Use it and/or lose it-experience effects on brain remodeling across time after stroke

The process of brain remodeling after stroke is time- and neural activity-dependent, and the latter makes it inherently sensitive to behavioral experiences. This generally supports targeting early dynamic periods of post-stroke neural remodeling with rehabilitative training (RT). However, the specific neural events that optimize RT effects are unclear and, as such, cannot be precisely targeted. Here we review evidence for, potential mechanisms of, and ongoing knowledge gaps surrounding time-sensitivities in RT efficacy, with a focus on findings from animal models of upper extremity RT. The reorganization of neural connectivity after stroke is a complex multiphasic process interacting with glial and vascular changes. Behavioral manipulations can impact numerous elements of this process to affect function. RT efficacy varies both with onset time and its timing relative to the development of compensatory strategies with the less-affected (nonparetic) hand. Earlier RT may not only capitalize on a dynamic period of brain remodeling but also counter a tendency for compensatory strategies to stamp-in suboptimal reorganization patterns. However, there is considerable variability across injuries and individuals in brain remodeling responses, and some early behavioral manipulations worsen function. The optimal timing of RT may remain unpredictable without clarification of the cellular events underlying time-sensitivities in its effects.