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

222 Citations (SciVal)


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
Pages (from-to)3341-3350
Number of pages10
Issue number12
Early online date28 Aug 2008
Publication statusPublished - 01 Dec 2008


  • Aged
  • Aged, 80 and over
  • Brain
  • Cerebellum
  • Exercise Therapy
  • Female
  • Gait Disorders, Neurologic
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mesencephalon
  • Middle Aged
  • Nerve Net
  • Stroke
  • Stroke Rehabilitation
  • Walking
  • Comparative Study
  • Journal Article
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Exercise
  • Plasticity
  • Locomotion
  • Rehabilitation
  • Fitness


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