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The Importance of Studying Interactions With Ovarian Hormones: Implications for Depressive Symptoms in Premenopausal and Menopausal Women

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The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in

The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in depression and anxiety has guided the research of not just recent studies but older studies as well, supporting the theory that gonadal hormones are associated with the mechanisms of emotional cognition. The scientific literature points towards a clear correlative relationship between gonadal hormones, especially estrogens, and emotion regulation. This thesis investigates the neural pathways that have been indicated to regulate mood and anxiety. Currently, the research points to the hypothalamic-pituitary-adrenal axis, which regulates the stress response through its ultimate secretion of cortisol through the adrenal cortex, and its modulated response when exposed to higher levels of estrogen. Another mechanism that has been investigated is the interaction of estrogen and the serotonergic system, which is noteworthy because the serotonergic system is known for its importance in mood regulation. However, it is important to note that the research seeking to determine the neurobiological underpinnings of estrogen and the serotonergic system is not expansive. Future research should focus on determining the direct relationship between cortisol hypersecretion and estrogens, the specific neurobiological effects of serotonergic receptor subtypes on the antidepressant actions of estrogens, and the simultaneous effects of the stress and serotonergic systems on depressive symptoms.

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2021-05

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Before-school running-walking club: effects on physical activity and on-task behavior

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Background: Childhood obesity is one of the most serious public health concerns in the United States and has been associated with low levels of physical activity. Schools are ideal physical activity promotion sites but school physical activity opportunities have decreased

Background: Childhood obesity is one of the most serious public health concerns in the United States and has been associated with low levels of physical activity. Schools are ideal physical activity promotion sites but school physical activity opportunities have decreased due the increased focus on academic performance. Before-school programs provide a good opportunity for children to engage in physical activity as well as improve their readiness to learn. Purpose: The purpose of this study was to examine the effect of a before-school running/walking club on children's physical activity and on-task behavior. Methods: Participants were third and fourth grade children from two schools in the Southwestern United States who participated in a before-school running/walking club that met two times each week. The study employed a two-phase experimental design with an initial baseline phase and an alternating treatments phase. Physical activity was monitored using pedometers and on-task behavior was assessed through systematic observation. Data analysis included visual analysis, descriptive statistics, as well as multilevel modeling. Results: Children accumulated substantial amounts of physical activity within the before-school program (School A: 1731 steps, 10:02 MVPA minutes; School B: 1502 steps, 8:30 MVPA minutes) and, on average, did not compensate by decreasing their physical activity during the rest of the school day. Further, on-task behavior was significantly higher on days the children attended the before-school program than on days they did not (School A=15.78%, pseudo-R2=.34 [strong effect]; School B=14.26%, pseudo-R2=.22 [moderate effect]). Discussion: Results provide evidence for the positive impact of before-school programs on children's physical activity and on-task behavior. Such programs do not take time away from academics and may be an attractive option for schools.

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2014

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Relationships Between the Inflammatory Responses of the Immune System and Periods of Critical Hormonal Shifts in Females Across the Lifespan: A Pregnancy Review

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In females, critical hormonal shifts occur during puberty, menstruation, pregnancy, and <br/>menopause. The fluctuating ovarian hormone levels across a woman’s lifespan likely contribute <br/>to inflammatory responses driven by the immune system, which is regulated by a variety of <br/>physiological pathways

In females, critical hormonal shifts occur during puberty, menstruation, pregnancy, and <br/>menopause. The fluctuating ovarian hormone levels across a woman’s lifespan likely contribute <br/>to inflammatory responses driven by the immune system, which is regulated by a variety of <br/>physiological pathways and microbiological cues. Pregnancy in particular results in drastic <br/>changes in circulating hormone profiles, and involves a variety of physiological changes, <br/>including inflammatory responses of the immune system. There is evidence that these effects are <br/>mediated, in part, by the significant hormone fluctuations that characterize pregnancy and <br/>postpartum periods. This thesis highlights and synthesizes important physiological changes <br/>associated with pregnancy, and their potential implications on cognitive and brain aging in <br/>women. A tertiary model of cognition is presented depicting interactions between hormonal <br/>history, reproductive history, and immune functions. This research is important to create a better <br/>understanding of women’s health and enhance medical care for women throughout pregnancy <br/>and across reproductive hormone shifts across the lifespan.

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2021-05

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Sit-to-stand task with physical and cognitive perturbations: A comparison of linear and nonlinear methods of analyzing postural data

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Variability is inherent in human movement, and poses a challenge to researchers attempting to measure balance. Human movement variability was analyzed using two methods: standard deviation and largest Lyapunov exponent. The experiment was a sit-to-stand task with physical and cognitive

Variability is inherent in human movement, and poses a challenge to researchers attempting to measure balance. Human movement variability was analyzed using two methods: standard deviation and largest Lyapunov exponent. The experiment was a sit-to-stand task with physical and cognitive perturbations. The physical perturbation consisted of stable and unstable platform conditions, while the cognitive perturbation consisted of a counting task. The data were collected from 24 healthy young adults. The purpose of this study was to compare the standard deviation and largest Lyapunov exponent as measures of stability, and to determine the Lyapunov exponent's sensitivity to cognitive perturbation. Evidence suggests that the Lyapunov exponent serves as a more accurate indicator of stability than standard deviation, and that it lacks sensitivity to the counting task.

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2016-12

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Cognitive control processes underlying continuous and transient monitoring processes in event-based prospective memory

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A converging operations approach using response time distribution modeling was adopted to better characterize the cognitive control dynamics underlying ongoing task cost and cue detection in event based prospective memory (PM). In Experiment 1, individual differences analyses revealed that working

A converging operations approach using response time distribution modeling was adopted to better characterize the cognitive control dynamics underlying ongoing task cost and cue detection in event based prospective memory (PM). In Experiment 1, individual differences analyses revealed that working memory capacity uniquely predicted nonfocal cue detection, while proactive control and inhibition predicted variation in ongoing task cost of the ex-Gaussian parameter associated with continuous monitoring strategies (mu). In Experiments 2A and 2B, quasi-experimental techniques aimed at identifying the role of proactive control abilities in PM monitoring and cue detection suggested that low ability participants may have PM deficits during demanding tasks due to inefficient monitoring strategies, but that emphasizing importance of the intention can increase reliance on more efficacious monitoring strategies that boosts performance (Experiment 2A). Furthermore, high proactive control ability participants are able to efficiently regulate their monitoring strategies under scenarios that do not require costly monitoring for successful cue detection (Experiment 2B). In Experiments 3A and 3B, it was found that proactive control benefited cue detection in interference-rich environments, but the neural correlates of cue detection or intention execution did not differ when engaged in proactive versus reactive control. The results from the current set of studies highlight the importance of response time distribution modeling in understanding PM cost. Additionally, these results have important implications for extant theories of PM and have considerable applied ramifications concerning the cognitive control processes that should be targeted to improve PM abilities.

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2015

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Cognitive changes across the menopause transition: a longitudinal evaluation of the impact of age and ovarian status on spatial memory

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Aging and the menopause transition are both intricately linked to cognitive changes

during mid-life and beyond. Clinical literature suggests the age at menopause onset can differentially impact cognitive status later in life. Yet, little is known about the relationship between behavioral

Aging and the menopause transition are both intricately linked to cognitive changes

during mid-life and beyond. Clinical literature suggests the age at menopause onset can differentially impact cognitive status later in life. Yet, little is known about the relationship between behavioral and brain changes that occur during the transitional stage into the post-menopausal state. Much of the pre-clinical work evaluating an animal model of menopause involves ovariectomy in rodents; however, ovariectomy results in an abrupt loss of circulating hormones and ovarian tissue, limiting the ability to evaluate gradual follicular depletion. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by selectively depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of menopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the cognitive effects of transitional menopause via VCD-induced follicular depletion over time, as well as to understand potential interactions with age, with VCD treatment beginning at either six or twelve months of age. Results indicated that subjects that experience menopause onset at a younger age had impaired spatial working memory early in the transition to a follicle-deplete state. Moreover, in the mid- and post- menopause time points, VCD-induced follicular depletion amplified an age effect, whereby Middle-Aged VCD-treated animals had poorer spatial working and reference memory performance than Young VCD-treated animals. Correlations suggested that in middle age, animals with higher circulating estrogen levels tended to perform better on spatial memory tasks. Overall, these findings suggest that the age at menopause onset is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study informs the field with respect to how the age at menopause onset might impact cognition in menopausal women, as well as provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition to attenuate age- and menopause- related cognitive decline, and produce healthy brain aging profiles in women who retain their ovaries throughout the lifespan.

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2015

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Progestogens impact cognition during the transition to menopause in the rat: dissociation of progestogen- and memory- type

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Progestogens, such as progesterone (P4), medroxyprogesterone acetate (MPA), and micronized progesterone (mP4), are given to ovary-intact women during the transition to menopause to attenuate heavy uterine bleeding and other symptoms. Both progesterone and MPA administration have been shown to impair

Progestogens, such as progesterone (P4), medroxyprogesterone acetate (MPA), and micronized progesterone (mP4), are given to ovary-intact women during the transition to menopause to attenuate heavy uterine bleeding and other symptoms. Both progesterone and MPA administration have been shown to impair cognition in ovariectomized (Ovx) rats compared to vehicle-treated controls. mP4, however, has yet to be investigated for cognitive effects in a preclinical setting. Further, progestogens affect the GABA (-aminobutyric acid) ergic system, specifically glutamic acid decarboxylase (GAD) the rate limiting enzyme necessary for synthesizing GABA. The goal of this experiment was to investigate the cognitive impact of P4, MPA, and mP4, in an ovary-intact transitional menopause model using 4-vinylcyclohexene diepoxide (VCD) and assess whether these potential changes were related to the GABAergic system. One group of rats received vehicle injections, and the remainder of the groups received VCD to induce follicular depletion, modeling transitional menopause in women. Vehicle or hormone administration began during perimenopause to model the time period when women often take progestogens alone. Rats then underwent testing to assess spatial working and reference memory in the water radial-arm maze (WRAM) and spatial reference memory in the Morris water maze (MWM). Results indicate that P4 and MPA improved learning for working memory measure, but only MPA impaired memory retention in the WRAM. For the WRAM reference memory measure, VCD only treated rats showed impaired learning and memory retention compared to vehicle controls; progestogens did not impact this impairment. Although GAD expression did not differ between treatment groups, in general, there was a relationship between GAD expression and WRAM performance such that rats that tended to have higher GAD levels also tended to make more WRAM working memory errors. Thus, while P4 and MPA have been previously shown to impair cognition in an Ovx model, giving these hormones early in an ovary-intact perimenopause model elicits divergent effects, such that these progestogens can improve cognition. Additionally, these findings suggest that the cognitive changes seen herein are related to the interaction between progestogens and the GABAergic system. Further investigation into progestogens is warranted to fully understand their impact on cognition given the importance of utilizing progestogens in the clinic.

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2019