Clonus is one manifestation of spasticity, and produces involuntary neuromuscular responses that can interfere with the ability to walk after spinal cord injury (SCI). Clonus results in oscillatory efferent output generated by repetitive afferent input and the activation of central neural oscillators. The frequency of clonus is similar when driven by different types of repetitive afferent stimuli such as during standing and stepping. Clonus can radiate across several spinal cord segments and the oscillatory efferent output is modulated by interneurons. Thus, clonus can be used as a physiological probe to understand the functional organization of interneuronal circuits. ? We propose to study clonus during manual stretch of the plantarflexors, standing, and stepping to assess whether repetitive afferent input can alter the functional interneuronal organization of the human spinal cord. ? We will assess whether the specific afferent input related to loading modulates the central oscillators that generate clonus to modify efferent output after severe SCI. We hypothesize that manual stretch of the plantarflexors, standing and stepping will result in different co-activation patterns of clonic EMG among ipsilateral and contralateral flexors and extensors. Also, if a higher level of load to the legs is provided during standing and stepping, the clonic EMG activity will be reduced with an increase in tonic activity of bilateral flexors and extensors. We have observed that when individuals after severe spinal cord injury undergo multiple stand or step training sessions clonus and spasticity are reduced. We propose that intensive training that provides specific sensory information related to loading can reconfigure spinal networks to modify and reduce clonus after severe SCI. We suggest that the repetitive afferent input related to loading induces significant and persistent functional reorganization of interneuronal circuits. We hypothesize that after intensive training the same afferent input will alter clonic EMG activity. ? The proposed studies will further our understanding of the mechanisms of clonus after severe SCI. Further, we will learn whether the spinal neural networks responsible for clonus interact with those that generate standing and stepping. We will also understand whether the repetitive presentation of specific sensory information by training can reconfigure spinal neural networks to generate more functional motor output. Clonus is routinely treated with drugs, or even invasive strategies, with the intent to diminish clonus to enhance motor function. Unfortunately, side effects, rebound spasticity and limited recovery of function are often reported. We suggest that anti-spasticity medication may actually be interfering with the neural circuits needed for standing and walking. If this is the case, then specific training that uses task appropriate sensory cues for standing and walking may alleviate clonus and spasticity, reduce the need for medication, and improve motor function in individuals with severe SCI. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS049209-03
Application #
7033032
Study Section
Special Emphasis Panel (ZRG1-MRS (01))
Program Officer
Kleitman, Naomi
Project Start
2005-04-01
Project End
2009-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
3
Fiscal Year
2006
Total Cost
$348,709
Indirect Cost
Name
University of Louisville
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
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Harkema, Susan J (2008) Plasticity of interneuronal networks of the functionally isolated human spinal cord. Brain Res Rev 57:255-64
Behrman, Andrea L; Harkema, Susan J (2007) Physical rehabilitation as an agent for recovery after spinal cord injury. Phys Med Rehabil Clin N Am 18:183-202, v