing-Shiang et al. (2009) Use of self-selected postures to regulate multi-joint stiffness during unconstrained tasks. PLoS One 4:e5411
Krutky, Matthew A; Trumbower, Randy D; Perreault, Eric J (2009) Effects of environmental instabilities on endpoint stiffness during the maintenance of human arm posture. Conf Proc IEEE Eng Med Biol Soc 2009:5938-41
Finley, James M; Perreault, Eric J; Dhaher, Yasin Y (2008) Stretch reflex coupling between the hip and knee: implications for impaired gait following stroke. Exp Brain Res 188:529-40
Cui, Lei; Perreault, Eric J; Maas, Huub et al. (2008) Modeling short-range stiffness of feline lower hindlimb muscles. J Biomech 41:1945-52
Perreault, Eric J; Chen, Kuifu; Trumbower, Randy D et al. (2008) Interactions with compliant loads alter stretch reflex gains but not intermuscular coordination. J Neurophysiol 99:2101-13
Rousche, Patrick; Schneeweis, David M; Perreault, Eric J et al. (2008) Translational neural engineering: multiple perspectives on bringing benchtop research into the clinical domain. J Neural Eng 5:P16-20

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