Brain Plus Spinal Stimulation for Cervical SCI
Condition: Spinal Cord Injuries; Spinal Cord Injury at C5-C7 Level; Tetraplegia/Tetraparesis
MeSH terms: Spinal Cord Injuries; Quadriplegia; Wounds and Injuries
Study type: Interventional

Summary: 
      The goal of this project is to strengthen residual corticospinal tract (CST) connections
      after partial injury using combined motor cortex and spinal cord stimulation to improve arm
      and hand function after spinal cord injury (SCI).

      To do this, the investigators will test the combination of transcranial magnetic stimulation
      (TMS) with transcutaneous spinal direct current stimulation (tsDCS) in individuals with
      chronic cervical SCI.
    

Detailed description: 
      For people with cervical SCI, regaining hand function is their highest priority. Most SCIs
      are motor incomplete, and even when complete, there is often significant amounts of spared
      spinal cord white matter. The goal of this project is to strengthen residual corticospinal
      tract (CST) connections after partial injury using combined motor cortex and spinal cord
      stimulation to improve arm and hand function.

      The team's research in rats, which has been refined in over a decade of study, demonstrates
      that brain and spinal cord stimulation fully restores motor skills in rats after CST injury.
      Most significant for the population of people living with SCI, this approach is effective in
      the chronic phase of injury.

      Recently, the investigators translated this electrical stimulation protocol into one that can
      be rapidly translated into people using non-invasive techniques. In rats, combined electrical
      intermittent theta burst stimulation (iTBS) of motor cortex with transcutaneous spinal direct
      current stimulation (tsDCS) activates the cervical spinal cord. This protocol, which is
      administered only 30 minutes a day for 10 days, causes large-scale sprouting of CST
      connections and full recovery of forelimb function. Thus, by combining brain and spinal cord
      electrical stimulation in rodents with corticospinal system injury durable CST axonal
      sprouting, strengthening of CST connections, and recovery is achieved.

      In this proposal, the investigators intend to bring this promising therapeutic approach to
      humans with cervical SCI. The team will study people with chronic, motor incomplete, SCI to
      test the safety and feasibility of this approach. The investigators' approach is non-invasive
      and, if shown to be effective, can be rapidly integrated into current clinical practice to
      help restore hand function in people with chronic SCI.

      Each subject will undergo four stimulation sessions of 4 hours or less. Outcomes focus on
      safety and neurophysiological transmission. The first session is used to determine the target
      muscle, optimal scalp site for TMS stimulation, assess cervical tsDCS tolerability, and
      measure maximal contraction force of the fingers, wrist, and elbow. The second through fourth
      sessions will assess the acute tolerability and effects of tsDCS with different intensities
      and electrode configurations in a randomized order. Each session will test a different
      electrode configuration and will be divided into two stages. The first stage will randomly
      deliver three 5-minute blocks of tsDCS at different randomized intensities (100%, 66% and 0%
      (sham) of tolerated intensity, as determined in Session 1) and assess changes in
      corticospinal and spinal excitability in response to TMS and peripheral nerve stimulation
      (PNS) of the target muscle. The second stage will assess the acute effects of 20-minutes of
      tsDCS delivered at two thirds the maximal tolerability on TMS- and PNS-evoked responses and
      performance of a motor task. Safety and tolerability will be closely monitored at all times.
    

Intervention name(s): transcutaneous spinal direct current stimulation (tsDCS) - coronal; transcutaneous spinal direct current stimulation (tsDCS) - caudal; transcutaneous spinal direct current stimulation (tsDCS) - rostral; intermittent theta burst stimulation (iTBS)
Intervention type(s): Device; Device; Device; Device
Intervention description(s): 20 minutes of tsDCS will be delivered at 66% of maximum tolerated intensity with cathode over C5-C7 transverse process on target side, anode over C5-C7 transverse process on non-target side.; 20 minutes of tsDCS will be delivered at 66% of maximum tolerated intensity with DCS cathode over ~T1-T4 posteriorly, anode over ~C5-T1 anteriorly; 20 minutes of tsDCS will be delivered at 66% of maximum tolerated intensity with DCS cathode over ~C3-C5 posteriorly, anode over ~C5-T1 anteriorly; 3 minutes of iTBS (a form of repetitive TMS) will be delivered during a 5-minute interval of DCS
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: transcranial magnetic stimulation; spinal direct current stimulation