Treadmill exercise activates subcortical neural networks and improves walking after stroke: A randomized controlled trial

Andreas R. Luft, Richard F. MacKo, Larry W. Forrester, Federico Villagra, Fred Ivey, John D. Sorkin, Jill Whitall, Sandy McCombe-Waller, Leslie Katzel, Andrew P. Goldberg, Daniel F. Hanley

Research output: Contribution to journalArticlepeer-review


Background and Purpose: Stroke often impairs gait thereby reducing mobility and fitness and promoting chronic disability. Gait is a complex sensorimotor function controlled by integrated cortical, subcortical, and spinal networks. The mechanisms of gait recovery after stroke are not well understood. This study examines the hypothesis that progressive task-repetitive treadmill exercise (T-EX) improves fitness and gait function in subjects with chronic hemiparetic stroke by inducing adaptations in the brain (plasticity). Methods: A randomized controlled trial determined the effects of 6-month T-EX (n≤37) versus comparable duration stretching (CON, n≤34) on walking, aerobic fitness and in a subset (n≤15/17) on brain activation measured by functional MRI. Results: T-EX significantly improved treadmill-walking velocity by 51% and cardiovascular fitness by 18% (11% and -3% for CON, respectively; P<0.05). T-EX but not CON affected brain activation during paretic, but not during nonparetic limb movement, showing 72% increased activation in posterior cerebellar lobe and 18% in midbrain (P<0.005). Exercise-mediated improvements in walking velocity correlated with increased activation in cerebellum and midbrain. Conclusions: T-EX improves walking, fitness and recruits cerebellum-midbrain circuits, likely reflecting neural network plasticity. This neural recruitment is associated with better walking. These findings demonstrate the effectiveness of T-EX rehabilitation in promoting gait recovery of stroke survivors with long-term mobility impairment and provide evidence of neuroplastic mechanisms that could lead to further refinements in these paradigms to improve functional outcomes.

Original languageEnglish (US)
Pages (from-to)3341-3350
Number of pages10
Issue number12
StatePublished - Dec 1 2008


  • Exercise
  • Fitness
  • Locomotion
  • Plasticity
  • Rehabilitation

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing


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