Spinal Cord Stimulation for Functional Recovery in Humans With Tetraplegia

In support of the long-term goal of developing new strategies to increase limb function after SCI, the objectives of this proposal are to: 1) Examine the behavioral and physiological effects of TESS on upper-limb muscles after cervical SCI; and 2) Maximize the recovery of reaching and grasping potential by using tailored TESS in a task-specific manner with motor training. Veterans with cervical spinal injuries and healthy volunteers will be recruited for this study.

Current studies demonstrate that electrical spinal stimulation, either invasive or noninvasive, can play an important role in rehabilitation strategies aimed at improving limb function in humans with SCI (Taccola et al., 2018). Among current stimulation strategies, one of the most promising candidates to emerge in recent years is transcutaneous electrical spinal stimulation (TESS). TESS is a noninvasive technique that can be tailored to the needs of each individual, where several segments of the spinal cord can be stimulated at the same time, and delivery can be programed to interact with a rehabilitation strategy during functional movements, such as reaching or grasping. A key element to TESS is its ability to access spared spinal cord networks with minimal discomfort. Although promising, the knowledge of TESS remains limited in scope and more studies are needed to further identify its efficacy.

In Aim 1, subjects will participate in two randomized sessions: 1) TESS, and 2) sham-TESS.\] In Aim 2, the investigators will examine the effect of stimulation and training for a total of 20 sessions (3 to 5 per week). Participants will be randomly assigned to: \[1) Closed-loop TESS applied during grasping + training, or 2) Closed-loop TESS applied during reaching + training.\]

AIM 1 Subjects with SCI and without SCI (controls) will participate in two testing sessions, separated by 2-3 days, using a crossover design. In each session, TESS or sham-TESS will be applied over the cervical spinal cord. Functional and physiological measures will be acquired before and after each session.

AIM 2 Develop methodologies to promote recovery of reaching and grasping movements. To accomplish this goal, the investigators will combine TESS applied in a closed-loop manner with massed practice upper-limb training. Participants will be assigned to one of three groups in a randomized order using a sham controlled design: \[1) Closed-loop TESS applied during grasping + training, 2) Closed-loop TESS applied during reaching + training, and 3) Closed-loop TESS applied during grasping \& reaching + training.\] TESS for 20-min will be followed by 60 min of massed practice exercise training (total=20 sessions).

Eligibility Criteria:
Inclusion Criteria:

Inclusion criteria for SCI:

* Male and female Veterans between 18-70 years
* Chronic SCI (1 year of injury)
* Cervical injury at C8 or above - damage between cervical spinal segments will be confirmed using MRI \[preliminary data (Benavides et al., 2020) and analysis of MRIs in \~100 participants with cervical SCI confirm that the investigators can meet our recruitment goals. Note that most SCI in humans damage several spinal cord segments

  * Verification of damage to cervical spinal segments will ensure that TESS electrodes will target the injured spinal cord (Benavides et al., 2020)
* Intact or impaired, but not absent, innervations in dermatomes C6, C7 and C8 during light touch and pin prick stimulus using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) sensory scores as tested before in our studies (Bunday and Perez, 2012; Bunday et al., 2018; Benavides et al., 2020; Jo and Perez, 2020)
* Able to produce a visible power grip with one hand
* Can score a minimum of two (2) in the cylindrical grasp the "Prehension Ability" GRASSP

  * This criterion was selected to ensure that hand impairment will not interfere with the ability to perform training and the proposed tests

Inclusion criteria for controls:

* Males and females (18-70 years)
* Right-handed
* Able to complete grasping

Exclusion Criteria:

Exclusion criteria for SCI and control subjects:

* 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 concussion, skull fractures (or any skull deficit), unexplained headaches in the last 6 months, 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 one who suffers from a spinal cord disease such as spinal stenosis, spina bifida, or herniated cervical disk