Eccentric-focused rehabilitation promotes myelin plasticity in individuals with chronic, incomplete spinal cord injury

Abstract

Background: Myelin plasticity has emerged as a novel mechanism by which the nervous system can change with experience, offering new potential for rehabilitation-induced recovery after neurotrauma. This first-in-human study investigated whether innovative, downhill locomotor rehabilitation promotes myelin plasticity in individuals with chronic, incomplete spinal cord injury (SCI). Methods: Of 20 individuals with SCI that enrolled, 4 passed the imaging screen and had myelin water imaging (MWI) before and after a 12-week (3 times/week) downhill locomotor treadmill training program (SCI+DH). One individual was excluded for imaging artifacts. Uninjured control participants (n=7) had two MWI sessions within the same day. Changes in myelin water fraction (MWF), a histopathologically-validated myelin biomarker, were analyzed in a priori motor learning and non-motor learning brain regions and the cervical spinal cord using statistical approaches appropriate for small sample sizes. Results: Within SCI+DH individuals, significantly more motor learning regions showed increased MWF than non-motor learning regions (p<.05). Compared to Control, MWF in the SCI+DH group increased in white matter underlying postcentral and precuneus cortices, combined motor learning brain regions, and ventral spinal cord (p<.05). To account for small sample size, an estimation-based approach showed the pattern of MWF increase was specific to training and region. Conclusion: Downhill training increased MWF in brain regions specifically associated with motor learning and in the ventral spinal cord. Trial Registration: ClincialTrials.gov (NCT02498548, NCT02821845). Funding: National Institutes of Health [F31NS096921 (TDF), R21HD082808 (DMB)], Craig H. Neilsen Foundation [316282 (DMB)], Foundation for Physical Therapy Research [Promotion of Doctoral Studies Level II Scholarship (TDF)]