PROJECT SUMMARY/ABSTRACT Individuals with chronic hemiparetic stroke typically have significant upper extremity motor impairments. These impairments include “associated reactions” and abnormal “muscle synergies”, characterized by inter- and intra- limb muscle coactivation patterns, respectively. It has been postulated that these motor impairments are due to an upregulation of the contralesional cortico-reticulospinal tract (CRST), after stroke-inflicted damage to corticofugal pathways. Neuroimaging in the brain, including functional magnetic resonance imaging (fMRI) and electromyography (EMG) studies, have widely substantiated this hypothesis, while leaving a tangible gap between measures of cortical neural function and skeletal muscle coactivation patterns. To our knowledge, neural activity in the spinal cord has not been investigated in the context of post-stroke motor impairments. Therefore, it is critical to integrate advanced fMRI methods in the human spinal cord with EMG techniques to investigate an increased reliance on the CRST in chronic hemiparetic stroke. The objectives of this research proposal are to investigate the neural mechanisms of post-stroke motor impairment and long-term to inform development of more targeted therapeutic interventions. If upregulation of the CRST is responsible for force generation in the paretic upper extremity, its characteristic bilateral and unilateral projections would be expected to drive associated reactions when activating the non-paretic hand, and muscle synergies in the paretic limb when activating the paretic hand. Spinal cord fMRI can provide direct insight into neural activation and motor pathway use in the human cervical spinal cord. In the proposed project, participants will perform unilateral isometric hand-grasping tasks; muscle activation will be measured with EMG and spinal cord neural activity will be measured with fMRI. Aim 1 will investigate the relationship of associated reactions and the lateralization of spinal cord neural activity. CRST-driven associated reactions are expected to elicit increased inter-limb muscle coactivation and more bilateral spinal cord neural activation when performing the task with the non-paretic hand. Aim 2 will investigate the relationship of abnormal motor synergies and the longitudinal extent of motor activation. Synergies driven by diffuse unilateral CRST projections are expected to elicit increased intra-limb muscle coactivation and an increased longitudinal extent of spinal cord activation. To execute this research project, the applicant will gain expertise in the neuropathophysiology of stroke and EMG, receive mentorship from experts in neuroscience and magnetic resonance imaging, and train in scientific communication, mentorship, and leadership. Northwestern University’s collaborative medical campus, with neuroimaging experts and state-of-the art research-dedicated MRI scanners, fosters a complete environment for scientific training and innovative res...