Elucidating the role of the contralesional corticoreticulospinal tract for lower limb function after stroke.

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Project Summary/Abstract Chronic walking impairments such as decreased walking speed, endurance, and independence are common after stroke and limit physical activity, quality of life, and community involvement. These walking impairments contribute to high healthcare costs and the development of secondary disabilities. Walking impairments tend to persist despite gait rehabilitation, partly because we lack a comprehensive understanding of which brain pathways contribute to lower limb and walking recovery after stroke. Emerging evidence suggests that ipsilaterally-descending motor pathways from the non-lesioned hemisphere to the stroke-affected limb, specifically the corticoreticulospinal tract, may be enhanced. However, the measurement tools used in prior work, when considered in isolation, provide limited insight into whether this pathway is functional enhanced and contributes to improved lower limb function. The primary objective of this proposal is to address this question with the long-term goal of improving gait rehabilitation after stroke by identifying recovery-related motor pathways that can be targeted. Our central hypothesis is that the corticoreticulospinal tract from the non-lesioned brain hemisphere to the more affected limb will be enhanced after stroke. The secondary objective of this proposal is to determine whether the strength of the corticoreticulospinal tract from the non-lesioned brain hemisphere influences lower limb motor control. To achieve the objectives of this proposal, two specific aims will be tested in individuals with chronic stroke with a range of impairment. In Aim 1, we will develop a multi-dimensional estimate of whether the corticoreticulospinal tract is enhanced after stroke by combining three measures used in prior research: functional magnetic resonance imaging (non-lesioned brain activation), diffusion tensor imaging (structural integrity), and transcranial magnetic stimulation (functional excitability). In Aim 2, the association between the strength of the corticoreticulospinal tract from the non-lesioned hemisphere and lower limb motor control will be assessed. This analysis will account for measures of stroke severity (lesion load and lower limb impairment). The proposed work would be the first to use a multifaceted approach to comprehensively and rigorously assess whether brain pathways from the non-lesioned hemisphere to the stroke-affected lower limb are enhanced after stroke. Results from this work will improve our understanding of the brain pathways that contribute to walking recovery after stroke, essential information for improving walking rehabilitation. The proposed work will also provide insight into how stroke impairment influences the mechanisms of recovery and the optimal rehabilitative strategy. Support for the central hypothesis will be a major breakthrough that supports the potential for neuromodulation applied to non-lesioned brain pathways pathways to lead to improvements in walking recovery after stroke. Improvements in walking rehabilitation that result from the proposed work could lead to substantial reductions in chronic walking impairment, disability, and societal cost of stroke.