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Description
Each year, millions of aging women will experience menopause, a transition from reproductive capability to reproductive senescence. In women, this transition is characterized by depleted ovarian follicles, declines in levels of sex hormones, and a dysregulation of gonadotrophin feedback loops. Consequently, menopause is accompanied by hot flashes, urogenital atrophy, cognitive

Each year, millions of aging women will experience menopause, a transition from reproductive capability to reproductive senescence. In women, this transition is characterized by depleted ovarian follicles, declines in levels of sex hormones, and a dysregulation of gonadotrophin feedback loops. Consequently, menopause is accompanied by hot flashes, urogenital atrophy, cognitive decline, and other symptoms that reduce quality of life. To ameliorate these negative consequences, estrogen-containing hormone therapy is prescribed. Findings from clinical and pre-clinical research studies suggest that menopausal hormone therapies can benefit memory and associated neural substrates. However, findings are variable, with some studies reporting null or even detrimental cognitive and neurobiological effects of these therapies. Thus, at present, treatment options for optimal cognitive and brain health outcomes in menopausal women are limited. As such, elucidating factors that influence the cognitive and neurobiological effects of menopausal hormone therapy represents an important need relevant to every aging woman. To this end, work in this dissertation has supported the hypothesis that multiple factors, including post-treatment circulating estrogen levels, experimental handling, type of estrogen treatment, and estrogen receptor activity, can impact the realization of cognitive benefits with Premarin hormone therapy. We found that the dose-dependent working memory benefits of subcutaneous Premarin administration were potentially regulated by the ratios of circulating estrogens present following treatment (Chapter 2). When we administered Premarin orally, it impaired memory (Chapter 3). Follow-up studies revealed that this impairment was likely due to the handling associated with treatment administration and the task difficulty of the memory measurement used (Chapters 3 and 4). Further, we demonstrated that the unique cognitive impacts of estrogens that become increased in circulation following Premarin treatments, such as estrone (Chapter 5), and their interactions with the estrogen receptors (Chapter 6), may influence the realization of hormone therapy-induced cognitive benefits. Future directions include assessing the mnemonic effects of: 1) individual biologically relevant estrogens and 2) clinically-used bioidentical hormone therapy combinations of estrogens. Taken together, information gathered from these studies can inform the development of novel hormone therapies in which these parameters are optimized.
ContributorsEngler-Chiurazzi, Elizabeth (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Sanabria, Federico (Committee member) / Olive, Michael F (Committee member) / Hoffman, Steven (Committee member) / Arizona State University (Publisher)
Created2013
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Description
The current paper presents two studies that examine how asymmetries during interpersonal coordination are compensated for. It was predicted that destabilizing effects of asymmetries are stabilized through the recruitment and suppression of motor degrees-of-freedom (df). Experiment 1 examined this effect by having participants coordinate line movements of different orientations. Greater

The current paper presents two studies that examine how asymmetries during interpersonal coordination are compensated for. It was predicted that destabilizing effects of asymmetries are stabilized through the recruitment and suppression of motor degrees-of-freedom (df). Experiment 1 examined this effect by having participants coordinate line movements of different orientations. Greater differences in asymmetries between participants yielded greater spatial deviation, resulting in the recruitment of df. Experiment 2 examined whether coordination of movements asymmetrical in shape (circle and line) yield simultaneous recruitment and suppression of df. This experiment also tested whether the initial stability of the performed movement alters the amount of change in df. Results showed that changes in df were exhibited as circles decreasing in circularity and lines increasing in circularity. Further, more changes in df were found circular (suppression) compared to line (recruitment) movements.
ContributorsFine, Justin (Author) / Amazeen, Eric L (Thesis advisor) / Amazeen, Polemnia G (Committee member) / Brewer, Gene A. (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Incidental learning of sequential information occurs in visual, auditory and tactile domains. It occurs throughout our lifetime and even in nonhuman species. It is likely to be one of the most important foundations for the development of normal learning. To date, there is no agreement as to how incidental learning

Incidental learning of sequential information occurs in visual, auditory and tactile domains. It occurs throughout our lifetime and even in nonhuman species. It is likely to be one of the most important foundations for the development of normal learning. To date, there is no agreement as to how incidental learning occurs. The goal of the present set of experiments is to determine if visual sequential information is learned in terms of abstract rules or stimulus-specific details. Two experiments test the extent to which interaction with the stimuli can influence the information that is encoded by the learner. The results of both experiments support the claim that stimulus and domain specific details directly shape what is learned, through a process of tuning the neuromuscular systems involved in the interaction between the learner and the materials.
ContributorsMarsh, Elizabeth R (Author) / Glenberg, Arthur M. (Thesis advisor) / Amazeen, Eric (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2013
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Description
There are several visual dimensions of food that can affect food intake, example portion size, color, and variety. This dissertation elucidates the effect of number of pieces of food on preference and amount of food consumed in humans and motivation for food in animals. Chapter 2 Experiment 1 showed that

There are several visual dimensions of food that can affect food intake, example portion size, color, and variety. This dissertation elucidates the effect of number of pieces of food on preference and amount of food consumed in humans and motivation for food in animals. Chapter 2 Experiment 1 showed that rats preferred and also ran faster for multiple pieces (30, 10 mg pellets) than an equicaloric, single piece of food (300 mg) showing that multiple pieces of food are more rewarding than a single piece. Chapter 2 Experiment 2 showed that rats preferred a 30-pellet food portion clustered together rather than scattered. Preference and motivation for clustered food pieces may be interpreted based on the optimal foraging theory that animals prefer foods that can maximize energy gain and minimize the risk of predation. Chapter 3 Experiment 1 showed that college students preferred and ate less of a multiple-piece than a single-piece portion and also ate less in a test meal following the multiple-piece than single-piece portion. Chapter 3 Experiment 2 replicated the results in Experiment 1 and used a bagel instead of chicken. Chapter 4 showed that college students given a five-piece chicken portion scattered on a plate ate less in a meal and in a subsequent test meal than those given the same portion clustered together. This is consistent with the hypothesis that multiple pieces of food may appear like more food because they take up a larger surface area than a single-piece portion. All together, these studies show that number and surface area occupied by food pieces are important visual cues determining food choice in animals and both food choice and intake in humans.
ContributorsBajaj, Devina (Author) / Phillips, Elizabeth D. (Thesis advisor) / Cohen, Adam (Committee member) / Johnston, Carol (Committee member) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2013
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Description
After natural menopause in women, androstenedione becomes the primary hormone secreted by the residual follicle deplete ovaries. Two independent studies, in rodents that had undergone ovarian follicular depletion, found that higher serum androstenedione levels correlated with increased working memory errors. This led to the hypothesis that androstenedione impairs memory. The

After natural menopause in women, androstenedione becomes the primary hormone secreted by the residual follicle deplete ovaries. Two independent studies, in rodents that had undergone ovarian follicular depletion, found that higher serum androstenedione levels correlated with increased working memory errors. This led to the hypothesis that androstenedione impairs memory. The current study directly tested this hypothesis, examining the cognitive effects of androstenedione administration in a rodent model. Middle-aged ovariectomized rats received vehicle or one of two doses of androstenedione (4 or 8 mg/kg daily). Rats were tested on a spatial working and reference memory maze battery including the water radial arm maze, Morris maze, and delay-match-to-sample task. Results showed that androstenedione at the highest dose impaired reference memory and working memory, including ability to maintain performance as memory demand was elevated. The latter was true for both high temporal demand memory retention of one item of spatial information, as well as the ability to handle multiple items of spatial working memory information. Glutamic acid decarboxylase (GAD) levels were measured in multiple brain regions to determine whether the gamma-aminobutyric acid (GABA) system mediates androstenedione's cognitive impairments. Results showed that higher entorhinal cortex GAD levels were correlated with poorer Morris maze performance, regardless of androstenedione treatment. These findings suggest that androstenedione, the main hormone produced by the follicle deplete ovary, is detrimental to spatial learning, reference memory, and working memory, and that spatial reference memory performance might be related to the GABAergic system.
ContributorsCamp, Bryan Walter (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Olive, Michael F (Committee member) / Conrad, Cheryl D. (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Cognitive function declines with normal age and disease states, such as Alzheimer's disease (AD). Loss of ovarian hormones at menopause has been shown to exacerbate age-related memory decline and may be related to the increased risk of AD in women versus men. Some studies show that hormone therapy (HT) can

Cognitive function declines with normal age and disease states, such as Alzheimer's disease (AD). Loss of ovarian hormones at menopause has been shown to exacerbate age-related memory decline and may be related to the increased risk of AD in women versus men. Some studies show that hormone therapy (HT) can have beneficial effects on cognition in normal aging and AD, but increasing evidence suggests that the most commonly used HT formulation is not ideal. Work in this dissertation used the surgically menopausal rat to evaluate the cognitive effects and mechanisms of progestogens proscribed to women. I also translated these questions to the clinic, evaluating whether history of HT use impacts hippocampal and entorhinal cortex volumes assessed via imaging, and cognition, in menopausal women. Further, this dissertation investigates how sex impacts responsiveness to dietary interventions in a mouse model of AD. Results indicate that the most commonly used progestogen component of HT, medroxyprogesterone acetate (MPA), impairs cognition in the middle-aged and aged surgically menopausal rat. Further, MPA is the sole hormone component of the contraceptive Depo Provera, and my research indicates that MPA administered to young-adult rats leads to long lasting cognitive impairments, evident at middle age. Natural progesterone has been gaining increasing popularity as an alternate option to MPA for HT; however, my findings suggest that progesterone also impairs cognition in the middle-aged and aged surgically menopausal rat, and that the mechanism may be through increased GABAergic activation. This dissertation identified two less commonly used progestogens, norethindrone acetate and levonorgestrel, as potential HTs that could improve cognition in the surgically menopausal rat. Parameters guiding divergent effects on cognition were discovered. In women, prior HT use was associated with larger hippocampal and entorhinal cortex volumes, as well as a modest verbal memory enhancement. Finally, in a model of AD, sex impacts responsiveness to a dietary cognitive intervention, with benefits seen in male, but not female, transgenic mice. These findings have clinical implications, especially since women are at higher risk for AD diagnosis. Together, it is my hope that this information adds to the overarching goal of optimizing cognitive aging in women.
ContributorsBraden, Brittany Blair (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Neisewander, Janet L (Committee member) / Conrad, Cheryl D. (Committee member) / Baxter, Leslie C (Committee member) / Arizona State University (Publisher)
Created2012
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Description
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

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.
ContributorsStylianou, Michalis (Author) / Kulinna, Pamela H. (Thesis advisor) / Van Der Mars, Hans (Committee member) / Amazeen, Eric (Committee member) / Adams, Marc (Committee member) / Mahar, Matthew T. (Committee member) / Arizona State University (Publisher)
Created2014
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Description
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

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.
ContributorsBall, Brett Hunter (Author) / Brewer, Gene A. (Thesis advisor) / Goldinger, Stephen (Committee member) / Glenberg, Arthur (Committee member) / Amazeen, Eric (Committee member) / Arizona State University (Publisher)
Created2015
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Description
An emerging literature on the relation between memory and importance has shown that people are able to selectively remember information that is more, relative to less important. Researchers in this field have operationalized importance by assigning value to the different information that participants are asked to study and remember. In

An emerging literature on the relation between memory and importance has shown that people are able to selectively remember information that is more, relative to less important. Researchers in this field have operationalized importance by assigning value to the different information that participants are asked to study and remember. In the present investigation I developed two experiments, using a slightly altered value-directed-remembering (VDR) paradigm, to investigate whether and how value modifies the dynamics of memory organization and search. Moreover, I asked participants to perform a surprise final free recall task in order to examine the effects of value in the recall dynamics of final free recall. In Experiment 1, I compared the recall dynamics of delayed and final free recall between a control and a value condition, in the latter of which numbers appeared next to words, in random order, denoting the value of remembering each word during recall. In Experiment 2, I manipulated the order of presentation of the values by adding an ascending and a descending condition where values were presented in either an ascending or a descending order, respectively. Overall, my results indicated that value affected several measures of delayed and final free recall, without, in most cases, taking away the serial position effects on those same measures.
ContributorsStefanidi, Aikaterini (Author) / Brewer, Gene A. (Thesis advisor) / Glenberg, Arthur (Committee member) / Goldinger, Stephen (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Nicotine is thought to underlie the reinforcing and dependence-producing effects of tobacco-containing products. Nicotine supports self-administration in rodents, although measures of its reinforcing effects are often confounded by procedures that are used to facilitate acquisition, such as food restriction, prior reinforcement training, or response-contingent co-delivery of a naturally reinforcing light.

Nicotine is thought to underlie the reinforcing and dependence-producing effects of tobacco-containing products. Nicotine supports self-administration in rodents, although measures of its reinforcing effects are often confounded by procedures that are used to facilitate acquisition, such as food restriction, prior reinforcement training, or response-contingent co-delivery of a naturally reinforcing light. This study examined whether rats acquire nicotine self-administration in the absence of these facilitators. A new mathematical modeling procedure was used to define the criterion for acquisition and to determine dose-dependent differences in rate and asymptote levels of intake. Rats were trained across 20 daily 2-h sessions occurring 6 days/week in chambers equipped with active and inactive levers. Each active lever press resulted in nicotine reinforcement (0, 0.015, 0.03, 0.06 mg/kg, IV) and retraction of both levers for a 20-s time out, whereas inactive lever presses had no consequences. Acquisition was defined by the best fit of a logistic function (i.e., S-shaped) versus a constant function (i.e., flat line) for reinforcers obtained across sessions using a corrected Akaike information criterion (AICc) as a model selection tool. The results showed an inverted-U shaped function for dose in relation to the percentage of animals that acquired nicotine self-administration, with 46% acquiring at 0.015 mg/kg, 73% at 0.03 mg/kg, and 58% at 0.06 mg/kg. All saline rats failed to acquire as expected. For rats that acquired nicotine self-administration, multiple model comparisons demonstrated that the asymptote (highest number of reinforcers/session) and half learning point (h; session during which half the assymptote had been achieved) were justified as free parameters of the reinforcers/session function, indicating that these parameters vary with nicotine dose. Asymptote exhibited an inverted U-shaped function across doses and half learning point exhibited a negative relationship to dose (i.e., the higher the dose the fewer sessions to reach h). These findings suggest that some rats acquire nicotine self-administration without using procedures that confound measures of acquisition rate. Furthermore, the modeling approach provides a new way of defining acquisition of drug self-administration that takes advantage of using all data generated from individual subjects and is less arbitrary than some criteria that are currently used.
ContributorsCole, Natalie (Author) / Neisewander, Janet L (Thesis advisor) / Sanabria, Federico (Thesis advisor) / Bimonte-Nelson, Heather A. (Committee member) / Olive, Michael F (Committee member) / Arizona State University (Publisher)
Created2011