Chronic spinal cord injury (SCI) is a debilitating disorder in Veterans and the broader U.S. population that does not have a cure. Veterans with severe SCI demonstrate permanent loss of sensory and motor function below their injury resulting in decreased quality of life and independence. Recently, electrical spinal neuromodulation has emerged as a potential approach to restore voluntary motor function and locomotion in persons with chronic SCI. However, spinal neuromodulation has yet to translate to clinical use due to small sample sizes in research studies and a lack of information on which patients would benefit. Here, the investigators propose a novel approach to evaluate the priorities and barriers faced by Veterans with SCI to use spinal neuromodulation, understand the neural connections remaining in Veterans with severe SCI, and determine potential functional improvements using non-invasive spinal neuromodulation technology. This research represents the first step towards deploying techniques that could dramatically improve function and quality of life for Veterans with SCI.

The International Standards for Neurological Classification of SCI (ISNCSCI) exam is used to classify spinal cord injury (SCI) severity by determining the neurological injury level and functional completeness of SCI. However, anatomical, physiological, and functional studies have indicated that many participants with ISNCSCI-defined complete SCI retain connectivity through the SCI lesion. Due to the heterogeneity of SCI and the small-N in prior spinal neuromodulation studies, there are no diagnostic criteria to determine how SCI lesion profile affects the ability to restore sensorimotor function in the presence of spinal neuromodulation. Development of this knowledge is necessary to design precise spinal neuromodulation approaches and clinical trials that could restore function and improve quality of life for Veterans with chronic SCI. First, stakeholders will be engaged to define research priorities, meaningful outcomes, and barriers to participation in neuromodulation trials. The potential impact of neuromodulation and priorities of Veterans with SCI and their caretakers will be assessed across a nationwide survey. Spinal neuromodulation will be evaluated to determine how it could impact clinical practice and treatment of Veterans though survey of SCI physicians. Qualitative feedback will be obtained from Veterans with SCI regarding the expected and achieved outcomes with neuromodulation prior to and after undergoing functional neuromodulation experiments. Next, baseline anatomical and physiological connectivity measurements across ISNCSCI scores will be established. Veterans with SCI across INSCSCI grades will be recruited to determine residual spinal connectivity. Spinal cord anatomy will be assessed above, below, and at the SCI lesion through MR neuroimaging. Descending corticospinal connectivity will be evaluated with transcranial magnetic stimulation and ascending afferent signals will be evaluated through somatosensory evoked potentials. Finally, functional spinal connectivity during spinal neuromodulation will be evaluated. Volitional motor output will be assessed with and without non-invasive spinal neuromodulation. The sensory effects of spinal neuromodulation will be assessed through user reports of pain and somatosensation. Potential functional improvements in activities of daily living will be assessed with and without spinal neuromodulation.

Inclusion Criteria:

• All participants must be able to independently read and understand study information materials necessary to ensure informed consent.
• All participants must have a chronic spinal cord injury occurring >1 year prior to study enrollment.
• Ability to follow simple commands in English.

Exclusion Criteria:

• Contraindications to the use of external magnetic or electrical stimulation (e.g., epilepsy, intracranial metal, implanted electrosensitive device, etc.)
• Significant neurological comorbidities that may affect neurophysiological recordings
• Functional disability prior to spinal cord injury
• Visual or auditory disorders limiting ability to participate in study procedures
• Pregnancy
• Primary psychiatric disorders or dissociative mental symptoms that impair informed consent
• Significant chronic pain that may preclude an MRI scan or performing neurorehabilitation exercises
• Frequent and significant spasticity that may preclude an MRI scan or neurorehabilitation exercises.

The PI will share de-identified datasets and results collected through this proposal by depositing these data at the National Library of Medicine (NLM) PubMed Central website repository as this is a VA supported data repository. The raw and processed neurophysiological data will be shared with supplementary metadata that includes information about the study methodology used to collect the data, details about the code, and definitions of variables.

The data will be posted following publication of the data in a scientific journal. It is anticipated that this project will produce approximately 1 publication per year after the second year, with the data published simultaneously. All of the data will be published at the conclusion of the study in five years. The deidentified data will be posted on publicly accessible servers and will be stored there permanently.

Deidentified data will be accessible by all who interested parties. Any further requests will be made and reviewed by the PI.

Due to the uniqueness of each injury, all staff will be aware of each participant's history. All participants will receive the same intervention.