In rehabilitating chronic motor-impaired stroke survivors with a brain computer interface (BCI), there is a fundamental gap in understanding how the brain changes with injury and in how a BCI can engage these dynamics to induce a functional recovery. The current barrier is the absence of a primate model that can test a BCI strategy in chronic stroke. The majority of animal models employ gray matter lesions, while the majority of clinically significant strokes involve the deeper white matter. The long-term goal of this project is to restore motor function by synergizing the patient's BCI rehabilitative strategy with their specific stroke-induced pathophysiology. The overall objective of this proposal is to create a nonhuman primate model for stroke that will examine the evolving physiology following a microvascular corticospinal tract (CST) lesion and test the impact of a neuroprosthetic intervention for functional restoration in the chronic setting. The central hypothesis is that BCI-driven motor rehabilitation for a CST injury will be effective when the control signals from the unaffected hemisphere are paired with proprioceptive feedback. The rationale for this research is that the animal model and the accrued scientific insights will create a mechanism-driven approach to neuroprosthetic solutions for stroke. Guided by strong preliminary evidence, we will test the central hypothesis with the following three specific aims: 1) Create a cortical electrode to enable multimodal measurements of the brain before and after a microvascular lesion to the CST, 2) Define acute and chronic alterations in cortical physiology and behavioral performance associated with a microvascular lesion to the CST, and 3) Restore motor function in macaque monkey with chronic CST injury using BCI rehabilitation. Under the first aim we will create a bihemispheric, MRI-invisible, micro-electrocorticographic (ECoG) implant that can measure the cortical physiology of ipsilesional and contralesional motor cortex and enable functional and anatomical magnetic resonance imaging. In the second aim, this implant, along with a new method for creating a stereotactic lesion to the posterior limb of the internal capsule, will enable us to link the micro-scale cortical electrophysiology with larger scale functional imaging as the brain changes from the central insult. Under the third aim, the chronically paretic monkeys will be rehabilitated using signal sources from the contralesional hemisphere. This project is innovative because it is a substantial departure from the status quo by expanding the role the unaffected hemisphere and bihemispheric interactions can play in BCI-mediated rehabilitation. The proposed research will be significant because the knowledge will create a critical bridge between motor function, electrophysiology, and functional imaging, which will vastly improve the characterization of how the cortical dynamics are perturbed with a white matter stroke and subsequently how these changes can be targeted for a tailored neuroprosthetic intervention. Ultimately, this will inform the development of novel treatments for stroke patients in the U.S.

Public Health Relevance

The proposed research is relevant to public health because developing primate models and technologies for the neuroprosthetic rehabilitation of chronic stroke will fundamentally expand the knowledge of how the brain changes with an injury and how it adapts when engaged with a brain computer interface to induce a functional recovery. Thus, the proposed research is relevant to the NINDS mission, which is to develop knowledge about the brain and to use that knowledge to reduce the burden of the neurologic disease of stroke.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section (BNVT)
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Kukke, Sahana Nalini
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Washington University
Schools of Medicine
Saint Louis
United States
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