Identification of New Neuroimaging Biomarkers to Quantify the Decline in Brain Connectivity in Veterans with SCI and Measure Neuroplasticity due to Exoskeletal-assisted Walking

Every 30 minutes someone suffers a spinal cord injury (SCI) in the United States. There are about 300,000 individuals with SCI in the US, with around 17,800 new cases registered each year. The Department of Veterans Affairs (DVA) has over 42,000 Veterans with SCI registered in their database, of which about 27,000 are actively followed as part of ongoing care and rehabilitation. This makes the DVA the largest healthcare system in the world providing lifelong spinal cord care. SCI drastically diminishes a person’s mobility, with life-long consequences. Individuals who experience this catastrophic event go from regular mobility to limited or no mobility below their neurological lesion, becoming wheelchair reliant to get around their home and community. Military service members when paralyzed are unable to return to active duty. This drastic change in mobility has downward spiraling effects on a person’s physical and psychological health, including chronic pain, muscle spasticity, bone health, bowel/bladder function, obesity, community isolation, depression, and premature death. An important secondary consequence of SCI and subsequent long-term immobility is the decline in neural connectivity in the corticospinal tract. Prior physical rehabilitation studies have reported partial recovery of motor function in persons with incomplete and complete SCI, alluding to a large plastic capacity and reorganization of damaged corticospinal connections after SCI. Prior studies investigating corticospinal reorganization associated with motor recovery after SCI in humans have primarily focused on the spinal cord; evidence of neural reorganization and improvements in brain connectivity in humans at the supraspinal level after SCI is non- existent and much needed. This critical gap in knowledge is primarily due to the lack of evidence-based biomarkers to quantify the decline in brain connectivity after SCI. Recent advances in technology have enabled functional near-infrared spectroscopy (fNIRS), a relatively low-cost, portable, and high temporal resolution imaging to quantify neural activity in various brain regions through hemodynamic changes based on the principle of neurovascular coupling. fNIRS-based biomarkers have tremendous potential to detect improvements in brain connectivity early in response to physical rehabilitation, prior to any detectable recovery in motor function. One mode of physical rehabilitation that is growing in popularity is exoskeletal-assisted walking (EAW). The DVA has already committed to providing a robotic exoskeleton for home use to every eligible Veteran with SCI. A question of considerable practical relevance is can EAW mimicking physiological gait patterns increase brain connectivity in Veterans with SCI? The aims of this work are to: (1) identify new fNIRS-based biomarkers to quantify the decline in brain connectivity in Veterans with SCI, and (2) assess the feasibility of improving brain connectivity to promote neuroplasticity using EAW. Forty (40) participants with chronic SCI, including both complete and incomplete injuries, and forty (40) AB age-matched participants will be recruited. The SCI group will consist of Veterans with SCI at any level with demonstrable spared hand movement. Aim 1: Resting-state Functional Connectivity, a measure of intrinsic baseline alterations in brain connectivity, will be quantified for the SCI and AB participants. Aim 2: Task-induced fNIRS-based neurovascular biomarkers of sensorimotor function, namely Task-based Functional Connectivity, Task-based Hemodynamic Response, and Breath Hold Hemodynamic Response will be quantified for the SCI and AB participants. Aims 1 and 2 will be completed in one visit. Aim 3: A subset of 30 participants with SCI will be recruited for a pilot trial to tease out potential improvements in brain connectivity in Veterans with SCI. The participants will be randomly assigned to an EAW group (n = 10) or a control group (n = 20). The EAW group will Project Number: 1I01RX005309-01A1 | Fiscal Year: 2026 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: Saikat Pal | Institution: JAMES J PETERS VA MEDICAL CENTER, BRONX, NY | Activity Code: I01 | Study Section: Spinal Cord Injury/Disorders & Neuropathic Pain[RRDA] View on NIH RePORTER: https://reporter.nih.gov/project-details/11104425