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

Abstract

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.

Figure 1

Participants flow through the trial.

Figure 2

Primary end points. Changes in measures of walking function and fitness in T-EX versus CON groups for the entire dataset (for statistical differences see text, error bars represent CI).

Figure 3

Cohort fMRI maps (voxel-based analysis). (A) showing brain regions where activation during paretic knee movement increased after T-EX training compared to stretching CON. Colored regions indicate areas with a statistically significant increase over time that was different between groups, the equivalent of a group * time interaction (P<0.05, random effects model, corrected for multiple comparisons, coordinates reference to the Montreal Neurological Institute reference brain). (B) showing brain regions where the change in activation occurring over the course of intervention (T-EX and CON subjects combined) correlates with the postpre difference in treadmill walking velocity (random effects factorial regression model, P<0.001 uncorrected).