Susanne M. Morton, PhD PT - US grants

[unreadable] DESCRIPTION (provided by applicant): The purpose of this Mentored Research Scientist Development Award is to prepare the candidate for a successful long-term career in medical rehabilitative research. The candidate will receive primary sponsorship from a senior-level scientist who will provide the candidate with a period of intensive, focused training in the areas of motor cortical neurophysiology, motor cortical plasticity following stroke, and the use of transcranial magnetic stimulation as a research tool to measure cortical excitability. The purpose of the research proposed here is to determine mechanisms of bilateral leg control in individuals with post stroke hemi paresis; specifically, to determine the effects of the sensorimotor state of one leg on the motor behavior of the opposite leg. Three studies will be undertaken to determine: 1) does damage to the motor cortex cause specific deficits in bilateral more than unilateral cyclical ankle movements? 2) to what extent do ipsilateral uncrossed corticospinal pathways contribute to unilateral and bilateral cyclical ankle movements in individuals with motor cortical stroke? and 3) does damage to the motor cortex impair bilateral leg motor responses to a novel unilateral perturbation during walking? To answer these questions, 3-D movement kinematics and electromyography will be recorded from subjects with hemi paresis caused by motor cortical stroke and healthy age- and gender-matched control subjects performing ankle movement tasks and walking. Results will help explain the specific function of the motor cortex and corticospinal pathway and will provide a basis for the development of novel rehabilitation techniques to recover normal locomotor's function in individuals with post-stroke hemi paresis. The mentorship provided in this plan will help direct the candidate toward independence as an investigator and lend significant progress toward the candidate's long-term research goal of understanding interlimb coordination during human locomotion and mechanisms for recovery of locomotor's function following neurological damage. RELEVANCE: This research will have broad impact on public health, as stroke is a leading cause of long-term disability and leaves many of its victims unable to walk without assistance (AHA 2005). Findings from these studies are expected to help lead to the development of new treatments aimed at stroke rehabilitation generally and gait recovery specifically. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Motor learning forms a foundation for rehabilitation interventions to treat patients with debilitating neurological disorders such as stroke. It is now known that the cerebellum is required for motor adaptations and motor learning. The motor cortex is also involved in motor learning, but its specific role is less clear. Recent studies indicate that the motor cortex may be more involved in the consolidation and/or retention phases of motor learning than in the initial acquisition. It is not known whether individuals with stroke involving the motor cortex have deficits in retention of newly acquired motor adaptations. Broadly, the purpose of this research is to determine the effects of unilateral stroke involving the primary motor output system on retention of a newly learned visuomotor walking adaptation in humans. Motion capture, electromyography and transcranial magnetic stimulation (TMS) will be used to record limb movements and to measure and modulate corticospinal excitability, respectively. In Aim 1, visual feedback during walking will be altered to induce a novel gait pattern in healthy and stroke-affected adults that, in stroke subjects, is designed to improve symmetry of single limb support durations between the legs. Initial adaptation and retention of the new walking pattern will be measured and compared across groups at several time periods. Subject with stroke are expected to show reduced retention but relatively intact adaptation. In Aim 2, low frequency inhibitory repetitive TMS (rTMS) will be applied over the primary motor cortex (M1) of the non- lesioned hemisphere in individuals with stroke prior to walking. Effects of rTMS on the acquisition and retention of the visuomotor walking adaptation will be measured and compared to a group of stroke subjects receiving sham stimulation. Single pulse TMS will be used to measure changes in corticospinal excitability before and after rTMS. We predict that inhibitory rTMS to the non-lesioned M1 will improve retention of the walking adaptation in stroke subjects, and will be associated with disinhibition of the lesioned M1. We also expect to find that the level of benefit from rTMS varies with lesion location. Results from the proposed aims will help determine whether individuals with stroke involving the primary motor output system have deficits in acquisition and/or retention of newly adapted walking patterns and whether this deficit can be temporarily improved using rTMS. This work is particularly important because 1) it will help determine the role of the motor cortex in acquisition and/or retention of motor adaptations, 2) it will support or refute the proposed mechanism of overly strong transcallosal inhibition from the non-lesioned hemisphere as a source of motor impairment in patients with stroke, and 3) it may lead to the development of novel therapies to enhance motor learning and retention in patients with motor disability due to stroke. PUBLIC HEALTH RELEVANCE: Results from these studies will provide novel insights into brain mechanisms of impaired motor learning following stroke. Importantly, findings are expected to help lead to the development of new rehabilitation interventions to enhance motor learning of locomotor patterns in patients with stroke. Thus, this work will have broad impact on public heath, as stroke is a leading cause of long-term disability and leaves many of its victims unable to walk without assistance.