DESCRIPTION (adapted from the Abstract): The long-term goals of this project are to examine the capacity for functional reorganization in the motor cortex of adult primates following brain injury, such as that occurring after stroke. These studies will use neurophysiological, neuroanatomical, optical imaging, and behavioral training techniques to examine functional reorganization in the primary motor cortex and the premotor cortex after focal vascular infarct, and the effects of physical use of affected muscles on the areal extent and time course of reorganization. In their previous studies, the researchers showed that lesions within the hand area of the primary motor cortex result in a further loss of hand representations in the adjacent, intact tissue. However, physical therapy introduced within days after the infarct prevented this secondary, dysfunctional loss of spared hand representations. To determine whether critical periods exist for the effects of rehabilitative therapy on behavioral and neurophysiological recovery, the researchers will compare functional maps of motor cortex before and a few months after the focal vascular infarct. They will introduce physical therapy at various time points after infarct to define an optimal window for rehabilitation. Further, they will examine the long-term effects of physical rehabilitation with respect to both plasticity in cortical motor maps and behavioral capacity. They will determine whether the effects of early rehabilitative therapy are persistent. In other experiments, the researchers will examine the neurophysiological bases for behavioral relapse that occurs about two weeks after infarct. Further, they will examine the structural bases for adaptive plasticity in the motor cortex after injury by studying changes in intracortical connectivity. Finally, the researchers will extend these studies to explore more widespread effects of focal infarcts on other cortical motor areas that are interconnected with the primary motor cortex. These studies have strong clinical relevance for understanding stroke and rehabilitation. The correlation of neurophysiological and neuroanatomical reorganization with functional recovery after brain damage may eventually lead to new approaches to rehabilitative medicine.