Identifying cortical and brainstem regions contributing to partial hand function post- stroke

Strokebridge Inc, Mountain View CA

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT The majority of individuals with hemiparetic ischemic stroke experience motor impairment in their upper extremity, specifically affecting the wrist and fingers. Wrist/finger weakness in these individuals is greater for extensors than flexors, causing a much higher difficulty in hand opening than closing. This problem is even more pronounced in severely impaired individuals who experience involuntary hand closure when trying hard to open it. Previous brain imaging studies have reported increased neural activity in motor, premotor and supplementary motor areas of both hemispheres, especially contralesional hemisphere, during hand movement in individual with stroke. Some have also reported this increased activity in contralesional motor cortices to be correlated with improved hand function post stroke. Moreover, our previous work in altered sensorimotor pathways post stroke, with the use of advanced MRI techniques, demonstrated an increased reliance on ipsilaterally projecting cortico- bulbo-spinal pathways in individuals with hemiparetic stroke. However, it is still unclear which cortical motor areas and motor pathways facilitate the preserved ability for wrist/fingers flexion and restrain the wrist/fingers extension after damage to the corticospinal pathway in stroke. Although it is unexplored in humans, animal studies of brainstem ipsilaterally projecting pathways have reported that the stimulation of reticulospinal and vestibulospinal tracts’ nuclei in brainstem would cause flexion at the ipsilateral limb; in other words, ipsilaterally projecting cortico-bulbo-spinal tracts tend to be flexion-biased. Given this information, we hypothesize that relatively preserved ability to flex wrist/fingers and limitation in ability to extend after stroke is the result of a greater reliance on contralesional motor cortices and brainstem motor nuclei of the ipsilaterally projecting cortico- bulbo-spinal pathways. The overall aim of this proposal, therefore, is to identify the activity in motor cortices (Aim 1) and ipsilaterally projecting motor pathways’ nuclei in brainstem (Aim 2) during separate hand opening and closing tasks in individuals with chronic hemiparetic ischemic stroke, using novel and high-resolution 7Tesla functional MRI (7T fMRI) methodology. Moreover, we hypothesize that higher reliance on contralesional motor cortices and their ipsilaterally projecting motor pathways’ nuclei in the brainstem is led to an increased functional connectivity between these motor centers in individuals with stroke (it will be tested in Aim 3). Successful completion of these specific aims will help elucidate the brain regions that facilitate partial hand function post stroke, and pave the way for the development of more effective and targeted therapeutic interventions for these individuals through utilizing the remaining brain regions and pathways post stroke.