Lower Limb Function After Spinal Cord Injury

This study plans to examine plasticity in corticospinal synapses of lower-limb muscles. it has been demonstrated that plasticity elicited at corticospinal synapses in the spinal cord result in enhancements in electromyographic (EMG) and force activity in upper-limb muscles. The first step in this proposal is to determine if synaptic plasticity can be elicited in corticospinal projections targeting lower-limb muscles in humans with SCI.

We will also study methods to strengthen corticospinal plasticity to promote recovery of leg clearance during training. We will use two novel strategies to enhance plasticity in corticospinal synapses of lower-limb muscles after SCI: a). administration of an N-methyl-D-aspartate (NMDA) receptor agonist (i.e. D-cycloserine), and b). Combine NMDA-induced corticospinal plasticity with training (2D lower limb training and locomotor training. Corticospinal synaptic plasticity is thought to depend on activation of NMDA receptors and D-cycloserine enhances motor skill behaviors in animals and humans will be enhanced by NMDA-induced corticospinal plasticity. An important strength of this aim is the combination of training and strategies that aimed at enhancing the synaptic efficacy of residual corticospinal projections. Training effects on physiological pathways will be explored and correlated with locomotor function

• D-Cycloserine (Drug), also known as Seromycin: 100 mg of Seromycin by mouth will be administered
• Placebo (Drug), also known as Placebo Drug: placebo pill will be administered instead of medication by mouth
• Training (Other): walking around a designated track at different speeds both forward and backward
• Stimulation (Other): magnetic stimulation and electrical stimulation may be applied
• Placebo Stimulation (Other): this is a fake stimulation that is administered but will be unknow to the subject.

Primary outcomes

• Changes in motor evoked potential size [30 minutes before and 30 minutes after intervention]

Sex: All, ages: 18 Years to 85 Years, accepts healthy volunteers

Inclusion Criteria:

* 4\. Inclusion criteria for individuals with SCI:

  * Male and females between ages 18-85 years of age
  * SCI ( ≥1 month of injury)
  * ASIA A, B,C and D
  * SCI above L5
  * Able to perform a visible contraction with dorsiflexor and hip flexor muscles (allowing testing of largely impaired patients)
  * Able to ambulate a few steps with or without an assistive device

Inclusion criteria for healthy controls:

* Male and females between ages 18-85 years of age
* Able to walk and complete lower-limb tests with both legs

Exclusion Criteria:

Exclusion criteria for individuals with SCI

* 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,
* 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, and
* 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.

Exclusion criteria for healthy controls:

* Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease,
* Any debilitating disease that causes exercise intolerance
* Premorbid, ongoing major depression or psychosis, altered cognitive status
* History of head injury or stroke,
* 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, and
* 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.

• Monica A Perez, PT, Phd, Principal investigator, Shirley Ryan AbilityLab