A study of the functional anatomy of motor recovery after stroke. (360G-Wellcome-071398_Z_03_A)

Treatment of disability after stroke relies on the delivery of specific therapies in the setting of the multidisciplinary team, but lacks a clear neurobiological rationale. Work in animals suggests that the brain has a remarkable capacity to remodel its pathways and connections after injury, and that these changes correlate with improved function. In order to promote an understanding of the neural basis of recovery in humans, I propose to examine firstly, the process of cerebral reorganisation after stroke and whether it can account for recovery of function, and secondly whether it is possible to manipulate this cerebral reorganisation in order to promote recovery. Cutting edge brain imaging techniques have developed to the point where a detailed appreciation of (1) the damage to brain structures and their connections, and (2) the function of the remaining brain areas, is possible. These studies have already suggested that parts of the brain normally only involved in more complex movements, help recovery of simple movements after stroke. In order to develop this theme, I will use magnetic resonance brain imaging techniques (at both 3 and 4.7 Tesla) to acquire physiological data from stroke patients and age matched controls. This approach will provide information about brain function (functional magnetic resonance imaging), grey and white matter structure (voxel based morphometry), anatomical connections (diffusion tensor imaging), cerebral perfusion (arterial spin labelling), and brain metabolism (magnetic resonance spectroscopy). In addition, neurophysiological data will be acquired using transcranial magnetic stimulation. By combining this anatomical and functional information in a way that has not previously been possible, a more thorough understanding of how brain reorganisation occurs, and how this relates to actual recovery, will emerge. Building on these studies, I plan to develop a functional imaging methodology that allows the investigation of proposed therapeutic interventions, and the degree to which they promote cerebral reorganisation and functional recovery in individual patients.