Biology Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2749
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Item ACUTE EXERCISE INDUCED MICROSTRUCTURAL AND FUNCTIONAL CHANGES IN THE HIPPOCAMPUS OF OLDER ADULTS(2023) Callow, Daniel; Carson, Jerome J; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Declining memory function is a common complaint of aging adults and a primary symptom of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The hippocampus is often the first brain area to exhibit noticeable deficits in age and pathologically-related cognitive decline and is a necessary structure for proper memory function. More specifically, the dentate gyrus (DG) and the third cornu ammonis area (CA3) of the hippocampus directly support mnemonic discrimination (MD), which is the process of reducing interference among new representations and distinctly encoding them as independent memories. Poor MD is associated with age and is a presymptomatic biomarker of cognitive decline and is believed to result from reduced neurogenesis, angiogenesis, and synaptogenesis within the DG/CA3 subregion of the hippocampus. While causes and treatments for memory decline remain elusive, lifestyle interventions, especially physical activity, have received attention as cost-effective and safe means of ameliorating and potentially preventing cognitive decline in a growing aging population. Animal and human studies suggest exercise benefits the hippocampal structure, preserving neurogenesis and angiogenesis in aging rodents and macrostructure and memory in older adults. However, the mechanisms by which exercise affects the human hippocampus remains a significant knowledge gap in the field and is a critical aspect in understanding the long-term impact exercise has on the aging hippocampus. To better address this gap, researchers have begun implementing acute exercise studies, which allow for greater control of non-exercise-related factors, are cheaper and more time efficient to conduct than training studies, and can predict and inform training-related adaptations. Unfortunately, limitations in the study designs, population tested, specificity of cognitive tasks, and spatial resolution of human imaging techniques have posed significant barriers to our understanding of how acute exercise relates to healthy brain aging at the functional and microstructural levels. Therefore, the objective of this dissertation was to expand our understanding of how acute aerobic exercise alters the function and microstructure of the aging hippocampus. Three within-subject studies were conducted comparing the relationship between a 30-minute bout of moderate to vigorous intensity aerobic exercise vs seated rest on MD performance, hippocampal microstructure, and high-resolution hippocampal-subfield microstructure and functional activity in healthy older adults. In study one, acute exercise preserved MD performance compared to decrements exhibited after seated rest in a pre and post-condition study design. In study two, a post-condition-only study design, acute exercise elevated microstructural diffusion within the hippocampus, indicative of a hippocampal neuroinflammatory response and upregulation of neurotrophic factors. Finally, in study three, a post-condition-only study design, we found that acute exercise resulted in lower MD, suppressed MD-related DG/CA3 network hyperactivity (indicative of healthier network function), and led to higher DG/CA3 extracellular diffusion. However, these neuroimaging-based correlates of hippocampal neuroplasticity and network function were not associated with differences in MD performance. These findings suggest that higher-intensity acute exercise can alter memory performance and stimulate neuroplasticity and neurotrophic cascades within the hippocampus and the DG/CA3 subfield, potentially via different mechanisms. Furthermore these results give insight into the immediate neurotrophic and behavioral effects of acute moderate to vigorous intensity aerobic exercise in older adults and provide new methods and tools for better understanding if and how exercise promotes healthy brain aging. Finally, these initial findings lay a foundation for optimizing exercise prescription and identifying future effective exercise treatments.Item Effects of early and concurrent parenting and child cortisol reactivity on hippocampal structure and functional connectivity during childhood: A prospective, longitudinal study(2017) Blankenship, Sarah Louise; Dougherty, Lea R; Riggins, Tracy; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Offspring of depressed mothers are at increased risk for emotional and behavioral disorders and social impairment. One proposed mechanism of risk transmission is through exposure to maladaptive parenting styles, as depressed mothers display higher levels of hostility and lower levels of support than non-depressed mothers. Rodent models indicate that the early parenting environment programs the endogenous stress response system, the hypothalamic-pituitary-adrenal (HPA) axis, through a cascade of epigenetic processes, ultimately elevating levels of glucocorticoid stress hormones (i.e., cortisol in humans). Elevated cortisol levels have been linked to both structural and functional changes in the hippocampus, a medial temporal lobe structure implicated in regulation of the HPA axis and the pathophysiology of depressive disorders. Despite elucidation of the pathways through which parenting influences neurobiological development in rodents, research examining these associations in humans is only emerging. The present study aimed to translate the rodent literature by examining the effects of early and concurrent parenting on hippocampal structure and functional connectivity during childhood, with a specific emphasis on exploring the mediating role of cortisol reactivity, in a longitudinal sample of offspring of depressed mothers and a community comparison group. At 3-6 and 5-10 years, observational measures of parenting and children’s salivary cortisol responses to a laboratory stressor were assessed. At 5-10 years, children completed structural and resting-state functional MRI scans. Findings revealed timing- and region-dependent associations. Early positive parenting predicted larger hippocampal head volumes whereas concurrent positive parenting predicted smaller body volumes. Early cortisol reactivity predicted larger body volumes whereas concurrent cortisol reactivity predicted smaller tail volumes. Concurrent parenting (positive and negative) predicted hippocampus subregion connectivity with regions of the cerebellum. Early cortisol reactivity predicted increased hippocampal connectivity with the cuneus and regions of the cingulate gyrus. There was a significant indirect effect of greater T1 Negative Parenting on smaller left hippocampal tail volume through increased concurrent cortisol reactivity. Significant interactions with maternal depression were also observed. This research provides a necessary translation of the rodent literature and elucidates possible timing-dependent neurobiological pathways through which early experience may confer increased risk for poor outcomes in human offspring.