Cognitive aging has profound effects on the hippocampus, a brain region that is critical for episodic memory formation and spatial navigation. Accurate episodic memory formation requires pattern separation, a neurocomputational process that orthogonalizes similar stimulus input into distinct neural representations and can be examined using behavioral mnemonic discrimination paradigms in humans. Age-related impairment in hippocampally-dependent cognition emphasizes the importance of identifying modulators of hippocampal plasticity. Critically, studies in older adults have demonstrated that greater cardiorespiratory fitness (CRF) is associated with greater volume of the hippocampus, mitigated age-related decline in spatial mnemonic discrimination, and better visuospatial memory. Nonetheless, how CRF modulates the underlying structural and functional neural correlates of mnemonic discrimination and spatial navigation in cognitive aging remains unknown. Therefore, the overall objective of this dissertation was to examine CRF as a modulator of hippocampal memory system structure and function, specifically regarding the hippocampally-dependent processes of mnemonic discrimination and spatial navigation, in cognitively healthy older adults. In a series of three experiments, we tested the central hypothesis that CRF enhances hippocampal plasticity and modulates the underlying neural correlates of mnemonic discrimination and spatial navigation in older adults. Data for these three experiments came from two studies. In the first, young adults (ages 18-35 years) and older adults (ages 55-85 years) underwent high-resolution fMRI to examine hippocampal subfield blood-oxygenation level-dependent (BOLD) signal during mnemonic discrimination. In the second, older adults (ages 60-80 years) underwent whole-brain, high-resolution fMRI to examine whole-brain BOLD signal during spatial navigation. In both studies, participants performed a submaximal treadmill test to estimate CRF and underwent high-resolution structural MRI to measure hippocampal subfield volumes as markers of neuroplasticity in the hippocampus. The primary goal of Experiment 1 was to examine the prediction that CRF is positively associated with mnemonic discrimination task performance and dentate gyrus (DG)/CA3 volume in older adults, given that these hippocampal subfields are thought to support pattern separation. Contrary to our initial prediction, we did not observe a relationship between CRF and mnemonic discrimination task performance or CRF and DG/CA3 volume. Instead, we observed a significant positive relationship between CRF and the volume of another hippocampal subfield, the bilateral subiculum, in older adult women, but not men. The primary goal of Experiment 2 was to examine the prediction that mnemonic discrimination-related BOLD signal in the hippocampal subfields is modulated by aging and CRF in young and older adults. In line with our initial prediction, there was a significant difference between young and older adults in right DG/CA2-3 BOLD signal during mnemonic discrimination task performance. Most importantly, CRF significantly modulated bilateral subiculum BOLD signal in an opposing fashion in young and older adults. The primary goal of Experiment 3 was to extend the current study beyond the function of the hippocampus in isolation and to examine whole-brain activation in association with an ecologically valid task that engages a large network of brain regions including but not limited to the hippocampus. We predicted that CRF modulates BOLD signal activation patterns driven by the employed spatial navigation task, specifically in brain regions in the frontal, parietal, and temporal cortices, and the cerebellum, given that the previously published literature in older adults has suggested that CRF enhances structural integrity in these regions in addition to the hippocampus. Our results demonstrated that CRF is significantly positively associated with BOLD signal in the right cerebellum lobule VIIa Crus I and Crus II, a region that has been implicated in sequence-based navigation. And, consistent with our results from Experiment 2, this relationship was observed in older adult women. Importantly, the findings of these experiments highlight novel targets of fitness-related neuroplasticity in the older adult brain, including the subiculum subfield of the hippocampus and the cerebellum lobule VIIa Crus I and Crus II. Furthermore, these findings underscore the importance of examining sex as a modulating factor of fitness-related neuroplasticity.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/43767 |
| Date | 02 February 2022 |
| Creators | Kern, Kathryn Leigh |
| Contributors | Schon, Karin |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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