Motor system plasticity in stroke models: intrinsically use-dependent, unreliably useful

Abstract

Background and Purpose: The natural response to disability in one limb is to learn new ways of using the other limb. This compensatory behavioral strategy after stroke has long been thought to contribute to persistent dysfunction in the paretic limb by encouraging its disuse. Our recent findings suggest that it goes beyond the encouragement of disuse to disrupt neural substrates of paretic limb functional improvements.

Methods: We overview recent findings from rodent models of chronic upper extremity impairments in which precise control and manipulation of forelimb experiences were used to understand bilateral and interhemispheric contributions to motor functional outcome.

Results: Skill learning with the less-affected (nonparetic) forelimb promotes neural plasticity in the contralesional motor cortex that subserves its function. At the same time, it exacerbates dysfunction and limits the efficacy of rehabilitative training in the paretic limb. The maladaptive effects of skill learning with the nonparetic forelimb are dependent on callosal connections and contralesional motor cortex, and linked with reduced neural activation of peri-infarct motor cortex during rehabilitative training.

Conclusions: These findings suggest that learning to rely on the nonparetic body side has the capacity to disrupt functionality in a region of the injured hemisphere that contributes to outcome of the paretic limb. Whether this effect generalizes across injury loci and functional modalities remains to be tested.

Keywords: experience-expectant plasticity; learned nonuse; manual skill; motor cortex; motor rehabilitative training.

Fig. 1

A, A rodent model of chronic upper extremity impairments resulting from focal ischemic damage to motor cortex (MC). Dots indicate movement representations revealed with intracortical microstimulation mapping (n=9 maps overlaid). B, Skilled reach training is used as a tool to investigate neural and behavioral effects of compensatory skill learning with the nonparetic forelimb. This training worsens function in the paretic limb and reduces the efficacy of subsequent rehabilitative training. C, Converging projections of ipsi and contralesional MC that contribute to forelimb movement. We hypothesize that learning with the nonparetic limb drives reorganizational patterns in converging projection areas that interfere with later change by experiences of the paretic limb. CFA, caudal forelimb area of primary MC, RFA, rostral forelimb area of premotor/supplementary MC.