Corticospinal Function After Spinal Cord Injury

Shirley Ryan AbilityLab

Status: Enrolling

Conditions: Spinal Cord Injury

Treatments: Other: Electrophysiology Assessment of Time Domain; Other: Training with some stimulation; Other: Electrophysiology Assessment of Location

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02451683

R01NS090622-01 (U.S. NIH Grant/Contract)

STU00210458

Details and patient eligibility

About

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.

Full description

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

Enrollment: 300 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Inclusion criteria for individuals with SCI:

  1. Male and females between 18-85 years,
  2. Chronic SCI (≥ 6 months post injury),
  3. Cervical injury at C8 or above,
  4. Intact or impaired but not absent innervations in dermatomes C6, C7, and C8 using the American Spinal Injury Association sensory scores, and
  5. 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:

1. Male and females between 18-85 years,
2. Right handed,
3. 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:

  1. Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
  2. Any debilitating disease prior to the SCI that caused exercise intolerance
  3. Premorbid, ongoing major depression or psychosis, altered cognitive status
  4. History of head injury or stroke
  5. Pacemaker
  6. Metal plate in skull
  7. History of seizures
  8. Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressants
  9. Pregnant females
  10. 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.
  11. History of brain tumor and or brain infection

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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300 participants in 3 patient groups

Electrophysiology Assessment of Time Domain

Other group

Description:

Assessment of electrophysiology in the time domain to examin temporal organization of corticospinal function

Treatment:

Other: Electrophysiology Assessment of Time Domain

Other: Training with some stimulation

Electrophysiology Assessment of Location

Experimental group

Description:

Assessment of electrophysiology to examine spatial organization of corticospinal function

Treatment:

Other: Training with some stimulation

Other: Electrophysiology Assessment of Location

Training with some stimulation

Active Comparator group

Description:

Training with non-invasive stimulation and training with sham stimulation

Treatment:

Other: Training with some stimulation