"April 2003" / Bibliography: leaves 124-144. / xvii, 144 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, School of Molecular and Biomedical Sciences, Discipline of Physiology, 2003

The leading cause of long-term disability among adults in industrialized countries is stroke. Exploration of the brain mechanisms involved during recovery from stroke is likely to yield information that can be used to promote better functional outcome. After focal motor cortical infarcts, reorganization of movement representations in the remaining motor cortex has been linked to both spontaneous recovery and recovery induced by rehabilitative training. However, the mechanisms and nature of cortical reorganization remain poorly understood. The central hypothesis of these dissertation studies is that synaptogenesis and structural reorganization in the cortex near the lesion are linked to spontaneous partial recovery and the beneficial effects of motor rehabilitative training after stroke-like injury. This was tested in a rat model of focal cortical ischemia by both behavioral and neuroanatomical measures in perilesion cortex. In separate studies, it was found that motor rehabilitative training on a skilled reaching task using the impaired forelimb after a unilateral ischemic lesion improved forelimb functional outcome and facilitated synaptogenesis in perilesion cortex. In addition, this improved functional recovery was disrupted by focal protein synthesis inhibition in perilesion cortex, suggesting the structural plasticity in this area plays an important role in regained function. Finally, it was also hypothesized that a therapy that enhances the efficacy of motor rehabilitation also enhances synaptic structural plasticity in perilesion cortex. Cortical electrical stimulation (CS) during motor rehabilitation has previously been shown to improve the efficacy of rehabilitation. Increased density of axodendritic synapses in perilesion cortex was found in rats that received cortical electrical stimulation of perilesion cortex during rehabilitation compared to rehabilitation alone, and the synaptic density was positively correlated with post-rehabilitation reaching performance. These findings suggest that CS-induced functional improvements may be mediated by synaptic structural plasticity in stimulated cortex. Together these studies indicate that, after a cortical lesion in rats, motor rehabilitation alone or in conjunction with other efficacious therapies can greatly enhance synaptic structural plasticity in perilesion cortex. Furthermore, these studies suggest that rehabilitation induced improvements in functional outcome are dependent upon the structural and functional integrity of the reorganized perilesion cortex.

Motor skill learning underlies much of what we do, be it hitting a tennis serve, playing the piano, or simply brushing our teeth. Yet despite its importance, little is known about the neural circuits that implement the learning process or how the motor program is represented in the brain. Here I explore the role of motor cortex through lesion studies in rats trained on a motor skill. First, I interrogate whether motor cortex is necessary for the production of a complex motor sequence by training animals to produce temporally precise self-initiated movement sequences on a lever-pressing task. The movement sequences that emerged over months of training were remarkably complex, yet very precise. This motor skill, once mastered, survives large bilateral motor cortex lesions, suggesting that motor cortex is not required for generating movement sequences after consolidation. Next, I explored the role of motor cortex in motor skills that require dexterous manipulations. Animals trained to make constrained spatially precise movements using a joystick were impaired after motor cortex lesions. The role of motor cortex thus depends on the nature of the movements involved but not on the sequencing of movements. Third, I explored the function of motor cortex in sensorimotor transformations by training animals on the same lever-pressing task but with external cues instead of self-initiated movement. Surprisingly, these animals were also not impaired after lesions, suggesting that the method of learning the motor sequence has no consequence once the motor sequences are consolidated. Lastly, I explored the role of motor cortex in learning motor skills. Animals that were lesioned after being exposed to the lever-pressing task could learn to adjust the timing of their movements, indicating that motor cortex is not required for adapting a previously-acquired motor sequence. Lesions of motor cortex prior to any training, however, severely disrupted learning. Even with extended training, animals were unable to fully master the task, demonstrating that motor cortex is necessary for the acquisition of new motor skills even when it is not required for their execution.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

A recent theory of motor control, based on optimal feedback control, posits that voluntary motor behaviour involves the sophisticated manipulation of sensory feedback. Although this theory can explain how people move in the world, it does not specifically describe how this control process is implemented by the nervous system. In this thesis, we propose and explore one physiological implication of this theory. Specifically, we hypothesize that rapid feedback responses should possess the key functional attributes of voluntary control because these two systems share a common neural pathway through motor areas of cerebral cortex. Our first four studies were designed to elaborate the functional attributes of the long-latency stretch reflex, a fast feedback response which occurs 50-100ms following the mechanical stretch of a muscle. Consistent with our hypothesis, we found that the long-latency response possesses many attributes commonly reserved for voluntary control: the long-latency response is continuously modulated by subject intent (Chapter 2), it compensates for the size-recruitment principle of the motoneuron pool (Chapter 3) and it accounts for the mechanical properties of the upper-limb (Chapter 5). Further investigation revealed that the long-latency response can be decomposed into two functionally-independent processes (Chapter 4), and that one of these components contributes all of the sophistication observed in Chapters 2 and 3. The goal of our fifth study was to investigate the neural basis of the long-latency response (Chapter 6). Our results provide strong evidence from both single-neuron recordings in non-human primates and transcranial magnetic stimulation in humans that primary motor cortex, which is known to be a critical node for voluntary control, also contributes to the sophistication of the long-latency response. Taken together, the studies presented in this thesis demonstrate that the long- latency response possesses several functional attributes typically reserved for voluntary control and that this sophistication likely arises via a transcortical pathway through primary motor cortex. / Thesis (Ph.D, Neuroscience Studies) -- Queen's University, 2011-01-18 09:19:24.579

The ease with which our brains learn to control our bodies belies intricate neural processing which remains poorly understood. We know that a network of brain regions work together in a carefully coordinated fashion to allow us to move from one place to another. In mammals, we know that the motor cortex plays a central role in this process, but precisely how its activity contributes to control is a matter of long and continued debate. In this thesis we demonstrate the need for developing mechanistic neural network models to address this question. Using such models, we show that contentious response properties of non-human primate primary motor cortex (M1) neurons can be understood as reflecting control processes which take into account the physics of the body. And we develop new computational techniques for teaching neural network models how to execute control. In the first study (Chapter 2), we critically examined a recently developed correlation-based descriptive model for characterizing the activity of M1 neuron activity. In the second study (Chapter 3), we developed neural network control laws which performed reaching and postural tasks using a physics model of the upper limb. We show that the population of artificial neurons in these networks exhibit preferences for certain directions of movement and certain forces applied during posture. These patterns parallel empirical observations in M1, and the model shows that the patterns reflect particular features of the biomechanics of the arm. The final study (Chapter 4) develops new techniques for building network models. To understand how the brain solves difficult control tasks we need to be able to construct mechanistic models which can do the same. And, we need to be able to construct controllers that compute via simple neuron-like units. In this study, we combine tools for automatic computation of derivatives with recently developed ideas about second-order approaches to optimization to build better neural network control laws. Taken together, this thesis helps develop arguments for, and the tools to build mechanistic neural network models to understand how motor cortex contributes to control of the body. / Thesis (Ph.D, Neuroscience) -- Queen's University, 2014-01-31 10:34:43.816

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (M. Med. Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 89-101).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1960. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.Med.Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 89-101). Also available in print.