Transspinal-Transcortical Paired Stimulation for Neuroplasticity and Recovery After SCI
Condition: Spinal Cord Injuries; Paraplegia, Spinal; Tetraplegia/Tetraparesis
MeSH terms: Spinal Cord Injuries; Paraplegia; Quadriplegia
Study type: Interventional

Summary: 
      People with spinal cord injury (SCI) have motor dysfunction that results in substantial
      social, personal, and economic costs. Uncontrolled muscle spasticity and motor dysfunction
      result in disabilities that significantly reduce quality of life. Several rehabilitation
      interventions are utilized to treat muscle spasticity and motor dysfunction after SCI in
      humans. However, because most interventions rely on sensory afferent feedback that is
      interpreted by malfunctioned neuronal networks, rehabilitation efforts are greatly
      compromised. On the other hand, changes in the function of nerve cells connecting the brain
      and spinal cord have been reported following repetitive electromagnetic stimulation delivered
      over the head and legs or arms at specific time intervals. In addition, evidence suggests
      that electrical signals delivered to the spinal cord can regenerate spinal motor neurons in
      injured animals. A fundamental knowledge gap still exists on neuroplasticity and recovery of
      leg motor function in people with SCI after repetitive transspinal cord and transcortical
      stimulation. In this project, it is proposed that repetitive pairing of transspinal cord
      stimulation with transcortical stimulation strengthens the connections between the brain and
      spinal cord, decreases ankle spasticity, and improves leg movement. People with motor
      incomplete SCI will receive transspinal - transcortical paired associative stimulation at
      rest and during assisted stepping. The effects of this novel neuromodulation paradigm will be
      established via clinical tests and noninvasive neurophysiological methods that assess the
      pathways connecting the brain with the spinal cord.
    

Detailed description: 
      Motor dysfunction after SCI results in substantial personal, social, and economic costs.
      Secondary complications related to muscle spasticity and motor dysfunction significantly
      reduce quality of life. Rehabilitation efforts are compromised because most therapeutic
      interventions rely heavily on sensory afferent feedback that is interpreted by malfunctioned
      neuronal networks. On the other hand, electrical signals delivered over the spine regenerate
      neurons of the spinal cord in injured animals, and paired associative stimulation produces
      enduring neuronal plasticity in healthy and injured humans and animals. A fundamental
      knowledge gap still exists on induction of functional neuroplasticity and recovery of leg
      motor function following repetitive pairing of transspinal cord stimulation with
      transcortical stimulation in people with motor incomplete SCI. Our central working hypothesis
      is that transspinal cord stimulation paired with transcortical stimulation strengthens
      corticospinal neuronal connections, decreases ankle spasticity, and improves leg motor
      function. This notion is based on the concept tested in the applicant's laboratory that this
      novel stimulation paradigm potentiates synaptic actions and activity of spared but
      compromised axons providing the necessary environment for functional neuroplasticity. The
      rationale of this research study is that neuromodulation methods that can modify effectively
      the input-output relations of cortical and spinal neuronal pathways in people with motor
      incomplete SCI are needed. Based on strong preliminary data, two specific aims will be
      addressed: Specific Aim 1: Establish induction of transspinal-transcortical paired
      associative stimulation (PAS) neuroplasticity and improvements in leg sensorimotor function
      in people with motor incomplete SCI when PAS is administered during robotic-assisted gait
      training. Cortical and corticospinal neuronal circuits via state-of-the-art
      neurophysiological methods in seated (Aim 1A), soleus H-reflex excitability during assisted
      stepping (Aim 1B), and sensorimotor function evaluated via standardized clinical tests (Aim
      1C) will be assessed before and after 15 sessions of transspinal-transcortical PAS delivered
      with subjects supine. Specific Aim 2: Establish induction of transcortical-transspinal PAS
      neuroplasticity and improvements in leg sensorimotor function in people with motor incomplete
      SCI when PAS is administered during assisted stepping. Cortical and corticospinal
      neuroplasticity via state-of-the-art neurophysiological methods in seated (Aim 2A), soleus
      H-reflex excitability during assisted stepping (Aim 2B), and leg sensorimotor function
      evaluated via standardized clinical tests (Aim 2C) will be assessed before and after 15
      sessions of transspinal-transcortical PAS delivered during assisted stepping. It is
      hypothesized that transspinal-transcortical PAS delivered at rest or during assisted stepping
      strengthens corticospinal connections, increases spinal inhibition, decreases ankle
      spasticity, and improves leg motor function. Further, transspinal-transcortical PAS delivered
      during assisted stepping normalizes the abnormal phase-dependent soleus H-reflex modulation
      commonly observed during stepping in people with motor incomplete SCI. To test the project
      hypotheses, 12 people with motor incomplete SCI will receive 20 sessions of
      transspinal-transcortical or transcortical-transspinal PAS during assisted stepping. In
      people with SCI, and assess improvements in leg motor function with standardized clinical
      tests. In all subjects, assessments of neuroplasticity in cortical, corticospinal, and spinal
      neuronal networks will be administered. These results will advance considerably the field of
      spinal cord research and change the standard of care because there is great potential for
      development of novel and effective rehabilitation strategies to manage spasticity and improve
      motor function after SCI in humans.
    

Intervention name(s): Transspinal-transcortical paired-associative stimiulation combined with robotic gait training; Transcortical-transspinal paired-associative stimiulation combined with robotic gait training
Intervention type(s): Device; Device
Intervention description(s): Individuals with spinal cord injury will receive 20 daily sessions of robotic gait training. During assisted stepping, they will receive also paired non-invasive transspinal stimulation and non-invasive brain stimulation during the stance phase of gait. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.; Individuals with spinal cord injury will receive 20 daily sessions of robotic gait training. During assisted stepping, they will receive also paired non-invasive brain stimulation and non-invasive transspinal stimulation during the stance phase of gait. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Individuals with Spinal Cord Injury will be assigned to receive robotic gait training with the Lokomat combined with paired non-invasive thoracolumbar transspinal stimulation and non-invasive brain stimulation.
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Spinal Cord Injury; Locomotor Training; Neuromodulation; Paired-Associative Stimulation