Spinal Muscle Impairments: Uncovering Therapeutic Targets for Improved Mobility after Amputation - MODIFIED PROJECT SUMMARY/ABSTRACT Following rehabilitation after a lower-extremity amputation, functional mobility deficits persist, and outcomes are mediocre. Identification of modifiable, novel factors that are prognostic for unfavorable outcomes that can be rehabilitation targets is critical. The lumbar spinal muscles, i.e., multifidi and erector spinae, are critical for postural stability and functional mobility. With limb amputation, increased spinal muscle effort is required to compensate for lower-limb muscle loss, but the spinal muscles are ill-equipped to meet increased demands. Our prior cross-sectional study found adults with lower-extremity amputation of >1 year (post-acute) have significant spinal muscle impairments, i.e., reduced extensor endurance, less multifidi muscle activity, and greater multifidi intramuscular fat indicating poorer muscle quality, and that these impairments are associated with worse functional mobility. The overarching goal of this research line is to determine if spinal muscle impairments are key prognostic factors for future mobility limitations in adults with lower-extremity amputation that should be rehabilitation targets in subsequent clinical trials. Knowledge gained will inform participant selection and intervention specificity, in that treatments can be matched to modifiable impairments. Treatment specificity is particularly critical for resolution of spinal muscle impairments. We will enroll 72 adults with post-acute lowerextremity amputation who will complete the primary outcome assessing mobility at 5 timepoints over 12 months. Non-modifiable and modifiable factors (e.g., spinal muscle metrics, pain, adiposity, hip strength) will be evaluated at baseline, 6- and 12-months. Novel, reliable, and valid ultrasound imaging methods developed by our team will be used to evaluate spinal muscles. Aim 1 will test whether baseline spinal muscle metrics are related to functional mobility over time in adults with post-acute lower-extremity amputation while considering non-modifiable factors and low back pain. We will specifically test whether low back pain is related to spinal muscle metrics and mobility, as ~45% of adults with lower-extremity amputation have low back pain, and in the general population, low back pain negatively impacts both spinal muscle and mobility. Aim 2 will identify modifiable factors at baseline and changes in modifiable factors related to mobility decline at 12 months. Aims will provide insight regarding the need for both rehabilitation treatment specificity (e.g., motor control exercises to enhance multifidi activity; low-load, long duration exercises to enhance endurance) and multi-faceted interventions (e.g., spine- and hip-directed) to reduce mobility decline. Results will inform precision, post-acute lower-extremity amputation rehabilitation, which is critical given population heterogeneity and poor functional outcomes.