Browsing by Subject "Motor Learning"

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    Multifocal Transcranial Direct Current Stimulation to Modulate Motor Learning
    (2025-03) Greenwell, Davin Ross; Riley, Zachary; Kaleth, Anthony; Naugle, Kelly; Streepey, Jake; Metzler-Wilson, Kristen
    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates neural excitability in targeted brain regions, influencing processes such as motor learning. While tDCS has been previously shown to benefit motor skill acquisition, much of this research has focused on relatively simple, unimanual tasks. Conversely, the effects of tDCS on more complex, bimanual motor tasks remain understudied, with existing findings often yielding mixed results. This inconsistency poses challenges for translating laboratory findings to functional, real-world motor skills, which frequently involve coordinated, two-handed movements and heightened cognitive demands. Emerging evidence suggests that multifocal tDCS paradigms, which simultaneously target multiple brain regions, may provide enhanced learning effects, particularly for complex motor tasks. Unlike traditional monofocal stimulation protocols that focus on the primary motor cortex (M1) or cerebellum individually, multifocal approaches may better address the neural dynamics underlying bimanual coordination and interhemispheric interactions. The purpose of this dissertation was to investigate the potential of multifocal tDCS to enhance motor learning in complex tasks, examining both unimanual and bimanual skill acquisition. This research involved a series of studies beginning with monofocal tDCS applied to M1 and the cerebellum during a non-dominant unimanual rhythm-timing task and culminating in a multifocal “tri-focal” stimulation protocol during a bimanual motor learning task. In Study One, we compared the effects of excitatory M1 stimulation against excitatory and inhibitory cerebellar and sham stimulation. While none of the monofocal tDCS conditions significantly enhanced learning compared to sham, small, non-significant trends were observed which informed the design of Study Two. Here, we observed that combining excitatory M1 stimulation with inhibitory cerebellar stimulation resulted in significant and robust improvements in motor learning. In Study Three, we found that bilateral M1 stimulation significantly enhanced the early stages of bimanual skill learning at lower intensities. However, Study Four revealed that increasing stimulation intensity or adding inhibitory cerebellar stimulation impaired bimanual learning. Together, these findings contribute to a growing understanding of how multifocal stimulation paradigms can be tailored to enhance motor learning in real-world tasks while underscoring the importance of carefully optimizing stimulation parameters to task-specific demands.
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    Neurabin's Influence on Striatal Dependent Behaviors
    (2022-08) Corey, Wesley; Cummins, Theodore; Berbari, Nicolas; Baucum, Anthony J., II.
    The striatum is a key brain region involved in regulating motor output and integration. The dorsal and ventral subdivisions of the striatum work in concert to mediate the reinforcing and motor behavioral outputs of the striatum. Moreover, dysfunction of these striatal regions is involved in various diseases including Parkinson’s disease and drug addiction. Therefore, understanding and characterizing biochemical and molecular changes within the striatum associated with these diseases is key in devolving novel therapeutics to treat these disease states. The main output neurons of the striatum are GABAergic, medium-spiny neurons (MSNs), and striatal functionality is mediated by neuroplastic changes in MSN activity. Within MSNs, dopaminergic receptor activation triggers a cascade of reversable phosphorylation, which is facilitated by the activation of specific protein kinases and inhibition of specific protein phosphatases. In comparison to the 350 serine/threonine protein kinases expressed within the striatum, there are only 40 major serine/threonine protein phosphatases. However, serine/threonine protein phosphatases, such as protein phosphatase 1 (PP1), gain their target specificity by interacting with phosphatase-targeting proteins. Within the striatum, the neurabins, termed neurabin and spinophilin, are the most abundant PP1 targeting proteins in dendritic spines. Spinophilin’s expression in the striatum has been strongly characterized, and spinophilin has been shown to regulate striatal-dependent motor-skill learning and amphetamine-induced locomotor sensitization. In contrast to spinophilin, neurabin’s expression within the striatum and its involvement in these striatal-dependent behaviors has not been fully probed. I found that neurabin expression in the striatum is not sex-dependent but is age-dependent. In addition to these data, I also present validation of new global, constitutive and conditional neurabin knock-out mouse lines. Finally, I present data that, unlike previous studies in spinophilin knockout mice, neurabin knockout mice have enhanced striatal-dependent motor-skill learning, but do not impact amphetamine-induced locomotor sensitization. Further characterization of neurabin’s expression in the striatum, and its role in these key striatal behaviors could provide a druggable target for therapeutics designed to address striatal dysfunction.