Corticospinal Function After Spinal Cord Injury

Study Overview
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Brief Summary
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The investigator's overall goal is to develop new strategies to test optimization of Spike-timing-dependent plasticity (STDP) doses to maximize strategy to restore upper and lower-limb motor function in individuals with spinal cord injury (SCI). The investigator proposes to use modern electrophysiological methods to enhance the efficacy of residual corticospinal connections. Defining the neural basis by which corticospinal volleys generate muscle responses will provide crucial information required to maximize residual motor output. The investigator's specific goals are to: 1) determine the temporal and spatial organization of corticospinal volleys and motor cortical representations of upper-limb muscles after incomplete cervical SCI and 2) develop methodologies to promote recovery of function. The investigator's focus on reach and grasp movements because of their importance in daily life activities.

Detailed Description
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This study will determine the temporal organization of corticospinal volleys during reach and grasp movements. Multiple descending volleys in the corticospinal tract generate multiple peaks in muscle responses (indirect (I)-waves). I-waves are a mechanism by which corticospinal neurons are transynaptically activated at periodic intervals of  1.5 ms. This periodic activation contributes to the recruitment of spinal motoneurons and generation of movement. we will use paired-TMS to examine I-waves in surface EMG recordings from upper-limb muscles during reach and grasp movements. We will also identify motor cortical maps of upper-limb muscles involved in reach and grasp movements. We will use TMS guided by a frameless neuronavigation system to define the size and location of motor cortical maps of upper-limb muscles during reach and grasp movements. We will be able to determine overlaps and functional interactions between distal and proximal arm motor cortical representations. Our preliminary data shows that finger and biceps cortical maps largely overlap during reach and grasp movements in controls but considerable less in patients

Official Title
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Corticospinal Function After Spinal Cord Injury

Conditions
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Spinal Cord Injury

Intervention / Treatment
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* Other: Electrophysiology Assessment of Time Domain
* Other: Electrophysiology Assessment of Location
* Other: Training with some stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for individuals with SCI: Male and females between 18-85 years, Chronic SCI (≥ 6 months post injury), Cervical injury at C8 or above, Intact or impaired but not absent innervations in dermatomes C6, C7, and C8 using the American Spinal Injury Association sensory scores, and Ability to reach and grasp a small object located at least 8 cm forward, above, and laterally without leaning forward with the trunk Inclusion criteria for healthy controls: Male and females between 18-85 years, Right handed, Ability to reach and grasp a small object located at least 8 cm forward, above, and laterally without leaning forward with the trunk Exclusion Criteria: Exclusion criteria for individuals with SCI and Healthy Controls: Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease Any debilitating disease prior to the SCI that caused exercise intolerance Premorbid, ongoing major depression or psychosis, altered cognitive status History of head injury or stroke Pacemaker Metal plate in skull History of seizures Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressants Pregnant females Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida or herniated cervical disk. History of brain tumor and or brain infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Electrophysiology Assessment of Time Domain<br>Assessment of electrophysiology in the time domain to examin temporal organization of corticospinal function | Other: Electrophysiology Assessment of Time Domain<br>* Kinematics, Spinal Cord Excitability and Cortical Spinal Motor Excitability.<br>Other: Training with some stimulation<br>* motor task combined with real or sham stimulation<br>|
| Experimental: Electrophysiology Assessment of Location<br>Assessment of electrophysiology to examine spatial organization of corticospinal function | Other: Electrophysiology Assessment of Location<br>* Kinematics, Spinal Cord Excitability and Cortical Spinal Motor Excitability<br>Other: Training with some stimulation<br>* motor task combined with real or sham stimulation<br>|
| Active Comparator: Training with some stimulation<br>Training with non-invasive stimulation and training with sham stimulation | Other: Training with some stimulation<br>* motor task combined with real or sham stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upper-limb motor function | measured by functional tests of hand/arm motor function | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortical Neurophysiological Outcome | measured by the maps area and overlap in millimeters | 5 months | 
| Change in Sensorimotor Function | measured by upper-limb movements scale from 1(dependent) to 7 (independent). | 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCI