Longitudinal Changes in the Cortico-Reticulospinal Tract Associated with High-Intensity Locomotor Training in Chronic Stroke

Introduction: High-intensity locomotor training (HIT) is recommended for improving walking capacity, but treatment responses are variable. Understanding the brain changes underlying responsiveness to training could provide insight into this variability. Emerging evidence suggests upregulation of the contralesional cortico-reticulospinal tract (CRST) may contribute to walking function after stroke. However, it is unclear whether CRST upregulation is supportive or maladaptive, and no studies have examined CRST changes after HIT. This study investigated how CRST and corticospinal tract (CST) strength and laterality reorganize, and their relationship with walking capacity after locomotor HIT. Methods: Ten participants with chronic stroke completed a 4-week no-intervention control phase then 4-weeks of HIT. Diffusion MRI and 6-minute walk distance were obtained at weeks 0, 4, and 8. Analysis tested changes in ipsilesional and contralesional CRST and CST strength and laterality. Associations between changes in tract laterality and walking capacity were examined. Results: During the treatment phase (vs. the control phase), there were significantly greater increases in contralesional CRST strength (1.02 SD [95% CI: 0.25, 1.79]), contralesional CRST laterality (4.44 [2.15, 6.72]), and 6-minute walk distance (33 meters [17, 50]). Walking capacity improvements were associated with changes in CRST laterality (r = 0.77, p = 0.01), but not CST laterality (r = -0.01, p = 0.98). Discussion: Following HIT, increases in contralesional CRST strength and laterality were observed. CRST laterality changes were strongly associated with walking improvements, suggesting a possible supportive role of contralesional CRST in mediating training-related improvements in walking function after stroke. Clinical trial registration: ClinicalTrials.gov Identifier: NCT02858349 , https://clinicaltrials.gov/study/NCT02858349?term=NCT02858349&rank=1.