Neurophysiological mechanisms of sensorimotor recovery from stroke
Supplementary Video S5.1: Example of a successful pellet retrieval and associated neural activity from the reaching rat. (77.38Mb)
Supplementary Video S5.2: Example of an unsuccessful pellet retrieval and associated neural activity from the reaching rat. (81.10Mb)
Supplementary Video S5.3: jPCA rotational dynamics fit to neural activity during all reaching trials from a single session. (14.61Mb)
Supplementary Video S5.4: Spatiotemporal activations corresponding to weighted activity in a single pair of basis vectors representing a plane in the dynamical system of the neural state space. (1.608Mb)
Video 6.1: Noisy result from automated 3D digit marker reconstruction of virtual markers on the rat forelimb during pellet retrievals without curation. (2.212Mb)
Video 6.2A: Curated virtual marker 3D reconstruction using a custom MATLAB interface to clean the kinematic outputs from DeepLabCut during a right-paw pellet retrieval. (507.9Kb)
Video 6.2B: Curated virtual marker 3D reconstruction using a custom MATLAB interface to clean the kinematic outputs from DeepLabCut during a left-paw pellet retrieval. (431.1Kb)
Video 6.3: Example of process noise introduced by (known) spurious marker pixel identity insertion. (1.276Mb)
Murphy, Maxwell DeWolf
University of Kansas
Copyright held by the author.
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Ischemic stroke often results in the devastating loss of nervous tissue in the cerebral cortex, leading to profound motor deficits when motor territory is lost, and ultimately resulting in a substantial reduction in quality of life for the stroke survivor. The International Classification of Functioning, Disability and Health (ICF) was developed in 2002 by the World Health Organization (WHO) and provides a framework for clinically defining impairment after stroke. While the reduction of burdens due to neurological disease is stated as a mission objective of the National Institute of Neurological Disorders and Stroke (NINDS), recent clinical trials have been unsuccessful in translating preclinical research breakthroughs into actionable therapeutic treatment strategies with meaningful progress towards this goal. This means that research expanding another NINDS mission is now more important than ever: improving fundamental knowledge about the brain and nervous system in order to illuminate the way forward. Past work in the monkey model of ischemic stroke has suggested there may be a relationship between motor improvements after injury and the ability of the animal to reintegrate sensory and motor information during behavior. This relationship may be subserved by sprouting cortical axonal processes that originate in the spared premotor cortex after motor cortical injury in squirrel monkeys. The axons were observed to grow for relatively long distances (millimeters), significantly changing direction so that it appears that they specifically navigate around the injury site and reorient toward the spared sensory cortex. Critically, it remains unknown whether such processes ever form functional synapses, and if they do, whether such synapses perform meaningful calculations or other functions during behavior. The intent of this dissertation was to study this phenomenon in both intact rats and rats with a focal ischemia in primary motor cortex (M1) contralateral to the preferred forelimb during a pellet retrieval task. As this proved to be a challenging and resource-intensive endeavor, a primary objective of the dissertation became to provide the tools to facilitate such a project to begin with. This includes the creation of software, hardware, and novel training and behavioral paradigms for the rat model. At the same time, analysis of previous experimental data suggested that plasticity in the neural activity of the bilateral motor cortices of rats performing pellet retrievals after focal M1 ischemia may exhibit its most salient changes with respect to functional changes in behavior via mechanisms that were different than initially hypothesized. Specifically, a major finding of this dissertation is the finding that evidence of plasticity in the unit activity of bilateral motor cortical areas of the reaching rat is much stronger at the level of population features. These features exhibit changes in dynamics that suggest a shift in network fixed points, which may relate to the stability of filtering performed during behavior. It is therefore predicted that in order to define recovery by comparison to restitution, a specific type of fixed point dynamics must be present in the cortical population state. A final suggestion is that the stability or presence of these dynamics is related to the reintegration of sensory information to the cortex, which may relate to the positive impact of physical therapy during rehabilitation in the postacute window. Although many more rats will be needed to state any of these findings as a definitive fact, this line of inquiry appears to be productive for identifying targets related to sensorimotor integration which may enhance the efficacy of future therapeutic strategies.
- Dissertations 
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