Motor System Plasticity in Stroke Models

Abstract

Functional impairment is a powerful incentive for behavioral change. The natural response to disability in one limb is to learn new ways of using the other limb. Animals, including humans, with upper extremity impairments spontaneously learn to use the less-affected (nonparetic) hand in novel ways to perform daily activities.1–3 In intact brains, the acquisition of manual skills depends on practice-dependent synaptic structural and functional reorganization of motor cortex (MC).4,5 After stroke, this skill acquisition overlaps with ongoing degenerative and regenerative responses to the injury, many of which are also neural activity dependent6,7 and sensitive to behavioral manipulations.8–10 When they converge on the same circuits, ischemia-induced and experience-driven remodeling responses interact.3 Learning to rely on the nonparetic hand is a particularly prevalent and profound form of poststroke behavioral compensation, but compensatory strategies can be found across different impairment modalities, body sides, and injury loci.11–13 Their development is among the most reliable consequences of brain injury survival. The implication is that understanding the brain’s typical adaptation to stroke will require understanding its interactions with compensatory behavioral changes. The compensatory reliance on the better functioning limb after stroke has long been thought to contribute to persistent dysfunction in the affected (paretic) limb by encouraging its disuse (ie, learned nonuse).14 Our recent findings suggest that it can go well beyond this to directly disrupt the neural substrates paretic limb functional improvements. Here we overview these findings, as revealed in rodent models of chronic upper extremity impairments using precise control and manipulation of forelimb experiences to understand bilateral and interhemispheric contributions to motor functional outcome. After unilateral ischemic MC damage in rats, a relatively subtle variation in behavioral experience—learning a single new motor skill with the nonparetic limb—reduces …