Jones, T. A. et al. Motor System Plasticity in Stroke Models: Intrinsically Use-dependent, Unreliably Useful. Stroke 44, S104–S106 (2013).

This paper summarizes the work on animal models to understand the effect of skill learning with the non-paretic limb on the recovery potential of the paretic limb.

Attempting to summarize a beautifully written summary paper, one always runs into the risk of doing a highly lossy compression. The paper is hardly two pages, and well written, so it is definitely worth a read.

"Functional impairment is a powerful incentive for behavioral change.

The development or adoption of various compensatory movements/strategies is one of the most reliable consequences of surviving a brain injury. The most prevalent and profound form of compensation is the increased use of the non-paretic limb.

This reliance is often believed to cause dysfunction of the impaired limb by encouraging disuse (learned non-use), i.e. the ability of the paretic limb is unaffected, but one simply learns not to use it. The impact of compensating with the less affected limb is on the decision-making side in this particular model.

But this is not entirely true. Using the non-paretic limb has a direct negative consequence on the recovery of the paretic limb.

• Following a brain lesion, learning a new skill with the non-paretic limb will reduce the responsiveness of the paretic limb to subsequent rehabilitation training. Any novel use of the non-paretic limb is likely to lead to such results. This is not seen in intact animals.
• This effect appears to be the direct consequence of the influence of the contralesional cortex on the peri-infarct region in the lesioned cortex. Learning a novel skill with the non-paretic limb reduces neuronal activation in the peri-infarct motor cortex. This reduced activation makes the peri-infarct region less responsive to rehabilitative training that would normally lead to increased activity in the peri-infarct region, which has been shown to promote functional improvements in the brain. These indicate that the behavioral consequences of compensating with the non-paretic limb are at least partly due to the disruption of functional reorganization capacity of the peri-infarct region.
• The callosal projections are the route for these disruptive effects. Transecting the callosal fibers prevents such changes from occurring.
• Bilateral lesions also remove this effect.
• Skill learning has been shown to lead to dendritic growth and synaptogenesis on the contralateral MC. Lesion to one side denervates the contralesional MC and thus leads to an exaggerated growth response on contralesional MC. The layer V pyramidal neuron in the contralesional MC project to the peri-infarct region.
• One possible explanation: Early after the lesion, the peri-infarct region is highly malleable. Converging projections to the peri-infarct region from the ispi- and contralesional MC interact to remodel the peri-infarct region. Learning to use the non-paretic limb leads sets the structure in this circuitry early on, which makes recovery of paretic limb more difficult at a later stage. This is very much like the experience-expectant plasticity seen during development: early during the sensitive period sculpts the neuronal circuitry through activity-dependent competition, after which the connections are resistant to change outside the sensitive period.

Remarks:

There is no mention of whether just increased use of the non-paretic limb leads to such deleterious effects on the recovery of the paretic limb. I am assuming it does not.

Following a lesion to one side of the brain, most use of the non-paretic side is likely to have some form of novel use. This is likely to be particularly true in the paretic side is the dominant side. Does this mean that recovery would be different depending on whether the paretic side is the previous dominant or non-dominant side? If it is the dominant side, the most use of the non-paretic (non-dominant) limb is likely to be novel for that limb. While, if the paretic side is the non-dominant side, then the use of the non-paretic (dominant) side is less likely to be novel. Additionally, this will also depend on the level of asymmetry in two limbs prior to the lesion.