Dentatothalamocortical electrical stimulation in post-stroke motor recovery

Cleveland Clinic Lerner Com-Cwru, Cleveland OH

Investigators

Linked publications, trials & patents

Abstract

DESCRIPTION (provided by applicant): Stroke is a very common condition in the population, affecting nearly 800.000 new American every year. A third of stroke patients maintain long term motor deficits severe enough to be disabling, despite rehabilitative efforts. New therapies to improve motor outcomes after stroke are needed. The long-term goal of this line of investigation is to develop a neurorestorative therapy to enhance motor recovery for patients who have suffered cortico-subcortical strokes. The investigators have demonstrated previously that electrical stimulation of the lateral cerebellar (dentate) nucleus (LCN) produces sustained increment in cortical excitability and that chronic LCN stimulation enhance recovery of motor function in an established 3-vessel occlusion rodent model of ischemic stroke. The hypothesis was developed based on 1) prior evidence suggesting a role for the cerebello-thalamo-cortical pathway (a net disynaptic excitatory pathway) in modulating cerebral cortical excitability; 2) evidence that cortical plasticity can be enhanced by augmenting cortical excitability; and 3) anatomical evidence that indicates the dentatothalamocortical pathway projects not only to the motor cortex but also to the premotor frontal and parietal cortical areas. These areas correspond to the perilesional zone in typical middle cerebral artery infarcts and are thought to be involved in local reorganization associated with motor recovery after stroke. Thus far, our results are promising and human translation is feasible given that the technology for deep brain stimulation (DBS) is already FDA approved for the treatment of movement disorders and has been proven safe in over 40,000 implants. This research proposal was designed to further develop this line of investigation with the goals of: a) identifying stimulation parameters that may drive motor recovery beyond the current results; b) addressing the question of optimal timing for stimulation onset and termination (i.e., therapeutic window), which will have a crucial impact in successful translation of this approach to humans and c) assessing a link between chronic LCN stimulation-induced motor recovery and perilesional cortical plasticity.