Avoiding performance and task confounds: Multimodal investigation of brain reorganization after stroke rehabilitation

Abstract

Stroke is the leading cause of disability worldwide despite significant advances in prevention and acute treatment. Thus there is an urgent need to understand the neural mechanisms of both spontaneous and rehabilitation-induced recovery. In the past 15 years, functional brain imaging has been used extensively to investigate recovery-related changes at the whole brain level (Calautti and Baron, 2003; Cramer et al., 1997; Krakauer, 2004; Marshall et al., 2000; Ward et al., 2003a, b). However, it has become apparent that functional imaging, when used alone to investigate post-stroke brain reorganization, has reached a near impasse. The reasons for this are briefly delineated here as they pertain to motor recovery. First, the definition of motor recovery has been surprisingly underemphasized even though it is obvious that the regions or patterns of activation identified will depend on the motor task in the scanner and on the out of scanner behavioral measures chosen as predictors in the image analysis. Second, measures of recovery are often crude and insensitive to the difference between compensatory improvements versus true recovery, or vicariation, of function. This is a real problem for functional imaging because compensatory adjustments will also often lead to activation changes even though they have nothing to do with true recovery. For example, use of more proximal limb muscles to aid distal control might lead to contralesional activation, as proximal muscles have more bilateral cortical representation, but of course this novel activation would not indicate reorganization after stroke. The situation becomes even worse when one considers that true recovery may in fact never occur, if strictly understood to mean a return to identical pre-morbid behavior due to identical neural computations, albeit performed at a new anatomical site. The implication is that tasks and measures have to be carefully chosen so that investigators know what they are attributing activation changes to. Third, functional