This proposal addresses the fundamental question of how to overcome disruption of muscle activation and coordination after neural injury such as stroke. Our goal is to understand interaction dynamics among all hierarchical levels. Our objectives are to determine signal generation and interactions between primary motor cortex (Ml) and spinal cord (SC) nehworks for the control of gross and fine movements and to chart the functional reorganization of Ml after stroke. Our central hypothesis is that the relative contribution and the hierarchy of interactions between Ml and SC mechanisms for the control of functional muscle groups or motor synergies will depend on the required dexterity of movement. For this purpose, data will be obtained from rats performing tasks that range from basic, stereotypical behaviors such as locomotion to more complex, dexterous behaviors such as walking on horizontal ladders with asymmetric rung position and reaching movements.
In Aim 1, we will probe the neural system at the cortical level with microelectrode arrays implanted bilaterally in Ml, at the spinal level with epidural electrode array over cervical enlargement, and in the peripheral system with intramuscular electrodes. The activity of single neurons and local field potential will be examined in the context of their contribution to the control of motor synergies. The organization between Ml, spinal pathways and sensory feedback mechanisms will be examined with paired stimulation of cortical and peripheral pathways.
In Aim 2, we will study how these corticospinal mechanisms reorganize and recover after a focal cortical damage by the reversible occlusion of middle cerebral artery. The proposed studies will reveal fundamental neural mechanisms of interactions between different levels of control hierarchy in animals before and after transient stroke. This ground work will help to develop strategies to restore functionality that improves symmetric gait and dexterity beyond intrinsic recovery capabilities of the motor control system. Results from these studies will be used to enhance neuroprosthetic technologies that restore function to patients who suffer motor dysfunction.

Public Health Relevance

A highly functioning ESC that will provide a vital service to the Stroke CoBRE junior investigators and to the greater WVU neuroscience and cardiovascular research community and help position us for competitiveness for center and program project grant applications. Success of this ESC is a necessary component of our development of a national center for excellence in basic and translational stroke research.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
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Special Emphasis Panel (ZGM1-TWD-C (C1))
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West Virginia University
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